Model Assessment Of Insulin Resistance Values Research Articles

Role of serum renalase levels in predicting the presence of metabolic syndrome in patients with polycystic ovary syndrome

ObjectiveThis study was designed to compare the serum renalase levels of polycystic ovary syndrome (PCOS) women with and without metabolic syndrome (MS) and those of healthy non-PCOS women. Materials and methodsSeventy-two patients diagnosed with PCOS and age-matched 72 healthy non-PCOS were included in the study. The PCOS group was divided into two groups as having metabolic syndrome or not. General gynecological and physical examination findings and laboratory results were recorded. Renalase levels in serum samples were determined using Enyzme-Linked ImmunoSorbent Assay method. ResultsMean serum renalase level was significantly higher in PCOS patients with MS compared with both PCOS patients without MS and healthy controls. Additionally, serum renalase correlates positively with body mass index, systolic and diastolic blood pressure, serum triglyceride and homeostasis model assessment-insulin resistance values among PCOS women. However, systolic blood pressure was found to be the only significant independent factor that can affect the serum renalase levels. A serum renalase level of 79.86 ng/L had a sensitivity of 94.7% and specificity of 46.4% in discriminating PCOS patients with metabolic syndrome from healthy women. ConclusionsSerum renalase level increases in women with PCOS in the presence of metabolic syndrome. Therefore, monitoring the serum renalase level in women with PCOS can predict the metabolic syndrome that may develop.

The self-nanoemulsifying drug delivery system of Petiveria alliacea extract reduced the homeostatic model assessment-insulin resistance value, interleukin-6, and tumor necrosis factor-α level in diabetic rat models.

Background and Aim:Metaflammation plays a significant role in the pathogenesis, development, and complication of diabetes mellitus (DM). This inflammation is associated with insulin resistance. Therefore, the inflammatory pathways have been targeted for pharmacological treatment. Petiveria alliacea can decrease blood glucose levels and has anti-inflammatory and antioxidant activities; however, there are still insufficient data regarding its efficacy for the treatment of DM. This study aimed to investigate the effect of the self-nanoemulsifying drug delivery system (SNEDDS) of P. alliacea leaf extract on the homeostatic model assessment (HOMA)-insulin resistance (IR) value and interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels in a streptozotocin (STZ)-induced diabetic rat model.Materials and Methods:Thirty-five diabetic rat models were randomly divided into five groups. The first group received the SNEDDS of P. alliacea leaf extract at a dose of 50 mg/kg body weight (BW), the second group received it at a dose of 100 mg/kg BW, the third group received it at a dose of 200 mg/kg BW, the fourth group received 18 mg of metformin, and the fifth group only received the SNEDDS formula. The treatment was administered once a day, orally, for 14 days. On the 15th day after treatment, the rats were sacrificed to obtain blood samples for cardiac examination. The IL-6, TNF-α, and insulin levels in the serum were measured using the enzyme-linked immunosorbent assay method. The HOMA-IR value was calculated using a formula.Results:The mean IL-6 and TNF-α levels were low in the group that received the SNEDDS of P. alliacea leaf extract. There was no significant difference in the insulin level in all treatment and control groups. However, a significant difference in the HOMA-IR value was noted between the group that received the SNEDDS of P. alliacea leaf extract and metformin and the group that did not receive treatment (p<0.05).Conclusion:The SNEDDS of P. alliacea leaf extract reduced the HOMA-IR value and suppressed the TNF-α and IL-6 levels in the STZ-induced diabetic rat model.

Reduced Free Fatty Acid Receptor 4 Gene Expression is Associated With Extreme Obesity and Insulin Resistance in Children.

Free fatty acid receptor 4 (FFAR4) is a G-protein-coupled membrane receptor highly expressed in macrophages that triggers anti-inflammatory effects and promotes insulin sensitization. We have previously found significant associations between the FFAR4 rs11187533 single nucleotide polymorphism (SNP) and various obesity comorbidity parameters. We aimed to verify the FFAR4 expression levels in children with obesity and the associated comorbidities. Thirty-eight children with obesity were studied. Clinical and anthropometric evaluation was performed. A venous sample under fasting conditions was obtained. Biochemical study included parameters of metabolic risk. DNA was extracted and genotyped for the rs11187533 FFAR4 SNP. Real-time PCR technique was performed to investigate the gene expression. Relative FFAR4 mRNA levels were determined according to the 2-ΔΔCt method. Significant differences in FFAR4 expression levels between the CC and CT-TT genotypes of the rs11187533 FFAR4 SNP were observed (P = 0.034). The minor allele T presented higher levels of FFAR4 expression. We found that a loss of FFAR4 expression was associated with extreme obesity (P = 0.032). The lowest FFAR4 expression levels were observed in children who had higher insulin (P = 0.008) and homeostasis model assessment insulin resistance values (P = 0.012) and lower quantitative insulin-sensitivity check index (P = 0.033). The underexpression of FFAR4 was associated with extreme obesity and parameters indicative of obesity comorbidities in children. This under expression could be partially influenced by the presence of the C allele rs11187533 FFAR4 SNP.

Effect of Yoga Therapy on Health Outcomes in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

The purpose of this study was to assess the effect of yoga therapy (YT) on health outcomes of women suffering from polycystic ovary syndrome (PCOS). Interventional studies, with postmenarchal and premenopausal females with PCOS who received YT, with any health outcome reported, were included. Scopus, Cochrane, PubMed, Embase, and Medline databases were electronically searched. Systematic review included 11 experimental studies, representing 515 participants with PCOS, out of which 2 randomized controlled trials (RCTs) were included for meta-analysis. Random effects model was applied using Review Manager Software version 5.4.1 and strength of evidence was assessed using GRADEpro Guideline Development Tool, 2020. Meta-analysis showed that YT may significantly decrease menstrual irregularity (MD -.41, 95% CI -.74 to -.08), clinical hyperandrogenism (MD -.70, 95% CI -1.15 to -.26), fasting blood glucose (MD -.22mmol/L, 95% CI -.44 to -.01), fasting insulin (MD -28.21pmol/L, 95% CI -43.79 to -12.63), and homeostatic model assessment-insulin resistance value (MD -.86, 95% CI -1.29 to -.43). Strength of evidence was "low." In conclusion, YT may have beneficial effects on health outcomes in women suffering from PCOS. However, low strength of evidence suggests need of conducting well-designed RCTs to assess the efficacy of YT for PCOS.

Lipid indices as simple and clinically useful surrogate markers for insulin resistance in the U.S. population

This study aimed to compare the accuracy of novel lipid indices, including the visceral adiposity index (VAI), lipid accumulation product (LAP), triglycerides and glucose (TyG) index, TyG-body mass index (TyG-BMI), and TyG-waist circumference (TyG-WC), in identifying insulin resistance and establish valid cutoff values. This cross-sectional study used the data of 11,378 adults, derived from the United States National Health and Nutrition Examination Survey (1999–2016). Insulin resistance was defined as a homeostasis model assessment-insulin resistance value above the 75th percentile for each sex and race/ethnicities. The area under the curves (AUCs) were as follows: VAI, 0.735; LAP, 0.796; TyG index, 0.723; TyG-BMI, 0.823, and; TyG-WC, 0.822. The AUCs for TyG-BMI and TyG-WC were significantly higher than those for VAI, LAP, and TyG index (vs. TyG-BMI, p < 0.001; vs. TyG-WC, p < 0.001). The cutoff values were as follows: VAI: men 1.65, women 1.65; LAP: men 42.5, women 42.5; TyG index: men 4.665, women 4.575; TyG-BMI: men 135.5, women 135.5; and TyG-WC: men 461.5, women 440.5. Given that lipid indices can be easily calculated with routine laboratory tests, these values may be useful markers for insulin resistance risk assessments in clinical settings.

Obesity of Sows at Late Pregnancy Aggravates Metabolic Disorder of Perinatal Sows and Affects Performance and Intestinal Health of Piglets.

Simple SummaryOur novel findings suggest that excessive backfat thickness of sows at days 109 of gestation exacerbates the metabolic disorder of perinatal sows, reduces the number and litter weight of piglets born alive, and adversely affects the intestinal health of sows and their offspring piglets. Moreover, the current study also provides an important theoretical reference for strengthening the control of body condition in sows during reproductive cycle.This study explored the effect of obesity of sows in late pregnancy on metabolic status of perinatal sows and performance, intestinal health, and immune system of offspring piglets. Sixty multiparous Landrance × Large White sows were selected in this study. Sows were divided into two groups according to backfat thickness (normal backfat thickness group, =17 mm; excessive backfat thickness group, ≥21 mm) at days 109 of gestation. The excessive backfat thickness of sows during late pregnancy decreased the total number and litter weight of piglets born alive. Compared with normal backfat thickness sows, the excessive backfat thickness sows had increased levels of plasma glucose, IL-6, and TNF-α and homeostasis model assessment insulin resistance values. The excessive backfat thickness also reduced total superoxide dismutase but increased thiobarbituric acid reactive substances in plasma of perinatal sows. Additionally, the fecal levels of TNF-α were increased but those of IL-10 were decreased in piglets from excessive backfat thickness sow. These findings indicate that the obesity of sows during late pregnancy aggravates the metabolic disorder of perinatal sows, reduces the number of piglets born alive, and adversely affects the intestinal health of sows and their offspring piglets.

Whole Grain Intake and Glycaemic Control in Healthy Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Backgrounds: There is growing evidence from both observational and intervention studies that Whole Grain (WG) cereals exert beneficial effects on human health, especially on the metabolic profile. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCT) to assess the acute and medium/long-term effect of WG foods on glycaemic control and insulin sensitivity in healthy individuals. Methods: A search for all the published RCT on the effect of WG food intake on glycaemic and insulin response was performed up to December 2016. Effect size consisted of mean difference (MD) and 95% CI between the outcomes of intervention and the control groups using the generic inverse-variance random effects model. Results: The meta-analysis of the 14 studies testing the acute effects of WG foods showed significant reductions of the post-prandial values of the glucose iAUC (0–120 min) by −29.71 mmol min/L (95% CI: −43.57, −15.85 mmol min/L), the insulin iAUC (0–120 min) by −2.01 nmol min/L (95% CI: −2.88, −1.14 nmol min/L), and the maximal glucose and insulin response. In 16 medium- and long-term RCTs, effects of WG foods on fasting glucose and insulin and homeostatic model assessment-insulin resistance values were not significant. Conclusions: The consumption of WG foods is able to improve acutely the postprandial glucose and insulin homeostasis compared to similar refined foods in healthy subjects. Further research is needed to better understand the long-term effects and the biological mechanisms.

Chronic binge alcohol administration impairs glucose-insulin dynamics and decreases adiponectin in asymptomatic simian immunodeficiency virus-infected macaques.

Alcohol use disorders (AUDs) frequently exist among persons living with HIV/AIDS. Chronic alcohol consumption, HIV infection, and antiretroviral therapy (ART) are independently associated with impairments in glucose-insulin dynamics. Previous studies from our laboratory have shown that chronic binge alcohol (CBA) administration decreases body mass index, attenuates weight gain, and accentuates skeletal muscle wasting at end-stage disease in non-ART-treated simian immunodeficiency virus (SIV)-infected male rhesus macaques. The aim of this study was to investigate whether CBA and ART alone or in combination alter body composition or glucose-insulin dynamics in SIV-infected male rhesus macaques during the asymptomatic phase of SIV infection. Daily CBA or sucrose (SUC) administration was initiated 3 mo before intrarectal SIV inoculation and continued until the study end point at 11 mo post-SIV infection. ART or placebo was initiated 2.5 mo after SIV infection and continued until study end point. Four treatment groups (SUC/SIV ± ART and CBA/SIV ± ART) were studied. CBA/SIV macaques had significantly decreased circulating adiponectin and resistin levels relative to SUC/SIV macaques and reduced disposition index and acute insulin response to glucose, insulin, and C-peptide release during frequently sampled intravenous glucose tolerance test, irrespective of ART status. No statistically significant differences were observed in homeostatic model assessment-insulin resistance values, body weight, total body fat, abdominal fat, or total lean mass or bone health among the four groups. These findings demonstrate CBA-mediated impairments in glucose-insulin dynamics and adipokine profile in asymptomatic SIV-infected macaques, irrespective of ART.

