Insulin Sensitivity In Obese Patients Research Articles

Macrophage activation marker sCD163 is associated with liver injury and hepatic insulin resistance in obese patients before and after Roux-en-Y gastric bypass.

BackgroundMacrophages are associated with metabolic complications to obesity including fatty liver disease and impaired hepatic and muscle insulin sensitivity (IS). Bariatric surgery induces weight loss and improves IS. We investigated associations between the macrophage activation marker soluble (s)CD163, alanine‐aminotransferase (ALT), and IS before and after Roux‐en‐Y Gastric Bypass (RYGB).MethodsWe analyzed sCD163 from 10 type 2 diabetes (T2D) and 10 obese patients with normal glucose tolerance (NGT) undergoing RYGB for associations with hepatic, adipose tissue, and muscle IS and ALT after 1‐week, 3, and 12 months postoperatively. IS was evaluated by hyperinsulinemic‐euglycemic clamp in combination with glucose tracer technique.ResultsPreoperative sCD163 correlated with ALT (r = 0.58, p = 0.007) and tended to associate inversely with hepatic (r = −0.39, p = 0.1) and adipose tissue (r = −0.39, p = 0.09), but not muscle IS. Following RYGB, sCD163 decreased significantly in all patients. The decrease in sCD163 during the first 3 months correlated inversely with the improvement of hepatic IS (r = −0.65, p = 0.01) and tended to be associated with changes in muscle IS (r = −0.45, p = 0.09). After 3 months sCD163 remained associated with ALT (r = 0.75, p < 0.001) and inversely with hepatic IS (r = −0.39, p = 0.1), but not muscle or adipose tissue IS. One year after RYGB, sCD163 correlated with ALT (r = 0.61, p = 0.007), but not with hepatic, adipose tissue, or muscle IS.ConclusionMacrophage activation is associated with liver injury and hepatic IS in obese patients. Improvements in these measures correlate during the first 3 months following RYGB, supporting a link between macrophages and hepatic IS in severe obesity and diabetes.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Relationship between Serum Indirect Bilirubin Level and Insulin Sensitivity: Results from Two Independent Cohorts of Obese Patients with Impaired Glucose Regulation and Type 2 Diabetes Mellitus in China.

Background Serum bilirubin is an endogenous antioxidant that has protective effects against obesity-related metabolic diseases. Objectives This study aimed to evaluate the characteristics of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) and their relationships with insulin sensitivity in obese patients with impaired glucose regulation and type 2 diabetes mellitus (IGR/T2DM) in China. Patients and Methods. Cohort 1 comprised obese patients (n = 71) was divided into the IGR/T2DM group (n = 38, obesity with IGR/T2DM) and control group (n = 33, obesity without IGR/T2DM). Insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique (HEC) with glucose disposal rate (GDR, M value). Cohort 2 comprised obese patients with IGR/T2DM who underwent metabolic surgery (n = 109) as complementary to cohort 1. Insulin sensitivity was evaluated with the Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS). Results In cohort 1, TBIL, DBIL, and IBIL were higher within the physiological range in the IGR/T2DM group compared with the control group; IBIL was positively correlated with M value (r = 0.342, p=0.044) in the IGR/T2DM group, and multivariate logistic regression showed that IBIL might be independent protective factors against insulin resistance (odds ratio (OR) = 0.602; 95% confidence interval (CI): 0.413–0.878; p=0.008). In cohort 2, at 1 month after metabolic surgery, serum bilirubin levels (TBIL, DBIL, and IBIL) increased, and the percentage change in IBIL was positively correlated with the change of the Matsuda Index (r = 0.195, p=0.045). Conclusions The relationships between different types of bilirubin and insulin sensitivity varied. Serum indirect bilirubin might be a protective factor that enhances insulin sensitivity.

Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice

Insulin resistance is a major cause of type 2 diabetes and metabolic syndrome. Macrophage infiltration into obese adipose tissue promotes inflammatory responses that contribute to the pathogenesis of insulin resistance. Suppression of adipose tissue inflammatory responses is postulated to increase insulin sensitivity in obese patients and animals. Sarsasapogenin (ZGY) is one of the metabolites of timosaponin AIII in the gut, which has been shown to exert anti-inflammatory action. In this study, we investigated the effects of ZGY treatment on obesity-induced insulin resistance in mice. We showed that pretreatment with ZGY (80 mg·kg-1·d-1, ig, for 18 days) significantly inhibited acute adipose tissue inflammatory responses in LPS-treated mice. In high-fat diet (HFD)-fed obese mice, oral administration of ZGY (80 mg·kg-1·d-1, for 6 weeks) ameliorated insulin resistance and alleviated inflammation in adipose tissues by reducing the infiltration of macrophages. Furthermore, we demonstrated that ZGY not only directly inhibited inflammatory responses in macrophages and adipocytes, but also interrupts the crosstalk between macrophages and adipocytes in vitro, improving adipocyte insulin resistance. The insulin-sensitizing and anti-inflammatory effects of ZGY may result from inactivation of the IKK /NF-κB and JNK inflammatory signaling pathways in adipocytes. Collectively, our findings suggest that ZGY ameliorates insulin resistance and alleviates the adipose inflammatory state in HFD mice, suggesting that ZGY may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial.

Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome. In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues. The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg-1 *min-1/(mU* l-1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg-1 *min-1/(mU *l-1); p < 0.05). Between group comparison of ISIClamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISIClamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISIClamp during hypoxic training. Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.

The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery.

Neurotensin is a peptide with effects on appetite and intestinal lipid absorption. Experimental data suggest a role in glucose homeostasis, while human data is missing. Here, 20 morbidly obese subjects either underwent biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB) in a randomized fashion. Before and 1 year after surgery, anthropometric data, body composition, clinical biochemistry, insulin sensitivity by means of euglycemic hyperinsulinemic clamps (HEC) and fasting plasma proneurotensin 1-117 were analyzed. Plasma proneurotensin increased significantly more 1 year after BDP than RYGB (P = 0.028), while weight loss was comparable. After metabolic surgery, proneurotensin correlated positively with insulin sensitivity (M-value) (r = 0.55, P < 0.001), while an inverse relationship with fasting glucose, HOMA-IR and HbA1c was observed (P < 0.05 for all components). After adjustment for age and gender, proneurotensin and BMI remained independently related with delta of M-value (β = 0.46 and β = 0.51, P < 0.05, resp.). From these data we conclude that proneurotensin positively correlates with insulin sensitivity uniquely after weight loss induced by metabolic surgery in humans. BDP leads to a stronger increase in the anorexigenic peptide compared to RYGB.

Mitochondrial respiratory capacity remains stable despite a comprehensive and sustained increase in insulin sensitivity in obese patients undergoing gastric bypass surgery.

It has been proposed, but not yet demonstrated by convincing evidence in published articles, that insulin resistance and mitochondrial respiratory function are causally related physiological phenomena. Here, we tested the prediction that weight loss-induced increase in insulin sensitivity will correlate with a corresponding change in mitochondrial respiratory capacity over the same time period. Insulin sensitivity was evaluated using the hyperinsulinaemic-euglycaemic clamp technique, and skeletal muscle mitochondrial respiratory capacity was evaluated by high-resolution respirometry in 26 patients with obesity. Each experiment was performed ~2months and 1-2weeks before, and ~4 and ~19months after Roux-en-Y gastric bypass (RYGB) surgery. A substantial weight loss was observed in all patients, and insulin sensitivity increased in all patients over the 21-months time period of the study. In contrast, skeletal muscle mitochondrial respiratory capacity, intrinsic mitochondrial respiratory capacity and mitochondrial content remained unchanged over the same time period. Among obese patients with and without type 2 diabetes undergoing RYGB surgery, intrinsic mitochondrial respiratory capacity in skeletal muscle is not correlated with insulin sensitivity before or after the surgical intervention. Mitochondrial respiratory function may not be germane to the pathophysiology and/or aetiology of obesity and/or type 2 diabetes.

Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans.

Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = -0.4 ∼ -0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ∼ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation.

The nicotinic acid analogue acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with acipimox acutely affects autonomic tone. We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Plasma glucose (4.7 vs. 4.9mmoll-1 , P=0.02) and serum FFA (0.05 vs. 0.41mmoll-1 , P<0.001) were significantly decreased during acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3ms, P=0.01), root mean square of successive differences (23.2 vs. 11ms, P=0.03) and high frequency (3.79 vs 3.60 ln (ms2 ), P=0.02) and these effects were reversed during clamping. Short-term inhibition of lipolysis by acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes.

