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Despite a favorable effect of imatinib on glucose metabolism in animal models, human reports are inconsistent. We retrospectively studied the long-term effect of imatinib on fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), LDL-cholesterol (LDL), and triglycerides (TGs) in a large HMO cohort of patients initiating therapy. In patients with diabetes (

Evidence on simultaneous changes in body mass index (BMI) and cognitive decline, which better reflect the natural course of both health phenomena, is limited.We capitalized on longitudinal data from 15,977 initially non-demented elderly from the Alzheimer's Disease Centers followed for 5 years on average. Changes in BMI were defined as (1) last minus first BMI, (2) mean of all follow-up BMIs minus first BMI, and (3) standard deviation of BMI change from baseline and all follow-up visits (representing variability).Participants with significant changes in BMI (increase or decrease of ≥5%), or who had greater variability in BMI, had faster cognitive decline. This pattern was consistent irrespective of normal (BMI 25; N = 5747), overweight (25 ≤ BMI 30; N = 6302), or obese (BMI ≥ 30; N = 3928) BMI at baseline.Stability in BMI predicts better cognitive trajectories suggesting clinical value in tracking BMI change, which is simple to measure, and may point to individuals whose cognition is declining.

Fatty acid-binding protein 4 (FABP4) is an adipokine with a key regulatory role in glucose and lipid metabolism. We prospectively evaluated the role of FABP4 in the pathophysiology of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes. Clinical and laboratory data were prospectively collected from consecutive children presenting with new-onset type 1 diabetes. In addition to blood chemistry and gases, insulin, C-peptide, serum FABP4 and NEFA were collected upon presentation and 48 h after initiation of insulin treatment. In a mouse model of type 1 diabetes, glucose, insulin, β-hydroxybutyrate and weight were compared between FABP4 knockout (Fabp4−/−) and wild-type (WT) mice. Included were 33 children (mean age 9.3 ± 3.5 years, 52% male), of whom 14 (42%) presented with DKA. FABP4 levels were higher in the DKA group compared with the non-DKA group (median [IQR] 10.1 [7.9–14.2] ng/ml vs 6.3 [3.9–7] ng/ml, respectively; p = 0.005). The FABP4 level was positively correlated with HbA1c at presentation and inversely correlated with venous blood pH and bicarbonate levels (p

Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic.To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic.A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL).Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P0.01 and P0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P0.01).Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.

Background: We compared glycemic outcomes and participant experience during MiniMed™ 780G Advanced Hybrid Closed Loop (AHCL) system use while announcing all meals vs. announcing meals at will. Methods: Participants with T1DM used the AHCL system at home during two 90 days phases in which they were given instructions first to announce all meals (AM) , and next, for meals containing up to 80 grams of carbohydrates, to announce meals at will (AMW) . Results: Fourteen subjects (males, mean age 44.3±11) with T1DM were enrolled, with a baseline A1C of 6.9±1%. Table 1 summarizes glycemic indices and AHCL data, demonstrating that patients chose to bolus only slightly less during AMW compared to AM (5.5 vs. 5.2 boluses) , without resultant deterioration in glycemic indices (A1c 6.4 vs. 6.5%, TIR 78.1 vs. 78.8%, p=ns) . Subjects surveyed regarding the option not to have to bolus for all meals experienced a significant reduction in reported effort to manage diabetes (p=0.045) and 86% endorsed worrying less about their diabetes. Most (93%) preferred the AMW phase of the study. Conclusion: The MinMed™ AHCL system is designed for optimal performance with meal announcement. Nonetheless, when meals containing < 80 grams of carbohydrates are consumed with announcement of meals at will, there is a slight reduction in the number of daily boluses with no decline in glycemic control, yet markedly less diabetes related distress and improved treatment satisfaction. Disclosure N. Minsky: None. R. Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. O. Cohen: Employee; Medtronic. N. Kurtz: Employee; Medtronic. A. Roy: Employee; Medtronic. B. Grosman: Employee; Medtronic. A. Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi. Consultant; Bayer AG, DreaMed Diabetes, Ltd. Research Support; Medtronic. Speaker's Bureau; Eli Lilly and Company.

