Central administration of vaspin inhibits glucose production and augments hepatic insulin signaling in high-fat-diet-fed rat.

OBJECTIVE: To investigate the effects of vaspin signaling conveyed by the brain on liver glucose fluxes in rats. METHODS: To determine the effects and underlying mechanisms of central vaspin signaling, normal-chow-diet- and high-fat-diet (HFD)-fed rats with or without hepatic branch vagotomy (HBV) received acute infusion of vaspin to the third cerebral ventricle or MK801, a dorsal vagal complex (DVC) N-methyl-D-aspartate (NMDA) receptor inhibitor, to the DVC during the pancreatic euglycemic clamp. RESULTS: Central administration of vaspin in HFD-fed rats significantly increased glucose infusion required to maintain euglycemia owing to an inhibition of glucose production during the clamps. These changes were accompanied by decreased hepatic phosphoenolpyruatecarboxykinase and G6Pase expression levels and increased hepatic insulin receptor, insulin receptor substrate-1, Akt kinase and the forkhead box-containing protein of the O subfamily-1 phosphorylation, suggesting improving hepatic insulin sensitivity in these animals. Conversely, selective HBV or DVC MK-801 infusion in HFD-fed rats blocked the effect of central vaspin on glucose production and hepatic insulin sensitivity. CONCLUSIONS: Our findings suggest that brain vaspin inhibited hepatic glucose production and improved insulin sensitivity via DVC to the hepatic branch of the vagus nerve in insulin resistance rats induced by HFD.

Transcription factor TIP27 regulates glucose homeostasis and insulin sensitivity in a PI3-kinase/Akt-dependent manner in mice.

BACKGROUND/OBJECTIVES: Juxtaposed with another zinc-finger gene 1 (TIP27 or JAZF1) is a 27-kDa transcription factor, and genome-wide association studies have recently revealed TIP27 to be associated with type 2 diabetes. However, little is known about its role in the regulation of metabolism. In this study, we investigated the effects of TIP27 overexpression on glucose homeostasis and insulin signaling in high-fat diet (HFD)-fed TIP27 transgenic (TIP27-Tg) mice and db/db mice. METHODS: We assessed the effects of TIP27 overexpression in both TIP27-Tg mice and db/db mice on glucose metabolism and changes in insulin sensitivity during glucose (GTT) and insulin (ITT) tolerance tests. A hyperinsulinemic-euglycemic clamp was performed on TIP27-Tg mice. Real-time quantitative PCR and western blotting were used to assess mRNA and protein expressions. RESULTS: TIP27 overexpression in TIP27-Tg mice and in db/db mice led to reduced total cholesterol and fasting plasma insulin levels, and enhanced glucose tolerance and insulin sensitivity during GTT and ITT. Hyperinsulinemic-euglycemic clamp experiments demonstrated that HFD-fed TIP27-Tg mice had lower hepatic glucose production and higher insulin sensitivity compared with nontransgenic littermates. In addition, the hepatic expressions of phosphoenolpyruate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) mRNAs and proteins were significantly decreased, whereas the phosphorylation of insulin receptor, insulin receptor substrate-1, adenosine monophosphate-activated protein kinase and Akt kinase (Akt) in the liver was significantly increased in HFD-fed TIP27-Tg mice compared with nontransgenic littermates. Adenovirus-mediated TIP27 overexpression in db/db mice also decreased the expression of gluconeogenic genes and increased the phosphorylation of insulin signaling molecules in the liver compared with controls. Finally, LY294002, a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, abolished the suppressive effect of TIP27 overexpression on PEPCK and G6Pase expression. CONCLUSIONS: TIP27 has an important role in glucose homeostasis through the regulation of hepatic glucose metabolism and insulin sensitivity. Furthermore, this regulation requires activation of PI3-kinase.

Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis.

