Retinopathy as an independent predictor of all-cause mortality in individuals with type 2 diabetes

AimsTo assess whether the presence and grade of diabetic retinopathy (DR) predict all-cause mortality, independent of risk factors for cardiovascular disease (CVD) and other complications, including diabetes-related kidney disease (DKD) and CVD, in individuals with type 2 diabetes mellitus.MethodsProspective cohort study that enroled 15,773 patients in 19 Italian centers in 2006–2008. DR ascertained by fundoscopy, DKD by albuminuria and estimated glomerular filtration rate, and prior CVD by hospital discharge records. All-cause mortality retrieved for 15,656 patients on 31 October 2015.ResultsThe adjusted risk of death was increased in patients with any DR (hazard ratio, 1.136 [95% confidence interval, 1.054;1.224] P < 0.0001), advanced DR, including severe non-proliferative and proliferative DR and diabetic macula edema (1.213 [1.097;1.340] P < 0.0001), and especially proliferative DR alone (1.381 [1.207;1.580] P < 0.0001), compared with those without DR. The impact of DR was more evident in patients without than in those with DKD or CVD. Mortality risk was increased in participants with DR alone, though much less than in those with DKD or CVD alone and particularly in those with both DR and DKD or CVD. DR grade was related to mortality in individuals without DKD or CVD, whereas it conferred no additional risk to those with albuminuric or nonalbuminuric DKD or established CVD.ConclusionsIn patients with type 2 diabetes mellitus, the excess mortality risk conferred by DR is relatively small and higher in those without DKD and CVD, suggesting that it may be mediated by the concurrent presence of these complications, even at a subclinical level.     

Interleukin-8 as an independent predictor of long-term clinical outcome in patients with coronary artery disease

Left ventricular torsion is a measurement derived from the twisting or wringing motion of the heart around its long axis. The calculation is made by measuring the magnitude of rotation at the apex of the heart, and subtracting the rotation at the base. Although the phenomenon of left ventricular twisting was first described in the 17th Century, it wasn't until the 1960s that the first invasive method of measurement was demonstrated. Silver tantalum clips were sutured into the epicardium during cardiac surgery and viewed using cineradiography. Non-invasive torsion measurement has been subsequently developed, adopting Magnetic Resonance Imaging and 2D echocardiography. Interest in the changes of different components of torsion, during various cardiac disease states has developed with the advent of these non-invasive measurement techniques. This review article summarises the history of the development of torsion analysis and describes the known changes of torsion during different clinical circumstances.     

Coronary artery disease in patients at low risk--apolipoprotein AI as an independent risk factor

Many risk factors for coronary artery disease (CAD) have been established by large epidemiological studies. However, some patients without the major risk factors still develop disease. Preliminary analysis of individuals referred for angiography, who had no major risk factors associated with CAD, indicated that apolipoprotein-AI (apoAI) was significantly lower in patients with positive angiograms. The hypothesis that apoAI was an independent risk factor for CAD in low risk populations was put forth. One thousand and seventy-five consecutive patients underwent angiography, lipid analysis, and completed a risk factor questionnaire. Individuals with total cholesterol<5.2 mmol/l, high density lipoprotein (HDL)-cholesterol>0.9 mmol/l, systolic blood pressure<140 mmHg and diastolic blood pressure<90 mmHg, no diabetes, and no family history of premature CAD in first degree relatives were selected. Fifty-four patients met these selection criteria, 29 having positive evidence of CAD and 25 with no evidence of disease. Multivariate analysis revealed that, after adjusting for age and gender, serum apoAI level was the only variable predictive of CAD. This effect was independent of HDL cholesterol level and fractional esterification rate of HDL (FER(HDL)). These results point to an important role for apoAI in the atherogenic process, particularly in populations with no major CAD risk factors. Decreased levels of apoAI or LpAI may initiate atherosclerosis in a highly selected group of low risk patients.     

