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Research article
Aurelian Bidulescu
Indiana University Bloomington School of Public Health
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8211-8309
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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 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.
Keywords
Leptin, Adiponectin, Type 2 Diabetes, African Americans, Insulin Resistance, Mediation, Observational Cohort, Obesity, Gender
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View the published article at BMC Endocrine Disorders.
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Received 07 Feb, 2020
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Editorial decision: Major revision
On 07 Feb, 2020
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Received 31 Jan, 2020
Reviewer #4 agreed
On 27 Jan, 2020
Reviewer #3 agreed
On 24 Jan, 2020
Reviewer #2 agreed
On 23 Jan, 2020
Reviewers invited
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Subject Areas
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A new preprint design is coming!
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See the published version of this preprint at BMC Endocrine Disorders.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Aurelian Bidulescu
Indiana University Bloomington School of Public Health
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8211-8309
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Endocrine Disorders.
Version 3
Posted 21 Feb, 2020
No community comments so far
Editor assigned
On 20 Feb, 2020
Submission checks complete
On 19 Feb, 2020
Editor invited
On 19 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 19 Feb, 2020
Editor assigned
On 17 Feb, 2020
Submission checks complete
On 16 Feb, 2020
Editor invited
On 16 Feb, 2020
No comments provided
Review #4 received
Received 07 Feb, 2020
Review #2 received
Received 07 Feb, 2020
Editorial decision: Major revision
On 07 Feb, 2020
Review #1 received
Received 31 Jan, 2020
Reviewer #4 agreed
On 27 Jan, 2020
Reviewer #3 agreed
On 24 Jan, 2020
Reviewer #2 agreed
On 23 Jan, 2020
Reviewers invited
Invitations sent on 20 Jan, 2020
Reviewer #1 agreed
On 20 Jan, 2020
Editor assigned
On 18 Jan, 2020
Submission checks complete
On 17 Jan, 2020
Editor invited
On 17 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Endocrinology & Metabolism
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Endocrine Disorders.
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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