Krishnarajah Nirantharakumar

Hypoglycaemia is associated with increased length of stay and mortality in people with diabetes who are hospitalized.

Diabet. Med. 29, e445–e448 (2012)

Does exercise improve glycaemic control in type 1 diabetes? A systematic review and meta-analysis.

Objective Whilst regular exercise is advocated for people with type 1 diabetes, the benefits of this therapy are poorly delineated. Our objective was to review the evidence for a glycaemic benefit of exercise in type 1 diabetes. Research Design and Methods Electronic database searches were carried out in MEDLINE, Embase, Cochrane’s Controlled Trials Register and SPORTDiscus. In addition, we searched for as yet unpublished but completed trials. Glycaemic benefit was defined as an improvement in glycosylated haemoglobin (HbA1c). Both randomised and non-randomised controlled trials were included. Results Thirteen studies were identified in the systematic review. Meta-analysis of twelve of these (including 452 patients) demonstrated an HbA1c reduction but this was not statistically significant (standardised mean difference (SMD) −0.25; 95% CI, −0.59 to 0.09). Conclusions This meta-analysis does not reveal evidence for a glycaemic benefit of exercise as measured by HbA1c. Reasons for this finding could include increased calorie intake, insulin dose reductions around the time of exercise or lack of power. We also suggest that HbA1c may not be a sensitive indicator of glycaemic control, and that improvement in glycaemic variability may not be reflected in this measure. Exercise does however have other proven benefits in type 1 diabetes, and remains an important part of its management.

Plasma homocysteine in polycystic ovary syndrome: does it correlate with insulin resistance and ethnicity?

background  Polycystic ovary syndrome (PCOS) is associated with insulin resistance and premature coronary artery disease (CAD). Hyperhomocysteinaemia is a recognized risk factor for atherosclerosis, particularly among migrant South Asians, and has recently been shown to be correlated positively with the degree of insulin resistance/hyperinsulinaemia.

Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women

BACKGROUND Previous studies have been unclear about the cardiovascular risks for metabolically healthy obese individuals. OBJECTIVES This study examined the associations among metabolically healthy obese individuals and 4 different presentations of incident cardiovascular disease in a contemporary population. METHODS We used linked electronic health records (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years of age or older and initially free of cardiovascular disease. We created body size phenotypes defined by body mass index categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of 1 of 4 cardiovascular presentations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and peripheral vascular disease). RESULTS During a mean follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.45 to 1.54), cerebrovascular disease (HR: 1.07; 95% CI: 1.04 to 1.11), and heart failure (HR: 1.96; 95% CI: 1.86 to 2.06) compared with normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease, and heart failure in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities. CONCLUSIONS Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities and similar risks for cardiovascular disease events.

All-Cause Mortality in Patients With Diabetes Under Treatment With Dapagliflozin: A Population-Based, Open-Cohort Study in The Health Improvement Network Database

Context Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting The Health Improvement Network database. Participants A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.

Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: A population-based cohort study

Background Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease. Methods and findings We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease. Conclusions Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.

All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study

AIM The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. METHODS We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541). RESULTS Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. CONCLUSIONS GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.

Intra-cluster and inter-period correlation coefficients for cross-sectional cluster randomised controlled trials for type-2 diabetes in UK primary care

BackgroundClustered randomised controlled trials (CRCTs) are increasingly common in primary care. Outcomes within the same cluster tend to be correlated with one another. In sample size calculations, estimates of the intra-cluster correlation coefficient (ICC) are needed to allow for this nonindependence. In studies with observations over more than one time period, estimates of the inter-period correlation (IPC) and the within-period correlation (WPC) are also needed.MethodsThis is a retrospective cross-sectional study of all patients aged 18 or over with a diagnosis of type-2 diabetes, from The Health Improvement Network (THIN) database, between 1 October 2007 and 31 March 2010. We report estimates of the ICC, IPC, and WPC for typical outcomes using unadjusted and adjusted generalised linear mixed models with cluster and cluster by period random effects. For binary outcomes we report on the proportions scale, which is the appropriate scale for trial design. Estimated ICCs were compared to those reported from a systematic search of CRCTs undertaken in primary care in the UK in type-2 diabetes.ResultsData from 430 general practices, with a median [IQR] number of diabetics per practice of 241 [150–351], were analysed. The ICC for HbA1c was 0.032 (95 % CI 0.026–0.038). For a two-period (each of 12 months) design, the WPC for HbA1c was 0.035 (95 % CI 0.030–0.040) and the IPC was 0.019 (95 % CI 0.014–0.026). The difference between the WPC and the IPC indicates a decay of correlation over time. Following dichotomisation at 7.5 %, the ICC for HbA1c was 0.026 (95 % CI 0.022–0.030). ICCs for other clinical measurements and clinical outcomes are presented. A systematic search of ICCs used in the design of CRCTs involving type-2 diabetes with HbA1c (undichotomised) as the outcome found that published trials tended to use more conservative ICC values (median 0.047, IQR 0.047–0.050) than those reported here.ConclusionsThese estimates of ICCs, IPCs, and WPCs for a variety of outcomes commonly used in diabetes trials can be useful for the design of CRCTs. In studies with observations taken at different time-points, the correlation of observations may decay over time, as reflected in lower values for the IPC than for the ICC. The IPC and WPC estimates are the first reported for UK primary care data.

Impact of diabetes on inpatient mortality and length of stay for elderly patients presenting with fracture of the proximal femur

INTRODUCTION Osteoporosis-related fractures of the proximal femur cause significant morbidity and result in an economic burden on societies. It remains debatable whether diabetic patients with proximal fracture of the femur demonstrate poorer outcomes in terms of hospital stay and mortality compared to non-diabetic controls. METHODS All patients over 65years old admitted to the University Hospital Birmingham during 2007-2010 with a diagnosis of a fracture of the proximal femur (total 1468 including 197 patients with diabetes) were analysed. Eligibility and case definitions were ascertained using electronic records. Multivariate analyses were conducted to control for the confounding effect of covariates, which may be associated with the outcomes of interest on the basis of biological plausibility and known risks. RESULTS In-patient mortality was estimated at 14.2% and 12% for the diabetic and non-diabetic patients respectively. Diabetes was not found to be a significant predictor of in-patient mortality, before and after adjustment for the covariates [Adjusted odds ratio 1.01 (95% CI 0.62-1.65)], in contrast to advancing age, male gender, co-morbidity score, low albumin and high creatinine concentrations. Similarly, median length of stay was greater in the diabetes patients, yet only by a day (20 versus 19 days). This was not statistically significant in either the unadjusted (p=0.17) or in the multivariate analysis (p=0.06). CONCLUSIONS Diabetic patients admitted with fracture of the proximal femur did not demonstrate significantly poorer outcomes in terms of in-patient mortality and length of stay compared to non-diabetic patients.

Inpatient electronic prescribing data can be used to identify ‘lost’ discharge codes for diabetes

Accurate assessment of missed discharge codes for diabetes is critical for effective planning of hospital diabetes services. We wished to estimate the frequency of missed discharge diagnostic codes for diabetes and the impact missed codes would have on diabetes‐related payments to the hospital.