Log Homeostasis Model Assessment Research Articles

The Mediterranean Diet Score Is More Strongly Associated with Favorable Cardiometabolic Risk Factors over 2 Years Than Other Diet Quality Indexes in Puerto Rican Adults

BackgroundMultiple diet quality scores have been used to evaluate adherence to specific dietary recommendations or to consumption of healthful foods and nutrients. It remains unknown which score can more strongly predict longitudinal changes in cardiometabolic risk factors. ObjectiveWe aimed to determine associations of 5 diet quality scores [AHA diet score (AHA-DS), Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI)-2005, Mediterranean diet score (MeDS), and Alternative Healthy Eating Index (AHEI)] with 2-y changes in cardiometabolic risk factors in adults 45–75 y old. MethodsData from the Boston Puerto Rican Health Study were analyzed (n = 1194). Diet quality scores were calculated from a baseline-validated food-frequency questionnaire. Multivariable-adjusted, repeated-subjects, mixed-effects models, adjusted for baseline measures, estimated associations between each z score and 14 individual cardiometabolic factors measured at 2 y. ResultsMeDS was significantly associated with lower 2-y waist circumference (β coefficient ± SE: −0.52 ± 0.26, P = 0.048); body mass index (BMI; −0.23 ± 0.08, P = 0.005); log-insulin (−0.06 ± 0.02, P = 0.005); log–homeostasis model assessment of insulin resistance (HOMA-IR; −0.05 ± 0.02, P = 0.030), and log–C-reactive protein (−0.13 ± 0.03, P = 0.0002). Similar but weaker associations were observed for the AHEI with BMI, insulin, and HOMA-IR. The AHA-DS was inversely associated with BMI (−0.17 ± 0.08, P = 0.033). Neither the HEI-2005 nor DASH was significantly associated with any variable. Traditional Puerto Rican foods consumed by individuals with high MeDSs included vegetables and meats in homemade soups, orange juice, oatmeal, beans and legumes, fish, whole milk, corn oil, and beer. ConclusionsThe MeDS comprises food components and scores associated with a favorable cardiometabolic profile over 2 y in Puerto Rican adults. An overall healthy diet may be particularly beneficial for maintaining a lower BMI. These results can help identify suitable measures of diet quality in epidemiologic studies and craft meaningful nutritional messages and dietary recommendations for the intended population. This study was registered at clinicaltrials.gov as NCT01231958.

Acculturation and Insulin Resistance among US Chinese Immigrant Women.

Chinese immigrants in the United States undergo a transition to increased chronic disease risk commonly attributed to acculturative changes. Longitudinal data to confirm this are lacking. We examined acculturation in relation to insulin resistance in a sample of Chinese immigrant women to determine differences by level of education and possible mediation by anthropometry and diet. Longitudinal study. Philadelphia, Pennsylvania. 305 Chinese immigrant women recruited October 2005 to April 2008 and followed until April 2010. Association of acculturation, measured using the General Ethnicity Questionnaire - American version (GEQA), with homeostasis model assessment (HOMA) score as an indicator of insulin resistance, modeled using generalized estimating equations to account for repeated measures over time. GEQA was associated with log HOMA score, but only in women with <9 years of education (beta [SE] = .09 [.04], P=.02; interaction P=.02). The association persisted with adjustment for body mass index, waist circumference, and dietary variables. These findings provide longitudinal evidence that insulin resistance increases with acculturation. However, the association was apparent only in less-educated immigrants and may be mediated by a pathway other than changes in anthropometry and diet.

Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study.

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima-media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8)ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised β=0·233, P<0·001), alanine transaminase (standardised β=0·194, P<0·001), log homeostasis model assessment index for insulin resistance (standardised β=0·181, P<0·001), TAG (standardised β=0·083, P=0·003), Hb (standardised β=0·080, P=0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised β=0·079, P=0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Uptake of aortic 18F-FDG is correlated with low-density lipoprotein cholesterol and leptin in a general population.

ObjectiveThis study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population.Methods 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings.ResultsBy multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (β = 0.001, p = 0.03) and log-leptin (β = 0.336, p<0.01) in all subjects.ConclusionTBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population.

Abstract P398: Uric Acid And Prehypertension: Salt Intake in Addition to Insulin Resistance are not Mediators.