The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N=16) and without (OB, N=27) type 2 diabetes was studied. At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition, hepatic glucose production (HGP), insulin-mediated glucose uptake (GIR), respiratory exchange ratio, hepatic insulin sensitivity and clearance were determined. GLUT4, intramuscular triglycerides (IMTG) and glycogen content were measured in skeletal muscle. Weight loss was 35-40kg, and approximately one-third of the total improvement in GIR in T2DM was observed after the diet-induced weight loss of only ~6kg (B). Insulin clearance, visceral fat and fasting plasma insulin also improved significantly after the diet (P<0.05). Throughout the study, HGP, GLUT4 and glycogen content did not change significantly, but IMTG decreased significantly consistent with significant increases in GIR. Metabolic flexibility and hepatic insulin sensitivity improved after RYGB. Metabolic improvements of RYGB are present already after the diet-induced weight loss prior to surgery. GLUT4 content in skeletal muscle cannot and IMTG content can only partly explain increases in GIR after RYGB.

Body composition and insulin sensitivity after high‐intensity interval training in overweight/obese patients

TO THE EDITOR: We have read with a great interest the article of Gillen et al. (1) recently published in Obesity on the shortterm effects of high-intensity interval training (HIIT) in obese women. They reported similar skeletal muscle adaptations (increased mitochondrial capacity) and similar (but modest) body composition improvement after short-term HIIT (6 weeks) in fasted or fed state obese women. Surprisingly, insulin sensitivity was not improved after 6 week of HIIT in both groups probably due to potential influence of patient’s diet (not reported in the article) and/or short-term training period. We would like to underlie the importance of patient’s diet and nutritional aspects (with exercise intervention) for body composition and insulin sensitivity improvements in obese population. Previous studies demonstrated that HIIT combined with Mediterranean diet (diet focused on nutrient quality, satiety, and palatability) optimally improved body composition and insulin sensitivity in obese patients (2-5). Those studies have found an improved body composition after shorter and longer term HIIT combined with Mediterranean diet (2-5), as well as an improved insulin sensitivity in obese patients (4,5). We have also developed an optimized, time efficient model of HIIT in obese patients (2,3,5), and HIIT combined with Mediterranean diet have superior effects on body composition and insulin sensitivity improvement compared to moderate intensity continuous exercise (3) or mediterranean diet alone (4). As the authors stated (1), compared to sprint interval training, HIIT is more adapted to obese population that often present comorbidities and low levels of fitness. We demonstrated that two 10-min sets of repeated bouts of 15-30 s at 80% of maximal aerobic power interspersed by 15-30 s passive recovery periods (representing 10 min of real exercise), 2-3 time/week are enough to improve body composition, insulin sensitivity, and cardiometabolic risk factors in obese patients. Regarding potential sex differences adaptations to HIIT, we showed similar improvement in body composition, fitness, and cardiometabolic risk factors in obese men and women (metabolically healthy or not) after 9 months of HIIT combined with Mediterranean diet (5). Similarly, we found that insulin sensitivity was similarly improved after the same intervention in obese men and women (Figure 1). In conclusion, intensive exercise intervention such as HIIT combined with Mediterranean diet can optimize health benefits (body composition, insulin sensitivity, and cardiometabolic risk factors) in obese patients, independently of their gender and/or obesity phenotype. O

Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following l-arginine supplementation

PurposeThe aim of this study is to evaluate the long-term influence of l-arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result.MethodsA randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of l-arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used.ResultsWe found that 6 months of l-arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P < 0.01) and zinc levels (Δ1.5 μmol/L, P < 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed (R = 0.80, P < 0.01). In the group of patients treated with l-arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted (R = −0.38, P < 0.05).Conclusions l-Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.

