Circulating adipokines and mRNA expression in adipose tissue and the placenta in women with gestational diabetes mellitus.

Maternal adipose tissue and the placenta secrete various molecules commonly called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin that are important players in the pathogenesis of insulin resistance. Gestational diabetes mellitus (GDM) is defined as a state of glucose intolerance characterized by ß-cell dysfunction and insulin resistance. To examine whether circulating adipokines and their mRNA expression in the adipose tissue and the placenta are altered in GDM pregnancy, we compared 15 GDM women [obese (BMI > 30) and non-obese (BMI < 30)] to 23 NGT (normal glucose tolerance) women [obese and non-obese], at the time of the Cesarean section. Circulating chemerin and leptin were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1, visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p = 0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women. Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1 correlated negatively with BMI. Serum TNF-α was significantly elevated in all obese compared to non-obese pregnant women and correlated positively with BMI. Adiponectin levels were reduced -although not significantly- in GDM- and NGT-obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6 levels did not differ significantly between groups. Chemerin mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was significantly higher compared to placenta in all women (6-to 24-times, p < 0.05). Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and its expression in placenta was negligible in all women. Although, leptin was expressed significantly higher in SAT compared to VAT and the placenta in all women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM and NGT) differed significantly when compared to NGT-non-obese women (3-times higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in GDM women complicated by obesity. This finding together with the positive association of chemerin and leptin with markers of insulin resistance, suggests that these adipokines and more especially chemerin and leptin accompanied by their adipose tissue expression could contribute to the increased insulin resistance and low grade inflammation that characterizes GDM-obese women.

Vinegar Consumption Increases Insulin-Stimulated Glucose Uptake by the Forearm Muscle in Humans with Type 2 Diabetes.

BACKGROUND AND AIMS: Vinegar has been shown to have a glucose-lowering effect in patients with glucose abnormalities. However, the mechanisms of this effect are still obscure. The aim of this randomised, crossover study was to investigate the effect of vinegar on glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal. MATERIALS AND METHODS: Eleven subjects with DM2 consumed vinegar or placebo (at random order on two separate days, a week apart), before a mixed meal. Plasma glucose, insulin, triglycerides, nonesterified fatty acids (NEFA), and glycerol were measured preprandially and at 30-60 min for 300 min postprandially from the radial artery and from a forearm vein. Muscle blood flow was measured with strain-gauge plethysmography. Glucose uptake was calculated as the arteriovenous difference of glucose multiplied by blood flow. RESULTS: Vinegar compared to placebo (1) increased forearm glucose uptake (p = 0.0357), (2) decreased plasma glucose (p = 0.0279), insulin (p = 0.0457), and triglycerides (p = 0.0439), and (3) did not change NEFA and glycerol. CONCLUSIONS: In DM2 vinegar reduces postprandial hyperglycaemia, hyperinsulinaemia, and hypertriglyceridaemia without affecting lipolysis. Vinegar's effect on carbohydrate metabolism may be partly accounted for by an increase in glucose uptake, demonstrating an improvement in insulin action in skeletal muscle. This trial is registered with Clinicaltrials.gov NCT02309424.

Effect of aliskiren on circulating endothelial progenitor cells and vascular function in patients with type 2 diabetes and essential hypertension.

BACKGROUND: The aim of this study was to investigate the effects of aliskiren on vascular function and endothelial progenitor cells (EPCs) in patients with type 2 diabetes and essential hypertension. METHODS: The study enrolled type 2 diabetic patients aged >50 years under stable glycemic control and first diagnosed mild essential hypertension. In phase A (n = 20), patients received aliskiren 150-300 mg daily for 3 months. In phase B (n = 12), hydrochlorothiazide (HCTZ) 12.5-25mg daily substituted for aliskiren for 3 more months. At baseline and at the end of each phase, we assessed (i) brachial blood pressure (BBP); (ii) central aortic systolic pressure (CSP), aortic augmentation index (Aix), and pulse wave velocity (PWV) as markers of arterial stiffness; (iii) brachial artery flow-mediated dilatation (FMD) as a marker of endothelial function; (iv) left ventricular (LV) twisting and untwisting as markers of LV function and (v) EPC numbers in culture of peripheral blood mononuclear cells. RESULTS: Aliskiren similarly reduced BBP and CSP, increased FMD (P < 0.001) and EPC numbers (P < 0.001), decreased PWV and Aix (P < 0.05), and improved LV twisting and untwisting (P < 0.05). Although substitution of HCTZ sustained BBP at similar levels, CSP and echocardiographic indices nearly returned at baseline levels, and the improvement of FMD, PWV, Aix, and EPC numbers was abolished. CONCLUSIONS: Aliskiren had a favorable effect on endothelial function and EPCs, reduced arterial stiffness, and improved LV twisting and untwisting. These effects were independent of BBP lowering, as they were not observed after the achievement of similar values of BBP with HCTZ.

