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Total and High-Molecular-Weight Adiponectin and Resistin in Relation to the Risk for Type 2 Diabetes in Women

Christin Heidemann, DrPH, MSc; Qi Sun, MD, ScD; Rob M. van Dam, PhD; James B. Meigs, MD, MPH; Cuilin Zhang, MD, PhD; Shelley S. Tworoger, PhD; Christos S. Mantzoros, MD, DSc; and Frank B. Hu, MD, PhD
[+] Article and Author Information

From Harvard School of Public Health, Massachusetts General Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center, Boston, Massachusetts, and National Institutes of Health, Bethesda, Maryland.


Grant Support: By the National Institutes of Health and the Intramural Research Program of the National Institute of Child Health & Human Development (grants CA87969, DK58845 and DK58785). Dr. Heidemann was supported by fellowships of the German Academic Exchange Service and the Hans & Eugenia Juetting Foundation. Dr. Meigs received a Career Development Award from the American Diabetes. Dr. Mantzoros was supported by discretionary grants from the Tanita Corporation and Beth Israel Deaconess Medical Center.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement:Study protocol: Available at http://www.channing.harvard.edu/nhs. Statistical code and data set: Available subject to approval by the Nurses' Health Study committees by contacting Dr. Hu (e-mail, nhbfh@channing.harvard.edu).

Requests for Single Reprints: Frank Hu, MD, PhD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02215; e-mail, frank.hu@channing.harvard.edu.

Current Author Addresses: Dr. Heidemann: Department of Epidemiology & Health Reporting, Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany.

Drs. Sun, van Dam, and Hu: Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115.

Dr. Meigs: General Medicine Division, Massachusetts General Hospital, 50 Staniford Street, Boston, MA 02114.

Dr. Zhang: Division of Epidemiology, Statistics & Prevention Research, National Institute of Child Health & Human Development, National Institutes of Health, 6100 Executive Boulevard, Room 7B03, MSC 7510, 9000 Rockville Pike, Bethesda, MD 20892-7510.

Dr. Tworoger: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA 02115.

Dr. Mantzoros: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, ST 816, 330 Brookline Avenue, Boston, MA 02215.

Author Contributions: Conception and design: C. Heidemann, R.M. van Dam, J.B. Meigs, C.S. Mantzoros, F.B. Hu.

Analysis and interpretation of the data: C. Heidemann, Q. Sun, S.S. Tworoger, F.B. Hu.

Drafting of the article: C. Heidemann, C. Zhang, F.B. Hu.

Critical revision of the article for important intellectual content: Q. Sun, R.M. van Dam, J.B. Meigs, S.S. Tworoger, C.S. Mantzoros, F.B. Hu.

Final approval of the article: C. Heidemann, Q. Sun, R.M. van Dam, J.B. Meigs, C. Zhang, S.S. Tworoger, C.S. Mantzoros, F.B. Hu.

Provision of study materials or patients: S.S. Tworoger, C.S. Mantzoros.

Statistical expertise: C. Heidemann, Q. Sun, S.S. Tworoger.

Obtaining of funding: J.B. Meigs, F.B. Hu.

Administrative, technical, or logistic support: F.B. Hu.

Collection and assembly of data: S.S. Tworoger, C.S. Mantzoros, F.B. Hu.


Ann Intern Med. 2008;149(5):307-316. doi:10.7326/0003-4819-149-5-200809020-00005
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Women who developed type 2 diabetes during follow-up had higher mean baseline values for BMI and waist circumference, were less physically active, and were more likely to have a family history of diabetes than those who remained without diabetes (Table 1). In addition, they had statistically significantly lower baseline concentrations of total and high-molecular-weight adiponectin, a lower ratio of high-molecular-weight to total adiponectin, and higher concentrations of resistin than did control participants.

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Figure 2.
Multivariate-adjusted odds ratio (95% CI) of developing type 2 diabetes, by continuous adipokine concentrations.

Spline regression models examining the possible nonlinear relation between type 2 diabetes and total adiponectin level (A), high-molecular-weight (HMW) adiponectin level (B), ratio of HMW to total adiponectin (C), and resistin level. Odds ratios are adjusted for the same variables as in the multivariate model, including body mass index, of Table 2. (D) Solid lines represent odds ratios, and dotted lines represent 95% CIs. Women with extremely low or high adipokine concentrations (<1st or >99th percentile) were excluded from these analyses (n = 41 for total adiponectin, n = 42 for HMW adiponectin, n = 43 for ratio of HMW to total adiponectin, and n = 42 for resistin).

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Figure 1.
Multivariate-adjusted odds ratio (95% CI) of developing type 2 diabetes, by joint analysis of adipokines.

Top. Total adiponectin and resistin. Center. High-molecular-weight (HMW) adiponectin and resistin. Bottom. Total adiponectin and HMW adiponectin. Odds ratios are adjusted for the same variables as in the multivariate model, including body mass index, of Table 2. Tertiles were calculated among control participants: ≤12.55 ng/mL, 12.56–18.36 ng/mL, and >18.36 ng/mL for resistin; ≤14.67 μg/mL, 14.68–21.19 μg/mL, and >21.19 μg/mL for total adiponectin; and ≤4.97 μg/mL, 4.98–8.58 μg/mL, and >8.58 μg/mL for HMW adiponectin.

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