Neil T. Raymond

Type 2 diabetes and cardiovascular risk in the UK south Asian community

A popular hypothesis for the greater prevalence of type 2 diabetes and cardiovascular disease in UK south Asians is that they have an increased susceptibility of developing insulin resistance in response to certain environmental factors, including obesity and adoption of a sedentary lifestyle. Insulin resistance is postulated as a central feature of the metabolic syndrome, culminating in type 2 diabetes, atherosclerotic vascular disease and CHD; a pathway potentially accelerated by migration/urbanisation. We describe and compare the prevalence of type 2 diabetes, cardiovascular disease and their associated risk factors in UK south Asian and white Caucasian populations to determine possible reasons for the increased preponderance of these diseases in south Asians, and highlight key evidence for optimal risk factor management. Finally, we describe a UK community-based programme that attempts to reduce the morbidity and mortality from type 2 diabetes and cardiovascular disease in south Asians through a new approach to management.

Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial

BACKGROUND Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes. METHODS In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969. FINDINGS We recorded significant differences between treatment groups in diastolic blood pressure (1.91 [95% CI -2.88 to -0.94] mm Hg, p=0.0001) and mean arterial pressure (1.36 [-2.49 to -0.23] mm Hg, p=0.0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0.03 [-0.04 to 0.11] mmol/L), systolic blood pressure (-0.33 [-2.41 to 1.75] mm Hg), or HbA1c (-0.15% [-0.33 to 0.03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio pound28 933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4.9 (95% CI 4.0-5.9) mm Hg, 3.8 (3.2-4.4) mm Hg, and 0.45 (0.40-0.51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0.04% [-0.04 to 0.13]), p=0.290). INTERPRETATION We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes.

Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation

To examine any potential role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in inflammation associated with chronic kidney disease we measured vitamin D metabolites, markers of inflammation and gene expression in 174 patients with a variety of kidney diseases. Urinary MCP-1 protein and renal macrophage infiltration were each significantly but inversely correlated with serum 1,25(OH)2D levels. Logistic regression analysis with urinary MCP-1 as binary outcome showed that a 10-unit increase in serum 1,25(OH)2D or 25OHD resulted in lower renal inflammation. Analysis of 111 renal biopsies found that renal injury was not associated with a compensatory increase in mRNA for the vitamin D-activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1), its catabolic counterpart 24-hydroxylase, or the vitamin D receptor. There was, however, a significant association between tissue MCP-1 and CYP27B1. Patients with acute renal inflammation had a significant increase in urinary and tissue MCP-1, macrophage infiltration, and macrophage and renal epithelial CYP27B1 expression but significantly lower levels of serum 1,25(OH)2D in comparison to patients with chronic ischemic disease despite similar levels of renal damage. In vitro, 1,25(OH)2D attenuated TNFalpha-induced MCP-1 expression by human proximal tubule cells. Our study indicates that renal inflammation is associated with decreased serum vitamin D metabolites and involves activation of the paracrine/autocrine vitamin D system.

Evaluation of delivery of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS)

Aims  We tested the hypothesis that enhanced care for diabetes, tailored to the needs of the South Asian community with Type 2 diabetes, would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality.

Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes.

RATIONALE Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes. OBJECTIVES To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes. METHODS A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals. MEASUREMENTS AND MAIN RESULTS Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0-93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44-5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA. CONCLUSIONS We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes.

Higher Prevalence of Retinopathy in Diabetic Patients of South Asian Ethnicity Compared With White Europeans in the Community: A cross-sectional study

OBJECTIVE—The purpose of this study was to compare prevalence and risk factors for diabetic retinopathy among U.K. residents of South Asian or white European ethnicity. RESEARCH DESIGN AND METHODS—This was a community-based cross-sectional study involving 10 general practices; 1,035 patients with type 2 diabetes were studied: 421 of South Asian and 614 of white European ethnicity. Diabetic retinopathy, sight-threatening retinopathy, maculopathy, and previous laser photocoagulation therapy were assessed after grading of retinal photographs. Data were collected on risk factors including age, duration, and treatment of diabetes, blood pressures, serum total cholesterol, and A1C. RESULTS—Patients of South Asian ethnicity had significantly higher systolic (144 vs. 137 mmHg, P < 0.0001) and diastolic (84 vs. 74 mmHg, P < 0.0001) blood pressure, A1C (7.9 vs. 7.5%, P < 0.0001), and total cholesterol (4.5 vs. 4.2 mmol/l, P < 0.0001). Diabetic retinopathy was detected in 414 (40%) patients (189 South Asian [45%] versus 225 white European [37%]; P = 0.0078). Sight-threatening retinopathy was detected in 142 (14%) patients (68 South Asian [16%] versus 74 white European [12%]; P = 0.0597). After adjustment for confounders, there were significantly elevated risks of any retinopathy and maculopathy for South Asian versus white European patients. CONCLUSIONS—Patients of South Asian ethnicity had a significantly higher prevalence of diabetic retinopathy and maculopathy, with significantly elevated systolic and diastolic blood pressure, A1C, and total cholesterol; lower attained age; and younger age at diagnosis. Earlier onset of disease and higher levels of modifiable risk factors make early detection of diabetes, annual referral for retinal screening, and intensive risk factor control key elements in addressing this health inequality.

