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November 8, 1995

Insulin Resistance and Non—insulin-dependent Diabetes

Author Affiliations

Institute for Research in Extramural Medicine Amsterdam, the Netherlands

JAMA. 1995;274(18):1426. doi:10.1001/jama.1995.03530180020016

To the Editor.  —Dr Pimenta and colleagues1 state that they tested the hypothesis that insulin resistance precedes impaired beta-cell function in people genetically predisposed to develop non—insulin-dependent diabetes mellitus (NIDDM), but their study could not address their primary hypothesis.First, Pimenta et al took care to match the control subjects to the subjects with a first-degree NIDDM relative for body mass index. But rather than body mass index simply being the "environmental factor,"1 it seems plausible that there is some genetic constitution that, in the presence of excess energy intake or diminished physical activity, manifests itself phenotypically as hyperinsulinemia and obesity.2,3 Thus, matching for obesity implies also matching, at least partially, for the insulin-resistant genotype, which clearly undermines the validity of the comparison between index and control groups with respect to the degree of genetically determined insulin sensitivity. Second, from the data on the age of the study

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