Associations of leptin and adiponectin with incident type 2 diabetes and interactions among African Americans: the Jackson Heart Study

Abstract

Background: Growing evidence suggests that leptin is critical for glycemic control. Impaired leptin signaling may also contribute to low adiponectin expression in obese individuals. We assessed the association of leptin and adiponectin with incident type 2 diabetes (T2D), their interactions with sex and obesity status, and mediation by insulin resistance.Methods: Study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, included those free of T2D at the baseline Exam 1. Incident T2D was defined as new cases at Exam 2 or Exam 3. We created separate Cox regression models (hazard ratios per log-transformed ng/mL of leptin and adiponectin) with and without insulin resistance, HOMA-IR. Mediation by insulin resistance was analyzed. Several interactions were assessed, including by sex, HbA1c, and obesity.Results: Among 3,363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was associated with incident T2D when modeled without HOMA-IR (HR=1.29, 95% CI=1.05-1.58). Among men, this positive association between leptin and T2D was significant (HR=1.33, 95% CI=1.05-1.69), but it was nonsignificant among women (HR=1.24, 95% CI=0.94-1.64); statistical interaction with sex was nonsignificant (p=0.65). The associations in all participants and in men were nullified by HOMA-IR (HR=0.99, 95% CI=0.80-1.22; HR=1.00, 95% CI=0.78-1.28, respectively), indicating mediation through insulin resistance (proportion mediated: 1.04), and were not observed in abdominally obese participants. Adiponectin was inversely associated with T2D even after adjustment for HOMA-IR in women (HR=0.68, 95% CI=0.55-0.84), but not in men (HR=0.80, 95% CI=0.62-1.04). The inverse association was present only among abdominally obese participants, and persisted after adjustment for HOMA-IR.Conclusions: Among African Americans in the Jackson Heart Study the association of leptin with incident T2D was explained by HOMA-IR. The association of leptin and incident T2D was mediated by insulin resistance and observed only among abdominally non-obese. Differences by sex appeared: men showed a significant association mediated by insulin resistance. Among abdominally obese participants, adiponectin was inversely associated with incident T2D even after adjustment for HOMA-IR.

Plasma adipokines and glycaemic progression among African Americans: Findings from the Jackson Heart Study

“…The observed positive association between high leptin and dysglycaemic progression is consistent with those from prior studies of the association of leptin and type 2 diabetes in sample of mostly Caucasians and Asian individuals, 9,11 though in some studies such an association was not obvious 10 . Our study complement and extend the findings from prior studies of adipokines among AAs, which did not examined the whole spectrum of hyperglycaemia (only focused on diabetes) and have also not accounted for the extent of inflammation 27,28 . Our findings, using a homogeneous sample of AAs, lend credence to putative role of leptin as a potential link between obesity and pathogenesis of type 2 diabetes 29 .…”

“…Previous reports have traditionally assessed the relations of adipokines with type 2 diabetes only, not examining the whole spectrum of dysglycaemia. [4][5][6][7][9][10][11][12][13][14][15][16]27,28 The observed positive association between high leptin and dysglycaemic progression is consistent with those from prior studies of the association of leptin and type 2 diabetes in sample of mostly Caucasians and Asian individuals, 9,11 though in some studies such an association was not obvious. 10 Our study complement and extend the findings from prior studies of adipokines among AAs, which did not examined the whole spectrum of hyperglycaemia (only focused on diabetes) and have also not accounted for the extent of inflammation.…”

“…10 Our study complement and extend the findings from prior studies of adipokines among AAs, which did not examined the whole spectrum of hyperglycaemia (only focused on diabetes) and have also not accounted for the extent of inflammation. 27,28 Our findings, using a homogeneous sample of AAs, lend credence to putative role of leptin as a potential link between obesity and pathogenesis of type 2 diabetes. 29 Our findings suggest that much of the association between leptin and subsequent dysglycaemia may be accounted for by obesity and possibly insulin resistance.…”

“…To our knowledge, this is the first population‐based study to prospectively evaluate the association of adipokines with dysglycaemic progression in AAs. Previous reports have traditionally assessed the relations of adipokines with type 2 diabetes only, not examining the whole spectrum of dysglycaemia 4–7,9–16,27,28 …”

Immune Response to SARS-CoV-2 Infection in Obesity and T2D: Literature Review

“…Evidence shows that leptin is involved in glucose metabolism, innate immune reactions and acute inflammation. The concentration of leptin in blood in obese patients with dyslipidemia is high, causing signaling alteration, promoting the development of insulin resistance and T2D [ 92 , 93 ]. In mice, it has been described an increase in leptin is associated with inflammatory markers in obese individuals [ 94 ], and in humans production of cytokines can be induce when leptin is administered exogenously [ 95 ].…”