Moulinath Banerjee

Diabetes and ethnic minorities

The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes incidence, prevalence, and disease progression varies by ethnic group. This review highlights unique aspects of the risk of developing diabetes, its overwhelming vascular complications, and their management mainly using data among South Asians and African-Caribbeans in the UK but also using non-UK data. It is concluded that although the origin of the ethnic differences in incidence need further clarification, many factors should be amenable to prevention and treatment in all ethnic groups worldwide.

Changes in arterial stiffness but not carotid intimal thickness in acromegaly

CONTEXT Acromegaly increases cardiovascular morbidity. We tested the hypothesis that increased arterial stiffness together with left ventricular hypertrophy may be a contributory factor. PATIENTS AND DESIGN Fifty-six patients (40 males, 54 ± 13 yr; 25 active disease, 31 in remission) and 46 healthy controls (30 males, 52 ± 13 yr) underwent measurements of aortic pulse wave velocity (PWV), carotid Doppler (IMT), echocardiography, and cardiovascular risk factors. RESULTS Mean serum IGF-I was 323 ± 286 ng/ml (sd score 1.8 ± 1.9) in all patients. Age, body mass index, diastolic blood pressure (BP), and lipid levels were similar comparing patients and controls. Systolic BP (130.8 ± 19.9 vs. 122 ± 14 mm Hg controls, P < 0.01) and PWV (11.7 ± 3.8 vs. 9.7 ± 2.8 m/sec, 95% confidence interval -3.4 to -0.7, P <0.01) were higher in patients than controls. Regression analysis revealed age, presence of acromegaly, systolic BP, and body mass index, inversely, as significantly and independently associated with PWV. No difference in carotid IMT was seen (0.8 ± 0.2 patients vs. 0.7 ± 0.2 mm controls, P = 0.5) or between active/controlled disease. In the subset of participants with echocardiography (n = 32), left ventricular mass was higher by a mean of 38.2 g (95% confidence interval -80.9 to +4.6, P = 0.08). CONCLUSION In summary, patients with acromegaly had independently and significantly increased aortic PWV as evidence of arterial stiffening but unaltered carotid IMT compared with controls, also influenced by age and systolic BP. Premature cardiovascular disease in patients with acromegaly is likely related to pressure-related arterial and left ventricular stiffening rather than atherosclerotic disease.

Vildagliptin in clinical practice: a review of literature

Vildagliptin is the second member of the DPP-IV inhibitor class of drugs licensed for the treatment of type 2 diabetes mellitus (T2DM). The novel action of these drugs has promoted a new outlook in the pathobiology of T2DM. This review undertakes to examine the clinical studies published to date, with the aim of evaluating the position of vildagliptin among the drugs that are now available to treat this common dysmetabolic state.

Pregnancy as the prodrome to vascular dysfunction and cardiovascular risk

In previously apparently healthy women, glucose intolerance and high blood pressure during pregnancy are common and frequently occur together. This article reviews the role of these gestational disorders as markers of vascular dysfunction and its pathophysiology. Mechanisms include alterations to function of large arteries and resistance vessels and to capillary blood flow. Much of the vessel pathology is seen in both gestational diabetes and hypertension. In women who have had transient diabetes during pregnancy and later redeveloped overt diabetes, cardiovascular risk is already elevated nearly fourfold before diagnosis, which is almost as high as the average risk after a clinical diagnosis of diabetes is made. This key finding suggests that vascular risk in such women is at least partly independent of overt hyperglycemia.

Evidence that multiple defects in lipid regulation occur before hyperglycemia during the prodrome of type-2 diabetes

Background Blood-vessel dysfunction arises before overt hyperglycemia in type-2 diabetes (T2DM). We hypothesised that a metabolomic approach might identify metabolites/pathways perturbed in this pre-hyperglycemic phase. To test this hypothesis and for specific metabolite hypothesis generation, serum metabolic profiling was performed in young women at increased, intermediate and low risk of subsequent T2DM. Methods Participants were stratified by glucose tolerance during a previous index pregnancy into three risk-groups: overt gestational diabetes (GDM; n = 18); those with glucose values in the upper quartile but below GDM levels (UQ group; n = 45); and controls (n = 43, below the median glucose values). Follow-up serum samples were collected at a mean 22 months postnatally. Samples were analysed in a random order using Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap mass spectrometer. Statistical analysis included principal component (PCA) and multivariate methods. Findings Significant between-group differences were observed at follow-up in waist circumference (86, 95%CI (79–91) vs 80 (76–84) cm for GDM vs controls, p<0.05), adiponectin (about 33% lower in GDM group, p = 0.004), fasting glucose, post-prandial glucose and HbA1c, but the latter 3 all remained within the ‘normal’ range. Substantial differences in metabolite profiles were apparent between the 2 ‘at-risk’ groups and controls, particularly in concentrations of phospholipids (4 metabolites with p≤0.01), acylcarnitines (3 with p≤0.02), short- and long-chain fatty acids (3 with p< = 0.03), and diglycerides (4 with p≤0.05). Interpretation Defects in adipocyte function from excess energy storage as relatively hypoxic visceral and hepatic fat, and impaired mitochondrial fatty acid oxidation may initiate the observed perturbations in lipid metabolism. Together with evidence from the failure of glucose-directed treatments to improve cardiovascular outcomes, these data and those of others indicate that a new, quite different definition of type-2 diabetes is required. This definition would incorporate disturbed lipid metabolism prior to hyperglycemia.

