Short-term Intensive Therapy in Newly Diagnosed Type 2 Diabetes Partially Restores Both Insulin Sensitivity and Beta-Cell Function in Subjects With Long-term Remission
Hu Y, Li L, Xu Y, et al.
Diabetes Care. 2011;34:1848-1853
The goal of this Chinese study was to examine the effect of intensive glycemic control therapy (IT) on insulin sensitivity and beta-cell function in newly diagnosed type 2 diabetic patients compared with persons with normal glucose tolerance (NGT) and those with impaired glucose tolerance (IGT). Investigators assigned 48 newly diagnosed type 2 diabetic patients to IT (continuous subcutaneous insulin infusion, multiple daily injections, or oral hypoglycemic agents) with the goal of achieving fasting plasma glucose (FPG) < 6.1 mmol/L (110 mg/dL) and postprandial glucose (PPG) < 8.0 mmol/L (144 mg/dL). Treatments were maintained for 2 weeks after the target was achieved, and patients were followed for 1 year. Hyperglycemia relapse was defined as FPG > 7.0 mmol/L (126 mg/dL) or PPG > 11.0 mmol/L (198 mg/dL). Patients who maintained optimal glycemic control for at least 12 months without medication were defined as being in remission, and those who relapsed during the 1-year follow-up were defined as nonremission. Those in remission received no medication, whereas the relapsed patients resumed oral hyperglycemic agents or IT during the 1-year follow-up period. Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-beta) and the disposition index.
After short-term IT, 21 of 48 newly diagnosed type 2 diabetic patients (44%) achieved remission for 1 year, and 27 patients had relapsed (nonremission). There were no apparent differences in therapeutic effectiveness among the 3 different therapies. Before IT, HOMA-IR in both remission (3.12 ± 1.4 [mean +/= SD]) and nonremission (2.70 ± 1.7) groups was significantly higher than that in IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) persons. After IT, HOMA-IR in the remission group after treatment (1.72 ± 0.8) and at 1 year (2.12 ± 1.3) was comparable with that in IGT and NGT groups (P > .05). However, in the nonremission group, HOMA-IR was reduced from 2.70 ± 1.7 before IT to 2.34 ± 1.4 immediately after IT and to 2.60 ± 1.9 at the 1-year follow-up. IT restored more HOMA-beta in the remission group (44.6 [95% CI, 32.1-69.1] after therapy; 51.9 [28.8-79.8] at 1 year) than in the nonremission group (26.5 [14.9-43.8] after therapy; 31.9 [18.8-52.7] at 1 year). Although more restoration of HOMA-beta was observed in the remission group than in the nonremission group, there was no statistical difference. Disposition index in the remission group was significantly higher than that in the nonremission group after IT and at 1 year.
Glycemic control is fundamental to the management of diabetes with the objective of (safely) reducing hyperglycemia to as near normal as possible. The current recommendation for newly diagnosed patients is immediate initiation of metformin. However, studies have shown that early intensive insulin therapy can induce and maintain diabetes remission.[3,4] One important and interesting finding of the current study is that similar remission was achieved with oral agents (metformin plus gliclazide if necessary) as with insulin. Treating diabetes intensively at diagnosis, regardless of therapy, achieved a 1-year remission rate of 44%. Thus, for the patient who wants to try lifestyle modification without drugs, as many do, it appears that such a strategy might be effective after first aggressively reducing hyperglycemia. Another interesting finding was that for patients who achieved remission, insulin sensitivity was nearly fully restored, but beta-cell function was only modestly improved after intensive therapy. This may therefore be an important marker of who can maintain glucose control with lifestyle-only therapy following a course of intensive glucose reduction.