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Parra Villasmil MG, Bellin MD. Risk Factors and Mechanisms for Diabetes in Pancreatitis. Gastroenterol Clin North Am 2025; 54:175-188. [PMID: 39880526 PMCID: PMC11780253 DOI: 10.1016/j.gtc.2024.08.002] [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] [Indexed: 01/31/2025]
Abstract
Diabetes (DM) can occur as a complication of acute, acute recurrent, or chronic pancreatitis, affecting more than 30% of adults with chronic pancreatitis. Data on the pathophysiology and management are limited, especially in pediatric population. Proposed mechanisms include insulin deficiency, insulin resistance, decreased pancreatic polypeptide, and possible beta-cell autoimmunity (in a small subset). Risk factors for developing diabetes in those with pancreatitis may include hypertriglyceridemia, obesity, necrotizing pancreatitis, exocrine pancreatic insufficiency, and pancreatic calcifications, among others. Further studies are required to understand pathophysiology of pancreatogenic DM, in order to define optimal treatment approaches.
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Affiliation(s)
- María Graciela Parra Villasmil
- Department of Pediatrics, Stead Family Children's Hospital, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Melena D Bellin
- Department of Pediatrics, University of Minnesota, MMC 391, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
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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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Bardugo A, Bendor CD, Libruder C, Lutski M, Zucker I, Tsur AM, Derazne E, Yaniv G, Gardner RC, Gerstein HC, Cukierman-Yaffe T, Lebenthal Y, Batty D, Tanne D, Furer A, Afek A, Twig G. Cognitive function in adolescence and the risk of early-onset stroke. J Epidemiol Community Health 2024; 78:570-577. [PMID: 38937113 DOI: 10.1136/jech-2024-222114] [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: 02/28/2024] [Accepted: 05/11/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND Stroke is increasingly prevalent at younger ages but the risk factors are uncertain. We examined the association between adolescent cognitive function and early-onset stroke. METHODS This was a nationwide population-based cohort study of 1 741 345 Israeli adolescents (42% women) who underwent comprehensive cognitive function tests at age 16-20 years, before mandatory military service, during 1987-2012. Cognitive function (range: 1-9) was categorised as low (1-3, corresponding to IQ score below 89), medium (4-7, IQ score range: 89-118), or high (8-9, IQ score above 118). Participant data were linked to the Israeli National Stroke Registry. Cox proportional hazard models were used to estimate risks for the first occurrence of ischaemic stroke during 2014-2018. RESULTS During 8 689 329 person-years of follow-up, up to a maximum age of 50 years, 908 first stroke events occurred (767 ischaemic and 141 haemorrhagic). Compared with a reference group of people with high cognitive function, body mass index-adjusted and sociodemographic-adjusted HRs (95% CIs) for early-onset stroke were 1.78 (1.33-2.38) in medium and 2.68 (1.96-3.67) in low cognitive function groups. There was evidence of a dose-response relationship (P for trend <0.0001) such that one-unit of lower cognitive function z-score was associated with a 33% increased risk of stroke (1.33; 1.23-1.42). These associations were similar for ischaemic stroke but lower for haemorrhagic stroke; persisted in sensitivity analyses that accounted for diabetes status and hypertension; and were evident before age 40 years. CONCLUSIONS Alongside adolescent obesity and hypertension, lower cognitive function may be a risk factor for early-onset stroke.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem, Israel
- Israel Defense Forces Medical Corps, Ramat Gan, Israel
- The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem, Israel
- Israel Defense Forces Medical Corps, Ramat Gan, Israel
- The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
- Department of Preventive Medicine and Epidemiology, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Carmit Libruder
- Israel Center for Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
| | - Miri Lutski
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Israel Center for Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
| | - Inbar Zucker
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Israel Center for Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
| | - Avishai M Tsur
- Department of Military Medicine, Hebrew University, Jerusalem, Israel
- Israel Defense Forces Medical Corps, Ramat Gan, Israel
- The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
- Department of Preventive Medicine and Epidemiology, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Medicine, Sheba Medical Center, Tel Hashomer, Israel
| | - Estela Derazne
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gal Yaniv
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel
| | - Raquel C Gardner
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel
| | | | - Tali Cukierman-Yaffe
- Department of Preventive Medicine and Epidemiology, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Israel
| | - Yael Lebenthal
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Institute of Pediatric Endocrinology, Diabetes and Metabolism, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - David Batty
- Department of Epidemiology and Public Health, University College London, London, UK
| | - David Tanne
- Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Ariel Furer
- Department of Military Medicine, Hebrew University, Jerusalem, Israel
- Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | | | - Gilad Twig
- The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
- Department of Preventive Medicine and Epidemiology, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Israel
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Naeh A, Maor-Sagie E, Hallak M, Toledano Y, Gabbay-Benziv R. Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity. Am J Obstet Gynecol 2024; 231:259.e1-259.e10. [PMID: 38360449 DOI: 10.1016/j.ajog.2023.11.1246] [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: 08/31/2023] [Revised: 11/20/2023] [Accepted: 11/21/2023] [Indexed: 02/17/2024]
Abstract
BACKGROUND The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.
