Low prevalence of rheumatoid arthritis among patients with pre-existing type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a non-autoimmune disease characterized by chronic hyperglycemia and increased non-enzymatic glycation of amino groups. Glycation occurs through a series of events eventually leading to the formation of irreversible "advanced glycation end-products" (AGEs). AGEs may affect the function of long-lived proteins, including cytokines, immunoglobulins and their receptors, resulting in a "less active" immune system. We aimed to test the hypothesis that a common inflammatory chronic disease, such as rheumatoid arthritis (RA), in which the earliest event is an inflammatory response to unknown stimulus, has a lower prevalence in these patients than in normoglycemic, non-diabetic subjects. METHODS: In this study, we compared the prevalence of RA in a prospectively followed outpatient cohort of patients with T2DM patients (n=1,630) with a control, matched, non-diabetic population (n=1,630). RESULTS: Among non-diabetic controls, 13 patients (prevalence 0.80%) with RA were identified. An almost 3-fold lower prevalence of RA (0.25%) was found in consecutive patients with T2DM (P=0.029). Most of the RA cases among participants with T2DM were diagnosed early after diabetes onset. The onset of RA in patients with T2DM occurred at significantly older age (64±15 years) as compared to the non-diabetes group (48±18 years; P=0.004). CONCLUSIONS: The prevalence of RA is lower and occurs in an older age in patients with pre-existing T2DM in comparison with people without T2DM.

Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis.

Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy.

The spatial QRS-T angle: implications in clinical practice.

The ventricular gradient (VG) as a concept was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. The contemporary spatial QRS-T angle is based on the concept of the VG and defined as its mathematical and physiological integral. Its current major clinical use is to assess the cardiac primary repolarization abnormalities in 3-dimensional spatial vectorial plans which are normally untraced in the presence of secondary electrophysiological activity in a 2-dimensional routine electrocardiogram (ECG). Currently the calculation of the spatial QRS-T angle can be easily computed on the basis of a classical ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local heterogeneity of the myocardial ventricular action potention duration. Recent population-based studies suggest that the spatial QRS-T angle is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary cardiovascular prevention efforts and should be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial QRS-T angle. The main focus is its role in ECG assessment of dispersion of repolarization, a key factor in arrythmogeneity.

Exercise improves cardiac autonomic function in obesity and diabetes.

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction.

"Brittleness" in diabetes: easier spoken than broken.

By definition, brittle diabetes (BD) is an unstable condition. Patients with BD suffer chronically from poor metabolic control, characterized by severe instability of glycemic values with frequent and unpredictable hypoglycemic and/or diabetic ketoacidosis episodes that cannot be attributed to failure in management. Quality of life is dramatically compromised because of very frequent acute complications leading to hospital admissions and because of premature chronic complications. It remains difficult to identify all patients with BD as diagnostic criteria are still not well defined. In practice, metabolic instability is manifested most obviously by chaotic glycemic profiles, which show greater and more unpredictable variation than in "stable" patients with diabetes. It is important that patients with BD are not adequately controlled, even by closely supervised, intensive insulin regimens, including continuous subcutaneous and/or intravenous insulin infusion. Their care is often very expensive in terms of time and resources, and their lives are constantly at risk for severe metabolic derangement. Management can also be frustrating and demoralizing for everyone involved, including the patient's family as well as the diabetes care team. Adopting a team approach, involving a broad range of disciplines, is essential in treating patients with BD and helping them to achieve and maintain both normoglycemia and quality of life.

Increased heart failure risk in normal-weight people with metabolic syndrome compared with metabolically healthy obese individuals.

