Abstract
BACKGROUND We aimed to determine whether metabolic syndrome (MetS) affects longitudinal trajectories of diabetic complications, including neuropathy, cardiovascular autonomic neuropathy (CAN), and kidney disease in American Indians with type 2 diabetes.METHODS We performed a prospective study where participants underwent annual metabolic phenotyping and outcome measurements. The updated National Cholesterol Education Program criteria were used to define MetS and its individual components, using BMI instead of waist circumference. Neuropathy was defined using the Michigan Neuropathy Screening Instrument index, CAN with the expiration/inspiration ratio, and kidney disease with glomerular filtration rate. Mixed-effects models were used to evaluate associations between MetS and these outcomes.RESULTS We enrolled 141 participants: 73.1% female, a mean (±SD) age of 49.8 (12.3), and a diabetes duration of 19.6 years (9.7 years) who were followed for a mean of 3.1 years (1.7 years). MetS components were stable during follow-up except for declining obesity and cholesterol. Neuropathy (point estimate [PE]: 0.30, 95% CI: 0.24, 0.35) and kidney disease (PE: –14.2, 95% CI: –16.8, –11.4) worsened over time, but CAN did not (PE: –0.002, 95% CI: –0.006, 0.002). We found a significant interaction between the number of MetS components and time for neuropathy (PE: 0.05, 95% CI: 0.01–0.10) but not CAN (PE: –0.003, 95% CI: –0.007, 0.001) or kidney disease (PE: –0.69, 95% CI: –3.16, 1.76). Systolic blood pressure (SBP, unit = 10 mmHg) was associated with each complication: neuropathy (PE: 0.23, 95% CI: 0.07, 0.39), CAN (PE: –0.02, 95% CI: –0.03, –0.02), and kidney disease (PE: –10.2, 95% CI: –15.4, –5.1).CONCLUSION In participants with longstanding diabetes, neuropathy and kidney disease worsened during follow-up, despite stable to improving MetS components, suggesting that early metabolic intervention is necessary to prevent complications in such patients. Additionally, the number of MetS components was associated with an increased rate of neuropathy progression, and SBP was associated with each complication.FUNDING The following are funding sources: NIH T32NS0007222, NIH R24DK082841, NIH R21NS102924, NIH R01DK115687, the Intramural Program of the NIDDK, the NeuroNetwork for Emerging Therapies, the Robert and Katherine Jacobs Environmental Health Initiative, the Robert E. Nederlander Sr. Program for Alzheimer’s Research, and the Sinai Medical Staff Foundation.TRIAL REGISTRATION ClinicalTrials.gov, NCT00340678.
Authors
Evan L. Reynolds, Gulcin Akinci, Mousumi Banerjee, Helen C. Looker, Adam Patterson, Robert G. Nelson, Eva L. Feldman, Brian C. Callaghan
Linear mixed-effects models for neuropathy (MNSI index), CAN (E/I ratio), and kidney disease (GFR) with individual MetS components and random subject-specific intercept
