Significant Decrease In HOMA-IR Research Articles

HOMA-IR level in obese type 2 diabetic rat model treated by Sleeve gastrectomy and pancreatic omentoplasty

Obesity is a health problem that occurs due to the wrong lifestyle, such as lack of physical activity and the wrong diet. Accumulation of adipose tissue in obesity may increases pro-inflammatory cytokines, particularly in pancreatic beta cells leading to type 2 diabetes mellitus (T2DM). Sleeve gastrectomy (SG) is an alternative therapy for T2DM in obese patients by losing about 40-60% of body weight and increasing GLP-1 secretion which stimulates increased insulin secretion. However, the SG procedure cannot reduce pro-inflammatory cytokines which promote damaged pancreatic cells. Pancreatic omentoplasty can suppress pro-inflammatory cytokines and promote the regeneration of damaged pancreatic cells. The goal of this study is to investigate HOMA-IR in obese rats with diabetes mellitus who underwent SG and pancreatic omentoplasty procedures. An experimental using pre and post-test control group design were done in this study. Eighteen Diabetes Mellitus rats were divided into 3 groups: K1 (SG), K2 (SG + Omentoplasty), and K3 (control). Blood glucose and insulin level were measured using a glucoDR Glucometer Bio-sensor kit and ELISA, respectively before and 10 days after the procedure. HOMA-IR measurement was calculated based on insulin and blood glucose level. A significant decrease of fasting blood gluocese levels were shown in all treatment groups of this study after day 10th. There was a significant increase in the insulin levels after day 10th. Highest decrease of the blood glucose levels and increase of the insulin levels were shown in group K2. Furthermore, a significant decrease of HOMA-IR was shown in the K2 on day 10th. From this study, we may conclude that SG and Pancreas Omentoplasty may significantly reduce the HOMA-IR value in obese rats with T2DM.

Abstract 57: Effect of successful parathyroidectomy on metabolic parameters in patients with primary hyperthyroidism

Background: Primary hyperparathyroidism (PHPT) had been associated with metabolic abnormalities including dysglycemia, hyperuricemia and dyslipidemia. The data regarding the effect of curative parathyroidectomy on metabolic variables is controversial.Aims and Objectives: To assess the metabolic parameters, including insulin resistance in patients with PHPT. To study the effect of curative parathyroidectomy on these metabolic parameters.Methods: Prospective observational, hospital based study involving 50 consecutive PHPT patients over a period of one year. We studied clinical and biochemical variables including, body mass index (BMI), an oral glucose tolerance test (OGTT, 75 g), fasting lipid profile, uric acid (UA), liver function test, fasting insulin levels and HOMA IR (excluding 8 diabetic patients) in all patients. Three months after curative surgery all the parameters were repeated.Results: The mean BMI, total cholesterol (TC), LDL, triglycerides (TG), UA, creatinine (Cr), fasting blood glucose (FBG) and 2hr post OGTT (PPBG) was 23±4.4 kg/m2, 160.81±44.64 mg/dl, 95.27± 36.81 mg/dl, 140.24±57.2 mg/dl, 5.07±1.57 mg/dl, 0.97 mg/dl, 86.88±11.2 mg/dl and 122.93±28.1 respectively. The mean HOMA-IR was 35.05±32.7. After surgery there was no significant change in TC (161.38± 45.85) LDL (91.1±34.51), TG (144.64±90.94), UA (4.43± 1.46), Cr (0.76± 0.34), FBG (90.52± 22.26) and PPBG (125.4±39.83 mg/dl). There was significant increase in BMI (23.9± 4.28 kg/m2) and significant decrease in HOMA-IR (14.76±10.43).Conclusion: Our follow-up of patients with operated PHPT revealed there was no significant change in metabolic parametres except for decrease in HOMA IR.

Metformin in non-diabetic patients with metabolic syndrome and diastolic dysfunction: the MET-DIME randomized trial.