Accumulating evidence link sugar-containing foods and beverages to adverse health outcomes. Non-Caloric Sweeteners (NCSs) are an alternative sugar source that lead to reduction in calories, and may mitigate body weight gain and hyperglycemia, especially in patients with diabetes. Yet, contradicting studies suggest that NCSs may mediate metabolic derangements. Here, we aim to assess long-term metabolic effects of chronic consumption of NCSs. To this aim, mice consuming either regular diet or high fat diet (HFD) were supplemented with NCSs in their drinking water at concentrations consumed by humans. Under HFD, mice consuming reb M or sucralose had significant lower body weight compared to fructose. In comparison to fructose consumption, a significantly lower blood glucose levels were observed in mice under chow diet drinking either sucralose or reb M. Under HFD, a significant decrease in blood glucose levels was found only in mice consuming ace-k. On HFD, all NCSs other than saccharin, resulted in significantly improved insulin sensitivity compared to fructose. A significant decrease in fasting glucose was found only in sucralose and reb M groups under these conditions. A trend towards higher levels of plasma insulin was observed in mice under HFD drinking either fructose or saccharin. None of the interventions caused a decrease in fluid consumption as compared to water, nor were significant differences in daily food intake, daily caloric intake or energy expenditure. RER displayed a normal nocturnal pattern in all groups and no significant change in voluntary physical activity was observed. As compared to fructose, NCS consumption decreased markers of NAFLD in obesity. In summary, our results suggest that chronic consumption of NCS do not result in any observed metabolic alternations, and may attenuate some of the metabolic derangements associated with fructose and high fat-based diet. Disclosure M.Rathaus: None. L.Azem: None. R.Livne: None. S.Ron: None. I.Ron: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.

Diabetes in general, and specifically in the context of obesity, is characterized by hyperglycemia resulting in non-enzymatic glycation of proteins, a key event in the pathophysiology of diabetes and its chronic complications. Yet, the full scope of molecular targets for glycation, particularly in liver, is incompletely understood. De-glycation, which removes the attached sugars, is controlled intracellularly by fructosamine-3-kinase (FN3K) , a kinase that phosphorylates the attached sugar and has been proposed to have a protective role against the deleterious effects of glycation related to diabetes. However, FN3K has been suggested to be ubiquitously expressed and to act as a constitutive housekeeping gene. Furthermore, whether intracellular de-glycation is regulated in physiological contexts and what factors are involved in its regulation remain unknown. Our data identify that regulation of protein glycation in liver is controlled by the key metabolic regulators PGC-1s (PGC-1alpha and PGC-1beta) in response to metabolic cues, particularly in the fed state. Liver-specific deletion of PGC-1s results in reduction of Fn3k expression and concomitant increase in specific protein glycation. In accordance, overexpression of PGC-1alpha in liver-derived cells induces Fn3k and a reduction in protein glycation. Purification of glycated proteins followed by mass spectrometric analysis reveals significant alterations in intracellular protein glycation in response to PGC1-alpha expression. Mechanistically, PGC-1alpha effect on Fn3k involves the activity of the transcription factor Foxo1. Thus, in liver, fasting and re-feeding govern intracellular protein glycation via PGC-1 dependent induction of FN3K. Our work reveals the scope and dynamic nature of the liver glycome, establishing the PGC1/FN3K axis as a key regulator of protein glycation. Disclosure E.Glick saar: None. Y.G.Daime: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker’s Bureau; Eli Lilly and Company. N.Minsky: None.

Background: Carb-counting is a significant burden for persons with diabetes who require insulin to mitigate postprandial hyperglycemia. A closed-loop (CL) system with auto meal-bolus that eliminates manual mealtime bolusing was studied in adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the KLUE application that detects eating hand-gestures using motion sensors. A smartphone algorithm converted eating hand-gestures to carb amounts that were relayed to the pump for automatic bolusing. For 6 days, participants (N=17, aged 18-75 years) with T1D used the system with the KLUE app disabled and completed traditional carb-counting and -entry (Baseline) . Thereafter, the KLUE app was enabled for 5 days and carb-counting/carb-entry was prohibited (Study) . Participants were given the same 5 test-meals (one/day) of varying caloric and carb sizes during both periods. Otherwise, they had no other meal restrictions. Results: No significant difference in TIR was observed between periods and time spent at Conclusion: Data suggest that the novel CL system maintains glycemic control similar to that with manual meal bolusing. By eliminating the burden of carb-counting, the new CL system may improve the quality of life in persons with T1D. Disclosure A.Roy: Employee; Medtronic. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. B.Grosman: Employee; Medtronic. D.Miller: Employee; Medtronic. T.Engel: None. O.Cohen: Employee; Medtronic. R.Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. S.Shalem: None. M.Laron hirsh: None. Y.Cohen: None.

