Tertile Of HOMA-IR Research Articles

Assessment HOMA as a predictor for new onset diabetes mellitus and diabetic complications in non-diabetic adults: a KoGES prospective cohort study

BackgroundHomeostasis model assessment for insulin resistance (HOMA-IR) is a biomarker for type 2 diabetes mellitus (T2DM). However, the role of HOMA-IR in the non-diabetic is unclear. This study aimed to determine whether IR measured HOMA-IR value is associated with new onset diabetes as well as vascular disease and can be used as an early predictor for diabetes and vascular diseases in non-diabetic participants.MethodsFrom a prospective community-based cohort of 10,030 individuals, 4314 individuals younger than 65 years and without diabetes were enrolled and divided into three groups by baseline HOMA-IR tertiles: low (n = 1454), moderate (n = 1414), and high (n = 1446). The primary outcome was new onset T2DM. Secondary outcomes were chronic kidney disease (CKD) and a composite of coronary artery disease, myocardial infarction, and stroke as macrovascular events.ResultsThe mean age was 51 years. The prevalence of hypertension and cholesterol and HbA1c were higher in the high HOMA-IR group. New onset T2DM (5.8%) and CKD (12.2%) incidence in the high HOMA-IR group was higher than that in the others. The prevalence of macrovascular events did not differ among groups. High-HOMA-IR was an independent risk factor for new onset T2DM (odds ratio 1.86 [1.17–2.96]; p = 0.01) and CKD (1.49 [1.12–1.98]; p = 0.01).ConclusionsHigh HOMA-IR was an early predictor of new onset T2DM and CKD, regardless of HbA1c in non-diabetic individuals. Further research on the specific cut off value will be needed.

Prognostic value of insulin resistance and hyperglycemia biomarkers for long-term risks of cardiometabolic outcomes

We found that individuals in the top tertile of HOMA-IR and with HbA1c-defined prediabetes have elevated risk of cardiometabolic outcomes.

2263-PUB: Consideration of Insulin Resistance Improves HbA1c-Based Type 2 Diabetes Risk Assessment

Background: T2D risk assessment is typically based on fasting glucose (FG) and HbA1c levels. We tested the hypothesis that HbA1c-based T2D risk assessment is improved by also considering another physiological axis, insulin resistance (IR), assessed using a fasting insulin (FI) homeostasis model (HOMA-IR). Methods: We followed 2,205 white individuals from the Framingham Heart Study without T2D (medication use or FG >=126 mg/dL) at baseline for a mean of 16 years. We used age-sex adjusted regression to model incident T2D as a function of baseline HbA1c and IR tertile of HOMA-IR (FI x FG/22.5). Results: Of 266 incident T2D cases, 205 (77%) were in HOMA-IR tertile 3, and of these, 135 (66% of 205) had HbA1c <5.7 (Table). Individuals in HOMA-IR tertile 3 had 16-year T2D CI rates of 20-35%. Both HbA1c and IR were independently associated with elevated incident T2D risk. We saw similar patterns in the 1,583 individuals with baseline FG <100 mg/dL. Conclusion: HbA1c and fasting insulin are commonly available clinical diagnostic tests. Combined consideration of high levels of both identifies the great majority of white individuals at highly increased risk for future T2D. Disclosure J.B. Meigs: Consultant; Self; Quest Diagnostics. B.C. Porneala: None. A. Leong: None. D. Shiffman: Employee; Self; Quest Diagnostics. J. Devlin: Employee; Self; Quest Diagnostics. M.J. McPhaul: Employee; Self; Quest Diagnostics.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease.

Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.

Healthy excessive weight in Portuguese women 4 years after delivery of a liveborn

ObjectiveTo quantify the prevalence of healthy excessive weight and determinants of metabolic profile, considering women's reproductive life. MethodsWe evaluated 1847 mothers of a birth cohort assembled after delivery and reevaluated 4years later. A healthy profile was defined as the absence of hypertension, diabetes, dyslipidemia, C-reactive protein <3mg/l and being below the second tertile of HOMA-IR. Adjusted odds ratios (OR) and confidence intervals (95% CI) were computed using multinomial logistic regression, taking women with normal BMI as the reference category of the outcome. ResultsFour years after delivery, 47% of women had normal BMI, 33% were overweight and 20% obese. In each BMI class, 61%, 33% and 12% presented a healthy metabolic profile, respectively. Family history of CVD/cardiometabolic risk factors was associated with a higher probability of obesity with a not healthy metabolic profile (OR=1.39 95% CI: 0.98–1.98). Women who breastfed the enrolled child for >26weeks and practiced physical exercise were less likely to be obese and metabolically unhealthy (OR=0.39 95% CI: 0.23–0.68; OR=0.48 95% CI: 0.33–0.70, respectively), with no effect on healthy excessive weight. ConclusionsThese results support the existence of a healthy excessive weight phenotype in women after motherhood, influenced by anthropometrics, genetic and lifestyles characteristics.

Long-Term Safety and Efficacy of Mipomersen in Patients with Familial Hypercholesterolemia Uncontrolled by Maximally Tolerated Lipid Lowering Therapy

s 291 Apo B, P , .0001 for all; Table 1). Age $65 years, abdominal obesity, and lower baseline high-sensitivity C-reactive protein (hs-CRP) were significant predictors of greater reductions in LDL-C, non-HDL-C, Apo B, total C, VLDL-C, TGs, and all lipid-lipoprotein ratios but not for changes in HDL-C or ApoAI. Age $65 years was associated with significantly greater attainment of LDL-C (,70 mg/dL, ,100 mg/dL) and non-HDL-C (,100 mg/dL, ,130 mg/dL) targets; abdominal obesity predicted higher attainment of nonHDL-C ,130 mg/dL, and lower baseline hs-CRP was associated with greater attainment of LDL-C ,70 mg/ dL and non-HDL-C ,100 mg/dL. The number of MetS factors (1-5) did not predict LDL-C–lowering treatment efficacy. Effects of gender, race, baseline TGs, baseline HDL-C, and concomitant therapy were limited. MetS, diabetes, blood pressure, fasting glucose, and HOMA IR tertiles were not predictive of any treatment response. Conclusions: This post hoc study in MetS subjects with CHD risk identified age $65 years, abdominal obesity, and lower baseline hs-CRP as factors that significantly influence treatment effects of E/S and atorvastatin on changes in LDL-C, non-HDL-C and Apo B, the current treatment targets suggested for reduction of CMR. The clinical benefits of simvastatin and atorvastatin have been established; the effect of ezetimibe on cardiovascular outcomes awaits results from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial.

Abstract P028: Higher Waist Circumference Identifies Insulin Resistance in Middle-age African-American Women Compared to Standard Metabolic Waist Thresholds for Europeans.

Introduction Waist circumference thresholds that predict insulin resistance (IR) or metabolic syndrome may differ by race and ethnicity. Notably, a recent analysis of data from young African American (AA) adults (age 35±8) indicated that for AA women, the waist circumference (WC) predicting the top tertile of IR (mean HOMA-IR=3.0) was higher (≥98cm) than the IDF and NCEP-ATPIII threshold (≥88cm) for central obesity of metabolic syndrome. Hypothesis This analysis tested the hypothesis that in middle-aged AA adults, the WC predicting IR would be similar to that found in young AA adults: in AA women, a higher WC would predict IR than the standard WC threshold for metabolic syndrome. Methods Participants were AA adults attending the first examination of the Jackson Heart Study (2000-2004). After restricting analysis to non-related persons, non-diabetic, ages 35-80, BMI 18.5-55, with non-missing HOMA-IR, the analytical data set comprised 2269 persons (1374 women); age 55±11 (mean±SD); HOMA-IR 3.6±2.2; BMI 31±6.4 kg/m 2 ; WC: women: 98.3±15.6cm, men: 100.2 ±13.7cm. By ROC analysis, WC was a significantly better predictor of HOMA-IR than BMI for women but not men, although the predictive Area Under the Curve (AUC) was greater for men than women for both variables: AUC for WC vs.BMI: 0.78 vs 0.77 for men (p=.13); 0.75 vs 0.72 for women (p&lt;.02). Due to lack of international standardization for insulin measures, IR was defined as the upper tertile (≥3.8) or upper quartile (≥4.4) of HOMA-IR. Mean HOMA-IR for the upper tertile was 5.9. For various thresholds of waist, the Youden index (sensitivity + specificity - 1) was calculated, as well as Pos Pred Value (PPV), Neg Pred Value (NPV), and diagnostic accuracy (DA) (prevalence*sensitivity + (1-prevalence)*specificity). The WC threshold that maximized the Youden index was considered the most appropriate for determining IR. Results The Youden index for predicting IR by WC maximized at 96cm for women and 104cm for men, with IR defined either as the upper tertile or the upper quartile of HOMA-IR. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy were necessarily affected by the definition of IR that determined prevalence; using the upper tertile of HOMA-IR to define IR, optimized WC thresholds had DA =0.66 for women and 0.74 for men. Conclusions The WC thresholds for identifying the top tertile of IR (96cm women; 104cm men) were comparable to those found for younger AA adults in a previous study (98cm women; 102cm men), notwithstanding the much higher mean HOMA-IR (5.9) of the upper tertile in this middle-aged group, compared to that (3.0) of the younger AA adults of the earlier study. For middle-age AA women, this analysis confirmed the finding of the earlier study of younger AA women, in that the waist circumference threshold identifying insulin resistance in AA women may be higher than that defining metabolic syndrome-related waist circumference in European women.

Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke

OBJECTIVEInsulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis.RESEARCH DESIGN AND METHODSWe performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points.RESULTSA total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67–43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23–54.44]; P = 0.029).CONCLUSIONSHigh IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.

Arterial Stiffness is Strongly Associated with Insulin Resistance in Chinese &amp;mdash;A Population-Based Study (Taichung Community Health Study, TCHS)

Few studies have investigated the association between insulin resistance and arterial stiffness in Chinese. We aimed to investigate this relationship in a population-based study of middle-aged Chinese. A total of 2,188 subjects aged 40 years and older were recruited in 2004 in Taiwan. The association between arterial stiffness (measured by brachial-ankle pulse wave velocity (baPWV)) and insulin resistance (represented by homeostasis model assessment (HOMA-IR) and fasting glucose levels) was studied by multiple logistic and linear regression analyses. The respective prevalence of diabetes and impaired fasting glucose (IFG) was 13.9% and 30.6% in males and 10.4% and 20.8% in females. Using multiple linear regression analyses, we found baPWV to be strongly associated with age, gender, body mass index (BMI), waist circumference (WC), systolic blood pressure (BP), diastolic BP, fasting glucose, and triglycerides. Compared to the lowest HOMA-IR tertile I and adjusting for age, BMI, WC, gender, triglycerides, systolic BP, diastolic BP, smoking, alcohol drinking, betel nut chewing, and physical activity, the odds ratios (95% confidence interval) of arterial stiffness for the higher HOMA-IR tertiles II and III were 1.15 (0.77-1.71) and 1.60 (1.05-2.46), respectively. Using a general linear model with adjustment for age, systolic BP, diastolic BP, BMI, WC, and triglycerides, baPWV was significantly lower in the diabetic group by 90.3 cm/sec in males and 100.5 cm/sec in females compared to the IFG group. When comparing the IFG group to the normal glucose group, baPWV was 28.5 cm/sec lower in males and 14.4 cm/sec lower in females. Arterial stiffness is independently associated with insulin resistance in Chinese middle-aged adults. Subjects with diabetes or IFG have higher baPWV than normoglycemic subjects.

Hypertension, Insulin Resistance, and Aldosterone: Sex‐Specific Relationships

African Americans, particularly men, have the highest morbidity and mortality rates from hypertension in the United States. The authors studied 527 African Americans in a general clinical research center to determine whether there are sex differences in the relationships between hypertension with insulin resistance (IR) and aldosterone, which are risk factors for cardiovascular disease. Measurements included ambulatory blood pressure (BP), anthropometric measures, plasma renin activity, plasma aldosterone (PA) concentration, and fasting serum lipids, glucose, and insulin. IR was estimated using the Homeostasis Model Assessment (HOMA) model. BP correlated with aldosterone in both sexes. However, both BP and PA correlated with IR in men, but not in women. Compared with men in the lower tertile of HOMA-IR, men in the upper tertile had higher mean systolic BP, a higher odds ratio of having hypertension, and higher levels of PA. The association of IR with both hypertension and PA in men, but not in women, may contribute to the high prevalence of cardiovascular disease in African American men.

Metabolic syndrome as a predictor of cardiovascular diseases and type 2 diabetes in Koreans

Background The purpose of this study was to investigate whether the presence of the NCEP-ATP III defined metabolic syndrome (MS) is associated with the future development of cardiovascular disease (CVD) and diabetes in Koreans. Methods The study subjects were recruited from among those who visited the Health Promotion Center at the Samsung Medical Center. 2435 subjects (1761 men and 674 women), 20 to 78 years of age, were enrolled and evaluated for the development of new onset CVD (coronary heart disease [CHD] and stroke) during a mean 8.7 years of follow-up. Results The prevalence of the MS at baseline was 21.7% (382/1761) and 11.4% (77/674) in men and women respectively, and the MS was found to be associated with the risk for CVD in both men and women (OR, 1.98; 95% CI, 1.30–3.03 in men, 4.04; 95% CI, 1.78–9.14 in women). More specifically, the MS was associated with the risk for future CHD (OR, 3.68; 95% CI, 1.93–7.01) in men and stroke (OR, 3.96; 95% CI, 1.58–9.94) in women. However, no statistical differences were found between the HOMA-IR tertiles with regard to the risk for CVD. After controlling for fasting plasma glucose (FPG) levels, the predictive power of the MS for an increased risk for diabetes was dramatically decreased (OR, from 3.69 to 1.77) in men, and it no longer was a predictor in women. Conclusions The NCEP-defined MS was found to be associated with the risk for future CVD, i.e., CHD in men and stroke in women.

Not all obese subjects of multiethnic origin are at similar risk for developing hypertension and type 2 diabetes

Backgrounds Whether insulin resistance and not obesity per se is the major contributor to clinical outcomes associated with obesity has not been fully established. This study evaluated in a group of obese Brazilians of multiethnic origin to what extent the prevalence of hypertension and other cardiometabolic risk factors varies as a function of the degree of insulin sensitivity. Methods The study involved 118 individuals (mean age of 44 ± 12 years; BMI = 38.6 ± 7.9 kg/m 2) without evidence of diabetes or cardiovascular disease. Insulin resistance was assessed by HOMA-IR index, which was used to stratify patients into tertiles. Results The mean HOMA-IR in tertile 1, the most insulin-sensitive group, was 2.7 ± 0.8 and in tertile 3, the most insulin-resistant group, 9.1 ± 2.4 ( P < 0.001). Mean arterial pressure showed a linear and significant variation across the HOMA-IR tertiles 1, 2, and 3 (94.3 ± 11.7; 98.7 ± 11.4; 105.0 ± 12.4 mm Hg), as did fasting plasma glucose (93.6 ± 12.1; 98.1 ± 12.7; 100.0 ± 11.0 mg/dL), uric acid (4.7 ± 1.4; 5.9 ± 1.9; 6.3 ± 1.4 mg/dL), HDL-cholesterol (48.1 ± 11.6; 46.5 ± 10.5; 42.2 ± 8.0 mg/dL), and plasma adiponectin (7.8 ± 3.3; 7.0 ± 2.8; 6.3 ± 6.5 µg/mL), respectively. The results indicated that 27.5% of our patients had dysglicemia, 28.2% had hypertriglyceridemia, and 30.7% had arterial hypertension in the most insulin-sensitive tertile, when compared with 51%, 53.8% and 79.4%, respectively, in the most insulin-resistant tertile. A stepwise regression analysis showed that only HOMA-IR and age independently affected the risk for increased systolic blood pressure. Conclusion In conclusion, our findings have shown that the risk of developing essential hypertension, type 2 diabetes, and cardiovascular disease is accentuated in obese individuals who are also more insulin resistant.

Abstract 3595: Inverse Association of Adiponectin with Insulin Resistance is Attenuated with the Escalation of Insulin Resistance: a Possible Finding of Adiponectin Resistance

Introduction: Adiponectin has been known to play an important role in the glucose and lipid metabolism, and thereby may be considered as a potential treatment target for diabetes mellitus or atherosclerotic diseases. Recently, some basic studies showed that adiponectin might not function in an insulin-resistant condition, a concept called “adiponectin resistance.” However, this concept has not been confirmed in human. Therefore, we assessed the hypothesis that the well-known inverse association between adiponectin and insulin resistance is weakened in the insulin-resistant state. Methods: We studied 2,316 middle-aged Japanese men without a medical history of cancer, cardiovascular disease, diabetes, hypertension, or dyslipidemia to determine whether or not the association between serum adiponectin levels and the insulin resistance index (HOMA-IR) differed according to insulin resistant states. Results: Mean age and body mass index of study subjects were 48±7 and 23±3, respectively. A multiple linear regression analysis revealed that log-adiponectin was inversely associated with log-HOMA-IR independently of covariates (β= − 0.235, P &lt;0.001). Subsequently, we re-analyzed after dividing study subjects according to the tertile of HOMA-IR. As shown in the Table , the inverse association between adiponectin and HOMA-IR was considerably weakened with the escalation of insulin resistance. Specifically, adiponectin was almost positively associated with HOMA-IR in insulin-resistant subjects (β= 0.114, P =0.059). Interestingly, statistically significant associations of adiponectin with triglyceride and HDL-C were uniformly observed in all tertiles. Conclusion: The inverse association of adiponectin with insulin resistance weakened with the escalation of insulin resistance, suggesting the existence of “adiponectin resistance” in insulin-resistant individuals. This adiponectin resistance may be restricted in glucose metabolism. Table. Coefficients of adiponectin in multiple linear regression analyses with independent variables

Association of Insulin Resistance and Hematologic Parameters: Study of a Middle-aged and Elderly Chinese Population in Taiwan

Chronic inflammation is a common feature related to changes in hematologic parameters in insulin resistance. The aims of this study were to explore the relationship between hematologic parameters and insulin resistance, and to establish a gerontologic profile for following studies. Residents aged over 40 years in 3 major townships in I-Lan County participating in the Adult Health Examination were invited for the study. Diagnosis of diabetes mellitus (DM) was done according to American Diabetes Association criteria. Insulin resistance was measured by homeostasis model assessment (HOMA-IR), and subjects with the highest tertile of HOMA-IR were defined as being insulin resistant. Hematologic parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, and platelet count were measured for comparisons. A total of 857 subjects (mean age, 64.6 +/- 11.2 years; male/female, 373/484) participated in this study. Their mean body mass index (BMI) was 24.5 +/- 3.7 kg/m2, and 42.4% of them were obese and 21.8% were overweight. The overall prevalence of DM was 15.4% (7.7% were previously diagnosed and 7.7% were newly diagnosed), and impaired fasting glucose was 7.2%. Trend analyses confirmed that age, BMI, HOMA-IR, WBC and platelet counts were significantly increased as glycemic metabolism exacerbated (p = 0.007, < 0.001, < 0.001, < 0.001 and 0.025, respectively). Compared with insulin-sensitive subjects, insulin-resistant subjects were more likely to be females (70.2% vs. 49.7%, p < 0.001), and had significantly higher BMI (26.2 +/- 3.9 kg/m2 vs. 23.7 +/- 3.3 kg/m2, p < 0.001), HOMA-IR (3.6 +/- 3.5 vs. 0.7 +/- 0.3, p < 0.001), WBC count (6686.9 +/- 1889.2/mm3 vs. 5942.9 +/- 1740.4/mm3, p < 0.001), and platelet count (243.5 +/- 70.9 x 10(3)/mm3 vs. 231.0 +/- 62.2 x 10(3)/mm3, p = 0.011), but not age (64.5 +/- 11.0 years vs. 64.6 +/- 11.4 years, p = 0.93) or RBC count (4.6 +/- 0.6 M/mm3 vs. 4.6 +/- 0.6 M/mm3, p = 0.76). When age and sex were controlled, HOMA-IR significantly correlated with WBC count (gamma = 0.23, p < 0.001) and platelet count (gamma = 0.09, p = 0.007). However, by multiple logistic regression, female gender, overweight and obesity, and elevated WBC count were all found to be independent risk factors of insulin resistance, but age, RBC and platelet counts were not. Elevated WBC count but not RBC count was significantly associated with insulin resistance and glycemic metabolism. The relationship between platelet count and insulin resistance deserves further investigations.

Comparison between HOMA‐IR and ISI‐gly in detecting subjects with the metabolic syndrome

To verify whether, as index of insulin resistance, ISI-gly (insulin sensitivity index) is more efficient than HOMA-IR (homeostatic model assessment) or QUICKI (quantitative insulin sensitivity check index) in detecting patients with the metabolic syndrome. Excluding patients with known diabetes, endocrine, liver and kidney diseases, we enrolled 553 subjects who were screened for metabolic abnormalities. After 5 days of a balanced weight maintenance diet, we performed an OGTT (oral glucose tolerance test) and measured fasting and 2-h postload blood sugar and insulin, from which we calculated ISI-gly, HOMA-IR and QUICKI, stratifying patients in tertiles. Statistical comparisons were performed for a number of metabolic variables between tertiles of the same index, as well as between tertiles of different indexes presumably expressing identical insulin resistance. All variables reflecting the metabolic syndrome were significantly more altered in the top as compared to the intermediate and the lowest tertile for HOMA-IR, the opposite for ISI-gly. Comparing homologous measurements of the top tertile of HOMA-IR with the lowest tertile of ISI-gly (presumably expressing identical insulin resistance), fasting glucose and insulin were significantly higher, while 2-h OGTT values were significantly lower. The opposite occurred comparing the lowest HOMA-IR to the highest ISI-gly tertile, the diagnostic predictive values of the latter in detecting metabolic derangements being also higher. Data from QUICKI 1st to 3rd tertiles exactly matched those obtained from HOMA-IR 3rd to 1st tertile. ISI-gly, which includes postload glucose and insulin concentrations, provides a more accurate estimate of whole-body insulin sensitivity than HOMA-IR or QUICKI, derived from fasting measurements only, thus constituting a more sensitive tool for screening and preventing metabolic abnormalities.

Soluble leptin receptor and soluble receptor-bound fraction of leptin in the metabolic syndrome.

In obesity, plasma leptin is high and soluble leptin receptor (sOb-R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb-R concentration and the bound-free ratio of leptin. sOb-R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle-aged obese or overweight men. Concentration of sOb-R and soluble receptor-bound fraction of leptin were lowest in the highest tertile of HOMA-IR. sOb-R and the bound-free ratio of leptin correlated with HOMA-IR, leptin concentration, and waist-to-hip ratio independently of age, BMI, and fat mass. Leptin and waist-to-hip ratio were the sole independent determinants of sOb-R concentration, and BMI, HOMA-IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb-R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb-R concentration and a lower fraction of bound leptin in men with the MS. IR and abdominal obesity are associated with low sOb-R concentration and low bound-free ratio of leptin independent of fat mass. Low sOb-R concentration and low bound-free ratio of leptin segregate with components of the MS. We suggest that low sOb-R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS.

Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease.

Insulin resistance is closely associated with atherosclerosis and cardiovascular mortality in the general population. Patients with end-stage renal disease (ESRD) are known to have insulin resistance, advanced atherosclerosis, and a high cardiovascular mortality rate. We evaluated whether insulin resistance is a predictor of cardiovascular death in a cohort of ESRD. A prospective observational cohort study was performed in 183 nondiabetic patients with ESRD treated with maintenance hemodialysis. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels at baseline, and the cohort was followed for a mean period of 67 mo. Forty-nine deaths were recorded, including 22 cardiovascular deaths. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly different between subjects in the top tertile of HOMA-IR (1.40 to 4.59) and those in the lower tertiles of HOMA-IR (0.28 to 1.39), and the hazard ratio (HR) was 2.60 (95% confidence interval [CI], 1.12 to 6.01; P = 0.026) in the univariate Cox proportional hazards model. In multivariate Cox models, the positive association between HOMA-IR and cardiovascular mortality remained significant (HR, 4.60; 95% CI, 1.83 to 11.55; P = 0.001) and independent of age, C-reactive protein, and presence of preexisting vascular complications. Further analyses showed that the effect of HOMA-IR on cardiovascular mortality was independent of body mass index, hypertension, and dyslipidemia. In contrast, HOMA-IR did not show such a significant association with noncardiovascular mortality. These results indicate that insulin resistance is an independent predictor of cardiovascular mortality in ESRD.