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Affiliation(s)
- Amir Naeh
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
| | - Esther Maor-Sagie
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Meuhedet Health Maintenance Organization, Haifa, Israel
| | - Mordechai Hallak
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Meuhedet Health Maintenance Organization, Haifa, Israel
| | - Yoel Toledano
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Meuhedet Health Maintenance Organization, Haifa, Israel
| | - Rinat Gabbay-Benziv
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
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Trikudanathan G, Abdallah M, Munigala S, Vantanasiri K, Jonason D, Faizi N, Schat R, Chauhan A, Freeman ML, Bellin MD. Visceral Fat Predicts New-Onset Diabetes After Necrotizing Pancreatitis. Pancreas 2024; 53:e240-e246. [PMID: 38266226 DOI: 10.1097/mpa.0000000000002292] [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] [Indexed: 01/26/2024]
Abstract
OBJECTIVES We aimed to estimate the incidence of new-onset diabetes (NOD) and identify risk factors for NOD in patients with necrotizing pancreatitis (NP). METHODS Necrotizing pancreatitis patients were reviewed for NOD, diagnosed >90 days after acute pancreatitis. Baseline demographics, comorbidities, clinical outcomes, computed tomography (CT) characteristics of necrotic collections, and CT-derived abdominal fat measurements were analyzed to identify predictors for NOD. RESULTS Among 390 eligible NP patients (66% men; median age, 51 years; interquartile range [IQR], 36-64) with a median follow-up of 400 days (IQR, 105-1074 days), NOD developed in 101 patients (26%) after a median of 216 days (IQR, 92-749 days) from NP. Of the NOD patients, 84% required insulin and 69% developed exocrine pancreatic insufficiency (EPI). Age (odds ratio [OR], 0.98), male sex (OR, 2.7), obesity (OR, 2.1), presence of EPI (OR, 2.7), and diffuse pancreatic necrosis (OR, 2.4) were independent predictors. In a separate multivariable model assessing abdominal fat on CT, visceral fat area (highest quartile) was an independent predictor for NOD (OR, 3.01). CONCLUSIONS New-onset diabetes was observed in 1 of 4 patients with NP, most within the first year and requiring insulin. Male sex, obesity, diffuse pancreatic necrosis, development of EPI, and high visceral adiposity identified those at highest risk.
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Affiliation(s)
- Guru Trikudanathan
- From the Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN
| | - Mohamed Abdallah
- From the Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN
| | - Satish Munigala
- Division of Infectious diseases, Washington University, St Louis, MO
| | | | | | | | | | | | - Martin L Freeman
- From the Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN
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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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Manrai M, Singh AK, Birda CL, Shah J, Dutta A, Bhadada SK, Kochhar R. Diabetes mellitus as a consequence of acute severe pancreatitis: Unraveling the mystery. World J Diabetes 2023; 14:1212-1225. [PMID: 37664472 PMCID: PMC10473947 DOI: 10.4239/wjd.v14.i8.1212] [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: 03/28/2023] [Revised: 05/19/2023] [Accepted: 07/06/2023] [Indexed: 08/11/2023] Open
Abstract
The occurrence of diabetes mellitus (DM) in pancreatitis is being increasingly recognized lately. Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis (AP). The incidence of diabetes after AP varies from 18% to 23% in 3 years and reaches up to 40% over 5 years. The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass, AP-induced autoimmunity, and alterations in the insulin incretin axis. Risk factors associated with increased risk of diabetes includes male sex, recurrent attacks of pancreatitis, presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis. Diagnosis of post-pancreatitis DM (PPDM) is often excluded. Treatment includes a trial of oral antidiabetic drugs in mild diabetes. Often, insulin is required in uncontrolled diabetes. Given the lack of awareness of this metabolic disorder after AP, this review will evaluate current information on epidemiology, risk factors, diagnosis and management of PPDM and identify the knowledge gaps.
