Christina Voulgari

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.

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.

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.

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.

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.

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.

The impact of metabolic syndrome on left ventricular myocardial performance

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.

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 association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with Type 2 diabetes mellitus

Diabet. Med. 27, 1420–1429 (2010)

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.