| OBJECTIVE: Diabetes mellitus is a group of metabolic diseases caused by a variety of pathogenetic factors and characterized by chronic hyperglycemia.Long-term hyperglycemia can damage multiple systems,leading to chronic progressive lesions in the eyes,kidneys,nerves,heart,blood vessels and other tissues and organs.Macrovascular complications are common chronic complication of diabetes mellitus,resulting in cardiovascular death accounting for 80% of the total mortality of type 2diabetes mellitus(T2DM).The pathological changes of macrovascular complications are atherosclerosis,which starts from the intima.Endothelial dysfunction leads to increased secretion of inflammatory factors and adhesion molecules,increased permeability,formation of a large number of foam cells,proliferation of smooth muscle cells,and increase of collagen fibers,resulting in thickening and hardness of the intima.As the disease progresses,focal thickening of the intima,hyaline degeneration of collagen fibers,necrosis of foam cells,deposition of necrotic materials and lipids,and even calcification may occur,forming atheromatous plaques.Arterial intima-media thickness is a recognized evaluation indicator of early atherosclerosis and a predictor of atherosclerotic cardiovascular disease(ASCVD).Impaired inhibition of glucagon secretion is an important part of the pathogenesis of diabetes,and glucagon plays a key role in maintaining glycolipid homeostasis,energy metabolism and weight control,and coagulation-fibrinolysis balance.In this study,we compare the level of fasting serum glucagon in different carotid intima-media thickness conditions and analyze the correlation between the glucagon and risk factors of atherosclerosis and carotidintima-media thickness,aiming to explore the relationship between atherosclerosis and glucagon in T2DM and to provide new ideas for prediction and intervention of ASCVD with T2DM.PARTICIPANTS AND METHODS: T2DM was diagnosed according to the 1999 WHO diagnosis and classification criteria;age ?18 years;without acute complication of diabetic ketoacidosis,hyperosmolar hyperglycemia syndrome,hypoglycemia coma,etc.within 3 months;without acute myocardial infarction,stroke,peripheral vascular occlusion and other acute ASCVD and/or thrombolysis,stenting,coronary artery bypass grafting and other revascularization treatment within 3 months;without serious infections,surgery,trauma and other stress conditions within 1 month;without hypercortisolism,acromegaly and other endocrine diseases affecting glucose metabolism;without history of anticoagulant drugs.The participants were divided into two groups according to the level of carotid intima-media thickness(CIMT): The CIMT thickening group was defined as those with CIMT? 1.0mm and / or atherosclerotic plaque,and the CIMT normal group was defined as those with CIMT<1.0mm.Gender,age,course of diabetes,smoking history and history of hypertension were recorded.Waist circumference,height,weight and blood pressure were measured.Venous blood was collected from the elbow in the fasting state to measure serum glucagon(Glc),C peptide(CP),fasting plasma glucose(FPG),glycated hemoglobin A1c(Hb A1c),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),Low density lipoprotein cholesterol(LDL-C),triglyceride(TG),lipoprotein a(Lp a).The Doppler ultrasonography of cervical vessels was performed by professional technicians.The mean value of carotid medial media thickness about 1 cm from the distal side of the bilateral carotid sinus was calculated for 3 consecutive cardiac cycles,and the maximum value of was recorded as CIMT.Calculate the body mass index(BMI),fasting serum glucagon-to-C peptide ratio(GCR).The differences of parameters between the normal CIMT group and the thickening group were compared,and the