The global prevalence of diabetes is increasing, with differing rates between men and women. Discrepancies in the literature regarding sex differences in postprandial glucose metabolism are likely due to heterogeneous study protocols and insufficient control of confounding factors such as age, body composition, and physical activity level. These factors significantly influence daily energy expenditure, making it crucial to consider individual energy needs when designing studies on glucose metabolism. Previous studies using fixed carbohydrate amounts or body weight normalization for meal size have yielded conflicting results due to lack of control for confounders. This study aimed to investigate sex differences in glucose metabolism after a balanced mixed meal normalized to each participant's daily energy expenditure, thereby controlling for several confounding factors.

Existing research on sex differences in postprandial glucose metabolism is inconsistent, largely due to variations in methodologies and insufficient control over confounding factors. Some studies using ad libitum caloric intake or fixed carbohydrate amounts showed higher postprandial glucose levels in women. Others, normalizing meals by body weight, also found differences. However, these approaches fail to account for crucial confounders like body composition, age, and physical activity, which significantly impact energy expenditure and glucose metabolism. The lack of studies using a meal size normalized to individual daily energy expenditure highlights the need for a more controlled approach.

Thirty-six healthy young adults (18 men, 18 women; age 18-35 years; normal weight) were recruited. After a standardized dinner the previous evening, participants arrived fasting and had an intravenous catheter inserted. Resting energy expenditure was estimated using the Harris-Benedict equation and multiplied by a physical activity level factor to determine individual daily energy expenditure. A balanced mixed meal (60% carbohydrates, 25% lipids, 15% proteins) providing 40% of the individual's daily energy expenditure was administered. Blood samples were drawn at 0, 10, 20, 30, 45, 60, 90, 120, and 180 minutes post-meal to measure serum glucose, insulin, and C-peptide. Anthropometric measurements (weight, height, waist circumference, skinfolds), abdominal ultrasound (SAT, VAT), and physical activity levels (IPAQ) were also collected. Statistical analysis involved t-tests or rank-sum tests for descriptive variables and linear mixed models to assess the effect of sex, time, and sex-time interaction on postprandial glucose, insulin, and C-peptide concentrations. Area under the curve (AUC) analysis was also performed.

Men and women did not differ significantly in age or BMI. However, men had larger waist circumferences and lower body fat percentages than women. As expected, men had greater daily energy expenditure than women. While fasting glucose was lower in women (83 ± 7 mg/dl) compared to men (89 ± 5 mg/dl, P=0.007), there were no significant differences in fasting insulin or C-peptide levels. Linear mixed models revealed no significant effect of sex or sex-time interaction on postprandial glucose, insulin, or C-peptide. Time was the only significant factor influencing these parameters. Postprandial glucose increased significantly at 20 minutes, peaking around 30-45 minutes, and then returning to baseline within 2 hours. Insulin and C-peptide also increased significantly postprandial, with insulin peaking slightly later in women (P=0.068). AUC analysis also demonstrated no significant differences in glucose, insulin, or C-peptide responses between sexes. Percentage changes from baseline also showed no significant differences between men and women for all parameters.

This study's novel approach, normalizing meal size to individual daily energy expenditure, provides compelling evidence against a sexual dimorphism in postprandial glucose metabolism in healthy young adults. Contrary to previous studies employing fixed carbohydrate loads or body weight normalization, which reported higher postprandial glucose in women, this study found no sex-based differences. The normalization method effectively controlled for confounding factors like body composition and physical activity, revealing the true metabolic response to an isocaloric, physiological meal. The similar postprandial insulin and C-peptide responses further support this finding. The results suggest that observed sex differences in previous studies may be attributed to variations in carbohydrate load relative to individual metabolic needs rather than an inherent sexual dimorphism in glucose regulation.

This study demonstrates that when controlling for individual daily energy expenditure, there is no significant difference in postprandial glucose, insulin, and C-peptide responses between men and women. This challenges previous findings suggesting a sexual dimorphism in carbohydrate metabolism and has important implications for diabetes prevention and management strategies. Further research is warranted in older populations to determine if these findings generalize across age groups.

The study's limitations include the use of predictive formulas for daily energy expenditure, although a recent study validates the accuracy of the Harris-Benedict formula in normal weight individuals. The relatively narrow age range (18-35 years) limits generalizability to other age groups. The exclusion of women using oral contraceptives and the focus on the follicular phase for female participants might influence results. The study did not investigate the role of sex hormones or other factors such as gastric emptying, gut hormones, and pancreatic function.