Obesity is a leading global health concern and a major risk factor for type-2 diabetes. Thus, identifying mechanisms linking obesity to insulin resistance is of great importance. Chronic low-grade inflammation of the adipose tissue (AT) observed in obesity has been shown as an important pathophysiological link between obesity and the development of systemic insulin resistance, by various mechanisms. Gap junction (GJ) intercellular-communication, primarily composed of connexin- (Cx) 43, has been recently reported to have immunomodulatory roles in various tissues, and increased Cx43 expression and GJ activity have been implicated in the response of various tissues to chronic stress conditions. We have therefore aimed to study the role of Cx43 in shaping the AT adaptive or maladaptive response to these cellular insults of obesity. In a diet-induced obesity mouse model we demonstrated an increase in Cx43 expression in the intact AT, which could be primarily attributed to increased Cx43 expression in adipocytes. In high fat diet-fed adipocyte-specific Cx43 knock-out mice (AdCx43KO) , we observed increased infiltration of macrophages to the AT as compared to wild-type (WT) mice. This was accompanied by morphologic changes in the AT, with increased variability in adipocyte size. While AdCx43KO mice did not significantly differ from WT mice in body weight, adiposity or food intake, the AdCx43KO mice demonstrated reduced whole-body insulin sensitivity assessed by insulin tolerance test. Mechanistically, we observed that adipocytes can interact directly with neighboring adipocytes as well as with macrophages via Cx43-composed gap junctions, an interaction that is likely to be key in attenuation of the tissue inflammatory response. Our results suggest an immunomodulatory and metabolic role for adipocyte-Cx43 in obesity. Disclosure S.Ron: None. I.Ron: None. M.Rathaus: None. R.Livne: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. Funding Israel Science Foundation (922/17)

Patients' satisfaction is a key determinant of treatment adherence and persistence, for optimal management of T2D. ATOS, a 12-month prospective observational study conducted in Asia, Middle East, North Africa, Latin America, and Eastern Europe, showed that initiation of Gla-300 in insulin-naïve people with T2D resulted in improved glycemic control with low rates of hypoglycemia. This analysis evaluated changes in treatment satisfaction and health status among participants. Data was collected using PRO questionnaires - Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change versions (DTSQc) , EuroQoL 5-dimension scale version 3L (EQ-5D-3L) at baseline, Month 3, 6 and 12. Overall, 3931 participants completed the questionnaires. Mean ±SD age was 57.5 ±10.6 years, duration of diabetes was 10.1 ±6.2 years and baseline HbA1c was 9.3 ±1.0 %. Treatment satisfaction improved over time (DTSQs score of 21.7 at baseline to 29.8 and 31.3 at Month 6 and 12, respectively) and perceived frequency of hyperglycemia decreased over 12 months. DTSQc results were aligned with DTSQs. EQ-5D-3L results showed that proportion of people with better health status increased over time (Table) . Results showed that initiating Gla-300 in insulin-naïve people with T2D across multiple geographic regions improved treatment satisfaction and health status. Disclosure N.Khan: None. G.R.Galstyan: n/a. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. A.Bhansali: None. H.Vargas-uricoechea: Advisory Panel; Sanofi, Speaker's Bureau; Abbott. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. A.Roborel de climens: Employee; IQVIA Inc., Sanofi. M.N.Mabunay: Employee; Sanofi. M.Coudert: Employee; Sanofi. V.Pilorget: None. Funding Sanofi

Background: Studies in children reported an association between increased body mass index (BMI) and risk for developing type 1 diabetes (T1D) . We studied the association between adolescent BMI and incident T1D in young adulthood in a nationwide cohort of 1,462,362 adolescents which was recently used to assess the association between adolescent BMI and early-onset type 2 diabetes (Diabetes Care 2020 Jul;43 (7) :1487-1495) . Methods: All Israeli adolescents, ages 16-19, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycemia. Data were linked to information about adult onset of T1D in the Israeli National Diabetes Registry. Weight and height were measured at the study entry. Cox proportional models were applied, with BMI analyzed both as a categorical and as a continuous variable. Islet autoantibody data were available for a subpopulation of the cohort. Results: There were 777 incident cases of T1D during 15,810,751 person-years (mean age at diagnosis 25.2±3.9 years) . BMI was associated with incident T1D. In a multivariable model adjusted for age, sex and socio-demographic variables, the hazard ratios (HRs) for T1D were 1. (95% CI 0.87-1.27) for the 50th-74th BMI percentiles, 1.41 (1.11-1.78) for the 75th-84th BMI percentiles, 1.54 (1.23-1.94) for adolescents with overweight (85th-94th percentiles) , and 2. (1.58-2.66) for adolescents with obesity (BMI≥95th percentile) . One increment in BMI standard deviation was associated with 25% greater risk for incidence of T1D (HR=1.25, 95%CI 1.17-1.32) . Association persisted when the definition of T1D included the presence of islet autoantibodies; when the study population was restricted to those with unimpaired health. Conclusions: Excessively high BMI in apparently healthy adolescents is associated with increased risk for incident T1D in early adulthood. Disclosure I.Zucker: None. D.Tzur: None. C.Melzer cohen: None. O.Pinhas-hamiel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Pfizer Inc. G.Chodick: None. I.Raz: None. A.Afek: None. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. G.Twig: None. Y.Zloof: None. A.Bardugo: None. A.M.Tsur: None. M.Lutski: None. Y.Cohen: None. T.Cukierman-yaffe: Research Support; European Association for the Study of Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. N.Minsky: None. E.Derazne: None. Funding This work was partially supported by an internal grant from the Israel Defense Forces Medical Corps.

