320-OR: ADA Presidents' Select Abstract: Risk Factors for Distal Symmetrical Polyneuropathy (DSPN) in the Diabetes Prevention Program (DPP) and the DPP Outcomes Study (DPPOS)
Authors: LEE CHRISTINE , CIARLEGLIO ADAM , EDELSTEIN SHARON , CRANDALL JILL P. , DABELEA DANA , GOLDBERG RONALD B. , KAHN STEVEN E. , KNOWLER WILLIAM C. , MA MAXWELL , WHITE NEIL , HERMAN WILLIAM H. ,   DPP RESEARCH GROUP
Published: June 2023

Objective: To evaluate how DSPN differs across the randomized DPP treatment groups and is associated with diabetes (DM) status, DM duration, and cumulative glycemic exposure.
Methods: In the DPP, adults ≥25 years of age at high risk for DM (n=3234) were randomized to determine the effects of intensive lifestyle modification (ILS) or metformin (MET) compared to placebo (PLA) on incident diabetes. After DPP ended, participants were invited to join the DPPOS during which metformin was continued in those randomized to receive it. DSPN was rigorously assessed in 1,792 participants at DPPOS year 17 based on both symptoms and signs (pinprick, vibration, and monofilament). Multivariable logistic regression models were used to determine whether DSPN was associated with randomized treatment group, DM status and duration, and cumulative glycemic exposure.
Results: At 21 years following DPP randomization, 66% had developed DM with median duration of 15 years. The prevalence of DSPN did not differ by DPP treatment group (21.5%, 21.5% and 21.9% in ILS, MET and PLA, respectively), but was slightly lower for those at risk for DM (19.6%) vs. those with DM (22.7%). There was a significant effect modification by age of the association between DPP treatment group and DSPN (p&lt;0.05): the odds ratio (OR) for DSPN with ILS vs PLA decreased by 3.7% (95% CI 0.6-6.7) with each 1 year increase in age. MET vs. PLA was not associated with DSPN and age did not influence the null association. In models adjusted for treatment group, demographics, cardiometabolic risks, and low vitamin B12 or B12 supplement use, DSPN was associated with DM status (OR 1.40, p&lt;0.001 vs. no DM), greater DM duration (OR 1.04 per 1 year, p&lt;0.001), and higher time-weighted HbA1c (OR 1.85 per 1% increase, p&lt;0.001).
Conclusions: The likelihood of DSPN was higher for those with DM, longer DM duration, and higher cumulative glycemic exposure. Although ILS did not prevent DSPN overall, there were ILS benefits with increasing age.

Disclosure
C.Lee: Employee; Pfizer Inc. N.White: None. W.H.Herman: Advisory Panel; National Committee for Quality Assurance, Consultant; Merck Sharp & Dohme Corp., Other Relationship; National Institutes of Health, American Diabetes Association. D.Research group: None. A.Ciarleglio: None. S.Edelstein: None. J.P.Crandall: Research Support; Abbott Diabetes. D.Dabelea: None. R.B.Goldberg: None. S.E.Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Other Relationship; Novo Nordisk. W.C.Knowler: None. M.Ma: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)