Adiponectin Trajectories Before Type 2 Diabetes Diagnosis: Whitehall II study

OBJECTIVE: The role of adiponectin in the natural history of diabetes is not well characterized. We set out to characterize prediagnosis trajectories of adiponectin in individuals who develop type 2 diabetes. RESEARCH DESIGN AND METHODS: In a case-cohort study (335 incident diabetes case and 2,474 noncase subjects) nested in the Whitehall II study, serum adiponectin was measured up to three times per participant (1991–1993, 1997–1999, and 2003–2004). Multilevel models adjusted for age and ethnicity were fitted to assess 13-year trajectories of log-transformed adiponectin preceding diabetes diagnosis or a randomly selected time point during follow-up (year(0)) based on 755/5,095 (case/noncase) person-examinations. RESULTS: Adiponectin levels were lower in diabetes case than in noncase subjects (median 7,141 [interquartile range 5,187–10,304] vs. 8,818 [6,535–12,369] ng/mL at baseline, P < 0.0001). Control subjects showed a modest decline in adiponectin throughout follow-up (0.3% per year, P < 0.0001) at higher levels in women than in men (difference at year(0): 5,358 ng/mL, P < 0.0001). Female case and early-onset case (age at diagnosis <52 years) subjects had a steeper decline than control subjects (slope difference −1.1% per year, P = 0.001 in females, −1.6% per year in early-onset case subjects, P = 0.034). In men, adiponectin slopes for case and noncase subjects were parallel. The slope differences by diabetes onset were largely attenuated after adjustment for changes in obesity, whereas the sex-specific slope differences were independent of obesity. CONCLUSIONS: Lower adiponectin levels were observed already a decade before the diagnosis of diabetes. The marked sex difference in trajectories suggests that sex-specific mechanisms affect the association between adiponectin levels and diabetes development.