BACKGROUND: Nutrition therapy for gastroparesis focuses on reducing meal size, fiber, fat intake, and increasing liquids intake relative to solid foods. Evidence to support these dietary interventions has been anecdotal. The aim of this study was to determine the effect of fat intake and solid/liquid meal consistency on symptoms in gastroparesis. METHODS: Twelve patients with gastroparesis were studied on four separate days receiving one of four meals each day in a randomized order: high-fat solid, high-fat liquid, low-fat liquid, and low-fat solid meal. At each visit, eight gastrointestinal symptoms were rated from 0 (none) to 4 (very severe) every 15 min, before and for 4 h after meal ingestion. KEY RESULTS: There was an increase in the total symptom score in the following order: high-fat solid > low-fat solid > high-fat liquid > low-fat liquid. For the high-fat solid meal, symptoms remained elevated throughout the 4 h postprandial period. Severity of nausea more than doubled after the high-fat solid meal, whereas the low-fat liquid meal caused the least increase in nausea. CONCLUSIONS & INFERENCES: A high-fat solid meal significantly increased overall symptoms among individuals with gastroparesis, whereas a low-fat liquid meal had the least effect. With respect to nausea, low-fat meals were better tolerated than high-fat meals, and liquid meals were better tolerated than solid meals. These data provide support for recommendations that low-fat and increased liquid content meals are best tolerated in patients with symptomatic gastroparesis.

Bodyweight in patients with idiopathic gastroparesis: roles of symptoms, caloric intake, physical activity, and body metabolism.

BACKGROUND: Most gastroparetic patients are underweight probably because of frequently experienced early satiety, nausea, and vomiting. Some gastroparesis (GP) patients, however, are overweight, for reasons that are not well understood. The aim of this study was to evaluate the factors that influence bodyweight such as resting energy and exercise-related expenditure, symptoms of early satiety, nausea and vomiting, and caloric intake in patients with idiopathic GP and in healthy controls. METHODS: Thirty-nine healthy controls and 29 subjects with idiopathic GP were studied. Resting energy expenditure (indirect calorimetry), body composition (bioelectrical impedance), dietary intake (Block Food Frequency Questionnaire), symptoms (Patient Assessment of Upper GI Symptoms), and physical activity (Paffenbarger exercise survey) were assessed. KEY RESULTS: Both median caloric intake (1242 vs 1804 kcal; p = 0.005) and caloric expenditure (486 vs 2172 kcal; p < 0.01) were significantly lower in patients with GP as compared to controls although BMI (25.8 ± 5.8 vs 24.3 ± 4.0 kg/m²) and resting energy expenditure (1327 ± 293 vs 1422 ± 243 kcal) were similar. On the other hand, the 12 GP patients who had gained weight (GW) since diagnosis had lower symptom severity (12.9 ± 4.4 vs 19.3 ± 6.3; p < 0.05), consumed more calories (1342 vs 1134 kcal; p = 0.08) and expended less calories for activity per week (406 vs 644 median kcal; p = 0.45) compared to the 17 GP patients who had lost weight or remained weight neutral (LW). CONCLUSIONS & INFERENCES: Patients with GP, although in energy balance, consumed and expended less calories than healthy controls. A subgroup of patients with GP who were less symptomatic, gained weight because of increased caloric intake and reduced energy expenditure.

The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis.

UNLABELLED: The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2-L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation. INTRODUCTION: rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis. METHODS: Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 µg, N = 89) or once-weekly intramuscular injection of elcatonin (200 U, N = 35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment. RESULTS: At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients (r = 0.45, p = 0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels (p = 0.008 and p = 0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2-L4 (r = 0.47, p = 0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group. CONCLUSION: The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation.

Increased plasma levels of nesfatin-1 in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Nesfatin-1, which is derived from nucleobindin2 (NUCB2), has been recently identified as a novel satiety regulator. However, its pathophysiological role in humans remains unknown. The aim of the present study was to investigate plasma nesfatin-1 levels and the association between plasma nesfatin-1 levels and various metabolic parameters in humans. MATERIALS AND METHODS: 74 subjects with newly diagnosed type 2 diabetes mellitus (nT2DM), 73 subjects with impaired glucose tolerance (IGT) and 73 subjects with normal glucose tolerance (NGT) were enrolled in this study. Plasma nesfatin-1 levels were measured by a commercially available enzyme- linked immunosorbent assay. RESULTS: Plasma nesfatin-1 levels were elevated in subjects with both nT2DM and IGT compared to controls (1.91±0.79 and 1.80±0.80 vs. 1.41±0.58 µ g/L, P<0.05 or P<0.01 ). Simple regression analysis showed that in subjects with IGT and nT2DM, plasma nesfatin-1 correlated positively with body mass index (BMI), hemoglobin A1c (HbA(1c)), fasting blood glucose (FBG), 2 h blood glucose after a glucose load (2hPBG), fasting plasma insulin (FINS) and the homeostasis model assessment of insulin resistance (HOMA(-IR)). Multivariate logistic regression analysis revealed that plasma nesfatin-1 was significantly associated with IGT and nT2DM, even after controlling for differences in BMI. CONCLUSION: Plasma nesfatin-1 concentrations were found to be elevated in subjects with both IGT and nT2DM and to be related with several clinical parameters known to be associated with insulin resistance.

Changes in serum runt-related transcription factor 2 levels after a 6-month treatment with recombinant human parathyroid hormone in patients with osteoporosis.

BACKGROUND: The mechanisms regulating the anabolic response of the skeleton for recombinant human PTH (1- 34) [rhPTH (1-34)] administration has not been fully elucidated. AIM: The aim of this study was to evaluate the effect of rhPTH (1-34) on serum levels of runt-related transcription factor 2 (Runx2) in women with osteoporosis. METHODS: Sixty post-menopausal women with osteoporosis (EO group) and 45 control subjects (NC group) were enrolled in this study. The EO group received daily injection of 20 µg rhPTH (1-34) plus oral 500 mg elemental calcium and 400 IU vitamin D3 for 6 months. Runx2 and Matrix metalloproteinase 13 (MMP-13) were measured with commercially available enzyme-linked immunosorbent assay kits. Bone mineral density (BMD) was also measured before and 6 months after rhPTH (1-34) treatment. RESULTS: Serum total Ca2+, phosphate, and bone-specific alkaline phosphatase were significantly increased (p<0.05 or p<0.01), and the lumbar spine BMD (LS-BMD) was also increased by 4% in patients with osteoporosis after treatment with rhPTH (1-34) (p<0.05). On the contrary, serum Runx2 and MMP-13 were significantly decreased at post treatment (13.1% and 36.6%, respectively, p<0.05 and p<0.01). At baseline, serum Runx2 positively correlated with MMP-13 (r=0.74, p<0.01), the correction remained after adjusting for age and body mass index. CONCLUSION: The daily injection of rhPTH (1-34) was able to stimulate bone formation. The therapy of 20 µg rhPTH (1- 34) for 6 months resulted in decrease of serum Runx2 and MMP-13. These changes might reflect the increase of active osteoblasts and the better bone homeostasis.

Glucagon-like peptide-1 receptor agonists versus insulin in inadequately controlled patients with type 2 diabetes mellitus: a meta-analysis of clinical trials.

To compare the effect and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RA) with insulin therapy on type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin and/or sulfonylurea. A systematic literature search on MEDLINE, Embase and Cochrane for randomized controlled trials (RCTs) was conducted using specific search terms 'GLP-1 insulin type 2 diabetes clinical trials' and eight eligible studies were retrieved. Data on mean change in haemoglobin A1c (HbA1C), weight loss, fasting plasma glucose (FPG), incidence of hypoglycaemia and gastrointestinal adverse events were extracted from each study and pooled in meta-analysis. Data on postprandial plasma glucose (PPG) and adverse events were also described or tabulated. Data from eight RCTs enrolling 2782 patients were pooled using a random-effects model. The mean net change [95% confidence interval (CIs)] for HbA1c, weight loss and FPG for patients treated with GLP-1 RA as compared with insulin was -0.14% (-2 mmol/mol) [95% CI; (-0.27, -0.02)%; p = 0.03]; -4.40 kg [95% CI; (-5.23, -3.56) kg; p < 0.01] and 1.18 mmol/l [95% CI; (0.43, 1.93) mmol/l; p < 0.01], respectively, with negative values favouring GLP-1 and positive values favouring insulin. The GLP-1 group was associated with a greater reduction in PPG than the insulin group. Overall, hypoglycaemia was reported less in the GLP-1 group [Mantel-Haenszel odds ratio (M-H OR) 0.45 (0.27, 0.76); p < 0.01], while there was no significant difference in occurrence of severe hypoglycaemia [M-H OR 0.65 (0.29,1.45); p = 0.29]. A significantly higher number of gastrointestinal adverse events were reported with GLP-1 group [M-H OR 15.00 (5.44,41.35) p < 0.01]. GLP-1 RA are promising new agents compared with insulin. Further prospective clinical trials are expected to fully evaluate the long-term effectiveness and safety of these therapies within the T2DM treatment paradigm.