Erectile dysfunction as a predictor of asymptomatic coronary artery disease in elderly men with type 2 diabetes

Objectives. Erectile dysfunction (ED) is a recognized predictor of asymptomatic coronary artery disease (CAD) in diabetic patients and represents the most common sexual dysfunction in older men with or without diabetes. No study has evaluated whether ED is able to predict the presence of asymptomatic CAD in elderly diabetic patients. Therefore, the aim of the present study is to evaluate whether ED is associated with asymptomatic CAD in 66 years or older men with type 2 diabetes. Methods. We consecutively enrolled 328 men with type 2 diabetes: 213 subjects were 65 years old or younger (GROUP A) and 115 were older than 65 years (GROUP B). After a systematic screening for asymptomatic CAD, the two study groups were stratified by the presence/absence of documented angiographic CAD. Forty-five subjects in the GROUP A and 37 in the GROUP B had CAD. ED has been evaluated by the validated International Index of Erectile Function-5 (IIEF-5) questionnaire. Results. In the GROUP A the prevalence of subjects with ED was significantly higher among subjects with than in those without CAD (31.1% vs 16.6%; p=0.030), while no significant difference in ED prevalence was observed between patients with and without CAD among older men (48.6% vs 39.7%; p=0.364). The multivariate analysis found that ED was significantly associated with asymptomatic CAD in younger (OR: 1.87; 95%CI:1.02-7.31; p=0.046), but not in older men. Conclusions. Our study shows that ED seems to lose its powerful role of predictor of asymptomatic CAD in elderly type 2 diabetic patients.     

Coronary artery disease screening in patients with diabetes

Coronary artery disease (CAD) is the most common cause of death in patients with diabetes. Many diabetics have asymptomatic CAD, and may benefit from early diagnosis. We review the recent literature to evaluate whether the current evidence supports screening for CAD in asymptomatic diabetics. Currently, no single screening modality has shown sufficient accuracy to determine which patients will have significant CAD. The combination of imaging modalities may show promise in improving the accuracy of screening, and limited data suggest that screening in this population may be associated with improved outcomes. However, based on the current evidence we presently do not recommend screening for CAD in this population.     

Proliferative diabetic retinopathy is a predictor of coronary artery disease in Japanese patients with type 2 diabetes

A retrospective cohort study was performed to investigate the relationship between diabetic retinopathy and coronary artery disease in 371 Japanese adult patients with type 2 diabetes. We found that proliferative retinopathy was significantly associated with an increased risk of coronary artery disease, even after adjustment for classical coronary risk factors.     

Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels <303 micromol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 micromol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p < or = 0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p < or = 0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality-including diuretic use-elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD.     

Carotid intima-media thickness as an independent predictor of coronary artery disease.

BACKGROUND: A noninvasive technique of measuring carotid artery intima-media thickness has recently generated considerable interest as a marker of atherosclerosis and in the prediction of clinical coronary events and coronary artery disease. The present study evaluated the association of carotid artery intima-media thickness in the prediction of coronary artery disease in a western Indian population. METHODS AND RESULTS: Carotid artery intima-media thickness was measured with a B-mode scan in an ongoing study of 266 patients, who were further subdivided into 4 subgroups: those with non-insulin dependent diabetes mellitus; hypertension; diabetes mellitus with hypertension; and those without diabetes or hypertension (labeled as controls). The maximal intima-media thickness greater than 0.8 mm at the far wall of the common carotid artery, excluding raised lesions and plaques, was selected as the highest value for comparison. The subgroups were further divided into those with and without apparent coronary artery disease. A statistically significant intima-media thickness greater than 0.8 mm was observed in 59.2% of the subjects with coronary artery disease as against 40.8% in those without the disease on univariate analysis. A higher incidence of intima-media thickness of more than 0.8 mm was observed in all subgroups with coronary artery disease as against those without the disease, which was most marked in the hypertensive group (22.2% v. 3.6%) and contributed to the increased arterial thickness in diabetics with concomitant hypertension. Multivariate regression analysis revealed carotid artery intima-media thickness to be associated with coronary artery disease with an odds ratio of 2.40. CONCLUSIONS: Carotid artery intima-media thickness is a simple, noninvasive and reproducible clinical tool to evaluate atherosclerosis and predict coronary artery disease in Indian subjects. Prospective studies in a larger number of subjects, particularly in those undergoing coronary angiography, will help in establishing the role of this technique.     

