The 5 components of the metabolic syndrome (MetS) increase the likelihood of developing diabetes, heart disease, and stroke, but their association with neuropathy and diabetic kidney disease (DKD) is less understood.

We examined the longitudinal association between the components of the updated National Cholesterol Education Program criteria for MetS, neuropathy and DKD in Pima Indians with type 2 diabetes, after substituting BMI for waist circumference. The primary outcome for neuropathy was the Michigan Neuropathy Screening Instrument index, for cardiovascular autonomic neuropathy (CAN) was the expiration/inspiration ratio, and for DKD was the Glomerular Filtration Rate. At baseline and during annual follow-up exams, participants underwent metabolic phenotyping and outcome measurements.

Linear mixed effects models with a random patient effect were used to evaluate the associations between the number of MetS components and neuropathy, CAN, and DKD outcomes. We also examined mixed models for each outcome with individual MetS components.

Between 11/1/2013 and 7/1/2019, we studied 141 Pima Indian subjects, who were followed an average of 3.2 years. The mixed effects models revealed a significant interaction between the number of MetS components and follow-up time for neuropathy (point estimate (PE): 0.07, CI: 0.02-0.11), indicating that the rate of neuropathy increases as the number of MetS components increases. Additionally, we found that neuropathy (year PE: 0.30, CI: 0.24,0.35) and DKD (PE: -14.2, CI: -16.8,-11.4), worsened over time, but CAN did not. The mixed models with individual MetS components revealed SBP was associated with each complication: neuropathy (PE: 0.23, CI: 0.07,0.39), CAN (PE: -0.02, CI: -0.03,-0.02) and DKD (PE: -10.2, CI: -15.4,-5.1).

Neuropathy progression was the complication most affected by the number of MetS components. Neuropathy and DKD worsened during follow-up, emphasizing how quickly these complications can change within this population.


E.L. Reynolds: None. R.G. Nelson: None. G. Akinci: Advisory Panel; Spouse/Partner; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Speaker’s Bureau; Spouse/Partner; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. R. Henn: None. A. Patterson: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation. B.C. Callaghan: None.


National Institutes of Health (R24DK082841, T32NS0007222, R01DK115687); Program for Neurology Research & Discovery; Robert and Katherine Jacobs Environmental Health Initiative; Robert E. Nederlander, Sr. Program for Alzheimer’s Research; Sinai Medical Staff Foundation

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