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Arakawa N, Aoyama T, Suwanai H, Toda G, Takamoto I, Okazaki Y, Kadowaki T, Yamauchi T. Elucidation of the clinical traits of diabetic chorea through a questionnaire survey of people with diabetic chorea from 59 Japanese hospitals. J Diabetes Investig 2024. [PMID: 39714319 DOI: 10.1111/jdi.14392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/21/2024] [Accepted: 12/11/2024] [Indexed: 12/24/2024] Open
Abstract
AIMS Diabetic chorea refers to sudden involuntary movements developing in people with diabetes mellitus and is known to occur mainly in those with severe hyperglycemia. We conducted a questionnaire survey of case-reporting facilities in Japan to elucidate their clinical characteristics. METHODS We searched the PubMed and Ichushi databases for case reports published from January 1, 2012, to December 31, 2017, using "diabetes" and "chorea" as keywords, and sent a questionnaire to the reporting institutions. RESULTS Data from a total of 64 cases were included in this study. While most cases had severe hyperglycemia at the onset of diabetic chorea, hypoglycemia/improvement of the plasma glucose served as the trigger for the symptom in 14 cases (21.9%). The Early Remission Group (≤6 months) consisted of 39 cases (60.9%), while the Prolonged Partial Remission Group (>6 months) included 25 cases (39.1%). In the Prolonged Partial Remission Group (>6 months), there were more cases with widespread involuntary movement symptoms, a higher number of cases exhibiting typical imaging findings, and a greater incidence of chorea onset after the initiation of antidiabetic treatment, including hypoglycemia. CONCLUSIONS Most reported cases of diabetic chorea in Japan were elderly persons with type 2 diabetes mellitus and severe hyperglycemia, although there were also some cases in which the symptom developed in the setting of hypoglycemia. It has been suggested that rapid plasma glucose correction and hypoglycemia might be associated with the risk of development and prognosis of diabetic chorea.
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Affiliation(s)
- Naoko Arakawa
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Department of Endocrinology and Metabolism, Tokyo Metropolitan Health and Medical Treatment Corporation Tama-Hokubu Medical Center, Tokyo, Japan
| | - Tomohisa Aoyama
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hirotsugu Suwanai
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Department of Diabetes, Metabolism, and Endocrinology, Tokyo Medical University, Tokyo, Japan
| | - Gotaro Toda
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Iseki Takamoto
- Department of Metabolism and Endocrinology, Ibaraki Medical Center, Tokyo Medical University, Tokyo, Japan
| | - Yukiko Okazaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takashi Kadowaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Toranomon Hospital, Tokyo, Japan
| | - Toshimasa Yamauchi
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Maity D, Guha Ray P, Fussenegger M. Glucose-Operated Widget (GLOW) for Closed-Loop Optogenetic Glycemic Control. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2408537. [PMID: 39210629 DOI: 10.1002/adma.202408537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 08/07/2024] [Indexed: 09/04/2024]
Abstract
Closed-loop control systems for precise control of therapeutic gene expression are promising candidates for personalized treatment of chronic ailments such as diabetes. Pancreatic iβ-cells are engineered with blue-light-inducible melanopsin to drive rapid insulin release by vesicular secretion from intracellular stores. In this work, a glucose-operated widget (GLOW) is designed as a component of a closed-loop control system for diabetes treatment by employing a probe that emits blue fluorescence in a glucose-concentration-dependent manner as a real-time glucose sensor to precisely control insulin release from these iβ-cells. As proof-of-concept of the complete control system, the probe is encapsulated together with iβ-cells in alginate-poly-(L-lysine) hydrogel-microbeads(400 µm in diameter and containing about 500 cells) called GLOWiβ (GLOW with iβ-cells), are subcutaneously implanted into type-1-diabetic (T1D) mice. Illumination by UV-A light at 390 nm results in glucose-concentration-dependent blue-light emission from the probe at 445 nm that in turn induces glucose-concentration-dependent insulin release from the iβ-cells in a fully reversible manner. Activation of the injected GLOWiβ at 390 nm for 15 min effectively restores normoglycemia within 60-120 min in a closed-loop manner in these diabetic mice. The system is robust, as normoglycemia is well maintained by daily activation for at least 7 days.
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Affiliation(s)
- Debasis Maity
- Department of Biosystems Science and Engineering, ETH Zurich, Klingelbergstrasse 48, Basel, CH-4056, Switzerland
| | - Preetam Guha Ray
- Department of Biosystems Science and Engineering, ETH Zurich, Klingelbergstrasse 48, Basel, CH-4056, Switzerland
| | - Martin Fussenegger
- Department of Biosystems Science and Engineering, ETH Zurich, Klingelbergstrasse 48, Basel, CH-4056, Switzerland
- Faculty of Science, University of Basel, Klingelbergstrasse 48, Basel, CH-4056, Switzerland
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Hou X, Yue S, Xu Z, Li X, Wang Y, Wang J, Chen X, Wu J. Joint Modifiable Risk Factor Control and Incident Stroke in Hypertensive Patients. J Clin Hypertens (Greenwich) 2024; 26:1274-1283. [PMID: 39340432 PMCID: PMC11555541 DOI: 10.1111/jch.14905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/28/2024] [Accepted: 08/31/2024] [Indexed: 09/30/2024]
Abstract
Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804-0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non-hypertensive population (HR: 1.251; 95% CI: 1.100-1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension.
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Affiliation(s)
- Xuefei Hou
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Suru Yue
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Zihan Xu
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Xiaolin Li
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Yingbai Wang
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Jia Wang
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Xiaoming Chen
- Department of EndocrinologyAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Jiayuan Wu
- Clinical Research Service CenterAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
- Guangdong Engineering Research Center of Collaborative Innovation Technology of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong ProvinceAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
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Tu L, He Y, Xu Y. Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus. Neural Regen Res 2024; 19:1177-1178. [PMID: 37905852 PMCID: PMC11467938 DOI: 10.4103/1673-5374.385867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/23/2023] [Accepted: 09/02/2023] [Indexed: 11/02/2023] Open
Affiliation(s)
- Longlong Tu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
| | - Yanlin He
- Brain Glycemic and Metabolism Control Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Yong Xu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
- Department of Molecular and Cellular Biology; Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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Li Y, Zhang L, Liu W, Deng J, Liu J, Zhou Y, Feng L, Chen J. The impact of the stress hyperglycemia ratio on the risk of contrast-associated acute kidney injury in patients undergoing coronary angiography: a large real-world cohort study. Diabetol Metab Syndr 2024; 16:107. [PMID: 38773666 PMCID: PMC11107003 DOI: 10.1186/s13098-024-01345-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 05/03/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND Contrast-associated acute kidney injury (CA-AKI) is an important complication in the perioperative period of coronary angiography (CAG). Dysglycemia is closely associated with the occurrence of CA-AKI. However, the association between stress hyperglycemia and CA-AKI in patients undergoing CAG remains unclear. The study aims to investigate the association of the stress hyperglycemia ratio (SHR) and CA-AKI under CAG in a large real-world cohort. METHODS This was a retrospective observational study, and patients undergoing CAG were enrolled. SHR is calculated by dividing the random blood glucose with the estimated average glucose derived from the glycosylated hemoglobin (HbA1c), and subjects were divided into five groups according to SHR. The outcome was CA-AKI defined as an increase in serum creatinine of ≥ 0.3 mg/dL (26.5 μmol/L) or 1.5-fold higher than normal levels in 48 h. The association was assessed with logistic regression and restricted cubic spline analysis. RESULTS In 19,965 participants (men: 73.3%, mean age: 63.1 ± 10.8 years) undergoing CAG, a total of 1,621 CA-AKI cases occurred. There were reverse J-shaped associations between the SHR and CA-AKI after adjustment for other confounding factors. Moreover, SHR improved the predictive effectiveness of the traditional Mehran score (AUC 0.65 vs 0.63, P < 0.001), a predictive model of CA-AKI in patients undergoing percutaneous coronary intervention. CONCLUSIONS There were reverse J-shaped associations of SHR with CA-AKI risk among patients undergoing CAG, and the assessment of SHR before CAG may assist clinicians in identifying patients at higher risk of CA-AKI.
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Affiliation(s)
- Yuqi Li
- Department of Cardiology, Zhongshan City People's Hospital, Zhongshan, 528400, China
| | - Liting Zhang
- Department of Cardiology, Zhongshan City People's Hospital, Zhongshan, 528400, China
| | - Weiqi Liu
- Department of Cardiology, Zhongshan City People's Hospital, Zhongshan, 528400, China
| | - Jingru Deng
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Jin Liu
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Yang Zhou
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Li Feng
- Department of Cardiology, Zhongshan City People's Hospital, Zhongshan, 528400, China
| | - Jiyan Chen
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
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Du Q, Shao R, Wang W, Zhang H, Liao X, Wang Z, Yin Z, Ai Q, Mai K, Tang X, Wan M. Vitamin D3 Regulates Energy Homeostasis under Short-Term Fasting Condition in Zebrafish (Danio Rerio). Nutrients 2024; 16:1271. [PMID: 38732518 PMCID: PMC11085765 DOI: 10.3390/nu16091271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 04/05/2024] [Accepted: 04/19/2024] [Indexed: 05/13/2024] Open
Abstract
Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.
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Affiliation(s)
- Qingyang Du
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Rui Shao
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Wentao Wang
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Hui Zhang
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Xinmeng Liao
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Zhihao Wang
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Zhan Yin
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Qinghui Ai
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Kangsen Mai
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
| | - Xiao Tang
- Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden
| | - Min Wan
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China
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Marx N, Kolkailah AA, Rosenstock J, Johansen OE, Cooper ME, Alexander JH, Toto RD, Wanner C, Espeland MA, Mattheus M, Schnaidt S, Perkovic V, Gollop ND, McGuire DK. Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin: A Secondary Analysis of Randomized Clinical Trials. JAMA Cardiol 2024; 9:134-143. [PMID: 38170502 PMCID: PMC10765314 DOI: 10.1001/jamacardio.2023.4602] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 10/06/2023] [Indexed: 01/05/2024]
Abstract
Importance Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype. Objective To evaluate the associations between hypoglycemia and CV outcomes. Design, Setting, and Participants This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023. Intervention Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial. Main Outcomes and Measures The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode. Results In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze. Conclusions and Relevance This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both. Trial Registration ClinicalTrials.gov Identifier: NCT01897532 (CARMELINA) and NCT01243424 (CAROLINA).
