A Prospective Study of Inflammatory Cytokines and Diabetes Mellitus in a Multiethnic Cohort of Postmenopausal Women
- From: MarilynMann <mannm@xxxxxxxxxxx>
- Date: Sun, 19 Aug 2007 13:55:37 -0700
A Prospective Study of Inflammatory Cytokines and Diabetes Mellitus in
a Multiethnic Cohort of Postmenopausal Women
Simin Liu, MD, ScD; Lesley Tinker, PhD, RD; Yiqing Song, MD, ScD;
Nader Rifai, PhD; Denise E. Bonds, MD; Nancy R. Cook, ScD; Gerardo
Heiss, MD; Barbara V. Howard, PhD; Gokhan S. Hotamisligil, MD, PhD;
Frank B. Hu, MD, PhD; Lewis H. Kuller, MD, DrPH; JoAnn E. Manson, MD,
DrPH
Arch Intern Med. 2007;167:1676-1685.
Background Inflammatory cytokines, including tumor necrosis factor ,
IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP),
have been related to both insulin resistance and type 2 diabetes
mellitus. However, prospective studies that comprehensively assess
their roles in the development of type 2 diabetes are few, especially
in minority populations.
Methods Among 82 069 postmenopausal women aged 50 to 79 years without
cardiovascular disease or diabetes mellitus who participated in the
Women's Health Initiative Observational Study, we prospectively
examined the relationships of plasma levels of tumor necrosis factor
receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-
up period of 5.9 years, 1584 women who had clinical diabetes were
matched by age, ethnicity, clinical center, time of blood draw, and
duration of follow-up to 2198 study participants who were free of the
disease.
Results After adjustment for matching factors and known diabetes risk
factors, all 3 markers were significantly associated with increased
diabetes risk; the estimated relative risks comparing the highest with
the lowest quartiles were 1.47 (95% confidence interval [CI],
1.10-1.97) for tumor necrosis factor receptor 2, 3.08 (95% CI,
2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for
trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and
hsCRP remained significant in each ethnic group. While no
statistically significant interactions were observed between ethnicity
and these biomarkers on diabetes risk, there were consistent trends
for the associations of hsCRP and IL-6 with increased diabetes risk in
all ethnic groups.
Conclusion These prospective data showed that elevated levels of IL-6
and hsCRP were consistently and significantly associated with an
increased risk of clinical diabetes in postmenopausal women.
Author Affiliations: Departments of Epidemiology (Dr Liu) and Medicine
(Dr Liu), University of California, Los Angeles; Division of
Preventive Medicine (Drs Liu, Song, and Manson) and Channing
Laboratory (Drs Hu and Manson), Department of Medicine, Brigham and
Women's Hospital, and Department of Laboratory Medicine, Children's
Hospital (Dr Rifai), Harvard Medical School, and Departments of
Epidemiology (Drs Liu, Cook, Hu, and Manson) and Genetics and Complex
Diseases (Dr Hotamisligil), Harvard School of Public Health, Boston,
Massachusetts; Public Health Division, Fred Hutchinson Cancer Research
Center, Seattle, Washington (Dr Tinker); Departments of Public Health
Sciences (Dr Bonds) and Medicine (Dr Bonds), University of Virginia,
Charlottesville; Department of Epidemiology, School of Public Health,
University of North Carolina at Chapel Hill (Dr Heiss); MedStar
Research Institute, Washington, DC (Dr Howard); and Department of
Epidemiology, University of Pittsburgh, School of Public Health,
Pittsburgh, Pennsylvania (Dr Kuller).
* * *
Markers That May Predict Diabetes In Still-healthy People Identified
Science Daily - In the first large scale, multiethnic study of its
kind, researchers at UCLA have confirmed the role played by three
particular molecules known as cytokines as a cause of Type 2 diabetes,
and further, have identified these molecules as early biological
markers that may be used to more accurately predict future incidences
of diabetes among apparently healthy individuals.
