Abstract: Diabetes is a well-recognised risk factor for atherosclerotic cardiovascular disease and in fact most diabetic patients die from vascular complications. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) indicate a consistent relationship between hyperglycaemia and the incidence of chronic vascular complications in patients with diabetes. Platelets are essential for haemostasis, and abnormalities of platelet function may cause vascular disease in diabetes. Diabetic patients have hyperreactive platelets with exaggerated adhesion, aggregation and thrombin generation. In summary, the entire coagulation cascade is dysfunctional in diabetes.This review provides a comprehensive overview of the physiological role of platelets in maintaining haemostasis and of the pathophysiological processes that contribute to platelet dysfunction in diabetes and associated cardiovascular diseases, with special emphasis on proteomic approaches and leukocyte-platelet cross-talk.

Abstract: Cardiovascular disease is the most common complication of type 2 diabetes mellitus (type 2 DM), accounting for approximately 80% of deaths. While atherosclerotic vascular disease accounts for much of the cardiovascular morbidity and mortality among diabetic patients, congestive heart failure (CHF) is another key complication associated with diabetes, with an incidence three to five times greater in diabetic patients than in those without diabetes. One of the most promising developments in the treatment of type 2 DM has been the introduction of the thiazolidinedione (TZD) class of drugs, which appear to have pleiotropic effects beyond glycaemic control. Enthusiasm has been tempered, however, by concerns for safety in patients with CHF, given reports of worsening heart failure symptoms and peripheral oedema. With the growing epidemic of type 2 DM and the increasing use of TZDs, such concern has important therapeutic implications for a population of patients with a high prevalence of often subclinical systolic and diastolic dysfunction. This review provides an overview of the currently available data regarding the effects of TZDs on fluid retention and cardiac function. Particular emphasis is placed on the mechanisms of development of peripheral oedema and its significance in patients with impaired left ventricular function. TZDs are well known to cause an expansion in plasma volume; there has also been concern that TZDs may have direct toxic effects on the myocardium, leading to impaired cardiac function. Studies to date do not support this hypothesis and in fact there is growing evidence from animal models and human trials that treatment with TZDs actually improves cardiac function. There are also preclinical data to suggest TZDs may protect the myocardium in the setting of ischaemic insult or the toxic effects of myocardial lipid deposition. Ongoing clinical trials examining the use of these agents in patients at risk for heart failure will probably provide further insight into the aggregate cardiovascular effects of this promising class of medications.

Abstract: Inflammation plays a central role in the pathogenesis of acute coronary syndromes, the prevalence of which is increased in individuals with diabetes. Monocytes and macrophages, T cells and mast cells contribute to the initiation, development and rupture of atherosclerotic plaques by synthesising a variety of pro-inflammatory cytokines, including interleukin 1beta, interleukin 6 and tumour necrosis factor alpha. Cytokines upregulate endothelial cell adhesion molecules, recruit leukocytes and induce smooth muscle cell migration and proliferation. Cytokines act systemically to initiate the acute phase response, up-regulating proteins involved in inflammation and haemostasis and resulting in a pro-inflammatory and pro-thrombotic state. Expression of tissue factor by inflammatory cells potently induces thrombus formation upon plaque rupture, leading to acute coronary syndromes. Inflammatory biomarkers, including C-reactive protein, complement proteins, interleukin 6 and white blood cell count, predict development of acute coronary syndromes. C-reactive protein has been widely studied and consistently predicts future acute coronary syndrome events.

Abstract: The pro-inflammatory CD40/CD40L dyad participates in atherogenesis. Plasma levels of the soluble ligand (sCD40L) predict cardiovascular events and are elevated in diabetic patients. This study compared CD40/CD40L surface expression on platelets and T lymphocytes of diabetic and control subjects, and tested whether glucose and advanced glycation end products (AGEs) stimulate sCD40L release. Constitutive and inducible surface expression of CD40/CD40L on platelets or T lymphocytes did not differ between diabetic patients (n=9) and controls (n=13). Platelets from diabetic patients contained higher intracellular CD40L than controls (p<0.05) and thrombin stimulated greater platelet sCD40L release in diabetic patients (15.11+16.77 ng/ml) compared to controls (3.64+2.03 ng/ml; p<0.05). Glucose and AGEs induced platelet sCD40L release and CD40L expression in mouse megakaryocytes. This study demonstrates elevated CD40L content and inducible release from platelets of diabetic patients, and identifies glucose and AGEs as potential triggers of expression and release accounting for the elevated sCD40L plasma levels in these patients. Diabetes Vasc Dis Res 2005;2:81‐7

