Homeostasis Model Assessment Levels Research Articles

Antiobesity effect of PEGylated conjugated linoleic acid on high-fat diet-induced obese C57BL/6J ( ob/ob) mice: attenuation of insulin resistance and enhancement of antioxidant defenses

This study was designed to test that dietary conjugated linoleic acids (CLA) used in a mixture of cis-9, trans-11 and trans-10, cis-12 isomers (40% each in weight) coupled to poly(ethylene glycol) (PEG) as PEGylated CLA (PCLA) act as mediators inducing or inhibiting specific metabolic pathways in high-fat (HF)-fed obese C57BL/6J ( ob/ob) mice. After an acclimatization period of 7 days, animals were given a normal (control) or HF diet, the latter being added either alone (HF) or with CLA, PEG or PCLA for 6 weeks. Although the food intakes were not different among the dietary groups, final body weights were significantly lower in the HF-PCLA group than in the HF group. Also the HF-PCLA diet strongly prevented the dramatic increase in blood low-density lipoprotein cholesterol observed with the HF diet, with no difference in high-density lipoprotein cholesterol between control, HF and HF-PCLA treatments. Furthermore, homeostasis model assessment levels showed a marked decrease in HF-PCLA-fed mice, preventing the increase found in mice fed the HF diet, and suggesting that PCLA lowered insulin resistance in HF-mice. The liver steatosis observed in mice fed the HF diet was also prevented by PCLA. Interestingly, the activity of mitochondrial glutathione peroxidase was increased by PCLA, which may enhance antioxidant defenses. Overall, PCLA exerted its beneficial effects through reduction of lipid accumulation and attenuation of insulin resistance induced by the HF diet in obese C57BL/6J ( ob/ob) mice, which might confer to these products antiobesity properties in other species.

ASSOCIATIONS BETWEEN 45T/G POLYMORPHISM OF THE ADIPONECTIN GENE AND PLASMA ADIPONECTIN LEVELS WITH TYPE 2 DIABETES

1. The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. 2. We performed a cross-sectional survey in a representative sample of 151 Uygur adults aged 24-80 years. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. 3. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein (P < 0.05) and total cholesterol (P < 0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity (P < 0.05) and higher levels of HOMA of insulin resistance (P < 0.05). 4. Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.

A Strong Interaction between Serum γ-Glutamyltransferase and Obesity on the Risk of Prevalent Type 2 Diabetes: Results from the Third National Health and Nutrition Examination Survey

Some studies have found an association of obesity with type 2 diabetes only among individuals with high normal serum gamma-glutamyltransferase (GGT) activity, not in those with low serum GGT. If this interaction reflected pathophysiology, it would have scientific and clinical importance. The findings failed to reach statistical significance, however, and no articles have focused on the topic. We investigated possible interactions between serum GGT and body mass index (BMI) and their effects on the risk of prevalent type 2 diabetes and homeostasis model assessment (HOMA) insulin resistance. We analyzed 4011 adults > or =40 years old who participated in the 3rd US National Health and Nutrition Examination Survey. BMI was associated with prevalent diabetes only among persons with high normal serum GGT activity (P for interaction = 0.002). In the highest serum GGT quartile, adjusted odds ratios for BMI 25-29.9, 30-34.5, and > or =35 kg/m(2) compared with BMI<25 kg/m(2) were 3.1, 5.1, and 6.2, respectively (P for trend <0.001). In the lowest serum GGT quartile, BMI was not associated with diabetes; corresponding adjusted odds ratios were 1.0, 0.9, 1.8, and 0.8 (P for trend = 0.551). After prevalent diabetes was excluded, there was a parallel interaction with HOMA levels (P for interaction <0.001). BMI was not associated with prevalent type 2 diabetes when GGT was low normal, suggesting that obesity itself may not be a sufficient risk factor for type 2 diabetes. Practically, this interaction can be useful in clinical settings to identify individuals at high risk for type 2 diabetes.

