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Which Comes First in Non—Insulin-Dependent Diabetes Mellitus: Insulin Resistance or Beta-Cell Failure? Both Come First

Gordon C. Weir, MD
JAMA. 1995;273(23):1878-1879. doi:10.1001/jama.1995.03520470086039.
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The curious physician trying to understand the pathogenesis of non—insulin-dependent diabetes mellitus (NIDDM) has every reason to be mystified by the barrage of conflicting claims about the primacy of beta-cell failure and insulin resistance.

How can the argument go on for so long without a clear answer? Probably because we keep trying to view NIDDM as being simpler than it really is, and because we expect that the first identifiable lesion will lead us to the primary cause. Since there is general agreement that a combination of both environmental and genetic forces leads to NIDDM, it is probably counterproductive to think in terms of a primary cause or something that comes first. The major environmental problem seems to be our modern obesity-promoting lifestyle of limited physical activity and abundant food. Not only is obesity associated with insulin resistance, but sedentary behavior by itself leads to reduced insulin action on muscle.


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