Metabolic syndrome (MetS) affects one out of 3 adults in the western world and is associated with preclinical diastolic dysfunction that impairs functional capacity and quality of life (QoL). This randomized trial was designed to evaluate if the addition of metformin to the standard treatment of non-diabetic patients with MetS improves diastolic dysfunction. Prospective, randomized, open-label, blinded-endpoint trial. Fifty-four non-diabetic adults with MetS and diastolic dysfunction were randomized to lifestyle counseling or lifestyle counseling plus metformin (target dose 1000 mg bid). The primary endpoint was the change in mean e' velocity (assessed at baseline, 6, 12 and 24 months). Secondary endpoints were improvements in insulin resistance, functional capacity and QoL. Linear mixed effects modeling was used for longitudinal data analysis using modified intention-to-treat (mITT) and per-protocol (PP) approaches. Forty-nine patients were included in the mITT analysis (mean age = 51.8 ± 6.4; 55% males). Metformin treatment was associated with a significant decrease in HOMA-IR. There was a significantly different mean change in e' velocity during the study period between trial arms, both in the mITT (at 24 months, change of +0.67 ± 1.90 cm/s in metformin arm vs. -0.33 ± 1.50 cm/s in control arm) and PP populations (+0.80 ± 1.99 cm/s in metformin arm vs. -0.37 ± 1.52 cm/s in control arm), using a random intercept linear mixed model. There were no significant differences in peak oxygen uptake and SF-36 scores between trial arms. Treatment with metformin of non-diabetic MetS patients with diastolic dysfunction, on top of lifestyle counseling, is associated with improved diastolic function.

Serum myokine levels after linear and flexible non-linear periodized resistance training in overweight sedentary women

ABSTRACT This study compared the capacity of linear-(LP) and non-linear periodized (NLP) resistance training to improve select myokines and metabolic parameters in overweight sedentary women. An additional purpose was to compare these variables between the overweight and lean women. Fitness- and age-matched overweight women between 28 and 43 years old were randomly allocated to LP (body fat [BF]% = 38.7 ± 2.6, n = 10), NLP (BF% = 39.3 ± 2.4, n = 9) and control (BF% = 39.8 ± 2.6, n = 9) groups. Lean women (BF% = 29.1 ± 2.3, n = 16) matched for age and fitness were also included for baseline comparison. Resistance training programmes (12 weeks, 3 d.wk−1, 9 exercises, 60–90% of 1-repetition maximum [1RM]) were performed with different periodization schemes. Glucose, insulin, interleukin (IL)−7, IL-15, and insulin-like growth factor (IGF)−1 levels were measured at baseline and after training. Overweight subjects had significantly lower IL-15, IGF-1 and higher insulin, glucose, and insulin resistance (homeostasis model assessment, HOMA-IR) than lean subjects at baseline (all, P < .05). IL-15 and VO2max increased significantly after NLP compared with CON, which was accompanied by a significant decrease in HOMA-IR (all, P < .03). Muscular endurance improved significantly in both models after training compared to CON (all, P < .01), but it increased more in NLP than in LP (P = .01). Both training protocols were equally effective at reducing BF% and increasing IGF-1, IL-7, muscle mass and bench press 1RM (P < .01). It appears that LP and NLP are both effective strategies for improving health markers in overweight women, but LP is not as effective as NLP to improve IL-15, HOMA-IR and aerobic capacity. Highlights Overweight women had a significantly lower IL-15 and IGF-1 compared to lean encounters, but no significant difference was noted for maximal strength, aerobic capacity, muscle mass, IL-7 and neutrophil/lymphocyte ratio. Twelve weeks of either linear or flexible non-linear periodized resistance training resulted in reduction in BF% and neutrophil/lymphocyte ratio, and increased IGF-1, IL-7, muscle mass and bench press 1RM, with no difference between the two training protocols. Linear protocol is not as effective as non-linear protocol to improve IL-15, HOMA-IR and aerobic capacity.

Metformin in non-diabetic patients with metabolic syndrome and diastolic dysfunction: the MET-DIME randomized trial

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Merck Background Metabolic syndrome (MetS) affects one out of 3 adults in the western world and is associated with preclinical diastolic dysfunction that impairs functional capacity and quality of life (QoL). Purpose This randomized trial was designed to evaluate if the addition of metformin to the standard treatment of non-diabetic patients with MetS improves diastolic dysfunction. Methods Prospective, randomized, open-label, blinded-endpoint trial. Fifty-four non-diabetic adults with MetS and diastolic dysfunction were randomized to lifestyle counseling or lifestyle counseling plus metformin (target dose 1000 mg bid). The primary endpoint was the change in mean e’ velocity (assessed at baseline, 6, 12 and 24 months). Secondary endpoints were improvements in insulin resistance, functional capacity and QoL. Linear mixed effects modelling was used for longitudinal data analysis using modified intention-to-treat (mITT) and per-protocol (PP) approaches. Results Forty-nine patients were included in the mITT analysis (mean age = 51.8 ± 6.4; 55% males). Metformin treatment was associated with a significant decrease in HOMA-IR. There was a significantly different mean change in e’ velocity during the study period between trial arms, both in the mITT (at 24 months, change of +0.67 ± 1.90cm/s in metformin arm vs. -0.33 ± 1.50cm/s in control arm) and PP populations (+0.80 ± 1.99cm/s in metformin arm vs. -0.37 ± 1.52cm/s in control arm), using a random intercept linear mixed model. There were no significant differences in peak oxygen uptake and SF-36 scores between trial arms. Conclusion Treatment with metformin of non-diabetic MetS patients with diastolic dysfunction, on top of lifestyle counseling, is associated with improved diastolic function. Abstract Figure.

Outcomes of metabolic surgery in obese patients with type 2 diabetes with respect to impact on beta cell function, insulin sensitivity and diabetes remission - A study from south India

Background and aimsMetabolic surgery is gaining popularity as a procedure for the treatment of morbid obesity among patients with type 2 diabetes (T2DM). The aim of the study was to evaluate the effects of metabolic surgery on beta cell function, insulin sensitivity and glycemic status in obese Asian Indian patients. MethodsThis is a prospective study of 26 patients with T2DM who underwent metabolic surgery. Complete diabetes remission was defined as FPG<100 mg/dl and HbA1c < 6%, without antidiabetic medications one-year post surgery. Anthropometry, HOMA-IR (insulin resistance), HOMA-insulin sensitivity, beta cell function and antidiabetic drug usage were measured at baseline, 6 months and 12 months post-surgery. ResultsThe overall duration of diabetes was 10.3 ± 5.4 years. At one year, 7 (27%) of 26 T2DM patients, achieved diabetes remission while the other 19 had improvement in diabetes status. ROC curves showed that those who had diabetes duration <8.5 years achieved remission. There was a significant decrease in HOMA-IR [3.7 ± 1.8 vs 1.4 ± 0.9 vs1.2 ± 0.6, p < 0.001] and improvement in HOMA-Insulin sensitivity [34 ± 17 vs 93 ± 50 vs 112 ± 62, p < 0.001] from baseline to 6 and 12 months post-surgery respectively. There was a significant (p < 0.001) reduction in the usage of anti-diabetes medications post-surgery. The limitations of this study are small sample size and limited follow up period of 1 year. ConclusionsAmong T2DM patients, metabolic surgery resulted in significant improvement in beta cell function and insulin sensitivity along with reduction in anti-diabetes medication. Diabetes remission was mainly seen in those who had duration of diabetes <8.5 years.

1848-P: Insulin Sensitivity and Metabolic Profile of Subjects with Type 2 Diabetes and Nonalcoholic Steatohepatitis after Exposure to Cenicriviroc: A Subanalysis of the CENTAUR Study

Introduction: In mice, C-C motif chemokine receptor (CCR)5 deletion protects against insulin resistance, hepatic steatosis, and glucose intolerance. We aimed to characterize the metabolic effects of cenicriviroc (CVC), a potent CCR2/5 inhibitor, in type 2 diabetes mellitus (T2DM) patients with nonalcoholic steatohepatitis (NASH) fibrosis from the Phase 2b CENTAUR study. Methods: Subjects from CENTAUR with T2DM, biopsy-proven NASH, and fibrosis Stages F1-3 were included. CVC-exposed subjects for 1 year (Arm A) and placebo (PBO) [Arms B and C] were analyzed. Liver, metabolic, and inflammatory biomarkers were analyzed. Homeostatic model assessments (HOMA-IR and -b) were calculated. Change (from baseline to Year 1) was compared between groups using a general parametric linear model analysis of covariance (2-sided ANCOVA) based on the mITT population. Results: Of the 289 subjects in CENTAUR, 134 (46%) had T2DM and were included in this analysis. Baseline characteristics were similar for CVC (n=76) and PBO (n=58) groups (mean ±SD): age 57.5 ±7.75 years vs. 55.41 ±8.65 years, HbA1c 7.30 ±1.29 vs. 7.20 ±1.21 %, BMI 33.02 ±5.25 vs. 35.16 ±7.67 kg/m2, NAS 5.25 ±1.06 vs. 5.52 ±1.13, and fibrosis scores of F1 (31.6%), F2 (21%), and F3 (47.4%) vs. F1 (24.2%), F2 (22.4%), and F3 (53.4%), respectively. At 1 year, there was a significant decrease in HOMA-IR and interleukin (IL)-6 in the CVC group. The least squares mean changes (SE) in HOMA-IR (p=0.0159) and IL-6 (p=0.0094), respectively, were −2.75 (1.27) and −1.9 (0.35) for CVC and 1.94 (1.45) and −0.5 (0.39) for PBO. After 1-year exposure to CVC or PBO, no significant differences vs. baseline in HOMA-b, HDL cholesterol, LDL cholesterol, ALT, and AST were noted. Conclusion: CVC may improve HOMA-IR and pro-inflammatory cytokine IL-6, suggesting that CVC could potentially improve insulin resistance in NASH patients. These findings warrant further investigation. Disclosure A.D. Coviello: Consultant; Self; GI Dynamics Inc., Novo Nordisk Inc. Research Support; Self; Allergan plc., GENFIT, Orthus Health. Speaker’s Bureau; Self; Novo Nordisk Inc. G. Rodriguez: Employee; Self; Allergan plc. E.B. Martins: Employee; Self; Allergan plc. Stock/Shareholder; Self; Allergan plc. N. Alkhouri: Research Support; Self; Allergan plc. M.F. Abdelmalek: None. Funding Allergan plc

