Whole Body Production of Butyrate, but Not of Acetate or Propionate, Is Reduced in Adults With Prediabetes

OBJECTIVES: According to the CDC, 38% of the adult US population have prediabetes. Previous studies reported a reduced abundance of butyrate producing bacteria in the colon of participants with prediabetes, potentially contributing to the progression to Type 2 Diabetes. We now studied whether the whole body production of short-chain fatty acids (SCFA: acetate, propionate, butyrate) are altered in middle aged/older adults with prediabetes. METHODS: We measured SCFA kinetics in 12 prediabetic (fasting glucose: 5.7–6.5 mM) and 25 healthy (fasting glucose < 5.7 mM) subjects, 40 years or older. In the fasted state, a pulse containing acetate[(13)C(2)], propionate[1-(13)C] and butyrate[1-13C] was administered intravenously while blood was sampled 4 times over a 30 min period. We measured tracer enrichments in plasma by GC-MS, whole body SCFA production from the area under the curve (AUC) and statistics by ANCOVA corrected for age, sex, and lean body mass as covariates with significance set at P< 0.05 and results expressed as means [95% CI]. RESULTS: The prediabetic subjects had a lower butyrate WBP (362 [270, 454] vs. 534 [403, 665] μmol/h, P = 0.021) while acetate WBP (18996 [15270, 23631] vs. 17431 [13478, 22544] μmol/h, P = 0.6049) and propionate WBP (1250 [1041, 1459] vs. 1322 [1053, 1590] μmol/h, P = 0.6624) were comparable. Plasma SCFA concentrations did not differ between the groups (all P >0.05). CONCLUSIONS: The reduced whole body production of butyrate observed in the prediabetic middle aged/older adults is probably related to the altered colonic bacterial composition. More research is required whether specific nutritional modulation of the colonic bacterial composition (e.g. fiber supplementation) is able to restore the butyrate WBP and can improve glucose control in adults with prediabetes. FUNDING SOURCES: None