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Deng H, Peng K, Zhang L, Lu J, Mei W, Shi X, Peng Y, Xu K, Li H, Wang Z, Lu G, Wang G, Lu Z, Cao F, Wen L. Clinical Outcomes in a Multicenter Cohort Involving 919 Patients With Hypertriglyceridemia-Associated Acute Pancreatitis. Am J Gastroenterol 2025:00000434-990000000-01549. [PMID: 39817674 DOI: 10.14309/ajg.0000000000003319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/30/2024] [Indexed: 01/18/2025]
Abstract
INTRODUCTION Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is one of the most common etiologies of acute pancreatitis (AP) worldwide. Compared with other etiologies, patients with HTG-AP may develop more severe AP, but previous studies yielded controversial conclusion due to the lack of adequate adjustment for the confounders. Therefore, the aim of this study was to examine the possibility and risk factors of developing severe AP in HTG-AP. METHODS Data from patients with an established diagnosis of AP were collected from January 2013 to December 2023 using a predesigned data collection form and were gathered from 5 tertiary cross-regional centers of China. HTG-AP was defined as serum triglyceride levels >500 mg/dL and excluded other etiologies. The possibility and risk factors of severe AP were assessed by multivariable logistic regressions after adjusting potential confounders. A prediction model was established and validated. RESULTS Between 2013 and 2023, we identified a total of 6,996 patients with AP, of whom 4,378 were included in the final analysis. Compared with other etiologies, patients with HTG-AP had a higher risk of developing severe AP (odds ratio: 1.897; 95% confidence interval: 1.380-2.608; P < 0.001) and organ failure. HTG-AP patients showed higher possibility for developing respiratory and circulation failure but renal failure compared with other etiologies. In HTG-AP patients, risk factors of severe AP included age, fasting blood glucose, white blood cell counts, and presence of pleural effusion. TG level was found not significantly associated with severity in HTG-AP patients. A prediction model incorporating these risk factors demonstrated an area under the curve (AUC) of 0.837 in the training and 0.883 in the testing set, with adequate calibration. DISCUSSION Using a multicenter cross-regional cohort, we demonstrated that HTG-AP had a higher risk of developing severe AP and organ failure. A risk prediction model for predicting severe AP was developed and effectively stratified patients.
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Affiliation(s)
- Hanzhang Deng
- Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing China
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Kaixin Peng
- Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing China
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Liang Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing China
| | - Jiongdi Lu
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Wentong Mei
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Xiaolei Shi
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilong Jiang Province, China
| | - Yunpeng Peng
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Kedong Xu
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Haoxuan Li
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zheng Wang
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Guotao Lu
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilong Jiang Province, China
| | - Gang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing China
| | - Zipeng Lu
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Feng Cao
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Li Wen
- Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
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ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Ebekozien O, Echouffo-Tcheugui JB, Ekhlaspour L, Gaglia JL, Garg R, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Selvin E, Stanton RC, Bannuru RR. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S27-S49. [PMID: 39651986 PMCID: PMC11635041 DOI: 10.2337/dc25-s002] [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: 07/15/2024] [Accepted: 09/12/2024] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Sun Y, Lu B, Hu Y, Lv Y, Zhong S. Glycemic Variability in Pancreatogenic Diabetes Mellitus: characteristics, Risks, Potential Mechanisms, and Treatment Possibilities. Int J Gen Med 2024; 17:4297-4309. [PMID: 39324147 PMCID: PMC11423834 DOI: 10.2147/ijgm.s477497] [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: 05/09/2024] [Accepted: 09/03/2024] [Indexed: 09/27/2024] Open
Abstract
In recent years, pancreatogenic diabetes mellitus has garnered significant attention due to its high incidence, complications, and mortality rates. Glycemic variability (GV) can increase the risk of pancreatogenic diabetes mellitus and its associated complications; however, the precise mechanism remains unclear. The effective control of GV is crucial for preventing the onset of pancreatic diabetes mellitus and improving prognosis. Both diet and antidiabetic medications have substantial effects on GV. However, many patients are prescribed suboptimal or even harmful drugs. Therefore, to provide a comprehensive treatment basis for clinicians to prevent and treat pancreatogenic diabetes mellitus, this study aimed to elucidate the relationship between GV and pancreatogenic diabetes mellitus; investigate the potential mechanisms (such as oxidative stress, inflammatory response, insulin resistance, and lipid metabolism disorders); provide lifestyle guidance; and recommend drug selections to reduce the GV in patients with pancreatogenic diabetes mellitus.
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Affiliation(s)
- Yuyan Sun
- Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China
| | - Bing Lu
- Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China
| | - Yuanwen Hu
- Department of Gastroenterology, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China
| | - Yingqi Lv
- Division of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
| | - Shao Zhong
- Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China
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Cho J, Petrov MS. Epidemiology of post-pancreatitis diabetes mellitus: insights from the COSMOS program. Expert Rev Endocrinol Metab 2024; 19:419-428. [PMID: 39037189 DOI: 10.1080/17446651.2024.2382958] [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: 01/07/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024]
Abstract
INTRODUCTION Post-pancreatitis diabetes mellitus (PPDM) has long been recognized as one of the most challenging sub-types of diabetes to manage. Part of the problem is that the earlier literature on epidemiology of PPDM was confusing because of the presence of selection bias. AREAS COVERED A concerted series of population-based nationwide studies on PPDM from New Zealand has recently been published as part of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS) program and is the main focus of the present article. EXPERT OPINION The foundational knowledge on epidemiology of PPDM generated by the COSMOS program is generalizable to the population at large. It brings the field closer to a comprehensive narrative of risk factors, burden, mortality, and morbidity outcomes of PPDM. In producing new knowledge on epidemiology of PPDM, it will be important to adhere to the guidelines on identification of PPDM in population-based datasets advanced in the present article.
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Affiliation(s)
- Jaelim Cho
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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Zhang J, Wang X, Lv Y, Hou J, Zhang C, Su X, Li L. Impact of stress hyperglycemia on long-term prognosis in acute pancreatitis without diabetes. Intern Emerg Med 2024; 19:681-688. [PMID: 38372886 DOI: 10.1007/s11739-023-03524-0] [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: 08/08/2023] [Accepted: 12/25/2023] [Indexed: 02/20/2024]
Abstract
Stress hyperglycemia has been confirmed as a strong predictor of poor short-term prognosis in acute pancreatitis. However, whether stress hyperglycemia affects the long-term prognosis of patients with acute pancreatitis is unclear. We aimed to investigate the effect of stress hyperglycemia on the long-term prognosis of non-diabetic patients with acute pancreatitis. This retrospective observational study was conducted on 4055 patients with acute pancreatitis from 1 January 2016 to 31 October 2020. The association between stress hyperglycemia and the prognosis was evaluated using regression modeling. There were 935(71.5%) normoglycemic and 373(28.5%) stress hyperglycemia patients. 46(12.3%) patients with stress hyperglycemia had evidence of diabetes compared with 33(3.5%) patients without stress hyperglycemia (P < 0.001). After multivariate adjustment, patients with stress hyperglycemia were more likely to have evidence of diabetes (OR 2.905, 95% CI 1.688-4.999) compared with normoglycemic. However, stress hyperglycemia is not associated with the recurrence of pancreatitis and progression to chronic pancreatitis. Stress hyperglycemia was independently associated with diabetes secondary to acute pancreatitis. Accordingly, a follow-up diabetes-screening program for AP with stress hyperglycemia is an important part of identifying the disease as soon as possible, delaying islet damage, and improving the prognosis of post-acute pancreatitis diabetes mellitus.
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Affiliation(s)
- Jun Zhang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Xiaoyuan Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Jiaying Hou
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Chi Zhang
- Department of Endocrinology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China.
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Wang Z, Zhang G, Fu J, Li G, Zhao Z, Choe H, Ding K, Ma J, Wei J, Shang D, Zhang L. Mechanism exploration and biomarker identification of glycemic deterioration in patients with diseases of the exocrine pancreas. Sci Rep 2024; 14:4374. [PMID: 38388766 PMCID: PMC10883946 DOI: 10.1038/s41598-024-52956-x] [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: 05/29/2023] [Accepted: 01/25/2024] [Indexed: 02/24/2024] Open
Abstract
The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.
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Affiliation(s)
- Zhen Wang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China
| | - Guolin Zhang
- Department of Cardiology II, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, China
| | - Jixian Fu
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Guangxing Li
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
| | - Zhihao Zhao
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
| | - HyokChol Choe
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
- Department of Clinical Medicine, Sinuiju Medical University, Sinuiju, Republic of Korea
| | - Kaiyue Ding
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
| | - Junnan Ma
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
| | - Jing Wei
- Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
| | - Dong Shang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China.
| | - Lin Zhang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116044, China.
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Li X, Petrov MS. Dietary Fibre for the Prevention of Post-Pancreatitis Diabetes Mellitus: A Review of the Literature and Future Research Directions. Nutrients 2024; 16:435. [PMID: 38337719 PMCID: PMC10857198 DOI: 10.3390/nu16030435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/30/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
Post-pancreatitis diabetes mellitus-the most common sequela of pancreatitis-leads to poorer glycaemic control compared with type 2 diabetes. Because post-pancreatitis diabetes mellitus is an exemplar of secondary diabetes (with a clear underlying cause), much post-pancreatitis diabetes mellitus is preventable or treatable early. Earlier literature established the important role of dietary fibre in reducing plasma glucose in individuals with type 2 diabetes. The present review benchmarks available evidence on the role of habitual dietary fibre intake in pancreatitis and post-pancreatitis diabetes mellitus. It also paves the way for future research on the use of dietary fibre in the post-pancreatitis setting.