Periodontitis contributes to aberrant metabolism in type 2 diabetes mellitus rats by stimulating the expression of adipokines.

Periodontitis has been associated with type 2 diabetes mellitus. We investigated the effects of local aberrant secretion of adipokines in diabetic rats on systemic metabolism. Otsuka Long-Evans Tokushima Fatty (OLETF) and non-diabetic Long-Evans Tokushima Otsuka rats were used as a diabetic model and associated control, respectively. Periodontitis was induced using a silk ligature for 36 wk. Rats were grouped into OLETF with (OP+) or without (OP-) periodontitis and Long-Evans Tokushima Otsuka with (LP+) or without (LP-) periodontitis. Alveolar bone resorption and destruction were evaluated by micro-computed tomography and hematoxylin and eosin staining. After 20 wk of periodontitis induction, lipids, insulin, interleukin-1, leptin and plasminogen activator inhibitor-1 were analyzed, and mRNA expressions of NF-κB, Mark8, TLR2 and -4, IKBKB and Nampt were evaluated by quantitative polymerase chain reaction in adipose tissue. After ligation, OLETF rats exhibited typical periodontitis lesions with the clinical features of type 2 diabetes mellitus. When compared with the OP(-) group, the area under curve of the oral glucose tolerance test and homeostatic model assessment-insulin resistance values were significantly higher in the OP(+) group. Micro-computed tomography showed that the OP(+) group had more bone resorption than the OP(-) group. When compared with the OP(-) group, the OP(+) group also exhibited higher total cholesterol (p < 0.05), leptin (p < 0.05), insulin (p > 0.05) and higher expression of Nampt (p < 0.05) and IKBKB (p < 0.05). The LP(+) group had a trend towards higher bone resorption when compared with the LP(-) group. Additionally, no difference in white adipose tissues or adipokines was found between LP(+) and LP(-) rats. Chronic periodontitis can alter lipid profiles in affected rats, elevate adipose tissue expression of Nampt and affect the metabolism of adipose tissue through the NF-κB pathway to inflame diabetes.

Epigenomic profiling in visceral white adipose tissue of offspring of mice exposed to late gestational sleep fragmentation.

BackgroundSleep fragmentation during late gestation (LG-SF) is one of the major perturbations associated with sleep apnea and other sleep disorders during pregnancy. We have previously shown that LG-SF induces metabolic dysfunction in offspring mice during adulthood.ObjectivesTo investigate the effects of late LG-SF on metabolic homeostasis in offspring and to determine the effects of LG-SF on the epigenome of visceral white adipose tissue (VWAT) in the offspring.MethodsTime-pregnant mice were exposed to LG-SF or control sleep (LG-SC) conditions during the last 6 days of gestation. At 24 weeks of age, lipid profiles and metabolic parameters were assessed in the offspring. We performed large-scale DNA methylation analyses using MeDIP coupled to microarrays (MeDIP-chip) in VWAT of 24-week-old LG-SF and LG-SC offspring (n=8 mice/group). Univariate multiple-testing adjusted statistical analyses were applied to identify differentially methylated regions (DMRs) between the groups. DMRs were mapped to their corresponding genes, and tested for potential overlaps with biological pathways and gene networks.ResultsWe detected significant increases in body weight (31.7 vs. 28.8 g; p=0.001), visceral (642.1 vs. 497.0 mg; p=0.002) and subcutaneous (293.1 vs. 250.1 mg; p=0.001) fat mass, plasma cholesterol (110.6 vs. 87.6 mg/dL; p=0.001), triglycerides (87.3 vs. 84.1 mg/dL; p=0.003) and HOMA-IR values (8.1 vs. 6.1; p=0.007) in the LG-SF group. MeDIP analyses revealed that 2148 DMRs (LG-SF vs. LG-SC; p< 0.0001, MAT algorithm). A large proportion of the DMR-associated genes have reported functions that are altered in obesity and metabolic syndrome, such as Cartpt, Akt2, Apoe, Insr1, etc. Overrepresented pathways and gene networks were related to metabolic regulation and inflammatory response.ConclusionsOur findings show a major role for epigenomic regulation of pathways associated with metabolic processes and inflammatory response in VWAT. LG-SF-induced epigenetic alterations may underlies increases in the susceptibility to obesity and metabolic syndrome in offspring.

