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Pramono A, Fitranti DY, Nugroho KH, Sobirin MA, Syauqy A. The Association between Unhealthy Food Consumption and Impaired Glucose Metabolism among Adults with Overweight or Obesity: A Cross-Sectional Analysis of the Indonesian Population. J Obes 2023; 2023:2885769. [PMID: 37006782 PMCID: PMC10060072 DOI: 10.1155/2023/2885769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 04/04/2023] Open
Abstract
BACKGROUND It has been shown that dietary patterns are associated with glucose control. However, the association between the types of food consumed and blood glucose in overweight or obese individuals is still unclear. The present study aimed to determine the association between unhealthy food consumption and impaired glucose metabolism in adults with overweight or obesity. METHODS The analysis presented in this study was based on the data from a population-based, cross-sectional, nationally representative survey (Indonesian Basic Health Research 2018/RISKESDAS 2018). The body mass index (BMI) was calculated as weight (kg)/height squared (m2) and was determined based on the World Health Organization (WHO) criteria for the Asian population. A validated questionnaire and food card were used to assess the diet. Fasting plasma glucose and 2-hpost-prandial glucose were employed to determine blood glucose markers. RESULTS In total, 8752 adults with overweight or obesity were included in this analysis. We found that consumption of sweet, grilled, and processed foods was associated with impaired fasting plasma glucose (IFG) before and after adjustment (p < 0.05). Consumption of high-fat foods was also associated with impaired glucose tolerance (IGT) for all models tested (p < 0.05). Furthermore, all models showed a link between processed food consumption and combined glucose intolerance (CGI) (p ≤ 0.001). CONCLUSIONS Differential food group consumption was associated with IFG, IGT, and CGI in Indonesian adults who were overweight or obese.
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Affiliation(s)
- Adriyan Pramono
- Department of Nutrition, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
- Center of Nutrition Research (Cenure), Diponegoro University, Tembalang, Semarang 50275, Indonesia
| | - Deny Y. Fitranti
- Department of Nutrition, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
- Center of Nutrition Research (Cenure), Diponegoro University, Tembalang, Semarang 50275, Indonesia
| | - K. Heri Nugroho
- Department of Internal Medicine, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
| | - M. Ali Sobirin
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
| | - Ahmad Syauqy
- Department of Nutrition, Faculty of Medicine, Diponegoro University, Tembalang, Semarang 50275, Indonesia
- Center of Nutrition Research (Cenure), Diponegoro University, Tembalang, Semarang 50275, Indonesia
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Papaetis GS. Pioglitazone, Bladder Cancer and the Presumption of Innocence. Curr Drug Saf 2022; 17:294-318. [PMID: 35249505 DOI: 10.2174/1574886317666220304124756] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 12/01/2021] [Accepted: 12/21/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue. Pioglitazone, the main thiazolidinedione in clinical practice, has shown cardiovascular and renal benefits in patients with type 2 diabetes, durable reduction of glycated hemoglobulin levels, important improvements of several components of the metabolic syndrome and beneficial effects of non-alcoholic fatty liver disease. OBJECTIVE Despite all of its established advantages, the controversy for an increased risk of developing bladder cancer, combined with the advent of newer drug classes that achieved major cardiorenal effects have significantly limited its use spreading a persistent shadow of doubt for its future role. METHODS Pubmed, Google and Scope databases have been thoroughly searched and relevant studies were selected. RESULTS This paper explores thoroughly both in vitro and in vivo (animal models and humans) studies that investigated the possible association of pioglitazone with bladder cancer. CONCLUSION Currently the association of pioglitazone with bladder cancer cannot be based on solid evidence. This evidence cannot justify its low clinical administration, especially in the present era of individualised treatment strategies. Definite clarification of this issue is imperative and urgently anticipated from future high quality and rigorous pharmacoepidemiologic research, keeping in mind its unique mechanism of action and its significant pleiotropic effects.
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Affiliation(s)
- Georgios S Papaetis
- Internal Medicine and Diabetes Clinic, Eleftherios Venizelos Avenue 62, Paphos, Cyprus.
- CDA College, 73 Democratias Avenue, Paphos, Cyprus
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Tao T, Zhang Y, Zhu YC, Fu JR, Wang YY, Cai J, Ma JY, Xu Y, Gao YN, Sun Y, Fan W, Liu W. Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study. J Clin Endocrinol Metab 2021; 106:e1420-e1432. [PMID: 32995892 PMCID: PMC8244122 DOI: 10.1210/clinem/dgaa692] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 09/24/2020] [Indexed: 12/14/2022]
Abstract
CONTEXT Up to 40% of patients with polycystic ovary syndrome (PCOS) have prediabetes; an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. OBJECTIVE To evaluate clinical efficacy of exenatide (EX), metformin (MET), or combination (COM) for prediabetes in PCOS. DESIGN Randomized, open-label, parallel-group controlled trial. SETTING Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. PATIENTS PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2 hour post glucose 7.8-11.0 mmol/L on oral glucose tolerance test [OGTT]). A total of 150 out of 183 eligible enrollees completed the study. INTERVENTION EX (10-20μg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. MAIN OUTCOME MEASURES Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic β-cell function parameters (secondary endpoints) and potential mechanisms were assessed. RESULTS Impaired glucose tolerance was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of the MET group (32%, 16/50) (P = .003 and .027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A 2-step hyperglycemic clamp study revealed that EX had led to higher postprandial insulin secretion than MET, potentially explaining the higher remission rate. CONCLUSIONS Compared with MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.
