Adiponectin trajectories before type 2 diabetes diagnosis: Whitehall II study

Abstract

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.

Figure 1

Model-predicted log-transformed adiponectin trajectories before the diagnosis of diabetes or end of follow-up in 335 incident diabetes case and 2,475 control subjects. A: Adiponectin trajectories by sex and incident diabetes status. B: Adiponectin trajectories by incident diabetes status in case subjects with early-onset diabetes. C: Adiponectin trajectories by incident diabetes status in case subjects with late-onset diabetes. D: Adiponectin trajectories by sex and incident diabetes status in case subjects with early-onset diabetes. E: Adiponectin trajectories by sex and incident diabetes status in case subjects with late-onset diabetes. Multilevel longitudinal modeling using linear growth models. All models are adjusted for age at the end of follow-up and for ethnicity (white/nonwhite). A shows a model additionally adjusted for sex, B and C are additionally adjusted for age at onset (early onset: <52 years of age at diagnosis), and D and E are adjusted for both sex and age at onset. Estimated for a hypothetical subject population 72% male, 92% white, and aged 63 years (A, C, and E) or 50 years (B and D) at year₀. Error bars show 95% CIs for the fixed effects. The tables show the number of measurements for each year at and before diabetes diagnosis and end of follow-up.