Background: Artificial intelligence-based decision support system (AI-DSS) for frequent insulin dose adjustment was demonstrated to be effective in improving glycemic control in our previous clinical trials. We aimed to assess the effectiveness of AI-DSS in real world diabetes clinics. Methods: Data was collected and evaluated from routine AI-DSS usage for individuals with type 1 diabetes treated at 21 diabetes clinics (in the USA and 2 in Israel) . Two analyses were made: (1) Insulin dose recommendations were compared for rate of agreement/disagreement between those suggested by the AI-DSS and the approved recommendations by health care providers (HCP) . (2) Glycemic outcomes were compared between baseline and after 3 months of AI-DSS use. Included in this analysis were individuals who had mean baseline glucose level ≥ 182 mg/dL and at least one AI-DSS recommendation within the 3-months. Results: A total of 8 recommendations, provided to 370 individuals, were evaluated. Full agreement on the direction of insulin dose adjustments was observed in 87%, 87%, and 83% of the basal rate, carbs ratio (CR) , and correction factor (CF) pump settings parameters, respectively. Full disagreement on the direction of dose change was observed in only 0.9%, 0.5%, and 1.2% for the basal rate, CR and CF, respectively. Glycemic outcome analysis included 1 eligible individuals (mean of 1.6 recommendations within a 3-month interval) . Average sensor percentage of time in range [70-180 mg/dL] increased by 4% (p=0.003) : 43% increased time in range by more than 5% and 33% increased by 10% or more. Time in hyperglycemia [> 180 mg/dL] was reduced by 5% (p Conclusion: A high rate of agreement with automated insulin adjustments was observed among HCPs at academic centers who used the AI-DSS in their workflow. Glycemic control was significantly improved for sub-optimally controlled individuals already after 3-months of follow up. Disclosure R.Nimri: Employee; DreaMed Diabetes, Ltd., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; DreaMed Diabetes, Ltd. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. I.Muller: Board Member; DreaMed Diabetes, Ltd. Y.Shtrit: Employee; DreaMed Diabetes, Ltd. M.Phillip: Advisory Panel; Dompé, Insulet Corporation, Medtronic, Pfizer Inc., Board Member; DreaMed Diabetes, Ltd., Consultant; QuLab Medical Ltd., Other Relationship; Dexcom, Inc., Dompé, DreaMed Diabetes, Ltd., Eli Lilly and Company, Medtronic, NG Solutions Ltd, Novo Nordisk, OPKO, Pfizer Inc., Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd., NG Solutions Ltd.

Lung neoplasms often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNETs) and PA constitute a unique entity and the impact of such co-diagnosis on patients’ outcome is yet to be defined. The study objective was to compare patients’ clinical characteristics with LNET to patients co-diagnosed with PA. A Retrospective, case-control study based on the Surveillance, Epidemiology, and End Results (SEER) registry database between 2000 and 2016. A total of 2947 patients with LNET, including 2913 with LNET alone (“Sporadic”) and 34 patients with both LNET and PA (“LNET-PA”). PA preceded LNET diagnosis in 85.3% of patients and had higher rates among LNET patients (34/2947) than with any cancer (p

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.

Aims Studies in children reported an association between increased body mass index (BMI) and risk for developing type 1 diabetes (T1D), but evidence in late adolescence is limited. We recently investigated the association between adolescent BMI and type 2 diabetes in young adulthood (Diabetes Care 2020, 43(7): 1487-95) and here we studied on the same cohort the association between late adolescent BMI and incident T1D. Methods All Israeli adolescents, ages 16-19, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycemia (n=1,462,362; 40% women). Data were linked to information about adult onset of T1D in the Israeli National Diabetes Registry. Weight and height were measured at study entry and BMI was computed and transformed to age- and sex-adjusted BMI percentiles according to US Center for Diseases Control. The definition of T1D was determined based on anti-diabetic drugs and was confirmed for a subpopulation of the cohort to which islet autoantibodies data were available. Cox proportional models were applied, with BMI analyzed both as a categorical and continuous variable. Results There were 777 incident cases of T1D during 15,810,751 person-years (mean age at diagnosis 25.2±3.9 years). The median follow-up period was 11.2 years (IQR 5.8-16.3), with follow-up length shorter for individuals with a higher BMI. The crude diabetes rate showed a consistent graded increase across BMI groups from underweight to obesity; 3.6 to 8.4 cases per 100,000 person-years, respectively. In a multivariable model adjusted for age, sex and socio-demographic variables, the hazard ratios (HRs) for T1D were 1.05 (95% CI 0.87-1.27) for the 50th–74th BMI percentiles, 1.41 (1.11–1.78) for the 75th–84th BMI percentiles, 1.54 (1.23–1.94) for adolescents with overweight (85th–94th percentiles), and 2.05 (1.58–2.66) for adolescents with obesity (BMI≥95th percentile)(reference group, 5th-49th BMI percentile group). One increment in BMI standard deviation was associated with 25% greater risk for incidence of T1D (HR=1.25, 95%CI 1.17-1.32). when the presence of one or multiple (≥2) islet antibodies was added as a criterion for T1D definition, the HRs among those with adolescent obesity were 2.90 (1.80-4.68) and 3.14 (1.68-5.88) respectively. Results were marginally affected by level of adjustment for sociodemographic background, were similar when analysis was stratified by sex, and also persisted when the study population was limited to adolescents with unimpaired health in order to mitigate confounding by coexisting illness. The fraction of type 1 diabetes attributed to adolescent overweight and obesity (Population attributable risk%; PAR%) was 10.1% (95%CI 6.3%-14.2%). Conclusions Adolescent overweight and obesity in apparently healthy adolescents were associated with increased risk for incident type 1 diabetes in early adulthood. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:24 p.m. - 1:30 p.m.

Objective: To examine the clinical differences in manifestation, treatment, and prognosis of thyroid-eye-disease (TED) between men and women. Methods: This is a longitudinal cohort study. Men and women, who diagnosed with TED and treated at a multidisciplinary TED clinic, were compared regarding differences in demographics, eye examination, disease activity, and quality of life evaluation. Results: TED was diagnosed in 132 patients during the study period, and they included 38 men (28.78%) and 94 women (71.21%). There were six men and 20 women with active disease (Clinical-Activity-Score (CAS) ⩾ 3) during the entire follow-up period ( p Conclusion: Active disease was more common in women and the time-from-diagnosis of TED to CAS ⩾ 3 was shorter among women. Moreover, the appearance QOL score of women was poorer. These findings should be taken into consideration when planning the timing of treatment and when choosing the best treatment for TED patients.

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.

BackgroundPersonality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality.MethodsWe performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011.ResultsThe study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up.ConclusionsPersonality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

The clinical benefits of insulin glargine 300 U/mL (Gla-300) have been confirmed in randomised clinical trials (EDITION programme and BRIGHT) and real-world studies in the USA and Western Europe. ATOS evaluated the real-world effectiveness and safety of Gla-300 in wider geographic regions (Asia, the Middle East, North Africa, Latin America and Eastern Europe).This prospective observational, international study enrolled adults (≥ 18 years) with type 2 diabetes mellitus (T2DM) uncontrolled [haemoglobin A1c (HbA1c) 7% to ≤ 11%] on one or more oral anti-hyperglycaemic drugs (OADs) who had been advised by their treating physician to add Gla-300 to their existing treatment. The primary endpoint was achievement of a pre-defined individualised HbA1c target at month 6.Of the 4550 participants included, 4422 (51.8% female) were eligible for assessment. The mean ± standard deviation (SD) age was 57.2 ± 10.8 years, duration of diabetes was 10.2 ± 6.2 years and baseline HbA1c was 9.28 ± 1.0%. The proportion of participants reaching their individualised glycaemic target was 25.2% [95% confidence interval (CI) 23.8-26.6%] at month 6 and 44.5% (95% CI 42.9-46.1%) at month 12. At months 6 and 12, reductions were observed in HbA1c (-1.50% and -1.87%) and fasting plasma glucose (-3.42 and -3.94 mmol/L). Hypoglycaemia incidence was low, and body weight change was minimal. Adverse events were reported in 283 (6.4%) participants, with 57 (1.3%) experiencing serious adverse events.In a real-world setting, initiation of Gla-300 in people with T2DM uncontrolled on OADs resulted in improved glycaemic control and low rates of hypoglycaemia with minimal weight change.Clinicaltrials.gov number NCT03703869.

Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P

Immigration from one cultural milieu to another has been associated with a greater risk for incident cardio-metabolic morbidity among adults. In this nationwide, population-based, cross-sectional study of data recorded from 1992 to 2016, we assessed the association between body mass index and blood pressure levels among adolescent immigrants, aged 16 to 19 years, of Ethiopian origin, and their secular trend of overweight and obesity. Adolescents of Ethiopian origin were classified as Israeli-born (n=16 153) or immigrants (N=23 487), with stratification by age at immigration. Adolescents whose fathers were at least 3 generations in Israel (n=277 789) served as a comparative group. Hypertensive-range blood pressure values adjusted for age, sex, and height served as outcome. Among adolescents of Ethiopian origin, overweight and obesity (body mass index ≥85th percentile), increased by 2.5 and 4-fold in males and females, respectively, during the study period, compared with a 1.5-fold increase among native Israeli-born males and females. The odds for hypertensive-range measurements increased with the length of residence in Israel: 7.3%, 10.6%, and 14.4% among males who immigrated at ages 12 to 19, 6 to 11.9, and 0 to 5.9 years, respectively; and 11.5%, 16.7%, and 19.3%, respectively, among females. Israeli-born Ethiopians had a significantly higher risk for hypertensive-range measurements at any body mass index level compared with native Israeli-born examinees, after adjusting for sociodemographic factors and health status. In conclusion, among Ethiopian Israeli adolescents, abnormal blood pressure correlates directly with the time-lapse since immigration. Immigrant populations require targeted surveillance and appropriate intervention.

Summary Background & aims While the world is extensively looking for alternatives to animal protein sources, it is not clear which plant sources can provide the requisite full complement of essential amino acids (EAAs). Wolffia globosa is an aquatic, edible duckweed, the smallest plant on earth, and it offers all nine EAAs, dietary fibers, polyphenols, iron, zinc and B12 vitamin. This work was designed to evaluate Mankai (a newly developed high-protein strain of W. globosa) as an optional bioavailable source of EAAs for humans (primary outcome), and of further nutrients such as vitamin B12, in comparison to well-established animal and plant protein sources; cheese and peas, respectively. Methods 36 men, subjected for 3 days to a stable diet and subsequent overnight (12 h) fast, were randomized to consume one of three iso-protein (30 g) based test-meals (soft cheese, green peas, Mankai). Blood samples were collected at 0, 30, 90 and 180 min. Results The 3 h blood concentrations of the EAAs: histidine, phenylalanine, threonine, lysine, and tryptophan, triggered by intake of Mankai, was essentially significant as compared to baseline (p 0.05 between groups). Although branched-chain-amino-acids (leucine/isoleucine, valine) increased significantly by Mankai within 3 h (p Conclusions Mankai may provide a high-quality substitute source for animal protein, and a potential bioavailable source of vitamin B12.

Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood.All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable.There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32).Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Autonomous cortisol secretion (ACS) is common in patients with adrenal incidentalomas (AI). ACS is associated with increased cardiovascular morbidity and mortality. Data regarding the association between radiological characteristics of adrenal adenomas, their hormonal functionality and metabolic outcomes, are scarce and inconclusive. In this study, we aim to delineate the association between radiological characteristics of AI, ACS and metabolic status.A cross-sectional study of 77 patients with AI who underwent a comprehensive hormonal evaluation. Radiological assessments were performed by an independent radiologist blinded to the clinical and hormonal phenotype of each case. Linear regression models were used to evaluate the association between post dexamethasone suppression test (DST) cortisol levels, metabolic indices and radiological measurements.Mean maximal adenoma diameter was greater in patients with versus without ACS (20.35 ± 6 vs. 27.09 ± 9.3 mm, respectively, p .01). Maximal adenoma diameter was found to be positively and linearly correlated with post-DST morning cortisol levels across their entire range (R = .474, p .01). Linear correlations between maximal adenoma diameter and indices of glycemic control showed a correlation coefficient (R) of .481 and .463 for fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c), respectively, p .01. When analysis included only patients with ACS, an R = .584 and R = .565 was observed for FPG and HbA1c, respectively (p .01 for both). The association between maximal adenoma diameter and both FPG and post-DST morning cortisol intensified in patients with metabolic syndrome.There is a quantitative positive mild correlation between AI size and both cortisol autonomy and metabolic parameters.

During pregnancy, fetal glucose production is suppressed, with rapid activation immediately postpartum. Fatty acid-binding protein 4 (FABP4) was recently demonstrated as a regulator of hepatic glucose production and systemic metabolism in animal models. Here, we studied the role of FABP4 in regulating neonatal glucose hemostasis. Serum samples were collected from pregnant women with normoglycemia or gestational diabetes at term, from the umbilical circulation, and from the newborns within 6 hours of life. The level of FABP4 was higher in the fetal versus maternal circulation, with a further rise in neonates after birth of approximately 3-fold. Neonatal FABP4 inversely correlated with blood glucose, with an approximately 10-fold increase of FABP4 in hypoglycemic neonates. When studied in mice, blood glucose of 12-hour-old WT, Fabp4-/+, and Fabp4-/- littermate mice was 59 ± 13 mg/dL, 50 ± 11 mg/dL, and 43 ± 11 mg/dL, respectively. Similar to our observations in humans, FABP4 levels in WT mouse neonates were approximately 8-fold higher compared with those in adult mice. RNA sequencing of the neonatal liver suggested altered expression of multiple glucagon-regulated pathways in Fabp4-/- mice. Indeed, Fabp4-/- liver glycogen was inappropriately intact, despite a marked hypoglycemia, with rapid restoration of normoglycemia upon injection of recombinant FABP4. Our data suggest an important biological role for the adipokine FABP4 in the orchestrated regulation of postnatal glucose metabolism.

The non-invasive self-monitoring of blood glucose (SMBG) has been the subject of intense investigation over recent decades. We conducted a pilot study designed to examine a novel non-invasive glucometer, the HGR GWave, utilizing radiofrequency (RF) sensing. Blood glucose levels assessed by this HGR prototype were compared to measurements performed by a hexokinase core laboratory assay during an oral glucose tolerance test (oGTT) for 5 subjects with type 2 diabetes. The HGR glucose meter readings were also compared to two Abbot Freestyle® glucose meters, which were also used for calibration. The accuracy of the results was evaluated through the calculation of relative absolute difference (RAD), specified percentage differences between 43 reference glucose measurements, and using comparator measurements. The median RAD was −4.787. We detected 79.04%, 92.99% and 97.64% of HGR readings within ±10%, ±15% and ±20% of the reference glucose measurements. The HGR readings had a high correlation with reference lab glucose measurements with R2 = 0.924 (95% CI 0.929–0.979, p &lt, 0.0001). When compared to the Freestyle® glucose meters 94.3% and 100% of the readings were within ±5% and ±10%, with R2 = 0.975 (0.975–0.994, 0.0001). The HGR prototype glucose meter was found to be accurate in detecting real-time blood glucose during an oGTT in this small pilot study. A study with a broader range of blood glucose levels is needed to further assess its accuracy and its suitability for clinical use.

BackgroundA Mediterranean diet is favourable for cardiometabolic risk.ObjectiveTo examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk.MethodsFor the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state.ResultsParticipants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p=0.073, HDG−1.4%; pConclusionsThe green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.Trial registration numberThis study is registered under ClinicalTrials.gov Identifier no NCT03020186.

Context A correlation between myopia and insulin resistance has been suggested. Objective We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood. Methods This population-based, retrospective, cohort study comprised 1 329 705 adolescents (579 543 women, 43.6%) aged 16 to 19 years, who were medically examined before mandatory military service during 1993 to 2012, and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right-eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up. Results There was an interaction between myopia and sex with T2D (P Conclusion For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis.

The coronavirus pandemic enforced social restrictions with abrupt impacts on mental health and changes to health behaviors. From a randomized clinical trial, we assessed the impact of culinary education on home cooking practices, coping strategies and resiliency during the first wave of the COVID-19 pandemic (March/April 2020). Participants (n = 28) were aged 25–70 years with a BMI of 27.5–35 kg/m2. The intervention consisted of 12 weekly 30-min one-on-one telemedicine culinary coaching sessions. Coping strategies were assessed through the Brief Coping with Problems Experienced Inventory, and resiliency using the Brief Resilient Coping Scale. Home cooking practices were assessed through qualitative analysis. The average use of self-care as a coping strategy by the intervention group was 6.14 (1.66), compared to the control with 4.64 (1.69), p = 0.03. While more intervention participants had high (n = 5) and medium (n = 8) resiliency compared to controls (n = 4, n = 6, respectively), this difference was not significant (p = 0.33). Intervention participants reported using home cooking skills such as meal planning and time saving techniques during the pandemic. The key findings were that culinary coaching via telemedicine may be an effective intervention for teaching home cooking skills and promoting the use of self-care as a coping strategy during times of stress, including the COVID-19 pandemic.

