Family history of diabetes impacts on interactions between minimal model estimates of insulin sensitivity and glucose effectiveness.
OBJECTIVE
Insulin resistance and glucose effectiveness (S(G)) are major determinants of glucose tolerance and independently predict the development of type 2 diabetes in individuals with a family history of disease. We examined the inter-relationship between insulin sensitivity (S(I)) and S(G) in offspring of two parents with type 2 diabetes and in individuals with no family history of diabetes.


METHODS
Fifty non-diabetic individuals, including 26 offspring of two type 2 diabetic parents (family history, FH+) and 24 with no family history of diabetes (FH-) similar in gender, age, ethnicity and body mass index (BMI) were studied. Each subject underwent a 100-g oral glucose tolerance test (OGTT) and insulin modified frequently sampled intravenous glucose tolerance, analysed using the Bergman's minimal model (MINMOD).


RESULTS
Thirteen subjects of the FH+ group and nine of the FH- group had impaired glucose tolerance (IGT). S(I) and S(G) were independent variables in the FH+ group, while they correlated highly with each other in the FH- group (r = 0.69, p = 0.0002). The relationship between S(I) and S(G) persisted when analysing the IGT and normal glucose tolerance subgroups separately, demonstrating that these associations were not because of differences in glycaemia. Consistently, S(G) strongly correlated with additional measures of insulin resistance only in the FH- group, including fasting insulin (r = 0.56, p = 0.004), homeostasis model assessment of insulin resistance (r = 0.57 p = 0.003) and BMI (r = 0.66, p = 0.0004).


CONCLUSIONS
These results demonstrate that familial factors impart important physiological differences in the inter-relationship between insulin-dependent and insulin-independent glucose disposal, which may be important in modulating risk for development of disease.
Department of Clinical Research, Joslin Diabetes Center, Boston, MA 02215, USA.
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Lopez
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Bouché
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Tatro
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Goldfine
D000328:Adult; D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004812:Epidemiologic Methods; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose