Sex-specific associations of serum short-chain fatty acids with glycaemic control: An Italian cross-sectional study in adults with type 1 diabetes

Objective: Short-chain fatty acids (SCFA) play a role in modulating glucose metabolism and are influenced by diet. Alterations in the SCFA-producing microbial ecosystem in individuals with type 1 diabetes (T1D) may contribute to impaired glycaemic control. This study investigated the relationships between serum SCFA levels, blood glucose control, and dietary habits in adults with T1D. Design: Observational study. Setting: The study was conducted at the diabetes outpatient clinic of Federico II University Teaching Hospital, Naples, Italy. Population: The study included 198 adults with T1D (100 men and 98 women), aged 18-79 years. Main outcome measures: Serum SCFA levels, blood glucose control, assessed by glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics, and dietary intake from a 7-day food record. Results: SCFA levels showed significant sex-specific differences (p<0.05). Therefore, to evaluate relationships between SCFA levels, glycaemic control and dietary habits, SCFA levels were categorised into sex-specific tertiles, and results were adjusted for age and body mass index. HbA1c and CGM metrics did not vary significantly across tertiles of acetate and butyrate. However, in women, higher propionate levels were associated with better glycaemic control, reflected by a greater percentage of glucose time-in-range (70-180 mg/dL) (66.2±12.3% vs 56.9±16.7%, low tertile; p=0.014), lower time-above-range (>180 mg/dL) (32.2±12.6% vs 41.2±17.2%, low tertile; p=0.011) and improved glucose management indicator (7.1±0.6% vs 7.5±0.6%, low tertile; p=0.027). Regarding eating habits, higher acetate tertiles were associated with higher intakes of total fat (p=0.041), polyunsaturated fatty acids (p=0.049) and monounsaturated fatty acids (p=0.021) in men only. Conclusion: These findings reveal a sex-specific association between serum propionate levels and blood glucose control in women with T1D. Importantly, this relationship appears independent of dietary factors. Trial registration number: NCT05936242.