October 18, 2008 (Newswise) - For men, but not women, higher levels of the protein albumin in the urine are a strong risk factor for diabetes, reports a study in the November issue of the Journal of Hypertension. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.Men's risk of diabetes rises steadily along with urinary albumin excretion (UAE) level, independent of other diabetes risk factors, the researchers conclude. The lead author was Dr. Jean-Michel Halimi of François Rabelais University, Tours, France.

The study included 3,851 men and women from an ongoing study of risk factors for insulin resistance syndrome, a pre-diabetic state. The subjects, aged 30 to 64 years, underwent measurement of UAE. Increased UAE levels, or microalbuminuria, are a key early sign of kidney disease-often caused by diabetes. Microalbuminuria is defined as a UAE between 20 and 200 mg/L (milligrams per litre).

The subjects were also evaluated for the five risk factors that make up the metabolic syndrome: elevated waist circumference, high triglyceride level, low HDL ("good") cholesterol level, high blood pressure, and high glucose level. People with any three of these risk factors are considered to have metabolic syndrome, which is linked to an increased risk of cardiovascular disease and diabetes.

As Albumin Excretion Increases, So Does Men's Diabetes Risk
During nine years' follow-up, diabetes developed in 171 subjects (132 men and 39 women). For men, the risk of diabetes increased steadily along with UAE. Diabetes risk was approximately doubled for men with UAE levels meeting the definition of microalbuminuria. For men with UAE levels over the 200 mg/L cut-off point for "macroalbuminuria"-indicating established kidney disease-the risk of diabetes was more than quadrupled.

For women, UAE was not a significant risk factor for diabetes.

The link between UAE and diabetes was even stronger after exclusion of men who had abnormal glucose levels at the beginning of the study. It also remained significant after adjustment for a wide range of other risk factors, including body weight, physical activity, smoking, and waist circumference; and for the development of insulin resistance during the first three years of follow-up.

Type 2 diabetes usually causes no symptoms in its early stages, and can go undiagnosed for years before serious complications occur. New approaches are needed to identifying patients at increased risk of diabetes, who may benefit from preventive measures. Patients with insulin resistance or metabolic syndrome are more likely to have elevated UAE. However, the relationship between UAE and the development of diabetes-with or without metabolic syndrome-has been unclear.

"UAE is a potent independent predictive marker of diabetes mellitus in men but not in women," Dr. Halimi and colleagues write. For men, diabetes risk rises steadily along with UAE level, independent of several major diabetes risk factors. The reasons for this relationship are unknown, although many interrelated factors may be involved.

"In conclusion, our findings indicate that albuminuria may improve the identification of men at risk of diabetes mellitus, beyond the presence of metabolic syndrome," Dr. Halimi and colleagues conclude. Measuring UAE may provide a simple new test to assess diabetes risk. The next step is studies to find out whether treatments to lower urine albumin can help to reduce the risk of diabetes.

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Journal of Hypertension (www.jhypertension.com) consistently attracts the most important and highly innovative papers from the current research; our commitment to rapid publication ensures that these are published in the fastest time possible. In addition to primary papers from world-renowned experts, the Journal contains authoritative reviews that summarize and evaluate the most significant recent developments. Also included are special reports, original short papers containing innovative and time-sensitive information. Journal of Hypertension is official journal of the International Society of Hypertension and the European Society of Hypertension.

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October 17, 2008 (Press Release) - A single molecule in the intestinal wall, activated by the waste products from gut bacteria, plays a large role in controlling whether the host animals are lean or fatty, a research team, including scientists from UT Southwestern Medical Center, has found in a mouse study.When activated, the molecule slows the movement of food through the intestine, allowing the animal to absorb more nutrients and thus gain weight. Without this signal, the animals weigh less.

The study shows that the host can use bacterial byproducts not only as a source of nutrients, but also as chemical signals to regulate body functions. It also points the way to a potential method of controlling weight, the researchers said.

"It's quite possible that blocking this receptor molecule in the intestine might fight a certain kind of obesity by blocking absorption of energy from the gut," said Dr. Masashi Yanagisawa, professor of molecular genetics at UT Southwestern and a senior co-author of the study, which appears online in Proceedings of the National Academy of Sciences.

Humans, like other animals, have a large and varied population of beneficial bacteria that live in the intestines. The bacteria break up large molecules that the host cannot digest. The host in turn absorbs many of the resulting small molecules for energy and nutrients.

"The number of bacteria in our gut far exceeds the total number of cells in our bodies," said Dr. Yanagisawa.

"It's truly a mutually beneficial relationship. We provide the bacteria with food, and in return they supply energy and nutrients," he explained.

Using mice, the researchers focused on two species of bacteria that break up dietary fibers from food into small molecules called short-chain fatty acids. Dr. Yanagisawa's team previously had found that short-chain fatty acids bind to and activate a receptor molecule in the gut wall called Gpr41, although little was known about the physiological outcome of Gpr41 activation.

The researchers disrupted communication between the bacteria and the hosts in two ways: raising normal mice under germ-free conditions so they lacked the bacteria, and genetically engineering other mice to lack Gpr41 so they were unable to respond to the bacteria.

In both cases, the mice weighed less and had a leaner build than their normal counterparts even though they all ate the same amount.

The researchers also found that in mice without Gpr41, the intestines passed food more quickly. They hypothesized that one action of Gpr41 is to slow down the motion that propels food forward, so that more nutrients can be absorbed. Thus, if the receptor cannot be activated, food is expelled more quickly, and the animal gets less energy from it.

Because mice totally lacking Gpr41 were still healthy and had intestinal function, the receptor may be a likely target for drugs that can slow, but not stop, energy intake, Dr. Yanagisawa said.

Other UT Southwestern researchers involved in the study were co-lead author and graduate student Abdullah Shaito; Dr. Toshiyuki Motoike, assistant professor of molecular genetics; research specialist Clay Willams; and Dr. Robert Hammer, professor of biochemistry. Researchers from Washington University School of Medicine, the Japan Science and Technology Agency and Howard Hughes Medical Institute in Chevy Chase, Md., also participated.

The study was funded by the National Science Foundation, the National Institutes of Health, the W.M. Keck Foundation, the Japan Science and Technology Agency and HHMI.