New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study.

сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity. 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera). Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1β (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-β (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains. Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.

Possible Association between Serum Hepcidin and Hemostatic Parameters in Chronic Renal Failure Rat Model: Influence of Inhibition of Angiotensin Converting Enzyme

AbstractBackground: Chronic renal failure (CRF) is usually asso-ciated with abnormal coagulation profile. Hepcidin is a major regulator of iron metabolism and was reported to have an impact on anemia, insulin resistance, dyslipidemia, inflam-mation and oxidative stress which were all reported to play a potential role in CRF induced coagulopathy. Renin angi-otensin system (RAS) is involved in the pathophysiology of CRF and can affect coagulation profile.Aim of Study: To evaluate changes in coagulation profile in a rat model of chronic renal failure and the possible asso-ciation of these changes with serum hepcidin level in relation to some metabolic, inflammatory and oxidative stress param-eters and to evaluate whether changes in these parameters induced by inhibition of angiotensin converting enzyme (ACE) can affect serum hepcidin level.Material and Methods: Forty adult male albino rats divided into: Group I (n=8): Control group: Rats received subcutaneous injection with the vehicle (0.3M NaHCO3, 5ml/Kg) once weekly for 5 weeks. Group II (n=16): Chronic renal failure-induced group (CRF): Rats received subcutaneous injection with folic acid (300mg/kg in 5ml) once weekly (dissolved in 0.3M NaHCO3) for 5 weeks. Group III (n=16): (CRF + captopril): Chronic renal failure was induced by folic acid as in group II with concomitant administration of the ACE inhibitor; captopril in a daily dose of (100mg/kg/day) orally by gastric gavage. The following was measured in all groups: Blood pressure, Kidney function, haematological and haemo-static parameters, HOMA-IR, lipid profile, CRP, IL6, MDA, SOD and histopathological examination was made.Results: There was a significant increase in serum hepcidin level in group II compared to control which was correlated positively with serum creatinine, blood urea and negatively with creatinine clearance, while its level decreased significantly in group III compared to group II. A significant increase in bleeding time, WBCT, PT, APTT, INR, FDPs, D dimer and protein C was found in group II compared to control with an increase in HOMA-IR, CRP, IL6, MDA, systolic and diastolic blood pressure and a significant decrease in Hb, MCV, MCH, platelet count, MPV and SOD. In group III, bleeding time, WBCT and protein C remained significantly elevated versus control and further increase in APTT was found versus group II. A significant decrease in FDPs and D dimer was found in group III versus group II with a significant decrease in HOMA-IR, TG, LDL, VLDL, CRP, IL6, MDA, systolic and diastolic BP.Conclusion: Chronic renal failure induced significant increase in hepcidin level associated with an abnormal coag-ulation profile. Hepcidin can indirectly affect coagulation profile through its effect on anaemia, IR, oxidative stress and inflammatory mediators. Inhibition of ACE by captopril caused significant improvement of renal function with significant decrease in hepcidin level and significant decrease in hyper-coagulopathy.

