2.1. Subjects and grouping

Patients with newly diagnosed T2DM (n = 108, defined as diagnosis within the previous 6 months) were consecutively enrolled for this prospective study from January 2015 to December 2015. The inclusion criteria were the following: age >18 years; newly diagnosed T2DM; and HbA1c between 9% and 11%. Patients with acute diabetic complications such as diabetic ketoacidosis or severe heart, liver, or kidney dysfunction were excluded. All patients provided written informed consent before participation.

The 108 patients were assigned to 2 groups to receive either intensive insulin therapy or OHAs (IIT and OHA, respectively) by using computer-generated random numbers. All patients were initially hospitalized for 2 weeks, and then discharged and followed up in outpatient clinics. The blood glucose was checked 7 to 8 times during hospitalization and 4 to 5 times after discharge by self-monitoring blood glucose.

Patients in the IIT group were administered intensive BIT (rapid-acting insulin analogs at 3 meals + insulin glargine at bedtime) + metformin 0.5 g tid, for 12 weeks. Patients in the OHA group received metformin 0.5 g tid + gliclazide sustained-release tablets (60–120 mg daily), with acarbose (50–100 mg tid), if the postprandial glucose reached >10 mmol/L, or pioglitazone 15 to 30 mg qd for body mass index >25 kg/m², for 12 weeks. The dose of OHAs or insulin was adjusted every 3 days to achieve or maintain within the following glycemic ranges: fasting glucose 4.4 to 6.1 mmol/L and postprandial glucose level 4.4 to 7.8 mmol/L. Remission was defined as achievement of target glycemic goal (HbA1c <7%) without use of hypoglycemic agents, lasting >6 months.

After 12 weeks, patients in the IIT group discontinued the insulin and were maintained on metformin; the patients were treated with other hypoglycemic agents (gliclazide sustained-release tablets 60–120 mg daily, with or without acarbose 50–100 mg tid, pioglitazone 15 mg qd). Patients in the OHA group remained with the original regimen. No lipid-lowering agents were used in either group. In the course of follow-up, OHAs were adjusted to maintain the glycemic goal. The patients discontinued the hypoglycemic agents and were encouraged with dietary and physical activity intervention for glycemic control, if they achieved the glycemic goal for more than 1 month on 2 or fewer hypoglycemic agents.

Thirty normal healthy volunteers were enrolled as the control group.