Hugh Mather

Cardiovascular Outcomes in Type 2 Diabetes: A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study

OBJECTIVE To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)—clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)—were recorded. RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (−32 vs. 4%, P = 0.001), total cholesterol (−7 vs. −0.3%, P = 0.004), and total−to-HDL cholesterol ratio (−12 vs. −0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. −2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (−18 vs. −6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of “definite CHD events” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.

Mortality and morbidity from diabetes in South Asians and Europeans : 11-year follow-up of the southall diabetes survey, London, UK

Over 20 % of middle aged and elderly South Asian people throughout the world have diabetes. The associated mortality and morbidity risks are unclear. We compared mortality and morbidity in a cohort of South Asian and European people with diabetes in London, UK, in an 11‐year follow‐up of a population‐based sample of 730 South Asians (mean age 55 in 1984) and 304 Europeans (mean age 67 in 1984) with diabetes aged 30 years and above in 1984. By 1995, 242 (33 %) of South Asians, and 172 (57 %) of Europeans had died. The all‐cause mortality rate ratio (South Asian versus European) was 1.50 (95 % CI 0.72–3.12) for those aged 30–54 years at baseline. Ethnic differences in mortality rates were abolished or reversed in people aged 65 years and above at baseline. The mortality rate ratio for circulatory deaths was 1.80 (95 % CI 1.03–3.16, p < 0.05) and for heart disease was 2.02 (95 % CI 1.04–3.92, p < 0.05) in those aged 30–64 years at baseline. Seventy‐seven per cent of South Asian deaths were caused by circulatory disease, compared with 46 % of European deaths. South Asian survivors were 3.8 times (95 % CI 1.8–8.0, p = 0.001) more likely to report a history of myocardial infarction than Europeans. South Asian adults with diabetes show a markedly increased predisposition to cardiovascular disease compared with Europeans, especially in younger people. This emphasizes the urgent need to reduce cardiovascular risk in this vulnerable group.

Comparison of prevalence and risk factors for microalbuminuria in South Asians and Europeans with Type 2 diabetes mellitus

Although Type 2 (non‐insulin‐dependent) diabetes mellitus (Type 2 DM) is more common in South Asians than in Europeans in the UK, very little is known about complications and their risk factors in South Asians. We sought microalbuminuria in a cross‐sectional study of 583 European and 889 South Asian Type 2 DM clinic attenders to Ealing Hospital, London, over 1 year. Albumin/creatinine ratios were measured in early morning urines. Prevalence of microalbuminuria was greater in South Asians compared to Europeans (40 % versus 33 % in men, p = 0.003, and 33 % versus 19 % in women, p < 0.0001). Glycaemic control was worse and prevalence of hypertension, retinopathy and heart disease was higher in South Asians. Key risk factors for microalbuminuria in both ethnic groups were glycaemic control, diabetes duration, blood pressure, triglyceride and retinopathy, but none accounted for the higher microalbuminuria prevalence in South Asians. Age and sex adjusted odds ratio for microalbuminuria was 1.78 (95 % CI 1.02, 2.82, p = 0.02) in South Asians versus Europeans. After adjustment for confounders, this became 2.07, 95 % CI 1.13, 3.79, p = 0.02. We conclude that microalbuminuria is more common in South Asians with Type 2 DM than in Europeans and, although risk factor relationships appeared similar in both groups, and some risk factors were more prominent in South Asians, this cannot account for the high prevalence of microalbuminuria observed in South Asians.

IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, −174G>C (rs1800795) and −573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 −174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 −573G>C and type 2 diabetes. The observed association of the IL6 −174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.

The scope for cardiovascular disease risk factor intervention among people with diabetes mellitus in England : a population-based analysis from the Health Surveys for England 1991-94

Aims To examine the scope for cardiovascular disease risk factor intervention among diabetic patients in England was examined using data from the Health Surveys for England 1991–94. This evaluation included calculating the proportion who require lipid lowering therapy according to the Standing Medical Advisory Committee (SMAC) guidelines.

Variability in vibration perception threshold among sites: a potential source of error in biothesiometry

Vibration perception threshold was measured with a biothesiometer by a single observer at both medial malleoli and both big toes in 110 diabetic patients aged 15-65 selected at random and in 64 non-diabetic subjects aged 20-65. The vibration perception threshold showed appreciable individual variation both between contralateral sites and between ipsilateral sites, differing by at least 30% between the big toes in 26 (24%) of the diabetic patients and 16 (25%) of the non-diabetic group. Variability between sites was significantly greater in the diabetics than the normal subjects. The vibration perception threshold exceeded published normal values at one or more sites in 22 of the diabetic patients but at all four sites in only four. The wide variability in vibration perception threshold among sites may be due to the tissue characteristics locally and, in diabetic patients, possibly to asymmetric neuropathy. Biothesiometer readings at single or unilateral sites may be unrepresentative or misleading.

Hyperkalaemia in diabetes: prevalence and associations.

Hyperkalaemia is associated with diabetes, but there are no recent reports of its prevalence and associations. Serum potassium concentrations were measured in all 1764 patients attending a diabetic clinic over a 12-month period and found to be > 5.0 mmol/l in 270 (15%), and > 5.4 mmol/l in 67 (4%). There was no other evident cause of hyperkalaemia in 41 of these 67 patients. These data serve to highlight the risk of dangerous hyperkalaemia in diabetic patients, particularly with concurrent administration of angiotensin-converting-enzyme inhibitors and potassium-sparing diuretics.

Insulin sensitivity in non-diabetic relatives of patients with non-insulin-dependent diabetes from two ethnic groups

OBJECTIVE Non‐insulin‐dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non‐insulin‐dependent diabetes from two different ethnic groups.

Increased secretion of 32,33 split proinsulin after intravenous glucose in glucose‐tolerant first‐degree relatives of patients with non‐insulin dependent diabetes of European, but not Asian, origin

OBJECTIVE The aetiology of non‐Insulin dependent diabetes Is unknown, but defective insulin Secretion is a feature. The disease also has a strong genetic basis and first‐degree relatives of patients have an increased risk of future diabetes. To investigate whether β‐cell dysfunction is an early feature of the disease, we studied insulin secretion In healthy first‐degree relatives of patients with non‐insulin dependent diabetes.

Relative Fasting Hypoinsulinaemia and Ultrasonically Measured Early Arterial Disease in Type 2 Diabetes

Macrovascular disease is the most important cause of morbidity and mortality in Type 2 (non‐insulin‐dependent) diabetes. Dyslipidaemia and hyperinsulinaemia have been proposed as aetiological factors. This paper describes the interrelationships between fasting serum insulin, serum lipids, and the extent of ultrasonically measured early arterial disease in Type 2 diabetic subjects screened for entry into a prospective study set up to ascertain whether improving serum lipids can alter the progress of arterial disease in Type 2 diabetes. Measurements were made of the initima media thickness (IMT) in the carotid artery, and an arterial ultrasound score (AUS) based on appearances of both carotid and femoral arteries was calculated for 192 established Type 2 diabetic subjects, males and females, mean age 51 (range 35–66) years, median duration of diabetes 3.5 years, with no known cardiovascular disease. Multiple regression analysis showed that carotid IMT increased with age and was inversely related to serum insulin (variance accounted for, R2, = 8.8 %, p = 0.0002). AUS increased with age and was related inversely to serum insulin, or to C‐peptide when this was substituted in the model. In addition to age and serum insulin, AUS was positively associated with non‐HDL cholesterol and negatively with HDL 3 cholesterol (R2 = 26 %, p = 0.0001). Early thickening and damage to the arterial wall in Type 2 diabetes may be related to relative fasting hypoinsulinaemia.