The Effect Of Glucagon On Newly Diagnosed Type 2 Diabetes

Objective:To investigate the effect of Glucagon on newly diagnosed Type 2 Diabetes. To observethedynamic transformation of glucagon and insulin level after the treatment with phosphor-Sitagliptin in the patients with initial Type 2 diabetes.Methods : 50 patients with newly diagnosed Type 2 diabetes, Hb A1c≤10%,FBG≥7.0mmol/L, 2h PG≥11.1mmol/Lbut ≤20.0mmol/L, according to the diagnostic criteria recommended by WHO at 1999, were enrolled in this study. These patients didn’t receive any administrations of drugs(such as glucocorticoid, diuretic and b-receptor blocker), which might affect the insulin sensitivity and/or the metabolism of carbohydrates; and had no gastrointestinal diseases or never received gastrointestinal operations. 48 healthy controls without any endocrinal or metabolic diseases were also enrolled, their OGTT test was normal. All the subjects were asked to have no diets for 12 hours, the length, body weight and blood pressure were measured at next morning, venous blood was also collected for the measurement of renal function, and the levels of serum total cholesterol(TCL), triglyceride(TG), low-density lipoprotein cholesterol(LDL), high-density lipoprotein cholesterol(HDL). Healthy controls drunk 75 g glucose dissolved in 350 m L pure water in 5 minutes. Patients with diabetes ate 100 g standard diet; the venous blood was collected for the measurement of glucagon, blood glucose and insulin level before and 15, 30, 60, 90 and 120 min after diet respectively. Patients with diabetes were administrated with 100 mg phosphor-Sitagliptin(once per day). After 3 months, the patients ate 100 g standard diet; the venous blood was collected for the measurement of glucagon, blood glucose and insulin level before and 30, 60, 120 and 180 min after diet respectively. The data were presented as mean ± SD, SPSS 13.0 performed the statistical analysis. One-way ANOVA followed by Bonferroni post-hoc test was used for pair-wise multiple comparisons. Mann-Whitney test was used to compare two samples without equal variances. Significant difference was set at p< 0.05.Results:1) In the patients with diabetes, the glucose level after diet was obviously increased compared with normal controls [0h:(9.5±0.9)mmol/l vs(5.1±0.3)mmol/l, 30min:(10.1±0.9)mmol/l vs(6.3±0.3)mmol/l, 60min:(15.3±1.3)mmol/l vs(7.8±0.3)mmol/l,120min:(12.3±1.0)mmol/l vs(5.9±0.2)mmol/l, 180min:(8.7±0.7)mmol/l vs(4.7±0.1)mmol/l(P<0.05). The levels of glucagon in diabetic patients were obviously higher than normal controls [0h:(149.2±7.8)ng/l vs(132.3±4.3)ng/l,30min:(188.1±8.5)ng/l vs(112.7±3.6)ng/l, 60min:(204.6±10.3) ng/l vs(105.8±3.4)ng/l, 120min:(158.2±9.2)ng/l vs(121.5±3.8)ng/l, 180min:(142.1±9.0)ng/l vs(127.4±3.9)ng/l](P<0.05). The level of glucagon in diabetic patients were increased after glucose administration, the level at 60 min was obviously higher than limosis(P<0.05), the level at 180 min retuned to limosis level. The level of glucagon in normal control was slightly decreased after 60 min, after that the levels gradually increased, the level at 180 min was lower than limosis, but there were no differences among different timing points(P>0.05); Insulin levels of diabetic patients after glucose administration were obvious lower than normal controls [0h:(8.2±0.9)m U/l vs(7.0±0.8)m U/l,30min:(12.5±1.1)m U/l vs(53.3±3.5)m U/l,60min:(27.5±3.8)m U/l vs(68.2±3.8)m U/l,120min:(32.9±2.7)m U/l vs(28.3±1.9)m U/l,180min:(14.5±1.4)m U/l vs(19.0±1.0)m U/l](P< 0. 05 、 0. 01). Insulin level of diabetic patients increased slowly after glucose administration, the levels at 60 min and 120 min after diet were higher than limosis(P< 0. 05), the level at 180 min returned to 30 min; Insulin level of normal controls incrased rapidly after diet, and reached to the peak 60 min(P < 0. 01), the level at 180 min returned to limosis level. 2) The blood glucose level was dramatically decreased after the treatment with Sitagliptin in the diabetic patients [0h:(7.3±0.8)mmol/l vs(9.5±0.9)mmol/l, 30min(9.2±1.1)mmol/l vs(10.1±0.9)mmol/l,60min:(12.2±1.2)mmol/l vs(15.3±1.3)mmol/l, 120min:(10.7±0.9)mmol/l vs(12.3±1.0)mmol/l,180min:(7.1±0.7)mmol/l vs(8.7±0.7)mmol/l](P<0.05). The glucagon levels at different timing points after treatment were lower than before [0h:(141.8±6.6)ng/l vs(149.2±7.8)ng/l, 30min:(162.7±6.9)ng/l vs(188.1±8.5)ng/l,60min:(182.4±7.8)ng/l vs(204.6±10.3)ng/l, 120min:(147.9±7.0)ng/l vs(158.2±9.2)ng/l, 180 min :(133.5±7.3)ng/l vs(142.1±9.0)ng/l](P<0.05). Meanwhile, insulin level was obviously increased [0h:(8.9±1.0)m U/l vs(8.2±0.9)m U/l,30min:(17.5±1.2)m U/l vs(12.5±1.1)m U/l,60min:(33.8±1.2)m U/l vs(27.5±3.8)m U/l,120min:(48.5±1.5)m U/l vs(32.9±2.7)m U/l,180min:(16.7±1.9)m U/l vs(14.5±1.4)m U/l](p< 0.05). Conclusion:1) compared with normal controls, the patients with initial Type 2 diabetes have a higher glucagon level, and insulin level is obviously lower at different timing points with a delayed timing of peak value. These data imply that the dysfunctions of α and β cells induce unbalances of insulin and glucagons, which make pathophysiological roles in the initiation and development of high blood glucose in type 2 diabetes. 2) Treatment with Sitagliptin for 3 months can properly control blood glucose, and obviously improve the irregular secretions of insulin and glucagons, optimize the functions of α and βcells, which has benefit effects on the management of hyperglycaemia in clinic.