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Affiliation(s)
- Tao Tao
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Correspondence and Reprint Requests: Tao Tao, Department of Endocrinology and Metabolism, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.160 Pujian Road, Pudong New District, Shanghai 200127, China. E-mail:
| | - Yi Zhang
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu-Chen Zhu
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jia-Rong Fu
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu-Ying Wang
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jie Cai
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing-Yu Ma
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Xu
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yi-Ning Gao
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yun Sun
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - WuQiang Fan
- Diabetes Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Wei Liu
- Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
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Lazo-Porras M, Bernabe-Ortiz A, Ruiz-Alejos A, Smeeth L, Gilman RH, Checkley W, Málaga G, Miranda JJ. Regression from prediabetes to normal glucose levels is more frequent than progression towards diabetes: The CRONICAS Cohort Study. Diabetes Res Clin Pract 2020; 163:107829. [PMID: 31465811 PMCID: PMC7239508 DOI: 10.1016/j.diabres.2019.107829] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 06/18/2019] [Accepted: 08/23/2019] [Indexed: 12/13/2022]
Abstract
AIMS This study aimed to (1) estimate the prevalence of prediabetes according to different definitions, (2) evaluate regression to normal glucose levels and progression towards T2DM, and (3) determine factors associated with regression and progression across four diverse geographical settings in a Latin American country. METHODS The CRONICAS Cohort Study was conducted in four different areas in Peru. Enrollment started in September 2010 and follow-up was conducted in 2013. Prediabetes, T2DM and normal glucose levels were determined according to definitions from the World Health Organization (WHO), American Diabetes Association (ADA), and National Institute for Health and Care Excellence (NICE). The main outcomes were regression to normal glucose levels and incidence of T2DM. Prevalence estimates and 95% confidence intervals (95% CI) were calculated. Crude and adjusted models using Poisson regression were performed and relative risk ratios (RRR) and 95% CI were calculated. RESULTS At baseline, the prevalence of prediabetes varied markedly by definition used: 6.5%(95% CI 5.6-7.6%), 53.6% (95% CI 51.6-55.6%), and 24.6% (95% CI 22.8-26.4%) according to WHO, ADA and NICE criteria, respectively. After 2.2 years of follow-up, in those with prediabetes, the cumulative incidence of regression to euglycemia ranged between 31.4% and 68.9%, whereas the incidence of T2DM varied from 5.5% to 28.8%. Factors associated with regression to normal glucose levels and progression to diabetes were age, body mass index, and insulin resistance. CONCLUSIONS Regression from pre-diabetes back to euglycemia was much more common than progression to diabetes.
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Affiliation(s)
- Maria Lazo-Porras
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru; CONEVID Unidad de Conocimiento y Evidencia, Universidad Peruana Cayetano Heredia, Lima, Peru.
| | - Antonio Bernabe-Ortiz
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
| | - Andrea Ruiz-Alejos
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.
| | - Liam Smeeth
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
| | - Robert H Gilman
- Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States; Área de Investigación y Desarrollo, Asociación Benéfica PRISMA, Lima, Peru.
| | - William Checkley
- Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.
| | - German Málaga
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru; CONEVID Unidad de Conocimiento y Evidencia, Universidad Peruana Cayetano Heredia, Lima, Peru; Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
| | - J Jaime Miranda
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru; Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
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Liu ZG, Li Y, Jiao JH, Long H, Xin ZY, Yang XY. MicroRNA regulatory pattern in spinal cord ischemia-reperfusion injury. Neural Regen Res 2020; 15:2123-2130. [PMID: 32394971 PMCID: PMC7716024 DOI: 10.4103/1673-5374.280323] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase (MAPK) signaling pathway was the most significantly enriched pathway among 24- and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020 (Research) 01].
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Affiliation(s)
- Zhi-Gang Liu
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yin Li
- School of Public Health, Jilin University, Changchun, Jilin Province, China
| | - Jian-Hang Jiao
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Hao Long
- Pain Clinic, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Zhuo-Yuan Xin
- The Key Laboratory of Zoonosis Search, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin Province, China
| | - Xiao-Yu Yang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
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Postprandial Reactive Hypoglycemia. MEDICAL BULLETIN OF SISLI ETFAL HOSPITAL 2019; 53:215-220. [PMID: 32377086 PMCID: PMC7192270 DOI: 10.14744/semb.2019.59455] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 06/20/2019] [Indexed: 02/07/2023]
Abstract
Reactive hypoglycemia (RH) is the condition of postprandially hypoglycemia occurring 2-5 hours after food intake. RH is clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min), and late RH (at 240–300 min). When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal. This leads to late but excessive secretion of the second-phase insulin secretion. Thus, late reactive hypoglycemia occurs. Elevated insulin levels also cause down-regulation of the insulin post-receptor on the muscle and fat cells, thus decreasing insulin sensitivity. The cause of the increase in insulin sensitivity in IRH at 3 h is not completely clear. However, there is a decrease in insulin sensitivity in late reactive hypoglycaemia at 4 or 5 hours. Thus, patients with hypoglycemia at 4 or 5 h who have a family history of diabetes and obesity may be more susceptible to diabetes than patients with hypoglycemia at 3 h. We believe that some cases with normal glucose tolerance in OGTT should be considered as prediabetes at <55 or 60 mg/dl after 4-5 hours after OGTT. Metformin and AGI therapy may be recommended if there is late RH with IFG. Also Metformin, AGİ, TZD, DPP-IVInhibitors, GLP1RA therapy may be recommended if there is late RH with IGT. As a result, postprandial RH (<55 or 60 mg/dl), especially after 4 hours may predict diabetes. Therefore, people with RH along with weight gain and with diabetes history in the family will benefit from a lifestyle modification as well as the appropriate antidiabetic approach in the prevention of diabetes.