EFFECTS OF LONG-TERM CONTINUOUS POSITIVE AIRWAY PRESSURE THERAPY (CPAP) ON EPICARDIAL FAT THICKNESS AND ARTERIAL STIFFNESS IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA AND HYPERTENSION

Background:obstructive sleep apnea (OSA) is associated with high prevalence of arterial hypertension (AH), obesity, violation of carbohydrate metabolism and dyslipidemia. However, the effects of CPAP therapy to improve epicardial fat thickness of the OSA patient with AH the are poorly understood and poorly studied.Study objective:the aim of the study was to investigate 12-month effects of CPAP therapy with auto-adaptation to inhalation and exhalation of the OSA patient with AH and metabolic disorders (A-Flex therapy) on epicardial fat thickness (EFT).Methods:to the prospective single-center study were included 310 patients with OSA and AH (273 male, 45,3 ± 10,4 yr.) with apnea-hypopnea index (AHI) &gt;5 events /hour. The night polygraphy study (PG) was performed to calculate AHI, oxygen desaturation index (ODI), mean nocturnal saturation (SpO 2 ) by the rules of American Academy of Sleep Medicine (AASM). The calculation of the epicardial fat thickness (EFT), the size and volume of the heart cavities, left ventricular mass index (LVMI) were performed by two-dimensional echocardiography. Endothelial functionof blood vessels determined by finger test was measured according to peripheral arterial tone (PAT). The reactive hyperemia index (RHI) and augmentation index (AI) was calculated. Optimal level of A-Flex therapy was adjusted at home. AHI, the level of air leakage, average pressure and compliance to CPAP treatment were established in accordance with international requirements.Results:after 3 months of A-Flex therapy we found a significant decrease of HOMA-IR -1,09 (95% Cl from -1,74 to -0,96; P=0,021), decrease AI -10.8% (95% Cl from -13,70 to -4.6; P=0,001), decrease EFT -1,26 mm (95% Cl from -2,2 to -0,95; P=0,001) in mild OSA patients. After 6 months of A-Flex therapy we found a significant decrease of HOMAIR -2,81 (95% Cl from -3,74 to -1,46; P=0,001), decrease AI -15.6 % (95% Cl from -17,23 to -11,75; P=0,001), decrease EFT -2,15mm (95% Cl from -3,2 to -1,5; P=0,001) in moderate OSA patients. After 12 months of A-Flex therapy we found a significant decrease of HOMA-IR -4,22 (95% Cl from -5,36 to -2,35; P=0,001), decrease AI -21,05 % (95% Cl from -26,5 to -17,4; P=0,001), decrease EFT -4,0 mm (95% Cl from-5,8 to -2,7; P=0,001) in severe OSA patients.Conclusions:The 12-month A-Flex therapy in moderate and severe OSA patients with AH has a significant therapeutic effect of stabilization systolic and diastolic blood pressure, level of blood lipids and epicardial fat thickness, level of endothelial dysfunction. The 12-month A-Flex therapy has to able to reduce the risks of cardiovascular events in moderate and severe OSA patients with acute metabolic manifestations.

Effect of Direct Acting Anti-viral Agents on Insulin Resistance in Chronic HCV Patients

Background: HCV infection is a major cause of chronic liver disease worldwide, ultimately leading to cirrhosis and hepatocellular carcinoma. Globally, it is estimated that up to 185 million people have been infected with HCV, and among these, according to the World Health Organization, ~ 130–150 millions are chronically infected. Recent estimates place to ~ 700,000 the yearly death toll of liver-related, long-term sequelae of HCV. In many regions of the world, where access to therapy is available, the number of deaths due to HCV has even surpassed. Aim of the work: The goals of our study is to evaluate the effect of direct antiviral agents (DAAs) on insulin resistance in chronic HCV patients receiving (daclatasvir + sofosbuvir +- ribavirin) for 12 weeks and 12 weeks post treatment. Methodology: The study was conducted at, Gastroenterology and Hepatology Unit, Police Authority Hospitals. It included 80 patients with chronic HCV infection (treatment naive patients). Patients were classified in to 4 groups: Group 1: 20 non diabetic, non-obese patients; Group 2: 20 diabetic, non-obese patients; Group 3: 20 obese, non-diabetic patients and Group 4: 20 diabetic, obese patients. Results: The current study showed highly significant decrease in HOMA-IR in all groups at end of treatment and 12 weeks post treatment. Conclusion: Antiviral therapy (DAAs) improves insulin resistance during HCV treatment. These findings suggest that HCV plays an etiological role in the pathogenesis of impaired glucose homeostasis. Moreover, the decrease of insulin resistance through viral eradication implicates clinical benefits by readily available regimens. Recommendations: Confirmation of the current results by conduction of larger scale studies.