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Affiliation(s)
| | - Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland 1023, New Zealand
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Zahariev OJ, Bunduc S, Kovács A, Demeter D, Havelda L, Budai BC, Veres DS, Hosszúfalusi N, Erőss BM, Teutsch B, Juhász MF, Hegyi P. Risk factors for diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Front Med (Lausanne) 2024; 10:1257222. [PMID: 38264039 PMCID: PMC10803425 DOI: 10.3389/fmed.2023.1257222] [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] [Received: 07/12/2023] [Accepted: 12/12/2023] [Indexed: 01/25/2024] Open
Abstract
Introduction Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as high as 59% over time. However, information on risk factors is limited. We aimed to identify risk factors for developing PD or DM following AP. Methods We systematically searched three databases up to 4 September 2023 extracting direct, within-study comparisons of risk factors on the rate of new-onset PD and DM in AP patients. When PD and DM event rates could not be separated, we reported results for this composite outcome as PD/DM. Meta-analysis was performed using the random-effects model to calculate pooled odds ratios (OR) with 95% confidence intervals (CI). Results Of the 61 studies identified, 50 were included in the meta-analysis, covering 76,797 participants. The studies reported on 79 risk factors, and meta-analysis was feasible for 34 risk factor and outcome pairs. The odds of developing PD/DM was significantly higher after severe and moderately severe AP (OR: 4.32; CI: 1.76-10.60) than mild AP. Hypertriglyceridemic AP etiology (OR: 3.27; CI: 0.17-63.91) and pancreatic necrosis (OR: 5.53; CI: 1.59-19.21) were associated with a higher risk of developing PD/DM. Alcoholic AP etiology (OR: 1.82; CI: 1.09-3.04), organ failure (OR: 3.19; CI: 0.55-18.64), recurrent AP (OR: 1.89; CI: 0.95-3.77), obesity (OR: 1.85; CI: 1.43-2.38), chronic kidney disease (OR: 2.10; CI: 1.85-2.38), liver cirrhosis (OR: 2.48; CI: 0.18-34.25), and dyslipidemia (OR: 1.82; CI: 0.68-4.84) were associated with a higher risk of developing DM. Discussion Severe and moderately severe AP, alcoholic and hypertriglyceridemic etiologies, pancreatic necrosis, organ failure, recurrent acute pancreatitis and comorbidities of obesity, chronic kidney disease liver disease, and dyslipidemia are associated with a higher risk of developing PD or DM. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021281983.
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Affiliation(s)
- Olga Julia Zahariev
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Stefania Bunduc
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Adrienn Kovács
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - Dóra Demeter
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Dietetic Services, Central Hospital of Northern Pest - Military Hospital, Budapest, Hungary
| | - Luca Havelda
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Bettina Csilla Budai
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Dániel Sándor Veres
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | - Nóra Hosszúfalusi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - Bálint Mihály Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Márk Félix Juhász
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Heim Pál National Pediatric Institute, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Translational Pancreatology Research Group, Interdisciplinary Center of Excellence for Research Development and Innovation University of Szeged, Szeged, Hungary
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Gaglia JL, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Selvin E, Stanton RC, Gabbay RA. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S20-S42. [PMID: 38078589 PMCID: PMC10725812 DOI: 10.2337/dc24-s002] [Citation(s) in RCA: 431] [Impact Index Per Article: 431.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Sun HY, Lin XY. Analysis of the management and therapeutic performance of diabetes mellitus employing special target. World J Diabetes 2023; 14:1721-1737. [PMID: 38222785 PMCID: PMC10784800 DOI: 10.4239/wjd.v14.i12.1721] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/31/2023] [Accepted: 10/23/2023] [Indexed: 12/14/2023] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantly by hyperglycemia. The most common causes contributing to the pathophysiology of diabetes are insufficient insulin secretion, resistance to insulin's tissue-acting effects, or a combination of both. Over the last 30 years, the global prevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure is found, this amount might climb to 430 million in the coming years. The major factors of the disease's deterioration include age, obesity, and a sedentary lifestyle. Finding new therapies to manage diabetes safely and effectively without jeopardizing patient compliance has always been essential. Among the medications available to manage DM on this journey are glucagon-like peptide-1 agonists, thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targeting receptors discovered more than 10 years ago. Despite the extensive preliminary studies, a few clinical observations suggest this process is still in its early stages. The present review focuses on targets that contribute to insulin regulation and may be employed as targets in treating diabetes since they may be more efficient and secure than current and traditional treatments.
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Affiliation(s)
- Hong-Yan Sun
- Department of Endocrine and Metabolic Diseases, Yantaishan Hospital, Yantai 264003, Shandong Province, China
| | - Xiao-Yan Lin
- Department of Endocrine and Metabolic Diseases, Yantaishan Hospital, Yantai 264003, Shandong Province, China
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Petrov MS, Olesen SS. Metabolic Sequelae: The Pancreatitis Zeitgeist of the 21st Century. Gastroenterology 2023; 165:1122-1135. [PMID: 37549751 DOI: 10.1053/j.gastro.2023.07.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 07/20/2023] [Accepted: 07/24/2023] [Indexed: 08/09/2023]
Abstract
Holistic management of pancreatitis means that gastroenterologists in the 21st Century should think beyond improving in-hospital outcomes of pancreatitis alone. In particular, there is considerable room for optimizing the management of new-onset diabetes, exocrine pancreatic insufficiency, and other metabolic sequelae of pancreatitis. The present article provides state-of-the-art information on classification, terminology, and burden of the common sequelae of pancreatitis. A high-risk group of patients with pancreatitis is identified, which is positioned to benefit the most from the metabolic sequelae surveillance program introduced in this article. The program involves continuous follow-up after pancreatitis diagnosis, with the focus on early identification of new-onset diabetes after pancreatitis and exocrine pancreatic insufficiency. The metabolic sequelae surveillance program is scalable and has the potential to reduce the burden of pancreatitis through tertiary prevention in the decades to come.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Søren S Olesen
- Department of Gastroenterology and Hepatology, Center for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark; Clinical Institute, Aalborg University, Aalborg, Denmark
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12
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Seguí Díaz M, Pérez Unanua MP, Peral Martínez I, López Serrano A, Aguirre Rodríguez JC. [Type 3 c diabetes: Approach from the first level doctor]. Semergen 2023; 49:102074. [PMID: 37672810 DOI: 10.1016/j.semerg.2023.102074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 07/21/2023] [Indexed: 09/08/2023]
Abstract
DM3c is diabetes (DM) of the exocrine pancreas that must be suspected whenever there is a history of chronic pancreatitis (CP), acute pancreatitis (AP) or recurrence (80% of cases) or new-onset DM in individuals from over 50 years of age without any other justification (negative autoimmunity tests, Glutamic Acid Decarboxylase antibodies). It is an entity misdiagnosed as type 2 diabetes (DM2) (90%) and therefore, if it is not suspected, it can go unnoticed. For its diagnosis, abdominal ultrasound, determination of the CA 19.9 tumor antigen (carbohydrate antigen 19-9), nuclear magnetic resonance (NMR) or computerized axial tomography (CT) are useful. The treatment is the same as DM2, although certain specifications depend on the type of drugs and with the particularity that in dealing with «fragile diabetes» greater caution must be taken with hypoglycemia (monitoring). Likewise, as it is a disease of the exocrine pancreas, it will have to be specifically treated to avoid metabolic, malabsorptive and/or nutritional alterations.
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Affiliation(s)
- M Seguí Díaz
- Unidad Básica de Salud de Es Castell, Menorca, España.
| | | | | | | | - J C Aguirre Rodríguez
- Centro de Salud Fortuny Velutti, Distrito Sanitario Granada Metropolitano, Granada, España
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13
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Charley E, Dinner B, Pham K, Vyas N. Diabetes as a consequence of acute pancreatitis. World J Gastroenterol 2023; 29:4736-4743. [PMID: 37664150 PMCID: PMC10473919 DOI: 10.3748/wjg.v29.i31.4736] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/17/2023] [Accepted: 07/28/2023] [Indexed: 08/18/2023] Open
Abstract
Diabetes is a highly prevalent disease that was initially simplified into three major types: Type 1, type 2 and gestational diabetes. With the global rise in incidence of acute pancreatitis (AP), a lesser-known type of diabetes referred to as diabetes of the exocrine pancreas (DEP) is becoming more recognized. However, there is a poor understanding of the inherent relationship between diabetes and AP. There is established data about certain diseases affecting the exocrine function of the pancreas which can lead to diabetes. More specifically, there are well established guidelines for diagnosis and management of DEP caused be chronic pancreatitis. Conversely, the sequelae of AP leading to diabetes has limited recognition and data. The purpose of this review is to provide a comprehensive summary of the prevalence, epidemiology, pathophysiology and future research aims of AP-related diabetes. In addition, we propose a screening and diagnostic algorithm to aid clinicians in providing better care for their patients.
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Affiliation(s)
- Ericka Charley
- Department of Gastroenterology, Creighton University - St. Joseph’s Hospital and Medical Center Phoenix, AZ 85013, United States
| | - Brett Dinner
- Department of Internal Medicine, Creighton University St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, United States
| | - Kimberly Pham
- Department of Internal Medicine, Creighton University St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, United States
| | - Neil Vyas
- Department of Gastroenterology, Creighton University St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, United States
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14
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García-Compeán D, Jiménez-Rodríguez AR, Muñoz-Ayala JM, González-González JA, Maldonado-Garza HJ, Villarreal-Pérez JZ. Post-acute pancreatitis diabetes: A complication waiting for more recognition and understanding. World J Gastroenterol 2023; 29:4405-4415. [PMID: 37576704 PMCID: PMC10415972 DOI: 10.3748/wjg.v29.i28.4405] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 06/22/2023] [Accepted: 07/11/2023] [Indexed: 07/26/2023] Open
Abstract
Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.
