Intensive insulin therapy in newly diagnosed type 2 diabetes.

The natural history of type 2 diabetes is characterised by worsening hyperglycaemia and progressive deterioration in function of the insulin-secreting pancreatic β cells. Despite intense investigative eff orts, the pathophysiological basis underlying β-cell dysfunction (and the concomitant loss of β-cell mass) remains unclear. Nevertheless, the central importance of declining β-cell function in type 2 diabetes is underscored by its correlation with a progressive loss of glycaemic control, which typically occurs over time. Although β-cell dysfunction contributes to worsening glycaemia, hyperglycaemia itself further undermines β-cell function. This so-called glucotoxicity is apparent in the observation that the fi rst-phase component of normal biphasic insulin secretion is abolished when the blood glucose concentration exceeds 6·4 mmol/L. Accordingly, early in the course of type 2 diabetes (ie, when suffi cient residual β-cell mass still exists), the glucose-lowering eff ect of antidiabetic therapy can be amplifi ed by improved endogenous insulin secretion secondary to the elimination of hyperglycaemia. Unfortunately, however, this eff ect is ultimately transient, because no oral antidiabetic agent has yet been shown to profoundly change the inexorable β-cell deterioration and worsening glycaemia in type 2 diabetes. Insulin therapy is usually instituted late in the course of type 2 diabetes, when glycaemic control can no longer be maintained with oral antidiabetics. Interestingly, however, as shown in limited studies up to now (table), early implementation of a short course of intensive insulin therapy by continuous subcutaneous insulin infusion or multiple daily injections can induce sustained euglycaemia (ie, off any antidiabetic therapy) in patients with type 2 diabetes. The “remission” of type 2 diabetes achieved in these studies persists for 1 year after the cessation of insulin therapy in about 40% of patients. Furthermore, Li and colleagues reported that patients who maintained euglycaemia off antidiabetic therapy for 1 year showed greater recovery of β-cell function than their counterparts, when assessed immediately after 2 weeks of continuous subcutaneous infusion. The suggestion has therefore been made that an improvement in β-cell function, especially restoration of fi rst-phase insulin secretion, might be responsible for the ability of intensive insulin therapy to induce sustained euglycaemia. In today’s Lancet, Jianping Weng and colleagues extend these concepts by reporting a randomised trial that compares the eff ects of temporary (2–5 weeks) intensive insulin therapy (continuous subcutaneous infusion or multiple daily injections) versus oral antidiabetics (ie, metformin, gliclazide, or, in most patients, both) on remission of diabetes and β-cell function in 382 newly-diagnosed patients with type 2 diabetes in nine centres in China. Glycaemic control was rapidly achieved (mean 7·9 days [SD 4·6]) in 92·1% of patients. When assessed 2 days after stopping therapy, fi rst-phase insulin secretion (measured by acute insulin response on an intravenous glucose-tolerance test) was signifi cantly increased with all three regimens. Importantly, remission at 1 year after therapy was signifi cantly higher in the insulin groups (continuous infusion, 51·1%; multiple injections, 44·9%) than in the oral antidiabetic group (26·7%). Moreover, in patients in remission, the decline in the acute insulin response See Editorial page 1723