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Homeostasis Model Assessment (homeostasi + model_assessment)
Selected AbstractsEarlier 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] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009R. E. Pratley Aim:, To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. Methods:, After a 2-week screening period, adult patients 18,80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, ,-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment ,-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. Results:, The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (,0.38%) and 25 mg (,0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels ,7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction ,0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of ,-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, ,0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63,64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0,2.5% across groups), and serious AEs (2.0,5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. Conclusions:, In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. [source] Robust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy databaseDIABETES OBESITY & METABOLISM, Issue 10 2008R. E. Pratley Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [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] Incidence of insulin resistance in obese subjects in a rural Japanese population: The Tanno and Sobetsu studyDIABETES OBESITY & METABOLISM, Issue 1 2005H. Ohnishi Objectives:, Although it is well known that obesity is closely related to insulin resistance, the incidence of the development of insulin resistance in people with obesity is not known. In this study, we investigated the incidence of insulin resistance in citizens of two rural communities in Japan. Subjects and methods:, The subjects were 102 men and 126 women over the age of 30 years selected from 1035 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1991 and 1998. Those who were on medication for hypertension, diabetes, hyperlipidaemia, coronary heart disease and cerebral vessel disease were excluded. The simple index to determine insulin resistance [i.e. homeostasis model assessment (HOMA-R) , 1.73] was used, and subjects who were determined to be positive for insulin resistance according to this index in 1991 were also excluded in order to determine the incidence of insulin resistance in subjects who had no abnormalities other than obesity. The systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), triglyceride level, high-density lipoprotein level, blood sugar level, serum insulin value and HOMA-R were measured in all subjects in 1991 and in 1998. Moreover, the subjects were divided into two groups according to BMI, a normal group consisting of subjects with BMI < 25 and an obesity group consisting of subjects with BMI , 25. We also compared the incidences of insulin resistance in normal and obesity groups of subjects who were newly determined to be positive for insulin resistance on the basis of data obtained from medical examinations conducted in 1998. Results:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group (25.0 vs. 4.5%). The results of logistic regression analysis showed that obesity was closely related to insulin resistance and that the relative risk of development of insulin resistance adjusted for age, sex, SBP, FPG and HDL was 3.193 (95% CI 1.085,9.401). Conclusions:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group in this study, suggesting that improvement in obesity is important for prevention of the occurrence of type 2 diabetes or atherosclerotic disease based on insulin resistance. [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] Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow-up studyDIABETIC MEDICINE, Issue 11 2007M. Shargorodsky Abstract Aims, Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long-term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. Methods, In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4,8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose-lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment,insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. Results, In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 ± 4.6 to 13.9 ± 4.7 ml/mmHg × 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 ± 1.2 to 5.1 ± 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 ± 5.4 to 8.9 ± 3.9 ml/mmHg × 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 ± 1.8 to 5.1 ± 1.5 ml/mmHg × 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). Conclusions, Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. [source] Reduced insulin secretion in normoglycaemic patients with ,-thalassaemia majorDIABETIC MEDICINE, Issue 12 2006N. G. Angelopoulos Abstract Aims To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with ,-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. Methods We measured fasting glucose, insulin and C-peptide levels in 24 patients with ,-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. Results Fasting glucose levels in patients were increased compared with control subjects (5.5 ± 0.12 vs. 4.7 ± 0.13 