W. Richmond

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.

Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study

AIMS The PREDICT Study is a prospective cohort study designed to evaluate coronary artery calcification score (CACS) as a predictor of cardiovascular events in type 2 diabetes (T2DM). METHODS AND RESULTS A total of 589 patients with no history of cardiovascular disease and with established T2DM had CACS measured, as well as risk factors, including plasma lipoprotein, apolipoprotein, homocysteine and C-reactive protein concentrations, homeostasis model assessment insulin resistance (HOMA-IR), and urine albumin creatinine ratio. Participants were followed for a median of 4 years and first coronary heart disease (CHD) and stroke events were identified as primary endpoints. There were 66 first cardiovascular events (including 10 strokes). CACS was a highly significant, independent predictor of events (P < 0.001), with a doubling in CACS being associated with a 32% increase in risk of events (29% after adjustment). Hazard ratios relative to CACS in the range 0-10 Agatston units (AU) were: CACS 11-100 AU, 5.4 (P = 0.02); 101-400 AU 10.5 (P = 0.001); 401-1000 AU, 11.9 (P = 0.001), and >1000 AU, 19.8 (P < 0.001). Only HOMA-IR predicted primary endpoints independently of CACS (P = 0.01). The areas under the receiver operator characteristic curve for United Kingdom Prospective Diabetes Study (UKPDS) risk engine primary endpoint risk and for UKPDS risk plus CACS were 0.63 and 0.73, respectively (P = 0.03). CONCLUSION Measurement of CACS is a powerful predictor of cardiovascular events in asymptomatic patients with T2DM and can further enhance prediction provided by established risk models.

Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries

OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history.

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH‐deficient adults

To study the effects of long‐term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH‐deficient adults.

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin‐mediated glucose disposal, basal and glucose‐stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL‐cholesterol (r=0.65, p<0.05), HDL2‐cholesterol (r=0.59, p<0.05), and apolipoprotein A1 (r=0.57, p<0.05) and negatively with apolipoprotein B (r=‐0.53, p<0.05) and total: HDL‐cholesterol ratio (r=‐0.68, p<0.01). Fasting C‐peptide correlated negatively with HDL‐cholesterol (r=‐0.76, p<0.01), HDL2‐cholesterol (r= −0.80, p<0.001) and apoprotein A1 (r=‐0.56, p<0.05) and positively with total:HDL‐cholesterol ratio (r=0.64, p<0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose‐stimulated plasma insulin and C‐peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL‐cholesterol independent of insulin insensitivity. In addition, fasting C‐peptide alone accounted for 70 % of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL‐cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.

Elevated leptin concentrations in growth hormone-deficient hypopituitary adults.

Hypopituitarism with growth hormone (GH) deficiency is associated with obesity characterized by central (abdominal) distribution of fat. Recent work has demonstrated that leptin, a product of obese gene, is raised in obesity.

The Effect of Glibenclamide and Metformin on Serum Lipoproteins in Type 2 Diabetes

In a cross‐over study, the effects of 3 months treatment with metformin or glibenclamide on body weight, blood glucose control, and serum lipoproteins were compared in 35 Type 2 diabetic patients, inadequately controlled by dietary therapy alone. Glibenclamide alone increased body weight (mean change + 2.75 kg; 95% confidence intervals − 1.95 to + 3.55 kg; p < 0.0001). Glibenclamide and metformin achieved equivalent blood glucose control, independent of initial body mass index. Neither drug affected serum triglyceride concentration. Metformin alone significantly reduced low density lipoprotein cholesterol (mean change − 0.34 mmol l−1; 95% confidence intervals − 0.12 to − 0.57 mmol l−1; p < 0.01). Neither drug altered high density lipoprotein or subfraction cholesterol.

The association of coronary calcium score and conventional cardiovascular risk factors in Type 2 diabetic subjects asymptomatic for coronary heart disease (The PREDICT Study)

Aim To determine the association between coronary calcification score (CACS) obtained by electron beam computed tomography (EBCT) and cardiovascular risk factors in Type 2 diabetic subjects entered into a prospective cohort study.

Plasma Antioxidants: Evidence for a Protective Role against Reactive Oxygen Species following Cardiac Surgery

Total plasma antioxidant status (TPAS), lipid peroxide concentration (LPX) and cardiac troponin T (cTnT) were measured in 24 patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Samples were obtained preoperatively and at 1.5 h, 6 h, 24 h and 72 h after CPB. The absolute TPAS values were significantly lower at 1.5 h, 6 h, 24 h and 72 h after CPB than were preoperative values (P < 0.05). The LPX concentration was significantly elevated at 1.5 h after CPB (P < 0.05). Cardiac troponin T concentrations were significantly elevated at all time points postoperatively (P < 0.05). Preoperative TPAS values were significantly correlated with the magnitude of fall in TPAS at 1.5 h (P < 0.05). The greater the fall in TPAS between 0 and 1.5 h, the less LPX was formed between 0 and 1.5 h. The LPX at 1.5 h displayed a significant correlation with cTnT release from myocardial myocytes (P < 0.05). These data provide evidence for the first time that the consumption of antioxidants during CABG surgery with CPB protects against the production of reactive oxygen species and subsequent myocyte necrosis. Furthermore, the availability of protective antioxidants is dependent upon preoperative TPAS.