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Affiliation(s)
- Nikolaus Marx
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany
| | - Ahmed A. Kolkailah
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas
| | | | - Odd Erik Johansen
- Therapeutic Area Cardiometabolism, Boehringer Ingelheim KS, Asker, Norway
| | - Mark E. Cooper
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - John H. Alexander
- Duke Clinical Research Institute, Duke Health, Durham, North Carolina
| | - Robert D. Toto
- Department of Internal Medicine, Division of Nephrology, The University of Texas Southwestern Medical Center, Dallas
| | - Christoph Wanner
- Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Mark A. Espeland
- Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Michaela Mattheus
- Biostatistics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany
| | - Sven Schnaidt
- Biostatistics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riß, Germany
| | - Vlado Perkovic
- Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales Sydney, Newtown, New South Wales, Australia
| | - Nicholas D. Gollop
- Therapeutic Area Cardiometabolism, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
| | - Darren K. McGuire
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas
- Parkland Health, Dallas, Texas
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Arecco A, Ottaviani S, Boschetti M, Renzetti P, Marinelli L. Diabetic striatopathy: an updated overview of current knowledge and future perspectives. J Endocrinol Invest 2024; 47:1-15. [PMID: 37578646 PMCID: PMC10776723 DOI: 10.1007/s40618-023-02166-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 07/24/2023] [Indexed: 08/15/2023]
Abstract
PURPOSE Diabetic striatopathy (DS) is a rare complication of poorly controlled diabetes mellitus (DM), characterized by hyperglycemia associated with chorea/ballism and characteristic reversible basal ganglia abnormalities on computed tomography (CT) and/or magnetic resonance imaging (MRI). We propose a narrative review of the literature on this topic, currently unknown to most, and about which physicians should be aware. We intend to summarize, critically review, and take to mean the evidence on this disorder, describing its typical features. METHODS We searched Pubmed for English-language sources using the following keywords in the title and the abstract: diabetic striatopathy, hyperglycemic non-ketotic hemichorea/hemiballism, chorea/hemichorea associated with non-ketotic hyperglycemia, diabetic hemiballism/hemichorea, chorea, hyperglycemia, and basal ganglia syndrome. We collected scientific articles, including case reports, reviews, systematic reviews, and meta-analyses from the years 1975 to 2023. We eliminated duplicate, non-English language or non-related articles. RESULTS Older Asian women are more frequently affected. Suddenly or insidiously hemichorea/hemiballism, mainly in the limbs, and high blood glucose with elevated HbA1c in the absence of ketone bodies have been observed. Furthermore, CT striatal hyperdensity and T1-weighted MRI hyperintensity have been observed. DS is often a treatable disease following proper hydration and insulin administration. Histopathological findings are variable, and no comprehensive hypothesis explains the atypical cases reported. CONCLUSION DS is a rare neurological manifestation of DM. If adequately treated, although treatment guidelines are lacking, the prognosis is good and life-threatening complications may occur occasionally. During chorea/hemiballism, we recommend blood glucose and HbA1c evaluation. Further studies are needed to understand the pathogenesis.
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Affiliation(s)
- A Arecco
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, 16132, Genoa, Italy
| | - S Ottaviani
- Section of Geriatrics, Department of Internal Medicine and Medical Specialties, University of Genova, 16132, Genoa, Italy
| | - M Boschetti
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, 16132, Genoa, Italy.
- IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy.
| | - P Renzetti
- IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy
| | - L Marinelli
- IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132, Genoa, Italy
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9
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Raafat S, Ahmed R, Mowafi I, Adel H. Relation between the Epicardial Fat Thickness and the Cardiac Conduction System in Children and Adolescents with Diabetes. Horm Res Paediatr 2023; 97:496-508. [PMID: 38071957 PMCID: PMC11446301 DOI: 10.1159/000535630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 11/29/2023] [Indexed: 10/03/2024] Open
Abstract
INTRODUCTION Atherosclerosis in patients with type 1 diabetes starts early in childhood with subclinical abnormalities. The epicardial fat thickness (EFT) is a novel method for detecting these early changes. Furthermore, electrocardiographic markers may be altered in patients with diabetes owing to early cardiovascular changes. This study aimed to determine the relationship between EFT and electrocardiographic markers in children with type 1 diabetes mellitus. METHODS Children with type 1 diabetes who were followed up at the Alexandria University Children's Hospital Diabetes Clinic were enrolled in this study. The study recruited three groups of participants, including 20 patients with a diabetes duration of less than 5 years, 20 patients with a diabetes duration of 5 years or more, and 20 healthy controls. All participants were evaluated with emphasis on anthropometric measurements, fasting blood glucose levels, and lipid profile. HbA1c levels were measured in the cohort with diabetes. All participants underwent electrocardiography for measurement of P-wave dispersion, corrected QT interval and its dispersion, and Tp-e measurement. Echocardiography was performed to measure the EFT. RESULTS Among all participants, EFT was significantly higher in children with a diabetes duration of ≥5 years (p = 0.009). Furthermore, P-wave dispersion was significantly prolonged in children with diabetes compared to that in nondiabetics (p = 0.041). There was a statistically significant correlation between EFT and P-wave dispersion in patients with diabetes aged ≥5 years (p = 0.021). CONCLUSIONS Measurement of EFT by echocardiography is a novel and easy way to predict early cardiovascular changes in children with diabetes, including conduction system disorders.
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Affiliation(s)
- Shaymaa Raafat
- Pediatric Endocrinology and Diabetes Unit, Pediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Reham Ahmed
- Pediatric Endocrinology and Diabetes Unit, Pediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ihsan Mowafi
- Pediatric Endocrinology and Diabetes Unit, Pediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Hani Adel
- Pediatric cardiology, Pediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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10
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Harris SB, Mohammedi K, Bertolini M, Carlyle M, Walker V, Zhou FL, Anderson JE, Seufert J. Patient and physician perspectives and experiences of basal insulin titration in type 2 diabetes in the United States: Cross-sectional surveys. Diabetes Obes Metab 2023; 25:3478-3489. [PMID: 37749746 DOI: 10.1111/dom.15240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/05/2023] [Accepted: 07/10/2023] [Indexed: 09/27/2023]
Abstract
AIM Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education. MATERIALS AND METHODS In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months. RESULTS In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%). CONCLUSIONS There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.
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Affiliation(s)
- Stewart B Harris
- Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada
| | | | | | | | | | | | | | - Jochen Seufert
- Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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11
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Inoue H, Kusano E, Shinkai Y, Ito H. A Case of Diabetic Chorea Secondary to Appetite Loss Due to COVID-19 Vaccination. Cureus 2023; 15:e49138. [PMID: 38130532 PMCID: PMC10733162 DOI: 10.7759/cureus.49138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2023] [Indexed: 12/23/2023] Open
Abstract
A 76-year-old woman with type 2 diabetes mellitus was admitted to our hospital with a complaint of involuntary movements of the limbs and face. Brain MRI demonstrated a bilateral high signal of putamen on the T1 weighted image, and she was diagnosed with diabetic chorea. She took a second dose of the COVID-19 vaccine 28 days before admission and lost her appetite. Consequently, her HbA1c level on admission decreased from 13.5% to 10.0% in 28 days. This case suggests that diabetic chorea could be induced by the rapid amelioration of a hyperglycemic state due to appetite loss after COVID-19 mRNA vaccination.
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Affiliation(s)
- Hideyuki Inoue
- Department of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, Tokyo, JPN
| | - Eiji Kusano
- Department of Internal Medicine, Wasshoi Clinic, Tokyo, JPN
| | | | - Hiroyuki Ito
- Department of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, Tokyo, JPN
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12
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Chambers ME, Nuibe EH, Reno-Bernstein CM. Brain Regulation of Cardiac Function during Hypoglycemia. Metabolites 2023; 13:1089. [PMID: 37887414 PMCID: PMC10608630 DOI: 10.3390/metabo13101089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/02/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023] Open
Abstract
Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this fall in glucose. The autonomic nervous system innervates the heart, and during hypoglycemia, can cause many changes. Clinical and animal studies have revealed changes in electrocardiograms during hypoglycemia. Cardiac repolarization defects (QTc prolongation) occur during moderate levels of hypoglycemia. When hypoglycemia is severe, it can be fatal. Cardiac arrhythmias are thought to be the major mediator of sudden death due to severe hypoglycemia. Both the sympathetic and parasympathetic nervous systems of the brain have been implicated in regulating these arrhythmias. Besides cardiac arrhythmias, hypoglycemia can have profound changes in the heart and most of these changes are exacerbated in the setting of diabetes. A better understanding of how the brain regulates cardiac changes during hypoglycemia will allow for better therapeutic intervention to prevent cardiovascular death associated with hypoglycemia in people with diabetes. The aim of this paper is to provide a narrative review of what is known in the field regarding how the brain regulates the heart during hypoglycemia.
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Affiliation(s)
| | | | - Candace M. Reno-Bernstein
- Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA (E.H.N.)
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13
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Obi MF, Sharma M, Namireddy V, Gargiulo P, Noel C, Hyun C, Gale BD. Variant of Wellen's syndrome in type 1 diabetic patient: A case report. World J Cardiol 2023; 15:462-468. [PMID: 37900265 PMCID: PMC10600782 DOI: 10.4330/wjc.v15.i9.462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 06/29/2023] [Accepted: 08/17/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Wellen's syndrome is a form of acute coronary syndrome associated with proximal left anterior descending artery (LAD) stenosis and characteristic electrocardiograph (ECG) patterns in pain free state. The abnormal ECG pattern is classified into type A (biphasic T waves) and type B (deeply inverted T waves), based on the T wave pattern seen in the pericodial chest leads. CASE SUMMARY We present the case of a 37-year-old male with history of type 1 diabetes mellitus (T1DM), gastroparesis, mild peripheral artery disease and right toe cellulitis on IV antibiotics who presented to the emergency department with nausea, vomiting and abdominal pain for 3 d and as a result couldn't take his insulin. Noted to have fasting blood sugar 392 mg/dL. Admitted for diabetic gastroparesis. During the hospital course, the patient was asymptomatic and denied any chest pain. On admission, No ECG and troponin draws were performed. On day 2, the patient became hypoxic with oxygen saturation 80% on room air, intermittent mild right-sided chest pain which he attributed to vomiting from his gastroparesis. Initial ECG done was significant for Biphasic T wave changes in leads V2 and V3 and elevated high sensitivity troponin. Patient was transitioned to cardiac intensive care unit and cardiac catheterization performed with result significant for extensive coronary artery disease. CONCLUSION This case highlights an exceptional manifestation of Wellen's syndrome, wherein the right coronary artery and circumflex artery display a remarkable 100% constriction, alongside a proximal LAD stenosis of 90%-95%. Notably, this occurrence transpired in a patient grappling with extensive complications arising from T1DM. Moreover, it underscores the utmost significance of promptly recognizing the presence of Wellen's syndrome and swiftly initiating appropriate medical intervention.
