Obesity is a very common disease worldwide, resulting from a disturbance in the energy balance. The metabolic syndrome is also a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. The major concerns of obesity and metabolic syndrome are the comorbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Sympathetic nervous system (SNS) activity is associated with both energy balance and metabolic syndrome. Sympathomimetic medications decrease food intake, increase resting metabolic rate (RMR), and thermogenic responses, whereas blockage of the SNS exerts opposite effects. The contribution of the SNS to the daily energy expenditure, however, is small ( approximately 5%) in normal subjects consuming a weight maintenance diet. Fasting suppresses, whereas meal ingestion induces SNS activity. Most of the data agree that obesity is characterized by SNS predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli. Weight loss reduces SNS overactivity in obesity. Metabolic syndrome is characterized by enhanced SNS activity. Most of the indices used for the assessment of its activity are better associated with visceral fat than with total fat mass. Visceral fat is prone to lipolysis: this effect is mediated by catecholamine action on the sensitive beta(3)-adrenoceptors found in the intraabdominal fat. In addition, central fat distribution is associated with disturbances in the hypothalamo-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome. Furthermore, SNS activity induces a proinflammatory state by IL-6 production, which in turn results in an acute phase response. The increased levels of inflammatory markers seen in the metabolic syndrome may be elicited, at least in part, by SNS overactivity. Intervention studies showed that the disturbances of the autonomic nervous system seen in the metabolic syndrome are reversible.

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.

In contrast to normal weight insulin-resistant individuals, metabolically healthy obese individuals show decreased HF risk in a 6-year follow-up study.

Context:The rate at which people eat has been suggested to be positively associated with obesity, although appetite and related gut hormones have not been measured. Objective:The objective of the study was to determine whether eating the same meal at varying speeds elicits different postprandial gut peptide responses. Design and Setting:This was a crossover study at a clinical research facility.Study Participants: Seventeen healthy adult male volunteers participated in the study. Intervention:A test meal consisting of 300 ml ice cream (675 kcal) was consumed in random order on two different sessions by each subject: meal duration took either 5 or 30 min. Main Outcome Measures:The postprandial response of the orexigenic hormone ghrelin and the anorexigenic peptides peptide YY and glucagon-like peptide-1 over 210 min was assessed. Visual analog scales for the subjective feelings of hunger and fullness were completed throughout each session.Results: Peptide YY area under the curve (AUC) was higher after the 30-min meal than after the 5-min meal (mean Ϯ SEM AUC 5 min meal: 4133 Ϯ 324, AUC 30 min meal: 5250 Ϯ 330 pmol/liter ⅐ min, P ϭ 0.004), as was glucagon-like peptide-1 AUC (mean Ϯ SEM AUC 5 min meal: 6219 Ϯ 256, AUC 30 min meal: 8794 Ϯ 656 pmol/liter ⅐ min, P ϭ 0.001). There was a trend for higher visual analog scale fullness ratings immediately after the end of the 30-min meal compared with immediately after the 5-min meal. There were no differences in ghrelin response.Conclusions: Eating at a physiologically moderate pace leads to a more pronounced anorexigenic gut peptide response than eating very fast. (J Clin Endocrinol Metab 95: 333-337, 2010)

Diabetic foot ulcers are often complicated by infection. Among pathogens, Staphylococcus aureus predominates. The prevalence of methicillin-resistant S. aureus (MRSA) in infected foot ulcers is 15-30% and there is an alarming trend for increase in many countries. There are also data that recognize new strains of MRSA that are resistant to vancomycin. The risk for MRSA isolation increases in the presence of osteomyelitis, nasal carriage of MRSA, prior use of antibacterials or hospitalization, larger ulcer size and longer duration of the ulcer. The need for amputation and surgical debridement increases in patients infected with MRSA. Infections of mild or moderate severity caused by community-acquired MRSA can be treated with cotrimoxazole (trimethoprim/sulfamethoxazole), doxycycline or clindamycin when susceptibility results are available, while severe community-acquired or hospital-acquired MRSA infections should be managed with glycopeptides, linezolide or daptomycin. Dalbavancin, tigecycline and ceftobiprole are newer promising antimicrobial agents active against MRSA that may also have a role in the treatment of foot infections if more data on their efficacy and safety become available.

Serum inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), and procalcitonin (PCT), have been used for the diagnosis of foot infections in patients with diabetes. However, little is known about their changes during treatment of patients with foot infections. The aim of this prospective study was to examine the performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. A total of 61 patients (age 63.1 ± 7.0 years, 45 men and 16 women, 7 with type 1 and 54 with type 2 diabetes) with untreated foot infection (34 with soft-tissue infection and 27 with osteomyelitis) were recruited. Diagnosis of osteomyelitis was based on clinical examination and was confirmed by imaging studies (X-ray, scintigraphy, magnetic resonance imaging). Determination of the inflammatory markers was performed at baseline, after 1 week, after 3 weeks, and after 3 months of treatment. At baseline, the values of CRP, ESR, WBC, and PCT were significantly higher in patients with osteomyelitis than in those with soft-tissue infections. The sensitivity and specificity for the diagnosis of osteomyelitis of CRP (cutoff value >14 mg/L) were 0.85 and 0.83, of ESR (cutoff value >67 mm/h) 0.84 and 0.75, of WBC (cutoff value >14 × 10(9)/L) 0.75 and 0.79, and of PCT (cutoff value >0.30 ng/mL) 0.81 and 0.71, respectively. All values declined after initiation of treatment with antibiotics; the WBC, CRP, and PCT values returned to near-normal levels at day 7, whereas the values of ESR remained high until month 3 only in patients with bone infection. From the inflammatory markers, ESR is recommended to be used for the follow-up of patients with osteomyelitis.

[1685][1686][1687][1688][1689][1690][1691][1692][1693]. Objective: The aim of this study was to test the hypothesis that baroreflex sensitivity (BRS), assessed by indirect measurement of aortic pressure, is blunted in obesity. Additionally, the potential effect of cardiac autonomic nervous system (ANS) activity, aortic compliance, and metabolic parameters on BRS of obese subjects was investigated. Research Methods and Procedures:A group of 30 women with BMI Ͼ30 kg/m 2 and a group of 30 controls with BMI Ͻ25 kg/m 2 were examined. BRS was estimated by the sequence technique, cardiac ANS activity by short-term spectral analysis of heart rate variability (HRV), and aortic compliance by the method of applanation tonometry. Results: BRS was lower in obese women (9.18 Ϯ 3.77 vs. 19.63 Ϯ 9.16 ms/mm Hg, p Ͻ 0.001). The median values (interquartile range) of the power of both the high-frequency and low-frequency components of the HRV were higher in the lean than in the obese participants Multivariate analysis demonstrated a significant and independent association between BRS and age (p ϭ 0.003), BMI (p Ͻ 0.001), and high-frequency power of HRV (p Ͻ 0.001). These variables explained 72% of the variation of BRS values. Discussion: BRS is severely reduced in obese subjects. BMI, age, and the parasympathetic nervous system activity are the main determinants of BRS. Baroreflex behavior is of clinical relevance because an attenuated BRS represents a negative prognostic factor in cardiovascular diseases, which are common in obesity.

OBJECTIVE -To compare survival rates after first amputation between patients with and without diabetes.RESEARCH DESIGN AAND METHODS -We performed a retrospective study of all nontraumatic amputations performed at our center in the years 1990 -1995 in patients with (n ϭ 100) and without (n ϭ 151) diabetes. Survival status was assessed from the first amputation until 31 December 2001.RESULTS -Altogether, 61% of the patients with and 54.3% of those without diabetes died 5.2 (4.5-5.8) and 5.3 (4.7-5.9) [mean (95% CI)] years after the first amputation, respectively (P ϭ 0.80). Survival was not different between patients with and without diabetes after controlling for the level (major versus minor) (P ϭ 0.67) or the cause (ischemia versus infection) of amputation (P ϭ 0.72). No sex differences were found for survival in either study group. Independent predictors of mortality in the diabetic group were duration of diabetes (P ϭ 0.05), history of stroke (P ϭ 0.02), and serum creatinine level (P Ͻ 0.0001), while in the nondiabetic group independent predictors were history of stroke (P ϭ 0.04), serum creatinine level (P ϭ 0.005), and higher white blood cell count (P ϭ 0.02). The peak incidence of amputations was observed in the decade of 67-76 years of age in both groups. Major amputations were more common among nondiabetic patients in all age-groups. Median hospital stay and postoperative complications were comparable between the two groups.CONCLUSIONS -All-cause mortality is high after an amputation in both diabetic and nondiabetic patients. Mortality rates, hospital stay, and postoperative complications are not different between diabetic and nondiabetic amputees. No modifiable factors, with the exception of nephropathy, were found to improve survival in amputees. Peripheral vascular disease and neuropathy are the main cause of amputations; prevention, therefore, of these complications is warranted to prevent amputations and the subsequent high mortality. Diabetes Care 27:1598 -1604, 2004D iabetes is the cause of almost 50% of all nontraumatic lower-extremity amputations worldwide (1-5). It is estimated that the lifetime risk for amputation in patients with diabetes is 10 -15%, 10 -30 times higher in comparison with the general population (2,3). Amputation is associated with a high rate of subsequent amputation and considerable health care cost in both patients with and without diabetes (6,7). Most amputations in diabetic patients are due to peripheral vascular disease, peripheral neuropathy, and infection, while in nondiabetic patients peripheral vascular disease is the main cause (2,8). Previous studies have demonstrated an increased mortality following an amputation in both diabetic and nondiabetic patients (4,9 -12). However, no recent data exist concerning the comparison in survival after an amputation between diabetic and nondiabetic patients. The primary objective of this study was to look at the outcome of amputees and compare it between those with and without diabetes to see if there are any modifiable risk fac...