University Times

Kidney disease in people with Type 1 diabetes related to how well insulin works

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 Pitt 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, professor and acting chairperson of GSPH's epidemiology department. "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," Orchard said.

Other risk factors in those that developed nephropathy included elevated LDL ("bad") cholesterol, triglycerides, white blood cell count 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," 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," he continued, "it may explain the longstanding observation that in type 1 diabetes, kidney disease predicts heart disease."

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. Untreated, nephropathy leads to end stage renal disease, in which the kidneys' entire filtration system closes down and the kidneys fail to function.

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Professor gets NARSAD funding

German Barrionuevo, a Pitt professor of neuroscience and psychiatry, has received an Independent Investigator Award of $100,000 from the National Alliance for Research on Schizophrenia and Depression to study the dynamics of synaptic transmission and calcium transients in the in vitro monkey prefrontal cortex during natural patterns of stimulation.

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Pitt physicist creates way to create, move excitons over long distances

A Pitt physicist has found a new way to create and move small bits of optical energy called excitons over relatively long distances, a development that could be an important step in creating semiconductors in which excitons are shuttled and controlled to form "excitonic circuits."

David Snoke, associate professor of physics and astronomy, and his research team used lasers and a type of nanoscale structure called a quantum well to direct excitons to travel several millimeters. The researchers reported their work in the Aug. 15 edition of Nature.

In conventional semiconductors, electrons or their absence (so-called holes) move in circuits to perform functions such as computation and storage of information. In his research, Snoke used laser light to separate an electron from an atom. The "excited" electron plus the hole remaining on the atom compose an exciton, which moves like an energy particle and could potentially carry information.

In most cases, excitons exist for only a few nanoseconds (billionths of a second) and travel only a few microns (millionths of a meter) before the electron and hole reunite and re-emit the light.

By using the quantum wells — fabricated from gallium arsenide and indium gallium arsenide by scientists at Lucent Technologies' Bell Laboratories — Snoke and his team were able to extend the amount of time the electron and hole were apart and, consequently, the distance the exciton traveled.

"A millimeter may not seem like a long distance, but with circuits now being designed on micron scales — that is, thousandths of a millimeter — a distance of a millimeter is tremendously long compared to typical circuit dimensions," said Snoke. "Therefore, the exciton particles can easily travel over the distances needed for computer circuits.

"These results open up the possibility of using excitonic signals to carry information just as an electronic charge is currently used," said Snoke. "Today's computer technology is based on sending electronic charges from place to place to carry information. Our new experiments may open up the possibility of 'excitonics' as a new way of sending information."

According to Snoke, previous experiments at Pitt have already shown that it is possible to apply a force on excitons to move them from one place to another using either pressure or an electric field. Given Snoke's recent results, the possibility now exists for excitonic circuits in which excitons are routed from one place to another.

The Pitt research project is supported by the National Science Foundation (NSF) and the U.S. Department of Energy.