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[IP] Insulin Resistance Best Predictor of Diabetic Nephropathy

Medscape Medical News
Insulin Resistance Best Predictor of Diabetic Nephropathy

Laurie Barclay, MD

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
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