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Aims To examine the usage and real-life effectiveness of intensification therapies in people with Type 2 diabetes treated with basal insulin. Methods We used population-based healthcare databases in Denmark during 2000-2012 to identify all individuals with a first basal insulin prescription (with or without oral drugs), and evaluated subsequent intensification therapy with bolus insulin, premixed insulin or glucagon-like peptide-1 ( GLP-1) receptor agonists. Poisson regression was used to compute the adjusted relative risks of reaching glycaemic control targets. Results We included 7034 initiators of basal insulin (median age 64 years, diabetes duration 5.3 years, 84% with oral co-medication and median (interquartile range) pre-insulin HbA1c level 77 (65-92) mmol/mol [9.2% (8.1-10.6%)]. Of these, 3076 (43.7%) received intensification therapy after a median of 11 months: 58.5% with premixed insulin, 29.0% with bolus insulin, 10.6% with GLP-1 receptor agonists, and 1.9% with more than one add-on. Overall, 22% had attained an HbA1c level of < 53 mmol/mol (< 7%) by 3-6 months after intensification, while 38% attained an HbA1c < 58 mmol/mol (< 7.5%). Compared with premixed insulin intensification, attainment of HbA1c < 53 and < 58 mmol/mol was similar with bolus insulin add-on [adjusted relative risk 1.03 (95% CI 0.86-1.24) and 1.02 (95% CI 0.91-1.15), and higher for GLP-1 receptor agonist add-on [adjusted relative risk 1.56 (95% CI 1.27-1.92) and 1.27 (1.10-1.47)] . Conclusions Among people with Type 2 diabetes, 22 and 38% reached a target HbA1c < 53 mmol/mol (< 7%) or < 58 mmol/mol (< 7.5%), respectively, after intensification of their basal insulin therapy. Compared with premixed insulin, target attainment was similar with bolus insulin and higher with GLP-1 receptor agonists. [ABSTRACT FROM AUTHOR]

Aims To identify individual predictors of early glycaemic control in people with Type 2 diabetes mellitus after initiation of first glucose-lowering drug treatment in everyday clinical practice. Methods Using medical registries, we identified a population-based cohort of people with a first-time glucose-lowering drug prescription in Northern Denmark in the period 2000-2012. We used Poisson regression analysis to examine patient-level predictors of success in reaching early glycaemic control [HbA1c target of < 53 mmol/mol (7%)] < 6 months after treatment start. Results Among the 38 418 people (median age 63 years), 27 545 (72%) achieved early glycaemic control. The strongest predictor of achieving early control was pre-treatment HbA1c level; compared with a pre-treatment HbA1c level of ≤ 58 mmol/mol (7.5%), the adjusted relative risks of attaining early control were 0.63 (95% CI 0.61-0.64) for baseline HbA1c levels of > 58 and ≤ 75 mmol/mol (> 7.5 and ≤ 9%), and 0.58 (95% CI 0.57-0.59) for a baseline HbA1c level of > 9% (> 75 mmol/mol). All other examined predictors were only weakly associated with the chance of achieving early control. After adjustment, the only characteristics that remained independently associated with early control (in addition to high baseline HbA1c) were being widowed (adjusted relative risk 0.95; 95% CI 0.93-0.97) and having a high Charlson comorbidity index score (score ≥ 3; adjusted relative risk 0.94; 95% CI 0.90-0.97). Conclusions In a real-world clinical setting, people with Type 2 diabetes mellitus initiating glucose-lowering medication had a similar likelihood of achieving glycaemic control, regardless of sex, age, comorbidities and other individual factors; the only strong and potentially modifiable predictor was HbA1c before therapy start. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population., Background: Epidemiologically, risk of IHD is inversely related to HDL cholesterol levels. Mutations in apolipoprotein (apo) A-I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHD and early death., Design: We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial infarction (MI) and mortality in 10 440 individuals in the prospective Copenhagen City Heart Study followed for 31 years. Results were validated in an independent case-control study (n = 16 035). Additionally, we determined plasma ratios of mutant to wildtype (WT) apoA-I in human heterozygotes and functional effects of mutations in adenovirus-transfected mice., Results: We identified a new mutation, A164S (1 : 500 in the general population), which predicted hazard ratios for IHD, MI and total mortality of 3.2 [95% confidence interval (CI): 1.6-6.5], 5.5 (95% CI: 2.6-11.7) and 2.5 (95% CI: 1.3-4.8), respectively, in heterozygotes compared with noncarriers. Mean reduction in survival time in heterozygotes was 10 years (P < 0.0001). Results for IHD and MI were confirmed in the case-control study. Furthermore, the ratio of mutant S164 to WT A164 apoA-I in plasma of heterozygotes was reduced. In addition, A164S heterozygotes had normal plasma lipid and lipoprotein levels, including HDL cholesterol and apoA-I, and this finding was confirmed in adenovirus-transfected mice., Conclusions: A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality without low HDL cholesterol levels., (© 2011 The Association for the Publication of the Journal of Internal Medicine.)