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Affiliation(s)
- Mukosolu Florence Obi
- Internal Medicine, Wyckoff Heights Medical Center, Brooklyn, NY 11237, United States.
| | - Manjari Sharma
- Internal Medicine, Wyckoff Heights Medical Center, Brooklyn, NY 11237, United States
| | - Vikhyath Namireddy
- Clinical Rotations, St Georges University, School of Medicine, True Blue 96038, Grenada
| | - Paul Gargiulo
- Internal Medicine, Wyckoff Heights Medical Center, Brooklyn, NY 11237, United States
| | - Chelsea Noel
- Clinical Rotations, St Georges University, School of Medicine, True Blue 96038, Grenada
| | - Cho Hyun
- Internal Medicine, Wyckoff Heights Medical Center, Brooklyn, NY 11237, United States
| | - Blossom De Gale
- Clinical Rotations, St Georges University, School of Medicine, True Blue 96038, Grenada
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14
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Tokarek J, Budny E, Saar M, Stańczak K, Wojtanowska E, Młynarska E, Rysz J, Franczyk B. Molecular Processes Involved in the Shared Pathways between Cardiovascular Diseases and Diabetes. Biomedicines 2023; 11:2611. [PMID: 37892985 PMCID: PMC10604380 DOI: 10.3390/biomedicines11102611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/17/2023] [Accepted: 09/18/2023] [Indexed: 10/29/2023] Open
Abstract
Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD-with the focus on the molecular mechanisms and the role of the microbiota.
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Affiliation(s)
- Julita Tokarek
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Emilian Budny
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Maciej Saar
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Kamila Stańczak
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Ewa Wojtanowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
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15
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Shao H, Shi L, Fonseca V, Alsaleh AJO, Gill J, Nicholls C. Cost-effectiveness analysis of once-daily insulin glargine 300 U/mL versus insulin degludec 100 U/mL using the BRAVO diabetes model. Diabet Med 2023; 40:e15112. [PMID: 37035994 DOI: 10.1111/dme.15112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 04/04/2023] [Accepted: 04/07/2023] [Indexed: 04/11/2023]
Abstract
AIMS A cost-effectiveness analysis was conducted to compare insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in insulin-naïve adults with type 2 diabetes (T2D) sub-optimally controlled with oral anti-diabetic drugs (OADs). METHODS The BRAVO diabetes model was used to assess costs and outcomes for once-daily Gla-300 versus once-daily IDeg-100 from a US healthcare sector perspective. Baseline clinical data were based on BRIGHT, a 24-week, non-inferiority, randomised control trial comparing Gla-300 and IDeg-100 in adults with T2D sub-optimally controlled with OADs (with or without glucagon-like peptide-1 receptor agonists). Treatment costs were based on doses observed in BRIGHT as well as net prices. Costs associated with complications were based on published literature. Lifetime costs (US$) and quality-adjusted life-years (QALYs) were predicted and used to calculate incremental cost-effectiveness ratio estimates; extensive scenario and sensitivity analyses were conducted. RESULTS Overall lifetime medical costs were estimated to be $327,904 and $330,154 for people receiving Gla-300 and IDeg-100, respectively; insulin costs were $43,477 and $44,367, respectively. People receiving Gla-300 gained 8.024 QALYs and 18.55 life-years, while people receiving IDeg-100 gained 7.997 QALYs and 18.52 life-years. Because Gla-300 was associated with a cost-saving of $2250 and 0.027 additional QALYs, it was considered to be dominant compared with IDeg-100. Results of the scenario and sensitivity analyses confirmed the robustness of the base case results. CONCLUSION Gla-300 was the dominant treatment option compared with IDeg-100 based on the willingness-to-pay threshold of $50,000/QALY. Results remained robust against a wide range of alternative assumptions on key parameters.
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Affiliation(s)
- Hui Shao
- Hubert Department of Global Health, Emory Rollins School of Public Health, Atlanta, Georgia, USA
- Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA
| | - Lizheng Shi
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA
| | - Vivian Fonseca
- School of Medicine, Tulane University, New Orleans, Louisiana, USA
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16
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Herold M, Szasz AM, Szentmartoni G, Martinek E, Madar-Dank V, Barna AJ, Mohacsi R, Somogyi A, Dank M, Herold Z. Influence of the duration of type 2 diabetes mellitus on colorectal cancer outcomes. Sci Rep 2023; 13:12985. [PMID: 37563292 PMCID: PMC10415401 DOI: 10.1038/s41598-023-40216-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 08/07/2023] [Indexed: 08/12/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested.
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Affiliation(s)
- Magdolna Herold
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, 1088, Hungary
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Gyongyver Szentmartoni
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Emoke Martinek
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Viktor Madar-Dank
- Department of the Institute for Dispute Resolution, New Jersey City University, Jersey City, NJ, 07311, USA
| | - Andras Jozsef Barna
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
- Department of Obstetrics and Gynecology, Saint Pantaleon Hospital, Dunaujvaros, 2400, Hungary
| | - Reka Mohacsi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Aniko Somogyi
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, 1088, Hungary
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary.
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17
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Tu L, Bean JC, He Y, Liu H, Yu M, Liu H, Zhang N, Yin N, Han J, Scarcelli NA, Conde KM, Wang M, Li Y, Feng B, Gao P, Cai ZL, Fukuda M, Xue M, Tong Q, Yang Y, Liao L, Xu J, Wang C, He Y, Xu Y. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. J Clin Invest 2023; 133:e163391. [PMID: 37261917 PMCID: PMC10348766 DOI: 10.1172/jci163391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 05/30/2023] [Indexed: 06/03/2023] Open
Abstract
Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.
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Affiliation(s)
- Longlong Tu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Jonathan C. Bean
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Yang He
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Hailan Liu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Meng Yu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Hesong Liu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Nan Zhang
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Na Yin
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Junying Han
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Nikolas A. Scarcelli
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Kristine M. Conde
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Mengjie Wang
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Yongxiang Li
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Bing Feng
- Brain glycemic and metabolism control department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Peiyu Gao
- Brain glycemic and metabolism control department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Zhao-Lin Cai
- Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, USA
| | - Makoto Fukuda
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Mingshan Xue
- Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, USA
| | - Qingchun Tong
- Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Yongjie Yang
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Lan Liao
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
| | - Jianming Xu
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
| | - Chunmei Wang
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Yanlin He
- Brain glycemic and metabolism control department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Yong Xu
- Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
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18
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Torres Roldan VD, Urtecho M, Nayfeh T, Firwana M, Muthusamy K, Hasan B, Abd-Rabu R, Maraboto A, Qoubaitary A, Prokop L, Lieb DC, McCall AL, Wang Z, Murad MH. A Systematic Review Supporting the Endocrine Society Guidelines: Management of Diabetes and High Risk of Hypoglycemia. J Clin Endocrinol Metab 2023; 108:592-603. [PMID: 36477885 DOI: 10.1210/clinem/dgac601] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Indexed: 12/12/2022]
Abstract
CONTEXT Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. OBJECTIVE To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. METHODS We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. RESULTS We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. CONCLUSION This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.
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Affiliation(s)
| | - Meritxell Urtecho
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
| | - Mohammed Firwana
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
| | | | - Bashar Hasan
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
| | - Rami Abd-Rabu
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
| | - Andrea Maraboto
- Knowledge and Evaluation Research Unit, Department of Medicine, Mayo Clinic, Rochester, MN 55902, USA
| | - Amjad Qoubaitary
- College of Arts and Science, University of San Francisco, San Francisco, CA 94117, USA
| | - Larry Prokop
- Department of Library Services, Mayo Clinic, Rochester, MN 55902, USA
| | - David C Lieb
- Division of Endocrine and Metabolic Disorders, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23501-1980, USA
| | - Anthony L McCall
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
| | - Zhen Wang
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA
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19
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Lee S, Lee S, Kim KM, Shin JH. Usefulness of continuous glucose monitoring of blood glucose control in patients with diabetes undergoing hemodialysis: A pilot study. Front Med (Lausanne) 2023; 10:1145470. [PMID: 37089609 PMCID: PMC10117913 DOI: 10.3389/fmed.2023.1145470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/21/2023] [Indexed: 04/25/2023] Open
Abstract
Background Blood glucose stability has recently been considered important in the treatment of diabetes. Both hypoglycemia and hyperglycemia can frequently occur in patients with diabetes undergoing hemodialysis. This study aimed to determine the usefulness of continuous glucose monitoring (CGM) for glycemic control and glycemic variability stabilization in patients with diabetes undergoing hemodialysis. Materials and methods Eighteen patients aged ≥18 years with type 1 or 2 diabetes and ≥3 months on hemodialysis at the Eulji Medical Center, Daejeon, Republic of Korea between November 2021 and May 2022 were included. Patients underwent 7 days CGM twice: the baseline study period (T0) and the follow-up study period (T1), at a 12 weeks interval. Physicians modified the treatment strategy according to the T0 results, and then patients conducted T1. As indicators of glycemic control, the mean glucose levels, glycated hemoglobin A1c (HbA1c), and time in range were measured. As indicators of glycemic variability, standard deviation (SD) and % coefficient variation (%CV) were measured. Results Data from 18 patients were analyzed. The mean glucose levels, HbA1c, SD, and %CV improved in T1 compared to T0 (P < 0.05). During T0, the mean glucose level was significantly lower on a day with hemodialysis than on a day without (P < 0.05), and SD and %CV were significantly higher on a day with hemodialysis than on a day without (P < 0.05). After the physicians modified the treatment according to the T0 results, there were no differences in the mean glucose levels, SD, and %CV between days with and without hemodialysis during T1. Conclusion Continuous glucose monitoring could be a promising tool for individualizing treatment strategies in patients with diabetes undergoing hemodialysis.
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Sanchez-Rangel E, Deajon-Jackson J, Hwang JJ. Pathophysiology and management of hypoglycemia in diabetes. Ann N Y Acad Sci 2022; 1518:25-46. [PMID: 36202764 DOI: 10.1111/nyas.14904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
In the century since the discovery of insulin, diabetes has changed from an early death sentence to a manageable chronic disease. This change in longevity and duration of diabetes coupled with significant advances in therapeutic options for patients has fundamentally changed the landscape of diabetes management, particularly in patients with type 1 diabetes mellitus. However, hypoglycemia remains a major barrier to achieving optimal glycemic control. Current understanding of the mechanisms of hypoglycemia has expanded to include not only counter-regulatory hormonal responses but also direct changes in brain glucose, fuel sensing, and utilization, as well as changes in neural networks that modulate behavior, mood, and cognition. Different strategies to prevent and treat hypoglycemia have been developed, including educational strategies, new insulin formulations, delivery devices, novel technologies, and pharmacologic targets. This review article will discuss current literature contributing to our understanding of the myriad of factors that lead to the development of clinically meaningful hypoglycemia and review established and novel therapies for the prevention and treatment of hypoglycemia.
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Affiliation(s)
- Elizabeth Sanchez-Rangel
- Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Jelani Deajon-Jackson
- Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Janice Jin Hwang
- Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA.,Division of Endocrinology, Department of Internal Medicine, University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, USA
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21
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McCrimmon RJ, Home P, Cheng A, Giorgino F, Fonseca V, Souhami E, Alvarez A, Picard P, Rosenstock J. Hypoglycaemia events with iGlarLixi versus premix biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes advancing from basal insulin: An analysis of the SoliMix trial. Diabetes Obes Metab 2022; 24:2391-2399. [PMID: 36054624 PMCID: PMC9804337 DOI: 10.1111/dom.14825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 01/05/2023]
Abstract
AIMS To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial. MATERIALS AND METHODS This exploratory analysis of SoliMix used logistic regression and negative binomial regression analyses to assess between-treatment differences in the incidence and rates of hypoglycaemia by time of day. A negative binomial model was used to derive estimated annualized hypoglycaemia rates as a function of HbA1c. RESULTS iGlarLixi was associated with lower incidence and rates of American Diabetes Association Level 2 (<54 mg/dL [<3.0 mmol/L]) hypoglycaemia during both night and day versus BIAsp 30. Incidence and rates of Level 1 (<70 to ≥54 mg/dL [<3.9 to ≥3.0 mmol/L]) hypoglycaemia were also mostly shown to be reduced with iGlarLixi versus BIAsp 30. Severe (Level 3) events were too few for analysis (n = 3). iGlarLixi was associated with lower modelled event rates of Level 2 and Level 1 hypoglycaemia over a wide range of HbA1c levels versus BIAsp 30. CONCLUSIONS These results show that the lower HbA1c levels and weight benefit seen with iGlarLixi versus premixed BIAsp 30 in people with type 2 diabetes advancing their basal insulin therapy in the SoliMix trial are also accompanied by a lower risk of hypoglycaemia at any time of day and across a broad range of HbA1c levels.
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Affiliation(s)
- Rory J. McCrimmon
- Division of Systems Medicine, School of MedicineUniversity of DundeeDundeeUK
| | - Philip Home
- Translational and Clinical Research InstituteNewcastle UniversityNewcastle upon TyneUK
| | - Alice Cheng
- Department of MedicineUniversity of TorontoTorontoOntarioCanada
| | - Francesco Giorgino
- Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic DiseasesUniversity of Bari Aldo MoroBariItaly
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Laha S, Rajput A, Laha SS, Jadhav R. A Concise and Systematic Review on Non-Invasive Glucose Monitoring for Potential Diabetes Management. BIOSENSORS 2022; 12:965. [PMID: 36354474 PMCID: PMC9688383 DOI: 10.3390/bios12110965] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/23/2022] [Accepted: 10/26/2022] [Indexed: 06/16/2023]
Abstract
The current standard of diabetes management depends upon the invasive blood pricking techniques. In recent times, the availability of minimally invasive continuous glucose monitoring devices have made some improvements in the life of diabetic patients however it has its own limitations which include painful insertion, excessive cost, discomfort and an active risk due to the presence of a foreign body under the skin. Due to all these factors, the non-invasive glucose monitoring has remain a subject of research for the last two decades and multiple techniques of non-invasive glucose monitoring have been proposed. These proposed techniques have the potential to be evolved into a wearable device for non-invasive diabetes management. This paper reviews research advances and major challenges of such techniques or methods in recent years and broadly classifies them into four types based on their detection principles. These four methods are: optical spectroscopy, photoacoustic spectroscopy, electromagnetic sensing and nanomaterial based sensing. The paper primarily focuses on the evolution of non-invasive technology from bench-top equipment to smart wearable devices for personalized non-invasive continuous glucose monitoring in these four methods. With the rapid evolve of wearable technology, all these four methods of non-invasive blood glucose monitoring independently or in combination of two or more have the potential to become a reality in the near future for efficient, affordable, accurate and pain-free diabetes management.
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Affiliation(s)
- Soumyasanta Laha
- Department of Electrical and Computer Engineering, California State University, Fresno, Fresno, CA 93740, USA
| | - Aditi Rajput
- Department of Electrical and Computer Engineering, California State University, Fresno, Fresno, CA 93740, USA
| | - Suvra S Laha
- Centre for Nano Science and Engineering (CeNSE), Indian Institute of Science, Bangalore 560012, India
| | - Rohan Jadhav
- Department of Public Health, California State University, Fresno, Fresno, CA 93740, USA
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Cha SA, Yun JS, Kim GH, Ahn YB. Impact of hypoglycemia at the time of hospitalization for heart failure from emergency department on major adverse cardiovascular events in patients with and without type 2 diabetes. Cardiovasc Diabetol 2022; 21:218. [PMID: 36271363 PMCID: PMC9585717 DOI: 10.1186/s12933-022-01651-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 09/23/2022] [Indexed: 11/15/2022] Open
Abstract
Background Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes. Methods From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality. Results During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0–82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4–25.1] vs. 23.8 [21.3–26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0–80.7] mL/min/1.73 m2 vs. 69.2 [45.8–89.5] mL/min/1.73 m2) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04–5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86–2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26–5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81–2.16; compared to the reference group (group without T2DM or hypoglycemia). Conclusions T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization.
Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01651-0.
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Affiliation(s)
- Seon-Ah Cha
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea.,Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Republic of Korea
| | - Jae-Seung Yun
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea
| | - Gee-Hee Kim
- Division of Cardiology, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yu-Bae Ahn
- Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Seoul, Republic of Korea.
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Qu F, Shi Q, Wang Y, Shen Y, Zhou K, Pearson ER, Li S. Visit-to-visit glycated hemoglobin A1c variability in adults with type 2 diabetes: a systematic review and meta-analysis. Chin Med J (Engl) 2022; 135:2294-2300. [PMID: 35952315 PMCID: PMC9771337 DOI: 10.1097/cm9.0000000000002073] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes. METHODS We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS). RESULTS In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was l.89 with 95% confidence interval (95% CI) l.46-2.45 (HbAlc-CV l.47, 95% CI l.26-l.72; HVS l.67, 95% CI l.34-2.09). CONCLUSIONS High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes.
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Affiliation(s)
- Furong Qu
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Qingyang Shi
- Department of Guideline and Rapid Recommendation, Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yang Wang
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yanjiao Shen
- Department of Guideline and Rapid Recommendation, Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Kaixin Zhou
- School of Life Science, University of Chinese Academy of Science, Beijing 100101, China
| | - Ewan R. Pearson
- Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
| | - Sheyu Li
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Department of Guideline and Rapid Recommendation, Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
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25
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Sendekie AK, Netere AK, Belachew EA. Hypoglycemic events and glycemic control effects between NPH and premixed insulin in patients with type 2 diabetes mellitus: A real-world experience at a comprehensive specialized hospital in Ethiopia. PLoS One 2022; 17:e0275032. [PMID: 36149907 PMCID: PMC9506660 DOI: 10.1371/journal.pone.0275032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/09/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Though initiation of insulin results in a significant change in glycemic levels, treating patients without significant hypoglycemic events remains difficult in diabetes patients initiated with different insulin-based regimens. This study assessed the association of hypoglycemic incidence and glycemic control between NPH and premixed insulin regimens in patients with type 2 diabetes mellitus (T2DM). METHODS This was a retrospective observational study in patients with T2DM who were treated with insulin-based therapy from 2015 to 2020 at the University of Gondar Comprehensive Specialized hospital. Average fasting blood glucose (FBG) between NPH and premixed insulin regimens was compared using an independent t-test. The Association of NPH and premixed insulin regimens with hypoglycemic incidences and glycemic control was examined by a logistic regression model. P < 0.05 was statistically significant. RESULTS From 405 participants, more than half (55.3%) were males with a mean age of 59.2(±9.1) years. Baseline mean HbA1C and FBG levels were 12.73(±1.1) % and 347.7(±48.5) mg/dl, respectively. Within a one-year follow-up period of insulin initiation, the rate of hypoglycemia was 13.1%. The incidence of hypoglycemia was significantly higher in patients initiated with premixed insulin compared with NPH insulin regimens (P < 0.001). After one year of insulin initiation, HbA1C decreased from 12.7 to 7.6 and from 12.8 to 7.3% and FBG levels decreased from 347.5 to 160.7 and from 348.2 to 147.3 mg/dl following initiation of NPH and premixed insulin, respectively. Patients treated with premixed-based insulin were found more likely to achieve target FBG compared with patients treated with NPH insulin regimens after one year of initiation (P = 0.02). CONCLUSION Premixed insulin-based regimen has found to have a higher hypoglycemic incidence, but a better level of glycemic control compared to NPH insulin-based therapy. Therefore, patients initiated with premixed insulin need to be highly vigilant and motivated to recognize the symptoms of hypoglycemia.
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Affiliation(s)
- Ashenafi Kibret Sendekie
- Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Adeladlew Kassie Netere
- Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Eyayaw Ashete Belachew
- Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
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Evaluation of the relationship between hemodialysis-related glycemic variability and hormonal profiles in patients with type 2 diabetes on hemodialysis: a pilot study. RENAL REPLACEMENT THERAPY 2022. [DOI: 10.1186/s41100-022-00429-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The number of dialysis patients with diabetes is currently increasing in Japan and a similar proportion worldwide. It was suggested that approximately 20% of these patients had hypoglycemia after dialysis session and most of these hypoglycemia were unconscious. Furthermore, it was suggested that glucose variabilities induced by hemodialysis may be related to insulin and insulin-counter hormones, such as glucagon, adrenocorticotropic hormone (ACTH), and cortisol and growth hormone, but conclusive evidence has not still been obtained.
Methods
We investigated in detail the glucose and hormonal profiles in 7 patients with type 2 diabetes on hemodialysis (all male, HbA1c 6.8 ± 2.1%, glycated albumin 24.7 ± 10.2%). All participants were attached continuous glucose monitoring (iPro2®). Blood glucose level, C-peptide immunoreactivity, plasma glucagon, ACTH, cortisol and growth hormone were measured by 7 points blood tests at before breakfast, after breakfast (predialysis), 2 h and 4 h after starting dialysis, after lunch and before/after dinner on the dialysis day and 6 points at before/after each meal on the non-dialysis day, and these relationship with blood glucose dynamics were examined. The meal contents were set to the indicated energy amount, and the same menu was served daily for breakfast, lunch, and dinner on dialysis and non-dialysis days of this study period. In addition, the start time of lunch on non-dialysis day was the same as the start time of lunch on the dialysis day.
Results
Serum C-peptide level was significantly increased by taking breakfast and lunch on the hemodialysis day, significantly decreased during hemodialysis, and was significantly lower before and after lunch on the hemodialysis day than on the non-hemodialysis day. Plasma glucagon level significantly decreased during hemodialysis and that before lunch on hemodialysis day was significantly lower than on non-hemodialysis day. ACTH, cortisol, and growth hormone did not show any changes related to hemodialysis.