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Yammine L, Kosten TR, Cinciripini PM, Green CE, Meininger JC, Minnix JA, Newton TF. Exenatide once weekly for smoking cessation: study protocol for a randomized clinical trial. Medicine (Baltimore) 2018; 97:e9567. [PMID: 29480848 PMCID: PMC5943874 DOI: 10.1097/md.0000000000009567] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Cigarette smoking is the greatest preventable cause of morbidity and premature mortality in the United States. Approved pharmacological treatments for smoking cessation are marginally effective, underscoring the need for improved pharmacotherapies. A novel approach might use glucagon-like peptide-1 (GLP-1) agonists, which reduce alcohol and drug use in preclinical studies. GLP-1 is produced in the intestinal L-cells and in the hindbrain. The peptide maintains glucose homeostasis and reduces food intake. Several GLP-1 agonists are used clinically to treat type 2 diabetes and obesity, but none have been tested in humans to reduce smoking. AIMS We will examine whether extended-release exenatide reduces smoking, craving, and withdrawal symptoms, as well as cue-induced craving for cigarettes. METHODS We will enroll prediabetic and/or overweight treatment seeking smokers (n = 90) into a double-blind, placebo-controlled, randomized clinical trial. Participants will be randomized in a 1:1 ratio to receive exenatide or placebo. All participants will receive transdermal nicotine replacement therapy (NRT) and behavioral counseling. Abstinence from smoking (verified via expired CO level of ≤5 ppm), craving (Questionnaire of Smoking Urges score), and withdrawal symptoms (Wisconsin Scale of Withdrawal Symptoms score) will be assessed weekly during 6 weeks of treatment and at 1 and 4 weeks posttreatment. Cue-induced craving for cigarettes will be assessed at baseline and at 3 weeks of treatment following virtual reality exposure. EXPECTED OUTCOMES We hypothesize that exenatide will increase the number of participants able to achieve complete smoking abstinence above that achieved via standard NRT and that exenatide will reduce craving and withdrawal symptoms, as well as cue-induced craving for cigarettes.
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Affiliation(s)
- Luba Yammine
- University of Texas Health Science Center at Houston
| | | | | | - Charles E. Green
- University of Texas Health Science Center at Houston
- University of Texas MD Anderson Cancer Center, Houston, Texas
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Bilgir O, Gökçen B, Bilgir F, Guler A, Calan M, Yuksel A, Aslanıpour B, Akşit M, Bozkaya G. Relationship Between Serum Macrophage Migration Inhibitory Factor Level and Insulin Resistance, High-Sensitivity C-Reactive Protein and Visceral Fat Mass in Prediabetes. Am J Med Sci 2017; 355:37-43. [PMID: 29289260 DOI: 10.1016/j.amjms.2017.10.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 10/15/2017] [Accepted: 10/24/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Growing evidence suggest that macrophage migration inhibitory factor (MIF) plays a vital role in glucose metabolism. We aimed to ascertain whether MIF levels are altered in subjects with prediabetes and also to determine the relationship between MIF and metabolic parameters as well as visceral fat mass. MATERIAL AND METHODS This cross-sectional study included 40 subjects with prediabetes and 40 age-, body mass index (BMI)- and sex-matched subjects with normal glucose tolerance. Circulating MIF levels were measured using enzyme-linked immunosorbent assay. Metabolic parameters of recruited subjects were evaluated. Visceral fat mass was measured using bioelectrical impedance method. RESULTS Circulating MIF levels were found to be elevated in subjects with prediabetes compared to controls (26.46 ± 16.98 versus 17.44 ± 11.80 ng/mL, P = 0.007). MIF positively correlated with BMI, visceral fat mass and indirect indices of homeostasis model assessment of insulin resistance. In linear regression model, an independent association was found between MIF levels and metabolic parameters, including BMI, visceral fat mass and homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses revealed that the odds ratio for prediabetes was higher in subjects in the highest quartile of MIF compared to those in the lowest quartile, after adjusting for potential confounders. CONCLUSIONS Increased MIF levels are associated with the elevation of prediabetic risk.
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Affiliation(s)
- Oktay Bilgir
- Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey.
| | - Belma Gökçen
- Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
| | - Ferda Bilgir
- Department of Internal Medicine, Katip Celebi University Medical School, Izmir, Turkey
| | - Aslı Guler
- Department of Family Physician, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
| | - Mehmet Calan
- Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
| | - Arif Yuksel
- Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
| | - Behnaz Aslanıpour
- Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, Izmir, Turkey
| | - Murat Akşit
- Department of Biochemistry, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
| | - Giray Bozkaya
- Department of Biochemistry, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey
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Rajapaksha H, Bhatia H, Wegener K, Petrovsky N, Bruning JB. X-ray crystal structure of rivoglitazone bound to PPARγ and PPAR subtype selectivity of TZDs. Biochim Biophys Acta Gen Subj 2017; 1861:1981-1991. [DOI: 10.1016/j.bbagen.2017.05.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 04/28/2017] [Accepted: 05/08/2017] [Indexed: 01/08/2023]
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Hemmingsen B, Sonne DP, Metzendorf M, Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev 2017; 5:CD012204. [PMID: 28489279 PMCID: PMC6481586 DOI: 10.1002/14651858.cd012204.pub2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. OBJECTIVES To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials; MEDLINE; PubMed; Embase; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform; and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was January 2017. SELECTION CRITERIA We included randomised controlled trials (RCTs) with a duration of 12 weeks or more comparing DPP-4 inhibitors and GLP-1 analogues with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS Two review authors read all abstracts and full-text articles and records, assessed quality and extracted outcome data independently. One review author extracted data which were checked by a second review author. We resolved discrepancies by consensus or the involvement of a third review author. For meta-analyses, we planned to use a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence using the GRADE instrument. MAIN RESULTS We included seven completed RCTs; about 98 participants were randomised to a DPP-4 inhibitor as monotherapy and 1620 participants were randomised to a GLP-1 analogue as monotherapy. Two trials investigated a DPP-4 inhibitor and five trials investigated a GLP-1 analogue. A total of 924 participants with data on allocation to control groups were randomised to a comparator group; 889 participants were randomised to placebo and 33 participants to metformin monotherapy. One RCT of liraglutide contributed 85% of all participants. The duration of the intervention varied from 12 weeks to 160 weeks. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains and did not perform meta-analyses because there were not enough trials.One trial comparing the DPP-4 inhibitor vildagliptin with placebo reported no deaths (very low-quality evidence). The incidence of T2DM by means of WHO diagnostic criteria in this trial was 3/90 participants randomised to vildagliptin versus 1/89 participants randomised to placebo (very low-quality evidence). Also, 1/90 participants on vildagliptin versus 2/89 participants on placebo experienced a serious adverse event (very low-quality evidence). One out of 90 participants experienced congestive heart failure in the vildagliptin group versus none in the placebo group (very low-quality evidence). There were no data on non-fatal myocardial infarction, stroke, health-related quality of life or socioeconomic effects reported.All-cause and cardiovascular mortality following treatment with GLP-1 analogues were rarely reported; one trial of exenatide reported that no participant died. Another trial of liraglutide 3.0 mg showed that 2/1501 in the liraglutide group versus 2/747 in the placebo group died after 160 weeks of treatment (very low-quality evidence).The incidence of T2DM following treatment with liraglutide 3.0 mg compared to placebo after 160 weeks was 26/1472 (1.8%) participants randomised to liraglutide versus 46/738 (6.2%) participants randomised to placebo (very low-quality evidence). The trial established the risk for (diagnosis of) T2DM as HbA1c 5.7% to 6.4% (6.5% or greater), fasting plasma glucose 5.6 mmol/L or greater to 6.9 mmol/L or less (7.0 mmol/L or greater) or two-hour post-load plasma glucose 7.8 mmol/L or greater to 11.0 mmol/L (11.1 mmol/L). Altogether, 70/1472 (66%) participants regressed from intermediate hyperglycaemia to normoglycaemia compared with 268/738 (36%) participants in the placebo group. The incidence of T2DM after the 12-week off-treatment extension period (i.e. after 172 weeks) showed that five additional participants were diagnosed T2DM in the liraglutide group, compared with one participant in the placebo group. After 12-week treatment cessation, 740/1472 (50%) participants in the liraglutide group compared with 263/738 (36%) participants in the placebo group had normoglycaemia.One trial used exenatide and 2/17 participants randomised to exenatide versus 1/16 participants randomised to placebo developed T2DM (very low-quality evidence). This trial did not provide a definition of T2DM. One trial reported serious adverse events in 230/1524 (15.1%) participants in the liraglutide 3.0 mg arm versus 96/755 (12.7%) participants in the placebo arm (very low quality evidence). There were no serious adverse events in the trial using exenatide. Non-fatal myocardial infarction was reported in 1/1524 participants in the liraglutide arm and in 0/55 participants in the placebo arm at 172 weeks (very low-quality evidence). One trial reported congestive heart failure in 1/1524 participants in the liraglutide arm and in 1/755 participants in the placebo arm (very low-quality evidence). Participants receiving liraglutide compared with placebo had a small mean improvement in the physical component of the 36-item Short Form scale showing a difference of 0.87 points (95% CI 0.17 to 1.58; P = 0.02; 1 trial; 1791 participants; very low-quality evidence). No trial evaluating GLP-1-analogues reported data on stroke, microvascular complications or socioeconomic effects. AUTHORS' CONCLUSIONS There is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with placebo substantially influence the risk of T2DM and especially its associated complications in people at increased risk for the development of T2DM. Most trials did not investigate patient-important outcomes.
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Affiliation(s)
- Bianca Hemmingsen
- Herlev University HospitalDepartment of Internal MedicineHerlev Ringvej 75HerlevDenmarkDK‐2730
| | - David P Sonne
- Gentofte Hospital, University of CopenhagenCenter for Diabetes Research, Department of MedicineKildegaardsvej 28HellerupDenmarkDK‐2900
| | - Maria‐Inti Metzendorf
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupMoorenstr. 5DüsseldorfGermany40225
| | - Bernd Richter
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupMoorenstr. 5DüsseldorfGermany40225
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Knop FK, Brønden A, Vilsbøll T. Exenatide: pharmacokinetics, clinical use, and future directions. Expert Opin Pharmacother 2017; 18:555-571. [PMID: 28085521 DOI: 10.1080/14656566.2017.1282463] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The first-in-class glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide, which was initially approved in 2005, is available in twice-daily (BID) and once-weekly (QW) formulations. Clinical trial data suggest both formulations are effective and safe for patients with type 2 diabetes (T2D), both as monotherapy and as part of combination therapy. Since exenatide was approved, several other GLP-1RAs have become available for clinical use. Areas covered: Many ongoing clinical trials involving exenatide BID and exenatide QW are investigating new indications (exenatide BID) and new end points and combination therapies (exenatide QW). This review provides an overview of the delivery and pharmacokinetics of both formulations of exenatide, reviews existing data in T2D, and summarizes ongoing investigations. Expert opinion: Exenatide BID and QW have substantial clinical benefits. Comparisons with other GLP-1RAs demonstrate some differences in efficacy and safety profiles that make assessment of benefit:risk ratios complex. Head-to-head comparisons of QW GLP-1RA formulations may assist in the ranking of GLP-1RAs according to efficacy and safety. Results on the impact of exenatide QW on cardiovascular outcomes are eagerly awaited. The potential clinical utility of exenatide BID in other indications will clarify whether exenatide holds clinical promise in diagnoses other than T2D.
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Affiliation(s)
- Filip K Knop
- a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.,b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.,c The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Andreas Brønden
- a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.,b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Tina Vilsbøll
- a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.,b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
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Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes. PLoS One 2016; 11:e0158703. [PMID: 27398720 PMCID: PMC4939956 DOI: 10.1371/journal.pone.0158703] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 05/18/2016] [Indexed: 02/06/2023] Open
Abstract
Background Exenatide’s effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. Objective We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. Design and Methods After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro. Results OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIRG decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P<0.001) without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040) and clamp-based insulinogenic indexes (P = 0.016), improved insulin secretion in vitro (P = 0.041), but had no noticeable effect on insulin sensitivity (P = 0.405). Conclusions In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes.