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Affiliation(s)
- Diego García-Compeán
- Department of Gastroenterology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Alan R Jiménez-Rodríguez
- Department of Gastroenterology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Juan M Muñoz-Ayala
- Department of Gastroenterology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Department of Gastroenterology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Héctor J Maldonado-Garza
- Department of Gastroenterology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Jesús Z Villarreal-Pérez
- Department of Endocrinology, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
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15
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Goodarzi MO, Petrov MS. Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management. Drugs 2023:10.1007/s40265-023-01913-5. [PMID: 37410209 PMCID: PMC10361873 DOI: 10.1007/s40265-023-01913-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2023] [Indexed: 07/07/2023]
Abstract
Post-pancreatitis diabetes mellitus, pancreatic cancer-related diabetes, and cystic fibrosis-related diabetes are often underappreciated. As a result, a substantial proportion of people with these sub-types of diabetes receive antidiabetic medications that may be suboptimal, if not harmful, in the context of their underlying disease of the exocrine pancreas. The present article delineates both classical (biguanides, insulin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, and meglitinides) and newer (glucagon-like peptide-1 receptor agonists, amylin analogs, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, D2 receptor agonists, bile acid sequestrants, and dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor co-agonists) therapies and provides recommendations for managing people with diabetes of the exocrine pancreas based on the most up-to-date clinical evidence. Also, several emerging directions (lipid-enriched pathways, Y4 receptor agonism, glucagon-like peptide-1 and glucagon receptor co-agonism) are presented with a view to informing the process of new drug discovery and development.
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Affiliation(s)
- Mark O Goodarzi
- Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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16
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Petrov MS. Fatty change of the pancreas: the Pandora's box of pancreatology. Lancet Gastroenterol Hepatol 2023; 8:671-682. [PMID: 37094599 DOI: 10.1016/s2468-1253(23)00064-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 04/26/2023]
Abstract
Prevention of common diseases of the pancreas or interception of their progression is as attractive in theory as it is elusive in practice. The fundamental challenge has been an incomplete understanding of targets coupled with a multitude of intertwined factors that are associated with the development of pancreatic diseases. Evidence over the past decade has shown unique morphological features, distinctive biomarkers, and complex relationships of intrapancreatic fat deposition. Fatty change of the pancreas has also been shown to affect at least 16% of the global population. This knowledge has solidified the pivotal role of fatty change of the pancreas in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. The pancreatic diseases originating from intrapancreatic fat (PANDORA) hypothesis advanced in this Personal View cuts across traditional disciplinary boundaries with a view to tackling these diseases. New holistic understanding of pancreatic diseases is well positioned to propel pancreatology through lasting research breakthroughs and clinical advances.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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17
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Shrivastav D, Dabla PK, Sharma J, Viswas A, Mir R. Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus: A narrative review of randomized control trials. World J Diabetes 2023; 14:919-929. [DOI: 10.4239/wjd.v14.i6.919 shrivastav d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2023] Open
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18
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Shrivastav D, Dabla PK, Sharma J, Viswas A, Mir R. Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus: A narrative review of randomized control trials. World J Diabetes 2023; 14:919-929. [PMID: 37383600 PMCID: PMC10294058 DOI: 10.4239/wjd.v14.i6.919] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/11/2023] [Accepted: 05/11/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Imbalance in generation and elimination of free radicals generate oxidative stress which modulates glucose metabolism and insulin regulation, resulting in the occurrence and progression of diabetes and associated complications. Antioxidant supplements in T2DM can be seen as a potential preventive and effective therapeutic strategy.
AIM To compare randomized controlled trials (RCTs) in which antioxidants have been shown to have a therapeutic effect in T2DM patients.
METHODS We systematically searched the electronic database PubMed by keywords. RCTs evaluating the effect of antioxidant therapy on glycaemic control as well as oxidant and antioxidant status as primary outcomes were included. The outcomes considered were: A reduction in blood glucose; changes in oxidative stress and antioxidant markers. Full-length papers of the shortlisted articles were assessed for the eligibility criteria and 17 RCTs were included.
RESULTS The administration of fixed-dose antioxidants significantly reduces fasting blood sugar and glycated hemoglobin and is associated with decreased malondialdehyde, advanced oxidation protein products, and increased total antioxidant capacity.
CONCLUSION Antioxidant supplements can be a beneficial approach for the treatment of T2DM.
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Affiliation(s)
| | - Pradeep Kumar Dabla
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Jitender Sharma
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Aroop Viswas
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Rashid Mir
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
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19
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Zhang J, Lv Y, Hou J, Zhang C, Yua X, Wang Y, Yang T, Su X, Ye Z, Li L. Machine learning for post-acute pancreatitis diabetes mellitus prediction and personalized treatment recommendations. Sci Rep 2023; 13:4857. [PMID: 36964219 PMCID: PMC10038980 DOI: 10.1038/s41598-023-31947-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 03/20/2023] [Indexed: 03/26/2023] Open
Abstract
Post-acute pancreatitis diabetes mellitus (PPDM-A) is the main component of pancreatic exocrine diabetes mellitus. Timely diagnosis of PPDM-A improves patient outcomes and the mitigation of burdens and costs. We aimed to determine risk factors prospectively and predictors of PPDM-A in China, focusing on giving personalized treatment recommendations. Here, we identify and evaluate the best set of predictors of PPDM-A prospectively using retrospective data from 820 patients with acute pancreatitis at four centers by machine learning approaches. We used the L1 regularized logistic regression model to diagnose early PPDM-A via nine clinical variables identified as the best predictors. The model performed well, obtaining the best AUC = 0.819 and F1 = 0.357 in the test set. We interpreted and personalized the model through nomograms and Shapley values. Our model can accurately predict the occurrence of PPDM-A based on just nine clinical pieces of information and allows for early intervention in potential PPDM-A patients through personalized analysis. Future retrospective and prospective studies with multicentre, large sample populations are needed to assess the actual clinical value of the model.
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Affiliation(s)
- Jun Zhang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Jiaying Hou
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, 831100, China
| | - Chi Zhang
- Department of Endocrinology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China
| | - Xuelu Yua
- Department of Endocrinology, Yixing Second People's Hospital, Wuxi, 214200, China
| | - Yifan Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Ting Yang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, 831100, China
| | - Zheng Ye
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China.
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Institute of Pancreas, Southeast University, Nanjing, 210009, China.
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China.
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Institute of Pancreas, Southeast University, Nanjing, 210009, China.
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20
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S19-S40. [PMID: 36507649 PMCID: PMC9810477 DOI: 10.2337/dc23-s002] [Citation(s) in RCA: 1099] [Impact Index Per Article: 549.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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21
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Ko J, Sequeira IR, Skudder-Hill L, Cho J, Poppitt SD, Petrov MS. Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis. Diabetologia 2023; 66:190-200. [PMID: 36194248 PMCID: PMC9729324 DOI: 10.1007/s00125-022-05793-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 08/08/2022] [Indexed: 12/14/2022]
Abstract
AIMS/HYPOTHESIS The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.
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Affiliation(s)
- Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Ivana R Sequeira
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition, National Science Challenge, Auckland, New Zealand
| | | | - Jaelim Cho
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Sally D Poppitt
- School of Medicine, University of Auckland, Auckland, New Zealand
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition, National Science Challenge, Auckland, New Zealand
- Riddet Centre of Research Excellence for Food and Nutrition, Palmerston North, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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22
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Infante M, Ricordi C. The unique pathophysiological features of diabetes mellitus secondary to total pancreatectomy: proposal for a new classification distinct from diabetes of the exocrine pancreas. Expert Rev Endocrinol Metab 2023; 18:19-32. [PMID: 36692892 DOI: 10.1080/17446651.2023.2168645] [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: 09/07/2022] [Accepted: 01/11/2023] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Diabetes of the exocrine pancreas (DEP; a.k.a. pancreatic diabetes or pancreatogenic diabetes or type 3c diabetes mellitus or T3cDM) refers to different diabetes types resulting from disorders of the exocrine pancreas. DEP is characterized by the structural and functional loss of glucose-normalizing insulin secretion in the context of exocrine pancreatic dysfunction. Among these forms, new-onset diabetes mellitus secondary to total pancreatectomy (TP) has unique pathophysiological and clinical features, for which we propose a new nomenclature such as post-total pancreatectomy diabetes mellitus (PTPDM). AREAS COVERED TP results in the complete loss of pancreatic parenchyma, with subsequent absolute insulinopenia and lifelong need for exogenous insulin therapy. Patients with PTPDM also exhibit deficiency of glucagon, amylin and pancreatic polypeptide. These endocrine abnormalities, coupled with increased peripheral insulin sensitivity, deficiency of pancreatic enzymes and TP-related modifications of gastrointestinal anatomy, can lead to marked glucose variability and increased risk of iatrogenic (insulin-induced) severe hypoglycemic episodes ('brittle diabetes'). EXPERT OPINION We believe that diabetes mellitus secondary to TP should not be included in the DEP spectrum in light of its peculiar pathophysiological and clinical features. Therefore, we propose a new classification for this entity, that would likely provide more accurate prognosis and treatment strategies.