Defining the Metabolic Syndrome Construct

It is controversial whether the clustering of certain metabolic abnormalities should be separately designated as the metabolic syndrome. We operationalized the "syndrome" concept and tested whether the metabolic syndrome was compatible with these operational constructs. The baseline cross-section of the Multi-Ethnic Study of Atherosclerosis recruited a population-based cohort of 6,781 individuals, aged 45-84 years, from six communities in the U.S. Metabolic syndrome components (waist circumference, blood pressure, fasting serum HDL cholesterol, triglycerides, and plasma glucose), homeostasis model assessment (HOMA) of insulin resistance (fasting glucose x insulin), and intimal-medial thickness (IMT) in the common and internal carotid arteries by B-mode ultrasound were measured. Higher syndrome component count is associated with higher HOMA levels (trend P < 0.001). Given the prevalence of individual components, the nonprevalence of any component or the co-prevalence of four or five components is greater than expected (chi2 P < 0.001). After accounting for the additive association of each component, the current definition of metabolic syndrome (co-prevalence of three or more components) does not have supra-additive association with thicker IMT in the common carotid (men: P = 0.075, women: P = 0.949) or internal carotid artery (men: P = 0.106, women: P = 0.121). The metabolic syndrome did not have supra-additive association with IMT, but its components clustered greater than chance expectation and a higher component count was associated with greater insulin resistance. The metabolic syndrome was compatible with two of three "syndrome" constructs tested.

Fasting Glucagon‐like Peptide‐1 and Its Relation to Insulin in Obese Children Before and After Weight Loss

To study the relationships between glucagon-like peptide-1 (GLP-1), weight status, insulin, and insulin resistance in the fasting state. Fasting GLP-1, glucose and insulin concentrations, insulin resistance index as homeostasis model assessment (HOMA), body mass index (BMI), and percentage body fat based on skinfold thickness measurements were determined in 42 obese (median age 11 years) and in 16 lean children of the same age. The HOMA model was used to calculate degree of insulin resistance. Furthermore, the changes in GLP-1, glucose, insulin, and HOMA in the course of 1 year were analyzed in the 42 obese children participating in an obesity intervention. GLP-1 concentrations did not differ significantly between obese and lean children. In multiple linear regression analyses, GLP-1 was significantly related to insulin (P = 0.028) and HOMA (P = 0.019) but not to glucose, age, sex, pubertal stage, BMI, or percentage body fat. The 15 obese children with substantial weight reduction demonstrated significantly (P < 0.05) decreased GLP-1, insulin, and HOMA levels, whereas these parameters did not change in 27 obese children without substantial weight loss. Changes in GLP-1 correlated significantly with changes in insulin (r = 0.46, P = 0.001) and HOMA (r = 0.28, P = 0.036) but not with changes in glucose, BMI, or percentage of body fat. In children, fasting GLP-1 concentrations are independent of age, sex, and pubertal stage. Although GLP-1 did not differ between lean and obese children, weight loss was associated with decreasing GLP-1. Inasmuch as GLP-1 levels were related to insulin concentrations in both cross-sectional and longitudinal analyses, we hypothesize a relationship between GLP-1 and insulin in the fasting state.

Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B 12 in patients with type 2 diabetes mellitus

Objectives Metformin is widely used in patients with type 2 diabetes but may decrease vitamin B 12 levels and increase levels of homocysteine (Hcy), a cardiovascular risk factor. Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, may reduce markers of inflammation. We investigated whether 6 weeks' treatment with metformin or rosiglitazone affects serum concentrations of Hcy, folate, or vitamin B 12 in subjects with newly diagnosed type 2 diabetes compared with controls. Methods We examined 165 patients with type 2 diabetes. Fasting blood samples, a physical examination, and a complete medical history were performed at the beginning and at the end of the treatment. All blood samples were obtained after a 12-h fast. Results After treatment, metformin use was associated with an increase in levels of Hcy by 2.36 μmol/l and decreases in folate and vitamin B 12 concentrations by −1.04 ng/ml and −20.17 pg/ml. During rosiglitazone treatment, Hcy levels decreased by −0.92 μmol/l; folate and vitamin B 12 levels remained unchanged. Metformin and rosiglitazone significantly decreased levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (total-C), HbA1c, insulin, and homeostasis model assessment (HOMA). Metformin also significantly decreased body weight. In controls, there was no change in Hcy, folic acid, vitamin B 12, TG, LDL, total-C, HbA1c, insulin, or HOMA levels. Homocysteine change did not correlate with insulin, folate, or vitamin B 12 changes in the metformin and rosiglitazone groups. Conclusions In patients with type 2 diabetes, metformin reduces levels of folate and vitamin B 12 and increases Hcy. Conversely, rosiglitazone decreases Hcy levels in this time period. The clinical significance of these findings remains to be investigated.

