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HOMA-IR
Selected AbstractsInitial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptinDIABETES OBESITY & METABOLISM, Issue 10 2010R. Retnakaran Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0,2 OADs were switched to 4,8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] Improvement of insulin sensitivity and ,-cell function by nateglinide and repaglinide in type 2 diabetic patients , a randomized controlled double-blind and double-dummy multicentre clinical trialDIABETES OBESITY & METABOLISM, Issue 4 2007J. Li Aim:, To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and ,-Cell function in patients with type 2 diabetes. Methods:, A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. Results:, A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A1c (HbA1c) (p > 0.05). However, the effect on HbA1c in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and ,-cell function indexes measured by HOMA-,, ,I30/,G30 and (,I30/,G30)/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and ,-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). Conclusions:, The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA1c is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and ,-cell function. [source] Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal womenDIABETES OBESITY & METABOLISM, Issue 3 2006A. D. Karelis Aim:, We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods:, Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic,euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (,1.7 mmol/l), blood pressure (,130/,85 mmHg) and fasting glucose (,6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0,1 vs. 2 vs. ,3 features of the metabolic syndrome. Results:, We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0,1 to ,3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions:, These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. [source] What predicts the occurrence of the metabolic syndrome in a population-based cohort of adult healthy subjects?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009S. Bo Abstract Background Metabolic syndrome (MS), the concurrence of hyperglycaemia, dyslipidaemia, hypertension and visceral obesity, increases cardiovascular risk and mortality. Predictors of MS were previously evaluated in patients without the full syndrome, but with some of its traits. This might confound the resulting associations. Methods The relationship between baseline variables and MS development was evaluated in healthy middle-aged subjects without any MS component at baseline, over a 4.5-year follow-up. Results From a population-based cohort of 1658 subjects, 241 individuals showed no MS components and 201 (83.4%) of them participated in a follow-up screening. At baseline, patients who developed the MS (n = 28/201; 13.9%) showed significantly higher Homeostasis Model Assessment-Insulin Resistance score (HOMA-IR) and C-reactive protein (CRP) values, and lower exercise level than subjects who did not. In a multiple logistic regression analysis, after multiple adjustments, the only baseline variable significantly (p < 0.01) associated with the MS was CRP (OR = 4.05; 95% CI 2.23,7.38; p < 0.001). Results did not change after adjusting for weight gain. The area under the receiver-operating curve was 0.83 for CRP after multiple adjustments. The optimal cut-off point of baseline CRP values was 2.1 mg/L, with 86% (95% CI 81,90) sensitivity and 75% (69,81) specificity in predicting the MS. Baseline CRP resulted associated with after-study glucose values in a multiple regression model (, = 0.14; 0.08,0.20; p < 0.001). Conclusions Higher baseline CRP values confer a significant increased risk of developing the MS in healthy subjects, independently of weight gain. Copyright © 2009 John Wiley & Sons, Ltd. [source] J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes: an 8-year follow-up of relatively lean Japanese individualsDIABETIC MEDICINE, Issue 8 2009M. Sakurai Abstract Aims, This study investigated the relationship between waist circumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods, The study participants were 3992 employees (2533 men and 1459 women, aged 35,55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results, During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1,45.0) vs. 54.3 (37.9,74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions, There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. [source] Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patientsDIABETIC MEDICINE, Issue 2 2009A. Esteghamati Abstract Aims, To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods, Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005,2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE , 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Results, HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7,6.2)]. Conclusions, In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE. [source] Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in menDIABETIC