Effect and mechanisms of action of vinegar on glucose metabolism, lipid profile, and body weight.

The aim of this review is to summarize the effects of vinegar on glucose and lipid metabolism. Several studies have demonstrated that vinegar can help reduce hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity. Other studies, however, have shown no beneficial effect on metabolism. Several mechanisms have been proposed to explain these metabolic effects, including delayed gastric emptying and enteral absorption, suppression of hepatic glucose production, increased glucose utilization, upregulation of flow-mediated vasodilation, facilitation of insulin secretion, reduction in lipogenesis, increase in lipolysis, stimulation of fecal bile acid excretion, increased satiety, and enhanced energy expenditure. Although some evidence supports the use of vinegar as a complementary treatment in patients with glucose and lipid abnormalities, further large-scale long-term trials with impeccable methodology are warranted before definitive health claims can be made.

Cytokines, diabetes mellitus and psychopathology: a challenging combination.

OBJECTIVES: The aim of this study was to investigate the association of IL-6, IL-12, and TNF-α with trait and state psychological factors in type 2 diabetic patients. DESIGN: Patients were divided in two groups. Group A consisted of 86 controlled diabetic patients (HbA1c<7) and the Group B consisted of 45 uncontrolled diabetic patients (HbA1c ≥ 7). SETTINGS: During the initial phase of the study (T0), blood samples were taken for measuring IL-6, IL-12 and TNF-α serum levels as well as a battery of psychometric instruments. One year later (T1), the uncontrolled diabetic patients were re-evaluated with the use of the same psychometric instruments and with the identical blood analysis. RESULTS: The average values of tnf-α were significantly different among controlled (7.73 ± 5.51) and uncontrolled patients (9.29 ± 4.52) at a significance level of 5% (p=0.009). Controlled diabetic patients show a statistically significant relationship between IL-6 and neuroticism (rp=0.303, p=0.010), and between IL-12 and psychotism, (rsp=0.382, p=0.001). Controlled diabetic patients show a statistically significant relationship between IL-12 and the act out hostility (rsp=-0.307, p=0.009). The scores of the psychometric tests differ significantly between the first and second evaluation. Acting out hostility and the direction of hostility increased when HbA1c values fell below the threshold of 7, while the total hostility index, as well as all other scales, dropped when patients controlled their metabolic profile. CONCLUSIONS: The present results provide evidence that IL-6, IL-12 and TNF-α are closely related to the course and treatment of type 2 diabetes.

Endothelial progenitor cells as a cardiometabolic risk factor marker in prediabetes.

OBJECTIVE: Endothelial progenitor cells (EPCs) have recently been considered as a potential novel marker of vascular integrity, atherosclerosis and cardiovascular risk. This study was performed to investigate the main determinants of EPC levels in individuals with prediabetes. DESIGN: Thirty-nine participants with newly diagnosed prediabetes were enrolled. Flow cytometric analysis was used to quantify EPCs (CD34+CD133+VEGFR-2+). Traditional risk factors, high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR) and anthropometric parameters, including ultrasonographic-determined visceral and subcutaneous fat, were recorded. RESULTS: In univariate analysis, EPC levels significantly correlated with waist circumference (p=0.017), mean arterial pressure (p=0.009), total cholesterol (p=0.003), hs-CRP (p=0.006), HOMA-IR (p=0.031) and visceral fat (p=0.040). However, in stepwise multivariate ordinal logistic regression analysis, only visceral fat retained its statistical significance (OR=0.79, 95%Cl:0.64-0.98, p=0.032). CONCLUSIONS: Visceral fat seems to be the main determinant of EPC levels in individuals with prediabetes and to form a plausible link between mild metabolic abnormalities, cardiovascular risk and vascular homeostasis process.