Association of Atrogin‐1 genotypes with Metabolic Syndrome Risk Factors in Caucasian Females

PURPOSE: Atrogin-1 is a regulator of the ATP-ubiquitin-proteasome system -dependent muscle proteolysis (UB’P), which is altered in diabetes and other catabolic states. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human Atrogin-1 gene on metabolic syndrome risk factors in a young, pre-diabetic population. METHODS: We analyzed three Atrogin-1 SNPs (rs4871385, rs6690663, rs3739287) in a Caucasian subpopulation (446 females; 312 males; age 24 ± 8 y) in a 12 wk supervised resistance training intervention. Fasting blood draws, ht, wt and resting blood pressure were collected from subjects prior to onset of an exercise training period. Genotyping was done using a TaqMan assay. Serum samples were assessed for glucose, insulin, triglycerides and HDL levels. Associations between the SNP and each phenotype were testing using ANCOVA with Sidak post-hoc tests. Each model included baseline body weight and age as covariates. RESULTS: In females, the G202A SNP (rs3739287) was found significantly affect homeostasis model assessment (HOMA) (GG: 1.04 ± 0.08 vs. AG/AA 1.71 ± 0.18; p = 0.0006), fasting glucose (GG: 85.08 ± 0.41 vs. AG/AA 87.09 ± 0.88; p = 0.0383), insulin (GG: 4.92 ± 0.28 vs. AG/AA 7.30 ± 0.61; p = 0.0005), and HDL (GG: 52.80 ± 0.64 vs. AG/AA 49.54 ± 1.39; p = 0.0341). CONCLUSIONS: These data suggest a sex-specific effect of Atrogin-1 G202A genotype on serum insulin, HOMA, glucose and HDL levels in young Caucasian females. The GG genotype appears to be protective of hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. This SNP may affect regulation of the AKT insulin response pathway via a down-regulation of Atrogin-1. ACKNOWLEDGEMENT: This study was supported by NINDS -1R01NS040606.

The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women

Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects. Cross-sectional analysis in 124 African women. Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA). Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations. Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.

Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy

Background and aimObesity in children may lead to insulin resistance and impaired glucose regulation over time. The aim of this study was to investigate the insulin resistance status and the frequency of impaired glucose regulation in obese children and adolescents from the Campania region (Southern Italy), where the prevalence of obesity is among the highest in Europe. Methods and resultsWe studied 100 (62 male) Italian obese children and adolescents (mean age 10.1±2.7years) and 50 (27 male) normal weight healthy subjects (mean age 10.2±2.7years). Anthropometric measures and biochemical tests were performed in all subjects. In obese patients an oral glucose tolerance test was also performed. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) index. A cut-off HOMA level of >2.5 in children and >4.0 in adolescents was used to identify an insulin-resistance status. Insulin resistance was found in 40.8% of obese children and 41.2% of obese adolescents, whereas it was found in 3.0% of normal children and none of the 17 normal adolescents (p<0.0001 and p<0.002, respectively). None of the subjects had impaired fasting glucose or diabetes, while 4 obese patients had impaired glucose tolerance (4%). ConclusionsImpaired glucose tolerance is still rare whereas insulin-resistance is already detectable in more than 40% of obese children and adolescents in Southern Italy. Our observations confirm that metabolic risk factors can be found at a very early age and strengthen the case for implementing programmes for prevention and treatment of childhood obesity.

