To evaluate the pathogenetic mechanisms responsible for development of diabetes in the genetically inherited disease maturity-onset diabetes of the young (MODY), we have investigated a pair of identical twins (19 yr old) from a MODY family. One twin had nondiabetic fasting plasma glucose values but impaired glucose tolerance (IGT), whereas the other suffered from frank diabetes (fasting plasma glucose 12.5 mM). Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. Therefore, our aim was to investigate insulin secretion and insulin action in the twins to find these differences and similarities. We found that fasting plasma insulin and C-peptide values were slightly increased in the twins, whereas the responses of insulin and C-peptide to oral glucose tolerance tests (OGTT) and meals were similar in the twins and within normal range. The insulin responses to OGTT were, however, lower than expected from the glucose values, indicating a β-cell defect. Despite elevated plasma insulin levels, basal hepatic glucose output (HGO) was normal in the IGT twin but increased by 75% in the diabetic twin. The maximally inhibitory effect of insulin on HGO, when estimated at euglycemia, was normal in the IGT twin but reduced by 60% in the diabetic twin. Furthermore, the maximal insulin-mediated glucose uptake in peripheral tissues was reduced by 40% in the diabetic twin. lular defect that is responsible for the insulin resistance appears to be a reduced cellular insulin binding and, in surplus, a postreceptor defect in glucose metabolism in the diabetic twin. These data indicate that a cellular defect in insulin action at the postreceptor level may be responsible for the progression from a state of IGT to frank diabetes, whereas the genetic defect in MODY may be localized to the β-cells. A primary insulin-receptor defect, however, cannot be excluded.
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Original Articles|
June 01 1988
Insulin Action and Insulin Secretion in Identical Twins With MODY: Evidence for Defects in Both Insulin Action and Secretion
Henning Beck-Nielsen;
Henning Beck-Nielsen
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Ole Hother Nielsen;
Ole Hother Nielsen
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Oluf Pedersen;
Oluf Pedersen
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Jens Bak;
Jens Bak
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Ole Faber;
Ole Faber
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Ole Schmitz
Ole Schmitz
Medical Department III, Aarhus Amtssygehus, Aarhus, Medical Department, Horsholm Sygehus and Hagedom Research Laboratorium
Copenhagen
Medical Department C, Aarhus Kommunehospital
Aarhus, Denmark
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Address correspondence and reprint requests to Henning Beck-Nielsen, MD, Hvidore Hospital, Emiliekildevej 1, DK-2930 Klampenborg, Denmark.
Diabetes 1988;37(6):730–735
Article history
Received:
September 15 1987
Revision Received:
November 18 1987
Accepted:
November 18 1987
Citation
Henning Beck-Nielsen, Ole Hother Nielsen, Oluf Pedersen, Jens Bak, Ole Faber, Ole Schmitz; Insulin Action and Insulin Secretion in Identical Twins With MODY: Evidence for Defects in Both Insulin Action and Secretion. Diabetes 1 June 1988; 37 (6): 730–735. https://doi.org/10.2337/diab.37.6.730
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