Conclusions
It was suggested that C-peptide and glucagon play an important role in hemodialysis-related glycemic variabilities in patients with type 2 diabetic hemodialysis.
Trial registration UMIN Clinical Trial Registry (Registration Number UMIN000018707). Registered 18 August 2015, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000021647.
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Danda VSR, Srinivas Rao P, Konda C, Lodha P. Acanthosis nigricans in Insulinoma: Reversible experiments of the nature. Med J Armed Forces India 2022; 78:S315-S318. [PMID: 36147425 PMCID: PMC9485756 DOI: 10.1016/j.mjafi.2019.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 06/11/2019] [Indexed: 10/25/2022] Open
Abstract
Acanthosis Nigricans is considered to be a skin marker of insulin resistance and atherosclerosis. It is rarely reported in cases of insulinoma where there is marked hyperinsulinaemia. We report two cases of insulinoma with acanthosis nigricans which regressed, concomitant with significant weight loss and reduction in blood pressure following surgical resection. This strengthens the hypothesis that hyperinsulinaemia is responsible for Acanthosis nigricans and atherosclerotic risk factors.
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Affiliation(s)
- Vijay Sheker R. Danda
- Department of Endocrinology, Gandhi Medical College/Gandhi Hospital, Musheerabad, Hyderabad, Telangana, 500003, India
| | - Paidipally Srinivas Rao
- Department of Endocrinology, Gandhi Medical College/Gandhi Hospital, Musheerabad, Hyderabad, Telangana, 500003, India
| | - Chaitanya Konda
- Department of Endocrinology, Gandhi Medical College/Gandhi Hospital, Musheerabad, Hyderabad, Telangana, 500003, India
| | - Piyush Lodha
- Department of Endocrinology, Gandhi Medical College/Gandhi Hospital, Musheerabad, Hyderabad, Telangana, 500003, India
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Miller RG, Costacou T. Cardiovascular Disease in Adults with Type 1 Diabetes: Looking Beyond Glycemic Control. Curr Cardiol Rep 2022; 24:1467-1475. [PMID: 35947333 DOI: 10.1007/s11886-022-01763-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE OF REVIEW Despite improvements in treatment, people with type 1 diabetes continue to have increased cardiovascular disease (CVD) risk. Glycemic control does not fully explain this excess CVD risk, so a greater understanding of other risk factors is needed. RECENT FINDINGS The authors review the relationship between glycemia and CVD risk in adults with type 1 diabetes and summarize evidence regarding other factors that may explain risk beyond glycemia. Insulin resistance, weight gain, sex differences, genetics, inflammation, emerging markers of risk, including lipid subclasses and epigenetic modifications, and future directions are discussed. As glycemic control improves, an increased focus on other CVD risk factors is warranted in type 1 diabetes. Novel markers and precision medicine approaches may improve CVD prediction, but a lack of type 1 diabetes-specific guidelines for lipids, blood pressure, and physical activity are likely impediments to optimal CVD prevention in this high-risk population.
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Affiliation(s)
- Rachel G Miller
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 130 N. Bellefield Avenue, Pittsburgh, PA, 15213, USA
| | - Tina Costacou
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 130 N. Bellefield Avenue, Pittsburgh, PA, 15213, USA.
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Hampton GS, Bartlette K, Nadeau KJ, Cree-Green M, Diniz Behn C. Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity. Front Physiol 2022; 13:895118. [PMID: 35991189 PMCID: PMC9388790 DOI: 10.3389/fphys.2022.895118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 07/08/2022] [Indexed: 12/30/2022] Open
Abstract
Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset obesity. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of tissue-specific insulin responses. Changes to the dynamics of insulin responses would alter glycemic control in response to a glucose challenge. To investigate the dynamics of insulin acting on adipose tissue, we developed a novel differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during an oral glucose tolerance test in female adolescents with obesity and IR. We compared these dynamics to the dynamics of insulin acting on muscle and liver as assessed with the oral minimal model applied to glucose and insulin data collected under the same protocol. We found that the action of insulin on glycerol peaks approximately 67 min earlier (p < 0.001) and follows the dynamics of plasma insulin more closely compared to insulin action on glucose as assessed by the parameters representing the time constants for insulin action on glucose and glycerol (p < 0.001). These findings suggest that the dynamics of insulin action show tissue-specific differences in our IR adolescent population, with adipose tissue responding to insulin more quickly compared to muscle and liver. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into the progression of metabolic disease in patient populations with diverse metabolic phenotypes.
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Affiliation(s)
- Griffin S. Hampton
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United States
| | - Kai Bartlette
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United States
| | - Kristen J. Nadeau
- Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States,Ludeman Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Melanie Cree-Green
- Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States,Ludeman Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Cecilia Diniz Behn
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United States,Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States,*Correspondence: Cecilia Diniz Behn,
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Meraz M, Vernon-Carter E, Bello-Perez L, Alvarez-Ramirez J. Mathematical modeling of gastrointestinal starch digestion-blood glucose-insulin interactions. Biomed Signal Process Control 2022. [DOI: 10.1016/j.bspc.2022.103812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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La Rose AM, Groenen AG, Halmos B, Bazioti V, Rutten MG, Krishnamurthy KA, Koster MH, Kloosterhuis NJ, Smit M, Havinga R, Mithieux G, Rajas F, Kuipers F, Oosterveer MH, Westerterp M. Increased atherosclerosis in a mouse model of glycogen storage disease type 1a. Mol Genet Metab Rep 2022; 31:100872. [PMID: 35782606 PMCID: PMC9248218 DOI: 10.1016/j.ymgmr.2022.100872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 04/16/2022] [Indexed: 12/02/2022] Open
Abstract
Glycogen storage disease type 1a (GSD Ia) is an inborn error of carbohydrate metabolism. Despite severe hyperlipidemia, GSD Ia patients show limited atherogenesis compared to age-and-gender matched controls. Employing a GSD Ia mouse model that resembles the severe hyperlipidemia in patients, we here found increased atherogenesis in GSD Ia. These data provide a rationale for investigating atherogenesis in GSD Ia in a larger patient cohort.
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Affiliation(s)
- Anouk M. La Rose
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Anouk G. Groenen
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Benedek Halmos
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Venetia Bazioti
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Martijn G.S. Rutten
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Kishore A. Krishnamurthy
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Mirjam H. Koster
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Niels J. Kloosterhuis
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Marieke Smit
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Rick Havinga
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Gilles Mithieux
- Université Claude Bernard Lyon 1, Université de Lyon, INSERM UMR-S1213, Lyon, France
| | - Fabienne Rajas
- Université Claude Bernard Lyon 1, Université de Lyon, INSERM UMR-S1213, Lyon, France
| | - Folkert Kuipers
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Maaike H. Oosterveer
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Marit Westerterp
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Corresponding author at: Department of Pediatrics, University Medical Center Groningen, ERIBA Building 3226 room 04.14, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
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Huang L, Chen Z, Chen R, Lin L, Ren L, Zhang M, Liu L. Increased fatty acid metabolism attenuates cardiac resistance to β-adrenoceptor activation via mitochondrial reactive oxygen species: A potential mechanism of hypoglycemia-induced myocardial injury in diabetes. Redox Biol 2022; 52:102320. [PMID: 35462320 PMCID: PMC9046456 DOI: 10.1016/j.redox.2022.102320] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 04/18/2022] [Indexed: 01/18/2023] Open
Abstract
The mechanism of severe hypoglycemia (SH)-induced cardiovascular disease in diabetes remains unknown. Our previous study found that SH inhibits cardiac function and lipid metabolism in diabetic mice. Conversely, in nondiabetic mice, SH does not induce cardiac dysfunction but promotes cardiac lipid metabolism. This study aims to clarify the effect of increased fatty acid metabolism on the resistance of cardiomyocytes to β-adrenoceptor activation during hypoglycemia in diabetes. Results revealed that cardiomyocytes with enhanced lipid metabolism were more vulnerable to damage due to β-adrenoceptor activation, which presented as decreased cell viability, disorder of mitochondrial structure, dissipation of mitochondrial membrane potential, dysfunction of mitochondrial oxidative phosphorylation, nonapoptotic damage, and accumulation of ROS and calcium from mitochondria to cytoplasm, all of which were partially reversed by mitochondrial antioxidant Mito-TEMPO. The SH-induced cardiac dysfunction, and reduction of myocardial energy metabolism in diabetic mice were rescued by Mito-TEMPO. Our findings indicate that high fatty acid metabolism crippled cardiac resistance to β-adrenoceptor hyperactivation, with mitochondrial ROS playing a pivotal role in this process. Reducing mitochondrial ROS in diabetes could disrupt this synergistic effect and prevent poor cardiac outcomes caused by SH.
Fatty acid metabolism lowers cardiac resistance to β-adrenoceptor activation via mtROS. Pretreatment with mitochondrial antioxidants prevents SH-induced cardiac outcomes. This synergistic effect might explicate the progression of other CV diseases.
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Affiliation(s)
- Lishan Huang
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhou Chen
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Ruiyu Chen
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Lu Lin
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Lingjia Ren
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Meilian Zhang
- Department of Ultrasound, Fujian Province Hospital for Women and Children, Fuzhou, China
| | - Libin Liu
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China.
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Hou K, Zhang S, Wu Z, Zhu D, Chen F, Lei ZN, Liu W, Xiao C, Chen ZS. Reconstruction of intestinal microecology of type 2 diabetes by fecal microbiota transplantation: Why and how. Bosn J Basic Med Sci 2022; 22:315-325. [PMID: 34761734 PMCID: PMC9162745 DOI: 10.17305/bjbms.2021.6323] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/13/2021] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia due to insulin resistance. Mounting evidence has correlated T2D to alterations in the composition of gut microbiota. Accordingly, targeting the gut microbiota has become an emerging strategy for T2D management. The aim of this article is to get a better insight into the rationale for targeting gut microbiota in T2D treatment. Thus, we herein reviewed the change of gut microbiota composition in T2D, factors shaping gut microbiota, and potential mechanisms behind the contribution of gut microbiota to T2D pathogenesis. At present, it has become possible to use intestinal microorganism capsules, bacteria liquid, and other preparations to carry out fecal microbiota transplantation for the treatment and intervention of T2D with insulin resistance and immune-mediated type 1 diabetes (T1D).
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Affiliation(s)
- Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, China
- Department of Endocrine and Metabolic Diseases, Shantou University Medical College, Shantou University, Shantou, Guangdong, China
| | - Shuo Zhang
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, China
- Department of Endocrine and Metabolic Diseases, Shantou University Medical College, Shantou University, Shantou, Guangdong, China
| | - Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, China
- Department of Endocrine and Metabolic Diseases, Shantou University Medical College, Shantou University, Shantou, Guangdong, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, China
| | - Fengwu Chen
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, China
| | - Zi-Ning Lei
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, New York, USA
| | - Weiting Liu
- Department of Teaching and Research Section, College of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
- Weiting Liu, College of Nursing, Anhui University of Chinese Medicine, No. 350, Longzihu Road, Hefei, Anhui, China
| | - Chuanxing Xiao
- Department of Pharmacy, College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Corresponding authors: Chuanxing Xiao, College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, No. 1, Huatuo Road, Fuzhou, Fujian, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, New York, USA
- Zhe-Sheng Chen, Institute for Biotechnology, St. John’s University, 8000 Utopia Parkway, Queens, New York, NY, USA
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Karayiannides S, Norhammar A, Landstedt-Hallin L, Friberg L, Pia L. Prognostic impact of type 1 and type 2 diabetes mellitus in atrial fibrillation and the effect of severe hypoglycaemia: A nationwide cohort study. Eur J Prev Cardiol 2022; 29:1759-1769. [PMID: 35580601 DOI: 10.1093/eurjpc/zwac093] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 04/24/2022] [Accepted: 05/11/2022] [Indexed: 11/14/2022]
Abstract
AIMS To compare prognosis between individuals without diabetes, type 1 and type 2 diabetes in a nationwide atrial fibrillation cohort in Sweden and study the significance of severe hypoglycaemia. METHODS Using data from all-inclusive national registers, 309,611 patients with non-valvular atrial fibrillation were enrolled during 2013-2014. Of these, 2,221 had type 1 and 58,073 had type 2 diabetes. Patients were followed for all-cause mortality until March 27, 2017, and for myocardial infarction, ischaemic stroke and first-ever diagnosis of heart failure or dementia until December 31, 2015. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox and competing risk regression. RESULTS Using individuals without diabetes as reference (HR = 1), the adjusted HRs in type 1 versus type 2 diabetes were for mortality 1.87 (CI 1.73-2.02) vs. 1.51 (CI 1.47-1.55), heart failure 1.59 (CI 1.42-1.78) vs. 1.41 (CI 1.34-1.48), myocardial infarction 2.49 (CI 2.17-2.85) vs. 1.70 (CI 1.59-1.81), ischaemic stroke 1.59 (CI 1.35-1.87) vs. 1.31 (CI 1.22-1.40) and dementia 1.46 (CI 1.15-1.85) vs. 1.28 (CI 1.18-1.40). Among individuals with type 2 diabetes, those with previous severe hypoglycaemia had increased risk of mortality (HR 1.26; CI 1.17-1.36) and dementia (HR 1.37; CI 1.08-1.73) compared with those without previous severe hypoglycaemia. CONCLUSION Presence of diabetes-regardless of type- in atrial fibrillation is associated with an increased risk of premature death, cardiovascular events and dementia. This increase is more pronounced in type 1 than in type 2 diabetes. A history of severe hypoglycaemia is associated with a worsened prognosis in type 2 diabetes.
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Affiliation(s)
- Stelios Karayiannides
- Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.,Center for Diabetes, Academic Specialist Center, Region Stockholm, Sweden
| | - Anna Norhammar
- Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Physiology, Capio St Görans Hospital, Stockholm, Sweden
| | - Lena Landstedt-Hallin
- Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
| | - Leif Friberg
- Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
| | - Lundman Pia
- Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.,Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
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Toyoda M, Saito N, Kimura M, Hatori N, Tamura K, Miyakawa M, Sato K, Kanamori A, Kobayashi K. Concomitant treatment with insulin and sodium-glucose cotransporter 2 inhibitors was associated with the renal composite outcome in Japanese patients with type 2 diabetes and chronic kidney disease: A propensity score-matched analysis. J Diabetes Investig 2022; 13:1520-1527. [PMID: 35524473 PMCID: PMC9434580 DOI: 10.1111/jdi.13825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/26/2022] [Accepted: 05/01/2022] [Indexed: 11/27/2022] Open
Abstract
Aims/Introduction We previously reported that sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment was associated with an improvement of the albumin‐to‐creatinine ratio in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. The present study clarified how concomitant insulin treatment (IT) with SGLT2i therapy influences the renal composite outcome (RCO). Materials and Methods We retrospectively evaluated 624 Japanese patients with type 2 diabetes mellitus and chronic kidney disease who underwent SGLT2i treatment. The renal composite outcome was set as progression of the stage of albuminuria or a ≥15% decrease in the estimated glomerular filtration rate per year. We developed a cohort model of patients managed with and without IT (Ins [+], Ins [−]) using propensity score matching methods. Furthermore, all patients in our study population were stratified into quintiles according to their propensity score. Results The incidence of the RCO was in Ins (+) patients significantly higher than that in Ins (−) (P = 0.033). The estimated hazard ratio for the RCO was 1.55 (P = 0.035) in Ins (+) patients. The change in the estimated glomerular filtration rate and albumin‐to‐creatinine ratio in the groups was not statistically significant. The analysis, which was based on the quintiles, showed a statistically significant difference between the Ins (+) and Ins (−) groups (P = 0.01); the odds ratio for the RCO in patients managed with IT was 2.20 (P = 0.01). Conclusions Concomitant administration of IT with SGLT2is influenced the RCO in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. We might need to consider the influence of concomitant agents on the renoprotective effects of SGLT2i therapy.
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Affiliation(s)
- Masao Toyoda
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan.,Division of Nephrology, Endocrinology and Metabolism, Department of internal medicine, Tokai University School of Medicine, lsehara, Japan
| | - Nobumichi Saito
- Division of Nephrology, Endocrinology and Metabolism, Department of internal medicine, Tokai University School of Medicine, lsehara, Japan
| | - Moritsugu Kimura
- Division of Nephrology, Endocrinology and Metabolism, Department of internal medicine, Tokai University School of Medicine, lsehara, Japan
| | - Nobuo Hatori
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masaaki Miyakawa
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan
| | - Kazuyoshi Sato
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan
| | - Akira Kanamori
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan
| | - Kazuo Kobayashi
- Committee of Hypertension and Kidney disease, Kanagawa Physicians Association, Yokohama, Japan.,Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Crabtree T, Ogendo JJ, Vinogradova Y, Gordon J, Idris I. Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ≥60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies. Expert Rev Endocrinol Metab 2022; 17:255-267. [PMID: 35614863 DOI: 10.1080/17446651.2022.2079495] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 05/16/2022] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Guidelines for type 2 diabetes (T2D) recommend individualized HbA1c targets to take into account patient age or frailty. We synthesized evidence from randomized controlled trials and observational studies for intensive glycemic control (HbA1c target ≤58 mmol/mol) versus standard care, in elderly (age ≥60 years) or frail adults with T2D. METHODS Searches were performed utilizing recognized terms for T2D, frailty, older age, and HbA1c control and outcomes of interest. Meta-analysis was performed where possible. Primary outcomes included all-cause mortality, severe hypoglycemia, and hospital admission rates. Vascular complications, cognitive decline, and falls/fractures were secondary outcomes. RESULTS 7,528 studies were identified of which 15 different clinical studies were selected. No difference was noted in all-cause mortality with intensive control (pooled hazard ratio 0.96, 95% confidence interval 0.90-1.03), but risk of severe hypoglycemia increased (2.45, 2.22-2.72). Intensive control was associated reductions in microvascular (0.73, 0.68-0.79) and macrovascular complications (0.84, 0.79-0.89). Outcome data for risk of hospitalization, cognition, and falls/fractures were limited. CONCLUSION Intensive glycemic control was associated with reduced rates of complications but increased severe hypoglycemia. Significant heterogeneity exists and the impact of different drug regimens is unclear. Caution is needed when setting glycemic targets in elderly or frail individuals.
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Affiliation(s)
- Thomas Crabtree
- Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK
- Division of Graduate Entry Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Jael-Joy Ogendo
- Division of Graduate Entry Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Yana Vinogradova
- Division of Primary Care, University of Nottingham, Nottingham, UK
| | - Jason Gordon
- Division of Graduate Entry Medicine and Health Sciences, University of Nottingham, Nottingham, UK
- Health Economic Outcomes Research, Birmingham, UK
| | - Iskandar Idris
- Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK
- Division of Graduate Entry Medicine and Health Sciences, University of Nottingham, Nottingham, UK
- Arthritis Centre for Musculoskeletal Ageing Research, University of Nottingham, NIHR, Nottingham BRC, University of Nottingham, UK
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de Carvalho LSF, Nogueira ACC, Bonilha I, Luchiari B, Benchimol A, Couri CEB, Borges JL, Barreto J, Sposito AC. Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis. Front Cardiovasc Med 2022; 9:876795. [PMID: 35571207 PMCID: PMC9098935 DOI: 10.3389/fcvm.2022.876795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/25/2022] [Indexed: 11/13/2022] Open
Abstract
AimTo assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE.MethodsA systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE.ResultsWe included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs.ConclusionsAchieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.
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Affiliation(s)
- Luiz Sergio Fernandes de Carvalho
- Laboratory of Data for Quality of Care and Outcomes Research, Clarity Healthcare Intelligence, Jundiaí, Brazil
- Catholic University of Brasília (UCB), Brasilia, Brazil
- Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil
| | - Ana Claudia Cavalcante Nogueira
- Catholic University of Brasília (UCB), Brasilia, Brazil
- Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil
| | | | - Beatriz Luchiari
- Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil
| | - Alexander Benchimol
- Cardiology Department, State Institute of Diabetes and Endocrinology, Rio de Janeiro, Brazil
| | | | | | - Joaquim Barreto
- Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil
| | - Andrei C. Sposito
- Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil
- *Correspondence: Andrei C. Sposito
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Iwahori T, Snoek F, Nagai Y, Spaepen E, Mitchell BD, Peyrot M. Conversations and Reactions Around Severe Hypoglycemia (CRASH): Japan Results From a Global Survey of People with T1DM or Insulin-Treated T2DM and Caregivers. Diabetes Ther 2022; 13:517-533. [PMID: 35199292 PMCID: PMC8934893 DOI: 10.1007/s13300-022-01211-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/24/2022] [Indexed: 12/01/2022] Open
Abstract
AIMS The CRASH study examined severe hypoglycemia (SH) experiences among people with diabetes (PWD) and caregivers across eight countries. Here we report findings from the Japan cohort, with references to data from the United Kingdom (UK) cohort. MATERIALS AND METHODS Adults with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) and caregivers (not necessarily related) were recruited from online patient panels. Participants who had experienced at least one SH event in the past 3 years were eligible for study inclusion. Participants completed an online survey regarding their experience with SH, its treatment, and actions during and after an event. RESULTS Of the 9367 PWD and caregivers from the online patient panels, 8475 participants were ineligible and a total of 53 Japanese participants (35 T1DM, 9 T2DM, 9 caregivers) completed the survey. Most SH incidents occurred at home and were unattended by a healthcare provider. For T1DM, 29% of Japan PWD and 13% of the UK PWD called an ambulance during an SH event; of these, 90% (Japan) and 50% (UK) were transported to hospital. Glucagon use was low (3% Japan and 10% UK for T1DM). Japanese respondents reported emotional impacts of SH, including feeling scared (86% T1DM, 56% T2DM), unprepared (63% T1DM, 78% T2DM), and helpless (60% T1DM, 33% T2DM). Despite the emotional burden, most PWD did not immediately discuss their SH event with a healthcare provider, with the majority (75% T1DM, 71% T2DM) waiting until their next doctor's appointment. CONCLUSION Conversations around SH between healthcare providers and PWD appear to be insufficient in Japan. An emotional burden of SH was reported by PWD and caregivers. Education regarding the prevention of SH and available treatment options may reduce SH events and improve treatment preparation, while alleviating PWD concerns.