Alpha-linolenic acid improves insulin sensitivity in obese patients

To explore the effects of α-linolenic acid on insulin sensitivity in obese patients. From October 2011 to April 2012, 16 patients received an oral dose of α-linolenic acid for 8 weeks.Oral glucose tolerance test (OGTT) and insulin releasing test were performed before and after treatment. Homeostasis model assessment insulin resistance (HOMA-IR) index and area under curve of insulin (AUCI) were calculated to evaluate the insulin sensitivity. The levels of serum triglyceride, free fatty acids (FFA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured after an overnight fast. Obese patients had significantly elevated serum insulin, triglyceride, FFA, IL-6 and TNF-α versus the subjects in normal control group (all P < 0.05). Obese patients were also more insulin-resistant than normal subjects based on a higher HOMA-IR (P < 0.05). Decreased serum insulin, triglyceride, FFA, IL-6 and TNF-α were observed after treatment. With the administration of α-linolenic acid, HOMA-IR and AUCI significantly decreased in obese patients (HOMA-IR: 1.8 ± 0.2 vs 1.2 ± 0.3, P < 0.05; AUCI: 1151 ± 505 vs 768 ± 347, P < 0.05). α-linolenic acid increases peripheral insulin sensitivity in obese patients and it may aid the prevention and treatment of type 2 diabetes mellitus and atherosclerotic vascular diseases.

Study of the Potential Association of Adipose Tissue GLP-1 Receptor with Obesity and Insulin Resistance

The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.

Chitosan improves insulin sensitivity as determined by the euglycemic-hyperinsulinemic clamp technique in obese subjects

In accordance with obesity is associated with insulin resistance and dyslipidemia and chitosan decrease weight and lipids, but its effect on insulin sensitivity is unknown. Our hypothesis for the research was that chitosan improves insulin sensitivity estimated with the euglycemic-hyperinsulinemic clamp technique in obesity. We undertook this study with the objective to determine the effect of chitosan on insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique in obese patients during a 3-month period. A randomized, double-blind clinical trial was carried out in 12 obese adults without diabetes mellitus. During a 3-month period, 6 patients received chitosan (750 mg, 3 times per day) 30 minutes before meals, and the other 6 subjects received placebo. Serum glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides (TG) were measured. Insulin sensitivity was estimated with the euglycemic-hyperinsulinemic clamp technique before and after the intervention. Insulin sensitivity increased significantly with the administration of chitosan (2.4 +/- 1.4 vs 3.6 +/- 1.4 mg kg(-1) min(-1); P = .043). In addition, there was a decrease in weight (90.7 +/- 14.2 vs 84.7 +/- 13.7 kg; P = .027), body mass index (34.3 +/- 2.7 vs 31.6 +/- 2.2 kg/m(2); P = .028), waist circumference (106 +/- 12 vs 99 +/- 9 cm; P = .028) and TG (2.4 +/- 0.9 vs 1.6 +/- 0.9 mmol/L; P = .028) in the chitosan group. In conclusion, 3-month administration of chitosan increased insulin sensitivity in obese patients and demonstrated a decrease in weight, body mass index, waist circumference, and TG.

Amino acid nutrition in fetal and neonatal growth: from animal studies to clinical applications

Studies of porcine milk composition over 18 years ago created a new direction of amino acid research. Specifically, the discovery of arginine (Arg) deficiency in sow milk led to the identification of glutamine and proline as the major substrates for Arg synthesis in piglets. Subsequent work resulted in the recognition that Arg is deficient in preterm infants with necrotizing enterocolitis and that its supplementation can ameliorate the gut disease. Further research on the ontogeny of Arg‐synthetic enzymes in the porcine intestine led to the discovery that the Arg family of amino acids is unusually abundant in allantoic fluids of swine and sheep during early gestation when placental growth is most rapid. This novel observation provided a strong basis for the effective use of Arg to improve embryonic/fetal survival and ameliorate intrauterine growth restriction in mammals (including pigs, sheep and humans) via enhancing NO‐mediated blood flow. Additional work to elucidate the underlying mechanisms led to another discovery that Arg reduces adiposity in pigs, sheep and rats. Notably, this knowledge has been translated into the use of Arg to promote white‐fat loss and improve insulin sensitivity in obese patients with type‐2 diabetes mellitus. Thus, animal models play an important role in developing new means to prevent and treat a wide array of major human diseases. Supported by NIH, USDA, AHA, and TAMU.

