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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., 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.

Background: The biological actions of vitamin D are mediated through the vitamin D receptor (VDR). Single-nucleotide polymorphisms (SNPs) in the VDR gene have been previously associated with adiposity traits. However, to our knowledge, few studies have included direct measures of adiposity and adipokine concentrations., Objective: We examined the association of tagging SNPs in the VDR gene with multiple adiposity measures, including waist circumference (WC), body mass index (BMI), body fat percentage, subcutaneous and visceral adipose tissue (VAT) volume, and serum adipokine (adiponectin and leptin) concentrations in adult African Americans (AAs)., Methods: Data from 3020 participants (61.9% women; mean age, 54.6 y) from the Jackson Heart Study were used for this analysis. Forty-five tag SNPs were chosen with the use of genotype data from the International HapMap project. We used linear regression to test the associations of imputed VDR SNPs with each of the traits, adjusted for age, sex, educational status, physical activity, smoking, alcohol intake, serum vitamin D concentration, European ancestry, and multiple testing., Results: The G allele of the SNP rs4328262 remained associated with increased VAT volume after multiple testing correction (β = 45.7; P < 0.001). The A allele of another SNP (rs11574070) was nominally associated with body fat percentage (β = 0.96; P = 0.002). None of the VDR SNPs analyzed showed any link with WC or BMI. The A allele of rs2228570 (β = 0.08; P = 0.001) for men and the T allele of rs2853563 (β = 0.04; P < 0.001) for women remained positively associated with serum adiponectin concentrations after multiple testing correction., Conclusion: Although we did not find any association for anthropometric measures, we did observe associations of VDR variants with serum adipokines and with the more metabolically active fat, VAT. Therefore, our findings demonstrate a possible role of VDR variants in regulating adipose tissue activity and adiposity among AAs., (© 2016 American Society for Nutrition.)

Background: Recent emphasis has been placed on elucidating the biologic mechanism linking socioeconomic status (SES) to cardiovascular disease (CVD). Positive associations of inflammatory biomarkers provide evidence suggestive of a biologic pathway by which SES may predispose to CVD. African Americans have disproportionately lower SES and have a higher prevalence of CVD risk factors compared to most ethnic/racial groups. Adiponectin (an anti-inflammatory marker) is also lower. The objective of this study was to assess the association of adiponectin with SES among African American men and women using the Jackson Heart Study., Methods: Study sample included 4340 participants. Linear regression was performed separately by SES and stratified by sex. Annual household income and level of education was used as proxies for SES. Crude, age, health behavior and health status adjusted models were analyzed. The main outcome was log-transformed adiponectin., Results: Men in the lowest income group had significantly higher adiponectin than those in the highest income group in the fully adjusted model (ß/standard error [se], p value = .16/.08, p = .0008. Men with < high school level of education had significantly higher adiponectin in the crude and age adjusted models than those with ≥ college degree (.25/.05, p < .0001; .14/.05/ p = .005, respectively). Women with some college or vocational training in the crude and age adjusted models had lower adiponectin compared to women with ≥ college degree (-.09/.03, p = .004; -.06/.03, p = .04, respectively)., Conclusion: Findings suggest a potential inverse biologic pathway between annual household income and adiponectin among African American men. There was no such finding among women. Findings suggest interventions should be targeted for higher SES African American men to improve adiponectin levels.

Background: African Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex., Results: There was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (β(SE) p = -.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (β(SE) p = -0.74(0.20), 0.0002)., Conclusions: These findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women.

Background: Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort., Methods: Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs)., Results: We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was negatively and significantly associated with BMI only in participants with a normal weight., Conclusions: In this large African American cohort, ADIPOQ variants were associated with adiponectin levels in a gender-dependent manner and the relationship of some of these variants with obesity and BMI was modulated by the PEA and obesity status respectively. This suggests that the effects of these polymorphisms on adiponectin and obesity phenotypes are subject to a strong interaction with genetic and environmental factors in African American population.

Background: Adiponectin is a biomarker that is associated with type 2 diabetes and hypertension. Lower circulating level is a risk factor. Higher levels are protective. African Americans have a higher prevalence of type 2 diabetes and hypertension and lower levels of adiponectin when compared to other racial/ethnic groups. Little is known about the association of adiponectin on these health outcomes among African Americans. The purpose of the study was to assess the association of adiponectin on type 2 diabetes and hypertension likelihood among African American men and women in the Jackson Heart Study., Methods: Separate multivariate logistic regressions were conducted stratified by sex based on cross-sectional data with type 2 diabetes and hypertension as the outcomes. Adiponectin was divided into four quartiles with the highest quartile as the reference. Data was collected from 2000-2004 on 3,663 participants. Data analysis was conducted in calendar year 2014. Two- tailed P < .05 was established as level of significance., Results: In the adjusted multivariate models, adiponectin level was inversely associated with type 2 diabetes among women (odds ratio [OR], 95% confidence interval [CI] = 1.47, [1.02, 2.11], P = .04). There was no association among men. Women with the lowest level of adiponectin were less likely to be hypertensive (OR, 95% CI = 0.66, [0.46, 0.95], p = .02). There was no association among men., Conclusion: Findings reveal differential associations between levels of adiponectin with type 2 diabetes and hypertension likelihood among African American women. More research is needed to elucidate this differential association.

Introduction: Directly proportional to body fat leptin influences the regulation of blood glucose through several mechanisms some of them influenced by adiponectin. In population studies high leptin levels have been associated with the development of type 2 diabetes mellitus (T2D), with differences by sex. Because African Americans have high prevalence of obesity and T2D, we assessed the association of leptin with T2D and its interaction with adiponectin in a large ongoing cohort study. The hypothesis was a direct association between leptin and T2D, with differences by sex and modulated by adiponectin. Methods: We included participants who were free of T2D (ADA 2004) at the baseline examination (Exam 1) from the Jackson Heart Study (JHS), a single-site, prospective cohort of risk factors of heart disease in African Americans in Jackson, Mississippi. Incident T2D was defined as new T2D cases among Exam 2 or Exam 3 participants. Separate logistic regression models (odds ratios per log-transformed unit of biomarker) included a minimally adjusted model for age, sex and BMI; a model with addition of systolic blood pressure, antihypertension medication, triglycerides, HDL-cholesterol and antihyperlipidemic medication, smoking, alcohol intake, physical activity and education level; and a full model with addition of insulin resistance, HOMA-IR, on top of these variables. Several interactions were assessed such as by sex and glycated hemoglobin, HgA1c. Results: Among our 3083 participants (mean age 53 years, 63% women) there were 584 incident T2D cases. Significant correlations were present among women for leptin with BMI (0.64) and HOMA-IR (0.30), and for adiponectin with HOMA-IR (-0.32) and HDL-cholesterol (0.39). Among men, significant correlations were found for leptin with BMI (0.76) and HOMA-IR (0.53); and for adiponectin with HOMA-IR (-0.28) and HDL-cholesterol (0.38). Leptin was directly associated with incident T2D in the minimally adjusted model (OR= 1.46; 95% C.I. 1.21, 1.77). The association remained in the additional model (OR=1.43, 95% C.I. 1.15-1.78). However the fully adjusted model showed no association between leptin and T2D (OR=0.97, 95% C.I. 0.76-1.24), indicative of a mediation through insulin resistance. The direct association between leptin and T2D was present in men (OR=1.54, 95% C.I. 1.18-1.99; association nullified by insulin resistance), but not in women (OR=1.30, 95% C.I. 0.96-1.76); although no statistical interaction was present (p=0.96). Adiponectin did not interact with leptin in their association with incident T2D (p=0.08). Effect modification was not present for HgA1c and leptin or adiponectin. Conclusion: Among our African American participants there was an association between leptin and incident T2D, explained by insulin resistance but not modulated by adiponectin. Differences by sex were present, men showing an association nullified by HOMA-IR. [ABSTRACT FROM AUTHOR]