Correlationships Between Fasting Glucagon,Glucagon/Insulin Ratio And Diabetic Duration Or Chronic Diabetic Complications In Type2Diabetes Patients

BackgroundGlucagon is an important hormone to induce glycemic up-regulation to counteract with insulin. Patients of type2diabetes (T2DM) generally manifest hyperglucagonemia whose glucagon secretion can’t be effectively repressed by glucose or insulin, which is one of the major mechansims for fasting or postprandial hyperglycemia. Until now, little articles are available concerning about the dynamics of blood glucagon concentration with the progression of diabetes duration and the correlationships between hyperglucagonemia and chronic diabetic complications.ObjectiveAnalyze the variation in fasting glucagon (FGLC) and fasting glucagon/insulin (FGLC/FINS) ratio of T2DM patients with different diabetic durations and the correlationships between FGLC, FGLC/FINS ratio and diabetes duration, glycemic control as well as chronic diabetic complications.Methods262T2DM patients separated into five groups by diabetes duration:<5years for group A;≧5years and<10years for group B;≧10years and<15years for group C;≧15years and<20years for group D;≧20years for group E. Collect and statistically analyze the fasting insulin (FINS), C peptide (FCP), FGLC, FGLC/FINS ratio, HOMA-IR, HOMA-β and other metabolic indexes of each group and expound their correlations with diabetes duration, fasting blood glucose (FBG) and glycosylated hemoglobin (HbAlc).Patients above separated into diabetic nephropathy (DN) group and non-diabetic nephropathy (N-DN) group, compare FGLC, FGLC/FINS ratio and other indexes of the two groups and analyze their correlationships with DN.Patients above separated into diabetic retinopathy (DR) group and non-diabetic retinopathy (N-DR) group, compare FGLC, FGLC/FINS ratio of the two groups and analyze their correlationships with DR.Patients above separated into diabetic peripheral neuropathy(DPN) group and non-diabetic peripheral neuropathy(N-DPN) group, compare FGLC, FGLC/FINS ratio and other indexes of the two groups and analyze their correlationships with DPN.Results1. Indexes that represent fasting beta cell function such as FINS, FCP and HOMA-β manifest downtrend among the A-E group and partial correlation shows they are negatively correlated with diabetic duration(r=-0.149,-0.318,-0.342; P=0.016,0.000,0.000). HOMA-IR of the five groups manifest no statistical difference and it is not correlated with diabetic duration. Fasting glucagon levels overall are not correlated with diabetic duration, but that of group A, B and C elevate in sequence (P<0.05) and are positively correlated with diabetes duration(r=0.333, P=0.000), whereas the fasting glucagon levels of group D and E are lower than group C (P<0.05) and are not correlated with diabetes duration. Fasting glucagon/insulin ratios of the A, B and C group also elevate in sequence (P<0.05), and the ratios of the D and E group are higher than the A and B group(P<0.05), close to the C group. Partial correlation shows FGLC/FINS ratio is positively correlated with diabetic duration(r=0.243, P=0.000).2. Partial correlation shows FBG and HbAlc are positively correlated with diabetic duration(r=0.250,0.138; P=0.000,0.026) and multiple stepwise regression analysis shows that FGLC or FGLC/FINS ratio is an important affecting factor of FBG (b’=1.090or0.260; P=0.000) and HbAlc(b’=0.576or0.147; P=0.000or0.028).3. The DN group manifests longer diabetic duration and higher FBG, FINS, HOMA-IR,FGLC,FGLC/FINS ratio than the N-DN group, and logistic regression analysis shows that FGLC or FGLC/FINS ratio is one of the risk factors of DN (OR=1.019or1.172; P=0.003or0.002)4. FGLC and FGLC/FINS ratio of the DR group and the N-DR group show no statistical difference (P>0.05) and logistic regression analysis does not show any correlationship between FGLC or FGLC/FINS ratio and DR.5. FGLC/FINS ratio of the DPN group is higher than the N-DPN group (P<0.05) but FGLC of the two groups show no statistical difference (P>0.05), and neither of the two indexes is the risk factor of DPN.Conclusions1. Fasting beta cell function of the T2DM patients attenuates with the progression of diabetic duration;2. Fasting glucagon concentration elevates with diabetes duration when the course of type2diabetes is less than15years and mildly reduces afterwards; glucagon/insulin ratio consistently elevates with the progress of diabetes duration; FGLC and FGLC/FINS ratio significantly affect the glycemia control of type2diabetes patients.3. FGLC or FGLC/FINS ratio is risk factor of DN and there is no correlationship between the two indexes and DR or DPN.