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Affiliation(s)
- Marco Infante
- Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, Miami, FL, USA
- Section of Diabetes and Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy
- Diabetes Research Institute Federation (DRIF), Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Rome, Italy
| | - Camillo Ricordi
- Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, Miami, FL, USA
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23
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Via MA. Diabetes and Parenteral Nutrition. CONTEMPORARY ENDOCRINOLOGY 2023:413-426. [DOI: 10.1007/978-3-031-44648-1_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Singh A, Aggarwal M, Garg R, Stevens T, Chahal P. Post-pancreatitis diabetes mellitus: insight on optimal management with nutrition and lifestyle approaches. Ann Med 2022; 54:1776-1786. [PMID: 35786076 PMCID: PMC9254994 DOI: 10.1080/07853890.2022.2090601] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Pancreatitis is the leading gastrointestinal cause of hospitalizations. There are multiple short- and long-term complications associated with pancreatitis. Post-pancreatitis diabetes mellitus (PPDM) is one of the less explored complications of pancreatitis. Nonetheless, it has attracted considerable attention during the last decade. PPDM is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM. However, there exists a knowledge gap amongst practitioners regarding diagnosis, complications, and management of PPDM. In this narrative, we aim to provide a brief review regarding risks, diagnosis and management of PPDM with a special focus on dietary and lifestyle management strategies.KEY MESSAGESPost-pancreatitis diabetes mellitus (PPDM) is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM.New-onset diabetes in patients with pancreatitis could also be an early marker of occult pancreatic malignancy.Management of PPDM is complex and requires a team-based approach including gastroenterologists, endocrinologists, primary care physicians, nutritionists, and behavioural health specialists.
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Affiliation(s)
- Amandeep Singh
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Manik Aggarwal
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Rajat Garg
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tyler Stevens
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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25
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Kimita W, Ko J, Li X, Bharmal SH, Petrov MS. Associations Between Iron Homeostasis and Pancreatic Enzymes After an Attack of Pancreatitis. Pancreas 2022; 51:1277-1283. [PMID: 37099767 DOI: 10.1097/mpa.0000000000002195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
OBJECTIVES Dysregulation of iron homeostasis and exocrine pancreatic dysfunction are linked but remain undefined in individuals with a history of pancreatitis. The objective is to investigate the relationship between iron homeostasis and pancreatic enzymes in individuals after a pancreatitis attack. METHODS This was a cross-sectional study of adults with a history of pancreatitis. Markers of iron metabolism (hepcidin and ferritin) and pancreatic enzymes (pancreatic amylase, pancreatic lipase, and chymotrypsin) were measured in venous blood. Habitual dietary iron intake data (total, heme, and nonheme iron) were collected. Multivariable linear regression analyses were performed while considering covariates. RESULTS One hundred and one participants were studied at a median of 18 months after their last pancreatitis attack. Hepcidin was significantly associated with pancreatic amylase (β coefficient, -6.68; 95% confidence interval, -12.88 to -0.48; P = 0.035) and heme iron intake (β coefficient, 0.34; 95% confidence interval, 0.08 to 0.60; P = 0.012) in the adjusted model. Hepcidin was not significantly associated with pancreatic lipase or chymotrypsin. Ferritin was not significantly associated with pancreatic enzymes and dietary iron intake. CONCLUSIONS An iron homeostasis-exocrine pancreas crosstalk exists in individuals after an attack of pancreatitis. The role of iron homeostasis in pancreatitis warrants high-quality purposely-designed studies.
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Affiliation(s)
- Wandia Kimita
- From the School of Medicine, University of Auckland, Auckland, New Zealand
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Intrapancreatic, Liver, and Skeletal Muscle Fat Depositions in First Attack of Acute Pancreatitis Versus Health. Am J Gastroenterol 2022; 117:1693-1701. [PMID: 35971231 DOI: 10.14309/ajg.0000000000001951] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 08/05/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Increased intrapancreatic fat deposition (IPFD) has emerged as a harbinger of pancreatic cancer and chronic pancreatitis. Although it is well recognized that diseases of the exocrine pancreas often lie on a continuum (with acute pancreatitis preceding the development of chronic pancreatitis and/or pancreatic cancer), whether increased IPFD predisposes to acute pancreatitis is unknown. This study aimed to compare fat depositions in the pancreas (as well as the liver and skeletal muscle) between individuals who developed first attack of acute pancreatitis and healthy individuals. METHODS This was a matched case-control study nested into population-based cohort. MRI on a single 3 T scanner was used to quantify intrapancreatic, liver, and skeletal muscle fat depositions using the same protocols in all study participants. Binary logistic regression with adjustment for body mass index and other possible confounders was performed. RESULTS Fifty individuals with first attack of nonnecrotizing acute pancreatitis comprised the case group and 100 healthy individuals comprised the control group. A 1% increase in IPFD (but not the other fat depositions) was significantly associated with a more than 30% higher chance of developing first attack of acute pancreatitis, consistently in both the unadjusted ( P = 0.004) and all adjusted models. Furthermore, a 1% increase in IPFD (but not the other fat depositions) was significantly associated with up to a 27% higher chance of developing first attack of acute pancreatitis in individuals with normotriglyceridemia, consistently in both the unadjusted ( P = 0.030) and all adjusted models. DISCUSSION Increased IPFD may predispose to the development of acute pancreatitis. This opens up opportunities for reducing the burden of acute pancreatitis by means of primary prevention.
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Factors Affecting the Circulating Levels of Oxyntomodulin in Health and After Acute Pancreatitis. Pancreas 2022; 51:774-783. [PMID: 36395403 DOI: 10.1097/mpa.0000000000002114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVES To investigate the factors associated with the circulating levels of oxyntomodulin in healthy individuals and individuals after an episode of acute pancreatitis (AP). METHODS Blood samples were collected from all participants after an overnight fast and analyzed for 28 biomarkers. Participants also underwent comprehensive body composition analysis on a 3-T magnetic resonance imaging scanner. Regression analyses were done to investigate the associations between oxyntomodulin and the studied factors. RESULTS The study included 105 individuals who had a primary diagnosis of AP and 58 healthy individuals. Peptide YY (B coefficient, 0.094; 95% confidence interval [95% CI], 0.164-0.123), pancreatic polypeptide (0.048; 95% CI, 0.030-0.066), and leptin (0.394; 95% CI, 0.128-0.661) had significant associations with oxyntomodulin in healthy individuals. Peptide YY was the most prominent factor associated with oxyntomodulin, explaining 60% of its variance in health. Cholecystokinin (0.014; 95% CI, 0.010-0.018), amylin (-0.107; 95% CI, -0.192 to -0.021), and glycated hemoglobin (-0.761; 95% CI, -1.249 to -0.273) had significant associations with oxyntomodulin in individuals after AP. Cholecystokinin was the most prominent factor associated with oxyntomodulin, explaining 44% of its variance after AP. CONCLUSIONS Factors affecting the circulating levels of oxyntomodulin are different in health and after AP. These insights will enable the determination of populations that benefit from oxyntomodulin therapeutics in the future.
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Olesen SS, Viggers R, Drewes AM, Vestergaard P, Jensen MH. Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality in Postpancreatitis Diabetes Mellitus Versus Type 2 Diabetes: A Nationwide Population-Based Cohort Study. Diabetes Care 2022; 45:1326-1334. [PMID: 35312752 DOI: 10.2337/dc21-2531] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/22/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Postpancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and associates with poor glycemic control. We investigated the risk of adverse diabetes-related outcomes in PPDM compared with type 2 diabetes. RESEARCH DESIGN AND METHODS In this Danish population-based cohort study, we included adults (>18 years) with incident PPDM or type 2 diabetes between 1998 and 2018 through national health registries. PPDM was further divided into acute (PPDM-A) and chronic (PPDM-C) subtypes. We ascertained risk of major adverse cardiovascular events (MACE), severe hypoglycemia, and all-cause mortality as well as incidence rates of severe hypoglycemia. We compared risk and incidence rates across diabetes subgroups using multivariate Cox and Poisson regression analyses. RESULTS We identified 383,325 people with incident type 2 diabetes, 3,418 with PPDM-A, and 2,461 with PPDM-C. Compared with type 2 diabetes, PPDM-C was associated with increased risks of severe hypoglycemia (hazard ratio [HR] 5.27, 95% CI 4.62-6.00, P < 0.001) and all-cause mortality (HR 1.54, 95% CI 1.45-1.64, P < 0.001). Similar patterns were observed for people with PPDM-A. Incidence rate ratios (IRRs) for severe hypoglycemia were increased in both PPDM-C (IRR 7.38, 95% CI 6.75-8.08, P < 0.001) and PPDM-A (IRR 3.76, 95% CI 3.36-4.21, P < 0.001) compared with type 2 diabetes. Findings were consistent in an analysis restricted to people on insulin and in an analysis including pancreatitis patients without diabetes as comparator group. CONCLUSIONS Compared with type 2 diabetes, PPDM is associated with excess risk of adverse diabetes-related outcomes. This has important implications for management.