The Role of Proinflammatory Cytokine Gene Polymorphisms for Development of Insulin Resistance After Renal Transplantation

Background Insulin resistance, a frequent prediabetic metabolic complication after renal transplantation, is generally linked to immunosuppressive drugs including corticosteroids, cyclosporine (CsA) or tacrolimus, as well as to age, cadaveric donors and ethnic factors. Cytokines are known to be inflammation modulatory substances that contribute to metabolic derangements after transplantation. The present study investigated the effects of cytokine gene polymorphisms on insulin resistance in renal transplant recipients. Patients and methods Sixty-one renal transplant recipients (37 men, 24 women; mean age: 39.3 ± 10.8 years) who attended regular clinical visits without a known history of diabetes were enrolled in the study. All patients were on a regimen of steroid, CsA, and mycophenolate mofetil. Venous blood samples were collected for biochemical analyses after an overnight fast at 08:00 pm. CsA trough levels, C-reactive protein, and fibrinogen were also estimated. Additional 10 mL of blood was withdrawn into an ethylenediamine tetraacetic acid–containing tube to determine cytokine genotypes (tumor necrosis factor-alpha [TNF-α] -238 G/A, transforming growth factor-beta [TGF-β] codon 10 -869 T/C). Insulin resistance was calculated by the homeostasis model assessment (HOMA) method using the values of fasting blood glucose (FBG) and insulin levels. Anthropometric indices as well as body height, weight, waist and hip circumferences were measured simultaneously to calculate body mass index (kg/m 2) and waist-to-hip ratio. Impaired fasting glucose (IFG) was described as an FBG ≥ 110 but < 126 mg/dL. Results IFG was detected in 27.9% of this study group. The HOMA index was significantly higher among patients with IFG compared with normal FBG (NoGT) (6.3 ± 4.5 vs 3.7 ± 1.5; P = .01). Neither FBG and insulin nor HOMA values correlated with antrophometric, metabolic, or inflammatory parameters. Cytokine genotype allele frequencies, age, sex, immunosuppressive and antihypertensive drug type and doses, CsA trough levels, and donor source (cadaveric/living) were similiar for patients with IFG and NoGT. Mutant allele carrier genotypes (AA + GA) for TNF-α -238 G/A showed higher fasting insulin (14.0 ± 7.9 vs 34.1 ± 17.7 μIU/mL; P = .04) and HOMA (4.01 ± 2.01 vs 7.95 ± 5.44; P = .002) levels than GG homozygote subjects. FBG, HOMA, and other metabolic and anthropometric indices were similiar between TGF-β codon 10 -869 T/C genotypes. The daily dose of steroid (mg/d) and A allele frequency for TNF-α -238 G/A genotype were significant predictors of HOMA index in linear regression analysis. Conclusion The present study revealed that beside the daily dose of steroids, TNF-α -238 G/A genotype may contribute to insulin resistance in renal transplant recipients. Further investigations may highlight the effects of cytokine gene heterogenity on insulin resistance in those patients.

Is reduced baroreflex gain a component of the metabolic syndrome? Insights from the LINOSA study

To assess the relationship between insulin resistance and baroreflex gain (BRS) in the context of the metabolic syndrome. Observational population study. We studied the healthy population of a small Mediterranean island (Linosa, about 0.5 square miles, 450 inhabitants) where genetic, psychosocial and behavioral bias is likely to be minimal for historical and social reasons. Baroreflex gain (BRS, by the frequency domain alpha index) and indices of autonomic regulation of the sino-atrial (SA) node derived from spectral analysis of RR interval variability were obtained, together with metabolic and behavioral indicators in the 144 participating subjects (age range 20-82 years). Carotid artery thickness (CCA) was also obtained with computer-aided ultrasound techniques. Insulin resistance was estimated by the homeostasis model assessment (HOMA), and subjects divided in tertiles accordingly. BRS appeared to be reduced progressively with increasing levels of HOMA (respectively, 21.0 +/- 2.6, 17.7 +/- 1.7, 15.7 +/- 1.9 ms/mmHg, P < 0.03), while spectral indices of autonomic SA regulation appeared to be only insignificantly affected. Conversely, CCA was significantly increased with increasing HOMA (P < 0.024). Furthermore, BRS appeared to be significantly correlated with various elements of the metabolic syndrome, with CCA and abdominal obesity showing the strongest link. In an otherwise healthy population, BRS, but not spectrally derived indices of SA node autonomic regulation, are progressively reduced with increasing severity of insulin resistance, possibly as a consequence of attendant carotid artery thickening.