MEDICINE, Issue 12 2007V. Rochira Abstract Aims The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2). Methods The effects of transdermal oestradiol (tE2) treatment at different dosages on insulin sensitivity were studied before tE2 treatment (phase 1), and after 6 months (phase 2) and 12 months of tE2 treatment (phase 3) by means of homeostasis model assessment,insulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), insulin tolerance test (ITT), and oral glucose tolerance test (OGTT). The latter was performed only in subject 1, as subject 2 suffered from Type 2 diabetes. Results The restoration of normal serum oestradiol led to improved insulin sensitivity, as shown by changes in HOMA-IR and QUICKI. The ITT provided evidence of improved insulin sensitivity during tE2 treatment. Insulin secretion after OGTT was reduced during tE2 treatment in subject 1. After 12 months of tE2 treatment, insulin sensitivity was improved compared with in phases 1 and 2. Conclusions The study suggests a direct involvement of oestrogens in insulin sensitivity, and supports a possible role of oestradiol : testosterone ratio, which may be as influencial as the separate actions of each sex steroid on glucose homeostasis. [source] Metabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipientsDIABETIC MEDICINE, Issue 6 2006P. Petruzzo Abstract Aims The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. Methods The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA1c and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. Results All patients from both groups had normal fasting glucose, body mass index and HbA1c values by selection. The homeostatic model (HOMA) ,-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. Conclusions The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages. [source] Familial factors in diabetic nephropathy: an offspring studyDIABETIC MEDICINE, Issue 3 2006E. Agius Abstract Aims Familial clustering of diabetic nephropathy in patients with Type 2 diabetes suggests that inherited factors predispose to diabetic nephropathy, but the nature of these factors is uncertain. The aim of the study was to compare the prevalence of known risk factors for nephropathy in non-diabetic offspring of Type 2 diabetic patients with and without nephropathy and in control subjects. Methods Three groups of patients were recruited with 40 or 41 subjects in each group. These were subjects having one Type 2 diabetic parent with nephropathy (DN); subjects having one parent with Type 2 diabetes without nephropathy (DnoN), and non-diabetic unrelated control subjects with no personal or parental history of diabetes (Control subjects). Results The median (interquartile range) albumin/creatinine ratio (ACR) was 1.40 (0.96,2.90) mg/mmol in DN; 0.94 (0.50,1.46) mg/mmol in DnoN and 1.22 (0.66,1.83) mg/mmol in Controls (anova: P = 0.03). ACR was higher in group DN than in DnoN (P < 0.006) and in Control subjects (P < 0.03), but there was no difference between DnoN and Control subjects. Twenty-four-hour ambulatory blood pressure monitoring showed mean daytime systolic blood pressure to be significantly higher in group DN than in DnoN (P < 0.02) or Control subjects (P < 0.01) (anova: P = 0.004). Fasting insulin, HOMA-IR, interleukin-6 (IL-6) and C-reactive protein (CRP) were similar in the three groups. Conclusion Our data provide further evidence that genetic factors are important in determining urinary albumin excretion and renal disease associated with Type 2 diabetes and suggest that genes that affect systemic arterial blood pressure but not those relating to insulin resistance or inflammation are likely to be implicated. [source] Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes.DIABETIC MEDICINE, Issue 9 2005The Skaraborg Project Abstract Aims The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of ,-cell secretory granules, activates KATP -channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. Methods A case,control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. Results Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). Conclusions We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors. [source] Low-dose metformin improves hyperglycaemia related to myotonic dystrophyDIABETIC MEDICINE, Issue 3 2005T. Kouki Abstract Background One of the clinical features of myotonic dystrophy is insulin resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity. Case report A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA1c 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA1c was decreased to 7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA1c was maintained (7.5%). Conclusion It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients. [source] Predictors of insulin sensitivity in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 7 2002E. Bonora Abstract Aims To identify the independent predictors of insulin sensitivity in Type 2 diabetes, and to establish whether isolated Type 2 diabetes (i.e. diabetes without overweight, dyslipidaemia and hypertension) is a condition of insulin resistance. Methods We examined 45 patients with non-insulin-treated Type 2 diabetes undergoing a 4-h euglycaemic hyperinsulinaemic clamp (20 mU/m2 per min) combined with 3H-3-D-glucose and 14C-U-glucose infusions and indirect calorimetry. We also examined 1366 patients with non-insulin-treated Type 2 diabetes randomly selected among those attending the Diabetes Clinic and in whom insulin resistance was estimated by Homeostasis Model Assessment (HOMA-IR). Results In the 45 patients undergoing glucose clamp studies, insulin-mediated total glucose disposal (TGD) was independently and negatively associated with systolic blood pressure (standardized , coefficient = ,0.407, P = 0.003), plasma triglycerides (,= ,0.355, P = 0.007), and HbA1c (,= ,0.350, P = 0.008). The overall variability of TGD explained by these variables was 53%. Overweight diabetic subjects with central fat distribution, hypertension, hypertriglyceridaemia and poor glycometabolic control had insulin-mediated TGD values markedly lower than their lean counterparts without hypertension, with normal triglycerides, and with good glycometabolic control (16 ± 5 vs. 31 ± 10 µmol/min per kg lean body mass, P < 0.01). Nevertheless, the latter still were markedly insulin-resistant when compared with sex- and age-matched non-diabetic control subjects (31 ± 10 vs. 54 ± 13 µmol/min per kg lean body mass, P < 0.01). In the 1366 Type 2 diabetic patients of the epidemiological study, HOMA-IR value was independently associated with HbA1c (, = 0.283, P < 0.0001), plasma triglycerides (, = 0.246, P < 0.0001), body mass index (, = 0.139, P < 0.001), waist girth (, = 0.124, P < 0.001) and hypertension (, = 0.066, P = 0.006). Conclusion Overweight, central fat distribution, dyslipidaemia, hypertension and poor glycometabolic control are strong independent predictors of insulin resistance in Type 2 diabetes. However, reduced insulin sensitivity can be found even when Type 2 diabetes is isolated and well controlled. Diabet. Med. 19, 535,542 (2002) [source] Increased insulin resistance and risk of incident cerebrovascular events in patients with pre-existing atherothrombotic diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2009D. Tanne Background and purpose:, Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events. Methods:, Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction ,6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles. Results:, Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94,1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97,1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category. Conclusions:, Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease. [source] Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 3 2009Essam KHEDR Abstract Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 ± 10.6 ,U/mL) was significantly lower than patients without rHuEPO (group B) (28.8 ± 7.7 ,U/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 ± 2.97, 7.98 ± 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA-IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 ± 3.2, 9.4 ± 7.2, respectively, P<0.001). Also, HOMA-IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 ± 2.85, 6.9 ± 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=,0.62, ,0.71, and ,0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients. [source] Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: Impact of obesity and ethnicity,HEPATOLOGY, Issue 1 2010Khoa D. Lam Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 ± 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI , 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of ,3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30, P = 0.005). Conclusion: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV. HEPATOLOGY 2010 [source] Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss,HEPATOLOGY, Issue 4 2009Nathan A. Johnson Weight loss remains the most common therapy advocated for reducing hepatic lipid in obesity and nonalcoholic fatty liver disease. Yet, reduction of body weight by lifestyle intervention is often modest, and thus, therapies which effectively modulate the burden of fatty liver but are not contingent upon weight loss are of the highest practical significance. However, the effect of aerobic exercise on liver fat independent of weight loss has not been clarified. We assessed the effect of aerobic exercise training on hepatic, blood, abdominal and muscle lipids in 19 sedentary obese men and women using magnetic resonance imaging and proton magnetic resonance spectroscopy (1H-MRS). Four weeks of aerobic cycling exercise, in accordance with current physical activity guidelines, significantly reduced visceral adipose tissue volume by 12% (P < 0.01) and hepatic triglyceride concentration by 21% (P < 0.05). This was associated with a significant (14%) reduction in plasma free fatty acids (P < 0.05). Exercise training did not alter body weight, vastus lateralis intramyocellular triglyceride concentration, abdominal subcutaneous adipose tissue volume, 1H-MRS,measured hepatic lipid saturation, or HOMA-IR (homeostasis model assessment of insulin resistance; P > 0.05). Conclusion: These data provide the first direct experimental evidence demonstrating that regular aerobic exercise reduces hepatic lipids in obesity even in the absence of body weight reduction. Physical activity should be strongly promoted for the management of fatty liver, the benefits of which are not exclusively contingent upon weight loss. (HEPATOLOGY 2009.) [source] Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines,HEPATOLOGY, Issue 1 2007Ian Homer Y. Cua The role of tumor necrosis factor ,, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCV-infected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P = 0.01), TNF, (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P = 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. By multiple linear regression, independent predictors of HOMA-IR included the body mass index, and the serum levels of leptin (positive correlation) and adiponectin (negative correlation), but not that of TNF, and IL6. Only TNF, levels were correlated with the extent of histological injury (portal/periportal inflammation, P = 0.02). Conclusion: Whereas leptin and adiponectin contribute to IR, none of the adipocytokines accounted for the elevated IR in HCV-infected subjects. The adipocytokines were not associated with histological features of chronic HCV infection except for TNF, which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity. (HEPATOLOGY 2007;46:66,73.) [source] Low prevalence of insulin resistance among HIV-infected children receiving nonnucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy in ThailandHIV MEDICINE, Issue 2 2009B Lee Background Highly active antiretroviral therapy (HAART) is reported to cause insulin resistance among adults, but effects on children are less clear. We attempted to describe the prevalence of insulin resistance among HIV-infected children receiving HAART. Methods Insulin resistance was assessed at 96 weeks of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based HAART (nevirapine or efavirenz with stavudine and lamivudine) among children in Chiang Mai, Thailand. Insulin resistance was defined as homeostasis model assessment for insulin resistance (HOMA-IR) ,3.16, fasting c-peptide ,4.40 ng/mL or fasting insulin ,25.0 ,U/mL. Impaired fasting glucose (IFG) was defined as glucose ,110 mg/dL. Measurements were analysed for associations with age, lipodystrophy, treatment regimen and clinical data. Results The prevalence of insulin resistance was 6.5%; no child had IFG. Those with insulin resistance were older with higher body mass index. Children ,10 years had higher HOMA-IR, c-peptide and insulin, but no difference was seen in the frequency of insulin resistance. No associations between insulin resistance and lipodystrophy or treatment regimen were detected. Conclusions Insulin resistance is uncommon among children receiving NNRTI-based HAART and is unrelated to lipodystrophy. [source] The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multicentre studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2008H. Gao Summary Aim:, To investigate the effects of extended-release metformin (MXR) compared with immediate-release metformin (MIR) on post-prandial glycaemic excursion, chronic glycaemia, lipid profiles, insulin resistance and islet function in type 2 diabetes. Methods:, A randomised, open-labelled, positive-controlled multicentre study was conducted on 150 Chinese patients with type 2 diabetes. After 2 weeks of run-in period with MIR, 150 subjects were randomised into MXR group and MIR group. The patients in MXR group were assigned to take MXR 1500 mg once daily after dinner, while the patients in MIR group were assigned to continue MIR 500 mg thrice daily after meals for 12 weeks. Standard meal tests were carried out at baseline and at the end of this study. Plasma glucose, serum insulin, HbA1c and lipid profiles were measured. Homeostasis model assessment (HOMA) was used to evaluate insulin resistance index (HOMA-IR) and islet ,-cell function index (HOMA-B). Results:, Either MIR or MXR modestly, but significantly decreased HbA1c levels and body mass index (BMI) after 12 weeks of treatment. However, there were no significant differences between two groups. The post-prandial glycaemia at 120 min after a standard meal in MXR group was higher than in MIR group (11.02 ± 3.08 mmol/l vs. 9.74 ± 2.61 mmol/l, p < 0.05). Moreover, no differences in the areas under curve of insulin release response, HOMA-B, HOMA-IR and lipid profiles were found within or between groups after 12 weeks of treatment. Conclusion:, The effects of once daily MXR on chronic glycaemia, BMI, lipid profiles, insulin resistance and islet function are comparable with that of thrice daily MIR in oriental population. [source] Adiponectin Is a Link Among Inflammation, Insulin Resistance, and High-Density Lipoprotein Cholesterol But Is Not Associated With Paraoxonase Activity in Premenopausal WomenJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2009Pinar Cetinalp-Demircan PhD The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol,linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=,.