ATOS was a 12-month prospective observational study in 18 countries outside US and Western Europe in insulin-naive adults with T2DM, uncontrolled (HbA1c >7-≤11%) on ≥1 oral antihyperglycemic drug. In this subgroup analysis participants were stratified by BL HbA1c: 50% of participants with BL HbA1c Disclosure N. Khan: None. A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. G. R. Galstyan: None. Funding Sanofi

ATOS, a prospective, 12-month observational study in 18 countries outside US and Western Europe, showed that initiation of Gla-300 in people with T2DM resulted in improved glycemic control with low rates of hypoglycemia and minimal weight change. Here we present the results from a subgroup analysis in participants with (N=581) or without (N=3841) a history of RI (~70% microalbuminuria, Table). Patients with RI were older (62.2±10.3 vs. 56.4±10.7 years), had a longer duration of T2DM (mean: 12.7±6.9 vs. 9.8±6.0 years) and more comorbidities than patients without RI. Baseline HbA1c was comparable between groups (9.3%). Physician-set individualized HbA1c (%) goals at baseline in the RI vs. non-RI groups were Disclosure A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. N. Khan: None. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. G. R. Galstyan: None. Funding Sanofi

ATOS was a 12-month prospective observational study in 18 countries outside US and Western Europe in insulin-naive adults with T2DM, uncontrolled (HbA1c >7-≤11%) on ≥1 oral anti-hyperglycemic drug. This subgroup analysis of ATOS compared the effectiveness and safety of Gla-300 in older (≥70 years [Y]; N=514) and younger ( Disclosure G. R. Galstyan: None. A. Tirosh: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; Self; DreaMed Diabetes, Ltd. H. Vargas-uricoechea: Advisory Panel; Spouse/Partner; Sanofi. M. N. Mabunay: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. N. Khan: None. Funding Sanofi

The incidence of adolescent hypertension is growing worldwide, mostly in conjunction with the growing obesity prevalence (1,2). Adolescent hypertension was shown to be a risk factor for cardiovascular and renal outcomes later in life, thus promoting current guidelines to screen all pediatric and adolescent population for hypertension (1,3). Here, we elucidate the association of adolescent hypertension and early-onset type 2 diabetes in a nationwide cohort of adolescents. In this population-based, retrospective cohort study we linked the Israeli Defense Forces conscription center database with the Israeli National Diabetes Registry (INDR). One year prior to mandatory military service at age 17 years, Israeli adolescents undergo comprehensive medical evaluation based on their medical history, an interview and physical examination that includes measurements of height, weight, and blood pressure. Included were adolescents who were examined between 1 January 1993 and 31 December 2016. Excluded were those with prior diagnosis of dysglycemia and those with missing baseline height or weight data (3.8% in total). Essential hypertension diagnosis was confirmed by a board-specified nephrologist based on a preexisting diagnosis or screening for hypertension as described previously (1). Briefly, adolescents with blood pressure measurement during the screening assessment of >140/90 mmHg were referred for further investigation. The final diagnosis was made when the average of 10 additional outpatient blood pressure measurements was >140/90 mmHg, when at least 50% of the measurements were above this level, and after exclusion of secondary hypertension. The primary outcome was incident type 2 diabetes as documented by the INDR, which captures all cases of diabetes in Israel with a sensitivity of 95.1% (2). Cox models were applied. Follow-up started at the day of the first medical examination and ended at the date of diabetes diagnosis, 31 December 2016, or death—whichever came first. Due to the previously described …

OBJECTIVE The relationship between acute pancreatitis and incident diabetes is unclear. We assessed whether a resolved single event of acute pancreatitis in childhood was associated with incident diabetes in adulthood. RESEARCH DESIGN AND METHODS A nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years [range 16–20]) who were examined before compulsory military service between 1979 and 2008 and whose data were linked to the Israeli National Diabetes Registry (INDR). Resolved pancreatitis was defined as a history of a single event of acute pancreatitis with normal pancreatic function at enrollment. Logistic regression analysis was applied. RESULTS Incident diabetes developed in 4.6% of subjects with resolved pancreatitis (13 of 281; none of these cases were identified as type 1 diabetes) and 2.5% among the unexposed group (44,463 of 1,801,716). Resolved acute pancreatitis was associated with incident diabetes with an odds ratio (OR) of 2.23 (95% CI 1.25–3.98) with adjustment for age, sex, and birth year. Findings persisted after further adjustments for baseline BMI and sociodemographic confounders (OR 2.10 [95% CI 1.15–3.84]). Childhood pancreatitis was associated with a diagnosis of diabetes at a younger age, with 92% of diabetes case subjects diagnosed before 40 years of age compared with 47% in the unexposed group (P = 0.002). The association accentuated when the study sample was limited to individuals of unimpaired health or normal BMI at baseline. CONCLUSIONS A history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is a risk factor for incident type 2 diabetes, especially at young adulthood.