Association of lean body mass with cardiometabolic risk factors in healthy postmenopausal women.

OBJECTIVE: Aim of this study was to investigate the association of total and regional lean body mass (LBM) with cardiometabolic risk factors in healthy obese and nonobese postmenopausal women. METHODS: A total of 150 postmenopausal women (age 54 ± 7 years, BMI 29.6 ± 5.8 kg/m2) underwent a comprehensive assessment of cardiometabolic risk, including metabolic syndrome (MS). Body composition analysis was performed with Dual-energy X-ray Absorptiometry, and multiple height-adjusted indices of total and regional LBM were evaluated. RESULTS: After controlling for age, diet, physical activity, and total fat mass, most indices of total, central, and peripheral LBM displayed significant positive correlations with cardiometabolic risk factors. Most associations were no longer significant after controlling for waist circumference, with the only exception of lean mass in the arms, which remained significantly associated with the presence and severity of MS (number of MS abnormalities), independently of central adiposity. A significant additive interaction was found between lean mass in the arms and waist circumference in increasing the prevalence of MS. CONCLUSIONS: LBM is unfavorably associated with cardiometabolic risk factors in healthy postmenopausal women. Whether LBM, especially in arms, is associated with cardiometabolic health independently of central fat distribution in postmenopausal women, merits further investigation.

Regional fat distribution and cardiometabolic risk in healthy postmenopausal women.

BACKGROUND: Regional fat distribution is an important determinant of cardiometabolic risk after menopause. The aim of the present study was to investigate the association between indices of fat distribution obtained by Dual-energy X-ray Absorptiometry (DXA) and representative cardiometabolic risk factors in a cohort of healthy postmenopausal women. METHODS: In this cross-sectional study, cardiometabolic risk factors were correlated with a variety of central and peripheral fat depots obtained by DXA, in a total of 150 postmenopausal women, free of diabetes and cardiovascular disease (age 54 ± 7 years, BMI 29.6 ± 5.8 kg/m(2), mean ± 1 SD). RESULTS: After adjusting for age and total adiposity, DXA-derived indices of central and peripheral fat distribution displayed opposite associations (positive versus negative) with the examined cardiometabolic risk factors. In multivariate regression analysis, thoracic fat mass % was an independent predictor of blood pressure, HOMA index and triglycerides, abdominal fat mass % was an independent predictor of high sensitivity C-reactive protein, and abdominal-to-gluteofemoral fat ratio was an independent predictor of high density lipoprotein cholesterol. An index of peripheral fat distribution, gluteofemoral fat mass %, proved to be the most important determinant of metabolic syndrome (Odds Ratio 0.76, 95% confidence intervals 0.67-0.87, p<0.001), independent of total and central adiposity. CONCLUSION: DXA-derived indices of regional fat distribution such as thoracic, abdominal and gluteofemoral fat, correlate significantly with cardiometabolic risk factors in healthy postmenopausal women, and may serve as clinically useful tools for evaluating cardiometabolic risk after menopause.

Insulin action in morbid obesity: a focus on muscle and adipose tissue.

The aim of this review is to summarize the mechanisms underlying insulin resistance in morbid obesity. Glucose regulation by insulin depends on the suppression of endogenous glucose production and stimulation of glucose disposal. In morbid obesity, glucose production by the liver is increased. Moreover, the sensitivity of glucose metabolism to insulin is impaired both in muscle (due to defects in insulin-stimulated glucose utilization and decreased blood flow) and in adipose tissue (due to decreased blood flow). However, recent studies suggest that expanded total fat mass becomes a major consumer of glucose providing a sink for glucose and compensating for insulin resistance. Metabolism and immunity are closely linked. Bearing in mind the crosstalk between inflammatory pathways and the insulin signaling cascade, adipose tissue derived cytokines may represent a link between inflammation and metabolic signals and mediate, at least in part, insulin resistance. Adipose tissue plays a crucial role by buffering daily influx of dietary fat, suppressing the release of non-esterified fatty acids into the circulation and increasing triacylglycerol clearance. However, in morbid obesity there is an impairment of the normal ability of adipose tissue to buffer fatty acids, despite hyperinsulinemia. Lipotoxicity gradually impairs insulin action in the liver and muscle, aggravating insulin resistance.