Relationship between 1,25-dihydroxy Vitamin D levels and homeostatic model assessment insulin resistance values in obese subjects.

In this study, our aim is to evaluate the insulin resistance and quality of life in obese subjects and nonobese subjects and to find out the Vitamin D (VD) status and correlations between obesity and control groups and also according to their quality of life scores. The study was carried out between May and October 2013 which is the period of VD synthesis in Turkey. The participants of this study were volunteering individuals - obese and nonobese individuals defined according to the body mass index (BMI) - that did not receive any VD support in the last 1-year and did not have any known chronic diseases. 1,25-OH VD status and homeostatic model assessment insulin resistance (HOMA-IR) values were evaluated. The study population consisted of 39 individuals with normal weight (23 women, 16 men) and 66 individuals categorized as obese (51 women, 15 men). The difference in HOMA-IR and VD values between the group of obese individuals and the group of nonobese individuals was significant (P < 0.001 vs. P <0.001). The median value of HOMA-IR was higher in the obese group than in the nonobese group (P < 0.001) while the median value of VD was higher in the nonobese group than in the obese group (P < 0.001). The results regarding the relationship of BMI with HOMA-IR and VD show that there was a positive correlation between HOMA-IR and BMI (rs = 0.507; P < 0.001) and there was a negative correlation between HOMA-IR and VD (rs = -0.316; P = 0.0001). Given serious diseases associated with low serum VD levels such as diabetes and cardiovascular disorders as well as low side effect incidence and low cost of VD treatment, it would be a reasonable approach to identify routine serum 25(OH) D and/or 1,25-OH VD levels of obese patients and administer a treatment to patients with low levels of VD.

Predictive Risk Factors in the Treatment of Gestational Diabetes Mellitus.

OBJECTIVEThis study aims to investigate predictive risk factors in the treatment of gestational diabetes mellitus (GDM).PATIENTS AND METHODSA total of 256 pregnant women who underwent 75 g oral glucose tolerance test (OGTT) during 24–28 weeks of pregnancy were included according to the World Health Organization criteria. Demographic characteristics of the patients, including age, parity, family history of diabetes, body weight before pregnancy, and body weight at the diagnosis of GDM, were recorded. Fasting insulin and hemoglobin A1c (HbA1c) values at the time of diagnosis were evaluated. The patients were divided into two groups: those requiring insulin treatment (insulin group, n = 89) and those receiving diet therapy (diet group, n = 167) during pregnancy according to the American Diabetes Association recommendations.RESULTSA total of 34.76% of the pregnant women with GDM required insulin treatment. The mean age of these patients was significantly higher compared to the diet group (34.9 ± 0.6 years vs. 31.9 ± 0.6 years; P = 0.004). Body mass index before pregnancy was also significantly higher in the insulin group than that in the diet group (32 ± 0.9 kg/m2 vs. 29 ± 0.7 kg/m2; P = 0.004). Fasting blood glucose (FBG) during OGTT was 105.6 ± 2.1 mg/dL and 96.7 ± 1.1 mg/dL in the insulin group and diet group, respectively (P < 0.001). There was no significant difference in fasting plasma glucose during OGTT between the groups (P = 0.069), while plasma glucose at two hours was 161.1 ± 6.8 mg/dL in the insulin group and 145.1 ± 3.7 mg/dL in the diet group (P = 0.027). At the time of diagnosis, HbA1c values were significantly higher in the insulin group compared to the diet group (5.3 ± 0.1 vs. 4.9 ± 0.1; P = 0.001). There was no significant difference in FBG and homeostasis model assessment-insulin resistance values between the groups (P = 0.908, P = 0.073).CONCLUSIONOur study results suggest that age, family history of diabetes, body weight before pregnancy, FBG, and HbA1c values are predictors for the necessity of insulin treatment.

