Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

TY - JOUR

T1 - Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

AU - Kelstrup, Louise

AU - Damm, Peter

AU - Mathiesen, Elisabeth R

AU - Hansen, Torben

AU - Vaag, Allan A

AU - Pedersen, Oluf Borbye

AU - Dalsgaard Clausen, Tine

PY - 2013/9

Y1 - 2013/9

N2 - Context: Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown. Objective: We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes. Design, Setting, and Participants: A cohort of 587 Caucasian offspring, without known diabetes, was followed up at the age of 18-27 years. We included 2 groups exposed to maternal diabetes in utero: offspring of women with gestational diabetes mellitus (n = 167) or type 1 diabetes (n =153). Two reference groups were included: offspring of women with risk factors for gestational diabetes mellitus but normoglycemia during pregnancy (n = 139) and offspring from the background population (n = 128). Main Outcome Measures: Indices of insulin sensitivity and insulin release were calculated using insulin and glucose values from a standard oral glucose tolerance test (120 minutes, 75 g glucose). Pancreatic β-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices. Results: Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes had reduced insulin sensitivity compared with offspring from the background population (both P<.005).Wedid not find any significant difference in absolute measures of insulin release. However, the disposition index was significantly reduced in both the diabetesexposed groups (both P < .005). Conclusion: Reduced insulin sensitivity as well as impaired pancreatic β-cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy.

AB - Context: Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown. Objective: We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes. Design, Setting, and Participants: A cohort of 587 Caucasian offspring, without known diabetes, was followed up at the age of 18-27 years. We included 2 groups exposed to maternal diabetes in utero: offspring of women with gestational diabetes mellitus (n = 167) or type 1 diabetes (n =153). Two reference groups were included: offspring of women with risk factors for gestational diabetes mellitus but normoglycemia during pregnancy (n = 139) and offspring from the background population (n = 128). Main Outcome Measures: Indices of insulin sensitivity and insulin release were calculated using insulin and glucose values from a standard oral glucose tolerance test (120 minutes, 75 g glucose). Pancreatic β-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices. Results: Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes had reduced insulin sensitivity compared with offspring from the background population (both P<.005).Wedid not find any significant difference in absolute measures of insulin release. However, the disposition index was significantly reduced in both the diabetesexposed groups (both P < .005). Conclusion: Reduced insulin sensitivity as well as impaired pancreatic β-cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy.

U2 - 10.1210/jc.2013-1536

DO - 10.1210/jc.2013-1536

M3 - Journal article

SN - 0021-972X

VL - 98

SP - 3793

EP - 3801

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -