TY - JOUR

T1 - Insulin resistance and impaired pancreatic beta-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

AU - Clausen, Tine D

PY - 2013/6/24

Y1 - 2013/6/24

N2 - Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate 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 two 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 GDM, but normo-glycemia 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 gram glucose). Pancreatic beta-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 <0.005). We did not find any significant difference in absolute measures of insulin release. However, the disposition index was significantly reduced in both the diabetes-exposed groups (both p <0.005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta 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 increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate 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 two 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 GDM, but normo-glycemia 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 gram glucose). Pancreatic beta-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 <0.005). We did not find any significant difference in absolute measures of insulin release. However, the disposition index was significantly reduced in both the diabetes-exposed groups (both p <0.005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta 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

C2 - 23796568

VL - 98

SP - 3793

EP - 3801

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -