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Estimated life expectancy for patients with type 1 diabetes in Scotland based on data from 2008 through 2010 indicated an estimated loss of life expectancy at age 20 years of approximately 11 years for men and 13 years for women compared with the general population without type 1 diabetes.

Aims/hypothesis The evidence on the association between pioglitazone use and bladder cancer is contradictory, with many studies subject to allocation bias. The aim of our study was to examine the effect of exposure to pioglitazone on bladder cancer risk internationally across several cohorts. The potential for allocation bias was minimised by focusing on the cumulative effect of pioglitazone as the primary endpoint using a time-dependent approach.Methods Prescription, cancer and mortality data from people with type 2 diabetes were obtained from six populations across the world (British Columbia, Finland, Manchester, Rotterdam, Scotland and the UK Clinical Practice Research Datalink). A discrete time failure analysis using Poisson regression was applied separately to data from each centre to model the effect of cumulative drug exposure on bladder cancer incidence, with time-dependent adjustment for ever use of Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3456-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. -014-3456-9 pioglitazone. These were then pooled using fixed and random effects meta-regression. Results Data were collated on 1.01 million persons over 5.9 million person-years. There were 3,248 cases of incident bladder cancer, with 117 exposed cases and a median follow-up duration of 4.0 to 7.4 years. Overall, there was no evidence for any association between cumulative exposure to pioglitazone and bladder cancer in men (rate ratio [RR] per 100 days of cumulative exposure, 1.01; 95% CI 0.97, 1.06) or women (RR 1.04; 95% CI 0.97, 1.11) after adjustment for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone. No association was observed between rosiglitazone and bladder cancer in men (RR 1.01; 95% CI 0.98, 1.03) or women (RR 1.00; 95% CI 0.94, 1.07). Conclusions/interpretation The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis.Diabetologia (2015) 58:493-504 DOI 10.1007/s00125

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The morphological development that accompanies increasing pulmonary blood flow and decreasing pulmonary vascular resistance with advancing gestational age has not been delineated. To study this point we developed a method of comparing pulmonary arterial vessels of the same generations in fetal lambs. Pulmonary arteries were perfused with glutaraldehyde solution at pressures appropriate for gestational age and then injected with an India ink-gelatin-Micropaque mixture. Using the dissecting microscope and serially prepared sections we studied successively smaller generations of arteries. We assessed the medial width/external diameter ratio in a total of 825 vessels from six fetal lambs of 85 to 140 days gestation. In fifth generation, or resistance vessels, this ratio remained constant over the gestational period studied (N = 529, Y = 0.16, slope = 0.0003). We measured the volume of 17-34 randomly selected sections from each of the six fetuses, counted the total number of fifth and sixth generation vessels in these sections, and calculated the total number of these vessels per right lung. This number increased from 0.10 X 10(6) to 4.08 X 10(6) with increasing gestational age. The number of vessels per unit volume increased from 7.2 X 10(3)/ml to 61.8 X 10(3)/ml or right lung over this gestational period. The results indicate that increased pulmonary blood flow and decreased pulmonary vascular resistance with advancing gestation are due to an increase in the total number of vessels and increased vasomotor reactivity is related to an increase in the total amount of smooth muscle while the thickness of muscle in individual vessels remains constant.

Aims Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c). Using the time‐weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF. Methods and results A time‐weighted mean HbA1c was calculated using all HbA1c measurements following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1–7.0%, 7.1–8.0%, 8.1–9.0%, and >9.0%). The relationship between time‐weighted mean HbA1c and all‐cause death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the study criteria. During a median follow‐up of 2.8 years, there were 826 (57.1%) deaths, with a crude death rate of 155 deaths per 1000 person‐years [95% confidence interval (CI) 144–166]. A Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1–8.0%) as the reference, showed a U‐shaped relationship between HbA1c and outcome [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8–3.4; HbA1c 6.1–7.0%, HR 1.4, 95% 1.1–1.7; HbA1c 8.1–9.0%, HR 1.3, 95% CI 1.0–1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4–2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 0.61–0.93) but not other drug classes. Conclusions In patients with T2DM and CHF, our study shows a U‐shaped relationship between HbA1c and mortality, with the lowest risk in patients with modest glycaemic control (HbA1c 7.1–8.0%) and those treated with insulin sensitizers.

The causes and mechanisms of CEDKA are unknown. CEDKA may be due as much to individual biological variance as to severity of underlying metabolic derangement of the child's state and/or treatment risk factors. Treatment recommendations for CEDKA and diabetic ketoacidosis are made taking into consideration possible mechanisms and risk factors but are intended as general guidelines only in view of the absence of conclusive evidence.

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