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Affiliation(s)
- Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, Maharashtra, India
| | - Anupam K Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Chhagan Lal Birda
- Department of Gastroenterology, All India Institutes of Medical Sciences, Jodhpur 342001, India
| | - Jimil Shah
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Aditya Dutta
- Department of Endocrinology, Max Hospital, New Delhi 110017, India
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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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: 3] [Impact Index Per Article: 1.5] [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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Deng L, Deng W. Association of Statin Usage and the Development of Diabetes Mellitus after Acute Pancreatitis. Clin Gastroenterol Hepatol 2023; 21:1675. [PMID: 35933073 DOI: 10.1016/j.cgh.2022.07.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Liling Deng
- Department of Endocrinology and School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Wuquan Deng
- Department of Endocrinology and School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
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Bardugo A, Bendor CD, Rotem RS, Tsur AM, Derazne E, Gerstein HC, Tzur D, Pinhas-Hamiel O, Cukierman-Yaffe T, Raz I, Hod M, Tirosh A, Lebenthal Y, Afek A, Chodick G, Twig G. Glucose intolerance in pregnancy and risk of early-onset type 2 diabetes: a population-based cohort study. Lancet Diabetes Endocrinol 2023; 11:333-344. [PMID: 37011646 DOI: 10.1016/s2213-8587(23)00062-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 03/01/2023] [Accepted: 03/01/2023] [Indexed: 04/05/2023]
Abstract
BACKGROUND The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood. METHODS For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. We included 177 241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7·8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5·3 mmol/L) or higher in the fasting state; 180 mg/dL (10·0 mmol/L) or higher at 1 h; 155 mg/dL (8·6 mmol/L) or higher at 2 h; and 140 mg/dL (7·8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. FINDINGS During a cumulative follow-up of 1 882 647 person-years, and with a median follow-up of 10·8 (IQR 5·2-16·4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2·6 (95% CI 2·4-2·9) per 10 000 person-years in women with gestational normoglycaemia, 8·9 (7·4-10·6) per 10 000 person-years in women with an abnormal GCT and normal OGTT, 26·1 (22·4-30·1) per 10 000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71·9 (66·0-78·3) per 10 000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3·39 [95% CI 2·77-4·16]; p<0·0001), in women with one abnormal OGTT value (9·11 [7·64-10·86]; p<0·0001), and in women with gestational diabetes (24·84 [21·78-28·34]; p<0·0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11·81 [95% CI 8·58-16·25]; p<0·0001), and in women with gestational diabetes and an abnormal fasting glucose (38·02 [32·41-44·61]; p<0·0001). INTERPRETATION Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy. FUNDING None.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Ran Shmuel Rotem
- Department of Environmental Health, Harvard T H Chan School of Public Health, Boston, MA, USA; Kahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Avishai M Tsur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine "B," Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Estela Derazne
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Moshe Hod
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Diabetes in Pregnancy Clinic, Perinatal Division, Department of Obstetrics and Gynecology, Beilinson Medical Campus, Petah Tiqva, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel
| | - Yael Lebenthal
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Central Management, Sheba Medical Center, Ramat Gan, Israel
| | - Gabriel Chodick
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Maccabitech, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel; The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Ramat Gan, Israel.
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11
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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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12
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Morphological and functional recovery following acute and acute recurrent pancreatitis in children: A prospective sequential 2-point evaluation. Pancreatology 2022; 22:698-705. [PMID: 35717306 DOI: 10.1016/j.pan.2022.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 05/13/2022] [Accepted: 06/03/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND The functional and morphological recovery following an episode of acute pancreatitis (AP) in children still remains ill understood as research exploring this is limited. We aimed to characterize the morphological and functional changes in pancreas following AP and ARP (acute recurrent pancreatitis) in children. METHODS Children with AP were followed prospectively and assessed at two time points at least 3 months apart, with the first assessment at least 3 months after the AP episode. Exocrine and endocrine functions were measured using fecal elastase and fasting blood sugar/HbA1c levels respectively. Morphological assessment was done using endoscopic ultrasound (EUS) and magnetic resonance imaging and cholangiopancreatography (MRI/MRCP). RESULTS Seventy-three children (boys:59%; mean age:8.4 ± 3.2years) were studied and 21 of them (29%) progressed to ARP. Altered glucose homeostasis was seen in 19 (26%) at first and 16 (22%) at second assessment and it was significantly more in ARP group than the AP group at first (42.8%vs19.2%; p = 0.03) as well as second assessment (38.1%vs15.3%; p = 0.03). Twenty-one children (28.7%) at first and 24 (32.8%) at second assessment developed biochemical exocrine pancreatic insufficiency. EUS detected indeterminate and suggestive changes of chronic pancreatitis in 21% at first (n = 38) and 27.6% at second assessment (n = 58). On MRCP, main pancreatic duct and side branch dilatation were seen in 15 (20.5%) and 2 (2.7%) children respectively. CONCLUSIONS More than one-quarter of children have evidence of altered glucose homeostasis and biochemical exocrine pancreatic insufficiency following an episode of AP. Similarly, morphological features of chronicity seen in some of the children suggest that a fraction of subjects may develop chronic pancreatitis on longer follow-up.
