Normoglycemic Diabetic Nephropathy: The Role of Insulin Resistance

The pathophysiology of diabetic nephropathy (DN) is complex and incompletely understood. Whereas hyperglycemia is clearly important, the role of insulin resistance (IR) is increasingly recognized. We present the case of a normotensive non-smoking obese woman with nephrotic syndrome who was found to have DN by biopsy. All measures of glucose metabolism, including fasting glucose, glycosylated hemoglobin, and oral glucose tolerance testing, were repeatedly normal with little exception. IR was documented, however, based on the presence of the metabolic syndrome and an elevated homeostasis model assessment of IR. We posit that this IR is central to the pathogenesis of our patient's lesion, and this may explain other cases of DN with normoglycemia. The literature supporting this concept is discussed.