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.
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. Methods: In a mother-offspring, historical cohort, the Israel military conscription dataset was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and performed 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 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 mother's late-adolescent characteristics (sociodemographic confounders and BMI) and pregnancy age were 1.2 (95%CI, 1.1-1.4) , 1.3 (95%CI, 1.2-1.5) , and 1.4 (95%CI, 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, were associated with increased odds for offspring overweight/obesity at late adolescence. Disclosure C.D.Bendor: None. Y.Lebenthal: Advisory Panel; Lilly, Novo Nordisk, Research Support; Novo Nordisk, Pfizer Inc., Speaker's Bureau; Pfizer Inc. A.Afek: None. G.Chodick: None. G.Twig: None. A.Bardugo: None. R.Rotem: None. E.Derazne: 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. D.Tzur: None. O.Pinhas-hamiel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Pfizer Inc. A.M.Tsur: 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.
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