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13
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Schwartz SS, Jellinger PS, Herman ME. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy’s safety profile. Postgrad Med 2016; 128:609-19. [DOI: 10.1080/00325481.2016.1191955] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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14
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Manaf A, Tjandrawinata RR, Malinda D. Insulin sensitizer in prediabetes: a clinical study with DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa. DRUG DESIGN DEVELOPMENT AND THERAPY 2016; 10:1279-89. [PMID: 27099473 PMCID: PMC4820281 DOI: 10.2147/dddt.s97568] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background The aim of this paper is to evaluate the efficacy and safety of DLBS3233, a novel bioactive fraction derived from Cinnamomum burmanii and Lagerstroemia speciosa, in improving insulin resistance and preserving β-cell performance in patients with impaired glucose tolerance (IGT). Patients and methods Eighty adult subjects with IGT, defined as 2-hour postprandial glucose level of 140–199 mg/dL, were enrolled in this two-arm, 12-week, double-blind, randomized, placebo-controlled preliminary study. Eligible subjects were randomly allocated to receive either DLBS3233 at a dose of 50–100 mg daily or placebo for 12 weeks. The study mainly assessed the improvement of homeostatic model-assessed insulin resistance (HOMA-IR), the 15-minute and 2-hour plasma insulin levels, and the oral disposition index. Results After 12 weeks, DLBS3233 improved insulin resistance better than placebo as reflected by a reduced HOMA-IR (−27.04%±29.41% vs −4.90%±41.27%, P=0.013). The improvement of the first- and second-phase insulin secretion was consistently greater in DLBS3233 group than placebo group (−144.78±194.06 vs −71.21±157.19, P=0.022, and −455.03±487.56 vs −269.49±467.77, P=0.033, respectively). Further, DLBS3233 also significantly better improved oral disposition index than placebo. No serious hypoglycemia, edema, or cardiovascular-related adverse events were found in either groups. Conclusion This study has shown that DLBS3233 at the dose of 50–100 mg once daily was well tolerated, and promisingly efficacious in improving insulin sensitivity as well as preserving β-cell performance in subjects with IGT.
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Affiliation(s)
- Asman Manaf
- Department of Internal Medicine, Faculty of Medicine, University of Andalas, Dr M Djamil Padang Hospital, Padang, Indonesia
| | | | - Desi Malinda
- Department of Internal Medicine, Faculty of Medicine, University of Andalas, Dr M Djamil Padang Hospital, Padang, Indonesia
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15
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Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin JR, Aguilar RB. The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell-Centric Classification Schema. Diabetes Care 2016; 39:179-86. [PMID: 26798148 PMCID: PMC5317235 DOI: 10.2337/dc15-1585] [Citation(s) in RCA: 201] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The current classification system presents challenges to the diagnosis and treatment of patients with diabetes mellitus (DM), in part due to its conflicting and confounding definitions of type 1 DM, type 2 DM, and latent autoimmune diabetes of adults (LADA). The current schema also lacks a foundation that readily incorporates advances in our understanding of the disease and its treatment. For appropriate and coherent therapy, we propose an alternate classification system. The β-cell-centric classification of DM is a new approach that obviates the inherent and unintended confusions of the current system. The β-cell-centric model presupposes that all DM originates from a final common denominator-the abnormal pancreatic β-cell. It recognizes that interactions between genetically predisposed β-cells with a number of factors, including insulin resistance (IR), susceptibility to environmental influences, and immune dysregulation/inflammation, lead to the range of hyperglycemic phenotypes within the spectrum of DM. Individually or in concert, and often self-perpetuating, these factors contribute to β-cell stress, dysfunction, or loss through at least 11 distinct pathways. Available, yet underutilized, treatments provide rational choices for personalized therapies that target the individual mediating pathways of hyperglycemia at work in any given patient, without the risk of drug-related hypoglycemia or weight gain or imposing further burden on the β-cells. This article issues an urgent call for the review of the current DM classification system toward the consensus on a new, more useful system.
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Affiliation(s)
- Stanley S Schwartz
- Main Line Health, Wynnewood, PA, and University of Pennsylvania, Philadelphia, PA
| | - Solomon Epstein
- Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Mount Sinai Hospital, New York, NY
| | - Barbara E Corkey
- Department of Medicine, Boston University School of Medicine, Boston, MA
| | - Struan F A Grant
- Division of Human Genetics and Center for Applied Genomics, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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16
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Affiliation(s)
- K M Venkat Narayan
- Emory Global Diabetes Research Center, Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA Department of Medicine, School of Medicine, Emory University, Atlanta, GA
| | - Unjali P Gujral
- Emory Global Diabetes Research Center, Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
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Abstract
People with elevated, non-diabetic, levels of blood glucose are at risk of progressing to clinical type 2 diabetes and are commonly termed 'prediabetic'. The term prediabetes usually refers to high-normal fasting plasma glucose (impaired fasting glucose) and/or plasma glucose 2 h following a 75 g oral glucose tolerance test (impaired glucose tolerance). Current US guidelines consider high-normal HbA1c to also represent a prediabetic state. Individuals with prediabetic levels of dysglycaemia are already at elevated risk of damage to the microvasculature and macrovasculature, resembling the long-term complications of diabetes. Halting or reversing the progressive decline in insulin sensitivity and β-cell function holds the key to achieving prevention of type 2 diabetes in at-risk subjects. Lifestyle interventions aimed at inducing weight loss, pharmacologic treatments (metformin, thiazolidinediones, acarbose, basal insulin and drugs for weight loss) and bariatric surgery have all been shown to reduce the risk of progression to type 2 diabetes in prediabetic subjects. However, lifestyle interventions are difficult for patients to maintain and the weight loss achieved tends to be regained over time. Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomised trials, such as the Diabetes Prevention Program and other studies. Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe. We have reviewed in detail the evidence base supporting the therapeutic use of metformin for diabetes prevention.