Abstract: Diabetes mellitus (DM) remains an important predictor for mortality in patients with ST-segment Elevation Myocardial Infarction (STEMI) although the use of reperfusion therapy has resulted in a considerable improvement of survival. Of importance, newly diagnosed diabetic patients and those with fasting glycaemia in the diabetes range have even worse outcomes compared to patients with known diabetes. Overall, 50% of all patients presenting with STEMI have abnormal glucose metabolism of which fewer than 50% are known diabetics. Obviously, the efficacy of reperfusion therapy in reopening the occluded artery is similar in STEMI patients with or without impaired fasting glycaemia, while the pre-existing decreased myocardial perfusion in STEMI patients with impaired fasting glycaemia persists after successful epicardial revascularisation. There is no doubt that improving microvascular perfusion within the ischaemic myocardium remains the ultimate goal of managing STEMI patients with impaired glucose metabolism. Identification of defective myocardial perfusion together with an aggressive antithrombotic regimen, reduction of the inflammatory response of the ischaemic myocardium and improvement of glycaemia control represent promising therapeutic approaches that deserve additional specific clinical investigations. This review examines all these important issues.

Abstract: The prevalence of type 2 diabetes (T2DM) is increasing rapidly and the age of presentation is falling. These changes are likely to be linked to the current obesity epidemic. Our objective was to compare the characteristics of younger patients with T2DM (diagnosed at age < 40 years) with those of older patients (diagnosed at age 50‐70 years). We identified 149 younger patients with T2DM, from our diabetes clinic database, and compared them with 217 older T2DM patients randomly identified from the same database. Younger patients with T2DM were more obese, more hypertriglyceridaemic, with lower high-density lipoprotein (HDL) cholesterol, higher total cholesterol/HDL ratio and worse initial and ongoing glycaemic control than older patients from the same clinic. Additional cardiovascular risk factors are associated with T2DM in the young. Treatment should be aimed at early modification of lifestyle and other forms of therapy to avoid long-term complications. Diabetes Vasc Dis Res 2005;2:73‐5

Abstract: Thiazolidinedione (TZD) compounds enhance insulin sensitivity and attenuate inflammation. The effect of the TZD compound, rosiglitazone (RSG) on both actions was evaluated in two groups of insulin-resistant subjects with minimal elevations of fasting plasma glucose (PG) concentration: group A (n=15, PG < 7.0 mmol/L) and group B (n=14, PG 7.0-8.3 mmol/L). Insulin action, quantified by the insulin suppression test, improved after three months of treatment in both groups, and concentrations of C-reactive protein, plasminogen activator inhibitor-1 and Eselectin all fell. Significant decreases in L-selectin and P-selectin were confined to group B, and concentrations of interleukin-6, intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1 did not fall in either group. Significant relationships were not discerned between enhanced insulin sensitivity and related variables and decreases in inflammatory/vascular markers, suggesting that RSG-induced changes in the latter variables in insulin-resistant individuals might be at least partly independent of the effects of the drug on insulin action.

Abstract: Activation of the receptor for advanced glycation end-products (RAGE) leads to a cascade of pro-inflammatory and pro-coagulant responses which are important in the pathogenesis of the vascular complications of diabetes mellitus. It is known that pro-inflammatory mechanisms underpin the development of type 2 diabetes. Our hypothesis is that RAGE may be involved in the evolution of insulin resistance in addition to mediating glucotoxic complications of diabetes mellitus. Methods: To investigate the relationship between RAGE allelic variation and insulin resistance, the Gly82Ser variant and three promoter variants (-429, -374, 63 bp deletion) were studied in 480 subjects of known relationship from 89 families characterised for insulin resistance (using homeostasis model assessment [HOMA]) and for atherothrombotic risk. Carriage of the -429 C allele was weakly associated with increased insulin resistance (p=0.02) when pedigree analysis was performed using SOLAR software. Results: Insulin resistance was estimated to have a heritability of 25.8% before the addition of covariates. Analysis of the relationship between RAGE and insulin resistance indicated that the -429 polymorphism reduced the unexplained heritability of insulin resistance after adjusting for covariates (age, sex, body mass index) from 17.5% of the total variance to 15.6% of the total variance. Conclusions: These preliminary results indicate that the RAGE gene may affect the development of insulin resistance or be in linkage disequilibrium with a locus involved in this process.

Abstract: Poteomics is the investigation of all the proteins and their various modifications making up a system, be that a cell, tissue or organism. The techniques involved in proteomics allow the global screening of complex samples of proteins and provide qualitative and quantitative evidence of altered protein expression. This lends itself to the investigation of the molecular mechanisms underpinning disease processes and the effects of treatment. This review describes the main techniques of proteomics and how they have begun to be applied to diabetes research.

