ArticlesEffect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial
Introduction
The UK Prospective Diabetes Study1, 2 has shown that β-cell function progressively deteriorates over time in people with type 2 diabetes mellitus, irrespective of lifestyle and existing pharmacological interventions. Notwithstanding, continued effort has been directed toward β-cell preservation or rejuvenation in an attempt to change or at least delay the natural course of type 2 diabetes.3 Other studies have indicated that, in newly diagnosed patients, short-term intensive insulin therapies that target overall glycaemic control, such as multiple daily insulin injections (MDI) and continuous subcutaneous insulin infusion (CSII), could improve β-cell function and result in extended remissions in which only diet was needed to maintain normoglycaemia.3, 4, 5, 6, 7, 8 The results of our previous study7 also suggest that the improvement of β-cell function, especially the restoration of the first-phase insulin secretion, could be responsible for the remission. Still unclear, however, is whether this disease-modifying effect is due to insulin therapy itself or the effects of simply eliminating glucotoxicity by achieving excellent glycaemic control, and which kind of initiation of early intensive therapy would be more beneficial.
We therefore did a multicentre, randomised, parallel-group trial to assess the efficacy of short-term intensive insulin therapy (including MDI and CSII) compared with oral hypoglycaemic agents on glycaemic control, remission rate, and β-cell function in patients with newly diagnosed type 2 diabetes. Several indicies were used for assessment of β-cell insulin-secretory capacity, including: HOMA B, which represents basal β-cell function; the first-phase insulin secretion after a glucose challenge, which represents the acute insulin response; and the ratio of plasma proinsulin to immunoreactive insulin (PI/IRI), which indicates β-cell secretory quality.9
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Methods
436 patients with newly diagnosed type 2 diabetes, according to WHO diagnostic criteria (1999),10 who had not received previous antihyperglycaemic therapy, were enrolled from nine centres in China between September, 2004, and October, 2006. The patients, aged 25–70 years, had levels of fasting plasma glucose between 7·0 mmol/L and 16·7 mmol/L. Patients were excluded if they had acute or severe chronic diabetic complications, severe intercurrent illness, or tested positive for glutamic acid
Results
Of the 436 patients screened, 410 were eligible and were randomised. 28 patients withdrew before receiving interventions (figure 1). The remaining 382 patients (mean age 51 years [SD 10], body-mass index 25·0 kg/m2 [3·0], and mean fasting plasma glucose 11·2 mmol/L [3·1]) were allocated to the CSII group (137), the MDI group (124), and the hypoglycaemic agents group (121).
Of these patients, 23 (four in the CSII group, six in the MDI group, and 13 in the oral hypoglycaemic agents group) did not
Discussion
Our results show that excellent glycaemic control could be successfully achieved in 7·9 days (SD 4·6) in most patients with mean fasting plasma glucose of 11·2 mmol/L (SD 3·1), irrespective of the use of CSII, MDI, or oral hypoglycaemic intervention. Of those patients who reached glycaemic targets, both fasting plasma glucose and 2-h postprandial plasma glucose concentrations rapidly corrected to near physiological range after treatment, and HbA1c was greatly improved after only 2–5 weeks.
In
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These authors contributed equally to the paper