Introduction: The association "uric acid and high blood pressure" is still matter of debate. Therefore, to distinguish serum uric acid as an independent factor for high blood pressure can start new trials to prevent hypertension. A paleoantropological rationale for this association was a knockout of uricase occurred during the Miocene among hominids that induced high levels of uric acid. As consequence, during food shortage times, high uric acid had an evolutionary benefit increasing salt-sensitivity for keep blood pressure and rising insulin resistance that maintaining high blood glucose levels provided fuel for the brain. Nowadays, the average levels of uric acid are substantially higher compared to chimpanzees, a uricase-deficient primate, and among remote populations as the yanomamo. Hypothesis: we assessed the hypothesis that the link between uric acid and blood pressure in individuals without hypertension is independent of sex, age, race, salt and alcohol intakes, glucose homeostasis, body-mass index and renal function. Methods: from the 15105 participants of the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) aged 35-74 years, we selected 7954 individuals (median age = 48 years-old; women =58.1; White = 56.6%) without hypertension, diabetes, previous cardiovascular diseases. The presence or not of prehypertension (7th JNC criteria) was the dependent variable and quartiles (Q) of serum uric acid, the independent variable. We applied an unconditional logistic regression adjusted for age and sex. After this, according to our hypothesis, we added the following variables: (1) 24-hour urinary sodium; (2) log Homeostasis Model Assessment (fasting blood glucose (mg/dL) х fasting insulin (mg/dL)/450), and (3) a full model, adding race, body-mass index, alcohol intake, and glomerular filtration rate by CKD-epi). Results: the uric acid quartiles ranges (md/dL) were Q1 ≤ 4.1; Q2:4.2-5.0; Q3:5.1-6.0; Q4: ≥ 6.1 and the number of participants were Q1= 1909; Q2=2029; Q3=2000; Q4= 2016. Considering Q1 as reference, the age-sex adjusted odds ratios (95% Confidence Interval) through the quartiles were: Q2= 1.22 (1.05-1.41); Q3= 1.40 (1.20-1.63); Q4= 2.03 (1.71-2.39) [P for trend &lt;0.001]. Adding 24 hour urinary sodium, the ORs (95% CI) were: Q2= 1.19 (1.01-1.40); Q3= 1.37 (1.16-1.62); and 1.94 (1.61-2.33) [P for trend &lt;0.001]. Adding HOMA-IR, the ORs (95% CI) were: Q2= 1.14 (0.97-1.34); Q3= 1.25(1.05-1.48); and Q4=1.62(1.34-1.96) [P for trend &lt;0.001]. Finally, for the full model the ORs were Q2= 1.04 (0.88-1.23); Q3= 1.05 (0.88-1.26) and Q4= 1.32(1.08-1.62) [P for trend &lt;0. 01]. Conclusion: Uric acid levels were correlated to prehypertension among a middle-aged urban population. It occurred independently of other variables classically associated to high blood pressure or the origin of higher uric acid in hominids.

Sedentary Lifestyle and Its Relation to Cardiovascular Risk Factors, Insulin Resistance and Inflammatory Profile

Introduction and objectivesTo analyze the association between sitting time and biomarkers of insulin resistance and inflammation in a sample of healthy male workers. MethodsCross-sectional study carried out in a sample of 929 volunteers belonging to the Aragon Workers’ Health Study cohort. Sociodemographic, anthropometric, pharmacological and laboratory data were collected: lipids—total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)—, insulin resistance—glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, insulin, and triglyceride/high-density lipoprotein cholesterol ratio—, and inflammatory profile—C-reactive protein and leukocytes. Information on sitting time and physical activity was assessed using a questionnaire. Sedentary behavior was analyzed in terms of prevalences and medians, according to tertiles, using a multivariate model (crude and adjusted linear regression) with biomarkers of inflammation and insulin resistance. ResultsThe most sedentary individuals had higher body mass index, greater waist circumference, and higher systolic blood pressure, with a significant upward trend in each tertile. Likewise, they had a worse lipid profile with a higher C-reactive protein level, homeostasis model assessment of insulin resistance index, triglyceride/high-density lipoprotein cholesterol ratio, and insulin concentration. In the multivariate analysis, we observed a significant association between the latter parameters and sitting time in hours (log C-reactive protein [β = 0.07], log homeostasis model assessment of insulin resistance index [β = 0.05], triglyceride/high-density lipoprotein cholesterol ratio [β = 0.23], and insulin [β = 0.44]), which remained after adjustment for metabolic equivalents-h/week. ConclusionsWorkers who spend more time sitting show a worse inflammatory and insulin resistance profile independently of the physical activity performed.