Abstract: Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function. Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Results are expressed as (mean +/- SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86 +/- 1.1 Ohms vs. 10.76 +/- 1.1 Ohms, p < 0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1 +/- 5.9% and 50.3 +/- 7.7% in healthy controls compared to 15.4 +/- 7% and 19.5 +/- 8.2% in T2DM (p < 0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance. In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.

Abstract: While neoangiogenesis in diabetes is of greatest clinical significance in the retina, the pathological formation of new blood vesselsalso develops in other vascular beds in diabetes, including the mesentery of the streptozotocin-induced diabetic rat. However, the contribution of bone marrow-derived cells to this process of vasculogenesis is unknown. In this study, male Sprague-Dawley rats were randomised to receive either streptozotocin or vehicle, and their mesenteric vasculature was examined after three weeks. Origins from bone marrow and endothelial cell differentiation were identified by immunolabelling for the stem cell factor receptor, c-kit and von Willebrand factor (vWF), respectively. Expression for the angiogenic chemokine, stromal derived factor-1 (SDF-1) was assessed by quantitative real-time polymerase chain reaction (PCR). At three weeks, rats with diabetes had a dramatic (190-fold) increase in lectin-labelled blood vessel profiles in the mesenteric bed (p < 0.0001) in association with a five-fold increase in SDF-1 mRNA (p < 0.01). Immunohistochemical studies identified abundant large, ovoid, lumen-forming, c-kit+ cells in the mesentery of diabetic, but not control, rats. Many of these c-kit+ cells also showed positive immunolabelling for vWF, consistent with endothelial differentiation. In conclusion, cells of bone marrow origin contribute to new vessel formation in the diabetic mesentery. This phenomenon may also apply to the neovascularisation that develops at clinically important sites such as in the retina.

Abstract: 51 Few therapeutic interventions for diabetes and vascular diseases can be permanently managed with just one agent. Most of these conditions are multifactorial in origin and pathogenesis, exhibit a variable and progressive natural history, and require attention to attendant risk factors and co-morbidities. There are targets to achieve and maintain, or aspire towards, and issues of compliance and quality of life to be balanced. Against this background, combinations of therapies have become commonplace, and single tablet ‘two-inone’ fixed-dose combinations are now emerging to facilitate regimens of multiple therapies. The use of combination therapy has a long tradition in diabetes. Combinations of different insulins in type 1 diabetes and combinations of different oral agents in type 2 diabetes are well established. Multiple therapies are also expected for long-term management of hypertension, most stages of cardiac failure, peripheral vascular disease and some dyslipidaemias. If we focus on type 2 diabetes, the United Kingdom Prospective Diabetes Study (UKPDS) found that, after three years of treatment with one antidiabetic agent, only about 50% of patients achieved a glycosylated haemoglobin (HbA1C) target of < 7%. By nine years of treatment with one agent, fewer than 30% of patients achieved this target. Most of those who did not achieve the target would be candidates for multiple oral antidiabetic therapy and/or intensified insulin treatment. The earlier use of two oral agents was once reserved for the rescue of those who had ‘failed’ monotherapy but it is now seen as an opportunity to achieve glycaemic targets sooner and for longer.

Abstract: There are few data concerning the relationship between diabetes mellitus, the metabolic syndrome and inflammation following elective percutaneous coronary intervention (PCI). The purpose of this study was to assess basal and peak levels of candidate cytokines in 40 patients undergoing elective PCI. Patients were categorised as having diabetes mellitus, the metabolic syndrome, or neither. Patients with the metabolic syndrome exhibited significantly greater levels of tumour necrosis factor-alpha over the study period, although this was unrelated to PCI. There was a trend for increased levels of interleukin-6 following PCI, primarily among patients with metabolic syndrome. Basal levels of monocyte chemoattractant protein-1 (MCP-1) were not different among study groups; however, the metabolic syndrome cohort had a trend towards increased circulating levels of MCP-1 after PCI. In this patient population, the metabolic syndrome correlates with a heightened inflammatory response following elective PCI.

Abstract: Diabetes mellitus has reached epidemic proportions worldwide. Patients with diabetes are at increased risk for acute coronary syndromes, and these syndromes lead to frequent morbidity and cardiovascular mortality. Emerging adjunctive pharmacological strategies coupled with the drug-eluting stent platform have resulted in improved adverse event rates for this high-risk group. This review will concentrate on the historical data associated with acute coronary syndromes in diabetes mellitus, focusing on revascularisation, drug-eluting stents and antiplatelet therapies.