Effect of oat intake on glycaemic control and insulin sensitivity: a meta-analysis of randomised controlled trials.

The present meta-analysis of randomised controlled trials (RCT) aimed to investigate the effect of oat intake on glycaemic control and insulin sensitivity. A literature search was carried out in PubMed, ScienceDirect Online and The Cochrane Library (up to October 2013) for RCT that assessed the effect of oat intake on glucose control and insulin sensitivity. A total of fifteen articles with 673 subjects met the inclusion criteria. A random-effects model was used when the overall pooled studies exhibited significant heterogeneity. Otherwise, a fixed-effects model was used. Compared with controls, oat intake significantly reduced the concentrations of fasting insulin by - 6·29 (95 % CI - 12·32, - 0·27) pmol/l (P= 0·04) and the values of glucose AUC (GAUC; 0-120 min) by - 30·23 (95 % CI - 43·65, - 16·81) min × mmol/l (P< 0·0001). There was a slight decrease in fasting glucose concentrations, glycated Hb concentrations and homeostatic model assessment-insulin resistance values in subjects who consumed oats, but the difference was not significant. In conclusion, oat intake significantly lowers fasting insulin concentrations and GAUC values. To further investigate the effect of oat intake on fasting glucose concentrations, additional long-term and high-quality RCT with a parallel design are required.

Coronary flow velocity reserve is impaired in hypertensive patients with hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) is an independent risk factor for coronary artery disease. Chronic HHcy induces coronary endothelial injury, and homocysteine (Hcy) inhibits insulin sensitivity by inducing endoplasmic reticulum stress in adipose tissue. However, the combined effects of chronic HHcy and hypertension on coronary artery endothelial function have still remained unclear. Fifty-one patients with essential hypertension (HT) were recruited, and were divided into nHT group (without HHcy) and H-type HT group (with HHcy). Forty healthy subjects were enrolled as controls. We assessed coronary artery endothelial function by coronary flow velocity reserve (CFVR). Hcy levels were significantly higher (15.60±6.58 vs 13.08±4.13 μmol l(-1), P<0.05), whereas CFVR values were significantly lower in the HT patients than in the control group (2.88±0.70 vs 3.23±0.54, P<0.05). Hcy levels were negatively correlated with CFVR value (r=-0.578, P<0.01, 95% confidence interval -0.085 to -0.046). The homeostasis model assessment-insulin resistance values were significantly higher (3.92±2.16 vs 2.72±1.50, P<0.05) , whereas CFVR values were significantly lower in H-type HT group than in nHT group (2.31±0.31 vs 3.25±0.62, P<0.01). Coronary artery endothelial function may be impaired in essential hypertensive patients with HHcy, and insulin resistance induced by HHcy may contribute to this damage.

Does Homeostasis Model Assessment Insulin Resistance Have a Predictive Value for Post-Coronary Artery Bypass Grafting Surgery Outcomes?

ObjectiveThis study aims to investigate whether pre-operative Homeostasis Model Assessment Insulin Resistance (HOMA-IR) value is a predictor in non-diabetic coronary artery bypass grafting patients in combination with hemoglobin A1c, fasting blood glucose and insulin levels.MethodsEighty one patients who were admitted to Cardiovascular Surgery Clinic at our hospital between August 2012 and January 2013 with a coronary artery bypass grafting indication were included. Patients were non-diabetic with <6.3% hemoglobin A1c and were divided into two groups including treatment and control groups according to normal insulin resistance (HOMA-IR<2.5, Group A; n=41) and high insulin resistance (HOMA-IR>2.5, Group B; n=40), respectively. Pre-operative fasting blood glucose and insulin were measured and serum chemistry tests were performed. The Homeostasis Model Assessment Insulin Resistance values were calculated. Statistical analysis was performed.ResultsThere was a statistically significant difference in fasting blood glucose and HOMA-IR values between the groups. Cross-clamping time, and cardiopulmonary bypass time were longer in Group B, compared to Group A (P=0.043 and P=0.031, respectively). Logistic regression analysis revealed that hemoglobin A1c was not a reliable determinant factor alone for pre-operative glucometabolic evaluation of non-diabetic patients. The risk factors of fasting blood glucose and cardiopulmonary bypass time were more associated with high Homeostasis Model Assessment Insulin Resistance levels.ConclusionOur study results suggest that preoperative screening of non-diabetic patients with Homeostasis Model Assessment Insulin Resistance may improve both follow-up visit schedule and short-term outcomes, and may be useful in risk stratification of the high-risk population for impending health problems.

