(P09-05-26) Sex- and Age-Stratified Effects of Carbohydrate Restriction on Lipoproteins and Postprandial Glycemic Responses

Objectives: Although free-sugar restricted and ketogenic diets can cause fat loss, they have divergent effects on lipoproteins and postprandial metabolism, which may vary by age and sex. We explored the changes in body composition, fasting lipoproteins, and postprandial insulin responses following free-sugar restricted and ketogenic diets by age and sex.

Methods: Exploratory analysis of a randomized trial of ketogenic (KD; < 8% carbohydrate) or low-free sugar (LS; < 5% free-sugar) diets in 35 participants (mean±SD BMI: 24.3±2.6 kg/m², age: 33±15 y) used baseline to week 4 changes in body fat, fasting biomarkers (BHB, LDL-C, total cholesterol, ApoB), and postprandial responses to a mixed-macronutrient test (incremental AUC glucose, insulin, C-peptide). Diet-group means were compared with unpaired t-tests and diet, subgroup [male (M) vs female (F), older (≥40y, O) vs younger (Y)], and diet:subgroup effects were tested via linear models with estimated marginal means.

Results: Mean (95% CI) fat loss was greater with KD [KD: -1.7 (-2.1 to -1.2), LS: -0.9 (-1.4 to -0.4) kg, P=0.02], with little evidence for sex- or age-specific effects (diet:sex P=0.08, diet:age P=0.4). Fasting LDL-C differed by diet [KD: 0.36 (0.11 to 0.60), LS: -0.29 (-0.55 to -0.04) mmol/L, P=0.001) increasing in males on KD [KD-F: 0.00 (-0.29 to 0.28), KD-M: 0.76 (0.45 to 1.06) mmol/L, diet:sex P=0.03]. Postprandial glucose increased more on KD [KD: 274 (200 to 347), LS: 69 (-21 to 159) mmol•min/L, P < 0.001] without significant diet:subgroup effects (P≥0.3). Postprandial C-peptide increased more on KD [KD: 140 (189 to 472), LS: -6 (-55 to 43) ng•min/mL, P=0.009], increasing more in older adults [KD-Y: 57 (-27 to 141), KD-O: 280 (171 to 389) ng•min/mL, diet:age P=0.01]. There was limited evidence for other diet:subgroup effects (all P≥0.09).

Conclusions: Four weeks of carbohydrate and free-sugar restriction may elicit sex-specific differences in fasting LDL-C and age-specific differences in postprandial C-peptide. Future studies should target lipoprotein profile and postprandial metabolism as potential targets for specifically-powered studies to investigate stratified nutrition recommendations.

Funding Sources: This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) within the National Institutes of Health (NIH).