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13
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Bendor CD, Bardugo A, Rotem RS, Derazne E, Gerstein HC, Tzur D, Pinhas-Hamiel O, Tsur AM, Cukierman-Yaffe T, Lebenthal Y, Afek A, Chodick G, Twig G. Glucose Intolerance in Pregnancy and Offspring Obesity in Late Adolescence. Diabetes Care 2022; 45:1540-1548. [PMID: 35670776 DOI: 10.2337/dc21-2634] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/25/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Gestational hyperglycemia is associated with deleterious neonatal outcomes, but long-term risks for offspring obesity are less clear. We estimated the odds for offspring adolescent overweight and obesity among mothers with gestational glucose intolerance. RESEARCH DESIGN AND METHODS In a mother-offspring historical cohort, the Israel military conscription data set was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and underwent two-step gestational diabetes screening (mean age, 31 years) with a 50-g glucose challenge test (GCT), followed by a 100-g oral glucose tolerance test (OGTT) if the result was abnormal. Glucose tolerance categories included gestational normoglycemia, abnormal GCT with normal OGTT, impaired glucose tolerance (IGT; one abnormal OGTT value), and gestational diabetes. The primary outcome was offspring overweight/obesity (BMI ≥85th percentile) at adolescence, measured prior to military conscription. Logistic regression models were applied. RESULTS Of 33,482 mother-offspring pairs, overweight and obesity were observed in 6,516 offspring. Across increasing categories of pregnancy glycemia, the proportions of offspring with adolescent overweight/obesity increased: normoglycemia, 19%; abnormal GCT with normal OGTT, 22%; gestational IGT, 24%; and gestational diabetes, 25% (P < 0.0001). Corresponding odds ratios after adjustment for the mother's late adolescent characteristics (sociodemographic confounders and BMI) and pregnancy age were 1.2 (95% CI 1.1-1.4), 1.3 (1.2-1.5), and 1.4 (1.3-1.6), respectively. Further adjustment for offspring birth weight percentile and sociodemographic variables did not materially change results. Associations were more pronounced with increasing obesity severity. CONCLUSIONS Gestational glucose intolerance, including categories not meeting the gestational diabetes threshold, was associated with increased odds for offspring overweight/obesity at late adolescence.
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Affiliation(s)
- Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Ran Shmuel Rotem
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA.,Kahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Estela Derazne
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel
| | - Avishai M Tsur
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Medicine "B," Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Endocrinology, Sheba Medical Center, Ramat Gan, Israel
| | - Yael Lebenthal
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Central Management, Sheba Medical Center, Ramat Gan, Israel
| | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Maccabitech, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem, and the Israel Defense Forces Medical Corps, Ramat Gan, Israel.,Institute of Endocrinology, Sheba Medical Center, Ramat Gan, Israel.,Department of Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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14
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Pinhas-Hamiel O, Bardugo A, Reichman B, Derazne E, Landau Z, Tokatly Latzer I, Lerner-Geva L, Rotschield J, Tzur D, Ben-Zvi D, Afek A, Twig G. Attention-Deficit/Hyperactivity Disorder and Obesity: A National Study of 1.1 Million Israeli Adolescents. J Clin Endocrinol Metab 2022; 107:e1434-e1443. [PMID: 34850003 DOI: 10.1210/clinem/dgab846] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE The incidences of obesity and attention-deficit/hyperactivity disorder (ADHD) have increased in parallel over recent decades. We assessed the association between obesity and ADHD in a national sample of adolescents. METHOD In a nationwide population-based study of 1 118 315 adolescents (57% males; mean age 17 years), risks of obesity were compared between individuals with severe and mild ADHD and those without ADHD. Diagnoses of ADHD were confirmed by specialists in either neurology or psychiatry. Adolescents requiring regular and continuous treatment with stimulants with no improvement of symptoms under treatment were classified as having severe ADHD; data were available from 2004 to 2019. During 2015 to 2019, the diagnosis of ADHD was defined, and 65 118 (16.76%) of 388 543 adolescents with mild symptoms who required medications only for learning or who used stimulants irregularly were defined as having mild ADHD. RESULTS The prevalence of severe and mild ADHD was 0.3% and 20.1%, respectively. Obesity was more prevalent among adolescents with severe ADHD than among those without ADHD (13.5% vs 7.5%). In the mild ADHD group 12.6% of males and 8.4% of females were diagnosed with obesity compared to 9.7% and 6.4%, respectively, in the non-ADHD group. The adjusted odds of severe ADHD for males and females with obesity were 1.77 (1.56-2.02) and 2.09 (1.63-2.66) times the odds for males and females with low-normal body mass index, respectively, and 1.42 (1.37-1.48) and 1.42 (1.34-1.50) for males and females with mild ADHD, respectively. The elevated risk persisted in several sensitivity analyses. CONCLUSIONS Both adolescents with severe and mild ADHD are at increased risk for obesity.