Abstract: In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, US, on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C.The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease.This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting.

Abstract: Diabetic patients with acute coronary syndromes are at high risk for cardiovascular complications but risk stratification in these patients remains challenging. Regularly, diabetic patients have a less typical clinical presentation, which could lead to delayed diagnosis and subsequent delayed initiation of treatment. Since diabetic patients derive particular benefit from aggressive anti-platelet therapy, early diagnostic and therapeutic risk stratification of these patients is of critical importance to improve their adverse outcome. Although the electrocardiogram remains a pivotal diagnostic tool in the evaluation of patients suspected of having an acute coronary syndrome, only significant ST-segment changes provide reasonable prognostic information. Therefore, repeated assessment of circulating protein biomarkers represents a valuable diagnostic tool for improving efficacy and safety of decision-making in these patients. The combined use of biomarkers reflecting distinct pathophysiological aspects, such as myocardial necrosis, vascular inflammation, oxidative stress and neurohumoral activation, may significantly improve triage of patients with chest pain. These tools may identify those patients that are at particularly high risk for short-term and/or long-term cardiovascular events. Eventually, tailored medical and interventional treatment of diabetic patients should help to prevent these cardiac events in a cost-effective manner.

Abstract: 101 Patients with diabetes mellitus exhibit an increased propensity to develop coronary artery disease, with its sequelae acute myocardial infarction and unstable angina. Given that the prevalence of diabetes is estimated to double over the next 20 years, the incidence of acute coronary syndromes in this high-risk population can be expected to increase dramatically. Moreover, once diabetic patients experience an acute coronary syndrome, they have a worse prognosis than non-diabetic patients. This is on the one hand due to a typically very diffuse and extensive pattern of arteriosclerosis in diabetic subjects and on the other hand to the clustering of cardiovascular risk factors associated with diabetes and insulin resistance. Among them, hypertension, dyslipidaemia, endothelial dysfunction, obesity and a pro-thrombotic and pro-inflammatory state contribute in particular to the increased risk and worse prognosis of these patients. Various studies have shown that evidence-based therapeutic options are applied less frequently in patients with diabetes, clearly contributing to their increased mortality. However, several studies, including reports from the Schwabing City Hospital acute myocardial infarction (AMI) registry, have demonstrated that the prognosis of diabetic patients with acute coronary syndromes (ACS) can be improved enormously if they are treated appropriately.

Abstract: 7 Diabetes mellitus is a well-established risk factor for the development of atherosclerotic vascular disease. In fact, recognition of this association dates back to the 1920s. During this time period, there has been a transition from deaths solely related to coma and infection in the preinsulin era to deaths most frequently related to vascular disease (the current situation). In fact, cardiovascular complications remain the number one cause of death among diabetic persons, accounting for nearly 60% of all case fatalities. Although much has been learned in recent years about the pathophysiology and treatment of patients with cardiovascular disease, diabetic subjects remain at unacceptable risk for both mortality and morbidity in relation to vascular events. This topic has been of increasing interest to physicians, scientists and other health care professionals in recent years. The magnitude of vascular risk among diabetic patients and the temporal trends in reducing this risk are the subject of much attention, study and debate in the current scientific literature. Previous work suggested that the improvement in both mortality and morbidity rates has lagged behind among diabetic patients, compared with their nondiabetic peers. However, a recent analysis of the Framingham database provides important insight into the vascular risk of persons with diabetes mellitus. Summary data from this study are shown in figure 1. The study analysed data from more than 8,000 individuals from both the original (1950–1966) and offspring (1977–1995) cohorts of Framingham. The figure highlights two germane issues. First, contrary to two previously published reports, there has been a significant and measurable reduction in important cardiovascular events for persons with (and without) diabetes mellitus. Subjects with diabetes had an approximate 50% reduction in the rate of myocardial infarction (MI), death from coronary heart disease (CHD) and stroke. This was true for both men and women in this study. Although the definition of diabetes evolved during the study, it does appear that the modern-day treatment strategy for diabetic patients with vascular disease leads to a measurable reduction in risk. Second, there remains a disproportionately high risk for subjects with diabetes. For example, the risk of vascular morbidity and mortality was approximately three times greater in the diabetic cohort, irrespective of the time period. These data are consistent with those from many other published reports showing that diabetes is associated with an inordinate risk of vascular complications. This unexplained elevated risk leads many to conclude that there are yet to be identified ‘diabetes-mediated’ biological drivers of vascular risk. In this issue of the Journal, Stratmann and Tschoepe suggest that the diabetic platelet may, in part, explain this increased vascular risk. In fact, there are many lines of evidence to suggest an augmented clinical benefit among diabetic patients being treated with antiplatelet agents. For example, patients with diabetes enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GPIIb/IIIa blockade (EPILOG), Evaluation of C7E3 for Prevention of Ischemic Complications (EPIC) and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials randomised to abciximab, a monoclonal antibody and inhibitor of the glycoprotein (GP) IIb/IIIa receptor, had a potentiated benefit which translated into a marked survival benefit. Additionally, metaanalyses of the major trials evaluating the efficacy of GP IIb/IIIa antagonists in the setting of an acute coronary syndrome clearly establish a marked reduction in adverse events, including mortality, for diabetic patients treated with these potent antiplatelet agents Beyond the platelet, there are numerous other potential biological drivers that may explain the increased vascular risk among diabetic patients. These areas of focused investigation will hopefully lead to additional insights into the high vascular risk associated with diabetes. This ongoing quest is critical in order to modulate vascular risk in this burgeoning population.