OBJECTIVES: The purpose of this study was to assess whether the metabolically healthy obese phenotype is associated with lower heart failure (HF) risk compared with normal-weight individuals with metabolic syndrome (MetS). BACKGROUND: Obesity and MetS often coexist and are associated with increased HF risk. It is controversial whether obese individuals with normal insulin sensitivity have decreased HF risk. METHODS: A total of 550 individuals without diabetes or baseline macrovascular complications were studied during a median follow-up of 6 years. Participants were classified by presence (n = 271) or absence (n = 279) of MetS and by body mass index (body mass index: <25 kg/m(2) = normal weight, n = 177; 25 to 29.9 kg/m(2) = overweight, n = 234; ≥ 30 kg/m(2) = obese, n = 139). MetS was diagnosed with the National Cholesterol Education Program Adult Treatment Panel III criteria. Left ventricular functional capacity, myocardial structure, and performance were assessed echocardiographically. RESULTS: Body mass index was not associated with increased HF risk. The presence of MetS conferred a 2.5-fold higher HF risk (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: 1.68 to 3.40). Overweight and obese individuals without MetS had the lowest 6-year HF risk (HR: 1.12, 95% CI: 0.35 to 1.33 [corrected] and HR: 0.41, 95% CI: 0.10 to 1.31, respectively) compared with normal-weight individuals with MetS (HR: 2.33, 95% CI: 1.25 to 4.36, p < 0.001). From the individual components of MetS, impaired fasting glucose (HR: 1.09, 95% CI: 1.06 to 1.10), high BP (HR: 2.36, 95% CI: 1.03 to 5.43), low high-density lipoprotein cholesterol (HR: 1.88, 95% CI: 1.29 to -2.77), and central obesity (HR: 2.22, 95% CI: 1.02 to 1.05) were all associated with increased HF risk. Factors commonly associated with MetS such as insulin resistance and inflammation (high-sensitivity C-reactive protein and microalbuminuria) were also independently associated with HF incidence. CONCLUSIONS: In contrast to normal weight insulin-resistant individuals, metabolically healthy obese individuals show decreased HF risk in a 6-year follow-up study.

The ECG vertigo in diabetes and cardiac autonomic neuropathy.

The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers a quick, noninvasive clinical and research screen for the early detection of cardiovascular disease in diabetes. In this paper, the clinical and research value of the ECG is readdressed in diabetes and in the presence of cardiac autonomic neuropathy.

Accuracy and precision of glucose monitoring are relevant to treatment decision-making and clinical outcome in hospitalized patients with diabetes.

BACKGROUND AND METHODS: The accuracy and precision of three blood glucose meters (BGMs) were evaluated in 600 hospitalized patients with type 1 (n = 200) or type 2 (n = 400) diabetes. Capillary blood glucose values were analyzed with Accu-Chek(®) Aviva [Roche (Hellas) S.A., Maroussi, Greece], Precision-Xceed(®) [Abbott Laboratories (Hellas) S.A., Alimos, Greece], and Glucocard X-Sensor(®) (Menarini Diagnostics S.A., Argyroupolis, Greece). At the same time plasma glucose was analyzed using the World Health Organization's glucose oxidase method. RESULTS: Median plasma glucose values (141.2 [range, 13-553] mg/dL) were significantly different from that produced by the BGMs (P < 0.001). The Accu-Chek Aviva underestimated hypoglycemia (plasma glucose ≤55 mg/dL) by a mean difference of 4.1 mg/dL (95% confidence interval [CI] 0-28 mg/dL), and the Precision-Xceed did so by a mean difference of 6.2 mg/dL (95% CI 0-29 mg/dL); the same was true for the Glucocard X-Sensor by a mean difference of 9.1 mg/dL (CI 0-57 mg/dL) (P < 0.001 for all BGMs). Hyperglycemia (plasma glucose ≥250 mg/dL) was overestimated with the Accu-Chek Aviva and the Precision-Xceed by a mean difference of 4.8 mg/dL (95% CI 0-41 mg/dL) and 10.4 mg/dL (CI 0-92 mg/dL), respectively; the same was true for the Glucocard X-Sensor by a mean difference of 20.3 mg/dL (95% CI 0-100 mg/dL) (P < 0.001 for all BGMs). Asymptomatic hypoglycemia was detected in 28% of type 1 and in 18% of type 2 diabetes patients. In all cases, the BGMs were unreliable in sensing hypoglycemia. Multivariate linear regression analysis demonstrated that low blood pressure and hematocrit significantly affected glucose measurements obtained with all three BGMs (P < 0.05). CONCLUSIONS: In hospitalized diabetes patients, all three frequently used BGMs undersensed hypoglycemia and oversensed hyperglycemia to some extent. Patients and caregivers should be aware of these restrictions of the BGMs.

Smoking cessation predicts amelioration of microalbuminuria in newly diagnosed type 2 diabetes mellitus: a 1-year prospective study.