differences of parameters among the GCR quartile groups,to study the correlation between parameters and GCR,and to analyze the influencing factors of theCIMT.RESULTS: A total of 202 patients with T2DM were recruited,including 161 in the CIMT thickening group and 41 in the CIMT normal group.1.Compared with the CIMT normal group,the CIMT thickening group had a higher proportion of males(65.8% vs 48.8%,P = 0.034),more smokers(50.3% vs29.3%,P = 0.017),more patients with hypertension(60.9% vs 31.7%,P = 0.001),elder age(61.68 10.45),older age(49.05 10.44),and longer duration of diabetes(10(6 ~ 18)years vs.9(3 ~ 13.5)years.P = 0.012],systolic blood pressure was higher [138(130 ~150)mm Hg vs.135(123 ~ 143)mm Hg,P = 0.049],fasting serum GCR was higher[80.65(53.68 ~ 132.77)vs.56.85(35.10 ~ 93.38),P = 0.013],and fasting C-peptide level was lower [1.42(0.93 ~ 2.03)ng/ml vs.2.18(1.30 ~ 2.98)ng/ml,P = 0.001].There were no significant differences in waist circumference,BMI,diastolic blood pressure,Hb A1 c,FPG,TC,HDL-C,LDL-C,Lp a and fasting serum glucagon level between the two groups(P>0.05).2.All patients were divided into groups Q1,Q2,Q3 and Q4 according to the quartile of fasting serum GCR from low to high.BMI and TG decreased as GCR increased(P =0.001,P = 0.001),and Hb A1 c and CIMT increased as GCR increased(P = 0.013,P =0.007)(table 2).Gender distribution,proportion of smokers,proportion of patients with hypertension,age,duration of T2DM,waist circumference,systolic blood pressure,diastolic blood pressure,FPG,TC,HDL-C,LDL-C,Lp a,and plaque formation ratio showed no statistical significance(P > 0.05).3.A linear correlation analysis was performed between fasting serum GCR and all clinical data.GCR was positively correlated with duration(r = 0.222,P = 0.001),Hb A1c(r = 0.225,P = 0.001),HDL-C(r = 0.162,P = 0.021),CIMT(r = 0.241,P =0.001),and plaque formation(r = 0.170,P = 0.030).And GCR was negatively correlated with waist circumference(r =-0.147,P = 0.036),BMI(r =-0.242,P = 0.001),TG(r =-0.260,P < 0.001).GCR had no correlation with gender,smoking,hypertension,age,systolic blood pressure,diastolic blood pressure,FPG,TC,LDL-C,Lp a(P > 0.05).4.A linear correlation analysis was performed between CIMT and all clinical data.CIMT was positively correlated with male(r =-0.154,P = 0.029),smoking(r = 0.162,P= 0.022),hypertension(r = 0.258,P < 0.001),age(r = 0.371,P < 0.001),duration(r =0.185,P = 0.009),SBP(r = 0.159,P = 0.024),and fasting serum GCR(r = 0.241,P =0.001).And it was negatively correlated with female(r =-0.154,P = 0.029)and TG(r=-0.274,P < 0.001).CIMT had no correlation with waist circumference,BMI,diastolic blood pressure,Hb A1 c,FPG,TC,HDL-C,LDL-C,Lp a,level of fasting serum glucagon(P > 0.05).5.Binary logistic regression analysis was performed with CIMT thickening or not as the result variable and gender(female),smoking,age,duration of disease,BMI,systolic blood pressure,Hb A1 c,fasting serum GCR,HDL-C,and TG as independent variables.The results showed that gender,age,systolic blood pressure and GCR had significant influence on CIMT,among which age [OR = 1.224(95% CI: 1.131~1.324),P <0.001],SBP [OR = 1.036(95% CI: 1.002)~1.072),P = 0.038],GCR [OR = 1.011(95% CI: 1.001~1.022),P = 0.032] is a risk factor and women [OR = 0.075(95% CI:0.013 to 0.430),P = 0.004)] is a protective factor.CONCLUSIONS: Fasting serum GCR is significantly elevated in CIMT-thickened T2DM patients,and there is no difference in glucagon level between the two groups.CIMT increases with increasing GCR and it has no correlation with glucagon level.GCR is positively associated with CIMT and is an independent risk factor for CIMT thickening.Fasting serum GCR may be a predictor of subclinical atherosclerosis in patients with T2DM. |
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