mmol/l, mean ± sem, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SCHOMA) was lower in thalassaemic patients (SCHOMA 88.5 ± 11.11 vs. 184.3 ± 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SCHOMA was higher in the patients with NFG compared with those with IFG patients (110.6 ± 17.63 vs. 66.3 ± 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISIHOMA) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SCHOMA (r = 0.45, P = 0.02) and negatively with ISIHOMA (r = ,0.43, P = 0.03). Conclusions These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in ,-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent. [source] Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, ,-cell function and cardiovascular risk profileDIABETIC MEDICINE, Issue 1 2003K. I. Birkeland Abstract Aims The present study investigated the variability in insulin sensitivity and ,-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM). Methods Fifty-four subjects aged 59.5 ± 6.1 (mean ± sd) years with NIDDM for 7.9 ± 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). ,-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B. Results The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The ,-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD,subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome. Conclusions The wide variations in insulin sensitivity and ,-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD. [source] The prevalence of the mitochondrial DNA 16189 variant in non-diabetic Korean adults and its association with higher fasting glucose and body mass indexDIABETIC MEDICINE, Issue 8 2002J. H. Kim Abstract Aims To evaluate the prevalence of the 16189 variant of mitochondrial DNA in Korean adults and its association with insulin resistance. Methods We investigated 160 non-diabetic subjects from a community-based diabetes survey conducted in Yonchon County, Korea in 1993. We extracted the DNA from peripheral blood and examined the 16189 variant by polymerase chain reaction and restrictive enzyme digestion. We compared body mass index (BMI), blood pressure, fasting plasma glucose, 2-h plasma glucose after 75 g glucose load, fasting insulin, cholesterol, and homeostasis model assessment of insulin resistance and ,-cell function between the subjects with 16189 variant and wild type. Results The prevalence of the 16189 variant in Korean adults was 28.8% (46 of 160). Subjects with the 16189 variant had higher fasting glucose and BMI than those with wild type, but fasting insulin, homeostasis model assessment of insulin resistance and ,-cell function, cholesterol, and blood pressure were not different between two groups. Conclusion Our results provide evidence for an association of a frequent mitochondrial polymorphism with higher fasting glucose and the risk factors of diabetes mellitus. [source] Age-related increase in haemoglobin A1c and fasting plasma glucose is accompanied by a decrease in , cell function without change in insulin sensitivity: evidence from a cross-sectional study of hospital personnelDIABETIC MEDICINE, Issue 3 2002A. P. Yates Abstract Aims To examine the influence of age on glucose homeostasis in a population of healthy, non-diabetic hospital personnel. Methods One hundred and twenty female and 71 male non-diabetic individuals (fasting plasma glucose < 7.0 mmol/l) were fasted overnight prior to blood sampling. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were measured using a BioRad Diamat automated HPLC, a Hitachi 747 analyser and a sensitive in-house radioimmunoassay, respectively. Mathematical modelling of the fasting glucose and insulin pairs (homeostasis model assessment (HOMA)) generated indices of pancreatic , cell function, HOMA-B and tissue insulin sensitivity HOMA-S. Results Spearman rank correlation analysis showed that in the whole group there was a significant negative correlation between age and HOMA-B (rs= ,0.218, P = 0.0022) and a significant positive correlation between age and both HbA1c (rs= 0.307, P = 0.0001) and FPG (rs= 0.26, P = 0.0003). There was no correlation between age and either FPI (rs= ,0.08, P = 0.266) or HOMA-S (rs= 0.024, P = 0.75). Analysis by gender showed the above associations to be present in the females (rs= ,0.243, P = 0.0076; rs= 0.304, P = 0.0007; rs= 0.32, P = 0.0004 for age vs. HOMA-B, HbA1c, and FPG, respectively). Again there was no correlation of age with FPI or insulin sensitivity. In the males there was a significant correlation of HbA1c with age (rs= 0.35, P = 0.002), but no significant correlation of age with any of the other parameters. Conclusions Glycaemic control deteriorates with age in healthy, non-diabetic individuals. Age-related rises in FPG and haemoglobin A1c result from a small but steady decline in pancreatic , cell function. Diabet. Med. 19, 254,258 (2002) [source] Hepatocyte growth factor is a significant risk factor for white matter lesions in Japanese type 2 diabetic patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010Futoshi Anan Eur J Clin Invest 2010; 40 (7): 585,590 Abstract Background, The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Elevated hepatocyte growth factor (HGF) levels are associated with a high mortality rate in type 2 diabetic patients. The preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with HGF and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Material and methods, Based on brain magnetic resonance imaging, 92 type 2 diabetic patients were divided into two groups: WML-positive group (age 60 ± 5 years, mean ± SD, n = 35) and WML-negative group (age 59 ± 6 years, mean ± SD, n = 57. The level of blood glucose was assessed by fasting plasma glucose, fasting immunoreactive insulin, homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). Results, The body mass index was higher in the WML-positive group than that in the WML-negative group (P < 0·005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < 0·01 and P < 0·0001 respectively). Fasting plasma glucose (P < 0·0001), insulin concentrations (P < 0·0001), HOMA index (P < 0·0001) and HGF (< 0·0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high HGF and insulin resistance (P < 0·0001 and P < 0·0001 respectively). Conclusion, The results of this preliminary study indicate that the presence of WML was associated with the high HGF and insulin resistance in Japanese patients with type 2 diabetes mellitus. [source] Metabolic and anti-inflammatory benefits of eccentric endurance exercise , a pilot studyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2008H. Drexel ABSTRACT Background, Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. Materials and methods, We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. Results, Forty-two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4·1%; P = 0·026), low-density lipoprotein (LDL) cholesterol (by 8·4%, P = 0·001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10·9%, P < 0·001), homeostasis model assessment of insulin resistance scores (by 26·2%, P = 0·017) and C-reactive protein (by 30·0%; P = 0·007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6·2%, P = 0·023), whereas concentric exercise improved triglyceride tolerance (by 14·9%, P = 0·022). Conclusions, Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti-inflammatory effects and is well applicable to sedentary individuals. [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] Diverse Effect of Inflammatory Markers on Insulin Resistance and Insulin-Resistance Syndrome in the ElderlyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2004Angela M. Abbatecola MD Objectives: To evaluate the potential association between different inflammatory markers and insulin resistance (IR), as well as insulin-resistance syndrome (IRS) in a large, population-based study of older, nondiabetic persons. Design: Cross-sectional study. Setting: Outpatient clinic in Greve in Chianti and Bagno a Ripoli (Italy). Participants: One thousand one hundred forty-six nondiabetic subjects ranging in age from 22 to 104. Measurements: Anthropometric measurements; plasma fasting levels of glucose, insulin, and cholesterol (total, high-density lipoprotein, low-density lipoprotein); homeostasis model assessment to estimate degree of insulin resistance; tumor necrosis factor , (TNF-,), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin receptor antagonist (IL-1ra), and C-reactive protein (CRP) plasma concentrations; diastolic, systolic, and mean arterial blood pressure; and echo-color-Doppler duplex scanning examination of carotid arteries. Results: Insulin resistance correlated with age (r=0.102; P<.001) and plasma levels of TNF-, (r=0.082; P=.007), IL-1ra (r=0.147; P<.001), IL-6 (r=0.133; P<.001), sIL-6R (r=,0.156; P<.001), and CRP (r=0.83; P<.001). Subjects in the upper tertile of IR degree were older and had higher serum levels of TNF-,, IL-1ra, and IL-6 and lower levels of sIL-6R than subjects in the lowest tertile. Independent of age, sex, body mass index, waist-to-hip ratio, triglycerides, drug intake, diastolic blood pressure, smoking habit, and carotid atherosclerotic plaques, higher IL-6 (t=2.987; P=.003) serum concentrations were associated with higher IR, whereas sIL-6R levels (t=,5.651; P<.001) were associated with lower IR. Furthermore, IL-1ra concentrations (t=2.448; P=.015) were associated with IRS, and higher sIL-6R plasma levels continued to correlate negatively with IRS. Conclusion: Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects. [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] Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metforminJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2009G. Derosa MD PhD Summary Background and objective:, Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods:, We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA1c), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion:, Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion:, Nateglinide improved glycemic control better than glibenclamide in combination with metformin. [source] Metformin,pioglitazone and metformin,rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndromeJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2006G. Derosa MD PhD Summary Background and objective:, Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. Methods:, This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration ,6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA1c), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. Results