Science + Technology

UCLA Researchers Identify Biological Markers That May Predict Diabetes in Still-Healthy People

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Inthe first large-scale, multiethnic study of its kind, UCLA researchers haveconfirmed the role played by three particular molecules known as cytokines incausing Type 2 diabetes and have identified these molecules as early biologicalmarkers that may be used to more accurately predict future diabetes in healthyindividuals.

Reportingin the Aug. 15 issue of the journal Archives of Internal Medicine, principalinvestigator Dr. Simin Liu, professor of epidemiology and medicine with a jointappointment at the UCLA School of Public Health and the David Geffen School ofMedicine at UCLA, and colleagues have identified three inflammatory cytokines,or messenger molecules — tumor necrosis factor-alpha (TNF-α), interleukin-6(IL-6) and high-sensitivity C-reactive protein (hs-CRP) — that may be one ofthe causes of Type 2 diabetes, which afflicts roughly 7 percent of the U.S.population.

Type2 diabetes is the most common form of diabetes and accounts for about 90 to 95percent of all diabetes cases. People with this condition produce insulin, buttheir bodies do not make enough of it or can't use it effectively.

Low-grade,chronic inflammation of the body, reflected by elevated levels of inflammatory cytokinesin the blood stream, may promote insulin resistance in the liver, muscles andthe vascular endothelium cells, the layer of thin, flat cells that lines theinterior surface of blood vessels. Inflammation can last for years beforeleading to Type 2 diabetes, hypertension or cardiovascular disease.

Ablood test that looks for high levels of inflammatory cytokines could serve asan accurate predictor of diabetes in still-healthy people, years ahead oftraditional risk-factor indicators such as obesity or insulin resistance. Thefinding also has implications for cancer research, according to Liu, sincepeople with diabetes are at greater risk of developing breast and coloncancers.

"Thisis a final confirmation of earlier studies about the underlying biology behindType 2 diabetes," said Liu, who is also a member of UCLA's Jonsson CancerCenter.

Butthose previous studies, Liu said, were either very small or were animal studies.The UCLA study was more extensive in scale and involved human study volunteers.

"Ourstudy identified 1,600 new cases of diabetes and measured the blood markers beforethey developed the disease," he said.

Researcherstook advantage of the Women's Health Initiative Observational Study (WHIO), anongoing, long-term study examining the association between behavior,socioeconomic status, diet and other factors and their effect on women'shealth. Liu and his colleagues took baseline-level measurements of inflammatorycytokines in apparently healthy women between the ages of 50 and 79 who had nosigns of diabetes, then tracked their health for the next six years.

TheWHIO involved some 82,000 postmenopausal women of various ethnicities,including whites, blacks, Hispanics, and Asians and Pacific Islanders. At thetime of follow-up, Liu and his colleagues compared 1,584 women, now diagnosedwith Type 2 diabetes, and matched them by age, ethnicity and other factors to2,198 other women in the study who remained free of the disease.

Whileall three cytokines were found to be significantly related to an increased riskof clinical diabetes, one — hs-CRP — appeared to be a more consistent predictorof increased risk in all four ethnic groups. These associations wereindependent of the traditional risk factors such as obesity and elevated levelsof glucose and insulin previously reported by Liu and his colleagues in thesame multiethnic sample.

"Thepro-inflammatory state is often linked to obesity, which can lead to insulinresistance," Liu said. "So identifying these markers by a simple blood test wellbefore a disease begins not only can help improve mechanistic understanding ofthe disease but also offer alternatives to lifestyle — hitting an optimalbalance of nutrition, for example, and engaging in more exercise — relativelysimple things that can prevent disease."

Thestudy involved 40 clinical centers nationwide and 12 authors from severalinstitutions, including Liu's former affiliation, Brigham and Women's Hospitaland Harvard Medical School.Funding support came from the National Institutes of Health's NationalInstitute of Diabetes and Digestive and Kidney Diseases.

The UCLA School of PublicHealth isdedicated to enhancing the public's health by conducting innovative research,training future leaders and health professionals, translating research intopolicy and practice, and serving local, national and international communities.For more information, see www.ph.ucla.edu.

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