Activated hypothalamic pituitary adrenal axis in patients with metabolic syndrome.

Metabolic syndrome (MetS) is correlated with the activity of hypothalamic-pituitary-adrenal axis (HPA), but the underlying mechanism still remains elusive. The aim of this study was to investigate the HPA axis function in patients with MetS. This case-control study included 159 people. They were divided into 2 groups. The first group included 73 healthy volunteers (control group: 19 males, 54 females, mean±SD: 49.9±7.5 years old, with BMI: 27.9±4.42 kg/m2) and the second group included 86 patients with MetS (case group: 48 males, 38 females, mean±SD: 52.2±7.6 years old, with BMI: 30.5±5.35 kg/m2). An oral glucose tolerance test (OGTT) was performed for all subjects after a 12-h overnight fast, and blood samples were obtained for determination of ACTH, cortisol, insulin, C-peptide, and glucose levels. Serum cortisol after an overnight dexamethasone suppression test was determined in both groups. Patients with MetS had serum cortisol levels after an overnight dexamethasone suppression test significantly higher than controls. During OGTT plasma ACTH levels were higher at all time points in patients with MetS compared to controls, whereas serum cortisol levels were comparable between the 2 groups. Plasma ACTH during OGTT was also correlated with most of the components of MetS. The HPA axis in patients with MetS seems to be more active as evidenced by the higher cortisol levels after the overnight dexamethasone suppression test and by the higher ACTH levels during OGTT. This functional hypercortisolism might be involved in the pathogenesis of the metabolic syndrome.

Ghrelin and leptin secretion in patients with moderate Alzheimer's disease.

BACKGROUND: Weight loss is a characteristic finding of patients with Alzheimer's disease (AD). It seems that precedes cognitive impairment by some years, but the underlying causes are not fully understood. Ghrelin and leptin are involved in energy homeostasis, and may be implicated in weight losing observed in these patients. OBJECTIVE: To examine the potential relationship between ghrelin and leptin levels and weight loss in patients with AD. DESIGN: The study included 27 patients (10 men and 17 women) with AD of moderate severity, and 23 controls (10 males and 13 females), matched for age and BMI. Body fat and lean mass content were assessed using a portable apparatus. Cognitive function was assessed with the Mini-Mental State Examination. Basal serum samples for the measurement of leptin, ghrelin, insulin and glucose were obtained, and serum ghrelin, insulin and glucose were measured after a 75-gr glucose load in both groups. RESULTS: Patients with Alzheimer Disease (AD) have lower lean mass content compared to controls. Basal ghrelin and leptin is similar in patients with AD and controls. The area-under-the-curve for ghrelin (AUC) is lower in male patients with AD compared to control males, while no difference was observed between females AD and controls. CONCLUSION: Male patients with AD, in contrast with female patients, fail to maintain a normal energy homeostasis even in the early stages of the disease, as shown by the decreased lean mass content in males AD compared to controls. Disruption of the normal compensatory modulation of ghrelin secretion might contribute to the metabolic changes observed in male patients with AD.

Ghrelin response to oral glucose load in hyperthyroidism, before and after treatment with antithyroid drugs.