Silent coronary artery disease in patients with type 2 diabetes mellitus

Abstract. The purpose of this study was to estimate the prevalence and risk factors of silent CAD in asymptomatic type 2 diabetic patients aged over 40 years. A total of 172 asymptomatic type 2 diabetic patients, mean age 54.42 years, with normal resting electrocardiogram were included in the study. Technetium-99m (Tc-99m) tetrofosmin cardiac single photon emission computed tomography myocardial scintigraphy with exercise testing or dipyridamole injection was performed on all patients. If this test was positive, coronary angiography was carried out and was considered to be positive with a stenosis of 70%. Abnormal perfusion pattern was found in 14 patients (8.14%). Significant coronary artery stenosis was found in 13 subjects (7.56%), confirming a high positive predictive value (92.86%) of this diagnostic procedure. A significant correlation was observed between silent CAD and male sex, retinopathy, hypertension, post-prandial blood glucose level, and low HDL-cholesterol level. Sex (OR=4.026; 95% CI, 1.187–13.659), hypertension (OR=5.564; 95% CI, 1.446–21.400) and retinopathy (OR=3.766; 95% CI, 1.096–12.948) were risk factors for CAD. Overall, 14.06% of asymptomatic male patients with type 2 diabetes mellitus presented silent CAD with significant angiographically documented coronary stenosis. This finding, along with the high positive predictive value of a noninvasive technique, indicates that routine screening for silent CAD would be useful in this patient subgroup especially when they have retinopathy or hypertension.     

Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes

Aims/hypothesis The goals of this study were to determine whether coronary calcium is associated with the presence of clinical cardiovascular disease in individuals with type 2 diabetes and if the measurement of abdominal aortic calcium may have an independent or added benefit as a surrogate marker for clinical vascular disease.Methods A cross-sectional study of subjects with type 2 diabetes enrolled in seven medical centres in the USA participating in a Veterans Affairs Cooperative Study of glycaemic control. Enrolled subjects included 309 veterans over 40 years of age with type 2 diabetes, with or without stable cardiovascular disease, who had inadequate glycaemic control (HbA₁c>7.5%) on oral agents and/or insulin. The study assessed lifestyle behaviours, standard cardiovascular risk factors and coronary artery and abdominal aorta calcification by electron beam computed tomography.Results Subjects with coronary artery or abdominal aorta calcification present had a strikingly higher prevalence of peripheral artery disease, coronary artery disease and all combined cardiovascular disease. Prevalence of each condition increased from 5- to 13-fold with increasing quintiles of coronary artery calcification and from 2- to 3-fold with increasing abdominal aorta calcification. These associations persisted after adjustment for lifestyle behaviours and standard cardiovascular risk factors.Conclusions/interpretation These results support the notion that vascular calcium in type 2 diabetes provides additional information beyond that of standard risk factors in identifying the presence of cardiovascular disease. Subclinical measures of atherosclerosis such as arterial calcification may help more precisely stratify these individuals and alert healthcare providers to those individuals who have particularly accelerated atherosclerosis.     

Apolipoprotein e4 allele is predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus

The presence of the apolipoprotein (Apo) e4 allele is reported to be associated with the increased risk of coronary artery disease (CAD), as well as the impairment of endothelium-dependent dilation in type 2 diabetes mellitus. Therefore, we hypothesized that the Apo e4 allele increases the death risk from coronary artery disease in type 2 diabetes. From January 1993 to December 1999, 36 type 2 diabetic patients with e4/4 or e4/3, 62 with e3/3 and 33 with e2/2 or e3/2 genotypes were recruited. All subjects were unrelated, elderly, type 2 diabetic patients with coronary artery disease, aged 60-84 years, with cardiac function at the Class I stage at time of enrollment. A follow-up study of 3-10 years was undergone. The results are as follows: At baseline, serum total cholesterol and low density lipoprotein (LDL) cholesterol concentrations were higher in subjects with e4/3 or e4/4 than in subjects with e2/2 or e3/2 (P = 0.026). Lipoprotein(a) concentration was lower in subjects with e2/2 or e3/2 than in subjects with e3/3 (P = 0.044) and e4/3 or e4/4 (P = 0.038). During the 3-10 years follow-up period, a total of 39 patients who died from CAD was recorded in this sample. Compared with patients with e3/3 (P = 0.030) and patients with e2/2 or e3/2 genotypes (P = 0.001), the mortality rate of CAD in patients with e4/3 or e4/4 genotypes was the highest (50%). Stepwise discriminant analysis revealed that in the diabetic population studied the Apo e4 allele was independently and significantly associated with CAD death (B = 0.64). However, the strength of the association decreased (B = 0.48) when total cholesterol, LDL-cholesterol and lipoprotein(a) were included in the model. Therefore, we concluded that Apo e4 allele increases the risk of CAD death in elderly patients with type 2 diabetes mellitus.     