and discussion:, No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA1c decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. Conclusion:, For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not. [source] Non-alcoholic fatty liver disease in Malaysia: A demographic, anthropometric, metabolic and histological studyJOURNAL OF DIGESTIVE DISEASES, Issue 1 2007Abdul MALIK BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is increasing rapidly in the Asia,Pacific region. There has been a paucity of studies from the region. The aims of this study were to define the demographic, anthropometric, metabolic and histological characteristics of patients with NAFLD in our local population and to determine independent predictors of severe liver fibrosis. METHODS: Patients with persistently raised liver enzymes and/or fatty liver detected on ultrasonography with exclusion of other liver disorders were prospectively recruited. Their insulin resistance was assessed using the homeostasis model assessment of insulin resistance score. A liver biopsy was performed in all cases for grading (for steatohepatitis) and staging (for fibrosis) of NAFLD. Independent risk factors for fibrosis were determined using multiple logistic regression analysis. RESULTS: Seventy-five patients were recruited: 39 men (52%) and 36 women (48%). The mean age of the patients was 47.0 ± 12.2 years. Of these, 58 patients (77.3%) were centrally obese, 29 patients (38.7%) were diabetic and 15 patients (20.0%) had impaired glucose tolerance. Insulin resistance was diagnosed in 62 out of 64 (96.9%) patients. Benign steatosis, nonalcoholic steatohepatitis and cirrhosis were diagnosed in three (4.3%), 59 (84.3%) and eight (11.4%) of 70 patients, respectively. Significant independent predictors of liver fibrosis were; male sex (P = 0.019, OR = 5.55, CI = 1.33,23.18) and Indian race (P = 0.013, OR = 8.21, CI = 1.56,43.16). CONCLUSIONS: The full histological spectrum of NAFLD was seen in our patients. The majority of patients were insulin resistant, centrally obese and either diabetic or had impaired glucose tolerance. The predictors of severe liver fibrosis were male sex and Indian race. [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] Diurnal triglyceridaemia and insulin resistance in mildly obese subjects with normal fasting plasma lipidsJOURNAL OF INTERNAL MEDICINE, Issue 1 2004C. J. M. Halkes Abstract. Objective., A novel method has been developed to study diurnal triglyceride (TG) profiles using repeated capillary self-measurements in an ,out-of-hospital' situation. We assessed the diurnal capillary TG (TGc) profile in males with mild obesity and evaluated the use of plasma and capillary TG as markers of insulin resistance. Design., Cross-sectional study. Setting and Subjects., Fifty-four lean (body mass index, BMI < 25 kg m,2) and 27 mildly obese (25 < BMI < 30 kg m,2), normolipidaemic males measured capillary TG concentrations on six fixed time-points over a 3-day period in an ,out-of-hospital' situation. Main outcome measures., The total area under the TGc curve (TGc-AUC) and incremental area under the TGc curve (TGc-IAUC) were used as estimation of diurnal triglyceridaemia. Fasting blood samples were obtained once. Food intake was recorded by all participants. Results., Obese and lean subjects had comparable fasting capillary TG concentrations (1.37 ± 0.40 mmol L,1 and 1.32 ± 0.53 mmol L,1, respectively). However, during the day, obese subjects showed a greater TG increase, resulting in significantly higher TGc-AUC (27.1 ± 8.4 and 23.0 ± 6.3 mmol h,1 l,1, respectively; P < 0.05) and TGc-IAUC (7.9 ± 5.8 and 4.6 ± 6.6 mmolh,1 L,1, respectively; P < 0.05). The total group of 81 males was divided into quartiles based on fasting plasma TG, fasting capillary TG, TGc-AUC and TGc-IAUC. Amongst these variables, TGc-AUC was the only significant discriminator of subjects with high homeostasis model assessment (HOMA) (insulin resistance) compared with low HOMA (insulin sensitive). Overall, BMI was the strongest determinant of HOMA. Conclusions., Diurnal TG profiles can be used to investigate postprandial lipaemia in both lean and mildly obese subjects and may help to detect subjects with an underlying disposition for hypertriglyceridaemia related to insulin resistance, i.e. the metabolic syndrome. [source] Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort studyJOURNAL OF INTERNAL MEDICINE, Issue 5 2003G. Engström Abstract., Engström G, Hedblad B, Nilsson P, Wollmer P, Berglund G, Janzon L (University of Lund, Malmö University Hospital, Malmö, Sweden). Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study. J Intern Med 2003; 253: 574,581. Objectives., To explore whether a reduced lung function is a risk factor for developing diabetes and insulin resistance (IR), and whether such relationship contributes to the largely unexplained association between lung function and incidence of cardiovascular disease (CVD). Design., Forced vital capacity (FVC) was assessed at baseline. Incidence of diabetes and IR [according to the homeostasis model assessment (HOMA) model] was assessed in a follow-up examination after 13.9 ± 2.6 and 9.4 ± 3.6 years for men and women, respectively. After the follow-up examination, incidence of CVD (stroke, myocardial infarction or cardiovascular death) was monitored over 7 years. Setting., Populations-based cohort study. Subjects., Initially nondiabetic men (n = 1436, mean age 44.6 years) and women (n = 896, mean age 49.8 years). Results., Prevalence of IR at the follow-up examination was 34, 26, 21 and 21%, respectively, for men in the first (lowest), second, third and fourth quartile of baseline FVC (P for trend <0.0001). The corresponding values for women were 30, 29, 25 and 17%, respectively (P for trend <0.001). Adjusted for potential confounders, the odds ratio (OR) for IR (per 10% increase in FVC) was 0.91 (CI: 0.84,0.99) for men and 0.89 (CI: 0.80,0.98) for women. FVC was similarly significantly associated with the incidence of diabetes (OR = 0.90, CI: 0.81,1.00), adjusted for sex and other confounders. The incidence of CVD after the follow-up examination was significantly increased only amongst subjects with low FVC who had developed IR (RR = 1.7, CI: 1.02,2.7). Conclusion., Subjects with a moderately reduced FVC have an increased risk of developing IR and diabetes. This relationship seems to contribute to the largely unexplained association between reduced lung function and incidence of CVD. [source] Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and ,-cell functionJOURNAL OF INTERNAL MEDICINE, Issue 2 2003I. Os Abstract., Os I, Høieggen A, Larsen A, Sandset PM, Djurovic S, Berg K, Os A, Birkeland K, Westheim A (University of Oslo; Ulleval University Hospital; and Aker University Hospital, Oslo, Norway). Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and ,-cell function. J Intern Med 2003; 253: 232,239. Objectives., To investigate possible associations between smoking habits and other coronary risk factors in postmenopausal women with known coronary heart disease (CHD). Setting., The study was conducted at a university clinic. Subjects., A total of 118 postmenopausal women with CHD verified with angiography, consecutively recruited. Interventions., Conventional treatment for CHD. The women were randomized to hormone replacement therapy (HRT) with transdermal 17-, oestradiol and medroxyprogesterone acetate, or to a control group. Results., Smokers were younger (P = 0.005), had lower body mass index (P = 0.04) and lipoprotein Lp(a) levels (P = 0.02) compared with nonsmokers. Smokers had reduced ,-cell function (homeostasis model assessment, P = 0.006), whereas whole blood viscosity (WBV) was higher at all shear rates. WBV was not affected by HRT over a 12-month period. Oestrone levels were higher in smokers. Conclusions., Smoking adversely affects insulin secretion (,-cell function) and WBV in postmenopausal women with established CHD, which could be of importance as a mechanism for the increased risk of CHD in smokers. The importance of smoking as a risk factor, overrides the effect of Lp(a), which is lower in smokers compared with nonsmokers. [source] Influence of insulin resistance on hepatic fibrosis and steatosis in hepatitis C virus (HCV) mono-infected compared with HIV,HCV co-infected patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009P. HALFON Summary Background, Insulin resistance (IR), the major feature of the metabolic syndrome, is also common in patients with chronic HCV infection. Liver fibrosis and steatosis are known potential outcome of chronic hepatitis B or C infection. Studies have shown that HIV positive individuals co-infected with HCV have more rapid live disease progression than those with HIV alone. Few data have reported the influence of IR on steatosis and fibrosis in the context of HIV-HCV coinfection. Aim, To test the association among insulin resistance (IR), liver fibrosis and liver steatosis in HIV,HCV and HCV-infected patients. Patients and methods, A total of 170 HIV,HCV-infected patients matched by age, gender and genotype with 170 HCV mono-infected patients were included. Patients were considered to be IR when the homeostasis model assessment of IR >2. Significant fibrosis was considered if METAVIR ,F2 and significant steatosis if ,10%. Results, Insulin resistance was independently associated in HCV patients with fibrosis [odds ratio (OR) = 2.04 (95% CI 1.02,4)], a body mass index (BMI) >25 kg/m² [OR = 3.33 (1.47,7.69)] and steatosis [OR = 3.33 (1.67,6.67)]. Fibrosis ,F2 was associated in HCV patients with high liver activity grade (,A2) [OR = 8.33 (3.85,16.67)], male gender [OR = 3.03 (1.33,7.14)] and IR [OR = 2.44 (1.15,5)]. In HIV,HCV patients, ,A2 [OR = 5.56 (1.64,20)] was associated with fibrosis. Steatosis ,10% was associated in HCV patients with IR [OR = 3.13 (1.59,6.25) and ,F2 (OR = 2.22 (1.15,4.17)]. In HIV,HCV, a BMI >25 kg/m² [OR = 3.85 (1.64,9.10)], ,A2 [OR = 2.16 (1.02,4.55); P = 0.044] and nucleoside reverse transcriptase inhibitor [OR = 3.61 (1.19,10.96); P = 0.023] were independently associated with significant liver steatosis. Conclusions, Insulin resistance is associated with liver fibrosis and steatosis in HCV mono-infected, but not in HIV,HCV co-infected patients. Significant liver fibrosis is associated with IR independent of liver steatosis only in HCV mono-infected patients. [source] | |||||||||||||||||||||||||||||||