BACKGROUND:Mild renal insufficiency has recently been recognized as an important risk factor for cardiovascular disease (CVD). The mechanisms underlying this association are incompletely understood. Increased left ventricular mass (LVM) is an independent risk factor for CVD, which is particularly common in end-stage renal disease (ESRD) and which has been shown to be associated with mild renal insufficiency. Increased arterial stiffness has also been shown to be an independent risk factor for CVD in ESRD and has also been associated with mild renal insufficiency. We hypothesized that the association between mild renal insufficiency and increased LVM could be mediated through increased arterial stiffness, and that this may be one of the pathways linking mild renal insufficiency to CVD. We therefore investigated, in a cross-sectional population-based study, the influence of increased arterial stiffness on the association between renal function and LVM.METHODS:The study population consisted of 742 elderly individuals (373 men and 369 women). Renal function was estimated by the serum creatinine level in micromol/L; by the Cockcroft-Gault formula in mL/min and by the Modification of Diet in Renal Disease (MDRD) formula. LVM was obtained by echocardiography.RESULTS:The mean estimates of renal function in men and women were, respectively, 103.7 (SD 17.0) and 86.8 (SD 11.2) micromol/L for the serum creatinine level; 63.4 (SD 12.9) and 61.4 (SD 11.0) mL/min/1.73 m(2) for the Cockcroft-Gault formula; and 59.7 (SD 10.8) and 60.9 (SD 10.5) mL/min per 1.73 m(2) for the MDRD formula. LVM was 93.1 (SD 26.4) g/m(2) in men and 86.7 (SD 22.3) g/m(2) in women. In men, impaired renal function, as estimated by the Cockcroft-Gault and the MDRD formula, was significantly associated with greater LVM after adjustment for age, glucose tolerance, hypertension, and prior CVD [regression coefficient beta (95% CI), 1.28 (0.22 to 2.33) g/m(2) and 1.63 (0.41 to 2.86) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. However, the association between impaired renal function and increased LVM was not statistically significant after adjustment for arterial stiffness estimates [regression coefficient beta (95% CI), 0.02 (-1.60 to 1.64) g/m(2) and 0.54 (-1.25 to 2.33) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. In women, impaired renal function was not significantly associated with greater LVM.CONCLUSION:Our study shows that in a general elderly population, even mild impairment of renal function is associated with adverse changes in left ventricular structure. In men, but not in women, this leads to greater LVM, a process that may be related to increases in arterial stiffness. Importantly, these novel findings suggest that such changes occur early in the process of renal functional deterioration, which may explain, in part, the increase in cardiovascular risk in men with mildly impaired renal function.

Objective - To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.Methods and Results - In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery ( absolute change in diameter [mu m]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 mu m (21.16; 75.98) and -32.15 mu m (-59.09; -5.20), but high homocysteine was not ( - 15.11 mu m ( - 42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.Conclusions - In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Aims To determine health-related quality of life (HRQoL) in the first year following diagnosis of Type 2 diabetes among newly diagnosed patients in general practice compared with patients detected by targeted population screening.Methods The study population consisted of 49 newly diagnosed patients in general practice and 116 screening-detected patients. HRQoL was operationalized as symptom distress, perceived health status and emotional well-being, that were assessed prospectively similar to2 weeks, 6 months and 12 months after the diagnosis of Type 2 diabetes, with the Type 2 Diabetes Symptom Checklist (DSC-type 2), the Short Form 36 (SF-36) and the Well-Being Questionnaire (W-BQ12), respectively.Results The DSC-type 2 total score (range 0-4) improved significantly within newly diagnosed patients in general practice (median at similar to2 weeks, 6 months and 12 months; 0.56, 0.21, 0.26; P = 0.000) and not within screening-detected patients (0.24, 0.24, 0.29; P = 0.093). Descriptives showed that newly diagnosed patients in general practice compared with screening-detected patients had consistently worse mean scores on all SF-36 mental health subscales Social Functioning, Role Emotional, Mental Health, Vitality, and all W-BQ12 scales at each time point. The differences were statistically significant for Role Emotional, Mental Health, Vitality (SF-36), and General well-being (W-BQ12). The SF-36 General Health (F = 3.7, P = 0.028) and Vitality (F = 4.5, P = 0.012) scores of newly diagnosed patients in general practice improved significantly over time, compared with screening-detected patients.Conclusions Newly diagnosed patients in general practice compared with screening-detected patients reported more diabetes-related symptom distress shortly after the diagnosis, and a consistently worse mental health status at each time point. Improved Vitality scores in newly diagnosed patients in general practice in the first year following diagnosis of Type 2 diabetes suggest a positive effect of diabetes treatment on HRQoL.