Effect of short hairpin RNA-mediated adiponectin/Acrp30 down-regulation on insulin signaling and glucose uptake in the 3T3-L1 adipocytes.

Adiponectin is a polypeptide hormone that is secreted by adipocytes with insulin-sensitizing and anti-inflammatory properties. The current study was to further investigate the role of adiponectin on glucose uptake and its underlying mechanism by down-regulation of adiponectin in 3T3-L1 adipocytes. Transfection of short hairpin RNA (shRNA)-vector significantly decreased adiponectin mRNA expression and its protein level in the cells. The down-regulation of adiponectin markedly reduced the cellular glucose uptake rate and increased intracellular triglyceride content. To study the mechanism of the physiologic action of adiponectin, several key regulatory factors in insulin signaling pathway were examined. The mRNA expression of insulin receptor substrate (IRS)-1 in both basal and insulin-stimulated states were down-regulated in the transfected cells (72% and 52% of controls, respectively), and the insulin-stimulated IRS-1 tyrosine phosphorylation was also significantly decreased. Adiponectin-deficient cells showed marked down-regulations of peroxisome proliferator-activated receptor alpha, glucose transporter (GLUT)-1, GLUT-4, hormone-sensitive lipase (HSL), and adipose triglyceride lipase. These results thus demonstrated that transfection of shRNA-vector effectively reduced the expression of adiponectin in 3T3-L1 adipocytes accompanied with a significant decrease in cellular glucose uptake rate and an increase in intracellular triglyceride content. Our data also suggested that adiponectin deficiency impair insulin action in vitro probably through the IRS-1 pathway, and increase intracellular fat accumulation partially through HSL down-regulation.

Circulating FGF-21 levels in normal subjects and in newly diagnose patients with Type 2 diabetes mellitus.

Fibroplast growth factor (FGF-21) is a recently discovered metabolic regulator. Its pathophysiologic role in humans remains unknown. In this study, we have investigated whether or not plasma FGF-21 level was different in patients with type 2 diabetes mellitus (T2DM) and non-diabetic controls. We also assessed associations between plasma FGF-21 body composition and several metabolic parameters. Fasting FGF-21 levels were significantly increased in patients with T2DM compared with controls (1.82+/-0.65 VS. 1.53+/-0.60 microg/L, P<0.05). In T2DM patients, fasting plasma FGF-21 correlate negatively with fasting blood glucose ( R= -0.31, P<0.05). Multiple regression analysis showed that FBG, plasma insulin and HOMA (IS) were independent influencing plasma FGF-21 levels. The present work suggests a potential role for FGF-21 in the pathogenesis of insulin resistance and T2DM.

Exenatide prevents fat-induced insulin resistance and raises adiponectin expression and plasma levels.

BACKGROUND: Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. METHODS: In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic-hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat-fed rats. RESULTS: Administration of exenatide (0.5 or 2.0 mug/kg twice daily x 6 weeks) prevented high-fat diet (HFD)-induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. CONCLUSIONS: These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat-induced insulin resistance.

Differential effects of sham feeding and meal ingestion on ghrelin and pancreatic polypeptide levels: evidence for vagal efferent stimulation mediating ghrelin release.

UNLABELLED: Ghrelin has been suggested to function as an appetite-stimulating signal from the gastrointestinal tract to the brain acting through a vagal afferent pathway. Ghrelin levels rise before meals and fall after meal ingestion. The purpose of this study was to investigate factors which regulate ghrelin release into the circulation by determining changes in systemic ghrelin concentrations after sham feeding and meal ingestion. METHODS: Fifteen normal subjects underwent sham feeding of a bacon and cheese toasted sandwich. Serial blood samples were obtained before and every 5 min for another 30 min during sham feeding and for 30 min after actual meal ingestion. Radioimmunoassay was used to measure plasma ghrelin and pancreatic polypeptide concentrations. RESULTS: During sham feeding, plasma ghrelin concentration increased from 1730+/-237 to 1917+/-269 pg/mL (P<0.05) and plasma pancreatic polypeptide increased from 417+/-50 to 841+/-97 pg/mL (P<0.01). Subsequent meal ingestion was characterized by an increase in pancreatic polypeptide from 782+/-88 to 1710+/-119 pg/mL (P<0.01), but no significant change in ghrelin levels. CONCLUSIONS: Plasma ghrelin and pancreatic polypeptide concentrations increase with sham feeding. This suggests a vagal efferent pathway mediating ghrelin release. In contrast to pancreatic polypeptide which rises with actual meal ingestion, ghrelin levels did not change.

