Diabetes treatments and their role in the development of DSPN over two decades

Aims: To evaluate the relationships between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment categories, diabetes status or duration, and total glycemic exposure around 21 years following DPP randomization.

Methods: In the DPP, 3,234 adults over 25 years old at high risk for diabetes were randomized into three groups: intensive lifestyle (ILS), metformin, or placebo, with the goal of preventing diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). During DPPOS, metformin treatment was continued, the placebo was stopped, ILS was conducted as semiannual group classes, and all participants were provided quarterly lifestyle classes. At the 17th year of DPPOS, symptoms and signs of DSPN were assessed in 1,792 participants using MNSI-Q and sensation to pinprick, vibration and 10g monofilament. 

Results: Twenty-one years after DPP randomization, 66% of the participants had developed diabetes. The prevalence of DSPN was similar across the initial treatment groups: 21.5% for both the intensive lifestyle (ILS) and metformin groups, and 21.9% for the placebo group. There was a significant interaction between the ILS treatment assignment and age, impacting DSPN prevalence (P<0.05). Specifically, odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals at the 17th year of the DPPOS. DSPN was slightly less prevalent among those at risk for diabetes (19.6%) compared to those with diagnosed diabetes (22.7%), and it was linked to longer durations of diabetes and higher time-weighted HbA1c levels (P values <0.001).

Conclusions: The likelihood of developing DSPN was similar across all DPP treatment groups but increased in participants with diabetes, longer diabetes durations, and higher cumulative glycemic exposure. ILS may provide long-term benefits in reducing DSPN in older adults.

Comments. DSPN is a common and debilitating complication of diabetes that significantly impacts quality of life and increases risks for severe complications like foot ulcers and amputations. Effective management of diabetes can decelerate the progression of DSPN in individuals with type 1 diabetes, yet it only yields limited benefits for those with type 2 diabetes. Understanding how lifestyle and medical interventions might influence its prevalence is crucial for developing strategies to mitigate this condition, especially early in diabetes or even in prediabetes. The study concludes that while the initial DPP interventions did not differ in their impact on DSPN prevalence, factors like diabetes status, duration, and especially cumulative glycemic exposure played significant roles. The findings suggest that interventions aimed at reducing glycemic exposure could potentially lower the risk of DSPN. Clinically, this emphasizes the importance of maintaining good glycemic control to prevent or delay the development of DSPN, and highlights the potential benefit of lifestyle interventions, particularly for older adults at risk of diabetes. However, the study has limitations including the absence of baseline DSPN data, potential survivorship bias, and treatment modifications during the study. The reliance on self-reported data and lack of adjustment for all potential confounders may also impact the accuracy and generalizability of the findings.

Zoltan Kender

Reference. Lee CG, Ciarleglio A, Edelstein SL, Crandall JP, Dabelea D, Goldberg RB, Kahn SE, Knowler WC, Ma MT, White NH, Herman WH; Diabetes Prevention Program Research Group. Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure. Diabetes Care. 2024 May 1;47(5):810-817. doi: 10.2337/dc23-2009. PMID: 38502874; PMCID: PMC11043227.

https://diabetesjournals.org/care/article/47/5/810/154385/Prevalence-of-Distal-Symmetrical-Polyneuropathy-by