Akkermansia muciniphila is Negatively Correlated with Hemoglobin A1c in Refractory Diabetes

Patients with refractory diabetes are defined as type 2 diabetes (T2D) patients; they cannot achieve optimal glycemic control and exhibit persistent elevations of hemoglobin A1c (HbA1c) ≥8% while on appropriate therapy. Hyperglycemia can lead to severe microvascular/macrovascular complications. However, in contrast to T2D, few studies have focused specifically on the gut microbiota in refractory diabetes. To examine this issue, we recruited 79 subjects with T2D and refractory diabetes (RT2D), and all subjects received standard therapy with Metformin or other hypoglycemic agents with or without insulin for at least one year. The α-diversity displayed no significant difference, whereas the β-diversity showed a marginal significance (p = 0.054) between T2D and RT2D. The evaluation of taxonomic indices revealed reductions in both Akkermansia muciniphila and Fusobacterium and a corresponding enrichment of Bacteroides vulgatus, Veillonella denticariosi among those with RT2D. These microbial markers distinguished RT2D from T2D with an acceptable degree of discrimination (area under the curve (AUC) = 0.719, p < 0.01) and were involved in several glucose-related functional pathways. Furthermore, the relative abundance of Akkermansia muciniphila was negatively correlated with HbA1c. Our combined results reveal unique features of the gut microbiota in RT2D and suggest that the evaluation of the gut microbiota could provide insights into the mechanisms underlying glycemic control and the impact of therapeutic modalities in patients with RT2D.