N-3 polyunsaturated acids in erythrocyte phospholipids are associated with insulin sensitivity in obese patients on a typical Serbian diet

This study examines the relationship between erythrocyte phospholipid FA composition and insulin sensitiv?ity in obese patients on a typical Serbian diet. In 30 patients, two insulin sensitivity groups were formed and their FAs analyzed. The shares of 22:5n-3, 22:6n-3, and total n-3 PUFAs, as well as a measure of ?5 desaturase activity (the 20:4n-6/20:3n-6 ratio) were lower in the insulin resistance group compared to the normal glucose tolerance group. The fasting insulin level and HOMA value were inversely related to the percentage of 22:5n-3, 22:6n-3, and total n-3 PUFAs. Our data indicate that the percentage of n-3 PUFAs in erythrocyte phospholipids is linked with insulin sensitivity parameters in obese patients.

Dual Endothelin Receptor Blockade Acutely Improves Insulin Sensitivity in Obese Patients With Insulin Resistance and Coronary Artery Disease

Endothelin (ET)-1 is a vasoconstrictor and proinflammatory peptide that may inhibit glucose uptake. The objective of the study was to investigate if ET (selective ET(A) and dual ET(A)+ET(B)) receptor blockade improves insulin sensitivity in patients with insulin resistance and coronary artery disease. Seven patients (aged 58 +/- 2 years) with insulin resistance and coronary artery disease completed three hyperinsulinemic-euglycemic clamp protocols: a control clamp (saline infusion), during ET(A) receptor blockade (BQ123), and during combined ET(A) (BQ123) and ET(B) receptor blockade (BQ788). Splanchnic blood flow (SBF) and renal blood flow (RBF) were determined by infusions of cardiogreen and p-aminohippurate. Total-body glucose uptake (M) differed between the clamp protocols with the highest value in the BQ123+BQ788 clamp (P < 0.05). The M value corrected by insulin was higher in the BQ123+BQ788 than in the control clamp (P < 0.01) or the BQ123 clamp (P < 0.05). There was no difference between the control clamp and the BQ123 clamp. Mean arterial pressure did not change during the control clamp, whereas it decreased during both the BQ123 (P < 0.01) and BQ123+BQ788 (P < 0.05) clamps. RBF increased and renal vascular resistance decreased in the BQ123+BQ788 clamp (P < 0.05) but not in the BQ123 clamp. There was no change in SBF in either clamp. Dual ET(A)+ET(B) receptor blockade acutely enhances insulin sensitivity in patients with insulin resistance and coronary artery disease, indicating an important role for endogenous ET-1.

Liposuction and diabetes type 2 development risk reduction in the obese patient

Obesity is a disabling disease which has gained greater attention worldwide and particularly in the United States. It significantly increases the risk for other diseases such as insulin independent diabetes mellitus also known as diabetes type 2. The most common surgical procedure for obesity is liposuction. It is traditionally performed either as small-volume liposuction or large-volume liposuction, the majority being small-volume liposuction procedures. Large-volume and small-volume liposuction have been clinically shown to improve insulin sensitivity in obese patients thus reducing their risk of developing type 2 diabetes. In this paper, evidence is presented to support the hypothesis that liposuction disrupts the pathway that brings about insulin insensitivity in the obese patient. It is proposed that using liposuction in the overall treatment of obesity could lead to an improvement in insulin sensitivity and thus greatly improve the quality of life of the obese patient.

Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-α or isoproterenol

In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-alpha (TNF-alpha), a cytokine largely expressed in adipose tissue, stimulates chronic lipolysis, which may be associated with increased systemic FFA and insulin resistance in obesity and NIDDM. In this study, we examined the role of metformin in inhibiting lipolytic action upon various lipolytic stimulations in primary rat adipocytes. Treatment with metformin attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-alpha-stimulated adipocytes. The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by metformin. A high concentration of glucose in the adipocyte culture promoted the basal rate of glycerol release and significantly enhanced the lipolytic action stimulated by either TNF-alpha or isoproterenol. Metformin not only inhibits the basal lipolysis simulated by high glucose, but also suppresses the high glucose-enhanced lipolysis response to TNF-alpha or isoproterenol. The antilipolytic action in adipocytes could be the mechanism by which cellular action by metformin reduces systemic FFA concentration and thus improves insulin sensitivity in obese patients and the hyperglycemic conditions of NIDDM.