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Aims: To estimate the coronary heart disease and cardiovascular disease risk associated with novel biomarkers in Type 2 diabetes mellitus., Methods: We measured baseline peripheral blood concentrations of soluble E-selectin, factor XIIa, thrombin-antithrombin III complex and plasminogen activator inhibitor-1 in 86 patients with Type 2 diabetes free of known coronary heart disease. We used Cox proportional hazard models to estimate multivariable-adjusted hazard ratios associated with biomarker levels for 10-year coronary heart disease risk (n = 33 events) or total cardiovascular disease risk (n = 45 events)., Results: At baseline, mean (sd) age was 62 years (7 years); 62 were men; and 43 had microalbuminuria. Soluble E-selectin demonstrated cross-sectional relationships with glucose and factor XIIa was related to plasminogen activator inhibitor-1 and triglycerides (all P < 0.05). Baseline log soluble E-selectin was significantly related to incident coronary heart disease and cardiovascular disease. Hazard ratios (95% CIs) associated with a 1-unit increase in log soluble E-selectin in age- and sex-adjusted models were: coronary heart disease : 4.6 (95% CI 1.9-11.3), P = 0.001; cardiovascular disease: 3.6 (95% CI 1.7-7.4, P = 0.001); and in multivariable-adjusted models were: coronary heart disease: 2.9 (95% CI 1.2-7.1, P = 0.02); cardiovascular disease: 2.3 (95% CI 1.1-4.8), P = 0.02. Factor XIIa was significantly related to incident cardiovascular disease. The hazard ratios associated with a 1-unit increase in factor XIIa in age- and sex-adjusted models was 1.5 (95% CI 1.1-1.9, P = 0.003) and in a multivariable-adjusted model was 1.3 (95% CI 1.0-1.6, P = 0.047). Plasminogen activator inhibitor-1 and thrombin-antithrombin III complex were not related to cardiovascular disease events., Conclusions: In our study, soluble E-selectin and factor XIIa were significantly related to 10-year incident macrovascular events in patients with Type 2 diabetes. These preliminary findings call for replication in larger studies., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims: We aimed to compare levels of urinary albumin excretion and the prevalence of microalbuminuria in UK South Asians and Europeans. Microalbuminuria predicts cardiovascular disease in European origin populations, but evidence from the general population of South Asians is lacking. Coronary heart disease (CHD) mortality is 40-50% higher in UK South Asians compared with the whole population, for reasons that are incompletely understood., Methods: Microalbuminuria was measured using the albumin-creatinine ratio in an age- and sex-stratified random sample of 1509 adults from European (n = 825), Indian (n = 259), Pakistani (n = 305) and Bangladeshi (n = 120) ethnic groups., Results: Levels of urinary albumin excretion were substantially higher in South Asians (geometric mean albumin creatinine ratio (95% confidence interval) 0.83 (0.75, 0.91)) than in Europeans (0.55 (0.51, 0.60)). Microalbuminuria was associated with older age, hypertension and diabetes, but independently of these risk factors urinary albumin excretion was higher in South Asians than Europeans., Conclusions: Urinary albumin excretion is higher and microalbuminuria more frequent in UK South Asians compared with the majority ethnic population. Microalbuminuria may be relevant to the causal pathways leading to the excess of cardiovascular mortality and possibly renal failure in UK South Asians.

Aims: To document uptake of influenza and pneumococcal vaccination in diabetic patients attending secondary care in the Northern Region, and to explore influencing factors., Methods: Diabetic patients attending out-patients in Middlesbrough, Gateshead and Newcastle were questioned from October 1999 to March 2000. Physicians inquired about influenza and pneumococcal vaccination status using a standardized questionnaire. Data collected included age, year of diagnosis, duration of diabetes, type of diabetes, and the presence of other recognized indications for vaccination., Results: Two hundred and sixty-eight diabetic patients, 42% (113/268) with Type 1 diabetes, 34% (91/268) with ischaemic heart disease, 10% (26/268) with chronic pulmonary disease (CPD) and 10% (27/268) with chronic renal disease, were questioned. Thirty-five percent (93/268) of patients received both influenza and pneumococcal vaccines, 24% (64/268) received only influenza vaccine, and none received pneumococcus vaccine alone. Most vaccinees received advice about influenza and pneumococcal vaccination from their general practitioner (90% (142/157) and 87% (81/93), respectively). A large number of non-vaccinees were unaware of the need for influenza and pneumococcal vaccination (69% (76/111) and 91% (159/175), respectively). Using multiple logistic regression co-existing CPD increased the odds of receiving influenza (odds ratio (OR) (95% confidence interval (CI)) = 1.99 (1.07-14.12)) or pneumococcal (OR = 3.77 (1.69-21.76)) vaccination. Furthermore, each 1-year increase in age increased the chance of receiving influenza or pneumococcal vaccination by 22% (OR = 1.22 (1.09-1.67) and 29% (OR = 1.29 (1.07-1.72)), respectively., Conclusions: Vaccination rates in these diabetic patients are unsatisfactory. Secondary care health professionals might increase rates by raising the topic in consultations. Diabet. Med. 18, 599-603 (2001)

Aims: To compare left ventricular mass (LVM) index and function in patients with Type 2 diabetes mellitus with and without microalbuminuria and to investigate the clinical determinants of left ventricular hypertrophy., Methods: Echocardiography, electrocardiography and 24-h ambulatory blood pressure monitoring were performed in microalbuminuric (n = 29) and normoalbuminuric (n = 29) patients with Type 2 diabetes and no clinical evidence of heart disease. Groups were individually matched for age, sex and diabetes duration and smoking status., Results: LVM index (62 (34-87) vs. 52 (33-89) g/m2.7, P = 0.04) and LVH prevalence, using two out of three definitions, were greater in patients with microalbuminuria (LVM/height2.7: 72 vs. 59%, P = 0.27, LVM/height: 66 vs. 38%, P = 0.04, LVM/body surface area: 59 vs. 31%, P = 0.03). Night-time systolic blood pressure (126 (99-163) vs. 120 (104-157) mmHg, P = 0.005) and the night/day systolic blood pressure ratio (0.92 (0.08) vs. 0.88 (0.06), P = 0.04) were higher in those with microalbuminuria. Systolic and diastolic function were similar in both groups. Linear regression analyses showed that body mass index (BMI) was significantly related to loge LVM index (R2 = 11.8%, P = 0.005) and a relationship with night/day systolic blood pressure was also suggested (R2 = 4.6%, P = 0.057)., Conclusions: In patients with Type 2 diabetes, LVH is more common and severe in those with microalbuminuria. Its presence may be related to raised night/day systolic blood pressure ratio and is significantly related to BMI. The high prevalence of LVH strengthens the case for echocardiographic screening in Type 2 diabetes to identify high risk patients who might benefit from aggressive cardiovascular risk factor intervention.

Aims: To test the common assumption that pregnant women who are sufficiently motivated to achieve very good HbA1c levels will record home blood glucose data accurately., Methods: A new device was used to download information from electronic blood glucose meters to assess the extent of selectivity in patient glucose diary-keeping., Results: In an index case, a woman with excellent ambient HbA1c (5.9%; upper limit of normal 6.1%) was observed to have 68% of preprandial blood glucose readings above the target range of 3.5-6.5 mmol/l and a mean (+/- SD) level of 8.9+/-3.9 mmol/l in the corresponding period. No such impression was conveyed by the home monitoring diary. Six pregnant women with well controlled Type 1 diabetes (mean HbA1c 6.6+/-0.2%) exhibited between 42 and 68% of preprandial readings above the target range., Conclusions: The frequency of hyperglycaemia has hitherto been underestimated in well controlled pregnant women whose near-perfect home monitoring record is apparently corroborated by near-normal HbA1c levels. These observations provide a hypothesis for understanding of the disappointing continuance of macrosomia despite excellent HbA1c levels throughout pregnancy.

Type 2 (noninsulin-dependent) diabetes mellitus (DM) affects about 3% of the UK population. Diabetes often coexists with a cluster of other potent cardiovascular risk factors, including hypertension, dyslipidaemia and increased tendency for thrombosis, and increases the risk of early death from cardiovascular causes by about threefold. Microalbuminuria or proteinuria also may be present, further increasing the risk of cardiovascular mortality. Cardiovascular risk factors must be treated aggressively in patients with Type 2 diabetes and control of blood pressure at 140/85 mm Hg or lower is a priority. The management of hypertension in patients from some ethnic groups demands special consideration because they have a high incidence of diabetes and hypertensive complications. Patients must be urged to adopt appropriate lifestyle changes in the first instance but additional drug treatment for hypertension is usually required. All the major classes of antihypertensive agents lower blood pressure in Type 2 diabetic patients but have different effects on metabolic risk factors in different ways. Low-dose thiazide diuretics, beta-blockers, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk. Individually, the effects of low-dose thiazide diuretics and beta-blockers on glucose and lipid metabolism is clinically insignificant, though in combination much larger metabolic effects are seen. ACE inhibitors and calcium channel blockers have no, or small, beneficial effects on glucose and lipid metabolism, while the greater beneficial effects of alpha1-blockers on lipid profiles may render them especially useful in the Type 2 diabetic patient. Long-acting calcium-channel blockers and ACE inhibitors protect renal function and are suitable as first line therapy in patients with microalbuminuria or proteinuria. Until results from the current batch of randomized, placebo-controlled trials comparing different classes of antihypertensive agents are available, the choice of antihypertensive agent is difficult. Addressing overall cardiovascular risk factors, rather than hypertension alone, is essential in the management of the hypertensive Type 2 diabetic patient.

The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

Several observations suggest that inherited factors are influential in the development of nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). Genetic components of the renin angiotensin system are possible candidate genes. The aim of this study was to determine the role of the hypertension associated angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in susceptibility to nephropathy in IDDM. We examined 264 Caucasoid patients with IDDM and overt nephropathy (as defined by persistent proteinuria in the absence of other causes, hypertension and retinopathy), 136 IDDM patients with long duration of diabetes and no nephropathy (LDNN group), 200 recently diagnosed IDDM patients (Sporadic Diabetic group), and 212 non-diabetic subjects. The AT1R gene polymorphism was assessed using the polymerase chain reaction and restriction isotyping. Genotype frequencies did not differ significantly between the sporadic diabetic group and the nephropathy group (p = 0.245), nor between the long duration non-nephropathy group and the nephropathy group (p = 0.250). Allele frequencies were not significantly different between the three groups (p = 0.753). We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.

Increased fracture frequency and low bone mass have each been reported in patients with diabetes. To see if these were related to increased bone resorption we have measured the urinary excretion of hydroxyproline in 73 patients with Type 1 (insulin-dependent) diabetes, 67 patients with Type 2 (non-insulin-dependent) diabetes, and 75 control subjects. Hydroxyproline excretion was increased in both types of diabetes: Type 1: 21 (10-36) (median (IQR) mumol mmol creatinine-1; Type 2: 25 (13-43) mumol mmol creatinine-1; control: 10 (6-22) mumol mmol creatinine-1 (p < 0.0001 and < 0.0002, respectively). Hydroxyproline excretion was not related to age, duration of diabetes or blood glucose control. Neither was it different in patients with or without retinopathy, neuropathy and macrovascular disease. However it was higher in patients with microalbuminuria at 35 (20-53) mumol mmol creatinine-1 than in those with normal protein excretion (25(13-37) mumol mmol creatinine-1 p = 0.03) or those with established proteinuria (18(8-26) mumol mmol creatinine-1 p = 0.001). We conclude that there is evidence of increased bone resorption in diabetes and that this is related to alterations in renal function.

It now seems worth while to identify Type 1 diabetic patients with microalbuminuria, as improved blood glucose control and reduction of arterial blood pressure will slow if not prevent the progression to persistent proteinuria. Measurement of albumin excretion rate (AER) in a timed urine sample remains the gold standard for the definition of microalbuminuria, but is not a practical screening procedure. Thus attempts have been made to relate the albumin concentration of albumin:creatinine ratio in random or first morning urine samples to AER. There is a weak correlation of albumin concentration (r = 0.32 to 0.68) and albumin:creatinine ratio (r = 0.43 to 0.54) in a random urine sample with AER, and low sensitivity and specificity of a variety of different albumin concentrations and albumin:creatinine ratios to predict microalbuminuria. The correlation of albumin concentration (r = 0.86 to 0.90) and albumin:creatinine ratio (r = 0.74 to 0.91) in an early morning urine sample with AER is stronger. Measurement of albumin:creatinine ratio in an early morning urine sample appears to be the most reliable method of screening for microalbuminuria, with sensitivity of 88 to 100% and specificity 81 to 100% depending on the cut-off ratio chosen and the definition of microalbuminuria used. If the albumin:creatinine ratio in an early morning urine sample is less than or equal to 3.5 mg mmol-1, the patient can be classed as normoalbuminuric and re-screened annually. If the ratio is greater than or equal to 10.0 mg mmol-1, confirmation of microalbuminuria should be sought in a timed urine collection and appropriate therapy begun.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a comparison of continuous intraperitoneal insulin infusion (CIPII) and continuous intravenous insulin infusion (CIVII) in 6 diabetic patients in whom severe hyperglycaemia and ketoacidosis could not be prevented with subcutaneous or intramuscular insulin. In the short term both methods were equally effective in maintaining glycaemic control. Blood glucose, glycerol, and 3-hydroxybutyrate levels were normal but lactate and pyruvate levels remained elevated with both treatments. Insulin requirements were significantly lower on CIPII than CIVII (70 vs 113 U/day, p less than 0.01). Intraperitoneal insulin delivery was associated with near physiological peripheral plasma insulin profiles in 3 patients. In the longer term CIVII was associated with frequent septicaemia and thrombosis, and was successful in preventing hospitalization for 6 months or more in only one patient. Despite technical problems with CIPII complications were less serious and hospital admission due to metabolic decompensation was prevented for 6 months or more in 3 patients. When subcutaneous insulin delivery is unsuccessful in the management of brittle diabetes, CIPII should be considered rather than CIVII because it is more likely to be successful and less likely to cause serious complications.

Twelve C-peptide negative insulin-dependent diabetic patients participated in a randomized cross-over study of 6 months treatment with twice or thrice daily insulin injection therapy and continuous subcutaneous insulin infusion (CSII). Standard, non-intensified management conditions were maintained throughout. Glycosylated haemoglobin levels were similar on both regimens (9.2 +/- 0.5% versus 9.0 +/- 0.4%; CSII vs injection therapy; (mean +/- SEM). Capillary blood glucose concentrations before breakfast (5.2 +/- 0.4 mmol/l vs 9.1 +/- 0.8 mmol/l), after lunch (6.5 mmol/l +/- 0.8 vs 7.9 +/- 1.0 mmol/l) and before the evening meal (5.0 +/- 0.7 mmol/l vs 7.7 +/- 0.7 mmol/l) were lower on CSII, as were 24-hour urine glucose excretion and total insulin dose (39.3 +/- 2.2 vs 49.8 +/- 4.0 U/day). There was a significant positive correlation between fasting blood glucose values and glycosylated haemoglobin on injection but not pump treatment. Thus although blood glucose control at some individual daytime points appeared lower on CSII, overall diabetic control was similar on the two regimens.