Insulin resistance, a condition commonly associated with the development of type 2 diabetes, is likely a major cause of kidney disease, or nephropathy, in people with type 1 diabetes, according to study results published by University of Pittsburgh Graduate School of Public Health (GSPH) researchers in the September issue of Kidney International, a journal of the International Society of Nephrology. "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," said principal investigator Trevor Orchard, M.D., professor and acting chair, department of epidemiology, GSPH. "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."
The study analyzed data from the Pittsburgh Epidemiology of Diabetes Complication Study (PEDCS), a 10-year prospective investigation based on a cohort of adults with type 1, or childhood-onset, diabetes. Of the 658 subjects in PEDCS, 485 did not have nephropathy at baseline and were followed for the current study.
Fifty-six of the 485 subjects developed nephropathy during either the first five years of follow-up, or during years 6-10. Researchers found that in all cases, strong relationships existed between nephropathy and insulin resistance throughout follow up, unlike other risk factors such as blood pressure and blood fats, which only predicted nephropathy in the short term.
To measure insulin resistance, investigators used a novel calculation based on waist-to-hip ratio, hypertension status and long-term blood sugar 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," said Dr. Orchard.
Other risk factors in those that developed nephropathy included elevated LDL ("bad") cholesterol, triglycerides, white blood cell count (a marker of inflammation) and blood pressure.
"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," Dr. Orchard said. "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," Dr. Orchard continued, "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."
Investigators also examined genetic markers of risk and found that three markers linked to blood pressure and blood fats also predicted kidney disease.
Insulin resistance results when insulin fails to enable cells to admit glucose, necessary for cells energy production. Glucose then builds up in the blood, and additional insulin is required.
Up to 40 percent of people with type 1 diabetes develop kidney disease, in which the kidneys tiny blood vessels are damaged and unable to filter wastes and excess water from the blood. Untreated, nephropathy leads to end stage renal disease (ESRD), in which the kidneys entire filtration system closes down and the kidneys fail to function. A patient with ESRD requires dialysis or a kidney transplant to live.
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