| Objective To investigate whether the degree of blood glucose fluctuations in brittle diabetic patients correlates with enteroglucagon levels.Methods Thirteen patients with brittle diabetes were included in this study as study subjects and were controlled with 14 patients with general type 1 diabetes and 10 healthy subjects.The mean glucose fluctuation amplitude(MAGE)of diabetic patients was measured by ambulatory glucose monitoring.All subjects had serum Cpeptide levels,serum total glucagon-like peptide-1(GLP-1),and gastric inhibitory peptide(GIP)measured by the bun meal test at scores 0,60,and 120,and the stools of the study subjects were analyzed by 16S rDNA amplicon sequencing using the Illumina NovaSeq 6000 sequencing platform for comparison between the three groups.Result1.Islet Function:Compared with the area under the C-peptide curve(AUCC-P)in the control group(CTR group)(3357 ± 817.5 pmol/L),AUCC-P was reduced in patients in both the fragile diabetes group(B-T1DM group)(258.9±58.2 pmol/L)and the general type 1 diabetes group(G-T1DM group)(375.4±95.7 pmol/L)(P<0.05),while the B-T1DM group compared to the G-T1DM group showed no significant difference between them(P>0.05).2.Blood Glucose Fluctuation:MAGE was significantly greater in the B-T1DM group(8.92± 1.80 mmol/L)compared with the G-T1DM group(6.50± 1.95 mmol/L)(P=0.003).3.Incretin.(1)GLP-1:The area under the GLP-1 curve(AUCGLP-1)of patients in the BT1DM group(23.54 ± 2.65 pmol/L)was lower than that in the CTR group(27.85 ± 2.43 pmol/L),with a statistical difference(P<0.0001),and the AUC GLP-1 of the G-T1DM group(26.79±2.02 pmol/L)was lower compared with that of the control group although there was a decrease but no statistical difference(P>0.05),and AUC GLP-1was significantly decreased in the BT1DM group compared with the G-T1DM group(P=0.001).(2)GIP::The area under the GIP curve(AUCGIP)of patients in the B-T1DM group(648.38±160.30 pg/ml)was lower than that of the CTR group(933.89±169.24 pg/ml),which was statistically different(P<0.0001),and the AUC GIP of the G-T1DM group(895.00±158.36 pg/ml)compared to the control group had decreased without statistical significance(P>0.05),and AUC GIP in the B-T1DM group was significantly decreased compared with the G-T1DM group(P<0.0001).4.Blautia abundance:compared to the control group(3.8881 ±0.2730),Blautia abundance was significantly lower in patients in the B-T1DM group(3.203 9± 0.4510)(P=0.0001),the relative abundance of Blautia in the G-T1DM group(3.6249±0.2609)was significantly lower compared to the CTR group(P=0.0260),and significantly decreased in the B-T1DM group compared to the GT1DM group(P=0.0033).5.Correlation analysis of Blautia,enterostatin and blood glucose fluctuations:Blautia abundance was significantly positively correlated with enterostatin AUC GLP-1 and AUC GIP(correlation coefficient values were r=0.449 and r=0.441,respectively);AUC GLP-Land AUC GIP were significantly negatively correlated with MAGE(correlation coefficient values were r=-0.420 and r=-0.410,respectively);Blautia abundance was significantly negatively correlated with MAGE(r=-0.408).0.420,r=-0.410);Blautia abundance was significantly negatively correlated with MAGE(r=-0.408).6.Mediation Effects:AUC GLP-1 mediates significantly,Blautia bacteria in affecting blood glucose fluctuations in patients with brittle diabetes is partly through AUC GLP-1,and this correlation is negative,correlation model:blood glucose fluctuations=16.475-0.109*Blautia bacteria abundance-0.332*AUC GLP-1Conclusion1.Enteroglucagon GLP-1 secretion levels and GIP secretion levels were significantly lower in patients with fragile diabetes compared to healthy controls and patients in the general type 1 diabetes group.2.The increased magnitude of blood glucose fluctuations in patients with fragile diabetes may be related to reduced intestinal GLP-1 secretion due to reduced abundance of Blautia intestinalis. |