The objective of the study was to assess the effect of smoking cessation on microalbuminuria in subjects with newly diagnosed type 2 diabetes mellitus (DM). From 500 smokers newly diagnosed with type 2 DM and microalbuminuria, only 193 (96 men/97 women; age, 56.4 ± 7.8 years) agreed to participate and were educated on smoking cessation, diet, and exercise. Pharmacological interventions were not different among the studied groups. All subjects were contacted by phone monthly with emphasis on smoking cessation. Anthropometric, biochemical parameters and urine specimens were obtained at baseline and at 12-month follow-up. Microalbuminuria was defined as an albumin to creatinine ratio of 30 to 299.9 µg/mg creatinine. Ankle brachial pressure index was determined by ultrasound. A total of 120 (62.2%) subjects quit smoking. Prevalence of microalbuminuria was reduced at 1 year to 72.6% in the subjects who quit smoking and to 22.5% in those who continued smoking (P = .015). Multivariate logistic regression analysis demonstrated that independently associated with the reduction in albumin to creatinine ratio (84.8 vs 28.7 µg/mg creatinine) were amelioration of glycemic control (P < .001), blood pressure (P = .02), dyslipidemia (P = .02), and insulin resistance (P = .05). Smoking cessation also reduced the prevalence of peripheral vascular disease (P = .03) and neuropathy (P = .04). From the pharmacological and lifestyle interventions, smoking cessation had the highest and an independent contribution to the reduction of microalbuminuria (P < .001). Smoking cessation in newly diagnosed type 2 DM patients is associated with amelioration of metabolic parameters, blood pressure, and the reduction of microalbuminuria. Stricter counseling about the importance of quitting smoking upon type 2 DM diagnosis is necessary to protect against the development of diabetic nephropathy and vascular complications.

The association between cardiac autonomic neuropathy with metabolic and other factors in subjects with type 1 and type 2 diabetes.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a common diabetes complication associated with poor prognosis. This cross-sectional study aimed to examine for associations between CAN and metabolic and other parameters in patients with either type 1 (T1DM) or type 2 (T2DM) diabetes. PATIENTS AND METHODS: A total of 600 patients (T1DM, n=200; T2DM, n=400) were recruited. Participants with overt nephropathy, macrovascular complications, and treated hypertension were excluded. CAN was diagnosed when two of the four classical autonomic function tests were abnormal. RESULTS: CAN was diagnosed in 42.0% and in 44.3% of the participants with T1DM and T2DM, respectively. Multivariate logistic regression analysis demonstrated that, in T1DM, the odds [OR (95% confidence intervals)] of CAN increased with higher waist circumference [1.36 (1.01-2.02)], systolic blood pressure [1.16 (1.03-1.31)], hypertension [1.19 (1.03-2.67)], smoking [1.10 (1.12-1.40], fasting glucose [1.01 (1.00-1.01)], HbA(1c) [1.69 (1.07-2.76)], pubertal diabetes onset [1.08 (1.03-1.24)], LDL cholesterol [1.01(1.00-1.02)], triglycerides [1.58 (1.24-1.48)], retinopathy [1.13 (1.04-1.41)], peripheral neuropathy [2.53 (1.07-2.99)], glomerular filtration rate [0.93 (0.87-0.99)], and microalbuminuria [1.24 (1.12-1.36)]. The same analysis in T2DM demonstrated that the odds of CAN increased with higher waist circumference [1.08 (1.00-1.39)], systolic blood pressure [1.06 (1.02-1.12)], hypertension [1.50 (1.24-2.03)], smoking [1.22 (1.14-1.49)], diabetes duration [1.20 (1.09-1.34)], fasting glucose [1.21 (1.12-1.31)], HbA(1c) [1.25 (1.08-1.45)], LDL cholesterol [1.35 (1.04-1.75)], triglycerides [1.30 (1.00-1.68)], retinopathy [1.24 (1.16-1.35)], peripheral neuropathy [1.79 (1.07-2.01)], glomerular filtration rate [0.96 (0.95-0.97)], and microalbuminuria [1.20 (1.14-1.36)]. CONCLUSIONS: CAN is common in diabetes and is associated with modifiable factors including central fat distribution, hypertension, dyslipidemia, worse diabetes control, and smoking, and with the other microvascular complications of diabetes. Our findings emphasize the need for a multifactorial intervention for the prevention of CAN.

Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies.

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.

The performance of a glucose-ketone meter in the diagnosis of diabetic ketoacidosis in patients with type 2 diabetes in the emergency room.