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Affiliation(s)
| | - Mike Gwilt
- />GT Communications, 4 Armoury Gardens, Shrewsbury, SY2 6PH UK
| | - Steven Hildemann
- />Merck KGaA, Darmstadt, Germany
- />Universitäts-Herzzentrum Freiburg–Bad Krozingen, Bad Krozingen, Germany
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18
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Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2015; 162:765-76. [PMID: 25867111 DOI: 10.7326/m14-2221] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Screening for type 2 diabetes mellitus could lead to earlier identification and treatment of asymptomatic diabetes, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), potentially resulting in improved outcomes. PURPOSE To update the 2008 U.S. Preventive Services Task Force review on diabetes screening in adults. DATA SOURCES Cochrane databases and MEDLINE (2007 through October 2014) and relevant studies from previous Task Force reviews. STUDY SELECTION Randomized, controlled trials; controlled, observational studies; and systematic reviews. DATA EXTRACTION Data were abstracted by 1 investigator and checked by a second; 2 investigators independently assessed study quality. DATA SYNTHESIS In 2 trials, screening for diabetes was associated with no 10-year mortality benefit versus no screening (hazard ratio, 1.06 [95% CI, 0.90 to 1.25]). Sixteen trials consistently found that treatment of IFG or IGT was associated with delayed progression to diabetes. Most trials of treatment of IFG or IGT found no effects on all-cause or cardiovascular mortality, although lifestyle modification was associated with decreased risk for both outcomes after 23 years in 1 trial. For screen-detected diabetes, 1 trial found no effect of an intensive multifactorial intervention on risk for all-cause or cardiovascular mortality versus standard control. In diabetes that was not specifically screen-detected, 9 systematic reviews found that intensive glucose control did not reduce risk for all-cause or cardiovascular mortality and results for intensive blood pressure control were inconsistent. LIMITATION The review was restricted to English-language articles, and few studies were conducted in screen-detected populations. CONCLUSION Screening for diabetes did not improve mortality rates after 10 years of follow-up. More evidence is needed to determine the effectiveness of treatments for screen-detected diabetes. Treatment of IFG or IGT was associated with delayed progression to diabetes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.
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Affiliation(s)
- Shelley Selph
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
| | - Tracy Dana
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
| | - Ian Blazina
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
| | - Christina Bougatsos
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
| | - Hetal Patel
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
| | - Roger Chou
- From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
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Chwastiak LA, Freudenreich O, Tek C, McKibbin C, Han J, McCarron R, Wisse B. Clinical management of comorbid diabetes and psychotic disorders. Lancet Psychiatry 2015; 2:465-476. [PMID: 26360289 DOI: 10.1016/s2215-0366(15)00105-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 03/06/2015] [Accepted: 03/09/2015] [Indexed: 12/17/2022]
Abstract
Individuals with psychotic disorders experience substantial health disparities with respect to diabetes, including increased risk of incident diabetes and of poor diabetes outcomes (eg, diabetes complications and mortality). Low-quality medical care for diabetes is a significant contributor to these poor health outcomes. A thoughtful approach to both diabetes pharmacotherapy and drug management for psychotic disorders is essential, irrespective of whether treatment is given by a psychiatrist, a primary care provider, or an endocrinologist. Exposure to drugs with high metabolic liability should be minimised, and both psychiatric providers and medical providers need to monitor patients to ensure that medical care for diabetes is adequate. Promising models of care management and team approaches to coordination and integration of care highlight the crucial need for communication and cooperation among medical and psychiatric providers to improve outcomes in these patients. Evidence-based programmes that promote weight loss or smoking cessation need to be more accessible for these patients, and should be available in all the settings where they access care.
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Affiliation(s)
- Lydia A Chwastiak
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
| | - Oliver Freudenreich
- Department of Psychiatry, Massachusetts General Hospital, Harvard University School of Medicine, Boston, MA, USA
| | - Cenk Tek
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | | | - Jaesu Han
- Department of Psychiatry, University of California, Davis, Sacramento, CA, USA; Department of Family and Community Medicine, University of California, Davis, Sacramento, CA, USA
| | - Robert McCarron
- Department of Psychiatry, University of California, Davis, Sacramento, CA, USA; Department of Family and Community Medicine, University of California, Davis, Sacramento, CA, USA
| | - Brent Wisse
- Department of Medicine, Division of Endocrinology, University of Washington School of Medicine, Seattle, WA, USA
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20
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Schwartz S, Herman M. Revisiting weight reduction and management in the diabetic patient: Novel therapies provide new strategies. Postgrad Med 2015; 127:480-93. [PMID: 25913393 DOI: 10.1080/00325481.2015.1043182] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Weight gain has been so synonymous with diabetes care that overweight/obesity is considered an intractable aspect of diabetes and its management. A healthy body mass index (BMI) is paramount, however, in preserving the cardiometabolic profile, slowing the course of the disease and extending the life expectancy of patients. It is also key to fostering a healthy and productive society at large. Two trends in care press us to challenge our assumptions about weight control in this population by reconsidering traditional approaches to the management of diabetes. First, new anti-diabetes drug classes have emerged that are more "weight-friendly" than previously available treatments and "gentler" on the faltering β cell. Second, novel anti-obesity agents are proving efficacious in patients with diabetes. This paper presents the composite of newer and older anti-obesity and anti-diabetic drugs. It makes recommendations for anti-diabetic regimens and processes of care that engender weight loss, or neutralize or minimize weight gain, while getting many patients to their glycated hemoglobin (HbA1c) goal. Anti-obesity agents that can be safely and effectively incorporated into these regimens for the patient needing supplemental support are reviewed in detail.