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Affiliation(s)
- Orit Pinhas-Hamiel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Aya Bardugo
- The Israeli Defense Forces Medical Corps and the Department of Military Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Brian Reichman
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- The Women and Children's Health Research Unit, Gertner Institute, Tel Hashomer, Israel
| | - Estela Derazne
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Zohar Landau
- Pediatrics Department, Barzilai Medical Center, Ashkelon, Israel
| | - Itay Tokatly Latzer
- Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Liat Lerner-Geva
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- The Women and Children's Health Research Unit, Gertner Institute, Tel Hashomer, Israel
| | - Jacob Rotschield
- The Israeli Defense Forces Medical Corps and the Department of Military Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Dorit Tzur
- The Israeli Defense Forces Medical Corps and the Department of Military Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Danny Ben-Zvi
- The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel
| | - Arnon Afek
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Central Management, Sheba Medical Center, Tel-Hashomer, Israel
| | - Gilad Twig
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- The Israeli Defense Forces Medical Corps and the Department of Military Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Institute of Endocrinology and Metabolism, Sheba Medical Center, Tel-Hashomer, Israel
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15
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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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16
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Shapiro M, Arbel C, Zucker I, Balmor GR, Lutski M, Derazne E, Beer Z, Pinhas-Hamiel O, Mosenzon O, Tzur D, Afek A, Tirosh A, Cukierman-Yaffe T, Gerstein HC, Rosenberg V, Chodick G, Raz I, Twig G. Asthma in Youth and Early-onset Type 2 Diabetes: A Nationwide Study of 1.72 Million Israeli Adolescents. J Clin Endocrinol Metab 2021; 106:e5043-e5053. [PMID: 34291806 DOI: 10.1210/clinem/dgab542] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood. METHODS This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests. RESULTS Type 2 diabetes developed in 58/9090 (0.64%), 507/97 059 (0.52%), 114/23 332 (0.49%), and 7095/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up >13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use. CONCLUSION Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years.
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Affiliation(s)
- Michael Shapiro
- Department of Internal Medicine T, Tel Aviv Sourasky Medical Center, Tel Aviv 6492601, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
| | - Chen Arbel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel
| | - Gingy Ronen Balmor
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Shamir (Assaf-Harofeh) Medical Center, Zerifin 70300, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Zivan Beer
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Department of Pediatric Endocrinology, Safra Children Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel
| | - Dorit Tzur
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Hertzel C Gerstein
- Department of Medicine, McMaster University, Hamilton, Ontario L8S 4M1, Canada
| | - Vered Rosenberg
- Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel
| | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel
| | - Gilad Twig
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
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17
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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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18
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Gariepy CE, Ooi CY, Maqbool A, Ellery KM. Demographics and risk factors for pediatric recurrent acute pancreatitis. Curr Opin Gastroenterol 2021; 37:491-497. [PMID: 34120130 PMCID: PMC8364486 DOI: 10.1097/mog.0000000000000764] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
PURPOSE OF REVIEW Approximately 20-30% of children who experience one episode of acute pancreatitis will have at least one additional episode. For some children, pancreatitis recurs multiple times and in a few years is followed by the diagnosis of chronic pancreatitis. Identifying risk factors for recurrent episodes and disease progression is critical to developing therapeutic interventions. RECENT FINDINGS Obesity is driving an increase in biliary stone disease and severe acute pancreatitis. Recurrent acute pancreatitis (RAP) may lead to the development of diabetes through autoimmune mechanisms. Cystic fibrosis or CFTR-related disorders may present as RAP and CFTR modulator therapy can increase or decrease the risk of acute pancreatitis in these populations. Children with Crohn disease have a three-fold risk of acute pancreatitis over the general population while children with ulcerative colitis are at increased risk for pediatric autoimmune pancreatitis, a disorder that may be distinct from autoimmune pancreatitis described in adults. Obstructive jaundice in the absence of identified mechanical factors may be a presenting sign of pediatric autoimmune pancreatitis. SUMMARY Pediatric RAP is a painful condition that leads to gland destruction and functional insufficiency. Risk factors are being clarified but preventive treatments remain elusive.