Management of coronary artery disease in patients with type 2 diabetes mellitus

Diabetes mellitus is as much a vascular disease as it is a metabolic disorder. The metabolic abnormalities associated with diabetes include hyperglycemia, and abnormal carbohydrate, fat, and protein handling. These abnormalities increase oxidative stress and activate the renin angiotensin system, which subsequently causes endothelial dysfunction and predisposes to atherosclerosis. Type 2 diabetes has reached epidemic proportions and because of its strong association with coronary artery disease (CAD), it is responsible for increasing cardiovascular morbidity and mortality in the United States. In this article we review some of the evidence and the rationale for comprehensive risk reduction to prevent and treat CAD in individuals with diabetes mellitus. The comprehensive risk reduction strategy includes lifestyle changes, glycemic control, and control of dyslipidemia and hypertension. Advances in revascularization techniques, and superior outcomes of coronary artery bypass grafting as an interventional modality over percutaneous coronary intervention, are discussed. We also identify controversies and issues that currently remain unresolved.     

2型糖尿病患者冠状动脉病变的观察

目的了解2型糖尿病患者冠脉病变的发生情况.方法应用电子束CT,对58例血糖异常者进行冠脉钙化发生率、钙化积分、软斑数、冠脉狭窄数等指标进行定量分析,以正常血糖及冠心病者作为对照.结果血糖耐量异常组、糖尿病组的冠脉钙化发生率较正常对照组明显升高(发生率分别为93.3%,96.4%,56.0%,P＜0.001),与冠心病组相当(90.9%,P＞0.05).血糖耐量异常组和糖尿病组的钙化积分值有高于正常组的趋势,但P＞0.05;血糖耐量异常组和糖尿病组的冠脉狭窄数和软斑数均明显高于正常组(2.200±2.024,2.964±1.915vs0.520±1.295,P＜0.05和2.467±2.360,2.893±1.771,vs 0.511±1.197,P＜0.05),与冠心病相当(2.273±1.679和2.372±1.819,P＞0.05).Spearman相关分析,结果显示钙化积分与年龄有关.软斑数和冠脉狭窄数与年龄、餐后血糖和胆固醇有关.结论2型糖尿病患者有明显的冠脉病变,EBT钙化检查及狭窄定量分析,对冠脉病变的早期诊断有重要临床价值.     

Albuminuria as a predictor of heart failure hospitalizations in patients with type 2 diabetes

BACKGROUND: Heart failure (HF) occurs more frequently and is a significant cause of mortality in diabetic patients. The purpose of the current study is to ascertain risk factors that are predictive of HF hospitalizations in type 2 diabetic patients. METHODS: Longitudinal observational study of type 2 diabetic patients with baseline diastolic blood pressures > or =80 mm Hg and no history of New York Heart Association class III-IV HF or a serum creatinine > or =2.5 mg/dL nested within a randomized clinical trial. The outcome measure of this study was the first occurrence of HF hospitalization over a 5-year follow-up period. RESULTS: Patients with overt albuminuria at baseline had a higher and earlier occurrence of HF hospitalizations than those with micro- or normoalbuminuria (13.6% versus 3.3%, odds ratio [OR]=3.1, 95% confidence interval [CI]=2.15-4.60, P<.0001). In the multiple logistic regression analyses, the presence of overt albuminuria (OR 5.4, 95% CI=2.3-12.5, P<.001), history of myocardial infarction (OR 4.6, 95% CI=1.6-13.1, P=.004) and a history of New York Heart Association Class I or II HF (OR 8.0, 95% CI=2.2-28.6, P=.0014) at baseline were independently associated with HF hospitalizations. CONCLUSIONS: Overt albuminuria predicts the occurrence of HF hospitalizations in type 2 diabetic patients. Thus early aggressive treatment of diabetic nephropathy should be investigated as a means of preventing of HF.     

The kynurenine:tryptophan ratio as a predictor of incident type 2 diabetes mellitus in individuals with coronary artery disease

Aims/hypothesis

The tryptophan metabolite kynurenine has potent immune modulatory and vasoactive properties. Experimental data implicate kynurenine in obesity-related morbidities. Epidemiological studies are, however, sparse. We evaluated associations of the plasma and urine kynurenine:tryptophan ratio (KTR) to incident type 2 diabetes.

Methods

We followed 2519 individuals with coronary artery disease (CAD; 73.1% men) without diabetes at baseline for a median of 7.6 years, during which 173 (6.9%) new incidences of type 2 diabetes were identified. Multivariate Cox regression analyses were applied to investigate the prospective relationships of plasma and urine KTR with new onset type 2 diabetes.

Results

At inclusion, mean (SD) age was 61.3 (10.4) years, BMI was 25.9 (3.71) kg/m² and median (interquartile range) HbA_1c was 5.6% (5.0%–6.0%) (38 [31–42] mmol/mol). Plasma KTR was not significantly related to type 2 diabetes risk. By contrast, urine KTR showed a strong positive association. Comparing quartile 4 with quartile 1, the HRs (95% CIs) were 2.59 (1.56, 4.30) and 2.35 (1.39, 3.96) in the age- and sex-adjusted and multivariate models, respectively.

Conclusions/interpretation

Urine KTR is a strong predictor of incident type 2 diabetes in individuals with CAD. Potential clinical implications and possible pathogenic roles of renal kynurenine excretion in type 2 diabetes development should be further elucidated.

     

Circulating oxidized low-density lipoprotein is an independent predictor for cardiac event in patients with coronary artery disease

Oxidized low-density lipoprotein (oxLDL) plays a crucial role in the development of atherosclerosis, however, the predictive value of circulating oxLDL for cardiac events (CE) in patients with coronary artery disease (CAD) has remained poorly understood. We prospectively studied 238 consecutive patients with documented CAD for up to 52 months until the occurrence of one of the following cardiac events: cardiac death, nonfatal myocardial infarction (MI), and refractory angina requiring revascularization. The plasma levels of oxLDL were measured by an enzyme-linked immunosorbent assay (ELISA) using the monoclonal antibody, DLH3. The levels of circulating oxLDL were significantly higher in patients with CE than in patients without CE (median 20.3 U/ml versus 17.6 U/ml, P = 0.002). Multivariate Cox models showed that higher level of oxLDL was an independent predictor of developing CE. The adjusted hazard ratios for CE were 3.15 (95% CI 1.47-6.76, P = 0.003) times higher in patients with the highest quartile of oxLDL levels and 1.88 (95% CI 0.90-3.95, P = 0.09) times higher in patients with the third quartile than in those within the lowest quartile. Thus, measurement of circulating oxLDL may be helpful in the assessment of future CE in patients with CAD.     

Paraoxonase 1 activity as a predictor of cardiovascular disease in type 2 diabetes

The role of paraoxonase 1 in cardiovascular disease complications in type 2 diabetes mellitus is not fully understood. We studied paraoxonase activity towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general linear models and univariate analysis. Adjusting for age revealed a reduction in activity towards paraoxon was associated with a significant increase in risk (p = 0.023) for cardiovascular disease complications in diabetic patients. Multivariate analysis of two plasma measures of paraoxonase activity using paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon was associated with a significant increase in risk (p = 0.045) for cardiovascular disease complications in diabetic patients. These analyses showed that a reduced paraoxonase activity towards paraoxon was associated with ethnicity. Based on multivariate analysis, subjects of Malay ethnic origin have significantly higher than expected activity (p = 0.008, compared to Indians), towards paraoxon than subjects of Chinese origin who in turn had higher than expected paraoxonase activity (p = 0.028, compared to Indians) Indian subjects.