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Affiliation(s)
- Stanley Schwartz
- Main Line Health System, University of Pennsylvania, Philadelphia,, PA , USA
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21
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Doi SAR, Ward GM. Examination of the fasting and 2-h plasma glucose in the light of impairment in beta-cell function: what does the epidemiological data tell us? Endocrine 2015; 48:170-8. [PMID: 24880620 DOI: 10.1007/s12020-014-0284-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Accepted: 05/02/2014] [Indexed: 10/25/2022]
Abstract
We re-assess the fasting plasma glucose (FPG) and 2-h post-load glucose (2HPG) in the diagnosis of both prediabetes and type 2 diabetes mellitus by developing a gold standard based on beta-cell function. The gold standard was developed in a cohort of 2,152 adult subjects without severe renal or liver dysfunction that also had a 2-h oral glucose tolerance test (OGTT) during the Third National Health and Nutrition Examination Survey. Beta-cell function was computed based on a composite of insulin secretion (determined based on the insulin and glucose responses to the OGTT) and the homeostasis model insulin resistance index. The X-tile program was used to generate the most appropriate categories of minor, moderate and severe impairment of beta-cell function based on the best discrimination of ln(insulin secretion). Subjects with a moderate or severe impairment in beta-cell function were used to define prediabetes and diabetes, respectively, and was the standard against which the FPG and 2HPG were evaluated. It is shown that the current definitions of diabetes by the FPG and 2HPG mirror those derived using impairment of beta-cell function as the gold standard. It is also shown that lowering the cutoff for the FPG does little to improve its use in the screening for prediabetes. A major finding is that the current 2HPG cutoff is inadequate and thus in need of revision to >6.7 mmol/L (>120 mg/dL) from 7.8 mmol/L (140 mg/dL) for the lower cutoff. The use of a model of beta-cell function and impairment of insulin secretion has thus put the utility of the FPG and 2HPG into perspective: We recommend that performing an OGTT be considered pivotal for accurate identification of subjects with impaired beta-cell function (and thus prediabetes) and a revision of the OGTT lower cutoff be considered based on the results of this study.
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Affiliation(s)
- Suhail A R Doi
- Clinical Epidemiology Unit, School of Population Health, University of Queensland, Brisbane, Herston Road, Herston, QLD, 4006, Australia,
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22
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[The association of hyperinsulinemia with cardiovascular risk and cancer poses new challenges in the treatment of the insulin resistance type 2 diabetes patient]. HIPERTENSION Y RIESGO VASCULAR 2015; 32:21-6. [PMID: 26179854 DOI: 10.1016/j.hipert.2014.06.001] [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: 06/12/2014] [Revised: 06/14/2014] [Accepted: 06/16/2014] [Indexed: 11/20/2022]
Abstract
Hyperinsulinemia has been associated with cardiovascular risk, both independently and by facilitating the development of other cardiovascular risk factors. It has also been associated by different routes with increased cancer risk. Thus, this makes it a priority to identify and treat the hyperinsulinemic patient early in order to delay or prevent cardiovascular risk and the development of type 2 diabetes mellitus (T2DM) and certain types of cancer. A new strategy is needed for the treatment of hyperglycemia in these patients, whose primary objective would be to achieve weight loss, reduce insulin resistance and thereby hyperinsulinemia. That is, prescribing insulin secretors and insulin should be used with caution in these patients.
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23
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Papaetis GS. Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes 2014; 5:817-834. [PMID: 25512784 PMCID: PMC4265868 DOI: 10.4239/wjd.v5.i6.817] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2014] [Revised: 09/10/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D.
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Schwartz S. Evidence-based practice use of incretin-based therapy in the natural history of diabetes. Postgrad Med 2014; 126:66-84. [PMID: 24918793 DOI: 10.3810/pgm.2014.05.2757] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The incretin class of anti-hyperglycemic agents, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-inhibitors, is an important addition to the therapeutic armamentarium for the management of appropriate patients with type 2 diabetes mellitus as an adjunct to diet and exercise and/or with the agents metformin, sulfonylureas, thiazolidinediones, or any combination thereof. More recently, US Food and Drug Administration (FDA)-approved indications for incretins were expanded to include use with basal insulin. This review article takes an evidence-based practice approach in discussing the importance of aggressive treatment for diabetes, the principles of incretin physiology and pathophysiology, use of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, and patient types and contexts where incretin therapy has been found beneficial, from metabolic syndrome to overt diabetes.
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Affiliation(s)
- Stanley Schwartz
- Affiliate, Main Line Health System, Ardmore, PA; Emeritus, Clinical Associate Professor of Medicine, University of Pennsylvania, Philadelphia, PA.
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25
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Ruby RJ, Armato JP, Pyke C, Peters AL. GLP-1 provoked severe hypoglycemia in an individual with type 2 diabetes and a benign insulinoma. Diabetes Care 2014; 37:e177-8. [PMID: 25061148 DOI: 10.2337/dc14-0514] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
| | | | - Charles Pyke
- Histology and Imaging, Novo Nordisk A/S, Bagsvaerd, Denmark
| | - Anne L Peters
- Division of Endocrinology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
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Comprehensive biomarker testing of glycemia, insulin resistance, and beta cell function has greater sensitivity to detect diabetes risk than fasting glucose and HbA1c and is associated with improved glycemic control in clinical practice. J Cardiovasc Transl Res 2014; 7:597-606. [PMID: 25070680 PMCID: PMC4137169 DOI: 10.1007/s12265-014-9577-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 07/15/2014] [Indexed: 12/29/2022]
Abstract
Blood-based biomarker testing of insulin resistance (IR) and beta cell dysfunction may identify diabetes risk earlier than current glycemia-based approaches. This retrospective cohort study assessed 1,687 US patients at risk for cardiovascular disease (CVD) under routine clinical care with a comprehensive panel of 19 biomarkers and derived factors related to IR, beta cell function, and glycemic control. The mean age was 53 ± 15, 42 % were male, and 25 % had glycemic indicators consistent with prediabetes. An additional 45 % of the patients who had normal glycemic indicators were identified with IR or beta cell abnormalities. After 5.3 months of median follow-up, significantly more patients had improved than worsened their glycemic status in the prediabetic category (35 vs. 9 %; P < 0.0001) and in the “high normal” category (HbA1c values of 5.5–5.6; 56 vs. 18 %, p < 0.0001). Biomarker testing can identify IR early, enable and inform treatment, and improve glycemic control in a high proportion of patients.
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Soliman A, DeSanctis V, Yassin M, Elalaily R, Eldarsy NE. Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups. Indian J Endocrinol Metab 2014; 18:274-282. [PMID: 24944918 PMCID: PMC4056122 DOI: 10.4103/2230-8210.131130] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Continuous glucose monitoring (CGM) systems are an emerging technology that allows frequent glucose measurements to monitor glucose trends in real time. Their use as a diagnostic tool is still developing and appears to be promising. Combining intermittent glucose self-monitoring (SGM) and CGM combines the benefits of both. Significant improvement in the treatment modalities that may prevent the progress of prediabetes to diabetes have been achieved recently and dictates screening of high risk patients for early diagnosis and management of glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia (prediabetes) especially in high risk patients appears to be an attractive approach. In this review we searched the literature to investigate the value of using CGMS as a diagnostic tool compared to other known tools, namely oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin (HbA1C) in high risk groups. Those categories of patients include adolescents and adults with obesity especially those with family history of type 2 diabetes mellitus, polycystic ovary syndrome (PCO), gestational diabetes, cystic fibrosis, thalassemia major, acute coronary syndrome (ACS), and after renal transplantation. It appears that the ability of the CGMS for frequently monitoring (every 5 min) glucose changes during real-life settings for 3 to 5 days stretches the chance to detect more glycemic abnormalities during basal and postprandial conditions compared to other short-timed methods.
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Affiliation(s)
- Ashraf Soliman
- Department of Pediatric, Alexandria University Children's Hospital, Alexandria, Egypt
| | - Vincenzo DeSanctis
- Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, 44121 Ferrara, Italy
| | - Mohamed Yassin
- Department of Hematology and Oncology, Alamal Hospital, Hamad Medical Center, Doha, Qatar
| | | | - Nagwa E Eldarsy
- Department of Pediatric, Alexandria University Children's Hospital, Alexandria, Egypt
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Mudaliar S. Choice of early treatment regimen and impact on β-cell preservation in type 2 diabetes. Int J Clin Pract 2013; 67:876-87. [PMID: 23952467 DOI: 10.1111/ijcp.12154] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Accepted: 02/15/2013] [Indexed: 12/21/2022] Open
Abstract
The progressive deterioration of glycaemic control in individuals with type 2 diabetes mellitus (T2DM) results from insulin resistance combined with the ongoing loss of β-cell function. Although it had been suggested that most β-cell dysfunction occurs after the development of T2DM, studies have documented a substantial early loss of β-cell function, particularly during the prediabetic state. In patients diagnosed with T2DM, β-cell function continues to decline despite treatment with commonly prescribed antihyperglycaemic medications, and ultimately exogenous insulin administration is required to maintain optimal glycaemic control. Thus, interventions to address the early decline in β-cell function could potentially alter the course of T2DM, preventing or delaying its onset and decreasing the incidence of complications. Original research and review articles on this topic were identified in a PubMed search from January 2000 through August 2012. Data from prospective studies and clinical trials suggest that lifestyle modifications and certain antihyperglycaemic medications, including thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and insulin, may preserve or enhance β-cell function. The implication of current data is that early initiation of lifestyle modifications and antihyperglycaemic agents that preserve β-cell function might reverse or delay progression to T2DM in those with prediabetes. Moreover, improved β-cell function may confer more durable glucose control and perhaps reduce/delay the incidence of diabetic complications. Long-term studies are needed to validate this hypothesis.
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Affiliation(s)
- S Mudaliar
- Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA, USA.
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Bergman M. Pathophysiology of prediabetes and treatment implications for the prevention of type 2 diabetes mellitus. Endocrine 2013; 43:504-13. [PMID: 23132321 DOI: 10.1007/s12020-012-9830-9] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 10/23/2012] [Indexed: 01/03/2023]
Abstract
Type 2 diabetes and other non-communicable diseases (NCD) are a growing public health challenge globally. An estimated 285 million people, corresponding to 6.4 % of the world's adult population has diabetes. This is expected to reach 552 million by 2030, 7.8 % of the adult population, with the African region expected to experience the greatest increase. A much larger segment of the world's population, approximating 79 million individuals in the US alone, has prediabetes. Multiple factors including genetic predisposition, insulin resistance, increased insulin secretory demand, glucotoxicity, lipotoxicity, impaired incretin release/action, amylin accumulation, and decreased β-cell mass play a causative role in the progressive β-cell dysfunction characteristic of prediabetes. Interventions preventing progression to type 2 diabetes should therefore delay or prevent β-cell failure. This article will first review the principal pathophysiological mechanisms underlying prediabetes and subsequently address treatment considerations based on these in the prevention of type 2 diabetes. In view of long-standing safety data with demonstrated efficacy and cost-effectiveness in the prevention of type 2 diabetes in high-risk individuals, metformin should be considered as initial therapy for those unable to comply with or lifestyle modification or where the latter has been ineffective in decreasing progression to type 2 diabetes.
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Affiliation(s)
- Michael Bergman
- Department of Medicine, Division of Endocrinology, NYU School of Medicine, 345 East 37th Street, Suite 313, New York, NY 10016, USA.
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