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Retnakaran R.,Sinai Center for Diabetes | Retnakaran R.,University of Toronto | Zinman B.,Sinai Center for Diabetes | Zinman B.,University of Toronto | Zinman B.,Samuel Lunenfeld Research Institute
Diabetes, Obesity and Metabolism | Year: 2012

The natural history of type 2 diabetes (T2DM) is characterized by progressive deterioration of pancreatic β-cell function, leading to worsening glycemia over time. As current antidiabetic therapies have not yet been shown to profoundly alter this natural history, many patients ultimately will require exogenous insulin therapy to obtain adequate glycemic control. Interestingly, the temporary use of short-term intensive insulin therapy early in the course of T2DM has recently emerged as a therapeutic option that may offer favourable long-term effects on β-cell function. Indeed, after receiving this treatment, many patients will experience sustained euglycemia without requiring any antidiabetic therapy. This apparent 'remission' of diabetes is likely secondary to improved β-cell function and can last for more than a year, although it is not sustained and hyperglycemia eventually will return. Nevertheless, owing to its effects on β-cell function, short-term intensive insulin therapy holds promise as a means for modifying the natural history of T2DM and warrants further study in this context. In this report, we will review the rationale and evidence underlying this interesting therapeutic option, and its implications for both clinical research and the management of patients with T2DM. © 2012 Blackwell Publishing Ltd.


Stein C.M.,Sinai Center for Diabetes | Kramer C.K.,Sinai Center for Diabetes | Kramer C.K.,University of Toronto | Zinman B.,Sinai Center for Diabetes | And 7 more authors.
Diabetic Medicine | Year: 2015

Aims: In patients with Type 2 diabetes, a short course of intensive insulin therapy can improve β-cell function and even induce transient remission of diabetes. However, not all patients respond to this therapy. Although the achievement of fasting glucose < 7.0 mmol/l one day after stopping intensive insulin therapy can identify patients in whom β-cell function has improved, we sought to determine clinical predictors for the early identification of such responders and the time course of response. Methods: We pooled data from two studies in which 97 patients with Type 2 diabetes mellitus (median 3 years duration) and HbA1c 51 ± 8.7 mmol/mol (6.8 ± 0.8%) underwent 4-8 weeks of intensive insulin therapy, consisting of basal detemir and pre-meal insulin aspart. They were classified as responders (n = 74) or non-responders (n = 23), defined by the achievement of fasting glucose < 7.0 mmol/l after stopping intensive insulin therapy. Results: On logistic regression analyses, duration of diabetes (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.56-0.92, P = 0.009) and baseline fasting glucose (OR = 0.40, 95% CI 0.24-0.68, P = 0.001) emerged as predictors of the likelihood of responding. Ninety per cent of patients with duration ≤ 4 years and fasting glucose ≤ 8.0 mmol/l responded to intensive insulin therapy. Despite having lower glucose levels during intensive insulin therapy, responders had less hypoglycaemia than non-responders (median 0.3 vs. 1.6 episodes/week, P < 0.0001), with rates of hypoglycaemia diverging sharply from the third week onwards. Conclusion: At baseline, shorter duration of diabetes and lower fasting glucose can identify patients most likely to benefit from short-term intensive insulin therapy. Most importantly, during therapy, responders had less hypoglycaemia from the third week onwards, despite lower glycaemia, suggesting that 2 weeks of intensive insulin therapy may be needed to improve endogenous islet function. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

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