Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial

Abstract

Purpose: Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years. Materials and methods: An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status. Results: Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p < 0.00012. Conclusion: The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health. Clinical Trial Registration: Clinicaltrials.gov NCT02519309.

Keywords: HbA1c; body composition; nutritional ketosis; reversal and remission; type 2 diabetes.

Figures

Figure 1

Flow chart of participants in each stage of the study from recruitment to 2 years post-enrollment and analysis.

Figure 2

Adjusted mean changes from baseline to 2 years in the CCI group for (A) HbA1c (−12% relative to baseline, P = 1.8 × 10−17), (B) Fasting insulin (−42% relative to baseline, P = 2.2 × 10−18).

Figure 3

Medication and insulin dose changes from baseline to 2 years for CCI and UC group completers. (A) Percent of completers taking diabetes medications, excluding metformin. (B) Mean ± SE prescribed insulin dose among baseline users. (C) Frequency of medication dosage and use change among prescribed users by diabetes medication class.

Figure 4

Adjusted mean changes from baseline to 2-years in the CCI group for (A) Weight (−10% relative to baseline, P = 8.8 × 10−28), (B) Central Abdominal Fat [CAF] (−15% relative to baseline, P = 1.6 × 10−21), (C) Systolic Blood Pressure (−4% relative to baseline, P = 2.4 × 10−6), (D) Diastolic Blood Pressure (−4% relative to baseline, P = 3.3 × 10−5) (E) Alanine aminotransferase [ALT] (−21% relative to baseline, P = 4.0 × 10−10), and (F) High sensitive C-reactive protein [hsCRP](−37% relative to baseline, P = 6.9 × 10−13).