Body composition determinants of metabolic phenotypes of obesity in nonobese and obese postmenopausal women.

OBJECTIVE: Although obesity is typically associated with increased cardiovascular risk, a subset of obese individuals display a normal metabolic profile ("metabolically healthy obese," MHO) and conversely, a subset of nonobese subjects present with obesity-associated cardiometabolic abnormalities ("metabolically obese nonobese," MONO). The aim of this cross-sectional study was to identify the most important body composition determinants of metabolic phenotypes of obesity in nonobese and obese healthy postmenopausal women. DESIGN AND METHODS: We studied a total of 150 postmenopausal women (age 54 ± 7 years, mean ± 1 SD). Based on a cardiometabolic risk score, nonobese (body mass index [BMI] ≤ 27) and obese women (BMI > 27) were classified into "metabolically healthy" and "unhealthy" phenotypes. Total and regional body composition was assessed with dual-energy X-ray absorptiometry (DXA). RESULTS: In both obese and nonobese groups, the "unhealthy" phenotypes were characterized by frequent bodyweight fluctuations, higher biochemical markers of insulin resistance, hepatic steatosis and inflammation, and higher anthropometric and DXA-derived indices of central adiposity, compared with "healthy" phenotypes. Indices of total adiposity, peripheral fat distribution and lean body mass were not significantly different between "healthy" and "unhealthy" phenotypes. Despite having increased fat mass, MHO women exhibited comparable cardiometabolic parameters with healthy nonobese, and better glucose and lipid levels than MONO. Two DXA-derived indices, trunk-to-legs and abdominal-to-gluteofemoral fat ratio were the major independent determinants of the "unhealthy" phenotypes in our cohort. CONCLUSIONS: The "metabolically obese phenotype" is associated with bodyweight variability, multiple cardiometabolic abnormalities and an excess of central relative to peripheral fat in postmenopausal women. DXA-derived centrality ratios can discriminate effectively between metabolic subtypes of obesity in menopause.

A novel risk classification paradigm for patients with impaired glucose tolerance and high cardiovascular risk.

We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests.

High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells.

Resistin and the proinflammatory cytokines, such as TNF- α , IL-6, and IL-1 ß , produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF- α , IL-6, and IL-1 ß production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF- α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1 ß production. By comparison, exposure to dexamethasone reduced TNF- α , IL-6, and IL-1 ß production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF- α , IL-6, and IL-1 ß from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

The association of the metabolic profile in diabetes mellitus type 2 patients with obsessive-compulsive symptomatology and depressive symptomatology: new insights.

OBJECTIVE: The aim of the present study was to explore the relationship between diabetes mellitus type 2, Obsessive- compulsive disorder (OCD) symptomatology and depressive symptomatology with the metabolic profile of diabetic patients. METHODS: One hundred and thirty-one diabetic patients were randomly selected. In the first assessment all participants completed the Zung Self Rating Scale (ZUNG) and the Maudsley O-C Inventory Questionnaire (MOCI). After 1 year, diabetic patients that were initially uncontrolled (n = 31) (HbA1c > 7) were re-evaluated by the same psychometric tools. From those 31 patients, 10 had managed to control their metabolic profile. RESULTS: In the first evaluation MOCI and the sub-scale of slowness were statistically related with the diabetic profile (controlled, HbA1c ≤ 7; uncontrolled, HbA1c > 7), with uncontrolled patients scoring significantly higher on the overall MOCI score and the factor of slowness of MOCI scale (P = 0.028). The analysis revealed a positive association between depressive symptomatology (P = 0.004) and obsessive-compulsive disorder symptomatology (P < 0.001) and the metabolic profile of the patients. In the second evaluation the patients that managed to control their metabolic profile scored lower in both ZDRS and MOCI, although these differences in scores failed to reach significance levels were indicative of a tendency. CONCLUSIONS: The present results provide initial evidence that diabetes mellitus type 2 is associated with obsessive-compulsive disorder symptomatology and depressive symptomatology.

