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Comparison of Plasma Insulin Levels after a Mixed-Meal Challenge in Children with and without Intrauterine Exposure to Diabetes

Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch (A.D.S., C.B.C., J.K., J.C.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016; BHF Glasgow Cardiovascular Research Centre (R.S.L.), University of Glasgow, Glasgow G12 8TA, United Kingdom; and Sanofi-Aventis Pharmaceuticals (P.A.T.), 75601 Paris Cedex 12, France

Address all correspondence and requests for reprints to: Joy C. Bunt, M.D., Ph.D., NIH/NIDDK/Obesity and Diabetes Clinical Research Section, 4212 North 16th Street, Room 541, Phoenix, Arizona 85016. E-mail: JBunt{at}mail.nih.gov.

Background: The diabetic intrauterine environment is a known risk factor for the development of diabetes in the offspring.

Objective: We compared anthropometric and metabolic characteristics of 41 nondiabetic children whose mothers developed diabetes either before (ODM, n = 19, 9.3 ± 1.1 yr) or after (OPDM, n = 22, 9.5 ± 1.3 yr) the pregnancy of interest. Maternal diabetes status was established from OGTT results before, during, and after the pregnancy of interest.

Design: After consuming a standardized diet for 2 d, a mixed-meal breakfast was given after an overnight fast. Fasting concentrations and responses of plasma glucose and insulin were evaluated using linear regression analyses to assess potential independent determinants of plasma insulin concentration at each time point.

Results: After adjustment for age and sex, there were no differences between ODM and OPDM children for maternal age at diagnosis, height, weight, body mass index, BMI z score, or percent body fat (dual energy x-ray absorptiometry). After adjusting for age, sex, percent body fat, and the corresponding glucose level at each time point, ODM had a lower plasma insulin level at the 15-min time point during the meal test than OPDM (P = 0.01).

Conclusion: A lower initial insulin response to a standard mixed-meal challenge can be detected in nondiabetic ODM compared with OPDM children as early as 9 yr of age. This response may be another indicator for an attenuated early insulin response and explain the increased risk for diabetes in these children.