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Affiliation(s)
| | - Frank Snoek
- Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Yukiko Nagai
- Eli Lilly Japan, K.K., Kobe, Hyogo, Japan.
- , 5-1-28 Isogamidori, Chuo-Ku, Kobe, 651-0086, Japan.
| | | | | | - Mark Peyrot
- Department of Sociology, Loyola University Maryland, Baltimore, MD, USA
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Liang B, Koye DN, Hachem M, Zafari N, Braat S, Ekinci EI. Efficacy of Flash Glucose Monitoring in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 3:849725. [PMID: 36992733 PMCID: PMC10012125 DOI: 10.3389/fcdhc.2022.849725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 01/17/2022] [Indexed: 11/13/2022]
Abstract
ObjectiveFlash glucose monitoring (FlashGM) is a sensor-based technology that displays glucose readings and trends to people with diabetes. In this meta-analysis, we assessed the effect of FlashGM on glycaemic outcomes including HbA1c, time in range, frequency of hypoglycaemic episodes and time in hypo/hyperglycaemia compared to self-monitoring of blood glucose, using data from randomised controlled trials.MethodsA systematic search was conducted on MEDLINE, EMBASE and CENTRAL for articles published between 2014 and 2021. We selected randomised controlled trials comparing flash glucose monitoring to self-monitoring of blood glucose that reported change in HbA1c and at least one other glycaemic outcome in adults with type 1 or type 2 diabetes. Two independent reviewers extracted data from each study using a piloted form. Meta-analyses using a random-effects model was conducted to obtain a pooled estimate of the treatment effect. Heterogeneity was assessed using forest plots and the I2 statistic.ResultsWe identified 5 randomised controlled trials lasting 10 – 24 weeks and involving 719 participants. Flash glucose monitoring did not lead to a significant reduction in HbA1c. However, it resulted in increased time in range (mean difference 1.16 hr, 95% CI 0.13 to 2.19, I2 = 71.7%) and decreased frequency of hypoglycaemic episodes (mean difference -0.28 episodes per 24 hours, 95% CI -0.53 to -0.04, I2 = 71.4%).ConclusionsFlash glucose monitoring did not lead to a significant reduction in HbA1c compared to self-monitoring of blood glucose, however, it improved glycaemic management through increased time in range and decreased frequency of hypoglycaemic episodes.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42020165688).
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Affiliation(s)
- Bonnie Liang
- Department of Medicine, Austin Health, Melbourne Medical School, University of Melbourne, Heidelberg, VIC, Australia
| | - Digsu N. Koye
- Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Mariam Hachem
- Department of Medicine, Austin Health, Melbourne Medical School, University of Melbourne, Heidelberg, VIC, Australia
| | - Neda Zafari
- Department of Medicine, Austin Health, Melbourne Medical School, University of Melbourne, Heidelberg, VIC, Australia
| | - Sabine Braat
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Elif I. Ekinci
- Department of Medicine, Austin Health, Melbourne Medical School, University of Melbourne, Heidelberg, VIC, Australia
- Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia
- *Correspondence: Elif I. Ekinci,
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Atkin SA, Moin ASM, Atkin SL, Butler AE. Hypoglycemia Impairs the Heat Shock Protein Response: A Risk for Heat Shock in Cattle? Front Vet Sci 2022; 9:822310. [PMID: 35224086 PMCID: PMC8866688 DOI: 10.3389/fvets.2022.822310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundHeat stress (HS) in cattle is a major debilitating problem, affecting health and milk yield. Physiologically, HS has been shown to lower blood glucose levels to 2.5 mmol/l (45 mg/dl) and results in upregulation of heat shock proteins (HSPs), eliciting the heat shock response (HSR) of which HSP90, 70 and 27 have been shown to be protective. However, it is unclear if the HSP response is blunted by decreased glucose, thereby preventing adaptive mechanisms. To address this question, this exploratory reverse translational study on the effects of hypoglycemia on the HSP pathway was undertaken.MethodsA human prospective, study in healthy control individuals (n = 23) was undertaken. Subjects underwent hyperinsulinemic-induced hypoglycemia [≤2.0 mmol/L (36 mg/dl)] with blood sampling at baseline, at hypoglycemia and for a 24-h post-hypoglycemia follow-up period. Proteomic analysis of the heat shock-related protein pathway, the pathway associated with HS in cattle, was performed.ResultsIn response to hypoglycemia, HS pathway proteins were significantly decreased (p < 0.05): HSP70 and HSP27 (at hypoglycemia); DnaJ homolog subfamily B member 1 (DNAJB1), Stress-induced-phosphoprotein 1 (STIP1) and the ubiquitin pathway proteins, Ubiquitin-conjugating enzyme (UBE2L3) and Ubiquitin-conjugating enzyme E2 N (UBE2N) (at 30-min post-hypoglycemia); HSP90 (at 2-h post-hypoglycemia). STIP1, UBE2L3, and UBE2N remained suppressed at 24-h.ConclusionHeat stress in cattle reduces blood glucose that, in turn, may blunt the HS pathway protective response, including HSP 90, 70, 27 and the ubiquitin proteins, leading to adverse outcomes. Monitoring of blood glucose in susceptible cattle may allow for earlier intervention and may also identify those animals at greatest risk to ensure that milk yield is not compromised.
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Affiliation(s)
- Samuel A. Atkin
- School of Veterinary Medicine, University of Liverpool, Liverpool, United Kingdom
| | | | | | - Alexandra E. Butler
- Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
- *Correspondence: Alexandra E. Butler ;
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Abstract
The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.
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Affiliation(s)
- Yoshiki Kusunoki
- Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Japan
| | - Kosuke Konishi
- Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Japan
| | - Taku Tsunoda
- Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Japan
| | - Hidenori Koyama
- Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Japan
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Afghahi H, Nasic S, Peters B, Rydell H, Hadimeri H, Svensson J. Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis. PLoS One 2022; 17:e0262880. [PMID: 35077471 PMCID: PMC8789125 DOI: 10.1371/journal.pone.0262880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022] Open
Abstract
Background
The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.
Methods
325 patients with diabetes and ESRD were followed (2008–2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.
Results
During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83–4.60 (HR 3.15, 95% CI 1.78–5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21–5.11; p = 0.014) were associated with increased risk of death.
Conclusion
The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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Affiliation(s)
- Hanri Afghahi
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Salmir Nasic
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Research and Development Center at Skaraborg Hospital, Skövde, Sweden
| | - Björn Peters
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- * E-mail:
| | - Helena Rydell
- Division of Renal Medicine, Department of Clinical Sciences Intervention and Technology, Karolinska Institute, Stockholm, Sweden
- Department of Internal Medicine, Swedish Renal Registry, Ryhov Regional Hospital, Jönköping, Sweden
| | - Henrik Hadimeri
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Johan Svensson
- Research and Development Center at Skaraborg Hospital, Skövde, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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Deng YX, Chang HY, Li H. Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes. Biomimetics (Basel) 2022; 7:15. [PMID: 35076493 PMCID: PMC8788472 DOI: 10.3390/biomimetics7010015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/01/2022] [Accepted: 01/08/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90-95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.
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Affiliation(s)
- Yi-Xiang Deng
- School of Engineering, Brown University, Providence, RI 02912, USA;
| | - Hung-Yu Chang
- Division of Applied Mathematics, Brown University, Providence, RI 02912, USA;
| | - He Li
- Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA
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Oba T, Nagao M, Kobayashi S, Yamaguchi Y, Nagamine T, Tanimura-Inagaki K, Fukuda I, Sugihara H. Perioperative glycemic status is linked to postoperative complications in non-intensive care unit patients with type-2 diabetes: a retrospective study. Ther Adv Endocrinol Metab 2022; 13:20420188221099349. [PMID: 35646304 PMCID: PMC9130836 DOI: 10.1177/20420188221099349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 04/21/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Perioperative hyperglycemia is a risk factor for postoperative complications in the general population. However, it has not been clarified whether perioperative hyperglycemia increases postoperative complications in patients with type-2 diabetes mellitus (T2D). Therefore, we aimed to analyze the relationship between perioperative glycemic status and postoperative complications in non-intensive care unit (non-ICU) hospitalized patients with T2D. MATERIALS AND METHODS Medical records of 1217 patients with T2D who were admitted to the non-ICU in our hospital were analyzed retrospectively. Relationships between clinical characteristics including perioperative glycemic status and postoperative complications were assessed using univariate and multivariate analyses. Perioperative glycemic status was evaluated by calculating the mean, standard deviation (SD), and coefficient of variation (CV) of blood glucose (BG) measurements in preoperative and postoperative periods for three contiguous days before and after surgery, respectively. Postoperative complications were defined as infections, delayed wound healing, postoperative bleeding, and/or thrombosis. RESULTS Postoperative complications occurred in 139 patients (11.4%). These patients showed a lower BG immediately before surgery (P = 0.04) and a higher mean postoperative BG (P = 0.009) than those without postoperative complications. There were no differences in the other perioperative BG parameters including BG variability and the frequency of hypoglycemia. The multivariate analysis showed that BG immediately before surgery (adjusted odds ratio (95% confidence interval [CI]), 0.91 (0.85-0.98), P = 0.01) and mean postoperative BG (1.11 (1.05-1.18), P < 0.001) were independently associated with postoperative complications. CONCLUSION Perioperative glycemic status, that is, a low BG immediately before surgery and a high mean postoperative BG, are associated with the increased incidence of postoperative complications in non-ICU patients with T2D.
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Affiliation(s)
- Takeshi Oba
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | | | - Shunsuke Kobayashi
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | - Yuji Yamaguchi
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | - Tomoko Nagamine
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | - Kyoko Tanimura-Inagaki
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | - Izumi Fukuda
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Diabetes and
Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo,
Japan
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45
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Nakhleh A, Shehadeh N. Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention. World J Diabetes 2021; 12:2036-2049. [PMID: 35047118 PMCID: PMC8696639 DOI: 10.4239/wjd.v12.i12.2036] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/16/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.