BACKGROUND: Diabetic ketoacidosis (DKA) is a serious metabolic complication. One of its precipitating causes is insulin omission. DKA requires early diagnosis and strict glucose control, which increases the use of glucose meters in the Emergency Room (ER). We aimed to determine the performance of a glucose-ketone meter in the diagnosis of DKA. METHODS: From 450 type 2 diabetes mellitus insulin-treated patients attending the ER with a capillary glucose level >13.9 mmol/L, 50 patients (26 men and 24 women, mean age 60.2 +/- 8.2 years) had DKA. Capillary glucose and beta-hydroxybutyrate (beta-OHB) were measured with the Precision-Xtra device (Abbott Laboratories, Abingdon, UK). Serum glucose and biochemical parameters were measured on an automatic analyzer; serum beta-OHB was determined using an enzymatic end-point spectrophotometric method. Urine ketones were determined using a semiquantitative assay (Ketodiastix, Bayer Diagnostics, Stoke Poges, Slough, UK). RESULTS: Serum and capillary beta-OHB values were highly correlated (r = 0.99, P < 0.001), and the mean difference between them was 0.49 mmol/L (95% confidence interval [CI], 0.35-0.95 mmol/L; P = 0.81). Similarly, serum and capillary glucose values were significantly correlated (r = 0.86, P < 0.001), and the mean difference between them was 0.43 mmol/L (95% CI, 0.82-0.93 mmol/L; P = 0.71). Patients with DKA were inadequately treated with insulin and missed clinic appointments: 80% of patients with DKA compared to 20% of patients without DKA. In all cases, DKA was attributed to insulin omission. Capillary ketonemia (beta-OHB >3.0 mmol/L) had the highest performance (sensitivity 99.87%, specificity 92.89%, positive predictive value 92.89%) for the diagnosis of DKA compared with serum ketonemia (sensitivity 90.45%, specificity 88.65%, positive predictive value 87.76%) or ketonuria (sensitivity 89.89%, specificity 52.73%, positive predictive value 41.87%). CONCLUSIONS: Implementation of measures such as home glucose and ketone monitoring can possibly decrease the number of hospital admissions due to DKA.

The impact of metabolic syndrome on left ventricular myocardial performance.

BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased cardiovascular morbidity and mortality. Recent prospective studies suggested that MetS is associated with increased risk of heart failure. In the present cross-sectional study, we examined the association between left ventricular myocardial performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic subjects, 275 without MetS and 275 with MetS, matched for gender, age and body mass index and free of clinically apparent macrovascular disease were studied. MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial performance was assessed using the Tei index. RESULTS: Both men and women with MetS had higher values of the Tei index, indicating worse myocardial performance, in comparison with those without MetS (p < 0.001). Participants with a cluster of more components of the MetS had higher Tei index values than those with fewer components of the MetS. In addition, among normotensive subjects, those with MetS had significantly higher Tei index values than subjects without MetS. Multivariate linear regression analysis, after adjustment for age and body mass index, demonstrated that MetS status and from the individual components of the MetS, high fasting blood glucose levels, higher blood pressure, low high density lipoprotein levels and high waist circumference were associated with worse myocardial performance. CONCLUSION: MetS is associated with subclinical myocardial dysfunction in both men and women. Strategies to reduce the cardiovascular burden and the risk of heart failure associated with MetS should aim at prevention of the MetS and its related conditions.

Moisture status of the skin of the feet assessed by the visual test neuropad correlates with foot ulceration in diabetes.

OBJECTIVE: To examine the association between the moisture status of the skin of the feet with foot ulceration in subjects with diabetes. RESEARCH DESIGN AND METHODS: A total of 379 subjects with diabetes were examined. Assessment of peripheral neuropathy was based on neuropathy symptom score, neuropathy disability score, vibration perception threshold, and the 10-g monofilament perception. The moisture status of the skin of the feet was assessed using the visual test Neuropad. RESULTS: Patients with foot ulceration had more severe peripheral neuropathy and more often an abnormal Neuropad response. Multivariate logistic regression analysis demonstrated that the odds of foot ulceration increased with measures of neuropathy but increased also with an abnormal Neuropad response. CONCLUSIONS: An abnormal Neuropad response correlates with foot ulceration in subjects with diabetes. This finding, if confirmed prospectively, suggests that the Neuropad test may be included in the screening tests for the prediction of foot ulceration.

Increased left ventricular arrhythmogenicity in metabolic syndrome and relationship with myocardial performance, risk factors for atherosclerosis, and low-grade inflammation.

Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors recently associated with left ventricular dysfunction. Limited data exist on the association between MetS and ventricular arrhythmogenicity. This study examined differences in ventricular arrhythmogenicity assessed by classic (QT interval) and newer (spatial QRS-T angle [spQRS-Ta]) electrocardiographic markers in subjects with and without MetS. A total of 306 subjects, 153 with and 153 without MetS, matched for sex and age were examined. The spQRS-Ta, which vectorcardiographically quantifies the deviation between the directions of ventricular depolarization and repolarization, was measured using a computer-based electrocardiograph. Left ventricular mass index and myocardial performance were evaluated echocardiographically. The spQRS-Ta was significantly higher in subjects with in comparison with those without MetS. Left ventricular mass index, QT interval, and its dispersion were not different between the 2 groups. Left ventricular myocardial performance was worse in subjects with MetS and was associated with higher values of the spQRS-Ta. Multivariate linear regression analysis demonstrated MetS status as the strongest predictor of ventricular arrhythmogenicity. Addition of the high-sensitivity C-reactive protein in the model increased the explained variance of the spQRS-Ta by 11%. In conclusion, ventricular arrhythmogenicity is present in MetS and is associated with myocardial dysfunction, risk factors for atherosclerosis, and low-grade inflammation. The independent association between the spQRS-Ta and MetS implies that the clustering of the metabolic disturbances has additional prognostic information than its individual components in terms of ventricular arrhythmogenicity and may explain in part the excess cardiovascular risk in subjects with MetS.

