- In newly diagnosed patients with type 2 diabetes, short-term intensive therapy (IT) with insulin or oral agents can result in long-term remission.
IT had a greater impact on improving insulin sensitivity than improving insulin resistance.
Study patients were Chinese with a baseline BMI of 25. It would be interesting to see if similar results are seen in obese individuals with diabetes.
Although the role of lifestyle changes in achieving and maintaining remission in this study was not assessed, patients with type 2 diabetes should be counseled on diet and exercise irrespective of the type of antihyperglycemic therapy they are receiving.
PLEASE NOTE: Each article is selected by faculty on the scientific merits of the new data. It is one part of a bundled series of articles that, as a group, provide a full and balanced perspective.
Insulin resistance and β-cell dysfunction contribute to the pathogenesis of type 2 diabetes. Metformin, which targets insulin resistance, is recommended as first-line treatment for type 2 diabetes. Sulfonylureas, which increase insulin secretion, are often added if further glucose lowering is needed. These medications are generally continued long term. As an alternative, short-term intensive therapy (IT) has been shown to result in long-term glycemic control in some patients, but the mechanisms responsible for this effect are not clear. A Chinese study investigated the role of insulin resistance and β-cell function in achieving long-term remission following short-term IT.
The study included 48 patients with type 2 diabetes (34 men, 14 women), 28 subjects with impaired glucose tolerance (IGT; 17 men, 11 women), and 12 subjects with normal glucose tolerance (NGT; 9 men, 3 women). The patients were randomized to 3 antihyperglycemic treatment arms: continuous subcutaneous insulin infusion (CSII), multiple daily insulin (MDI) injections, or oral hypoglycemic agents (OHA). Treatments were maintained for 2 weeks after reaching the glycemic target of fasting plasma glucose (FPG) <6.1 mmol/L (109.8 mg/dL) and postprandial plasma glucose (PPG) <8.0 mmol/L (144 mg/dL). After treatment was stopped, patients were advised to implement lifestyle changes, and glycemic control was monitored every month for the first 3 months, then every 3 months. Patients were classified as having remission if they maintained glycemic control for at least 12 months without medication.
The CSII group achieved the glycemic target in 6.4 ± 3.4 days, the MDI group in 7.1 ± 3.1 days, and the OHA group in 11.6 ± 5.5 days (P <.05 for CSII/MDI versus OHA). There was no difference in response rates with the 3 therapies: Short-term IT resulted in remission in 21/48 patients (44%; 8 CSII, 6 MDI, 7 OHA), while 27/48 patients (56%; 8 CSII, 6 MDI, 7 OHA) were classified as nonremission. The remission and nonremission groups had similar blood glucose levels and lipid profiles at baseline, but FPG, PPG, and triglycerides were significantly lower after IT in the remission group than in the nonremission group. FPG, PPG, and A1C were significantly lower at 1-year follow-up in the remission group than in the nonremission group (Figure).
Figure. Fasting plasma glucose and postprandial glucose values in remission and nonremission groups before intensive therapy, after intensive therapy, and at 1-year follow-up
Baseline homeostatic model assessment for insulin resistance (HOMA-IR), a measure of insulin sensitivity, was significantly higher in the remission (3.12 ± 1.4) and nonremission (2.70 ± 1.7) groups than in the IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) groups. In the remission group, HOMA-IR was significantly reduced to levels comparable to those in the IGT and NGT groups immediately following IT (1.72 ± 0.8) and after 1 year (2.12 ± 0.3), while in the nonremission group, HOMA-IR showed no significant change after IT (2.34 ± 1.4) or at 1 year (2.60 ± 1.9).
HOMA-β, a measurement of β-cell function, was significantly lower at baseline in the remission (18.4) and nonremission (9.91) groups than in the IGT (82.7) and NGT groups (86.4). After IT and at 1 year, there was a significant increase in HOMA-β from baseline in both the remission and nonremission groups (P <.001). The increase in HOMA-β was greater in the remission group (44.6 after IT; 51.9 at 1 year) than in the nonremission group (26.5 after IT; 31.9 after 1 year), but the difference was not statistically significant. Acute insulin response of insulin (AIRins), another measurement of β-cell function, showed similar results: AIRins was significantly lower in the remission and nonremission groups than in the IGT and NGT groups at baseline, and significantly improved in both groups following IT. However, restoration of β-cell function in both groups was modest: the remission group achieved only about 24.0% and 18.4% of NGT based on HOMA-β and AIRins, respectively, while the nonremission group achieved 12.7% and 9.5% of NGT based on HOMA-β and AIRins, respectively.
Prior to this study, it was thought that the main benefit of short-term glycemic control was to remove glucose toxicity in the pancreas and restore pancreatic ß-cell function. However, based on the results of this study, restoration of insulin sensitivity appeared to play a greater role than improvement of β-cell function.
Hu Y, Li L, Xu Y, et al. Short-term intensive therapy in newly diagnosed type 2 diabetes partially restores both insulin sensitivity and β-cell function in subjects with long-term remission. Diabetes Care. 2011;34:1848-1853.