Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes

J Diabetes Complications. 2016 Jul;30(5):873-9. doi: 10.1016/j.jdiacomp.2016.03.008. Epub 2016 Mar 11.


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.

Keywords: American Indians; Cardiovascular autonomic neuropathy; Diabetic nephropathy; Kidney biopsy; Type 2 diabetes.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arizona
  • Autonomic Nervous System / physiopathology
  • Autonomic Nervous System Diseases / complications
  • Autonomic Nervous System Diseases / ethnology
  • Autonomic Nervous System Diseases / physiopathology*
  • Biopsy
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / physiopathology*
  • Cardiovascular System / innervation
  • Cardiovascular System / physiopathology
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetic Angiopathies / ethnology
  • Diabetic Angiopathies / physiopathology
  • Diabetic Cardiomyopathies / ethnology
  • Diabetic Cardiomyopathies / physiopathology
  • Diabetic Nephropathies / ethnology
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology*
  • Diabetic Neuropathies / ethnology
  • Diabetic Neuropathies / physiopathology*
  • Female
  • Humans
  • Indians, North American
  • Kidney / innervation
  • Kidney / pathology
  • Kidney / physiopathology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Renal Insufficiency / complications
  • Renal Insufficiency / ethnology
  • Renal Insufficiency / pathology
  • Renal Insufficiency / physiopathology*
  • Sclerosis
  • Severity of Illness Index