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Affiliation(s)
- Cheryl E. Gariepy
- Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA
| | - Chee Y. Ooi
- School of Women's and Children's Health, Medicine, University of New South Wales, Australia; Sydney Children's Hospital Randwick, New South Wales, Australia
| | - Asim Maqbool
- Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Kate M. Ellery
- UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
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19
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Bardugo A, Derazne E, Zucker I, Bendor CD, Puris G, Lutski M, Pinhas-Hamiel O, Cukierman-Yaffe T, Mosenzon O, Schechter M, Tzur D, Afek A, Tirosh A, Gerstein HC, Raz I, Twig G. Adolescent Thyroid Disorders and Risk for Type 2 Diabetes in Young Adulthood. J Clin Endocrinol Metab 2021; 106:e3426-e3435. [PMID: 34050759 DOI: 10.1210/clinem/dgab382] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Indexed: 02/08/2023]
Abstract
CONTEXT Thyroid hormones play a key role in systemic metabolism, yet the relationship between thyroid dysfunction and risk for type 2 diabetes is unclear. OBJECTIVE To assess type 2 diabetes risk in adulthood among adolescents with thyroid disorders. DESIGN AND SETTING A nationwide, population-based study of Israeli adolescents who were examined before military recruitment during 1988 to 2007 and were followed until December 31, 2016. PARTICIPANTS 1 382 560 adolescents (mean age 17.3 years). INTERVENTIONS The diagnosis of thyroid disorders was based on recent thyroid function tests. Data were linked to the Israeli National Diabetes Registry. Cox proportional hazard models were applied. MAIN OUTCOME MEASURES Type 2 diabetes incidence. RESULTS During a mean follow-up of 18.5 years, 1.12% (69 of 6,152) of adolescents with thyroid disorders were diagnosed with type 2 diabetes vs 0.77% of adolescents without thyroid disorders. The hazard ratio (HR) for type 2 diabetes was 2.3 (95% CI, 1.8-2.9) among those with thyroid disorders, after adjustment for sex, birth-year, body mass index, and sociodemographic confounders. The increased diabetes risk was observed in both men and women, with the presence or absence of obesity, and in the absence of other health conditions and was associated with different types of thyroid disorders. It was also similar when the outcome was defined as type 2 diabetes diagnosed at or before the age of 30 years (HR 2.3, 95% CI, 1.5-3.5). CONCLUSIONS Thyroid disorders diagnosed in adolescence are a risk factor for early-onset type 2 diabetes in both men and women.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Gal Puris
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Meir Schechter
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | | | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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20
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Yi Y, Sun X, Liang B, He N, Gibson-Corley KN, Norris AW, Engelhardt JF, Uc A. Acute pancreatitis-induced islet dysfunction in ferrets. Pancreatology 2021; 21:839-847. [PMID: 33994067 PMCID: PMC8355067 DOI: 10.1016/j.pan.2021.04.008] [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: 01/13/2021] [Revised: 04/22/2021] [Accepted: 04/24/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP. METHODS We injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining. RESULTS Cerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection. CONCLUSIONS Acute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.
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Affiliation(s)
- Yaling Yi
- Department of Anatomy and Cell Biology, Iowa City, IA, USA
| | - Xingshen Sun
- Department of Anatomy and Cell Biology, Iowa City, IA, USA
| | - Bo Liang
- Department of Anatomy and Cell Biology, Iowa City, IA, USA
| | - Nan He
- Department of Anatomy and Cell Biology, Iowa City, IA, USA
| | - Katherine N Gibson-Corley
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrew W Norris
- Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA; Department of Pediatrics, lowa City, IA, USA; Department of Biochemistry, Iowa City, IA, USA
| | - John F Engelhardt
- Department of Anatomy and Cell Biology, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA
| | - Aliye Uc
- Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA; Department of Pediatrics, lowa City, IA, USA; Department of Radiation Oncology; University of Iowa, Iowa City, IA, USA.