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Affiliation(s)
- Søren S Olesen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark
| | - Rikke Viggers
- Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn M Drewes
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Peter Vestergaard
- Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Morten H Jensen
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.,Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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Lee N, Park SJ, Kang D, Jeon JY, Kim HJ, Kim DJ, Lee KW, Boyko EJ, Han SJ. Characteristics and Clinical Course of Diabetes of the Exocrine Pancreas: A Nationwide Population-Based Cohort Study. Diabetes Care 2022; 45:1141-1150. [PMID: 35226735 DOI: 10.2337/dc21-1659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 02/04/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The natural course of diabetes of the exocrine pancreas (DEP) is not well established. We aimed to compare the risk of insulin initiation, diabetic complications, and mortality between DEP and type 2 diabetes. RESEARCH DESIGN AND METHODS Using the Korean National Health Insurance Service-Health Screening Cohort between 2012 and 2017, we divided patients with diabetes into those with diabetes without prior pancreatic disease (indicated type 2 diabetes, n = 153,894) and diabetes with a prior diagnosis of pancreatic disease (indicated DEP, n = 3,629). ICD-10 codes and pharmacy prescription information were used to define type 2 diabetes, DEP, and acute and chronic diabetes complications. Kaplan-Meier curves were produced to compare insulin use over time between groups. We created logistic regression models for odds of progression to diabetic complications and mortality. RESULTS DEP was associated with a higher risk of insulin use than type 2 diabetes (adjusted hazard ratio 1.38 at 5 years [95% CI 1.30-1.47], P < 0.0001). Individuals with DEP showed higher risks of hypoglycemia (odds ratio 1.85 [1.54-2.21], P < 0.0001), diabetic neuropathy (1.38 [1.28-1.49], P < 0.0001), nephropathy (1.38 [1.27-1.50], P < 0.0001), retinopathy (1.10 [1.01-1.20], P = 0.0347), coronary heart disease (1.59 [1.48-1.70], P < 0.0001), cerebrovascular disease (1.38 [1.28-1.49], P < 0.0001), and peripheral arterial disease (1.34 [1.25-1.44], P < 0.0001). All-cause mortality was higher in those with DEP (1.74 [1.57-1.93], P < 0.0001) than in those with type 2 diabetes. CONCLUSIONS DEP is more likely to require insulin therapy than type 2 diabetes. Hypoglycemia, micro- and macrovascular complications, and all-cause mortality events are higher in DEP compared with type 2 diabetes.
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Affiliation(s)
- Nami Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
| | - So Jeong Park
- Data Science Team, Hanmi Pharmaceutical Co., Ltd, Seoul, South Korea
| | - Dongwoo Kang
- Data Science Team, Hanmi Pharmaceutical Co., Ltd, Seoul, South Korea
| | - Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
| | - Kwan-Woo Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
| | - Edward J Boyko
- Veterans Affairs Puget Sound Health Care System, Seattle, WA
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
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Norbitt CF, Kimita W, Bharmal SH, Ko J, Petrov MS. Relationship between Habitual Intake of Vitamins and New-Onset Prediabetes/Diabetes after Acute Pancreatitis. Nutrients 2022; 14:nu14071480. [PMID: 35406092 PMCID: PMC9003206 DOI: 10.3390/nu14071480] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 02/01/2023] Open
Abstract
Vitamins have many established roles in human health. However, the role of habitual dietary intake of vitamins in glucose homeostasis in individuals after acute pancreatitis (AP) is yet to be elucidated. The aim was to investigate the associations between habitual intake of fat- and water-soluble vitamins/vitamers and markers of glucose metabolism (fasting plasma glucose (FPG), homeostasis model assessment insulin resistance (HOMA-IR) index, and homeostasis model assessment β-cell function (HOMA-β)) in individuals after AP. A total of 106 participants after AP were included in this cross-sectional study and were grouped based on glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Habitual intake of seven fat-soluble vitamins/vitamers and seven water-soluble vitamins were determined by the EPIC-Norfolk food frequency questionnaire. Multiple linear regression analyses were conducted using five statistical models built to adjust for covariates (age, sex, daily energy intake, visceral/subcutaneous fat volume ratio, smoking status, daily alcohol intake, aetiology of AP, number of AP episodes, cholecystectomy, and use of antidiabetic medications). In the NODAP group, three fat-soluble vitamins/vitamers (α-carotene, β-carotene, and total carotene) were significantly associated with HOMA-β. One water-soluble vitamin (vitamin B3) was also significantly associated with HOMA-β in the NODAP group. None of the studied vitamins were significantly associated with FPG or HOMA-IR in the NODAP group. Prospective longitudinal studies and randomised controlled trials are now warranted to investigate if the observed associations between vitamin/vitamer intake and NODAP are causal and to unveil the specific mechanisms underlying their involvement with NODAP.
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Petrov MS, Taylor R. Intra-pancreatic fat deposition: bringing hidden fat to the fore. Nat Rev Gastroenterol Hepatol 2022; 19:153-168. [PMID: 34880411 DOI: 10.1038/s41575-021-00551-0] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 02/07/2023]
Abstract
Development of advanced modalities for detection of fat within the pancreas has transformed understanding of the role of intra-pancreatic fat deposition (IPFD) in health and disease. There is now strong evidence for the presence of minimal (but not negligible) IPFD in healthy human pancreas. Diffuse excess IPFD, or fatty pancreas disease (FPD), is more frequent than type 2 diabetes mellitus (T2DM) (the most common disease of the endocrine pancreas) and acute pancreatitis (the most common disease of the exocrine pancreas) combined. FPD is not strictly a function of high BMI; it can result from the excess deposition of fat in the islets of Langerhans, acinar cells, inter-lobular stroma, acinar-to-adipocyte trans-differentiation or replacement of apoptotic acinar cells. This process leads to a wide array of diseases characterized by excess IPFD, including but not limited to acute pancreatitis, chronic pancreatitis, pancreatic cancer, T2DM, diabetes of the exocrine pancreas. There is ample evidence for FPD being potentially reversible. Weight loss-induced decrease of intra-pancreatic fat is tightly associated with remission of T2DM and its re-deposition with recurrence of the disease. Reversing FPD will open up opportunities for preventing or intercepting progression of major diseases of the exocrine pancreas in the future.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Roy Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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Bharmal SH, Cho J, Ko J, Petrov MS. Glucose variability during the early course of acute pancreatitis predicts two‐year probability of new‐onset diabetes: A prospective longitudinal cohort study. United European Gastroenterol J 2022; 10:179-189. [PMID: 35188346 PMCID: PMC8911543 DOI: 10.1002/ueg2.12190] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 12/09/2021] [Indexed: 12/12/2022] Open
Abstract
Background Acute pancreatitis (AP) is the largest contributor to diabetes of the exocrine pancreas. However, there is no accurate predictor at the time of hospitalisation for AP to identify individuals at high risk for new‐onset diabetes. Objective To investigate the accuracy of indices of glucose variability (GV) during the early course of AP in predicting the glycated haemoglobin (HbA1c) trajectories during follow‐up. Methods This was a prospective longitudinal cohort study of patients without diabetes at the time of hospitalisation for AP. Fasting blood glucose was regularly measured over the first 72 h of hospital admission. The study endpoint was the HbA1c trajectories ‐ high‐increasing, moderate‐stable, normal‐stable ‐ over two years of follow‐up. Multinomial logistic regression analyses were conducted to investigate the associations between several common GV indices and the HbA1c trajectories, adjusting for covariates (age, sex, and body mass index). A sensitivity analysis constrained to patients with non‐necrotising AP was conducted. Results A total of 120 consecutive patients were studied. All patients in the high‐increasing HbA1c trajectory group had new‐onset diabetes at 18 and 24 months of follow‐up. Glycaemic lability index had the strongest significant direct association (adjusted odds ratio = 13.69; p = 0.040) with the high‐increasing HbA1c trajectory. High admission blood glucose, standard deviation of blood glucose, and average real variability significantly increased the patients' odds of taking the high‐increasing HbA1c trajectory by at least two‐times. Admission blood glucose, but not the other GV indices, had a significant direct association (adjusted odds ratio = 1.46; p = 0.034) with the moderate‐stable HbA1c trajectory. The above findings did not change materially in patients with non‐necrotising AP alone. Conclusions High GV during the early course of AP gives a prescient warning of worsening HbA1c pattern and new‐onset diabetes after hospital discharge. Determining GV during hospitalisation could be a relatively straightforward approach to early identification of individuals at high risk for new‐onset diabetes after AP.
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Affiliation(s)
| | - Jaelim Cho
- School of Medicine University of Auckland Auckland New Zealand
| | - Juyeon Ko
- School of Medicine University of Auckland Auckland New Zealand
| | - Maxim S. Petrov
- School of Medicine University of Auckland Auckland New Zealand
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Lv Y, Zhang J, Yang T, Sun J, Hou J, Chen Z, Yu X, Yuan X, Lu X, Xie T, Yu T, Su X, Liu G, Zhang C, Li L. Non-Alcoholic Fatty Liver Disease (NAFLD) Is an Independent Risk Factor for Developing New-Onset Diabetes After Acute Pancreatitis: A Multicenter Retrospective Cohort Study in Chinese Population. Front Endocrinol (Lausanne) 2022; 13:903731. [PMID: 35692404 PMCID: PMC9174455 DOI: 10.3389/fendo.2022.903731] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Numerous studies validated frequent glucose dysfunction in patients with acute pancreatitis (AP). However, the prevalence of new-onset diabetes in individuals after a first episode of AP varies widely among previous studies. This study aims to determine the incidence of post-acute pancreatitis diabetes mellitus (PPDM-A) in Chinese people and further identify potential risk factors that influence diabetes development in patients with AP. METHODS This was a multi-center retrospective cohort study including 6009 inpatients with a first attack of AP. A total of 1804 patients with AP without known endocrine pancreatic disorders or other pancreatic exocrine diseases were eligible for analysis. Data was collected from medical records by hospital information system and telephone follow-ups after discharge. The multiple logistic regression analysis was established to evaluate the potential influencing factors of PPDM-A. RESULTS The prevalence of newly diagnosed diabetes after a first episode of AP in China was 6.2%. Data showed that patients who developed PPDM-A were more likely to be younger (X2 = 6.329, P = 0.012), experienced longer hospital stays (X2 = 6.949, P = 0.008) and had a higher frequency of overweight or obesity (X2 = 11.559, P = 0.003) compared to those with normal glycemia. The frequency of stress hyperglycemia on admission (X2 = 53.815, P < 0.001), hyperlipidemia (X2 = 33.594, P < 0.001) and non-alcoholic fatty liver disease (NAFLD) (X2 = 36.335, P < 0.001) were significantly higher among individuals with PPDM-A compared with control group. Also, patients with PPDM-A were more likely to be hyperlipidemic AP (X2 = 16.304, P = 0.001) and show a higher degree of severity (X2 = 7.834, P = 0.020) and recurrence rate (X2 = 26.908, P < 0.001) of AP compared to those without diabetes. In addition, multiple logistic regression analysis indicated that stress hyperglycemia, hyperlipidemia, NAFLD and repeated attacks of AP were the independent influence factors for developing PPDM-A. CONCLUSION Our study first demonstrated the prevalence of secondary diabetes in Chinese patients after AP. The disorder of glucose metabolism in individuals with AP should be regularly evaluated in clinical practice. Further studies are needed to verify the relationship between liver and pancreas in keeping glucose homeostasis under AP condition.