[Cyst of the common bile duct with acute abdomen]. / Choledochuszyste mit akutem Abdomen.

Congenital cysts of the bile duct are well-documented anomalies of the biliary tree. Choledochal cysts frequently cause malignant changes in the epithelial lining. In such patients, the prognosis is very poor mainly because of the lack of typical symptoms in the early stages. The incidence of carcinoma in patients with bile duct cysts is estimated at 2.5 % to 15 %, compared to an incidence of 0.012 % to 0.48 % in patients without bile duct cysts. We report the case of a 32-year-old Vietnamese woman with a history of acute epigastric pain. Exploratory surgery was performed, and the segment containing the cyst and the ectopic pancreas was resected. Sonography pointed the way, and resection would have been necessary even without the abdominal symptoms.

Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes.

Most obese individuals have elevated plasma levels of free fatty acids (FFA) which are known to cause peripheral (muscle) insulin resistance. They do this by inhibiting insulin-stimulated glucose uptake and glycogen synthesis. The mechanism involves intramyocellular accumulation of diacylglycerol and activation of protein kinase C. FFAs also cause hepatic insulin resistance. They do this by inhibiting insulin-mediated suppression of glycogenolysis. On the other hand, FFAs support between 30 and 50 % of basal insulin secretion and potentiate glucose-stimulated insulin secretion. The insulin stimulatory action of FFAs is responsible for the fact that the vast majority ( approximately 80 %) of obese insulin resistant people do not develop type 2 diabetes. They are able to compensate for their FFA mediated insulin resistance with increased FFA mediated insulin secretion. Individuals who are unable to do this (probably for genetic reasons) eventually develop type 2 diabetes. FFAs have recently been shown to activate the IkappaB/NFkappaB pathway which is involved in many inflammatory processes. Thus, elevated plasma levels of FFAs are not only a major cause of insulin resistance in skeletal muscle and liver but may, in addition, play a role in the pathogenesis of coronary artery disease.

Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes.

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor kappa B kinase/nuclear factor kappa B system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.

Branched-chain amino acid supplementation during bed rest: effect on recovery.

Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced (P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

The relationship between post-traumatic symptoms and life in exile in a clinical group of refugees from the former Yugoslavia.

OBJECTIVE: To investigate the association between life situation factors and post-traumatic symptoms among refugees from the former Yugoslavia. METHOD: Twenty-six refugees from the former Yugoslavia were examined by the Harvard Trauma Questionnaire during psychiatric treatment, and 3 years later. At follow-up they also answered a questionnaire regarding their life situations. RESULT: A higher post-traumatic symptom level at follow-up was associated with a pattern of negative living conditions such as open unemployment, social isolation, and a high dependence on social welfare. Gender differences were found regarding the factors most related to symptom severity. CONCLUSION: The results indicate that a main problem in this patient group may be how to break vicious circles of high symptom levels and a poor life situation which suggests a need for integrated rehabilitation efforts.

Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction.

Plasma free fatty acids (FFA) play important physiological roles in skeletal muscle, heart, liver and pancreas. However, chronically elevated plasma FFA appear to have pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral and hepatic insulin resistance and, while the precise action in the liver remains unclear, a model to explain the role of raised FFA in the development of skeletal muscle insulin resistance has recently been put forward. Over 30 years ago, Randle proposed that FFA compete with glucose as the major energy substrate in cardiac muscle, leading to decreased glucose oxidation when FFA are elevated. Recent data indicate that high plasma FFA also have a significant role in contributing to insulin resistance. Elevated FFA and intracellular lipid appear to inhibit insulin signalling, leading to a reduction in insulin-stimulated muscle glucose transport that may be mediated by a decrease in GLUT-4 translocation. The resulting suppression of muscle glucose transport leads to reduced muscle glycogen synthesis and glycolysis. In the liver, elevated FFA may contribute to hyperglycaemia by antagonizing the effects of insulin on endogenous glucose production. FFA also affect insulin secretion, although the nature of this relationship remains a subject for debate. Finally, evidence is discussed that FFA represent a crucial link between insulin resistance and beta-cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes.