Insulin Resistance Best Predictor of Diabetic Nephropathy

Laurie Barclay, MD

August 30, 2002

Sept. 3, 2002 — Insulin resistance is most predictive of diabetic nephropathy in the long-term, according to the results of a 10-year prospective study published in the September issue of Kidney International. Blood pressure and lipids were only predictive of nephropathy in the short-term. Type 1 diabetics without insulin resistance therefore appear to have a low risk of kidney disease, and the secret to preventing nephropathy appears to be through lifestyle changes that can help prevent insulin resistance.

"Kidney disease is a major lethal complication for people with diabetes, particularly those with type 1 diabetes, and until now there has been no clear explanation for its cause beyond blood sugar itself," lead author Trevor Orchard, MBBCh, MMedSci, from the University of Pittsburgh Graduate School of Public Health in Pennsylvania, says in a news release. "We now suspect that reducing or preventing insulin resistance, possibly through exercise, weight loss and drugs, may help people with type 1 diabetes avoid nephropathy."

Of 658 adults with type 1 diabetes enrolled in the Pittsburgh Epidemiology of Diabetes Complication Study, 485 did not have nephropathy at baseline. To measure insulin resistance, the investigators used a novel calculation based on waist-to-hip ratio, hypertension status, and long-term blood glucose levels.

"Although our measure of insulin resistance is an estimate based on easier-to-measure factors, it is strongly correlated with the gold standard — euglycemic clamp studies — and clearly stands out as the leading predictor of kidney disease in this study," Orchard says.

Over 10 years of follow-up, 56 of the 485 subjects developed nephropathy. Risk of developing nephropathy was strongly linked to insulin resistance throughout follow-up (P<.0001), but blood pressure, blood lipid profile, elevated low-density lipoprotein cholesterol, triglycerides, and white blood cell count only predicted nephropathy during the first five years of follow-up. Three genetic markers linked to blood pressure and blood lipids also increased risk of nephropathy, with odds ratios for each marker ranging from 2.9 to 7.1.

"The good news is that not all people with type 1 diabetes are insulin resistant, and for them the risk of kidney disease now appears to be low," Orchard says. "Even for someone with type 1 diabetes who is genetically predisposed to insulin resistance, the secret to avoiding nephropathy may well be to prevent insulin resistance through lifestyle changes such as proper diet, exercise, smoking cessation and perhaps medication. Another intriguing finding from this study is that since insulin resistance also predicts heart disease, it may explain the longstanding observation that in type 1 diabetes, kidney disease predicts heart disease. In other words, insulin resistance may be the 'common ground' for both complications."

Kidney Int. 2002;62(3):963-970

Reviewed by Charlotte E. Grayson, MD