Plasma Adiponectin and Insulin Resistance in New Onset Hypertension

The data related to association among hypertension, insulin resistance, and plasma adiponectin concentration is controversial. We aimed to evaluate the relationships among these factors in a young hypertensive group who had no confounding factors. Thirty newly diagnosed and formerly untreated hypertensive males (mean age 23.4 +/- 4.0 yr; body mass index: 24.9 +/- 2.2 kg/m2), and 60 healthy control subjects (mean age 22.5 +/- 3.2 yr; body mass index: 24.6 +/- 1.6 kg/m2) were enrolled. Insulin resistance was calculated by homeostasis model assessment (HOMA). The two groups were similar in terms of age, body mass index, fasting glucose, total cholesterol, HDL and LDL cholesterol, adiponectin, insulin, HOMA, and hsCRP levels. Mean triglyceride levels in hypertensive patients were significantly higher than the controls (p = 0.02). These results indicate that young, newly diagnosed, uncomplicated patients with hypertension have similar plasma adiponectin levels and insulin sensitivities when compared to healthy controls. We suggest that high blood pressure itself may not be associated with insulin resistance or low adiponectin levels in patients with new onset, uncomplicated hypertension.

Interleukin-6–174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position −174 ( G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6–174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 –174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients ( p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C− (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C− carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6–174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance “IL-6-sensitive”, while C− carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.

Pioglitazone Treatment Increases Spontaneous Growth Hormone (GH) Secretion and Stimulated GH Levels in Polycystic Ovary Syndrome

Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood sampling for measurement of GH. Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant changes were observed in Ferriman Gallwey score or androgen levels. Pioglitazone treatment significantly increased GHRH-stimulated GH levels and 24-h pulsatile GH secretion, probably directly or indirectly due to improved insulin sensitivity.

Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome

Background. – In West of Scotland Coronary Prevention Study (WOSCOPS), development of type 2 diabetes mellitus (DM) was found to decrease by 30% in pravastatin-treated patients. In the study, it is suggested that pleiotropic effects of pravastatin may be responsible too as well as its lipid lowering effect. Objective. – The aim of this study was to assess the effects of pravastatin treatment on the insulin resistance in patients with metabolic syndrome with impaired glucose tolerance (IGT), by Homeostasis Model Assessment (HOMA) test, insulin sensitivity indices and glucose half activation time (glucose t1/2). Methods. – Study population consisted of 25 women who were diagnosed with metabolic syndrome. At baseline and 10 weeks after the 20 mg/daily tablet pravastatin treatment, waist/hip circumference, body weight and arterial blood pressure measurements, plasma glucose, total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol, transaminases, glycosylated haemoglobin (A1C) and insulin level measurements were obtained along with HOMA test and insulin tolerance test after 12 h of fasting. Insulin sensitivity indices and glucose t1/2 were assessed. Results. – After the treatment, a statistically significant decrease was observed in arterial blood pressure values ( P < 0.0001). While plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and triglyceride levels were found to decrease significantly and HDL-cholesterol levels increased significantly, a decrease in baseline insulin levels, an increase in insulin sensitivity levels were observed along with an decrease in glucose t1/2. Related to the improvement in aforementioned parameters, statistically significant decreases were noted in HOMA, postprandial and fasting glucose levels and A1C values ( P < 0.0001). Conclusion. – Our study suggests that using pravastatin in the dyslipidemia treatment of metabolic syndrome with IGT may be an effective approach by its advantageous effects on insulin resistance. Based on this result, it is possible to say that this can be a risk lowering treatment approach for the development of type 2 DM.

