Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes
Open accessAbstract
Aims Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic nephropathy (DN). We investigated the relationship between DN structural lesions and CAN.Methods Sixty three Pima Indians with type 2 diabetes underwent kidney biopsies following a 6-year clinical trial testing the renoprotective efficacy of losartan vs. placebo. CAN was assessed a median 9.2years later. CAN variables included expiration/inspiration ratio (E/I), standard deviation of the normal R-R interval (sdNN), and low and high frequency signal power and their ratio (LF, HF, LF/HF); lower values reflect more severe neuropathy. Associations of CAN with renal structural variables were assessed by linear regression adjusted for age, sex, diabetes duration, blood pressure, HbA1c, glomerular filtration rate, and treatment assignment during the trial.Results Global glomerular sclerosis was negatively associated with sdNN (partial r=-0.35, p=0.01) and LF (r=-0.32, p=0.02); glomerular basement membrane width was negatively associated with all measures of CAN except for LF/HF (r=-0.28 to -0.42, p<0.05); filtration surface density was positively associated with sdNN, LF, and HF (r=0.31 to 0.38, p<0.05); and cortical interstitial fractional volume was negatively associated with HF (r=-0.27, p=0.04).Conclusions CAN associates with DN lesions.
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Early detection of CAN may enable tailored interventions that prevent progression and reduce risks of CVD, arrhythmias, myocardial dysfunction leading to CHF, CKD, and all-cause mortality.
“Timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including CVD, cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure (CHF), CKD, and all-cause mortality.547,614,617–625”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [618]
The Introduction (page not provided) associates CAN with increased all-cause mortality, and the Discussion (page not provided) reports associations with renal decline and CKD. The paper does not establish that early detection or tailored interventions prevent CAN progression or reduce those risks, and it does not address the claimed reductions in CVD, arrhythmias, or myocardial dysfunction leading to CHF. (LLM, conf=0.86)
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References 41 · Cited by 24
Research works printed but not linked: 1
- [28]Belsley DA Kuh E Welsch RE Regression diagnostics: Identifying influential observations and sources of collinearity 1980 Hoboken, New Jersey John Wiley and Sons
- Authors
- Wheelock, K. M., Jaiswal, M., Martin, C. L., Fufaa, G. D., Weil, E. J., Lemley, K. V., Yee, B., Feldman, E., Brosius, F. C., Knowler, W. C., Nelson, R. G., & Pop-Busui, R.
- Affiliations
- University of Michigan (US)
- University of Southern California (US)
- Southwest Kidney Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Nelson, Robert G.
- ORCID
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 30
- Issue
- 5
- Pages
- 873-879
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- PMC
- PMC4912901
- OpenAlex
- W2295288842
- Cited by
- 24
- References
- 41
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 7 · 2016: 2
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hl102334-05)
- National Heart, Lung, and Blood Institute (R01-HL-102334)
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK069062, P30DK020572)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- cardiac autonomic neuropathy, diabetic nephropathy, type 2 diabetes, Pima Indians, Native Americans, renal biopsy, glomerulosclerosis, heart rate variability, losartan, renal protection
- MeSH terms
- Adult, Arizona, Autonomic Nervous System, Autonomic Nervous System Diseases, Biopsy, Cardiovascular Diseases, Cardiovascular System, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Diabetic Neuropathies, Female, Humans, Indians, North American, Kidney, Longitudinal Studies, Male, Middle Aged, Sclerosis, Severity of Illness Index, Cohort Studies, Renal Insufficiency, Diabetic Cardiomyopathies
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