Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative general practitioners, who were invited to initiate or intensify insulin therapy when necessary in 523 patients with type 2 diabetes (mean age: 65.5 years; mean HbAk: 8.8%). The initiation of insulin therapy (glargine in > 50%) was justified by insufficient glycaemic control (96%) and its intensification (replacement of insulin NPH or premixed insulins by insulin glargine, eventually with the addition of a short-acting insulin analogue) aimed at improving glucose control (58%), avoiding hypoglycaemia (17%) or both (17%). After a follow up of 6:1 months, HbAlc level decreased from 8.79% to 7.52% (-1.27%; 95% confidence interval: -1.43, -1.11; p<0.001). Overall 27.6% of patients reached an HbAl, < 7% versus 5.9% at inclusion (p<0.001), with rather few hypoglycaemia and a high physi- cian confidence level regarding insulin therapy. These results should encourage general practitioners to initiate insulin therapy at an earlier stage and to intensify it when necessary in patients with insufficiently controlled type 2 diabetes.

Aim - PREDICTIVE (Predictable Results and Experience in Diabetes Through intensification and Control to Target: an International Variability Evaluation) is a mutti-national study designed to evaluate the safety and efficacy of insulin detemir (Levemir (R)) in "real world" medical practice. The aim of the study is to report the PREDICTIVE results of the Belgian type 1 diabetic cohort.Methods - Two hundred and thirty-two patients treated with a basal-bolus insulin scheme were considered for analysis. Seventy-eight percent of those patients were previously treated with insulin glargine as a basal insulin, while 22 % received NPH, before switching to Levemir (R).Results - Mean age and duration of diabetes were 45 +/- 15 and 18 +/- 13 years, respectively (means +/- SD). HbA(1)C was 8.3 +/- 1.2 %. We observed (at weeks 12 and 26 after baseline) a significant reduction in all hypoglycaemic events including major hypoglycaemias after switching to detemir (p<0.0001). There was no change in HbA(1)C. Fasting blood glucose decreased from 170 +/- 49 to 158 +/- 45 mg/dl at week 26 (p<0.009), while fasting blood glucose variability was reduced from 69 +/- 35 to 57 +/- 30 mg/dl at week 26 (p<0.0001). Total insulin doses increased during the trial from 0.74 +/- 0.28 to 0.82 +/- 0.14 U/kg/day (p<0.0007). No weight gain was observed during the study. Patient's satisfaction increased significantly (from 6.3 +/- 1.5 to 7.2 +/- 1.6 at week 26, p<0.0001).Conclusion - This report from the Belgian cohort of PREDICTIVE extends the safety and efficacy data of insulin detemir in type 1 diabetic patients treated with a basal-bolus insulin scheme.

Type 2 diabetes is a progressive disease characterised by deteriorating β-cell function and glycaemic control. To counter this, affected individuals require regular intensification of their antidiabetes treatments to provide appropriate metabolic control. However, current treatment options – such as sulphonylureas, thiazolidinediones and insulins – induce weight gain, which can reduce patient acceptance and/or compliance with treatment and may have significant health implications. In addition, many of the antidiabetic therapies raise the risk of hypoglycaemic episodes. Therefore, patients, physicians and healthcare providers are looking for new therapeutic options to address this large and growing burden of diabetes. Incretin-based therapies – including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors – are becoming a popular treatment option for patients with type 2 diabetes because they offer many benefits compared with other antidiabetic therapies. First, incretin-based therapies are associated with significant reductions in glycated haemoglobin (HbA1c) with a low inherent risk of hypoglycaemic events. In addition, GLP-1 receptor agonists are associated with reductions in bodyweight and systolic blood pressure. Incretin-based therapies such as liraglutide also offer the potential to improve β-cell function, an important underlying mechanism of type 2 diabetes.

The incidence and prevalence of diabetes (and especially type 2 diabetes) are increasing worldwide. The World Health Organization (WHO) estimates that worldwide 171 million people suffered from diabetes in 2000, and predicts that by 2030 their number will increase to more than 300 million.1 Due to the initially often silent course of the disease and thus late diagnosis, and also because of gross undertreatment of hyperglycaemia and additional cardiovascular risk factors, diabetes is a major cause of morbidity and mortality. Microvascular complications – such as retinopathy, neuropathy and nephropathy – and macrovascular disease cause human suffering, but are also a major burden to healthcare resources worldwide.

We have previously shown the presence in a Nicotiana sylvestris protoplast-derived plant of both a nuclear mutation conferring male sterility (ms4) and a mtDNA reorganisation, named U, characterised by the amplification of substoichiometric mtDNA fragments generated by recombination in the parent T mtDNA. Here we show by physical mapping that the recombining repeats are in direct orientation, thus generating two subgenomes both of which are amplified in the U organisation to the detriment of the parent molecule, and are maintained through sexual reproduction. The nuclear ms4 mutation is likely to have play a role in the shift in mitochondrial molecule equilibrium, as higher levels of recombinant fragments were present in protoplast-derived T calli carrying the ms4 allele than in wild type calli or leaves. The MS4 gene could then lead to conflictual situation. However, subgenomic molecules were counter-selected during the regeneration process, suggesting the existence of different selective pressures in differentiated and non-differentiated cells. The U organisation is associated with higher stem height and late flowering, characters that may not be neutral from a selection point of view. The U equilibrium is an unusual example of sudden mtDNA reorganisation, without obvious differences in genetic information and with only a limited phenotypic impact.