Effect of Direct Acting Anti-viral Agents on Insulin Resistance in Chronic HCV Patients

Background: HCV infection is a major cause of chronic liver disease worldwide, ultimately leading to cirrhosis and hepatocellular carcinoma. Globally, it is estimated that up to 185 million people have been infected with HCV, and among these, according to the World Health Organization, ~ 130–150 millions are chronically infected. Recent estimates place to ~ 700,000 the yearly death toll of liver-related, long-term sequelae of HCV. In many regions of the world, where access to therapy is available, the number of deaths due to HCV has even surpassed. Aim of the work: The goals of our study is to evaluate the effect of direct antiviral agents (DAAs) on insulin resistance in chronic HCV patients receiving (daclatasvir + sofosbuvir +- ribavirin) for 12 weeks and 12 weeks post treatment. Methodology: The study was conducted at, Gastroenterology and Hepatology Unit, Police Authority Hospitals. It included 80 patients with chronic HCV infection (treatment naive patients). Patients were classified in to 4 groups: Group 1: 20 non diabetic, non-obese patients; Group 2: 20 diabetic, non-obese patients; Group 3: 20 obese, non-diabetic patients and Group 4: 20 diabetic, obese patients. Results: The current study showed highly significant decrease in HOMA-IR in all groups at end of treatment and 12 weeks post treatment. Conclusion: Antiviral therapy (DAAs) improves insulin resistance during HCV treatment. These findings suggest that HCV plays an etiological role in the pathogenesis of impaired glucose homeostasis. Moreover, the decrease of insulin resistance through viral eradication implicates clinical benefits by readily available regimens. Recommendations: Confirmation of the current results by conduction of larger scale studies.

The influence of correction of vitamin D deficiency on the formation of the stable virological&#x0D; response during therapy of genotype-1 chronic hepatitis C with PEGylated interferon-alpha-2 and ribavirin

Aim. To study effects of correction of vitamin D deficiency on the outcome of antiviral therapy (AVT) with PEGylated interferon alpha 2 (peg-IFN-α-2) and Ribavirin (RBV) in patients with genotype -1 chronic hepatitis C (CHC-1). Materials and methods. The study included 90 patients with primary HCV-1 and deficiency of vitamin D. In all patients of them, insulin resistance (HOMA-IR), body mass index (BMI), viral load, vitamin D levels, stage of liver fibrosis and polymorphism of the IL-28B gene were evaluated. Antiviral therapy included PEG-IFN-α-2 and RBV in combination with water-soluble vitamin D at a dose of 2000 mg/day. 55 patients were assigned to HCV-1 (study group). 35 patients with CHC-1 (control group) were given only PEG-IFN-α-2 + RBV. Results. Vitamin D level was inversely correlated with HOMA-IR, BMI (R = -0,5; R = -0,5; R = -0,4; respectively, p &lt;0.05, Spearman) and inverse relationship between the level of vitamin D (25-Oh), BMI and HOMA-IR (β for BMI=-0,433 (95% CI -1,863;-0,697, p&lt;0.001), HOMA-IR=-0,252 (95% Cl -1,873;-0,229, p=0,013) was documented based on the multiple regression analysis. In the study group, sustained virological response (SVR) was achieved in 74.5% of the patient compared with 42.9% in the control group; OR SVR in patients of the study group was 6.8 (95% Cl 2,90-16.09, p=0.002). SVR was reached in 66.7% and 22.2% patients of the study group with BMI&gt;25 kg/m2 and controls respectively. OR SVR in patients with BMI over 25 kg/m2 who received cholecalciferol at AVT was 7.0 (95% Cl 1.66-29,23, p=0.01, Fisher test). In the patients with HOMA-IR&gt;2.0, the frequency of SVR in the study qnd control groups was 66.7% and 37.5% respectively; OR SVR in patients with HOMA-IR&gt;2.0 receiving colecalciferol at AVT was 3.3 (95% Cl 1.1-9.9, p=0.03, Fisher's exact test). In the study group a statistically significant decrease of HOMA-IR (p&lt;0.001, Wilcoxon test) and undesirable effects of antiviral therapy (р&lt;0,05) was documented. Conclusions. The addition of colecalciferol at a daily dose of 2000 IU to PEG-IFN-alpha-2+RBV therapy is safe and significantly increases the efficiency of AVT from 40.0 up to 74.5% (p=0.002), improves OR SVR up to 7.0 (95% Cl 1.66-29,23, p=0.01) in patients with BMI &gt;25 kg/m2 and up to 3.3 (95% Cl 1.1-9.9, p=0.03) in patients with HOMA-IR&gt;2; it significantly reduces HOMA-IR (p&lt;0,0001) and the frequency of adverse effects (p&lt;0.05).