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Affiliation(s)
- Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jun Zhang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ting Yang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jinfang Sun
- Key Laboratory of Environmental, Medicine Engineering, Ministry of Education, school of Public Health, Southeast University, Nanjing, China
| | - Jiaying Hou
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Zhiwei Chen
- Department of Endocrinology, Hunan Provincial People’s Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China
| | - Xuehua Yu
- Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, China
| | - Xuelu Yuan
- Department of Endocrinology, Yixing Second People’s Hospital, Wuxi, China
| | - Xuejia Lu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ting Xie
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ting Yu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Gaifang Liu
- Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, China
- *Correspondence: Ling Li, ; Chi Zhang, ; Gaifang Liu,
| | - Chi Zhang
- Department of Endocrinology, Hunan Provincial People’s Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China
- *Correspondence: Ling Li, ; Chi Zhang, ; Gaifang Liu,
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- *Correspondence: Ling Li, ; Chi Zhang, ; Gaifang Liu,
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Li G, Sun J, Zhang J, Lv Y, Liu D, Zhu X, Qi L, Chen Z, Ye Z, Su X, Li L. Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis. Front Endocrinol (Lausanne) 2022; 13:839865. [PMID: 35498402 PMCID: PMC9046596 DOI: 10.3389/fendo.2022.839865] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 12/12/2022] Open
Abstract
Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein-protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA-mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level.
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Affiliation(s)
- Guoqing Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jinfang Sun
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Jun Zhang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Dechen Liu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
- Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiangyun Zhu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Liang Qi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zhiwei Chen
- Department of Endocrinology, Hunan Provincial People’s Hospital, First Affiliated Hospital of Hunan Normal University, Hunan, China
| | - Zheng Ye
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
- *Correspondence: Xianghui Su, ; Ling Li,
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
- *Correspondence: Xianghui Su, ; Ling Li,
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Li L, Pandol SJ. Editorial: Interaction between endocrine and exocrine pancreas. Front Endocrinol (Lausanne) 2022; 13:967066. [PMID: 35966106 PMCID: PMC9372586 DOI: 10.3389/fendo.2022.967066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 06/24/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
- Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- *Correspondence: Ling Li, ; S. J. Pandol,
| | - S. J. Pandol
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Basic and Translational Pancreatic Research, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- *Correspondence: Ling Li, ; S. J. Pandol,
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Qi L, Wei Q, Ni M, Liu D, Bao J, Lv Y, Xia H, Wang Q, Wang L, Su J, Sj P, Li L. Pancreatic and gut hormone responses to mixed meal test in post-chronic pancreatitis diabetes mellitus. DIABETES & METABOLISM 2021; 48:101316. [PMID: 34929379 DOI: 10.1016/j.diabet.2021.101316] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE . - More than one-third of chronic pancreatitis patients will eventually develop diabetes, recently classified as post-chronic pancreatitis diabetes mellitus (PPDM-C). This study was aimed to investigate the pancreatic and gut hormone responses to a mixed meal test in PPDM-C patients, compared with non-diabetic chronic pancreatitis (CP), and type 2 diabetes patients or healthy controls. DESIGN AND METHODS .- Sixteen patients with PPDM-C, 12 with non-diabetic CP as well as 10 with type 2 diabetes and healthy controls were recruited. All participants underwent mixed meal tests, and blood samples were collected for measurements of blood glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, peptide YY, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Indices of insulin sensitivity and secretion were calculated. Repeated measures analysis of variance was performed. RESULTS . - Participants with PPDM-C exhibited decreases in both fasting and postprandial responses of C-peptide (P < 0.001), insulin (P < 0.001), ghrelin (P < 0.001) and PYY (P = 0.006) compared to participants with type 2 diabetes and healthy controls. Patients with CP showed blunted glucagon, PP and incretin reactions, while the responses were increased in patients with PPDM-C compared to controls. The level of insulin sensitivity was higher for PPDM-C than type 2 diabetes (P < 0.01), however the indices for early/late-phase and overall insulin secretion (P < 0.01) were lower. CONCLUSIONS .- Patients with PPDM-C are characterized by decreased C-peptide, insulin, ghrelin and PYY responses, and similar levels of glucagon, PP, GIP and GLP-1 compared to those with type 2 diabetes. The above findings, when confirmed in a larger population, may prove helpful to establish the diagnosis of PPDM-C, and should promote study on underlying pathophysiological mechanisms.
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Affiliation(s)
- Liang Qi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Qiong Wei
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Institute of Pancreas, Southeast University, Nanjing, China
| | - Muhan Ni
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Dechen Liu
- Institute of Pancreas, Southeast University, Nanjing, China; Department of Clinical Science and Research, Zhongda Hospital, Southeast University, Nanjing, China
| | - Jiantong Bao
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Hong Xia
- Department of Endocrinology, Jintan District People's Hospital Affiliated to Jiangsu University, Changzhou, China
| | - Qian Wang
- Department of Endocrinology, Jintan District People's Hospital Affiliated to Jiangsu University, Changzhou, China
| | - Lei Wang
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
| | - Jianhua Su
- Jintan District People's Hospital Affiliated to Jiangsu University, Changzhou, China.
| | - Pandol Sj
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Institute of Pancreas, Southeast University, Nanjing, China.
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Olesen SS, Svane HML, Nicolaisen SK, Kristensen JK, Drewes AM, Brandslund I, Beck-Nielsen H, Nielsen JS, Thomsen RW. Clinical and biochemical characteristics of postpancreatitis diabetes mellitus: A cross-sectional study from the Danish nationwide DD2 cohort. J Diabetes 2021; 13:960-974. [PMID: 34240829 DOI: 10.1111/1753-0407.13210] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/24/2021] [Accepted: 07/05/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Postpancreatitis diabetes mellitus (PPDM) is a common metabolic sequalae of acute and chronic pancreatitis. We conducted a cross-sectional study to examine the proportion of PPDM among patients clinically diagnosed with type 2 diabetes (T2D) in Denmark and their clinical and biochemical characteristics. METHODS We identified all past diagnoses of pancreatitis among patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort through linkage with national health registries. Using International Classification of Diseases, Tenth Revision codes we categorized patients as PPDM and further divided them into acute/chronic subtypes (PPDM-A and PPDM-C). We assessed PPDM prevalence and examined associations with clinical and biochemical parameters using log binomial or Poisson regression to calculate age-/sex-adjusted prevalence ratios (aPRs). RESULTS Among 5564 patients with a clinical diagnosis of T2D, 78 (1.4%) had PPDM. Compared to T2D, PPDM patients were more often underweight or normal weight (body mass index ≤25.0 kg/m2 : aPR 2.3; 95% confidence interval [CI]: 1.6-3.2) and had lower waist-to-hip ratio (≤0.95/≤0.80 in men/women: aPRs 1.8; 95% CI: 1.2-2.7). PPDM patients had lower plasma amylase levels (<17 U/L: aPRs 2.2; 95% CI: 1.1-4.3), higher insulin sensitivity (homeostatic model assessment 2S [HOMA2S] >63: aPR 2.0; 95% CI: 1.2-3.2) and tended to have worse glycaemic control (HbA1c ≥8.0%: aPRs 1.4; 95% CI: 0.8-2.4). PPDM-A was largely indistinguishable from T2D, whereas PPDM-C had impaired insulin secretion, higher insulin sensitivity, and worse glycemic control. CONCLUSIONS The proportion of PPDM among patients with clinically diagnosed T2D is ~1.5% in an everyday clinical care setting. Glucose metabolism of PPDM-A is largely indistinguishable from T2D, whereas PPDM-C differs in relation to insulin secretion and sensitivity.
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Affiliation(s)
- Søren Schou Olesen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
| | | | | | | | - Asbjørn Mohr Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Ivan Brandslund
- Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark
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Bharmal SH, Kimita W, Ko J, Petrov MS. Cytokine signature for predicting new-onset prediabetes after acute pancreatitis: A prospective longitudinal cohort study. Cytokine 2021; 150:155768. [PMID: 34823207 DOI: 10.1016/j.cyto.2021.155768] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/26/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND/PURPOSE Acute inflammation of the pancreas often leads to metabolic sequelae, the most common of which is new-onset prediabetes (and, ultimately, diabetes). However, there is a lack of studies on predictors of this sequela. The aim was to investigate whether cytokines/chemokines measured at baseline are predictive of new-onset prediabetes after acute pancreatitis (NOPAP). METHODS This was a prospective longitudinal cohort study (as part of the LACERTA project) that included 68 individuals with non-necrotising acute pancreatitis who had no diabetes mellitus. Of them, 17 individuals had prediabetes at baseline and during follow-up, 37 individuals had normoglycaemia at baseline and during follow-up, and 14 individuals had normoglycaemia at baseline and developed NOPAP during follow-up. A commercially available human cytokine/chemokine multiplex kit was used to measure a total of 28 analytes at baseline. Multinomial regression analyses were conducted to investigate the associations between the cytokines/chemokines and the three study groups. RESULTS Interleukin-1β and interferon γ significantly predicted progression to NOPAP with an odds ratio (95% confidence interval) of 1.097 (1.002, 1.201) and 1.094 (1.003, 1.192), respectively (after accounting for age, sex, body mass index, and aetiology of acute pancreatitis). None of the studied cytokines/chemokines showed statistically significant associations with the antecedent prediabetes group (after accounting for the above covariates). CONCLUSION Elevated levels of interleukin-1β and interferon γ in acute pancreatitis individuals with normoglycaemia at baseline may predict progression to NOPAP during follow-up.