Magnesium, Insulin Resistance and Body Composition in Healthy Postmenopausal Women

Objective: This study was conducted to determine the association between magnesium (Mg), body composition and insulin resistance in 136 sedentary postmenopausal women, 50 to 77 years of age.Methods: Diabetics, hypertensives and women on hormonal replacement therapy were excluded and the remaining 74 were divided according to BMI≥25 (obese: OG) and BMI<25 kg/m2 (non-obese: NOG). Nutritional data disclosed that intakes were high for protein and saturated fat, low for carbohydrates, polyunsaturated fat and Mg and normal for the other nutrients, according to recommended dietary allowances (RDA). Mg values in red blood cells (RBC-Mg) and plasma (P-Mg), were determined, as were fasting glucose, and insulin levels, Homeostasis Model Assessment (HOMA), body mass index (BMI), body fat percent (BF %), abdominal fat (AF) and free fat mass (FFM).Results: RBC-Mg values were low in both groups when compared with normal values. There were significant differences in body composition parameters, HOMA and insulin levels, with higher basal insulin levels in OG. RBC-Mg was directly correlated with insulin, HOMA and FFM in both groups, according to Pearson correlations. HOMA in OG was also directly correlated with BMI, FFM and AF. In NOG, HOMA was only correlated with FFM. The low RBC-Mg levels observed were probably due to low Mg intake and to deregulation of factors that control Mg homeostasis during menopause.Conclusions: Both Mg deficit and obesity may independently lead to a higher risk for insulin resistance and cardiovascular disease.

Insulin sensitivity and hepatic steatosis in obese subjects with normal glucose tolerance

Hepatic steatosis has recently been associated with insulin resistance and other metabolic abnormalities as a possible feature of the metabolic syndrome, but it is still uncertain how hepatic steatosis and insulin sensitivity are connected. Furthermore, obesity is a well characterized insulin resistant condition that is often associated with hepatic steatosis. The aim of this study was to verify whether hepatic steatosis further worsens insulin sensitivity in obese subjects by comparing the degree of insulin sensitivity in obese subjects with normal glucose tolerance on the basis of the presence or absence of hepatic steatosis. We analyzed 86 obese patients whose alcohol intake was less than 20 g/day and who showed no signs of viral hepatopathy. All of the subjects had normal glucose tolerance as shown by an oral glucose tolerance test. Insulin resistance was estimated using the homeostasis model assessment (HOMA) method and the diagnosis of steatosis was determined by an ultrasound scan of the liver. The subjects were comparable in terms of body mass index (BMI), lipid profile and serum uric acid levels; those with hepatic steatosis were slightly older and tended to have higher systolic blood pressure and fasting glycemia levels. The HOMA values were significantly higher in the group with hepatic steatosis (4.48 +/- 2.22 vs 3.11 +/- 1.47, p=0.002). There was no linear correlation between HOMA and alanine aminotransferase (ALT) levels, but a close linear correlation between HOMA and BMI (r=0.40; p<0.001). The effect of hepatic steatosis on HOMA remained significant after adjusting for age and gender (covariance analysis, p=0.006). When BMI was added to the covariance analysis, hepatic steatosis retained its statistical significance. Our data suggest that hepatic steatosis can increase insulin resistance independently of obesity.

Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: A comparison of two distinct populations

Objectives: We sought to determine what differences, if any, existed between white and Mexican American women with polycystic ovary syndrome (PCOS) and whether the same values for fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment (HOMA) might be applied when screening both ethnic groups for insulin resistance. Study Design: Eighty-three consecutive women suspected to have PCOS but who demonstrated absence of other endocrine disorders comprised the study population. Nineteen healthy ovulatory women volunteered as controls. Fasting serum samples were obtained for determination of thyroid-stimulating hormone (TSH), prolactin, glucose, insulin, free and total testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate in the early proliferative phase. An oral glucose load was administered, and blood samples for glucose and insulin were drawn at 1, 2, and 3 hours. Those with impaired glucose tolerance or diabetes mellitus were excluded from our final study population. Four different groups were defined: (1) women with PCOS and insulin resistance, (2) women with PCOS without insulin resistance, (3) women with irregular cycles but without PCOS or another identifiable endocrinopathy, and (4) regular, cycling control subjects. Each group was subdivided by ethnicity (white or Mexican American). A total of 65 white and 37 Mexican American women were studied, including control subjects. Results: Among all study participants, Mexican American women with PCOS had significantly higher mean values for body mass index, fasting insulin, and HOMA but lower mean fasting glucose/insulin levels than white women. When group 1 patients (PCOS with insulin resistance) were compared between ethnic groups, mean fasting insulin and HOMA levels were significantly lower and glucose/insulin ratios higher in white than in Mexican American women. A single cutoff value for insulin resistance in PCOS was insensitive when applied to both ethnic groups. A fasting insulin value >20 μU/mL, HOMA value > 3.8, and glucose/insulin value <7.2 were reasonable screening values in our population of white women, whereas a fasting insulin value >23 μU/mL, HOMA value >4.5, and glucose/insulin ratio <4.0 were feasible screening values in Mexican American women. Conclusions: We conclude that (1) Mexican American women with PCOS are more insulin resistant than white women, (2) the incidence of insulin resistance is higher in Mexican American women with PCOS than in white women, (3) a single “screening” value for PCOS-related insulin resistance screening cannot be applied to both white and Mexican American women, and (4) normative values for insulin resistance screening in the PCOS population should be individualized for different racial or ethnic populations. (Am J Obstet Gynecol 2002;187:1362-9.)

The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking.

To evaluate the relationship between levels of serum insulin, the homeostasis model assessment (HOMA) and IGF-binding protein-1 (IGFBP-1) as factors related to myocardial infarction (MI) risk, and their interaction with lifestyle-related risk factors. The Stockholm epidemiology programme (SHEEP), a case-control study, consisting of 749 first-time MI cases (510 men, 239 women) and 1101 healthy controls (705 men, 396 women) was used. The risk of developing MI was assessed by calculating odds ratios (OR) and synergistic interactions (SI) between serum insulin, IGFBP-1, HOMA and other variables related to MI risk (including smoking) in men and women. Subjects with elevated levels of insulin and HOMA (>75th percentile) had increased MI risks when compared with individuals with low levels. ORs for elevated insulin and HOMA (adjusted for age and residential area) for men: insulin 1.6 (95% confidence interval (CI) 1.3-2.1) and HOMA 1.5 (95% CI 1.1-1.9) and for women: insulin 2.1 (95% CI 1.5-2.9) and HOMA 1.9 (95% CI 1.3-2.8). Women with low levels of IGFBP-1 (<10th percentile) showed a tendency towards elevated MI risk even if this was not statistically significant (OR 1.5 (95% CI 0.9-2.6)). Smokers with high levels of serum insulin had greatly increased MI risk (OR for men: 4.7 (95% CI 3.0-7.2) and OR for women: 8.1 (95% CI 4.5-14.8)). SI scores based upon these interactions were statistically significant. These results might have preventive cardiovascular implications as they clearly suggest that subjects with insulin resistance are particularly susceptible to the hazards of smoking.

Insulin resistance affects endothelium-dependent acetylcholine-induced coronary artery response.

This study was designed to investigate the relationship between insulin resistance and the acetylcholine-induced endothelium-dependent coronary artery response in patients without angiographically significant atherosclerotic coronary artery disease and to elucidate the pathophysiological significance of insulin resistance in the early stages of coronary atherosclerosis. Insulin resistance was calculated from fasting plasma glucose and insulin concentration using homeostasis model assessment in 40 patients suspected of having ischaemic heart disease, but without angiographic evidence of atherosclerotic coronary artery disease defined as a discrete stenosis or intimal irregularity. They were selected for an acetylcholine provocation test in both left and right coronary arteries. The homeostasis model assessment level was higher in 16 acetylcholine-positive patients than in 24 acetylcholine-negative patients (1.84+/-1.24 vs 0.72+/-0.62, P<0.01). Comparisons of the percentage change in vessel lumen diameter after the acetylcholine test in each of proximal, mid and distal segments of three coronary arteries among the three groups of low (less than 0.7; n=13), intermediate (0.7 to 1.4; n=13), and high homeostasis model assessment level (more than 1.4; n=14) revealed that a higher level resulted in a worse acetylcholine-induced constrictive response in coronary arteries. These results suggest that there is an association between high insulin resistance and coronary vascular endothelial cell dysfunction, and that insulin resistance may be an indicator of early stage coronary artery atherosclerosis not detectable by angiography.