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux. Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P=0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (P<0.001), directly with arterial insulin concentration (P<0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P=0.044). Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level

SummaryIn agreement with the results of animal studies, the plasma osteocalcin level is positively associated with improved glucose tolerance and insulin secretion and sensitivity. In addition, the plasma osteocalcin level is inversely associated with the development of diabetes; however, the plasma adiponectin level may not be involved in osteocalcin-mediated energy metabolism in humans.IntroductionRecent animal studies have suggested crosstalk between bone and energy metabolism through osteocalcin. The aims of this study were to determine whether or not osteocalcin is associated with the improved glucose tolerance and insulin secretion and sensitivity, and whether or not the association is dependent on the plasma adiponectin level in humans.MethodsFour hundred twenty-five subjects, 19–82 years of age (mean age, 53 years), were enrolled. An oral glucose tolerance test (OGTT) and OGTT-based methods that were validated against the euglycemic clamp were determined. Total osteocalcin, leptin, and total adiponectin levels were measured.ResultsThe plasma levels of total osteocalcin were significantly different between the normal glucose tolerance, pre-diabetes, and diabetes groups. The glucose levels and homeostasis model assessment insulin resistance values varied inversely with the osteocalcin tertiles, and OGTT-based insulin secretion (HOMA-B%, disposition index) and insulin sensitivity indices (Stumvoll’s and OGIS indices) were increased with the tertiles. Although the plasma adiponectin level was positively correlated with the osteocalcin level, no changes in the association were noted between the plasma osteocalcin level and the glucose tolerance or insulin secretion and sensitivity indices after adjustment for the plasma adiponectin level. Based on multiple logistic regression analysis, the plasma osteocalcin level was inversely associated with the development of type 2 diabetes mellitus independent of age, gender, body mass index, and fasting plasma glucose and plasma adiponectin levels.ConclusionsCirculating osteocalcin level is associated with improved glucose tolerance and insulin secretion and sensitivity independent of the plasma adiponectin level in humans.

Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal incidentalomas: a cause-effect relationship?

The objective of the study was to assess insulin resistance (IR) and metabolic syndrome (MS) in patients with nonfunctioning adrenal incidentalomas (NFAIs). Among a total cohort of 46 patients with adrenal incidentalomas, we studied 29 patients with NFAIs (mean age, 54 ± 9 years; body mass index, 29 ± 3 kg/m 2) and 37 age-, sex-, and body mass index–matched healthy controls. Besides the endocrine workup, IR was evaluated using fasting glucose and insulin concentrations, homeostasis model assessment of IR, and quantitative insulin sensitivity check index. In a subgroup of patients undergoing an oral glucose tolerance test, Matsuda index and total area under the curve for glucose and insulin were also evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and other biochemical parameters were measured with standard techniques. Body composition was determined with dual-energy x-ray absorptiometry. Patients with NFAIs exhibited higher fasting glucose, insulin, and homeostasis model assessment of IR values; decreased quantitative insulin sensitivity check index and Matsuda index; and an increased—although not statistically significant—area under the curve for glucose and insulin compared with controls ( P < .05). In addition, they exhibited higher systolic and diastolic blood pressure, triglycerides, and γ-glutamyltransferase and lower high-density lipoprotein cholesterol levels compared with controls ( P < .05). Patients with NFAIs were all obese with a central type of fat accumulation and increased appendicular lean mass. Indices of IR showed a positive correlation with indices of MS ( P < .05), but no correlation with markers of hormonal activity. Nonfunctioning adrenal incidentalomas are characterized by IR, hypertension, dyslipidemia, and fatty liver disease, all of them being components of MS. Thus, patients with NFAIs should be screened for MS during their initial workup to identify those at cardiometabolic risk and implement the appropriate interventions.