Published February 8, 2023 - More info
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.
Evan L. Reynolds, Gulcin Akinci, Mousumi Banerjee, Helen C. Looker, Adam Patterson, Robert G. Nelson, Eva L. Feldman, Brian C. Callaghan
Original citation: JCI Insight. 2021;6(10):146849. https://doi.org/10.1172/jci.insight.146849
Citation for this corrigendum: JCI Insight. 2023;8(3):168732. https://doi.org/10.1172/jci.insight.168732
For this article, we used the Michigan Neuropathy Screening Instrument combined index (MNSI index) to measure neuropathy longitudinally in 141 Pima American Indians. We were contacted by the authors who developed the MNSI index and were notified of an error in their published manuscript (1, 2).
Specifically, the cutoff reported by Herman et al. to determine neuropathy was incorrect. The corrected cutoff for neuropathy is MNSI index > 2.5407, rather than MNSI index > 3.2516. While we primarily used the continuous MNSI index in our paper, we also reported the prevalence that met this cutoff during each year of follow-up. In light of this information, we reanalyzed our data with the corrected cutoff.
The text in Results and Methods is corrected as follows:
At baseline, 32.9% of participants met the cutoff for neuropathy (MNSI index > 2.5407 ), which generally increased during follow-up (27.4% in year 1, 40.6% in year 2, 59.8% in year 3, 57.6% in year 4, and 55.3% in year 5).
To provide additional clinical context to our primary neuropathy measurement, we also determined the number of participants meeting the predefined cutoff for neuropathy based on the MNSI index (MNSI index > 2.5407) (66).
See the related article at The determinants of complication trajectories in American Indians with type 2 diabetes.