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Affiliation(s)
| | - Wandia Kimita
- School of Medicine, University of Auckland, New Zealand
| | - Juyeon Ko
- School of Medicine, University of Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, New Zealand.
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Wicks M, Barr EL, Maple-Brown L. Pancreatitis and Post-Pancreatitis Diabetes in Central Australia. Intern Med J 2021; 53:568-576. [PMID: 34779564 DOI: 10.1111/imj.15620] [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: 08/12/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Pancreatitis and diabetes are common among Aboriginal people of Central Australia. The contribution of pancreatitis to the development of Post-Pancreatitis Diabetes-Mellitus (PPDM) is not known. AIMS To describe among Aboriginal and non-Aboriginal people living in Central Australia, (i) the prevalence and aetiology of Acute (AP) and Chronic Pancreatitis (CP) and, (ii) diagnosis of new onset diabetes after pancreatitis. METHODS Retrospective medical record review of patients ≥ 15 years admitted to hospitals in the Central Australia Health Service between 2009 and 2018 with pancreatitis. Prevalence as a proportion of the resident population and aetiology of AP and CP were determined. Diagnosis of new onset diabetes after admission with pancreatitis was assessed. RESULTS Of the 638 patients assessed, 73% were Aboriginal and 48% female. The annual prevalence in 2009 and 2018 for AP was 171 and 203 per 100 000 persons, and for CP was 206 and 114 per 100 000 persons, respectively. Rates were high in Aboriginal people. Alcohol aetiology was most common in Aboriginal people at (66%) and biliary aetiology in non-Aboriginal people (37%). A diagnosis of diabetes after pancreatitis was detected in 125 of 438 (29%) patients who did not have diabetes diagnosis previously recorded, and 20 of the 22 tested for diabetes-associated antibodies were negative, fitting criteria for PPDM. CONCLUSION Prevalence of AP and CP in Central Australia was higher in Aboriginal than non-Aboriginal people. Few patients with diabetes recorded after pancreatitis had appropriate PPDM diagnostic testing. Inter-disciplinary education on the diagnosis of PPDM is required. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Mary Wicks
- Menzies School of Health Research, Alice Springs
| | - Elizabeth Lm Barr
- Menzies School of Health Research, Charles Darwin University NT, Australia.,Baker Heart and Diabetes Institute Vic, Australia
| | - Louise Maple-Brown
- Menzies School of Health Research, Charles Darwin University NT, Australia.,Department of Endocrinology, Royal Darwin Hospital
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Norbitt CF, Kimita W, Ko J, Bharmal SH, Petrov MS. Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis. Nutrients 2021; 13:3978. [PMID: 34836234 PMCID: PMC8618003 DOI: 10.3390/nu13113978] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/26/2021] [Accepted: 11/02/2021] [Indexed: 12/13/2022] Open
Abstract
Associations between habitual dietary intake of minerals and glucose metabolism have been extensively studied in relation to metabolic disorders. However, similar research has yet to be conducted in individuals after acute pancreatitis (AP). The main aim was to investigate the associations between habitual intake of 13 minerals and glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Associations between the dietary intake of minerals and markers of glucose metabolism (glycated haemoglobin and fasting plasma glucose) were also studied. The EPIC-Norfolk food frequency questionnaire was used in a cross-sectional fashion to determine the habitual intake of 13 dietary minerals. ANCOVA as well as multiple linear regression analyses were conducted and five statistical models were built to adjust for covariates. The study included 106 individuals after AP. In the NODAP group, intake of 4 minerals was significantly less when compared with the NAP group: iron (B = -0.076, p = 0.013), nitrogen (B = -0.066, p = 0.003), phosphorous (B = -0.046, p = 0.006), and zinc (B = -0.078, p = 0.001). Glycated haemoglobin was significantly associated with iodine intake (B = 17.763, p = 0.032) and manganese intake (B = -17.147, p = 0.003) in the NODAP group. Fasting plasma glucose was significantly associated with manganese intake (B = -2.436, p = 0.027) in the NODAP group. Habitual intake of minerals differs between individuals with NODAP, T2DM, and NAP. Prospective longitudinal studies and randomised controlled trials are now warranted to further investigate the associations between mineral intake and NODAP.
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Affiliation(s)
| | | | | | | | - Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland 1023, New Zealand; (C.F.N.); (W.K.); (J.K.); (S.H.B.)
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Kimita W, Bharmal SH, Ko J, Cho J, Petrov MS. Relationship between Energy Balance and Circulating Levels of Hepcidin and Ferritin in the Fasted and Postprandial States. Nutrients 2021; 13:3557. [PMID: 34684558 PMCID: PMC8539037 DOI: 10.3390/nu13103557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/08/2021] [Accepted: 10/09/2021] [Indexed: 02/07/2023] Open
Abstract
Markers of iron metabolism are altered in new-onset diabetes, but their relationship with metabolic signals involved in the maintenance of energy balance is poorly understood. The primary aim was to explore the associations between markers of iron metabolism (hepcidin and ferritin) and markers of energy balance (leptin, ghrelin, and the leptin/ghrelin ratio) in both the fasted and postprandial states. These associations were also studied in the sub-groups stratified by diabetes status. This was a cross-sectional study of individuals without disorders of iron metabolism who were investigated after an overnight fast and, in addition, some of these individuals underwent a mixed meal test to determine postprandial responses of metabolic signals. The associations between hepcidin, ferritin, and leptin, ghrelin, leptin/ghrelin ratio were studied using several multiple linear regression models. A total of 76 individuals in the fasted state and 34 individuals in the postprandial state were included. In the overall cohort, hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was -883.45 ± 400.94; p = 0.031) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was -148.26 ± 61.20; p = 0.018) in the fasted state. The same associations were not statistically significant in the postprandial state. In individuals with new-onset prediabetes or diabetes (but not in those with normoglycaemia or longstanding prediabetes or diabetes), hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was -806.09 ± 395.44; p = 0.050) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was -129.40 ± 59.14; p = 0.037). Leptin appears to be a mediator in the link between iron metabolism and new-onset diabetes mellitus. These findings add to the growing understanding of mechanisms underlying the derangements of glucose metabolism.
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Affiliation(s)
| | | | | | | | - Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland 1023, New Zealand; (W.K.); (S.H.B.); (J.K.); (J.C.)
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Kimita W, Bharmal SH, Ko J, Cho J, Petrov MS. Effect of β-hydroxybutyrate monoester on markers of iron metabolism in new-onset prediabetes: findings from a randomised placebo-controlled trial. Food Funct 2021; 12:9229-9237. [PMID: 34606529 DOI: 10.1039/d1fo00729g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: People with prediabetes often have altered iron metabolism and may benefit from mild exogenous ketosis, which can now be successfully achieved thanks to recent developments in chemistry of food components. Objective: The objective was to investigate the effect of acute exogenous ketone monoester (β-hydroxybutyrate) on plasma levels of markers of iron metabolism in people with prediabetes. Methods: Eighteen participants with new-onset prediabetes after acute pancreatitis aged 18 years or above took part in randomised controlled cross-over trial in Auckland, New Zealand. After an overnight fast, participants consumed the exogenous ketone supplement or placebo. Blood samples were collected in the fasted state (0 minutes) and then serially every 30 minutes for 150 minutes. Both participants and study personnel were blinded to the intervention/placebo allocation. Repeated measures analysis of variance was performed using total area under the curve to determine the change in hepcidin and ferritin over time after consumption of the exogenous ketone supplement and placebo. Results: Consumption of the exogenous ketone supplement significantly elevated blood levels of β-hydroxybutyrate from 0.20 mmol L-1 at baseline to 3.50 mmol L-1 at 30 minutes (p < 0.05) and remained significantly elevated for the duration of the trial. The total area under the curve of hepcidin was 340.5 ± 121.1 ng mL-1 after the exogenous ketone supplementation as compared with 343.2 ± 119.6 ng mL-1 min-1 after the use of placebo (p = 0.91). The total area under the curve of ferritin was 786.7 ± 129.1 ng mL-1 min-1 after the exogenous ketone supplementation as compared with 776.9 ± 131.4 ng mL-1 min-1 after the use of placebo (p = 0.10). Conclusion: Acute supplementation of β-hydroxybutyrate did not significantly affect the circulating levels of hepcidin or ferritin in people with prediabetes. Long-term effects of β-hydroxybutyrate warrant investigations in the future.
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Affiliation(s)
- Wandia Kimita
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Sakina H Bharmal
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Jaelim Cho
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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Viggers R, Jensen MH, Laursen HVB, Drewes AM, Vestergaard P, Olesen SS. Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study. Diabetes Care 2021; 44:2045-2052. [PMID: 34362812 DOI: 10.2337/dc21-0333] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/10/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS In a Danish nationwide population-based cohort study, we identified all individuals with adult-onset diabetes in the period 2000-2018 and categorized them as having type 1 diabetes, type 2 diabetes, or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, and classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. RESULTS Among 398,456 adults with new-onset diabetes, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes, and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years versus 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence rate ratio 0.6 [95% CI 0.6-0.7]; P < 0.001). A sizeable proportion of patients with PPDM were classified as having type 2 diabetes (44.9%) and prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared with type 2 diabetes (hazard ratio 3.10 [95% CI 2.96-3.23]; P < 0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30 [95% CI 4.01-4.56]; P < 0.001). CONCLUSIONS PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.
