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Diabet. Med. 30, 46–55 (2013) Abstract Aims Whether long-term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long-term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group. Methods This long-term follow-up (median 10 years, interquartile range 9.0–10.5) of the three-arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1-year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow-up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually. Results After 10 years’ follow-up from Diabetes Prevention Program baseline, major reductions were seen for systolic (−2 to −3) and diastolic (−6 to −6.5 mmHg) blood pressure, and for LDL cholesterol (−0.51 to −0.6 mmol/l) and triglycerides (−0.23 to −0.25 mmol/l) in all groups, with no between-group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study. Conclusion Overall, intensive lifestyle intervention achieved, with less medication, a comparable long-term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.

Aims The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed. Methods Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains. Results At study end, HbA1c reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.25–0.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.52–1.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.32–5.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.89–14.18)] and mental health domains [+2.46 (95% CI 0.10–4.82)]. For mental component score, Cohen’s effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI –2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine. Conclusions In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.

Diabet. Med. 27, 556–562 (2010) Abstract Aims The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone. Methods In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. Results One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA1c), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA1c

Type 2 diabetes currently accounts for over 100 billion dollars in annual healthcare expenditure in the United States and 28% of the national (Medicare) healthcare budget for elderly Americans. In our inner-city hospital, 20% of all 950 beds are occupied by patients with diabetes; and 28-38% of patients receiving cardiac care in Coronary Care Units, catheterization laboratories or cardiovascular surgery, have diabetes as an underlying disorder. Both computer modelling and controlled clinical trials suggest that intensive therapy of diabetes can reduce significantly the morbidity and costs associated with this increasingly common disorder. Early detection of carbohydrate intolerance holds great promise for preventing the onset, progression and complications of Type 2 diabetes. To date our efforts have been futile, with 20% of newly diagnosed Type 2 diabetic patients already complicated by retinopathy and 14% complicated by peripheral vascular disease. It is now clear that high-risk individuals can be identified, and intervention trials are underway to test the hypothesis that Type 2 diabetes (and its attendant cardiovascular risks) can be prevented. The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP NIDDM) in Canada and Europe has randomized 1200 individuals with impaired glucose tolerance (IGT) into a three-year trial to prevent disease progression. The Diabetes Prevention Program (DPP) in the US has randomized almost 3000 individuals with IGT into a six-year, three-arm study testing the efficacy of intensive lifestyle and pharmacological therapy in disease progression. Together, these studies should provide a public health model for the recognition of high-risk individuals and interventions to stem the epidemic of Type 2 diabetes. For those patients suffering with Type 2 diabetes already, pancreas transplantation remains an extreme intervention with the potential for 'curing' diabetes. Although applied usually to patients with Type 1 diabetes, experience is accumulating of transplantation in Type 2 diabetic patients with end-stage renal disease. Outcomes for these individuals are as good as for Type 1 diabetes. Islet-cell transplants, in fact, have been more successful in Type 2 diabetes compared with Type 1. Improved islet-cell availability, better immunosuppression, and the possibility of antigen masking make this technology a major hope for the future.