Effects of a Low-Carbohydrate Dietary Intervention on Hemoglobin A(1c): A Randomized Clinical Trial

IMPORTANCE: Low-carbohydrate diets decrease hemoglobin A(1c) (HbA(1c)) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA(1c) among individuals with HbA(1c) in the range of prediabetes to diabetes not treated by diabetes medications is limited. OBJECTIVE: To study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA(1c) among individuals with elevated untreated HbA(1c). DESIGN, SETTING, AND PARTICIPANTS: This 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA(1c) of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022. INTERVENTIONS: Participants were randomized to a low-carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. The low-carbohydrate diet group received dietary counseling. MAIN OUTCOMES AND MEASURES: Six-month change in HbA(1c) was the primary outcome. Outcomes were measured at 0, 3, and 6 months. RESULTS: Of 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA(1c) was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA(1c) (net difference, –0.23%; 95% CI, –0.32% to –0.14%; P < .001), fasting plasma glucose (–10.3 mg/dL; 95% CI, –15.6 to –4.9 mg/dL; P < .001), and body weight (–5.9 kg; 95% CI, –7.4 to –4.4 kg; P < .001). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA(1c) not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03675360