Maternal and Neonatal Influences on, and Reproducibility of, Neonatal Aortic Pulse Wave Velocity

Aortic pulse wave velocity (aPWV), a noninvasive measure of vascular stiffness, is an independent predictor of cardiovascular disease both before and in overt vascular disease. Its characteristics in early life and its relationship to maternal factors have hardly been studied. To test the hypothesis that infant aPWV was positively related to maternal anthropometry and blood pressure (BP) at 28 weeks gestation, after adjusting for neonatal anthropometry and BP, 148 babies born in Manchester were measured 1 to 3 days after birth. A high reproducibility of aPWV, assessed in 30 babies within 3 days of birth, was found with a mean difference between occasions of −0.04 m/s (95% CI: −0.08 to 0.16 m/s). Contrary to our hypothesis, a significant inverse relation was found between neonatal aPWV (mean: 4.6 m/s) and maternal systolic BP (mean: 108.9 mm Hg; r=−0.57; 95% CI: −0.67 to −0.45) but not maternal height nor weight. Neonatal aPWV was positively correlated with birth length, birth weight, and systolic BP. In multiple regression, neonatal aPWV remained significantly inversely associated with maternal systolic BP (adjusted β coefficient: −0.032; 95% CI: −0.040 to −0.024; P<0.001), after adjustment for maternal age, birth weight, length, and neonatal BP (all independently and positively related to aPWV) and for gestational age, maternal weight, and height (unrelated). These results suggest that infant aPWV may be a useful index of infant vascular status, is less disturbing to measure than infant BP, and is sensitive to the gestational environment marked by maternal BP.

Metastatic breast carcinoma presenting with profound hypocalcemia.

Hypocalcemia is a rare complication of malignancy. We present the case of a 30-year-old lady presenting with a grand mal seizure due to profound hypocalcemia. She was subsequently found to be hypoparathyroid and was diagnosed with metastatic breast carcinoma. Treatment with goserelin and exemestane produced a significant reduction in her tumor load and a correction of her hypocalcemia, which was initially refractory to treatment. We believe this to be the first case of metastatic breast carcinoma actually presenting with hypocalcemia and feel that clinicians should be aware of this rare complication.

Risk Factors for Failure of Direct Current Cardioversion in Patients with Type 2 Diabetes Mellitus and Atrial Fibrillation

Introduction Type 2 diabetes mellitus (T2DM) is a well-recognised risk factor for cardiovascular disease and the prevalence of atrial fibrillation (AF) is higher among patients with T2DM. Direct current cardioversion (DCCV) is an important management option in persistent AF. We sought to determine independent risk factors for immediate and short-term outcomes of DCCV for treatment of AF in patients with T2DM. Methods Retrospective outcome analysis of DCCV for persistent AF in 102 T2DM patients compared with 102 controls. Results DCCV was successful in 68 (66.6%) people with T2DM compared to 86 (84.3%) in the control group (P = 0.003). After initial successful cardioversion, only 38 (37.2%) T2DM patients remained in sinus rhythm compared to 63 (61.8%) in the control group (P = 0.007) at a median follow-up of 74.5 days (IQR 69.4–77.4). Multiple logistic regression analysis showed that the presence of T2DM (P = 0.014), digoxin use (P = 0.01), statin use (P = 0.005), left-atrial size (P = 0.01), and LV ejection fraction (P = 0.008) were independent risk factors for immediate DCCV failure. T2DM (P = 0.034) was an independent risk factor for AF relapse. Among patients with T2DM, previous DCCV (P = 0.033), digoxin use (P = 0.035), left-atrial size (P = 0.01), LV ejection fraction (P = 0.036), and HbA1c (P = 0.011) predicted immediate failure of DCCV whilst digoxin use (P = 0.026) was an independent risk factor for relapse of AF. Conclusion T2DM, higher HbA1c, digoxin treatment, and structural and functional cardiac abnormalities are independent risk factors for immediate DCCV failure and AF relapse.

Potential Mechanism of SGLT2i Induced Euglycaemic Diabetic Ketoacidosis

Sodium glucose co-transporter 2 inhibitors are a new group of drugs available to treat patients with type 2 diabetes mellitus. Recently, FDA has sounded a warning of higher risk of Diabetes ketoacidosis among patients treated with this group of agents. This article reviews the available evidence to build a potential hypothesis to explain the development of this complication.

Screening for cardiovascular risk factors in patients admitted for acute coronary syndrome

To the Editor: Diabetes mellitus (DM) is associated with cardiovascular disease and patients with diabetes have worse outcomes after myocardial infarction (MI) compared with those without (1). The prevalence of undiagnosed type 2 diabetes (T2DM) and glucose intolerance is high in patients admitted with acute coronary syndromes. (2). Furthermore, patients with CVD, irrespective of their age, have a prognosis which worsens with increasing glycaemia (3). The current prevalence of diabetes among inpatients in UK hospitals is 5.5–31% (4), rising to 20–25% in high risk patient groups (5). This retrospective audit was undertaken to examine the assessment of glycaemia, lipids and blood pressure management of patients admitted to the Medical Admissions Unit (MAU) of Central Manchester University Hospitals NHS Foundation Trust with a provisional diagnosis of Acute Coronary Syndrome (ACS) between 01 May 2007 and 31 August 2007. We used the Joint British Societies Guideline-2 (JBS2) guidelines (6) as standards for this audit. Data were collected from the medical notes after discharge. All data here are expressed as Mean, 95% CI unless stated otherwise. Significance of the differences was tested by Student’s t-test.