The effect of metformin and pioglitazone on glucagon of patients with diabetes and metabolic syndrome

Abstract

Objective To observe and evaluate the effects of metformin and pioglitazone on blood glucose, insulin, glucagon, β-cell function and insulin resistance among patients with diabetes and metabolic syndrome, so as to discuss the role of pancreatic α cells in pathogenesis of type 2 diabetes mainly caused by insulin resistance and the change of α-cell function after treatment. Methods A total of 60 patients diagnosed with diabetes and metabolic syndrome were selected in Beijing Chaoyang District Diabetes Center from April 2012 to April 2013 and divided with random number table into metformin group (treated with metformin 0.5 g orally thrice a day for 1 year, n=30) and pioglitazone group (treated with pioglitazone 15 mg orally once a day for 1 year, n=30). 30 normal healthy people who had physical examination at the Center during the same period were enrolled into the control group, matched in age and gender with the intervention groups. The general condition of the 3 groups, and blood levels of glucose, insulin, and glucagon, insulin sensitivity index (ISI)-Matsuda, homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function index (HOMA-β), 1-phase index, 2-phase index, and insulin secretion sensitivity index (ISSI) at baseline in the 3 groups and after treatment in the metformin group and the pioglitazone group were measured and calculated. Results Compared with the control group before treatment, the intervention groups as a whole had significantly higher fasting glucagon level [(146.22±25.41) pmol/L vs. (21.31±7.85) pmol/L, P=0.002] and area under curve (AUC) of glucagon [(469.84±13.12) pmol/(L·h) vs. (100.94±7.73) pmol/(L·h), P=0.006]. Compared with the results before treatment, the metformin group exhibited significantly reduced fasting glucose [(6.46±1.38) mmol/L vs. (7.54±0.43) mmol/L, P=0.031], fasting insulin [(119.22±69.01) pmol/L vs. (139.38±71.13) pmol/L, P=0.042], fasting glucagon [(91.69±22.11) pmol/L vs. (142.81±24.56) pmol/L, P=0.029], AUC of glucose [(25.19±1.31) mmol/(L·h) vs. (32.68±1.12) mmol/(L·h), P=0.043], AUC of insulin [(468.65±20.10) pmol/(L·h) vs. (786.32±21.37) pmol/(L·h), P=0.017], and AUC of glucagon [(280.60±8.26) pmol/(L·h) vs. (487.14±14.31) pmol/(L·h), P=0.032]; while the pioglitazone group after treatment also showed significantly decreased fasting glucose [(6.58±2.21) mmol/L vs. (7.68±0.59) mmol/L, P=0.028], fasting insulin [(107.92±17.81) pmol/L vs. (144.66±74.43) pmol/L, P=0.033], fasting glucagon [(76.07±20.57) pmol/L vs. (148.34±28.94) pmol/L, P=0.025], AUC of glucose [(25.58±1.22) mmol/(L·h) vs. (35.07±1.38) mmol/(L·h), P=0.038], AUC of insulin [(435.54±19.30) pmol/(L·h) vs. (854.75±20.61) pmol/(L·h), P=0.013], and AUC of glucagon [(223.43±5.83) pmol/(L·h) vs. (458.55±12.96) pmol/(L·h), P=0.026]. The before-after-treatment differences were significantly smaller in the metformin group than in the pioglitazone group in terms of fasting insulin [(20.16±2.98) mmol/L vs. (36.74±2.88) mmol/L, P=0.011], fasting glucagon [(51.12±3.67) pmol/L vs. (72.27±4.58) pmol/L, P=0.016], AUC of insulin [(317.67±13.45) pmol/(L·h) vs. (419.21±15.44) pmol/(L·h), P=0.031] and AUC of glucagon [(206.54±9.66) pmol/(L·h) vs. (235.12±10.29) pmol/(L·h), P=0.046]. Conclusions Glucagon in patients with diabetes and metabolic syndrome is higher than that in normal individuals. Metformin and pioglitazone can decrease the level of glucagon in patients with metabolic syndrome and diabetes as well as improve the glucose control, β-cell function and insulin resistance, suggesting improving effect of these two drugs on α-cell function. Pioglitazone manifests a stronger effect than metformin does. Key words: Metformin; Pioglitazone; Glucagon; Insulin