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A Systematic Review and Meta-analysis

Shanshan Li, MD, MSc; Hyun Joon Shin, MD, MPH, MS; Eric L. Ding, ScD; Rob M. van Dam, PhD

JAMA. 2009;302(2):179-188.

Context  The association of obesity with development of type 2 diabetes may be partly mediated by altered secretion of adipokines by adipose tissue. Greater adiposity down-regulates secretion of adiponectin, an adipokine with anti-inflammatory and insulin-sensitizing properties. The strength and consistency of the relation between plasma adiponectin and risk of type 2 diabetes is unclear.

Objective  To systematically review prospective studies of the association of plasma adiponectin levels and risk of type 2 diabetes.

Data Sources  A systematic search of the MEDLINE, EMBASE, and Science Citation Index Expanded databases using adiponectin and diabetes and various synonyms and reference lists of retrieved articles up to April 10, 2009.

Study Selection  We included prospective studies with plasma adiponectin levels as the exposure and incidence of type 2 diabetes as the outcome variable.

Data Extraction  Two reviewers independently extracted data and assessed study quality. Generalized least-squares trend estimation was used to assess dose-response relationships. Pooled relative risks and 95% confidence intervals were calculated using random-effects models to incorporate between-study variation.

Results  Thirteen prospective studies with a total of 14 598 participants and 2623 incident cases of type 2 diabetes were included in the meta-analysis. Higher adiponectin levels were monotonically associated with a lower risk of type 2 diabetes. The relative risk of type 2 diabetes was 0.72 (95% confidence interval, 0.67-0.78) per 1–log µg/mL increment in adiponectin levels. This inverse association was consistently observed in whites, East Asians, Asian Indians, African Americans, and Native Americans and did not differ by adiponectin assay, method of diabetes ascertainment, duration of follow-up, or proportion of women. The estimated absolute risk difference (cases per 1000 person-years) per 1–log µg/mL increment in adiponectin levels was 3.9 for elderly Americans and 30.8 for Americans with impaired glucose tolerance.

Conclusion  Higher adiponectin levels are associated with a lower risk of type 2 diabetes across diverse populations, consistent with a dose-response relationship.

Author Affiliations: Departments of Epidemiology (Drs Li and van Dam) and Nutrition (Drs Shin, Ding, and van Dam), Harvard School of Public Health, Boston, Massachusetts; Framingham Union Hospital Metro West Medical Center, Framingham, Massachusetts (Dr Shin); and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (Dr van Dam).

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