Diabetes

Five-year patient-reported outcomes of individualized nutrition therapy supporting nutritional ketosis in adults with type 2 diabetes 

Type 2 diabetes (T2D) can affect health and well-being far beyond blood glucose control. This study examined five-year changes in sleep, depressive symptoms, and knee pain among adults participating in a digitally delivered continuous care program providing individualized carbohydrate-reduced nutrition therapy supporting nutritional ketosis.

The analysis followed participants from the intervention arm of a non-randomized clinical trial. Of 194 participants who completed the initial two-year study, 169 entered the three-year extension, and 122 were retained at five years. Participants were advised to consume <30 g carbohydrate/day and achieve nutritional ketosis, defined as blood β-hydroxybutyrate (BHB) of 0.5–3.0 mmol/L, with individualized adjustments.

The program provided ongoing digital health coaching, medical care, nutrition guidance, and medication management. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), and knee outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results/Key Findings

• Sleep: PSQI scores improved significantly at every follow-up, with estimated mean reductions of 19–25% at five years. Among participants with baseline and five-year data, the proportion classified as poor sleepers fell from 63% to 48% (p=0.01).
• Depressive symptoms: In the overall cohort, depressive symptoms improved significantly at 10 weeks, one year, and two years, but were no longer significantly different from baseline at five years. However, participants with clinically elevated depressive symptoms at baseline maintained improvements at five years, with estimated CES-D scores decreasing from 23.3 to 18.0.
• Knee pain and function: All five KOOS domains improved significantly at five years. Among participants reporting weekly knee pain at baseline, 57–74% achieved a ≥10-point minimal clinically important improvement, including 69% for pain and 74% for knee-related quality of life.
• Long-term symptom burden: Few participants developed new clinically elevated sleep or depressive symptoms during follow-up, suggesting relative stability among those without these concerns at baseline.

Conclusion

The authors concluded that five years of digitally delivered, individualized carbohydrate-reduced nutrition therapy supporting nutritional ketosis was associated with durable improvements in sleep and knee pain and sustained reductions in depressive symptoms among participants with elevated symptoms at baseline. Overall, the findings support the potential of metabolically focused, digitally supported care to improve multiple patient-reported outcomes in adults with T2D.