Primary mucosa-associated lymphoid tissue thyroid lymphoma: a rare thyroid neoplasm of extrathyroid origin.

Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin's lymphoma of B cell origin, following by Hodgkin's disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto's thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.

Arterial stiffness is associated with increased monocyte expression of adiponectin receptor mRNA and protein in patients with coronary artery disease.

BACKGROUND: Arterial stiffness and carotid intima-media thickness (IMT) constitute validated cardiovascular prognostic markers. Adiponectin and its receptors 1 (AdipoR1) and 2 (AdipoR2) are involved in coronary artery disease (CAD). We investigated whether AdipoR1 and R2 mRNA and protein expression are associated with arterial stiffness, IMT and extent of coronary atherosclerosis. METHODS: We studied 71 patients (61 men, 10 women) with angiographically proven CAD. We measured: (i) monocyte expression of AdipoR1 and AdipoR2 mRNA (quantitative real-time PCR) and protein expression (flow cytometry) (iii) adiponectin, metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) blood levels, (iv) carotid-femoral artery pulse wave velocity (PWV) and carotid IMT. RESULTS: Patients with multi-vessel CAD had higher AdipoR1 and AdipoR2 mRNA than those with single-vessel (P < 0.05). PWV was associated with AdipoR1 mRNA (r = 0.474), AdipoR1 protein (r = 0.228), AdipoR2 mRNA (r = 0.716), AdipoR2-protein (r = 0.261), adiponectin (r = 0.236), and MMP-9 (r = 0.350) (P < 0.05, for all correlations). After adjustment for age, sex, waist-hip ratio, and mean blood pressure both AdipoR1 and AdipoR2 mRNA remained independent determinants of PWV (R(2) = 0.35 and R(2) = 0.57, P < 0.05). IMT was also associated with AdipoR2 mRNA, AdipoR2 protein, and MMP-9 (P < 0.05). Increased expression of ADR2 mRNA significantly related to MMP-9 (r = 0.210), and CRP (r = 0.531) (P < 0.05). CONCLUSION: Increased mRNA and protein expression of adiponectin receptors is related with increased aortic stiffness, coronary and peripheral atherosclerosis in patients with CAD. The interrelation of AdipoR2 with inflammatory markers, PWV and IMT suggests a compensatory increase of these receptors to counteract the excess inflammatory and atherogenic process in CAD. Thus, adiponectin receptors may provide a potential therapeutic target of agents activating their beneficial action.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.42.

Increases in muscle blood flow after a mixed meal are impaired at all stages of type 2 diabetes.

OBJECTIVE: In type 2 diabetes, although the impairment of postprandial muscle blood flow response is well established, information on the effect of this impairment on glucose uptake and lipid metabolism is controversial. DESIGN: Postprandial forearm blood flow responses and metabolic parameters were assessed in a cross-sectional study of subjects at various stages of insulin resistance. PATIENTS: Eleven healthy subjects (CONTROLS), 11 first-degree relatives of type-2 diabetics (RELATIVES), 10 patients with impaired glucose tolerance (IGT), 10 diabetic patients with postprandial hyperglycaemia (DMA), and 13 diabetic patients with both fasting and postprandial hyperglycaemia (DMB). MEASUREMENTS: All subjects received a meal. Blood was drawn from a forearm deep vein and the radial artery at specific time-points during a period of 360 min for measurements of glucose, insulin, triglycerides and nonesterified-fatty acids. Forearm muscle blood flow was measured with strain-gauge plethysmography. Glucose uptake and ISI Index were calculated. RESULTS: Peak-baseline muscle blood flow was higher in CONTROLS (3.32 ± 0.4) than in RELATIVES (0.53 ± 0.29), IGT (0.82 ± 0.2), DMA (1.44 ± 0.34), DMB (1.23 ± 0.35 ml/min/100 ml tissue), P < 0.001. Glucose uptake (AUC(0-360,) µmol/100 ml tissue) was higher in CONTROLS (1023 ± 132) than in RELATIVES (488 ± 42), IGT (458 ± 43), DMA (347 ± 63), DMB (543 ± 53), P < 0.001. ISI index, postprandial triglycerides and nonesterified-fatty acids behaved in a similar way. Peak-baseline muscle blood flow correlated positively with glucose uptake (r = 0.440, P = 0.001) and ISI index (r = 0.397, P = 0.003), and negatively with postprandial triglycerides (r = -0.434, P = 0.001) and nonesterified-fatty acids (r = -0.370, P = 0.005). CONCLUSIONS: These results suggest that increase in muscle blood flow after a meal is impaired at all stages of type-2 diabetes. This defect influences glucose uptake and is associated with impaired lipid metabolism in the postprandial state.

