Comparison of the Ketogenic Ratio of Macronutrients With the Low-Carbohydrate Diet Score and Their Association With Risk of Type 2 Diabetes in Postmenopausal Women: A Secondary Analysis of the Women's Health Initiative

Background: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD Score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown.

Objective: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD Score, and evaluate their association with type 2 diabetes mellitus (T2DM).

Design: Secondary analysis of the Women's Health Initiative with 17.9 ± 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9 × grams fat + 0.46 × grams protein) / (0.1 × grams fat + 0.58 × grams protein + grams net carbohydrate), a value ≥1.5 is the minimum threshold for a ketogenic diet.

Participants/setting: One hundred twenty-five nine hundred eighty-two postmenopausal women without diabetes (aged 50 to 79 years) enrolled in the multicenter Women's Health Initiative observational study and clinical trials were included.

Main Outcome Measures: Risk of self-reported incident T2DM.

Statistical Analyses Performed: Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, Women's Health Initiative study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios and 95% CIs for T2DM among quintiles of the ketogenic ratio.

Results: A total of 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28 to 0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the hazard ratio for diabetes was 1.24 (95% CI 1.18 to 1.31; P < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the hazard ratio for diabetes was 1.36 (95% CI 1.29 to 1.43; P < 0.001) for the LCD Score and 1.13 (95% CI 1.07 to 1.19; P < 0.001) for the simplified ketogenic ratio in fully adjusted models.

Conclusions: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD Scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM.