Explore the vast range of titles available.

Aims/hypothesis The aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin. Methods We used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n = 36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n = 12,852 in whom 381 cancers occurred). Records from these cohorts were linked to cancer registry data up to the end of 2005. We used Cox proportional hazards models for survival analyses. Results Those receiving any insulin glargine (n = 3,959) had the same incidence rate for all cancers as those not receiving insulin glargine (HR 1.02, 95% CI 0.77-1.36, p = 0.9 in the fixed cohort) The subset of patients using insulin glargine alone (n = 447) had a significantly higher incidence of all cancers than those using other insulins only (n = 32,295) (HR 1.55, 95% CI 1.01-2.37, p = 0.045), and those using insulin glargine with other insulins (n = 3,512) had a slightly lower incidence (HR 0.81, 95% CI 0.55-1.18, p = 0.26). There were important differences in baseline characteristics between these three groups, although the risk ratios were broadly unaltered on adjustment for these. Overall, there was no increase in breast cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79-2.83, though insulin glargine only users had a higher rate than those using non-glargine insulin only (HR 3.39, 95% CI 1.46-7.85, p = 0.004). Among type 2 diabetic incident insulin users, no significant difference between the three groups was observed with respect to all cancer or breast cancer. All the above HRs are adjusted for age, calendar time prior cancer and type of diabetes, as appropriate, and are stratified according to sex. Conclusions/interpretation Overall, insulin glargine use was not associated with an increased risk of all cancers or site-specific cancers in Scotland over a 4 year time frame. Given the overall data, we consider the excess of cases of all cancers and breast cancer in the subgroup of insulin glargine only users to more likely reflect allocation bias rather than an effect of insulin glargine itself.

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.

Aims/hypothesis As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA₁c, weight, insulin-dose requirement and adverse effects. Methods We constructed evidence tables and fitted a fixed-effects model (inverse variance method) in order to assess heterogeneity between studies and give a crude measure of each overall treatment effect. Results Of 197 studies identified, nine involved randomisation with informed consent of patients with type 1 diabetes to metformin (vs placebo or comparator) in either a parallel or crossover design for at least 1 week. We noted marked heterogeneity in study design, drug dose, age of participants and length of follow-up. Metformin was associated with reductions in: (1) insulin-dose requirement (5.7-10.1 U/day in six of seven studies); (2) HbA₁c (0.6-0.9% in four of seven studies); (3) weight (1.7-6.0 kg in three of six studies); and (4) total cholesterol (0.3-0.41 mmol/l in three of seven studies). Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p < 0.001) but no significant reduction in HbA₁c (absolute reduction 0.11%, p = 0.42). No reported trials included cardiovascular outcomes. Conclusions/interpretation Metformin reduces insulin-dose requirement in type 1 diabetes but it is unclear whether this is sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes.

Aims/hypothesis The aim of this study was to examine the prevalence of and risk factors for diabetic retinopathy in people with newly diagnosed type 2 diabetes mellitus, using Scottish national data. Methods We identified individuals diagnosed with type 2 diabetes mellitus in Scotland between January 2005 and May 2008 using data from the national diabetes database. We calculated the prevalence of retinopathy and ORs for risk factors associated with retinopathy at first screening. Results Of the 51,526 people with newly diagnosed type 2 diabetes mellitus identified, 91.4% had been screened by 31 December 2010. The median time to first screening was 315 days (interquartile range [IQR] 111–607 days), but by 2008 the median was 83 days (IQR 51–135 days). The prevalence at first screening of any retinopathy was 19.3%, and for referable retinopathy it was 1.9%. For individuals screened after a year the prevalence of any retinopathy was 20.5% and referable retinopathy was 2.3%. Any retinopathy at screening was associated with male sex (OR 1.19, 95% CI 1.14, 1.25), HbA 1c (OR 1.07, 95% CI 1.06, 1.08 per 1% [11 mmol/mol] increase), systolic BP (OR 1.06, 95% CI 1.05, 1.08 per 10 mmHg increase), time to screening (OR for screening >1 year post diagnosis = 1.12, 95% CI 1.07, 1.17) and obesity (OR 0.87, 95% CI 0.82, 0.93) in multivariate analysis. Conclusions/interpretation The prevalence of retinopathy at first screening is lower than in previous UK studies, consistent with earlier diagnosis of diabetes. Most newly diagnosed type 2 diabetic patients in Scotland are screened within an acceptable interval and the prevalence of referable disease is low, even in those with delayed screening.

Aims/hypothesis Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. Methods Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999–2008. Results There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p  = 3 × 10 −5 ), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). Conclusions/interpretation Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Background Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. Methods 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. Results People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA 1 c accounted for the effects of T2DM. HbA 1 c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) −0.096, p = <0.008 and −0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β −0.099; p = 0.006 and −0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA 1 c and ACh (β −0.043; p = 0.3), but not between HbA 1 c and SNP (β −0.105; p = 0.02). Conclusions In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for “advanced disease” than concomitant CVD, although this requires prospective validation.