Objectives.  Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications.

OBJECTIVE - Type 2 diabetes and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease (CVD) risk. Increased left ventricular mass (LVM) is thought to increase CVD risk through several unfavorable cardiac changes. Type 2 diabetes and IGM are associated with increased LVM, but the underlying mechanism is unclear. We investigated the association between glucose tolerance status (GTS) and LVM and explored whether any such association could be mediated through increased arterial stiffness, impaired endothelial function, or the presence of atherosclerosis.RESEARCH DESIGN AND METHODS - We used ultrasound to measure LVM, carotid and femoral stiffness, carotid-femoral transit time, and flow-mediated vasodilation (FMD) and tonometry to estimate compliance and augmentation index. The study population (n = 780) consisted of 287 individuals with normal glucose metabolism (NGM), 179 with IGM, and 314 with type 2 diabetes, and the mean age was 68.4 years.RESULTS - in women, after adjusting for age, height, BMI, and mean arterial pressure, LVM increased significantly with deteriorating GTS (LVM 157 g in NGM, 155 g in IGM, and 169 g in type 2 diabetes; P for trend <0.018). Additional adjustment for arterial stiffness, FMD, or the presence of atherosclerosis did not materially alter the results, even though these variables were significantly associated with both GTS and LVM. Indexes of hyperglycemia/-insulinemia or insulin resistance explained at most 7% of the association between GTS and LVM. In men, no statistically significant associations were observed.CONCLUSIONS - Our data expand the conceptual view of the pathogenesis of GTS-related changes in LVM because we show that the increase in LVM in women is independent of increased arterial stiffness, impaired FMD, or the presence of atherosclerosis. In addition, we show that this increase in LVM is only minimally explained by indexes of hyperglycemia/-insulinemia or insulin resistance. Our data may, in part, explain the increased CVD risk seen in women with deteriorating GTS.

AIMS:To examine the impact of the diagnosis of Type 2 diabetes on psychological well-being and perceived health status in subjects who participated in a targeted population-screening programme.METHODS:This study was conducted within the framework of a screening project in the general (aged 50-75 years) Dutch population. The final study population consisted of 259 subjects with a high-risk score on the Symptom Risk Questionnaire; 116 of whom were subsequently detected with Type 2 diabetes and 143 who were non-diabetic. The impact was assessed approximately 2 weeks (shortly) and 6 and 12 months after the diagnosis, using the 12-item Well-Being Questionnaire (W-BQ12) and the Medical Outcomes Study Short Form 36 (SF-36), respectively. Analyses of co-variance (ancova) were used.RESULTS:Approximately 2 weeks after the diagnosis, no significant mean differences were found on either the W-BQ12 or the SF-36, between the screening-detected Type 2 diabetes subjects and the non-diabetic subjects. Six months after the diagnosis, we found lower scores in the screening-detected Type 2 diabetes subjects compared with the non-diabetic subjects on the SF-36 dimensions Role Physical (mean difference (95% CI); -8.2 (-16.2; -0.1); P = 0.046) and Role Emotional (mean difference (95% CI); -7.9 (-15.3; -0.5); P = 0.038). One year after the test results, no significant mean differences were found between both groups on either instrument (W-BQ12; SF-36).CONCLUSIONS:The diagnosis of Type 2 diabetes has no substantial adverse or positive effect on psychological well-being and perceived health status, shortly, and 6 and 12 months after the diagnosis.