Hypertension and other morbidities with Cushing's syndrome associated with corticosteroids: a review.

Corticosteroids constitute an ideal treatment for various inflammatory and autoimmune disorders due to their anti-inflammatory and immunomodulatory actions. However, corticosteroids have a considerable number of side effects, including hypertension, diabetes, lipid disorders, sleep apnea, osteoporosis, myopathy, and disorders of coagulation and fibrinolysis, which are components of Cushing's syndrome (CS). Corticosteroid-induced side effects are dependent on the formulation, route, dose, and time of exposure. However, the underlying pathogenetic mechanisms have not been clearly defined. A large body of evidence supports the role of an imbalance between vasoconstriction and vasodilation with possible links to nitric oxide, prostanoids, angiotensin II, arginine vasopressin, endothelins, catecholamines, neuropeptide Y, and atrial natriuretic peptide. Increased oxidative stress, renin-angiotensin system activation, increased pressor response, metabolic syndrome, and sleep apnea appear to be pathogenetically involved as well. The ideal treatment is the withdrawal of corticosteroids, which is most often impossible due to the exacerbation of the underlying disease. Alternatively, a careful plan, including the proper selection of the formulation, time, and route, should be made, and each side effect should be treated properly. The focus of the research should be to develop synthetic corticosteroids with anti-inflammatory effects but fewer metabolic effects, which so far has been unsuccessful.

Glycoxidation and wound healing in diabetes: an interesting relationship.

Impaired diabetic wound healing (WH) constitutes a serious diabetic complication with increased morbidity, mortality and health expenditure. The exact pathogenetic mechanisms have not been fully clarified. A variety of hyperglycemia and oxidative stress related factors, have been proposed, including advanced glycaction end products (AGE). The existing literature data, support the role of AGE in the pathogenesis of diabetic complications, namely micro- and macro- angiopathy which underlie delayed diabetic WH. In addition, a large body of evidence support a direct negative effect of AGE in the WH process by their interference with various components involved in the cascade following skin injury. Endogenously formed or exogenously derived AGE, in a similar manner, affect negatively the WH process in diabetes. It is obvious that further studies are needed to clarify the exact role of AGE in the impaired diabetic WH and offer possible new therapeutic strategies.

Insulin effects in muscle and adipose tissue.

The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues). These insulin effects serve to encourage the synthesis of carbohydrate, fat and protein, therefore, insulin can be considered to be an anabolic hormone.

Thyroid disease in older people.

Several changes in thyroid hormone secretion, metabolism, and action occur with the increase in age. Aging is often associated with a decrease in serum thyroid stimulating hormone and T3 levels, whereas serum free T4 levels usually remain unchanged. The prevalence of thyroid dysfunction is higher in the elderly as compared to the younger population. In elderly individuals the non-specific clinical manifestations of thyroid hormone excess or deprivation can cause confusion in the clinical setup; while some of the symptoms of thyroid disease are similar to those in younger patients, it is not uncommon for both hyperthyroidism and hypothyroidism to be manifested in subtle ways in older patients, often mimicking symptoms of aging or masquerading as diseases of the cardiovascular, gastrointestinal, or nervous system. In addition, diagnosis of thyroid disorders is commonly complicated, due to chronic, non-thyroidal illness or medication therapy. Early diagnosis and treatment of overt thyroid disorders is crucial, since these disorders are associated with increased morbidity and mortality in the elderly, usually due to common coexistent diseases such as diminished cardiovascular reserve. Treatment of subclinical thyroid disease should also be considered, based on a combination of age, symptoms and risk factors in the individual patients. In addition, both prevalence and aggressiveness of thyroid cancer increase with age. This review summarizes the changes of thyroid function, as well as the clinical manifestations and treatment of thyroid disorders with advancing age.