Combination of nateglinide with thiazolidinediones in Type 2 diabetes.

Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. Treatment of Type 2 diabetes should aim to restore and sustain the normal relationship between insulin sensitivity and secretion. Nateglinide is a rapid-onset, short-acting insulin-secretion enhancer that restores early-phase insulin secretion, reduces postprandial glucose excursions and prevents long-term hyperinsulinemia. Given its mechanism of action, it is evident that nateglinide would be more effective when used in combination with an insulin sensitizer, such as the thiazolidinediones. Thiazolidinediones do not stimulate insulin release and, therefore, are potentially suitable candidates for combination therapy with an insulin-secretion enhancer, such as nateglinide. Combination therapy of thiazolidinediones with nateglinide is effective, carries low risk of hypoglycemia and is suitable for patients with moderate renal impairment, although weight gain and edema are common side effects. Further studies are needed to determine whether nateglinide in combination with thiazolidinediones will help clinicians better achieve their treatment goals in targeting Type 2 diabetes. Moreover, comparative studies between nateglinide and medications targeting postprandial glycemia, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, are necessary. This article summarizes data concerning the mechanism of action, efficacy and safety of therapy with nateglinide and thiazolidinediones as monotherapy and in combination treatment, and aims at a better understanding of the substrate defects their synergy hopes to defy.

Assessment of the Spatial QRS-T Angle by Vectorcardiography: Current Data and Perspectives.

The concept of the ventricular gradient (VG) was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. Spatial vectorcardiography is based on the concept of the VG. Its current major clinical use is to identify primary [heterogeneity of ventricular action potential (VAP) morphology] in the presence of secondary [heterogeneity in ventricular depolarization instants] T-wave abnormalities in an ECG. Nowadays, the calculation of the spatial VG can be computed on the basis of a regular routine ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local VAP duration heterogeneity. Recent population-based studies suggest that the spatial VG is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary prevention efforts and can be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial VG. The main focus is the role of the spatial VG in ECG assessment of dispersion of repolarization, a key factor in arrhythmogeneity.

High rates of comorbid conditions in patients with type 2 diabetes and foot ulcers.

UNLABELLED:   Background/Aim. Foot ulceration is one of the most important diabetic complications that results in major medical, social, and economic consequences for patients, their families, and society as a whole. Previous studies have shown increased mortality in patients with diabetes with foot ulcers; however, the reason for the high mortality in this group of patients is not known. The aim of this cross-sectional study was to investigate prevalence rates of comorbid conditions in patients with diabetes and foot ulcers. METHODS: A total of 742 patients with type 2 diabetes (234 with foot ulcers and 508 without ulcers), consecutively attending the outpatient diabetes and diabetic foot clinics of the authors' hospital were reviewed. Clinical examination was performed to classify ulcers as neuropathic or neuroischemic, microvascular and macrovascular complications, as well as laboratory tests that were reviewed from medical records. RESULTS: Patients with diabetes with and without foot ulcers did not differ significantly in terms of age, sex, smoking habits, glycemic control, and prevalence rates of hypertension, dyslipidemia, and cerebrovascular disease. Known duration of diabetes was longer (P < 0.001), while the values of body mass index (P = 0.03) and creatinine clearance (P = 0.003) were lower in the patients with foot ulcers than in those without ulcers. In addition, prevalence rates of coronary artery disease (P = 0.005), lower extremity arterial disease (P < 0.001), retinopathy (P < 0.001), and nephropathy (P = 0.04), were higher in the patients with foot ulcers compared to those without ulcers. Additionally, duration of diabetes was longer and the prevalence rates of microvascular and macrovascular complications as well as hypertension, dyslipidemia, and smoking were much higher in the patients with neuroischemic ulcers in comparison to those with neuropathic ulcers. CONCLUSION: The high mortality rates in patients with diabetes and foot ulcers may be due to the high prevalence rates of comorbid conditions, especially coronary artery disease and nephropathy.

A review of nateglinide in the management of patients with type 2 diabetes.

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic beta-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective "gate-keeper" in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality.