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: We included study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, that were 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 our 3363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was directly associated with incident T2D when modeled without HOMA-IR (HR = 1.29, 95% CI = 1.05-1.58). This direct association between leptin and T2D was significant among men (HR = 1.33, 95% CI = 1.05-1.69), but 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. (Continued on next page)Conclusions: Among African Americans in the Jackson Heart Study the association of leptin with incident type 2 diabetes was mediated by insulin resistance. This association was present only among abdominally non-obese participants. 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. Our results should inform future clinical trials that aim to reduce the burden of type 2 diabetes through the modification of serum levels of leptin and adiponectin.

Association of adiponectin & leptin with insulin resistance in type-2 diabetes

“…In thepresent study, the mean age for cases was 42.98±8.16 years and controls was 36.75±5.84 years which was in accordance with a study done by Diwan et al 12 The present study revealed that mean BMI for control group was 22.56±4.13 and T2DM(Study group) was 25.85±4.34. These findings were similar to the study reported by Lalrindiki et al 13 Present study reports that mean Waist Circumference (WC) in T2DM group were more i.e 99.51±3.65 cm than in control group i.e 86.74±8.09 cm which was in accordance to the study reported by Aurelian Bidulescu et al 14 and contradictory to the study done by Lalrindiki et al 13 Similarly our study revealed that mean waist hip ratio (WHR) were increased in T2DM group than in control group which is almost similar to the findings of Lalrindiki et al 13 Increased Waist circumference (WC) and Waist hip ratio (WHR) in T2DM group could be attributed to the fact that such individuals may have accumulated fat levels.…”

“…Similarly our study results revealed that serum insulin and HOMA-IR were increased in T2DM. These findings were similar to the study reported by Aurelian Bidulescu et al 14 Present study results highlights that Adiponectin is positively correlated with HDL, TC, and LDL while other anthropometric indices markers of insulin resistance and Triglycerides had negative correlation which is in accordance with the study reported by Prema Adhikari et al 15 Similarly, leptin is negatively correlated with HDL while other anthropometric indices markers of insulin resistance and Triglycerides had positive correlation similar to the study reported by Amita yadav et al 16…”

Adiposity, related biomarkers, and type 2 diabetes after gestational diabetes: The Diabetes Prevention Program

“…In order to evaluate the possibility of confounding by BMI, we fit models testing the association of leptin and incident T2D without adjustment TA B L E 2 Cox proportional hazards regression models testing the association of adiposity-related biomarkers with progression to T2D per 1-SD increase in each biomarker, overall and stratified by history of GDM for BMI and found an HR for T2D of 1.179 (p < 0.001) and 0.880 (p = 0.093) for a 1-SD change in women without and with a history of GDM, respectively, compared with a BMI-adjusted HR of 1.126 (p = 0.016) and 0.776 (p = 0.013), suggesting that confounding by BMI did not explain the difference in associations of leptin with T2D risk that we observed in women without and with a history of GDM. Differences in age across the cohorts are also unlikely to explain differences in the observed association of leptin with T2D risk, as average age was similar among the previous reports (ranging from 52 to 56 years among studies reporting a mean value for age) (28)(29)(30)32). Another possibility is menopausal status.…”

“…with increased risk of incident T2D or worsening hyperinsulinemia, independent of BMI or adiposity in large longitudinal cohorts (28)(29)(30). In the Jackson Heart Study, a longitudinal cohort of Black participants (n = 3,363), higher circulating leptin levels were associated with higher odds of T2D over 7 years, independent of BMI, overall and among male participants only (HR for 1-unit increase in log leptin level in ng/mL overall = 1.3 [95% CI: 1.1-1.6]; in men…”

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].…”