Interview Date: June 2009
From the Special Topic of
According to our 2009 analysis of diabetes research,
the work of Dr. JoAnn E. Manson ranks at #8 by total cites,
based on 102 papers cited a total of 6,033 times between
January 1, 1999 and February 28, 2009. In
Essential Science IndicatorsSM from
Reuters, Dr. Manson's work can be found in the field of
Clinical Medicine, where she is in the top 1% of authors.
She has also been named a Highly Cited Researcher in this
Dr. Manson is the Chief of the Division of Preventive
Medicine at Brigham and Women's Hospital, as well as
Professor of Medicine and the Elizabeth Fay Brigham
Professor of Women's Health at Harvard Medical School.
In this interview, ScienceWatch.com
talks with Dr. Manson about her highly cited work
Would you tell us a bit about your
educational background and research experiences?
I’m a physician epidemiologist with training in Internal Medicine and
Endocrinology. I’ve had a long-term clinical interest in the care of
patients with diabetes, but it wasn’t until my Endocrinology
fellowship in the early 1980s that I became interested in doing research on
the prevention and risk prediction of diabetes. Even at that time, type 2
diabetes seemed like a largely preventable disease through lifestyle
modifications—and the evidence for that has only grown stronger over
"...the burgeoning epidemic of
obesity, especially among children and
adolescents, raises enormous concern for a
future pandemic of type 2 diabetes in the
United States and around the
As a result of this interest, I sought additional training in epidemiology
and biostatistics in order to be able to do this research. I received an
MPH in 1984 and a doctorate in epidemiology (DrPH) from the Harvard School
of Public Health in 1987. Since that time, I’ve been actively
involved in diabetes research, including the assessment of lifestyle
factors and biomarker predictors, in several large-scale prospective
cohorts including the Harvard Nurses’ Health Study, the Women’s
Health Study, and the Women’s Health Initiative. I’ve also been
involved in several randomized clinical trials that have addressed diabetes
How did you get involved in diabetes research, and
what is your primary focus within the field?
As mentioned above, my interest was really sparked during my fellowship
training in Endocrinology. I was seeing many patients with advanced
complications of diabetes, both microvascular and macrovascular. It seemed
important to be able to intervene earlier in the disease process, even
before the development of glucose intolerance and overt diabetes. Obesity
was clearly a dominant risk factor but I was interested in studying other
lifestyle factors as well, such as physical activity and dietary
interventions, and I wanted to understand how to identify high-risk
individuals who might benefit the most from lifestyle modifications and
Your most-cited paper in our analysis is the 2001
JAMA paper, "C-reactive protein, interleukin 6, and risk of
developing type 2 diabetes mellitus" (Pradhan AD, et al.,
286: 327-34, 18 July 2001), which has been cited close to 1,000
times. Would you walk our readers through this paper and why you think
it is so highly cited?
The inspiration for this paper was the emerging evidence that inflammation
plays a crucial role in the pathogenesis of both cardiovascular disease and
diabetes and may even serve as the link between these commonly co-existing
conditions. Since the publication of our paper in JAMA in 2001,
the evidence has just grown stronger that subclinical systemic inflammation
is a risk factor for insulin resistance, glucose intolerance, and
We assessed the predictive role of biomarkers of inflammation, including
hsCRP and IL-6, in predicting risk of future diabetes and found that the
prediagnostic plasma levels of these inflammatory markers were
substantially higher in the women who were later diagnosed with diabetes
than in the women who remained free of diabetes. For example, even after
adjusting for other known risk factors for diabetes, the relative risk of
type 2 diabetes was four-fold elevated for women in the highest vs. lowest
quartile of hsCRP and about two-fold elevated for the highest vs. lowest
quartile of IL-6.
We later published other articles confirming and extending these findings
in other cohorts. These relationships help to explain the strong link
between obesity and the risk of type 2 diabetes. Adipose tissue is now
recognized as a dynamic endocrine organ that has systemic effects. In
particular, abdominal and visceral fat secretes bioactive proteins
(adipocytokines), including IL-6, adiponectin, resistin, and retinol
binding protein, that influence insulin resistance as well as inflammation
(including modulating the synthesis of CRP downstream) and may affect the
risk of both diabetes and cardiovascular disease.
Many of your papers appear to deal with the
influence of lifestyle (smoking, diet, activity levels, etc.) on the
risk of developing diabetes. Would you talk a little bit about this
aspect of your work?
