A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes

Abstract

Background: Type 2 diabetes (T2D) is typically managed with a reduced fat diet plus glucose-lowering medications, the latter often promoting weight gain.

Objective: We evaluated whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of a comprehensive intervention, thereby improving glycemic control, decreasing medication use, and allowing clinically relevant weight loss.

Methods: This study was a nonrandomized, parallel arm, outpatient intervention. Adults with T2D (N=262; mean age 54, SD 8, years; mean body mass index 41, SD 8, kg·m^-2; 66.8% (175/262) women) were enrolled in an outpatient protocol providing intensive nutrition and behavioral counseling, digital coaching and education platform, and physician-guided medication management. A total of 238 participants completed the first 10 weeks. Body weight, capillary blood glucose, and beta-hydroxybutyrate (BOHB) levels were recorded daily using a mobile interface. Hemoglobin A_1c (HbA_1c) and related biomarkers of T2D were evaluated at baseline and 10-week follow-up.

Results: Baseline HbA_1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had an HbA_1c level of <6.5%. After 10 weeks, HbA_1c level was reduced by 1.0% (SD 1.1%; 95% CI 0.9% to 1.1%, P<.001), and the percentage of individuals with an HbA_1c level of <6.5% increased to 56.1% (147/262). The majority of participants (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10 weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced or eliminated. At follow-up, 47.7% of participants (125/262) achieved an HbA_1c level of <6.5% while taking metformin only (n=86) or no diabetes medications (n=39). Mean body mass reduction was 7.2% (SD 3.7%; 95% CI 5.8% to 7.7%, P<.001) from baseline (117, SD 26, kg). Mean BOHB over 10 weeks was 0.6 (SD 0.6) mmol·L^-1 indicating consistent carbohydrate restriction. Post hoc comparison of the remote versus on-site means of education revealed no effect of delivery method on change in HbA_1c (F_1,260=1.503, P=.22).

Conclusions: These initial results indicate that an individualized program delivered and supported remotely that incorporates nutritional ketosis can be highly effective in improving glycemic control and weight loss in adults with T2D while significantly decreasing medication use.

Keywords: Hb A1c; ketosis; mobile health; type 2 diabetes; weight loss.

Figure 1

Relative frequency distribution of participant weekly average beta-hydroxybutyrate (BOHB) concentrations. An observed weekly average BOHB concentration on the border of 2 bins is placed in the bin holding the larger values. Evidence of carbohydrate restriction exhibited by elevated ketones was present in the first week in the majority of subjects and maintained for the duration of the study. All reported BOHB concentrations greater than 3.0 were in participants taking a sodium-glucose cotransporter-2 inhibitor, except for one (4.4 mmol•L−1) in which we suspect elevated BOHB due to increased exercise and another (6.0 mmol•L−1) in which we suspect participant data entry error. Excluding this 1 value, average BOHB concentrations for this participant ranged from 0.4 to 1.4 mmol•L⁻¹.

Figure 2

Hemoglobin A1c (HbA1c) changes by baseline level. Error bars represent SD; the dotted line represents the threshold for diagnosis of type 2 diabetes. Significant reductions in HbA1c level from baseline to follow-up were observed in subjects whose baseline HbA1c level was ≥7.5% (mean 9.0%, SD 1.3% to 7.2%, SD 1.1%, P<.001) and between 6.5% and 7.4% (mean 6.9%, SD 0.3% to 6.2%, SD 0.5%, P<.001). For those whose baseline HbA1c level was <6.5%, HbA1c level was improved but not significantly after correcting for multiple comparisons (mean 6.1%, SD 0.3% to 5.8%, SD 0.4%, P=.03). *Represents significant difference from baseline.

Figure 3

Frequency of medication dose changes by drug class. Bars represent total users of each drug with the type of dose change (increase, no change, decrease, or elimination) stacked within the bar and the relative frequency noted next to each section. The total number of users is noted at the top of each bar. The proportion of participants who were prescribed the drug was significantly different between baseline and follow-up for insulin (χ2₁=21.4, P<.001), sulfonylureas (χ2₁=54.0, P<.001), and sodium-glucose cotranporter-2 (SGLT-2) inhibitors (χ2₁=17.9, P<.001) but not for dipeptidyl peptidase-4 (DPP-4) inhibitors (χ2₁=6.9, P=.009), thiazolidinediones (χ2₁=1.3, P=.25), glucagon-like peptide-1 (GLP-1) receptor agonists (χ2₁=0.5, P=.50), or metformin (χ2₁=0.8, P=.36).

Figure 4

Hemoglobin A1c (HbA1c) level at baseline and 10-11 weeks per change in insulin dosage. Insulin users who were able to eliminate or reduce their use of the drug also significantly reduced their HbA1c level (7.9%, SD 1.5%, to 6.6%, SD 0.9%, P<.001 and 8.8%, SD 1.8%, to 7.4%, SD 1.2%, P<.001, respectively). Six users with no change in insulin dose achieved a reduction in HbA1c level, although it was not statistically significant (8.2%, SD 1.8%, to 7.6%, SD 1.2%, P=.25). Despite an increased insulin dosage in 4 users, HbA1c level increased but the difference was not significant (8.3%, SD 0.4%, to 8.7%, SD 0.8%, P=.61).

Figure 5

Participant weight loss over 10 weeks. Part “a”—weight change over 10 weeks for all participants. Solid line represents the mean; dotted lines represent one standard deviation from the mean. Part “b”—individual body weight changes as percentage of starting body weight at 10 weeks for completers (n=238). Part “c”—individual body weight changes as percentage of starting body weight for each noncompleter at the time of removal from study. For the 21 dropouts, time to drop out was 6 (SD 3) weeks (n=3 participants are still enrolled in the study but did not complete 10-week follow-up testing).