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor ,, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol,linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations. [source] Hydroxypropylated Tapioca Starch Retards the Development of Insulin Resistance in KKAy Mice, a Type 2 Diabetes Model, Fed a High-Fat DietJOURNAL OF FOOD SCIENCE, Issue 7 2009Makoto Tachibe ABSTRACT:, The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS, degree of substitution = 0.180) was investigated in male KKAy mice. Mice were fed a purified high-fat (20%) diet without or with HPTS (5% or 10%) for 33 d. Gelatinized tapioca starch (TS) was used as a reference. Fasting blood glucose concentrations, days 14 and 28, were significantly lower in the 10% HPTS group compared with the reference. In an oral glucose tolerance test (OGTT), day 28, blood glucose concentrations in the 5% HPTS group, at 60, 90, and 120 min, and in the 10% HPTS group, at 30, 60, and 90 min after oral administration of glucose, were significantly lower compared with the reference. The area under the glucose curve (AUC) for glucose in both HPTS groups was significantly lower compared with the reference. Energy intake was significantly lower in the 10% HPTS group compared with the reference. At the end of the experiment, adiponectin concentrations were significantly higher in the 10% HPTS group compared with the reference. A homeostasis model assessment of insulin resistance (HOMA-IR) tended to be lower in the 10% HPTS group compared with the reference, whereas a quantitative insulin sensitivity check index (QUICKI) was significantly higher in both HPTS groups compared with the reference. These results show that HPTS retards the development of insulin resistance in KKAy mice fed a high-fat diet. [source] High-Hydroxypropylated Tapioca Starch Improves Insulin Resistance in Genetically Diabetic KKAy MiceJOURNAL OF FOOD SCIENCE, Issue 3 2009R. Kato ABSTRACT:, The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS) with a varying degree of substitution (DS: 0.058, 0.091, and 0.180) was investigated in rats and KKAy mice, an animal model of type 2 diabetes. The positive incremental area under the curve (IAUC) for glucose significantly decreased as the DS of HPTS increased. The IAUC after intragastric intubation of the highest HPTS (HPTS-III, DS = 0.180) was 55% of the IAUC of tapioca starch (TS). After 28 d, fasting blood glucose and insulin concentrations were significantly lower in rats fed HPTS-III (50 g/kg diet) than in those fed TS (P < 0.05). In KKAy mice fed HPTS-III (50 or 100 g/kg diet) for 33 d, as compared with TS, there was a delay in the detection of glucose in urine and also a decreased incidence of finding glucose in urine on days 7, 21, and 28; in addition, the AUCs for glucose in the oral glucose tolerance test on days 14 and 28 were significantly lower (P < 0.05 and P < 0.05, respectively). The plasma adiponectin concentration and the quantitative insulin sensitivity check index (QUICKI) were significantly higher in mice fed HPTS-III than in those fed TS (P < 0.01), whereas the homeostasis model assessment of insulin resistance (HOMA-IR) was lower (P < 0.01). Energy intake was significantly lower in mice fed HPTS-III than in those fed TS. These findings show that HPTS with a high DS resists digestion by ,-amylase and improves insulin resistance in KKAy mice by decreasing energy intake. However, the potential mechanism by which HPTS-III decreases energy intake is unclear at present. [source] Specific insulin sensitivity and leptin responses to a nutritional treatment of obesity via a combination of energy restriction and fatty fish intakeJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 6 2008I. Abete Abstract Background, Nutritional strategies to treat obesity often influence neuroendocrine factors related to body weight control. The present study aimed to investigate whether the inclusion of three fatty fish servings per week within a hypocaloric diet may have specific healthy effects on insulin and leptin functions. Methods, Thirty-two subjects (body mass index = 31.6 ± 3.5 kg m,2) aged 36 ± 7 years, were assigned to a control or fish-based energy-restricted diet over an 8-week period. Anthropometry, body composition, lipid profile, leptin and insulin values were measured at the start and at the end of the dietary intervention. Results, Both experimental diets resulted in a similar mean weight loss (control = 5.3 ± 2.6% versus fish-based = 5.5 ± 2.5%; P = 0.783). A significant reduction in insulin resistance, as determined by the homeostatic model assessment index (HOMA-IR = insulin × glucose/22.5), was observed after the fish-based intervention. The change in circulating leptin was higher in the fish-based diet compared to the control group. Sixteen percent of the variability in the change of