This study's objective was to determine whether there is familial clustering of insulin sensitivity (SI) or insulin-independent glucose uptake (SG), which would be evidence that they are genetically determined traits. Outpatients had a 3-h intravenous glucose tolerance test. Nondiabetic individuals (n = 183), ranging in age from 16 to 60 yr, were from 105 families that had 2 parents with non-insulin-dependent diabetes mellitus. Of these families, 62 contributed 1 offspring, 21 contributed 2, 13 contributed 3, 6 contributed 4, and 2 and 1 contributed 5 and 6, respectively. The minimal model of glucose disposal and the glucose and insulin values from the intravenous glucose tolerance tests were used to estimate SI and SG. The intraclass correlation coefficient was used to compare the within-family variability of SI and SG with the respective between-family distributions. The intraclass correlation coefficients were 0.26 (P = 0.008) for SI and 0.081 (P = 0.45) for SG. SI and SG were uncorrelated (r = −0.059, P = 0.42). The intraclass correlation of SI could not be explained by familial clustering of fasting insulin or ideal body weight. Finally, the 10 families with the lowest values of SI had a significantly higher within-sibship variability of SI than the other 33 families (P < 0.001, F test). SI but not SG showed familial clustering, which is consistent with a polygenic determinant of SI. In addition, a large within-family variability of SI in some families is compatible with a major gene effect with a dominant mode of inheritance. Thus, defects in genes affecting SI are plausible candidates for determinants of familial clustering of non-insulin-dependent diabetes mellitus.
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Original Articles|
July 01 1992
Familial Clustering of Insulin Sensitivity
Blaise C Martin;
Blaise C Martin
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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James H Warram;
James H Warram
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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Bernard Rosner;
Bernard Rosner
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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Stephen S Rich;
Stephen S Rich
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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J Stuart Soeldner;
J Stuart Soeldner
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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Andrzej S Krolewski
Andrzej S Krolewski
Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center
Boston
Departments of Epidemiology and Biostatistics, Harvard University School of Public Health
Boston, Massachusetts
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Address correspondence and reprint requests to James H. Warram, MD, ScD, Epidemiology and Genetics Section, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.
Diabetes 1992;41(7):850–854
Article history
Received:
October 30 1991
Revision Received:
March 03 1992
Accepted:
March 03 1992
PubMed:
1612199
Citation
Blaise C Martin, James H Warram, Bernard Rosner, Stephen S Rich, J Stuart Soeldner, Andrzej S Krolewski; Familial Clustering of Insulin Sensitivity. Diabetes 1 July 1992; 41 (7): 850–854. https://doi.org/10.2337/diab.41.7.850
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