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Affiliation(s)
- Rikke Viggers
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark .,Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Morten Hasselstrøm Jensen
- Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark.,Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Henrik Vitus Bering Laursen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark.,Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Peter Vestergaard
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Endocrinology, Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Søren Schou Olesen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Gastroenterology and Hepatology, Mech-Sense and Centre for Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
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Bharmal SH, Kimita W, Ko J, Petrov MS. Pancreatic and gut hormones as predictors of new-onset prediabetes after non-necrotising acute pancreatitis: a prospective longitudinal cohort study. Endocr Connect 2021; 10:715-724. [PMID: 34097643 PMCID: PMC8284951 DOI: 10.1530/ec-21-0229] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Early identification of individuals at high risk for metabolic derangements after an attack of acute pancreatitis (AP) is critical with a view to tertiary preventing of this disease. The aim was to investigate whether fasting pancreatic and gut hormones at baseline were predictive of future risk of new-onset prediabetes after acute pancreatitis (NOPAP) in individuals with non-necrotising AP. METHODS This was a prospective longitudinal cohort study that included 69 consecutive non-diabetic participants with AP, of whom 55% (n = 38) had normoglycaemia both at baseline and during follow-up, 25% (n = 17) had prediabetes both at baseline and during follow-up, and 20% (n = 14) were normoglycaemic at baseline but developed NOPAP during follow-up. The associations between the study groups and circulating fasting levels of pancreatic and gut hormones (insulin, glucagon, C-peptide, amylin, glucose-dependent insulinotropic peptide, glucagon-like peptide-1, pancreatic polypeptide, and peptide YY) were studied using multinomial regression in both unadjusted and adjusted analyses. RESULTS Elevated plasma insulin and glucagon at baseline were significantly associated with NOPAP (adjusted odds ratio 1.99, 95% CI 1.01 to 3.92 and adjusted odds ratio 3.44, 95% CI 1.06 to 11.19, respectively). The same hormones had no significant association with antecedent prediabetes in AP. The other studied hormones were not significantly associated with the study groups. CONCLUSIONS Normoglycaemic AP individuals with elevated fasting levels of insulin and glucagon at baseline constitute a high-risk group for future NOPAP.
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Affiliation(s)
- Sakina H Bharmal
- School of Medicine, University of Auckland, Auckland, New Zealand
- Correspondence should be addressed to S H Bharmal or M S Petrov: or
| | - Wandia Kimita
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
- Correspondence should be addressed to S H Bharmal or M S Petrov: or
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Abdominal fat distribution modulates the metabolic effects of exogenous ketones in individuals with new-onset prediabetes after acute pancreatitis: Results from a randomized placebo-controlled trial. Clin Nutr ESPEN 2021; 43:117-129. [DOI: 10.1016/j.clnesp.2021.03.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 03/08/2021] [Indexed: 12/13/2022]
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Cho J, Pandol SJ, Petrov MS. Risk of cause-specific death, its sex and age differences, and life expectancy in post-pancreatitis diabetes mellitus. Acta Diabetol 2021; 58:797-807. [PMID: 33590329 PMCID: PMC9254257 DOI: 10.1007/s00592-021-01683-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 01/27/2021] [Indexed: 12/13/2022]
Abstract
AIMS The aim was to investigate sex- and age-stratified risks of cause-specific death and life expectancy in individuals with post-pancreatitis diabetes mellitus (PPDM). METHODS Nationwide data on mortality in New Zealand were obtained. For two head-to-head comparisons (PPDM versus type 2 diabetes mellitus [T2DM]; PPDM versus type 1 diabetes mellitus [T1DM]), the groups were matched on age, sex, and calendar year of diabetes diagnosis. Multivariable Cox regression analyses were conducted to estimate risks of vascular, cancer, and non-vascular non-cancer mortality. Remaining life expectancy at age of diabetes diagnosis was estimated using the Chiang II method. RESULTS A total of 15,848 individuals (1,132 PPDM, 3,396 T1DM, and 11,320 T2DM) were included. The risks of vascular mortality and non-vascular non-cancer mortality did not differ significantly between PPDM and T2DM or T1DM. PPDM was associated with a significantly higher risk of cancer mortality compared with T2DM (adjusted hazard ratio, 1.32; 95% confidence interval, 1.08-1.63) or T1DM (adjusted hazard ratio, 1.65; 95% confidence interval, 1.27-2.13). The risk of cancer mortality associated with PPDM (versus T2DM) was significantly higher in women than in men (p for interaction = 0.003). This sex difference in cancer mortality risk was also significant in the comparison between PPDM and T1DM (p for interaction = 0.006). Adults of both sexes with PPDM had the lowest remaining life expectancy (in comparison with T2DM or T1DM) up to 64 years of age. CONCLUSIONS People with PPDM have a higher risk of cancer mortality compared with those with T2DM or T1DM. This is especially pronounced in women. Young and middle-aged adults with PPDM have a lower life expectancy compared with their counterparts with T2DM or T1DM.
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Affiliation(s)
- Jaelim Cho
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Stephen J Pandol
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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Petrov MS. Post-pancreatitis diabetes mellitus: investigational drugs in preclinical and clinical development and therapeutic implications. Expert Opin Investig Drugs 2021; 30:737-747. [PMID: 33993813 DOI: 10.1080/13543784.2021.1931118] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Post-pancreatitis diabetes mellitus is one of the most common types of secondary diabetes. The pharmaceutical armamentarium in the field of diabetology can be broadened if the design of novel drugs is informed by pathogenetic insights from studies on post-pancreatitis diabetes mellitus.Areas covered: The article provides an overview of preclinical and clinical studies of compounds selectively antagonizing the gastric inhibitory peptide receptor, simultaneously stimulating both the glucagon-like peptide-1 and glucagon receptors, and activating ketogenesis.Expert opinion: The current pharmacotherapy for post-pancreatitis diabetes mellitus is relatively ineffective. This type of diabetes represents a unique platform for rigorous, efficient, and practical search for glucose-lowering therapeutic candidates. Various methods of gastric inhibitory peptide receptor (expressed in the pancreas) antagonism have undergone extensive preclinical testing in diabetes, with promising compounds being trialed in man. Molecular mimicry with oxyntomodulin ─ an extra-pancreatic hormone homologous with pancreatic hormone glucagon and involved in the regulation of exocrine pancreatic function ─ could be harnessed. The emerging findings of a salutary effect of ketosis mimetics in people with prediabetes set the stage for a novel approach to preventing diabetes.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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Li X, Kimita W, Cho J, Ko J, Bharmal SH, Petrov MS. Dietary Fibre Intake in Type 2 and New-Onset Prediabetes/Diabetes after Acute Pancreatitis: A Nested Cross-Sectional Study. Nutrients 2021; 13:nu13041112. [PMID: 33805259 PMCID: PMC8066410 DOI: 10.3390/nu13041112] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/18/2022] Open
Abstract
The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (β = −0.154, p = 0.006), insoluble fibre (β = −0.133, p = 0.01), and soluble fibre (β = −0.13, p = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (β = −0.069, p = 0.004) and nuts (β = −0.039, p = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (β = −0.054, p = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.
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Coderre L, Debieche L, Plourde J, Rabasa-Lhoret R, Lesage S. The Potential Causes of Cystic Fibrosis-Related Diabetes. Front Endocrinol (Lausanne) 2021; 12:702823. [PMID: 34394004 PMCID: PMC8361832 DOI: 10.3389/fendo.2021.702823] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/06/2021] [Indexed: 12/16/2022] Open
Abstract
Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity, affecting more than 50% of adult CF patients. Despite this high prevalence, the etiology of CFRD remains incompletely understood. Studies in young CF children show pancreatic islet disorganization, abnormal glucose tolerance, and delayed first-phase insulin secretion suggesting that islet dysfunction is an early feature of CF. Since insulin-producing pancreatic β-cells express very low levels of CFTR, CFRD likely results from β-cell extrinsic factors. In the vicinity of β-cells, CFTR is expressed in both the exocrine pancreas and the immune system. In the exocrine pancreas, CFTR mutations lead to the obstruction of the pancreatic ductal canal, inflammation, and immune cell infiltration, ultimately causing the destruction of the exocrine pancreas and remodeling of islets. Both inflammation and ductal cells have a direct effect on insulin secretion and could participate in CFRD development. CFTR mutations are also associated with inflammatory responses and excessive cytokine production by various immune cells, which infiltrate the pancreas and exert a negative impact on insulin secretion, causing dysregulation of glucose homeostasis in CF adults. In addition, the function of macrophages in shaping pancreatic islet development may be impaired by CFTR mutations, further contributing to the pancreatic islet structural defects as well as impaired first-phase insulin secretion observed in very young children. This review discusses the different factors that may contribute to CFRD.
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Affiliation(s)
- Lise Coderre
- Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, Canada
| | - Lyna Debieche
- Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, Canada
- Département de médecine, Université de Montréal, Montréal, QC, Canada
| | - Joëlle Plourde
- Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, Canada
- Département de médecine, Université de Montréal, Montréal, QC, Canada
| | - Rémi Rabasa-Lhoret
- Division of Cardiovascular and Metabolic Diseases, Institut de recherche clinique de Montréal, Montréal, QC, Canada
- Département de nutrition, Université de Montréal, Montréal, QC, Canada
- Cystic Fibrosis Clinic, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
| | - Sylvie Lesage
- Immunology-Oncology Section, Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada
- *Correspondence: Sylvie Lesage,
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