Hyperthyroidism is characterized by hyperphagia and increased basal metabolic rate. Ghrelin peptide is implicated in food intake through activation of the orexigenic neuropeptide Y/agouti related protein in the arcuate nucleus of hypothalamus. Also different studies suggested that ghrelin might play a role in states of energy insufficiency, controlling body weight. We therefore evaluate ghrelin levels in severe hyperthyroidism before and after medical treatment when euthyroidism was achieved, in order to evaluate its possible role in the increase of appetite and in the metabolic changes observed in hyperthyroidism. Serum ghrelin and insulin levels were measured after an oral glucose tolerance test (OGTT), in 7 severe hyperthyroid female patients, before and after medical treatment when euthyroidism was achieved. Body mass index (BMI), percentage of body fat and lean mass was also estimated in hyperthyroidism as well as in euthyroidism. Basal insulin levels were statistically higher in hyperthyroid patients with respect to euthyroid state after treatment (p=0.02, t=3.379), while homeostasis model assessment (HOMA) index for insulin sensitivity was statistically higher in hyperthyroidism (group 1) compared to euthyroidism (group 2) (1.64+/-0.69 vs 0.78+/-0.44, p=0.019, t=3.389). Fasting ghrelin concentrations were significantly reduced in group 1 compared to group 2 (938+/-578 pg/ml vs 1402+/-566 pg/ml, p<0.05, t=-2.489). Oral glucose loading induced suppression of ghrelin level in both groups, but the area under the curve for ghrelin during the OGTT in euthyroidism was greater compared to hyperthyroidism (p=0.05, t=-2.485). After medical treatment, a statistically significant increase in BMI (23.1+/-4.3 vs 25.9+/-5.1) (p=0.007, t=-4.399) was also observed. In hyperthyroidism, basal ghrelin levels showed a negative correlation with BMI (p=0.042, r=-0.829), insulin (p<0.001, r=-1.000), and HOMA index (p=0.019, r=-0.886). No correlation was found between ghrelin levels and thyroid hormone values. Ghrelin levels are decreased in hyperthyroidism and increase when euthyroidism is achieved. BMI and insulin are the main factors that influence ghrelin concentration in hyperthyroidism. T3 and T4 levels do not influence ghrelin levels. There is no evidence that ghrelin is responsible for the increase appetite seen in hyperthyroidism.

Serum adiponectin levels in different types of non alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis.

BACKGROUND AND STUDY AIMS: In recent studies adiponectin has been implicated in the pathogenesis of non alcoholic liver disease (NAFLD), a common chronic liver disease with a broad spectrum of histopathologic findings. The aim of this study was to investigate the correlation between serum adiponectin levels and steatosis, necroinflammation and fibrosis in different types of NAFLD patients. PATIENTS AND METHODS: Forty three patients with elevated liver enzymes and biopsy proven non alcoholic fatty liver disease and 38 patients with clinically diagnosed NAFLD and permanently normal liver enzymes were prospectively enrolled in the study. Patients with biopsy proven NAFLD were divided into two groups: non alcoholic steatohepatitis (NASH): 25 patients and simple steatosis: 18 patients. Serum adiponectin levels were measured with an ELISA immunoassay, and BMI, fasting serum glucose, total and HDL cholesterol, fasting triglyceride levels and insulin resistance were determined. RESULTS: Groups did not differ in age, sex, BMI, waist circumference and HOMA - IR. Only patients with confirmed NASH had lower serum adiponectin levels in comparison to NAFLD patients with both abnormal (6.6 +/- 4.7 microg/mL vs 10.8 +/- 5.6 microg/mL, p = 0.01) as well as normal liver enzymes (6.6 +/- 4.7 microg/mL vs 9.2 +/- 4.8 microg/mL, p = 0.01). For the whole NAFLD group with elevated liver enzymes no correlation was found between serum adiponectin levels and the degree of liver steatosis or fibrosis stage. Also no correlation was found between adiponectin levels and BMI, ALT, AST, gamma GT or HOMA-IR. CONCLUSIONS: Patients with established NASH have lower serum adiponectin levels than NAFLD patients with normal or abnormal liver enzymes. Adiponectin was not associated with the severity of hepatic fibrosis.

Medial arterial calcification is frequently found in patients with microalbuminuria.

The presence of medial arterial calcification (MAC), often referred to as Moncheberg's sclerosis, was sought in patients with long-standing diabetes mellitus. One hundred patients aged 22-50 years were initially divided into two groups, those with neuropathy and those without. As expected, the incidence of MAC was significantly higher in the neuropathy group (40% vs. 20%). When the patients were divided into two groups, those with MAC and those without, it appeared that the incidence of MAC was very high in patients who had microalbuminuria (57% vs. 13%) and particularly when microalbuminuria was combined with neuropathy (40% vs. 7%). It is concluded that microalbuminuria is a strong predicting factor of medial arterial sclerosis independent of neuropathy.

Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in patients with coronary artery disease independent of obesity.

Insulin resistance and hyperinsulinemia both in normal persons and those with non-insulin dependent diabetes mellitus (NIDDM) (type 2 diabetes) appears to be related to obesity. It seems also that insulin plays a role in modulating the obesity-related factors (eg, hyperinsulinemia, hyperglycemia, hypertension, hypertriglyceridemia, hypercholesterolemia, low concentrations of high-density lipoprotein cholesterol) and takes its place among the many risk factors for coronary artery disease (CAD) associated with obesity. Insulin resistance and hyperinsulinemia could play the same role in pathogenesis of CAD independently of obesity. The authors determined blood glucose and immunoreactive insulin and plasma triglyceride concentrations in the fasting state at 60 and 120 minutes after a glucose load of 75 g in 68 patients (54 men, 14 women) with angiographic evidence of CAD and in 65 healthy volunteers matched to the patients for age, gender, and body mass index (43 men and 22 women). Patients with CAD and the healthy volunteers were categorized as obese (body mass index > or = 26 kg/m2) and nonobese (body mass index < 26 kg/m2). Four groups of subjects were analyzed: Group A included 40 healthy (28 men and 12 women) nonobese volunteers; group B, 25 healthy (15 men and 10 women) obese volunteers; group C, 39 (30 men and 9 women) nonobese patients with CAD; and group D, 29 (24 men and 5 women) obese patients with CAD. Fasting and postchallenged 60- and 120-minute glucose values were similar in groups A and C. However, significantly higher insulin values (mU/L) were observed in group C than in group A during fasting (12.2+/-6.2 vs 91+/-3, p<0.05), and postchallenged at 60 minutes (103.1+/-53.2 vs 71.9+/-64.3, p<0.01) and 120 minutes (57.9+/-41.2 vs 44.9 +/-41.3, p<0.01). Fasting glucose and insulin values were similar in groups B and D. However, significantly higher glucose (mg/dL) and insulin values were observed in group D than in group B postchallenged at 60 and 120 minutes: glucose at 60 minutes (188.7 +/-45.1 vs 154.2+/-37.5, p<0.05); insulin at 60 minutes (127.5+/-98.5 vs 112.1+/-81.1, p<0.05); glucose at 120 minutes (124.2+/-46.1 vs 99.5+/-28.9, p<0.05); insulin at 120 minutes (86.1+/-57.6 vs 62.8+/-27.9, p<0.05). The glucose and insulin values during 60- and 120-minute fasting as well as postchallenged were similar in groups B and C. Significantly higher plasma triglyceride concentrations were observed in group C than in group A (149.0+/-64.1 vs 114.6+/-46.6, p<0.01) and in group D compared with group B (229.4+/-104.7 vs 144.9+/-65.1, p<0.001). Plasma triglyceride concentrations were similar in groups B and C. The authors conclude that patients with documented CAD are insulin resistant independently of obesity.

Absorption of ciprofloxacin in patients with diabetic gastroparesis.

The purpose of this study was to assess the pharmacokinetic profile of ciprofloxacin in 12 patients with diabetic gastroparesis. Patients received both a single 500-mg oral (p.o.) dose and a single 400-mg intravenous (i.v.) dose of ciprofloxacin separated by a 1-week washout period. Pharmacokinetic parameters (means +/- standard deviations) for the p.o. and i.v. doses were as follows: areas under the concentration-time curve from 0 h to infinity, 9.74 +/- 2.59 and 11.78 +/- 3.18 micrograms.h/ml, respectively; maximum concentrations of drug in serum, 2.13 +/- 0.67 and 4.21 +/- 1.07 micrograms/ml, respectively; and half-lives, 4.03 +/- 0.58 and 4.20 +/- 0.58 h, respectively. The ratio of the areas under the concentration-time curves from 0 h to infinity for the p.o. and i.v. doses was 0.84, with a 90% confidence interval of 0.68 to 0.98; the mean absolute bioavailability was calculated to be 67% (range, 43 to 82%). From these data it appears that ciprofloxacin is adequately absorbed in patients with diabetic gastroparesis.