High-Sensitivity C-Reactive Protein Is Associated With Incident Type 2 Diabetes 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.

Download Full-text

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

BMC Endocrine Disorders ◽

10.1186/s12902-020-0511-z ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Aurelian Bidulescu ◽

Paul C. Dinh ◽

Shabir Sarwary ◽

Emily Forsyth ◽

Maya C. Luetke ◽

...

Keyword(s):

Type 2 Diabetes ◽

African Americans ◽

Jackson Heart Study ◽

Incident Type ◽

Heart Study ◽

Incident Type 2 Diabetes

Download Full-text

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

10.21203/rs.2.21466/v1 ◽

2020 ◽

Author(s):

Aurelian Bidulescu ◽

Paul C. Dinh ◽

Shabir Sarwary ◽

Emily Forsyth ◽

Maya C. Luetke ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

African Americans ◽

Cox Regression ◽

Leptin Resistance ◽

Jackson Heart Study ◽

Incident Type ◽

Heart Study ◽

Incident Type 2 Diabetes

Abstract Background: Growing evidence suggests that leptin is critical for glycemic control. 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) 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=1.32, 95% CI=1.08-1.61). 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. Conclusions: The leptin and incident T2D association mediated by insulin resistance was observed only among abdominally non-obese African Americans in the Jackson Heart Study, suggestive of a ‘leptin resistance’ phenomenon. Differences by sex appeared: men showed a significant association mediated by insulin resistance.

Download Full-text

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

10.21203/rs.2.21466/v3 ◽

2020 ◽

Author(s):

Aurelian Bidulescu ◽

Paul C. Dinh ◽

Shabir Sarwary ◽

Emily Forsyth ◽

Maya C. Luetke ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

African Americans ◽

Cox Regression ◽

Inverse Association ◽

Jackson Heart Study ◽

Incident Type ◽

Heart Study ◽

Incident Type 2 Diabetes

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 3,363 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 explained by HOMA-IR. The association of leptin and incident T2D was mediated by insulin resistance and present 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.

Download Full-text

Abstract 020: C-reactive Protein As A Moderator And Insulin Resistance As A Mediator For The Association Between Endothelin-1 And Type 2 Diabetes Progression Among African Americans In The Jackson Heart Study

Circulation ◽

10.1161/circ.143.suppl_1.020 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Xiang Gao ◽

Steven R Horbal ◽

Hao Fan ◽

Le Su ◽

Solomon K Musani ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

African Americans ◽

C Reactive Protein ◽

Reactive Protein ◽

Heart Study ◽

Diabetes Progression ◽

Adjusted Model ◽

Multivariable Adjusted Model

Objective: Little is known about the moderation and mediation factors among the association between endothelin-1 (ET-1) level and type 2 diabetes progression in African Americans. We explored the role of high sensitivity C-reactive protein (hsCRP) as a moderator and homeostatic model assessment of insulin resistance (HOMA-IR) as a mediator for the association between ET-1 level and type 2 diabetes progression among African Americans enrolled in the Jackson Heart Study (JHS). Methods: We included 1,692 participants free of prediabetes and diabetes at baseline, who attended Exam 1 of the JHS in 2000-2004 and Exam 3 in 2009-2013, and with measured ET-1 level at Exam 1. Incident prediabetes and diabetes were ascertained at Exam 3. We used a sequential regression model procedure. Zou’s modified Poisson multivariable models were used to calculate risk ratios (RR) and 95% confidence intervals (CI) for prediabetes and diabetes. Effect modification was assessed in the multivariable adjusted model. Valeri and VanderWeele’s mediation analysis approach was utilized to evaluate mediation. Results: A higher log-transformed ET-1 level was detected when comparing non-diabetes versus prediabetes and diabetes participants (p-value for trend = 0.03). Compared to quartile 1 (<0.9 pg/mL) of ET-1, quartile 2 (0.9-1.2 pg/mL) of ET-1 was significantly associated with higher risk of prediabetes (RR=1.19 [95% CI 1.02, 1.38]) and diabetes (RR=1.19 [95% CI 1.02, 1.40]). This association only remained significant for diabetes in the multivariable adjusted model (RR=1.20 [95% CI 1.02, 1.40]) and was not attenuated after adjusted for hsCRP (RR=1.20 [95% CI 1.03, 1.40]), HOMA-IR (RR=1.20 [95% CI 1.02, 1.40]), and both hsCRP and HOMA-IR (RR=1.20 [95% CI 1.03, 1.40]) in quartile 2 of ET-1.The risk of elevated ET-1 level on diabetes was higher in participants with increased hsCRP level in the multivariable adjusted model (RR=1.06 [95% CI 1.02, 1.09]), and further adjusted for HOMA-IR (RR=1.06 [95% CI 1.02, 1.09]. The indirect effect of ET-1 on prediabetes through HOMA-IR is 0.96 (P<0.01), but not found for hsCRP (p=0.26). The total effect of ET-1 on prediabetes mediated by HOMA-IR is 47%. No such mediation effect of HOMA-IR was found among diabetes participants. Conclusions: African Americans with higher ET-1 levels have a higher risk of prediabetes and diabetes. Additionally, the risk of diabetes is elevated among those African Americans with increased hsCRP levels. The mediation analysis result supports that ET-1 is involved in the stage of glucose metabolism imbalances leading to diabetes progression.

Download Full-text