Background-Type 2 diabetes (DM-2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. In nondiabetic individuals, increased arterial stiffness is an important cause of cardiovascular disease. Associations between DM-2 and IGM and arterial stiffness have not been systematically investigated.Methods and Results-In a population-based cohort (n=747; 278 with normal glucose metabolism, 168 with IGM, and 301 with DM-2; mean age, 68.5 years), arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. After adjustment for age, sex, and mean arterial pressure, DM-2 was associated with increased carotid, femoral, and brachial stiffness, whereas IGM was associated only with increased femoral and brachial stiffness. Carotid but not femoral or brachial stiffness increased from IGM to DM-2. Standardized betas (95% CI) for IGM and DM-2, compared with normal glucose metabolism, were -0.06 (-0.23 to 0.10) and -0.37 (-0.51 to -0.23) for carotid distensibility; -0.02 (-0.18 to 0.18) and -0.25 (-0.40 to -0.09) for carotid compliance; -0.05 (-0.23 to 0.13) and 0.25 (0.10 to 0.40) for carotid elastic modulus; -0.70 (-0.89 to -0.51) and -0.67 (-0.83 to -0.52) for femoral distensibility; and -0.62 (-0.80 to -0.44) and -0.79 (-0.94 to -0.63) for femoral compliance. The brachial artery followed a pattern similar to that of the femoral artery. Increases in stiffness indices were explained by decreases in distension, increases in pulse pressure, an increase in carotid intima-media thickness, and, for the femoral artery, a decrease in diameter. Hyperglycemia or hyperinsulinemia explained only 30% of the arterial changes associated with glucose tolerance. Adjustment for conventional cardiovascular risk factors did not affect these findings.Conclusions -IGM and DM-2 are associated with increased arterial stiffness. An important part of the increased stiffness occurs before the onset of DM-2 and is explained neither by conventional cardiovascular risk factors nor by hyperglycemia or hyperinsulinemia.

AIMS:To determine the risk perception of Type 2 diabetes in participants in a stepwise population-screening programme.METHODS:This study was carried out within the framework of a stepwise Type 2 diabetes population screening in the general (age 50-75 years) Dutch population. Main outcome measures were perceived risk of having diabetes and perceived seriousness of diabetes, based on a self-report questionnaire, completed before being informed about the diagnosis (Type 2 diabetes yes/no) of the screening procedure. Among 7736 participants, the risk perception of 217 screening-detected participants was compared with 4435 with a low-risk profile for undiagnosed Type 2 diabetes.RESULTS:Of 7736 participants, 43.5% could not give an estimate of their risk of having diabetes, 31.2% estimated their risk to be 0% and 25.3% estimated their risk to be 10% or higher. Compared with 4435 participants with an objectively low risk profile, 217 screening-detected participants were more likely to answer 'I do not know' (52.4% vs. 40.1%, P < 0.001), perceived their risk less often to be 0% (19.3% vs. 34.7%, P < 0.001), and slightly more often perceived their risk to be 10% or higher (28.3% vs. 25.2%, P < 0.001). Overall, more than half of the total population, including both participants with a low risk profile and the screening-detected participants, perceived diabetes as a (very) serious disease. Higher age, obesity and taking anti-hypertensive drugs did not translate into a higher perceived risk.CONCLUSIONS:Among screening-detected participants the seriousness of Type 2 diabetes was generally acknowledged, whilst the perceived risk of having Type 2 diabetes was low, despite the presence of risk factors.

OBJECTIVE:To investigate whether screening-detected diabetic patients differ from diabetic patients newly diagnosed in general practice with regard to the presence of microvascular complications.RESEARCH AND DESIGN METHODS:Diabetic patients, identified by a population-based targeted screening procedure consisting of a screening questionnaire and a fasting capillary whole-blood glucose measurement followed by diagnostic testing, were compared with patients newly diagnosed with diabetes in general practice. Retinopathy was assessed with fundus photography, impaired foot sensitivity was assessed with Semmes-Weinstein monofilaments, and the presence of microalbuminuria was measured by means of the albumin-to-creatinine ratio (ACR).RESULTS:A total of 195 screening-detected type 2 diabetic patients and 60 patients newly diagnosed in general practice participated in the medical examination. The prevalence of retinopathy was higher in screening-detected type 2 diabetic patients than in patients newly diagnosed in general practice, but not significantly higher. The prevalence of retinopathy was 7.6% (95% CI 4.6-12.4) in screening-detected type 2 diabetic patients and 1.9% (0.3-9.8) in patients newly diagnosed in general practice. The prevalence of impaired foot sensitivity was similar in both groups, 48.1% (40.9-55.3) and 48.3% (36.2-60.7), respectively. The ACR was 0.61 (interquartile range 0.41-1.50) in screening-detected type 2 diabetic patients and 0.99 (0.53-2.49) in patients newly diagnosed in general practice. The difference in prevalence of microalbuminuria was not statistically significant. The prevalence of microalbuminuria was 17.2% (95% CI 12.5-23.2) and 26.7% (17.1-39.0) in screening-detected type 2 diabetic patients and patients newly diagnosed in general practice, respectively.CONCLUSIONS:Targeted screening for type 2 diabetes (with a screening questionnaire as a first step) resulted in the identification of previously undiagnosed diabetic patients with a considerable prevalence of microvascular complications.

BACKGROUND:Several studies have reported differences in the mortality risk between diabetic subjects detected by screening and known diabetic patients. We studied mortality in relation to diabetes duration, and the contribution of other cardiovascular risk factors to the elevated risk.MATERIALS AND METHODS:Participants were type 2 diabetic subjects (n = 174) of a population-based cohort study. Of these, 95 were diagnosed by screening. Known diabetic subjects were grouped into two categories of diabetes duration, with a median duration of 2.4 and 11.2 years, respectively. We assessed the contribution of classical cardiovascular risk factors (dyslipidaemia, hypertension, and prior myocardial infarction), and of new cardiovascular risk factors (microalbuminuria, von Willebrand factor, sVCAM-1 and C-reactive protein) to the mortality risk during nearly 10 years of follow up. Cox's proportional hazards model was used to study the association of diabetes duration and mortality.RESULTS:The age- and sex-adjusted relative risks of mortality were 2.06 (95% C.I. 1.04-4.10) and 3.19 (1.64-6.20) for the patients with short- and long-term diabetes compared with the screening-detected diabetic subjects, respectively. Adjustment for cardiovascular risk factors resulted in a reduction of mortality risk in both groups: 1.13 (0.51-2.50) and 2.39 (1.18-4.83), respectively. Mortality risk significantly increased with increasing diabetes duration, even after multiple adjustment (P-value for trend ranged from < 0.001-0.018).CONCLUSIONS:Mortality risk increased with increasing diabetes duration. In subjects with short diabetes duration the mortality risk could largely be attributed to other risk factors. In subjects with a longer diabetes duration, however, the elevated mortality risk was independent of these cardiovascular risk factors.

OBJECTIVE To describe a population-based two-step screening procedure for type 2 diabetes and to study the cardiovascular risk profile of the patients identified by the screening. RESEARCH DESIGN AND METHODS The first step of the screening procedure consisted of the Symptom Risk Questionnaire (SRQ), and the second step was a fasting capillary glucose measurement. In subjects with an SRQ score of >6 and a capillary glucose level of >5.5 mmol/l, an oral glucose tolerance test was performed. RESULTS A total of 11,679 inhabitants of the West-Friesland region of the Netherlands, aged 50-75 years, were invited. Of the inhabitants, 9,169 (78%) responded, and, of those, 417 had previously diagnosed diabetes. The SRQ score was calculated for 7,736 participants, and 3,301 of those had a score of >6. A total of 2,885 subjects (87.3%) attended for capillary glucose measurement. Diagnostic testing was carried out in 509 participants, and we identified 217 diabetic patients. In these patients detected by screening, mean HbA(1c) was 6.7% (+/-1.4). Hypertension and high total cholesterol levels (>5.0 mmol/l) were present in 70%, 33% had high triglyceride (>3.0 mmol/l) or low HDL cholesterol levels (<1.0 mmol/l in men and <1.1 mmol/l in women), and 40% were obese (BMI > or =30 kg/m(2)). CONCLUSIONS The high response rate was the main feature of the screening by means of the Symptom Risk Questionnaire and fasting capillary glucose measurement followed by diagnostic testing. The 217 diabetic patients detected by the screening were characterized by relatively low HbA(1c) levels and by a cardiovascular risk profile typical of diabetic patients.