Aims/hypothesis We compiled up to date estimates of the absolute and relative risk of all-cause mortality in patients with type 1 diabetes in the UK. Materials and methods We selected patients with type 1 diabetes (n=7,713), and for each of these diabetic subjects five age- and sex-matched control subjects without diabetes (n=38,518) from the General Practice Research Database (GPRD). Baseline was 1 January 1992; subjects were followed until 1999. The GPRD is a large primary-care database containing morbidity and mortality data of a large sample representative of the UK population. Deaths occurring in the follow-up period were identified. Results The study comprised 208,178 person-years of follow-up. The prevalence of type 1 diabetes was 2.15/1,000 subjects in 1992 (mean age 33 years, SD 15). Annual mortality rates were 8.0 per 1,000 person-years (95% CI 7.2-8.9) in type 1 diabetic subjects compared with 2.4 per 1,000 person-years (95% CI 2.2-2.6) in those without diabetes (hazard ratio [HR]=3.7, 95% CI 3.2-4.3). The increased mortality rates in patients with type 1 diabetes were apparent across all age-bands. The HR was higher in women (HR=4.5, 95% CI 3.5-5.6 compared with non-diabetic women) than men (HR=3.3, 95% CI 2.7-4.0), such that the sex difference (p<0.0001) in mortality in the non-diabetic population was abolished (p=0.3) in the type 1 diabetic patients. The predominant cause of death in patients with type 1 diabetes was cardiovascular disease. Conclusions/interpretation Despite advances in care, UK mortality rates in the past decade continue to be much greater in patients with type 1 diabetes than in those without diabetes.

Aims/hypothesis The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening. Methods This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy. Results The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years. Conclusions/interpretation Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.

Aims/hypothesis The aim of this study was to explore the relationships between type 2 diabetes mellitus, area-based socioeconomic status (SES) and cardiovascular disease mortality in Scotland. Methods We used an area-based measure of SES, Scottish national diabetes register data linked to mortality records, and general population cause-specific mortality data to investigate the relationships between SES, type 2 diabetes and mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CbVD), for 2001–2007. We used negative binomial regression to obtain age-adjusted RRs of mortality (by sex), comparing people with type 2 diabetes with the non-diabetic population. Results Among 216,652 people aged 40 years or older with type 2 diabetes (980,687 person-years), there were 10,554 IHD deaths and 4,378 CbVD deaths. Age-standardised mortality increased with increasing deprivation, and was higher among men. IHD mortality RRs were highest among the least deprived quintile and lowest in the most deprived quintile (men: least deprived, RR 1.94 [95% CI 1.61, 2.33]; most deprived, RR 1.46 [95% CI 1.23, 1.74]) and were higher in women than men (women: least deprived, RR 2.84 [95% CI 2.12, 3.80]; most deprived, RR 2.04 [95% CI 1.55, 2.69]). A similar, weaker, pattern was observed for cerebrovascular mortality. Conclusions/interpretation Absolute risk of cardiovascular mortality is higher in people with diabetes than in the non-diabetic population and increases with increasing deprivation. The relative impact of diabetes on cardiovascular mortality differs by SES, and further efforts to reduce cardiovascular risk both in deprived groups and people with diabetes are required. Prevention of diabetes may reduce socioeconomic health inequalities.

Aims/hypothesis Diabetic ketoacidosis is a potentially life-threatening complication of diabetes and has a strong relationship with HbA 1c . We examined how socioeconomic group affects the likelihood of admission to hospital for diabetic ketoacidosis. Methods The Scottish Care Information – Diabetes Collaboration (SCI-DC), a dynamic national register of all cases of diagnosed diabetes in Scotland, was linked to national data on hospital admissions. We identified 24,750 people with type 1 diabetes between January 2005 and December 2007. We assessed the relationship between HbA 1c and quintiles of deprivation with hospital admissions for diabetic ketoacidosis in people with type 1 diabetes adjusting for patient characteristics. Results We identified 23,479 people with type 1 diabetes who had complete recording of covariates. Deprivation had a substantial effect on odds of admission to hospital for diabetic ketoacidosis (OR 4.51, 95% CI 3.73, 5.46 in the most deprived quintile compared with the least deprived). This effect persisted after the inclusion of HbA 1c and other risk factors (OR 2.81, 95% CI 2.32, 3.39). Men had a reduced risk of admission to hospital for diabetic ketoacidosis (OR 0.71, 95% CI 0.63, 0.79) and those with a history of smoking had increased odds of admission to hospital for diabetic ketoacidosis by a factor of 1.55 (95% CI 1.36, 1.78). Conclusions/interpretation Women, smokers, those with high HbA 1c and those living in more deprived areas have an increased risk of admission to hospital for diabetic ketoacidosis. The effect of deprivation was present even after inclusion of other risk factors. This work highlights that those in poorer areas of the community with high HbA 1c represent a group who might be usefully supported to try to reduce hospital admissions.