The influence of parental history of diabetes and offspring birthweight on offspring glucose metabolism in adulthood

Background. Links are well established between both family history of diabetes and reduced birthweight and increased risk of diabetes in adulthood. Objectives. 1) To investigate the influence of parental history of type 2 diabetes (T2DM) on offspring birthweight and adult offspring glucose tolerance status in non-diabetic offspring of patients with T2DM and 2) to study the associations of birthweight with measures of pancreatic beta-cell function and insulin sensitivity. Design. Family cohort study. Population. Offspring of patients with verified T2DM diagnosed after age 40 years with a spouse without known diabetes. Methods. Oral glucose tolerance tests and frequently sampled intravenous glucose tolerance tests (FSIGT) in nondiabetic offspring. Birthweight and length obtained from birth records. Results. Among 122 offspring with maternal history of T2DM, 14.8% had diabetes compared to 8.0% in 137 offspring with paternal history of diabetes, p=0.09. Offspring with maternal history of T2DM had a mean birthweight 196g higher than offspring with paternal T2DM (3 651±640g (mean±SD) vs. 3 456±472g (p=0.01)). Nondiabetic offspring with birthweights in the lowest tertile had significantly higher plasma glucose levels after an oral glucose tolerance test (OGTT) [Area under the curveglucOGTT, mean (95%CI), 1 795 (1 725‐1 866) vs. 1 683 (1 613‐1 753) mmol/L/min, p=0.02], and lower insulin sensitivity index calculated from a frequentlysampledintravenousglucosetolerancetest‐Si9.60[10 ‐5 (min ∗ pmol/L) ‐1 ] (8.23‐10.97)vs.11.79(10.41‐13.18),p=0.02‐inadulthoodcomparedtooffspring with birthweights in the upper tertile. Conclusions. Offspring with a family history of maternal T2DM have higher birthweights than those with paternal T2DM. Low birthweight associates with elevated plasma glucose levels after an oral glucose load and decreased insulin sensitivity in adulthood. Abbreviations: AIR, acute serum insulin responses; AUC, area under the curve; BMI, body mass index; FSIGT, frequently sampled intravenous glucose tolerance test;OGTT,oralglucosetolerancetest;Sg,glucoseeffectiveness;Si,insulinsensitivity index; T2DM, type 2 diabetes