Reports from Belgium, Japan and Wales highlight recent research in diabetes.

Study 1: Diabetes mellitus and fasting glucose are strongly predictors of a poor outcome in males with coronary artery disease and impaired left ventricular function.

Scientists in Belgium recently conducted a study “to evaluate the prognostic value of impaired fasting glucose and diabetes mellitus in male patients with coronary artery disease and poor left ventricular function. and results From a prospective database on patients referred for gated myocardial perfusion imaging between 1998 and 2002 all male patients with a history of coronary artery disease and poor left ventricular function were selected.”

“Poor function was defined as left ventricular ejection fraction (<=)40%. Subjects were classified as nondiabetics with fasting blood glucose levels <110 mg/dL, nondiabetics with impaired fasting glucose (fasting blood glucose between 110 and 125 mg/dL) and diabetics.

Median follow-up was 2.7 years. End points were all-cause mortality, cardiac death and hospitalization for heart failure,” wrote N.R. van de Veire and colleagues, State University Ghent Hospital.

They found, “One hundred and sixty patients were selected (age 65(plusminus)9 years and left ventricular ejection fraction 29(plusminus)8%). In univariate analysis atrial fibrillation, NYHA class, glycaemia and diabetes mellitus discriminated between survivors and nonsurvivors.

“In Cox multivariate regression analysis for all-cause mortality only NYHA class and diabetes mellitus remained significant. Kaplan Meier analysis showed that diabetics had the worst survival and nondiabetics with glucose <110 mg/dL had the best survival. Nondiabetics with impaired fasting glucose had intermediate survival. Analysis for cardiac death/hospitalization for heart failure showed similar results.”

The researchers concluded, “In male patients with coronary artery disease and impaired left ventricular function diabetes mellitus and fasting glucose are strongly predictive of poor outcome. Diabetics have the worst prognosis but nondiabetics with impaired fasting glucose also are at higher risk compared to nondiabetics with low fasting blood glucose.”

van de Veire and colleagues published their study in Acta Cardiologica (Diabetes and impaired fasting glucose as predictors of morbidity and mortality in male coronary artery disease patients with reduced left ventricular function. Acta Cardiol, 2006;61(2):137-143).

For additional information, contact N.R. van de Veire, State University of Ghent Hospital, Dept. Cardiovascular Diseases, Pintelaan 185, B-9000 Ghent, Belgium.

Study 2: Advanced insulin-dependent diabetes mellitus incurred not only right ventricular remodeling but also overt resting left ventricular systolic dysfunction.

According to recent research from Japan, “It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. Eighteen weeks after a streptozotocin injection was given to Wistar-Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted.”

S. Nemoto and colleagues at Fukushima Medical University determined, “Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats.

“The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats.”

The authors concluded, “Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.”

Nemoto and colleagues published their study in Circulation Journal (Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats. Circ J, 2006;70(3):327- 334).

For additional information, contact M. Kawaguchi, Fukushima Medical University, Dept. Internal Medicine 1, 1 Hikarigaoka, Fukushima 9601295, Japan.

Study 3: Increased plasma markers of oxidative stress are associated with coronary heart disease in males with diabetes mellitus.

“Increased oxidative stress is associated with coronary heart disease (CHD We examined the association between plasma markers of oxidative stress and CHD in a crosssectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes,” researchers in Wales report.

J.W. Stephens and colleagues at the University of Wales Swansea described, “Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDLcholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII).”

The data showed, “Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; p=0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7 vs 19.7%; p=0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/ mmol; p=0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4 vs 35.1%; p=0.003).

“No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (80% vs 37.1 (7.9)%; p=0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99-3.70; p=0.04). This remained unchanged after adjustment for classic risk factors.”

The researchers concluded, “A cross-sectional and prospective association exists between baseline plasma measures of oxidative stress and CHD risk. The association with prospective CHD risk remained after adjustment for ‘traditional’ risk factors, implying an independent role for oxidative stress in CHD risk.”

Stephens and colleagues published their study in Clinical Chemistry (Increased plasma markers of oxidative stress are associated with coronary heart disease in males with diabetes mellitus and with 10-year risk in a prospective sample of males. Clin Chem, 2006;52 (3):446-452).

For additional information, contact J.W. Stephens, University of Wales Swansea, School of Medicine, Swansea SA2 8PP, W Glam, Wales.