Reporting in the August 15 issue of the journal Archives of Internal
Medicine, Simin Liu, professor of epidemiology and medicine with a
joint appointment in the School of Public Health and the David Geffen
School of Medicine at UCLA, and colleagues have identified three
inflammatory cytokines (cytokines are messenger molecules) tumor
necrosis factor-alpha (TNF-á); interleukin-6 (IL-6); and high-
sensitivity C-reactive protein (hs-CRP) that may be one of the causes
of type 2 diabetes which afflicts roughly seven percent of the U.S.
population.
Type 2 diabetes is the most common form of diabetes; about 90 to 95
percent of people who have diabetes have type 2. People with this
condition produce insulin, but either their bodies don't make enough
of it, or can't effectively use it.
Low-grade chronic inflammation of the body, which is reflected by
elevated levels of inflammatory cytokines in the blood stream, may
promote insulin resistance in the liver, muscles, and the vascular
endothelium cells, the layer of thin, flat cells that lines the
interior surface of blood vessels. Such inflammation can last for
years before leading to type 2 diabetes, cardiovascular disease, or
hypertension.
A blood test that looks for high levels of inflammatory cytokines
could serve as an accurate predictor of diabetes in still-healthy
people, years ahead of the traditional risk factors of obesity or
insulin resistance. The finding also has implication for cancer
research as well, said Liu, since people with diabetes are at greater
risk of developing breast and colon cancers.
"This is a final confirmation of earlier studies about the underlying
biology behind type 2 diabetes," said Liu, who is also a member of the
UCLA Jonsson Comprehensive Cancer Center. But those studies, he said,
were either very small or animal studies. By comparison, he said,
their study was more extensive in scale and involved human study
volunteers. "Our study identified 1,600 new cases of diabetes and
measured the blood markers before they developed the disease."
The researchers took advantage of the Women's Health Initiative
Observational Study (WHIOS), an ongoing, long term study that was
designed to examine the association between behavior, socioeconomic
status, diet, and other factors and the effect on a woman's health.
Liu and colleagues took baseline level measurements of inflammatory
cytokines in apparently healthy women without any signs of diabetes
who were between the ages of 50 and 79 years-old, then tracked their
health for the next six years.
The WHIOS study involved some 82,000 postmenopausal women who cut
across multiple ethnicities, including whites, blacks, Hispanics, and
Asian/Pacific Islanders. At the time of follow-up, Liu and colleagues
compared 1,584 women, now diagnosed with type 2 diabetes, and matched
them by age, ethnicity and other factors to 2,198 other women in the
study who remained free of the disease.
While all three cytokines were found to be significantly related to an
increased risk of clinical diabetes, hs-CRP appeared to be a more
consistent predictor of increased risk in all four ethnic groups.
These associations were independent of traditional risk factors such
as obesity or elevated levels of glucose and insulin, previously
reported by Liu and colleagues in the same multiethnic sample.
"The pro-inflammatory state is often linked to obesity," said Liu,
"which can lead to insulin resistance. So, identifying these markers
by a simple blood test well before a disease begins not only can help
improve mechanistic understanding of the disease, but also offer
alternatives to lifestyle--hitting an optimal balance of nutrition,
for example, and engaging in more exercise - relatively simple things
that can prevent disease."
The study involved 40 clinical centers nationwide, and 12 authors from
several institutions including Liu's former affiliation, Brigham and
Women's Hospital and Harvard Medical School. Liu was principal
investigator of the study. Funding support came from the National
Institute of Diabetes and Digestive and Kidney Diseases from the
National Institutes of Health.
* * *
This seems like an important study. I know I had my hs-CRP checked
once, but I'll have to ask my doctor about the others.
Marilyn
.
- Prev by Date: Re: See who's editing Wikipedia
- Next by Date: Re: Relation of Body Mass Index to Outcome in Patients With Known or Suspected Coronary Artery Disease
- Previous by thread: Re: OT -- hedge fund speak
- Next by thread: Re: Relation of Body Mass Index to Outcome in Patients With Known or Suspected Coronary Artery Disease
- Index(es):
Relevant Pages
|
