Diet-induced Insulin Resistance Precedes Other Aspects of the Metabolic Syndrome

This study was designed to examine the effects of a high-fat refined-sugar (HFS) or a low-fat complex-carbohydrate (LFCC) diet on insulin-stimulated skeletal muscle glucose transport, plasma insulin, blood pressure, plasma triglycerides, plasma glycerol, body weight, and body fat in female Fischer rats. Insulin-stimulated glucose transport was significantly reduced in the HFS group at 2 wk, 2 mo, and 2 yr, whereas serum insulin was significantly elevated at all time points. Blood pressure was not significantly elevated in the HFS group until 12 mo, and all HFS animals were hypertensive by 18 mo. Glycerol, triglycerides, and abdominal fat cell size were not significantly different at 2 wk but were significantly elevated in the HFS rats at 2 and 6 mo. Body weight was similar in both groups until 20 wk on the diet, when the HFS rats started to gain more weight. These results demonstrate that insulin resistance and hyperinsulinemia occur before the other manifestations of the metabolic syndrome and that diet, not obesity, is the underlying cause.