Glycemic variability in insulin treated type 2 diabetes with well-controlled hemoglobin A1c and its response to further treatment with acarbose

Background Glycemic variability, an HbA1c-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus （T2DM） with HbA1c<6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose. Methods Eighty-six T2DM patients who used premixed insulin analogue （insulin aspart 30） twice daily and had HbA1c <6.5% and 20 controlled subjects with normal glucose regulation （NGR） were monitored using the continuous glucose monitoring （CGM） system. The mean amplitude of glycemic excursions （MAGE）, mean of daily differences （MODD） were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level<3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups: low-MAGE group with MAGE<3.4 mmol/L （L-MAGE） and high-MAGE group with MAGE >3.4 mmol/L （H-MAGE）. H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system. Results After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR （P<0.01）. Twenty-four percent （n=11） in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% （n=2） in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night （hypoglycemic events: 24% vs. 5%, x=640, P<0.01）. MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value （r=-0.32 and 0.26, respectively, P<0.05）. After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased （40%, P<0.01, and 15%, P<0.05, respectively）, but remained higher than in the subjects with NGR （P<0.05）; 2% （n=1） had a total of 1 hypoglycemic event, incidence significantly decreased （2% vs. 24%, x=9.61, P<0.01）. Conclusions CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbA1c in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.