adjusted-leptin could be explained (P = 0.034) by the HOMA index change and the type of diet. Conclusions, Three servings a week of fatty fish included in an energy-restricted diet appears to be a valid strategy for specifically improving insulin sensitivity and leptin levels in obese subjects, which could involve a better body weight regulation after a nutritional intervention period. [source] Calcium intake and its relationship with adiposity and insulin resistance in post-pubertal adolescentsJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 2 2008L. C. Dos Santos Abstract Background, Dietary calcium intake has been described as being a negative contributor to adiposity. In adolescents, this relationship is not well established. The objectives of the present study were to compare the calcium intake of normal-weight and obese adolescents and to evaluate its relationship with adiposity and insulin resistance. Methods, A cross-sectional analysis of 96 post-pubertal adolescents; 47 normal weight and 49 obese, mean age 16.6 (SD ± 1.3) years. Body composition was assessed by dual-energy X-ray absorptiometry. Dietary intake was evaluated using a 3-day dietary record. The biochemical evaluation comprised the measurements of serum lipids, lipoproteins, glucose and insulin. Insulin resistance was calculated using the Homeostasis Model Assessment of Insulin resistance (HOMA-IR). Results, The mean calcium intake, adjusted for energy, was lower in obese adolescents, 585.2 (±249.9) mg, than in normal weight adolescents, 692.1 (±199.5) mg. Only 4% of adolescents had an adequate intake of calcium. Calcium intake was inversely associated with body trunk fat, insulin and HOMA-IR in the obese group. The quartile analysis of calcium intake provided evidence that girls in the highest quartile had decreased adiposity and insulin resistance. Conclusions, This study showed a negative relationship between calcium intake and body fat and insulin resistance, mainly in obese girls, and demonstrates the importance of an increased dietary calcium intake. [source] Serum HCV RNA levels and HCV genotype do not affect insulin resistance in nondiabetic patients with chronic hepatitis C: a multicentre studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009E. TSOCHATZIS Summary Background, Chronic hepatitis C (CHC) induces insulin resistance (IR) and subsequently diabetes. Aim, To examine viral, metabolic and histological predictors of IR in 275 CHC patients to test the hypothesis that IR differs among HCV genotypes and that viral replication directly affects IR. Methods, We studied 275 nondiabetic treatment-naïve CHC patients. Histological lesions were evaluated according to Ishak. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). Results, HOMA > 3.0 was found in 37% of patients, independently associated with higher BMI and GGT. In genotype non-3 patients, HOMA > 3.0 was associated with higher BMI and GGT values, while no significant association was noted in genotype 3 patients. In non-obese patients with minimal fibrosis, HOMA > 3.0 was found in 20% of cases without significant differences among genotypes. No association between HOMA > 3.0 and HCV-RNA levels was found. Severe fibrosis (stage 5,6) related to older age (OR:1.048), HOMA-IR (OR:1.177), necroinflammation (OR: 2.990) and higher ALT (OR: 1.009) and GGT (OR:1.006). Conclusions, IR develops at early stages of CHC without significant differences among genotypes. It is more frequent in obese patients with steatosis and contributes to fibrosis progression. However, IR does not seem to be associated with viraemia and therefore its exact pathogenetic mechanism in CHC remains elusive. [source] Clinical trial: low plasma cholesterol and oxidative stress predict rapid virological response to standard therapy with peginterferon and ribavirin in HCV patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009F. ANGELICO Summary Background, Rapid virological response (RVR) is the best predictor of sustained response to standard HCV treatment. Aim, To evaluate predictive factors of RVR. Methods, Sixty-five patients (mean age 52.6 ± 13.8; 37 genotype-1, and 28 genotypes-2/3) were consecutively treated with pegIFN-alpha2a or 2b once weekly plus daily ribavirin based on body weight for 24 or 48 weeks, according to genotype. RVR was defined as undetectable HCV-RNA at week 4. Results, Twenty-seven percent of patients achieved RVR in genotypes 1 and 60.7% in genotypes 2/3 (P < 0.01). Rapid responders had higher mean serum baseline total and LDL-cholesterol levels (P < 0.01). RVR was 20.0% in the bottom tertile of total cholesterol and 63.6% in the top tertile (P < 0.01). HCV-RNA levels at week 4 were positively correlated with baseline serum insulin (P < 0.01), HOMA-IR (P < 0.01), body mass index (P < 0.05) and number of components of metabolic syndrome (P < 0.01) and negatively correlated with cholesterol levels (P < 0.05). At multivariate analysis, age, LDL-cholesterol, HCV genotype and serum 8-iso-PGF2alpha, a marker of oxidative stress, were independent predictors