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21
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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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22
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Ko J, Skudder-Hill L, Cho J, Bharmal SH, Petrov MS. Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis. World J Gastroenterol 2021; 27:3357-3371. [PMID: 34163117 PMCID: PMC8218354 DOI: 10.3748/wjg.v27.i23.3357] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/14/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND New-onset prediabetes/diabetes after acute pancreatitis (NODAP) is the most common sequela of pancreatitis, and it differs from type 2 prediabetes/diabetes mellitus (T2DM).
AIM To study the associations between circulating levels of pancreatic amylase, pancreatic lipase, chymotrypsin and fat phenotypes in NODAP, T2DM, and health.
METHODS Individuals with NODAP (n = 30), T2DM (n = 30), and sex-matched healthy individuals (n = 30) were included. Five fat phenotypes (intra-pancreatic fat, liver fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using the same magnetic resonance imaging protocol and scanner magnet strength for all participants. One-way analysis of covariance, linear regression analysis, and relative importance analysis were conducted.
RESULTS Intra-pancreatic fat deposition (IPFD) was higher in NODAP (9.4% ± 1.8%) and T2DM (9.8% ± 1.1%) compared with healthy controls (7.8% ± 1.9%) after adjusting for covariates (P = 0.003). Similar findings were observed in regards to visceral fat volume (P = 0.005), but not subcutaneous fat volume, liver fat, or skeletal muscle fat. Both IPFD (β = -2.201, P = 0.023) and visceral fat volume (β = -0.004, P = 0.028) were significantly associated with circulating levels of pancreatic amylase in NODAP, but not in T2DM or healthy individuals. Of the five fat phenotypes, IPFD explained the highest amount of variance in pancreatic amylase concentration (R2 = 15.3% out of 41.2%). None of the phenotypes contributed meaningfully to the variance in pancreatic lipase or chymotrypsin.
CONCLUSION Both NODAP and T2DM are characterized by increased IPFD and visceral fat volume. However, only NODAP is characterized by significant inverse associations between the two fat phenotypes and pancreatic amylase.
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Affiliation(s)
- Juyeon Ko
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | | | - Jaelim Cho
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | - Sakina H Bharmal
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
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23
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Bardugo A, Fishman B, Libruder C, Tanne D, Ram A, Hershkovitz Y, Zucker I, Furer A, Gilon R, Chodick G, Tiosano S, Derazne E, Tzur D, Afek A, Pinhas-Hamiel O, Bendor CD, Yaniv G, Rotem RS, Twig G. Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood. Stroke 2021; 52:2043-2052. [PMID: 33980044 DOI: 10.1161/strokeaha.120.033595] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
[Figure: see text].
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.)
| | - Boris Fishman
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.).,Hypertension Unit, Internal Medicine D (B.F.), Sheba Medical Center, Ramat Gan, Israel.,The Dr. Pinchas Bornstein Talpiot Medical Leadership Program (B.F., G.Y., G.T.), Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Carmit Libruder
- Israel Center for Disease Control, Ministry of Health, Ramat Gan (C.L., A.R., Y.H., I.Z.)
| | - David Tanne
- Rambam Health Care Campus and Rappaport Faculty of Medicine, Haifa, Israel (D. Tanne)
| | - Amit Ram
- Israel Center for Disease Control, Ministry of Health, Ramat Gan (C.L., A.R., Y.H., I.Z.)
| | - Yael Hershkovitz
- Israel Center for Disease Control, Ministry of Health, Ramat Gan (C.L., A.R., Y.H., I.Z.)
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.).,Israel Center for Disease Control, Ministry of Health, Ramat Gan (C.L., A.R., Y.H., I.Z.)
| | - Ariel Furer
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.)
| | - Roy Gilon
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.)
| | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.).,Maccabitech (G.C.), Maccabi Healthcare Services, Tel Aviv, Israel
| | - Shmuel Tiosano
- Division of Cardiology, Leviev Heart and Vascular Center (S.T.), Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Estela Derazne
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.).,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.)
| | - Arnon Afek
- Central Management (A.A.), Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Orit Pinhas-Hamiel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital (O.P.-H.).,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Cole Daniel Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.)
| | - Gal Yaniv
- The Dr. Pinchas Bornstein Talpiot Medical Leadership Program (B.F., G.Y., G.T.), Sheba Medical Center, Ramat Gan, Israel.,Department of Diagnostic Imaging (G.Y.).,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
| | - Ran Shmuel Rotem
- Kahn-Sagol-Maccabi Research and Innovation Institute (R.S.R.), Maccabi Healthcare Services, Tel Aviv, Israel.,Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (R.S.R.)
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan (A.B., B.F., A.F., R.G., E.D., D. Tzur, C.D.B., G.T.).,The Dr. Pinchas Bornstein Talpiot Medical Leadership Program (B.F., G.Y., G.T.), Sheba Medical Center, Ramat Gan, Israel.,Institute of Endocrinology (G.T.).,Sackler Faculty of Medicine, Tel Aviv University, Israel (B.F., I.Z., G.C., S.T., E.D., A.A., O.P.-H., G.Y., G.T.)
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24
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Tsur AM, Hershkovich S, Zucker I, Lutski M, Pinhas-Hamiel O, Vivante A, Fischman M, Amir O, Rotchild J, Gerstein HC, Cukierman-Yaffe T, Friedensohn L, Mosenzon O, Derazne E, Tzur D, Tirosh A, Afek A, Raz I, Twig G. Stuttering and Incident Type 2 Diabetes: A Population-Based Study of 2.2 Million Adolescents. J Clin Endocrinol Metab 2021; 106:978-987. [PMID: 33449080 DOI: 10.1210/clinem/dgaa988] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE To investigate the association between stuttering in adolescence and incident type 2 diabetes in young adulthood. METHODS This nationwide population-based study included 2 193 855 adolescents of age 16 to 20 years who were assessed for military service between 1980 and 2013. Diagnoses of stuttering in adolescence were confirmed by a speech-language pathologist. Diabetes status for each individual as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent body mass index. RESULTS Analysis was stratified by sex (Pinteraction = 0.035). Of the 4443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared with 25 678 (2.1%) men without stuttering (adjusted odds ratio [OR] 1.3; 95% CI, 1.1-1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR = 1.5; 95% CI, 1.01-2.2), or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR = 1.4; 95% CI, 1.1-1.7). The association was stronger in later birth cohorts, with an adjusted OR of 2.4 (1.4-4.1) for cases of type 2 diabetes before age 40. Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes, compared with 10 139 (1.1%) women without stuttering (OR = 2.03; 95% CI, 0.48-2.20). CONCLUSIONS Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men.
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Affiliation(s)
- Avishai M Tsur
- The Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel
- Department of Medicine "B," Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 5266202, Israel
| | - Asaf Vivante
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Maya Fischman
- Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel
| | - Ofer Amir
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Jacob Rotchild
- The Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | | | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Limor Friedensohn
- The Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dorit Tzur
- The Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Arnon Afek
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Gilad Twig
- The Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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25
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Bardugo A, Bendor CD, Zucker I, Lutski M, Cukierman-Yaffe T, Derazne E, Mosenzon O, Tzur D, Beer Z, Pinhas-Hamiel O, Ben-Ami M, Fishman B, Ben-Ami Shor D, Raz I, Afek A, Gerstein HC, Häring HU, Tirosh A, Levi Z, Twig G. Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood. J Clin Endocrinol Metab 2021; 106:e34-e44. [PMID: 33075820 DOI: 10.1210/clinem/dgaa753] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Indexed: 02/08/2023]
Abstract
CONTEXT The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVE To assess type 2 diabetes risk among adolescents with NAFLD. DESIGN AND SETTING A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. PARTICIPANTS A total of 1 025 796 normoglycemic adolescents were included. INTERVENTIONS Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. MAIN OUTCOME MEASURES Type 2 diabetes incidence. RESULTS During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). CONCLUSIONS Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Zivan Beer
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Michal Ben-Ami
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Boris Fishman
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Internal Medicine D and Hypertension Unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Dana Ben-Ami Shor
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | | | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research, Tübingen, Germany
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Zohar Levi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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Simchoni M, Hamiel U, Pinhas-Hamiel O, Zucker I, Cukierman-Yaffe T, Lutski M, Derazne E, Beer Z, Behar D, Keinan-Boker L, Mosenzon O, Tzur D, Afek A, Tirosh A, Raz I, Twig G. Adolescent BMI and early-onset type 2 diabetes among Ethiopian immigrants and their descendants: a nationwide study. Cardiovasc Diabetol 2020; 19:168. [PMID: 33023586 PMCID: PMC7542395 DOI: 10.1186/s12933-020-01143-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 09/27/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND We assessed in a nationwide cohort the association between adolescent BMI and early-onset (< 40 years) type 2 diabetes among Israelis of Ethiopian origin. METHODS Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. RESULTS 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. CONCLUSIONS Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.
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Affiliation(s)
- Maya Simchoni
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Uri Hamiel
- Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Pediatric Endocrinology, Safra Children Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Zivan Beer
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | | | - Lital Keinan-Boker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel.
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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