Associations of leptin 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. 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.

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

10.21203/rs.2.21466/v2 ◽

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: 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.

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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.

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High-Sensitivity C-Reactive Protein Is Associated With Incident Type 2 Diabetes Among African Americans: The Jackson Heart Study

Diabetes Care ◽

10.2337/dc15-0221 ◽

2015 ◽

Vol 38 (9) ◽

pp. 1694-1700 ◽

Cited By ~ 34

Author(s):

Valery S. Effoe ◽

Adolfo Correa ◽

Haiying Chen ◽

Mary E. Lacy ◽

Alain G. Bertoni

Keyword(s):

Type 2 Diabetes ◽

African Americans ◽

High Sensitivity ◽

Jackson Heart Study ◽

C Reactive Protein ◽

Incident Type ◽

Reactive Protein ◽

Heart Study ◽

Incident Type 2 Diabetes

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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

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Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study

Journal of Clinical & Translational Endocrinology ◽

10.1016/j.jcte.2019.100210 ◽

2020 ◽

Vol 19 ◽

pp. 100210 ◽

Cited By ~ 4

Author(s):

Sean Lee ◽

Mary E. Lacy ◽

Mathew Jankowich ◽

Adolfo Correa ◽

Wen-Chih Wu

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

African Americans ◽

Jackson Heart Study ◽

Heart Study

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Abstract MP05: Leisure-Time Running and Incident Type 2 Diabetes

Circulation ◽

10.1161/circ.131.suppl_1.mp05 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Duck-chul Lee ◽

Carl J. Lavie ◽

Timothy S. Church ◽

Xuemei Sui ◽

Steven N. Blair

Keyword(s):

Type 2 Diabetes ◽

Lower Risk ◽

Leisure Time ◽

Cox Regression ◽

Smoking Status ◽

Physical Activities ◽

Incident Type ◽

Incident Type 2 Diabetes

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.

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Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001425 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001425

Author(s):

Cornelia Then ◽

Christina Gar ◽

Barbara Thorand ◽

Cornelia Huth ◽

Holger Then ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Waist Circumference ◽

Vascular Complications ◽

Model Assessment ◽

Incident Type ◽

The Metabolic Syndrome ◽

Incident Type 2 Diabetes

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

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