of RVR. Conclusions, Our prospective study supports a role of low serum total and LDL-cholesterol and of oxidative stress as positive independent predictive factors of poor RVR in HCV patients. [source] Hepatitis C virus directly associates with insulin resistance independent of the visceral fat area in nonobese and nondiabetic patientsJOURNAL OF VIRAL HEPATITIS, Issue 9 2007M. Yoneda Summary., Insulin resistance (IR) is known to be associated with the visceral adipose tissue area. Elucidation of the relationship between hepatitis C virus (HCV) and IR is of great clinical relevance, because IR promotes liver fibrosis. In this study, we tested the hypothesis that HCV infection by itself may promote IR. We prospectively evaluated 47 patients with chronic HCV infection who underwent liver biopsy. Patients with obesity, type 2 diabetes mellitus (DM), or a history of alcohol consumption were excluded. IR was estimated by calculation of the modified homeostasis model of insulin resistance (HOMA-IR) index. Abdominal fat distribution was determined by computed tomography. Fasting blood glucose levels were within normal range in all the patients. The results of univariate analysis revealed a significant correlation between the quantity of HCV-RNA and the HOMA-IR (r = 0.368, P = 0.0291). While a significant correlation between the visceral adipose tissue area and the HOMA-IR was also observed in the 97 control, nondiabetic, non-HCV-infected patients (r = 0.398, P < 0.0001), no such significant correlation between the visceral adipose tissue area and the HOMA-IR (r = 0.124, P = 0.496) was observed in the patients with HCV infection. Multiple regression analysis with adjustment for age, gender and visceral adipose tissue area revealed a significant correlation between the HCV-RNA and the HOMA-IR (P = 0.0446). HCV is directly associated with IR in a dose-dependent manner, independent of the visceral adipose tissue area. This is the first report to demonstrate the direct involvement of HCV and IR in patients with chronic HCV infection. [source] Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon ,-2b plus ribavirinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009C.-J. CHU Summary Background, Cross-sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim, To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon ,-2b/ribavirin. Methods, A total of 133 biopsy-proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic fibrosis was graded by the METAVIR scoring system. Results, Mean HOMA-IR progressively elevated along with the severity of hepatic fibrosis (F1,F2 fibrosis: 2.55 ± 0.16 vs. F3,F4 fibrosis: 3.61 ± 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3,F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (,600 000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 ± 0.89 vs. 10.19 ± 0.55 ,U/mL, P < 0.001) and HOMA-IR values (3.76 ± 0.23 vs. 2.50 ± 0.15, P < 0.001). Multivariate analyses showed that F1,F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA-IR < 2 (odds ratio: 7.15, P = 0.005) and pre-treatment hepatitis C virus RNA < 600 000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR. Conclusions, Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon ,-2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy. [source] Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver diseaseLIVER INTERNATIONAL, Issue 4 2009Jung Won Yun Abstract Objective: The association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and metabolic syndrome has been documented for obese men and middle-aged men. This study was designed to determine the relationship between NAFLD and the oral glucose tolerance test (OGTT) to predict preclinical diabetes in nondiabetic young male patients (<30 years old). Methods: A total of 75 male patients who had elevated liver enzymes and who were diagnosed with NAFLD were enrolled in this study. A standard 75 g OGTT was carried out on all patients. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined as a fasting plasma glucose (FPG) level ,100 mg/dl but <126 mg/dl, and a 2-h post-load glucose on the OGTT of ,140 mg/dl, but <200 mg/dl respectively. Results: According to the OGTT results, 24 (32%) patients were diagnosed as having IGT and 12 (16%) patients were diagnosed as having diabetes. Among the 48 patients with normal fasting glucose, 18 (37.6%) patients showed abnormal glucose tolerance (15 had IGT and three had diabetes). The NAFLD patients with abnormal glucose tolerance showed significant differences in age, weight, body mass index, waist,hip ratio, alanine aminotransferase, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, triglyceride, insulin, FPG and homeostasis model for insulin resistance (HOMA-IR). Multiple regression analysis showed that age, FPG and HOMA-IR were independent predictors of abnormal glucose tolerance. Conclusions: Although the patients were young men, an OGTT should be recommended for NAFLD patients with elevated liver enzymes and IFG to predict the risk of type 2 diabetes. [source] | |||||||||||||||||||||||||||||||