I believe that lifestyle factors are powerful determinants of most chronic
diseases, including type 2 diabetes and cardiovascular disease. We
published a paper from the Nurses’ Health Study in 2001 indicating
that at least 90% of cases of type 2 diabetes could be prevented by
lifestyle modifications, including exercising regularly, maintaining a
healthy weight, avoiding tobacco, and following a diet low in refined
carbohydrates and trans fats. We were fortunate to be one of the first
research groups to document the benefits of physical activity in preventing
type 2 diabetes, even after accounting for effects on adiposity.
"...type 2 diabetes seemed like a
largely preventable disease through lifestyle
modifications—and the evidence for that
has only grown stronger over
We’ve had a wonderful group of colleagues working on diabetes in our
research group, trying to learn as much as possible about diabetes
prevention in these large-scale cohorts. In particular, I’d like to
thank and acknowledge the enormous contributions of Drs. Frank Hu, Walter
Willett, James Meigs, and Aruna Pradhan. As Chief of the Division of
Preventive Medicine at our hospital, I believe strongly in the power of
prevention and am committed to disseminating knowledge and research in this
area. What we need now is a better understanding of how to best implement
and translate this knowledge, how to effect sustained behavior changes at
the individual and population levels. Some of this
translation/implementation can best be achieved through changes in the
built environment, food industry practices, and public policy initiatives.
One of your more recent papers is the February 2009
Diabetes Care paper, "Circulating levels of resistin and risk
of type 2 diabetes in men and women: Results from two prospective
cohorts" (Chen BH, et al., 32: 329-34, February 2009).
What exactly is resistin and what sort of role did this paper discover
it plays in diabetes?
Resistin is another one of the adipocytokines, or the bioactive proteins
produced in adipose tissue, which has links to both inflammation and
insulin resistance. It’s a polypeptide and its exact role in humans
has been controversial. In mice, resistin is secreted primarily by
adipocytes and has potent effects on insulin resistance and sensitivity. In
humans, resistin is produced by both adipocyte and mononuclear cells.
Although resistin levels tend to be higher among obese individuals in most
studies, the link with insulin resistance has been weaker than for some of
the other adipocytokines.
What are your hopes for progress in diabetes
research over the next decade?
My hope is for a cure for diabetes and the identification of powerful
prevention tools. Of course, the burgeoning epidemic of obesity, especially
among children and adolescents, raises enormous concern for a future
pandemic of type 2 diabetes in the United States and around the world. One
area that is of great interest to me is the potential role of vitamin D
supplementation in reducing the risks of diabetes and cardiovascular
disease. We plan a large-scale randomized trial of vitamin D in 20,000
Americans and hope to begin recruitment for the trial soon. Vitamin D may
even have a role in reducing health disparities, as vitamin D deficiency is
a particularly major problem among African Americans.
What would you like the "take-away lesson" about
your research to be?
That type 2 diabetes is a largely preventable disease and that lifestyle
factors really do matter. We are very excited about the potential role of
vitamin D and hope that this research will lead to new interventions to
curb the diabetes epidemic and to close the gap in health disparities by
race and ethnicity. And we hope that, with additional research on
biochemical and genomic biomarkers, it will be possible to improve risk
prediction of diabetes and target intervention to those who are most likely
JoAnn E. Manson, MD, DrPH
Division of Preventive Medicine
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA, USA
JoAnn Manson 's current
In Essential Science Indicators, with
1,266 cites: Anderson GL, et al.,
"Effects of conjugated, equine estrogen in postmenopausal
women with hysterectomy—the Women's Health Initiative
randomized controlled trial," JAMA-J. Am. Med.
Assn. 291(14): 1701-12, 14 April 2004.
In this special topic with 939 cites:
Pradhan AD, et al., "C-reactive protein,
interleukin 6, and risk of developing type 2 diabetes
mellitus," JAMA-J. Am. Med. Assn. 286(3): 327-34,
18 July 2001. 939 cites.
Essential Science Indicators from
JoAnn Manson is featured in
New Hot Paper comment in the field of Clinical Medicine
Fast Breaking Paper comment in the
field of Clinical Medicine (Nov. 2008).
KEYWORDS: DIABETES MELLITUS, TYPE 2 DIABETES, LIFESTYLE
MODIFICATIONS, BIOMARKER PREDICTORS, MICROVASCULAR COMPLICATIONS,
MACROVASCULAR COMPLICATIONS, OBESITY, GLUCOSE INTOLERANCE, C-REACTIVE
PROTEIN, INTERLEUKIN 6, ADIPOSE TISSUE, ADIPOCYTOKINES, RESISTIN,