Premature cardiovascular events and mortality in south Asians with type 2 diabetes in the United Kingdom Asian Diabetes Study - effect of ethnicity on risk

Abstract Background/Aim: People of south Asian origin have an excessive risk of morbidity and mortality from cardiovascular disease. We examined the effect of ethnicity on known risk factors and analysed the risk of cardiovascular events and mortality in UK south Asian and white Europeans patients with type 2 diabetes over a 2 year period. Methods: A total of 1486 south Asian (SA) and 492 white European (WE) subjects with type 2 diabetes were recruited from 25 general practices in Coventry and Birmingham, UK. Baseline data included clinical history, anthropometry and measurements of traditional risk factors – blood pressure, total cholesterol, HbA1c. Multiple linear regression models were used to examine ethnicity differences in individual risk factors. Ten-year cardiovascular risk was estimated using the Framingham and UKPDS equations. All subjects were followed up for 2 years. Cardiovascular events (CVD) and mortality between the two groups were compared. Trial registration number: ISRCTN 38297969. Findings: Significant differences were noted in risk profiles between both groups. After adjustment for clustering and confounding a significant ethnicity effect remained only for higher HbA1c (0.50 [0.22 to 0.77]; P = 0.0004) and lower HDL (−0.09 [−0.17 to −0.01]; P = 0.0266). Baseline CVD history was predictive of CVD events during follow-up for SA (P < 0.0001) but not WE (P = 0.189). Mean age at death was 66.8 (11.8) for SA vs. 74.2 (12.1) for WE, a difference of 7.4 years (95% CI 1.0 to 13.7 years), P = 0.023. The adjusted odds ratio of CVD event or death from CVD was greater but not significantly so in SA than in WE (OR 1.4 [0.9 to 2.2]). Limitations: Fewer events in both groups and short period of follow-up are key limitations. Longer follow-up is required to see if the observed differences between the ethnic groups persist. Conclusion: South Asian patients with type 2 diabetes in the UK have a higher cardiovascular risk and present with cardiovascular events at a significantly younger age than white Europeans. Enhanced and ethnicity specific targets and effective treatments are needed if these inequalities are to be reduced.

Obstructive Sleep Apnea and Diabetic Nephropathy: A cohort study

OBJECTIVE Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Obstructive sleep apnea (OSA) is common in type 2 diabetes and increases oxidative stress. Hence, OSA could promote the development and progression of DN. RESEARCH DESIGN AND METHODS This was a cohort study in adults with type 2 diabetes. Patients with known OSA or ESRD were excluded. DN was defined as the presence of albuminuria or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. DN progression was based on eGFR measurements. OSA was defined as apnea hypopnea index (AHI) ≥5 events/h. Serum nitrotyrosine abundance (a marker of nitrosative stress) was measured by ELISA. RESULTS A total of 224 patients were included. OSA and DN prevalence was 64.3 and 40.2, respectively. DN prevalence was higher in patients with OSA (OSA+) compared with those without OSA (OSA−) (49.3% vs. 23.8%, P < 0.001). After adjustment, OSA (odds ratio 2.64 [95% CI 1.13–6.16], P = 0.02) remained independently associated with DN. After an average follow-up of 2.5 (0.7) years, eGFR decline was greater in OSA+ compared with OSA− patients (median −6.8% [interquartile range −16.1 to 2.2] vs. −1.6% [−7.7 to 5.3%], P = 0.002). After adjusting, both baseline OSA (B = −3.8, P = 0.044) and AHI (B = −4.6, P = 0.02) remained independent predictors of study-end eGFR. Baseline serum nitrotyrosine abundance (B = −0.24, P = 0.015) was an independent predictor of study-end eGFR after adjustment. CONCLUSIONS OSA is independently associated with DN in type 2 diabetes. eGFR declined faster in patients with OSA. Nitrosative stress may provide a pathogenetic link between OSA and DN. Interventional studies assessing the impact of OSA treatment on DN are needed.

Comparative incidence of Type I diabetes in children aged under 15 years from South Asian and White or Other ethnic backgrounds in Leicestershire, UK, 1989 to 1998.

Abstract.Aims/hypothesis: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds. Methods: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989–98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95 %-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared. Results: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100 000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant. Conclusion/interpretation: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background. [Diabetologia (2001) 44 [Suppl 3]: B 32–B 36]

Prevalence of microalbuminuria and hypertension in South Asians and white Europeans with type 2 diabetes: a report from the United Kingdom Asian Diabetes Study (UKADS)

Microalbuminuria is more common in South Asian individuals compared to white Europeans. The aim of this study was to determine the relationship between blood pressure and microalbuminuria in a cohort of patients with type 2 diabetes in these two ethnic groups. These further data were analysed from 552 patients (311 South Asian patients and 241 white Europeans) who had microalbuminuria screening data collected. Prevalence of microalbuminuria was significantly higher in South Asian compared with white European patients (31% versus 20%, p=0.007). Among patients with normal, untreated blood pressure, the proportion who had microalbuminuria was three times higher among South Asian patients compared with the white European group (30.7% versus 10.1%, p=0.049, relative risk = 3.1 [1.0–9.5]). In addition, despite their higher cardiovascular risk, South Asian patients were less likely to be prescribed a statin or antihypertensive drug treatment. In conclusion, thresholds and targets for treatment of cardiovascular risk factors in South Asians may need to be lower than those for white Europeans, and targeted intervention will be required to achieve this.