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Affiliation(s)
- Afif Nakhleh
- Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Naim Shehadeh
- Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa 3109601, Israel
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46
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Yun JS, Ko SH. Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes. Metabolism 2021; 123:154838. [PMID: 34333002 DOI: 10.1016/j.metabol.2021.154838] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/07/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023]
Abstract
With the advances in diabetes care, the trend of incident cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) has been decreasing over past decades. However, given that CVD is still a major cause of death in patients with diabetes and that the risk of CVD in patients with T2DM is more than twice that in those without DM, there are still considerable challenges to the prevention of CVD in diabetes. Accordingly, there have been several research efforts to decrease cardiovascular (CV) risk in T2DM. Large-scale genome-wide association studies (GWAS) and clinical cohort studies have investigated the effects of factors, such as genetic determinants, hypoglycaemia, and insulin resistance, on CVD and can account for the unexplained CV risk in T2DM. Lifestyle modification is a widely accepted cornerstone method to prevent CVD as the first-line strategy in T2DM. Recent reports from large CV outcome trials have proven the positive CV effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with high CVD risk. Overall, current practice guidelines for the management of CVD in T2DM are moving from a glucocentric strategy to a more individualised patient-centred approach. This review will discuss the current epidemiologic trends of CVD in T2DM and the risk factors linking T2DM to CVD, including genetic contribution, hypoglycaemia, and insulin resistance, and proper care strategies, including lifestyle and therapeutic approaches.
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Affiliation(s)
- Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
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47
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Senior PA. Glucose as a modifiable cause of atherosclerotic cardiovascular disease: Insights from type 1 diabetes and transplantation. Atherosclerosis 2021; 335:16-22. [PMID: 34520887 DOI: 10.1016/j.atherosclerosis.2021.09.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/26/2021] [Accepted: 09/01/2021] [Indexed: 02/09/2023]
Abstract
Diabetes is a major risk factor for cardiovascular (CV) disease. In contrast to the clear benefits from treatments which reduce blood pressure and lipids, clinical trials targeting blood glucose have not shown clear CV benefits. Interventions to intensify glycemic control early in the course of diabetes may have benefits in long term observational studies (DCCT-EDIC/UKPDS), but may not be helpful if introduced late in the course of type 2 diabetes (ACCORD, ADVANCE, VA-DT). More recent CVOT in high risk subjects suggest that the benefits of SGLT2 and GLP1-RA are glucose-independent. Type 1 diabetes provides a "cleaner" model to study the links between glucose and cardiovascular disease. Abnormalities of glucose regulation in type 1 diabetes is not restricted to hyperglycemia, but includes glycemic variability and hypoglycemia. Increasingly the mechanisms linking glycemic variability and hypoglycemia as key mediators of cardiovascular complications are being understood. Furthermore, data from pancreas and islet transplantation showing reduced cardiovascular mortality and regression of intima-media thickness supports a causal role for glucose in the pathogenesis of atherosclerosis, but suggests that restoration of normal glucose regulation may be required to demonstrate substantial impact on CV risk accrued over decades of type 1 diabetes. Considering the limited organ supply and risks of immunosuppression, advances in biology (stem cell derived beta cells) or technology (automated insulin delivery systems) will be required to provide a scalable solution to deliver optimal glucose control and reduce CV risk for people with type 1 diabetes.
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Affiliation(s)
- Peter A Senior
- Division of Endocrinology and Metabolism. Director, Alberta Diabetes Institute. Charles A. Allard Chair in Diabetes Research. University of Alberta, 1.005 Li Ka Shing Centre for Health Research Innovation Edmonton, AB, T6G 2E1, Canada.
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48
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Improved Glycemic Control and Variability: Application of Healthy Ingredients in Asian Staples. Nutrients 2021; 13:nu13093102. [PMID: 34578981 PMCID: PMC8468310 DOI: 10.3390/nu13093102] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/27/2021] [Accepted: 09/03/2021] [Indexed: 11/17/2022] Open
Abstract
A reduction in carbohydrate intake and low-carbohydrate diets are often advocated to prevent and manage diabetes. However, limiting or eliminating carbohydrates may not be a long-term sustainable and maintainable approach for everyone. Alternatively, diet strategies to modulate glycemia can focus on the glycemic index (GI) of foods and glycemic load (GL) of meals. To assess the effect of a reduction in glycemic load of a 24 h diet by incorporating innovative functional ingredients (β-glucan, isomaltulose) and alternative low GI Asian staples (noodles, rice)on glycemic control and variability, twelve Chinese men (Age: 27.0 ± 5.1 years; BMI:21.6 ± 1.8kg/m2) followed two isocaloric, typically Asian, 24h diets with either a reduced glycemic load (LGL) or high glycemic load (HGL) in a randomized, single-blind, controlled, cross-over design. Test meals included breakfast, lunch, snack and dinner and the daily GL was reduced by 37% in the LGL diet. Continuous glucose monitoring provided 24 h glycemic excursion and variability parameters: incremental area under the curve (iAUC), max glucose concentration (Max), max glucose range, glucose standard deviation (SD), and mean amplitude of glycemic excursion (MAGE), time in range (TIR). Over 24h, the LGL diet resulted in a decrease in glucose Max (8.12 vs. 6.90 mmol/L; p = 0.0024), glucose range (3.78 vs. 2.21 mmol/L; p = 0.0005), glucose SD (0.78 vs. 0.43 mmol/L; p = 0.0002), mean amplitude of glycemic excursion (2.109 vs. 1.008; p < 0.0001), and increase in 4.5-6.5mmol/L TIR (82.2 vs. 94.6%; p = 0.009), compared to the HGL diet. The glucose iAUC, MAX, range and SD improved during the 2 h post-prandial window of each LGL meal, and this effect was more pronounced later in the day. The current results validate the dietary strategy of incorporating innovative functional ingredients (β-glucan, isomaltulose) and replacing Asian staples with alternative low GI carbohydrate sources to reduce daily glycemic load to improve glycemic control and variability as a viable alternative to the reduction in carbohydrate intake alone. These observations provide substantial public health support to encourage the consumption of staples of low GI/GL to reduce glucose levels and glycemic variability. Furthermore, there is growing evidence that the role of chrononutrition, as reported in this paper, requires further examination and should be considered as an important addition to the understanding of glucose homeostasis variation throughout the day.
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Fahrmann ER, Adkins L, Driscoll HK. Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 2021; 44:2132-2139. [PMID: 34233927 PMCID: PMC8740933 DOI: 10.2337/dc20-2757] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 05/25/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Literature suggests that severe hypoglycemia (SH) may be linked to cardiovascular events only in older individuals with high cardiovascular risk score (CV-score). Whether a potential relationship between any-SH and cardiovascular disease exists and whether it is conditional on vascular damage severity in a young cohort with type 1 diabetes (T1D) without apparent macrovascular and no or mild-to-moderate microvascular complications at baseline is unknown. RESEARCH DESIGN AND METHODS We evaluated data of 1,441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study volunteers (diabetes duration 1-15 years) followed for ∼30 years. Time-dependent associations between any-SH and ischemic heart disease (IHD: death, silent/nonfatal myocardial infarct, revascularization, or confirmed angina) and associations between interactions of any-SH with surrogates of baseline micro-/macrovascular damage severity and IHD were analyzed. Diabetes duration, steps on DCCT Early Treatment Diabetic Retinopathy Study severity scale (DCCT-ETDRS), Diabetes Complications Severity Index (DCSI), and CV-scores were considered as surrogates of baseline micro-/macrovascular damage severity. RESULTS Without interactions, in the minimally adjusted model controlling for confounding bias by age and HbA1c, SH was a significant IHD factor (P = 0.003). SH remained a significant factor for IHD in fully adjusted models (P < 0.05). In models with interactions, interactions between SH and surrogates of microvascular complications severity, but not between SH and CV-score, were significant. Hazard ratios for IHD based on SH increased 1.19-fold, 1.32-fold, and 2.21-fold for each additional year of diabetes duration, DCCT-ETDRS unit, and DCSI unit, respectively. At time of IHD event, ∼15% of 110 participants with SH had high CV-scores. CONCLUSIONS In a young cohort with T1D with no baseline macrovascular complications, surrogates of baseline microvascular damage severity impact the effect of SH on IHD. Older age with high CV-score per se is not mandatory for an association of SH with IHD. However, the association is multifactorial.
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Affiliation(s)
- Elke R Fahrmann
- Internal Medicine/Endocrinology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV
| | - Laura Adkins
- Department of Mathematics, Marshall University, Huntington, WV
| | - Henry K Driscoll
- Internal Medicine/Endocrinology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.,VA Medical Center, Huntington, WV
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50
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Porcellati F, Di Mauro S, Mazzieri A, Scamporrino A, Filippello A, De Fano M, Fanelli CG, Purrello F, Malaguarnera R, Piro S. Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin? Biomolecules 2021; 11:biom11091281. [PMID: 34572493 PMCID: PMC8464883 DOI: 10.3390/biom11091281] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/23/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.
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Affiliation(s)
- Francesca Porcellati
- Department of Medicine and Surgery, Perugia University School of Medicine, Via Gambuli 1, 06126 Perugia, Italy; (F.P.); (A.M.); (M.D.F.); (C.G.F.)
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; (S.D.M.); (A.S.); (A.F.); (F.P.); (S.P.)
| | - Alessio Mazzieri
- Department of Medicine and Surgery, Perugia University School of Medicine, Via Gambuli 1, 06126 Perugia, Italy; (F.P.); (A.M.); (M.D.F.); (C.G.F.)
| | - Alessandra Scamporrino
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; (S.D.M.); (A.S.); (A.F.); (F.P.); (S.P.)
| | - Agnese Filippello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; (S.D.M.); (A.S.); (A.F.); (F.P.); (S.P.)
| | - Michelantonio De Fano
- Department of Medicine and Surgery, Perugia University School of Medicine, Via Gambuli 1, 06126 Perugia, Italy; (F.P.); (A.M.); (M.D.F.); (C.G.F.)
| | - Carmine Giuseppe Fanelli
- Department of Medicine and Surgery, Perugia University School of Medicine, Via Gambuli 1, 06126 Perugia, Italy; (F.P.); (A.M.); (M.D.F.); (C.G.F.)
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; (S.D.M.); (A.S.); (A.F.); (F.P.); (S.P.)
| | - Roberta Malaguarnera
- Faculty of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
- Correspondence: ; Tel.: +39-0935-536577
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; (S.D.M.); (A.S.); (A.F.); (F.P.); (S.P.)
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