Ketogenic Ratio of Macronutrients and Risk of Diabetes Among Postmenopausal Women

Abstract

Abstract Objectives To evaluate the association of the ketogenic ratio of macronutrients (KR) with incidence of diabetes (DM). Methods Dietary information was obtained at baseline from postmenopausal women enrolled in the Women's Health Initiative (WHI) clinical trials (not including the intervention arm of dietary modification trial) and observational study. Participants were excluded if they had prevalent diabetes or unknown status of diabetes at baseline or reported energy intakes <600 or >5000 kilocalories. The KR was calculated as follows: (0.9*grams fat + 0.46*grams protein) divided by (0.1*grams fat + 0.58*grams protein + grams total carbohydrate – grams total fiber). A KR value 1.5 is considered the minimum threshold to predict a ketogenic diet. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between KR and risk of DM. Follow-up time was the number of days from enrollment to the first instance of incident DM. Results Among 128 752 participants, there were 19 439 incident cases of DM with median follow-up time of 20.7 years. The median KR was 0.36 and 12 participants (<0.0001%) exceeded the KR threshold for a ketogenic diet. After adjustment for age, race/ethnicity, comorbidities, education, income, marital status, health insurance, smoking, DM family history, hormone use, energy intake, HEI scores, physical activity, region, and WHI arm, each KR quintile was associated with increased risk of DM. Comparing extreme quintiles of KR, the adjusted HR (95% CI) for diabetes was 1.32 (1.26–1.39; Ptrend < 0.0001). The association remained significant after further adjustment for BMI, with an adjusted HR (95% CI) of 1.22 (1.16–1.29; Ptrend < 0.0001) comparing the highest with lowest quintile of KR. We were unable to show an association of exceeding the KR threshold with DM due to the small number of participants who exceeded the KR threshold. Conclusions The KR was positively associated with incidence of DM. However, we are unable to draw conclusions about ketogenic diets because the majority of participants were below the KR threshold for a ketogenic diet. Funding Sources This work was supported by the Fraternal Order of Eagles Diabetes Research Center with funding from the National Institutes of Diabetes and Digestive and Kidney Diseases.