Abstract: The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients.Aims This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients.Methods Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va).Results Compared to controls, diabetic patients had compromised Ve at rest (8.5. ± 1.7 vs...

Abstract: The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.

Abstract: Acute coronary syndromes are associated with a high risk for subsequent major cardiovascular events and with a risk for mortality that remains substantially increased for many months following the acute phase. Patients with type 2 diabetes mellitus are especially vulnerable and encounter excessive long-term mortality. Effective management of patients with type 2 diabetes following acute coronary syndromes requires aggressive multidisciplinary efforts for reduction of several risk factors, including meticulous control of blood glucose. The evidence for different medication and treatment strategies capable of improving the outcomes is reviewed and the currently available recommendations are summarised.

Abstract: The aim of this study was to assess the performance of the Finnish Diabetes Risk Score as a screening tool for undetected type 2 diabetes (T2D), abnormal glucose tolerance (AGT) and metabolic syndrome in the general population. In a cross-sectional, population-based survey, a total of 4,622 subjects aged 45‐74 years were invited to a health examination that included an oral glucose tolerance test. Full data with risk score estimate and glucose tolerance status were available for 2,966 subjects without a prior history of diabetes. The risk score was associated with the presence of previously undiagnosed T2D, AGT, metabolic syndrome and cardiovascular risk factors. The area under the receiver operating curve for the prevalence of undiagnosed diabetes was 0.72 in men and 0.73 in women. The sensitivity using a cutoff risk score of 11 to identify undiagnosed diabetes was 66% in men and 70% in women; the corresponding false-positive rates were 31% and 39%, respectively. The area under the receiver operating curve for detecting the metabolic syndrome was 0.72 in men and 0.75 in women. The Finnish Diabetes Risk Score can be used as a selfadministered test to screen subjects at high risk for T2D. It can also be used in the general population and clinical practice to identify undetected T2D, AGT and the metabolic syndrome. Diabetes Vasc Dis Res 2005;2:67‐72

Abstract: The vascular research technique flow-mediated dilatation (FMD) non-invasively estimates vascular endothelial function by quantifying the increase in brachial arterial diameter in response to reactive hyperaemia after release of a distal occlusive pneumatic cuff. It was first used in 1992 to describe endothelial dysfunction in normal individuals who were likely to develop atherosclerosis. Subsequently, studies have demonstrated similar impairments in other at-risk subjects, with impaired glucose tolerance, hypercholesterolaemia or hypertension. Others have shown that brachial responses correlate with coronary endothelial function, and are partially mediated by nitric oxide. There have been problems with the technique, however. Responses are confounded by age, time of day, gender and menstrual cycle. An inverse relationship has been described between resting brachial diameter and the size of response. Reproducibility is another difficulty: some groups have never managed to establish the technique. These problems have been examined by an international task force, which sought to standardise all aspects of brachial artery reactivity measurement. We hypothesised that the variation in reported results could be explained partly by the location on the arm of the ultrasound probe used to measure brachial artery diameter. Change in diameter or in function of the vessel along its length might affect the results obtained. In our prospective, randomised study nine healthy fasted volunteers were studied at the same time on two consecutive days, with the ultrasound probe located either proximally or distally on the upper arm. Each day, the measurements were repeated after a 15-minute interval at the same location on the arm. Care was taken to ensure consistency in location of occlusive cuff and duration of occlusion. The mean (SD) distance between the distal and proximal sites was 131(25) mm.