Add on DPP-4 inhibitor alogliptin alone or in combination with pioglitazone improved β-cell function and insulin sensitivity in metformin treated PCOS

ABSTRACTPurpose: Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR. Materials and methods: In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34.4 ± 6.5 years, BMI 39.0 ± 4.9 kg/m2, HOMA-IR 4.82 ± 2.52, mean ± SD). Model derived parameters of glucose homeostasis from the meal tolerance test (MTT) were determined. The ability of the β-cell function was assessed by the adaptation index (AI). Results: MET-ALO and MET-ALO-PIO resulted in a significant decrease of HOMA-IR (by 1.6±2.3 (p=0.039) and 2.9±3.3 (p=0.001), respectively) and an increase in insulin sensitivity (IS) after meal ingestion (oral glucose IS) by 31.4±97.5 ml·min–1·m–2 (p=0.007) vs 39.0±58.1 ml·min–1·m–2 (p=0.039), respectively. AI across the entire group was significantly improved from 329.6±200.6 to 442.5±303.9 (p=0.048). Conclusions: ALO alone and in combination with PIO improved IR along with dynamic IS and meal related β-cell function when added to MET treated PCOS.

Hyperproliferative syndrome in gynecology and obesity

The article deals the problem of obesity in the aspect of development of hyperproliferative pathology of the reproductive system. Article shows the efficiency and safety of treatment of comorbid pathology via targeted phytonutrients, particularly the combination of indole-3-carbinol and epigallocatechin-3-gallate.The study involved 50 women of reproductive age with adenomyosis, diffuse form of fibrocystic breast disease, and obesity. The study group consisted of 25 patients who received lynestrenol (5.0 mg per day from 5 to 25 day of menstrual cycle) and Epigalin® (2 capsules twice a day), the comparison group – patients with lynestrenol monotherapy (5.0 mg per day from 5 to 25 day of menstrual cycle). Treatment duration was 6 months.All the examined patients complained of increase in breast volume, increased sensitivity and soreness of the breasts in the second phase of the menstrual cycle. Women are also worried about the pain of aching in the lower abdomen, which prevailed before menstruation, menstrual dysfunction, spotting before and after menstruation. Evaluation of anthropometric data showed that waist circumference (a marker of excess visceral fat associated with the presence of insulin resistance) in all studied patients exceeded 85 cm. The presence of visceral obesity was associated with signs of dyslipidemia (high cholesterol, increased levels of low-density lipoproteins) and violation of carbohydrate metabolism, which manifested in increase in fasting glucose and HOMA-IR index.After completion of treatment in all patients decreased symptoms of engorgement, increased sensitivity and breast tenderness in the second phase of the menstrual cycle. Normalization of menstrual function noted at 82.0% of women. In addition, in women of main group significantly decreased levels of total cholesterol and low density lipoprotein cholesterol; improved carbohydrate metabolism, recorded a significant decrease in HOMA-IR index.The study authors conclude that multi-target therapy (indole-3-carbinol – 200 mg and epigallocatechin-3-gallate – 45 mg) not only carries a complex effect on the body, which manifests itself in the inhibition of pathological hyperplastic processes in the hormone-dependent tissues and organs of the female reproductive system, but also is an optimal and safe in the treatment of hyperproliferative diseases of the female reproductive system in the background of obesity, because it promotes the normalization of lipid and carbohydrate metabolism in this group of patients.

The effects of genistein supplementation on fructose induced insulin resistance, oxidative stress and inflammation

AimsThis experimental study was designed to investigate the effects of 10weeks genistein administration on oxidative stress and inflammation in serum and liver of rats fed with fructose. Main methods6–8weeks old, 40 male Sprague-Dawley rats were included. Group 1 (control) was fed with standard chow food and 100μl/kg/day/rat dimethyl sulfoxide (DMSO) administered subcutaneously; group 2 (genistein) with standard chow food and 0.25mg/kg/day/rat genistein; group 3 (fructose) with standard chow food and drinking water 20% fructose, group 4 (fructose+genistein) with standard chow food, drinking water with 20% fructose and 0.25mg/kg/day/rat genistein. TNF-α, IL-6, visfatin as inflammatory markers and 8-isoprostane as a oxidative stress marker were measured by ELISA, glucose, triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol by enzymatic colorimetric method, AST and ALT by kinetic UV method. Key findingsSignificantly high 8-isoprostane levels in serum (p<0.001) and liver (p<0.05) in group 3 compared to control group indicate that presence of oxidative stress. Significantly high TNF-α and IL-6 levels in serum (p<0.05) and liver (p<0.01) and visfatin levels in serum (p<0.001) of group 3 indicate inflammation accompanying insulin resistance and oxidative stress. Genistein administration to fructose group causes a significant decrease in HOMA-IR (p<0.001) and LDLC (p<0.05) level. Significantly lower serum 8-isoprostane (p<0.01) level indicates the antioxidant effect of genistein and significantly lower liver TNF-α (p<0.01), serum, liver IL-6(p<0.01) and serum visfatin (p<0.01) levels reflect the antiinflammatory effects of genistein. SignificanceGenistein administration to rats fed with fructose causes an ameliorating effect on HOMA-IR values and lipid status markers in addition to its antioxidant and antiinflammatory effects.

Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue.

Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue. To evaluate this hypothesis, 16 obese individuals were studied before and 7-8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls. Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p < 0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis. These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB.

Bis(α-furancarboxylato)oxovanadium(IV) Exerts Durable Antidiabetic Effects and Suppresses Matrix Metalloproteinase-2 Activity in Spontaneous Type 2 Diabetic KKAy Mice

Vanadium compounds maintain euglycemic effects in diabetic rats long after drug withdrawal and bis(α-furancarboxylato)oxovanadium(IV) (BFOV) possesses potent antidiabetic effects in diabetic rats. Here, we investigated the treatment and posttreatment effects of BFOV in diabetic Kuo Kondo [1, 2] with Ay gene (KKAy) mice, and whether these effects were associated with changes in matrix metalloproteinases (MMPs). KKAy mice received normal saline or BFOV initially at 70μmol/kg/day for 1month, which was tapered to 17μmol/kg/day in the next 2months and discontinued thereafter. Compared to diabetic controls, fasting plasma glucose (FPG) was reduced by 46 and 19% in KKAy mice after 70μmol/kg BFOV for 1month and 3months after BFOV withdrawal, respectively. OGTT and ITT showed improved glucose tolerance and a better response of FPG to insulin with a significant decrease in HOMA-IR and a marked rise in the insulin sensitivity index after 70μmol/kg BFOV for 1month and 4months after BFOV withdrawal (P <0.05 in all vs. diabetic controls). BFOV treatment resulted in a moderate but significant reduction in body weight and systolic blood pressure (SBP) at 1month of treatment and 4months following BFOV withdrawal (P <0.05 in all vs. diabetic controls). Gelatin zymography showed that serum MMP2 activity was significantly reduced and immunoblotting assays further showed that MMP2 expression was markedly downregulated in the liver after 1month of treatment with 70μmol/kg and 4months after BFOV withdrawal (P <0.05 in all vs. diabetic controls). These results suggested that BFOV possessed potent treatment and posttreatment effects in KKAy mice with improved metabolic profile and reduced body weight and SBP. Furthermore, these effects were associated with decreased MMP2 expression and activity in diabetic KKAy mice.

Effects of continuous positive airway pressure upon the un-treatment hour changes of blood glucose level in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes

To assess the effects of short-term continuous positive airway pressure (CPAP) upon un-treatment hour glucose control via a continuous glucose monitoring system (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes (OWD). A total of 23 case of hospitalized OWD were recruited. CGMS was applied for 2 days before and 4 days during CPAP treatment. The treatment hour (6 h, 0:00 - 6:00) and un-treatment hour (14 h, 6:00 - 22:00) glucose level and glucose variability were analyzed. Insulin resistance was assessed with fasting plasma blood glucose (FPG), plasma insulin (FINS) and homeostatic model assessment of insulin resistance index (HOMA-IR). The short-term CPAP treatment corrected sleep-disordered breathing and induced significant decreases of treatment and un-treatment hour glucose level ((7.07 ± 2.02) mmol/L vs (6.34 ± 1.57) mmol/L, (8.04 ± 1.99) mmol/L vs (7.64 ± 1.81) mmol/L, both P < 0.05). Glucose variability of treatment and un-treatment hours significantly decreased after CPAP treatment (0.41 ± 0.24 vs 0.29 ± 0.18, 1.02 ± 0.50 vs 0.78 ± 0.45, all P < 0.05). Short-term treatment also induced an increase of insulin sensitivity, as indicated by a significant decrease of HOMA-IR (4.02 ± 2.07 vs 3.08 ± 1.58, P < 0.05). Short-term CPAP treatment in OWD may improve not only insulin resistance but also blood glucose and glucose variability during treatment and un-treatment hours.