Sedentarismo y su relación con el perfil de riesgo cardiovascular, la resistencia a la insulina y la inflamación

Introduction and objectivesTo analyze the association between sitting time and biomarkers of insulin resistance and inflammation in a sample of healthy male workers. MethodsCross-sectional study carried out in a sample of 929 volunteers belonging to the Aragon Workers’ Health Study cohort. Sociodemographic, anthropometric, pharmacological and laboratory data were collected: lipids—total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)—, insulin resistance—glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, insulin, and triglyceride/high-density lipoprotein cholesterol ratio—, and inflammatory profile—C-reactive protein and leukocytes. Information on sitting time and physical activity was assessed using a questionnaire. Sedentary behavior was analyzed in terms of prevalences and medians, according to tertiles, using a multivariate model (crude and adjusted linear regression) with biomarkers of inflammation and insulin resistance. ResultsThe most sedentary individuals had higher body mass index, greater waist circumference, and higher systolic blood pressure, with a significant upward trend in each tertile. Likewise, they had a worse lipid profile with a higher C-reactive protein level, homeostasis model assessment of insulin resistance index, triglyceride/high-density lipoprotein cholesterol ratio, and insulin concentration. In the multivariate analysis, we observed a significant association between the latter parameters and sitting time in hours (log C-reactive protein [β =0.07], log homeostasis model assessment of insulin resistance index [β = 0.05], triglyceride/high-density lipoprotein cholesterol ratio [β = 0.23], and insulin [β = 0.44]), which remained after adjustment for metabolic equivalents-h/week. ConclusionsWorkers who spend more time sitting show a worse inflammatory and insulin resistance profile independently of the physical activity performed.Full English text available from:www.revespcardiol.org/en

Changes in procoagulants track longitudinally with insulin resistance: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study

To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance. Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37years at year7, to year20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years7 and 20 and four groups reflecting changes were defined: 'low' (low at years7 and 20), 'stable' (low/middle at years7 and 20, but not both low at years7 and 20), 'high' (high at year7 and low/middle at year20; or low/middle at year7 and high at year20) and 'highest' (high at years7 and 20). Linear regression models were used to evaluate 13-year changes (year20-year7) in fibrinogen level and factors VII, VIII and von Willebrand change groups in relation to insulin resistance measures. Homeostasis model assessment of insulin resistance (year20) and changes in log homeostasis model assessment of insulin resistance (year20-year7) were significantly associated with the 13-year increase in fibrinogen (P<0.001). Compared with participants in the low group, those in the high group had significantly higher levels of homeostasis model assessment of insulin resistance (year20) and changes in homeostasis model assessment of insulin resistance (year20-year7) for fibrinogen factor VII and von Willebrand factor (P<0.017). No significant associations were observed between fibrinogen VIII and insulin resistance measures. An increase in fibrinogen level and persistently high levels of factor VII and von Willebrand factor are significantly associated with increased risk of insulin resistance. These findings provide new insight into the mechanisms to explain the heightened risk for thrombosis in adults with insulin resistance/diabetes.

Positive association between high‐sensitivity C‐reactive protein and incidence of type 2 diabetes mellitus in Japanese workers: 6‐year follow‐up

Elevated high-sensitivity C-reactive protein (hs-CRP), a marker of low-grade systemic inflammation, may be involved in the etiology of type 2 diabetes mellitus (T2DM). However, whether inflammation precedes development of T2DM independent of cigarette smoking and obesity remains to be confirmed. We studied 4213 civil servants in a local government in Japan aged 35-66 years at baseline in 2002, who donated blood samples and were followed 6 years. Hazard ratios (HR) of T2DM according to the hs-CRP quartiles [range Q1: 0.02-0.18 (reference), Q2: 0.18-0.33, Q3: 0.33-0.67 and Q4: 0.67-9.62 mg/L) were estimated by Cox proportional hazards model adjusted for gender, age, body mass index, alcohol intake, smoking status (current, past and never), number of cigarettes per day, physical activity, family history of diabetes (Model 1) and variables in Model 1 + glucose (Model 2). The geometric mean [95% confidence interval (CI)] of hs-CRP was 0.36 mg/L (0.34-0.37). During the follow-up, 156 new T2DM cases were confirmed. In total sample, Model 2 HRs (95% CIs) for hs-CRP quartiles Q2-Q4 compared with Q1 were 0.69 (0.36-1.26), 1.47 (0.91-2.39) and 1.78 (1.10-2.88), respectively (p for linear trend = 0.014). Stratified analysis revealed that a statistically significant association was observed only in normal weight non-current smokers with Model 2 HRs (CIs) being 0.79 (0.29-2.17), 2.63 (1.25-5.56) and 3.19 (1.49-6.86) for Q2-Q4 compared with Q1, respectively (p for linear trend = 0.0006). The relationship did not change materially after further adjusting for log-homeostasis model assessment or exclusion of past smokers. These findings imply that higher hs-CRP itself or existence of chronic systemic inflammation precedes onset of T2DM independent of obesity and smoking.

Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease.

BackgroundEpicardial fat, quantified in a single multi-slice computed tomography (MSCT) slice, is a reliable estimate of total epicardial fat volume (EFV). We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV) in pre-dialysis chronic kidney disease (CKD) patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC).Methods94 pre-dialysis stage 3–5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected.ResultsMean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m2. Mean ssEFV was 5.03 ± 2.4 cm3. By univariate analysis, body mass index (BMI) (r = 0.53; P = <0.0001), abdominal obesity (r = 0.51; P < 0.0001), high density lipoprotein (HDL) cholesterol (r = − 0.39; P = <0.0001), insulin resistance (log homeostasis model assessment of insulin resistance (log HOMA-IR)) (r = 0.38, P = 0.001), log interleukin-6 (IL-6) (r = 0.34; P = 0.001), and log urinary albumin to creatinine ratio (UACR) (r = 0.30, P = 0.004) demonstrated the strongest associations with ssEFV. Log coronary artery calcification (log CAC score) (r = 0.28, P = 0.006), and log fibroblast growth factor-23 (log FGF-23) (r = 0.23, P = 0.03) were also correlated with ssEFV. By linear regression, log CAC score (beta =0.40; 95% confidence interval (CI), 0.01-0.80; P = 0.045), increasing levels of IL-6 (beta = 0.99; 95% CI, 0.38 – 1.61; P = 0.002), abdominal obesity (beta = 1.86; 95% CI, 0.94 - 2.8; P < 0.0001), lower HDL cholesterol (beta = −2.30; 95% CI, – 3.68 to −0.83; P = 0.002) and albuminuria (log UACR, beta = 0.81; 95% CI, 0.2 to 1.4; P = 0.01) were risk factors for increased ssEFV.ConclusionsIn stage 3–5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

Use of insulin sensitizers for the treatment of major depressive disorder: A pilot study of pioglitazone for major depression accompanied by abdominal obesity

This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference>35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Pioglitazone decreased depression symptom severity from a total IDS score of 40.3±1.8 to 19.2±1.8 at Week 12 (p<.001). Among partial responders (≥25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration=24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (-0.8±0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (-0.87±0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects. These data are limited by a small sample size and an open-label study design with no placebo control. Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.

Relationship between sleep apnea, fat distribution, and insulin resistance in obese children.

Obstructive sleep apnea (OSA) is associated with obesity, inflammation, and insulin resistance. The role of fat distribution in OSA pathogenesis has not been established in children. The objective of the study is to examine the relationship between fat distribution, OSA, and insulin resistance in an unselected population of obese children. All obese (BMI > 95th percentile) children (ages 5-18 y) seen at a pediatric obesity clinic were invited to participate. Subjects underwent polysomnography, and were tested for dyslipidemia, inflammation, and insulin resistance measured by the homeostasis model assessment (HOMA). In a subset of subjects, magnetic resonance (MRI) imaging was used to determine the abdominal visceral and subcutaneous adipose tissue areas and magnetic resonance spectroscopy (MRS) spectroscopy was used to intramyocellular lipids in leg muscles. 31 obese subjects enrolled and completed polysomnography and serum testing, and 19 subjects underwent MRI/MRS. The mean age was 12.6 ± 3.0 y and the mean body mass index (BMI) was 39.5 ± 11.2 kg/m(2). Forty-eight percent had OSA (mean apnea hypopnea index [AHI] 6.26 ± 6.77 events/h) Subjects with OSA had significantly increased BMI, log HOMA, triglycerides, and leptin compared to those without OSA. In regression analysis, only BMI z-score was associated with log HOMA. In the subset of patients with imaging data, visceral fat area was strongly predictive of AHI (p = 0.003, r(2) = 0.556). BMI z-score, gender, and age were not predictive. Visceral fat distribution is independently predictive of OSA severity in obese children.

Caffeine and Insulin Resistance in Pregnancy

Outside pregnancy, acute caffeine consumption is associated with insulin resistance. We investigated if during pregnancy plasma concentrations of caffeine and its metabolite, paraxanthine, were associated with insulin resistance. Caffeine, paraxanthine, glucose, and insulin were measured and insulin resistance estimated by homeostasis model assessment (HOMA) in banked samples from 251 fasting subjects at mean gestational age of 20.3 ± 2.0 weeks. Analysis of covariance and adjusted logistic regression were performed. Most (96.4%) women had caffeine and/or paraxanthine present. Caffeine concentrations in the upper two quartiles (>266 ng/mL) were associated with threefold higher odds of having higher insulin resistance estimated by log HOMA ≥75th percentile (third quartile odds ratio [OR], 3.02; 95% confidence interval [CI]: 1.21 to 7.54 and fourth quartile OR, 2.95; 95% CI: 1.19 to 7.31). Paraxanthine concentrations in the upper quartile (>392 ng/mL) were also associated with threefold higher odds of having higher insulin resistance (OR, 3.04; 95% CI: 1.28 to 7.25). Adjusted mean HOMA in the first caffeine-to-paraxanthine ratio quartile was 1.5 ± 2.2 versus 1.3 ± 2.3 in the fourth quartile ( P < 0.01). Both high caffeine and paraxanthine concentrations were associated with insulin resistance, but slow versus fast metabolism did not make an important difference.

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic glucose clamps in rhesus monkeys.

The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SI(Clamp) (r ≈ 0.4-0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies.

Relation of Plasma Homocysteine to Arterial Stiffness in Black and White Young Adults (from the Bogalusa Heart Study)

The aim of this study was to determine the association between homocysteine and arterial wall stiffness in a biracial (black and white) community-based cohort of asymptomatic young adults. That increased plasma homocysteine was adversely associated with atherothrombosis was well recognized. However, findings about the association of homocysteine and arterial wall stiffness, an indicator of vascular damage, were conflicting. Plasma homocysteine and other cardiovascular disease risk-factor variables were measured in 735 white and 294 black subjects aged 24 to 44 years enrolled in the Bogalusa Heart Study. Large-artery stiffness was assessed in terms of aorta-femoral pulse wave velocity (af-PWV) using echocardiography Doppler. Men versus women had higher fasting homocysteine (8.85 vs 7.32 micromol/L; p <0.01), and blacks versus whites had higher af-PWV (5.47 vs 5.24 m/s; p <0.01). In bivariate analyses, log-transformed homocysteine significantly correlated with af-PWV (p = 0.0004). In multivariate stepwise regression analyses, systolic blood pressure, age, heart rate, log-homocysteine, log-Homeostasis Model Assessment of Insulin Resistance, and smoking, in that order, were independently and positively associated with af-PWV. In conclusion, plasma homocysteine was an independent correlate of arterial stiffness in asymptomatic black and white young adults and may be a potential marker for cardiovascular disease risk in this age group.

Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls

Although body composition, insulin sensitivity, and lipids are markedly altered in overweight adolescents, hormonal associations with these parameters have not been well characterized. Growth hormone (GH) deficiency and hypercortisolemia predispose to abdominal adiposity and insulin resistance, and GH secretion is decreased in obese adults. We hypothesized that low-peak GH on the GH-releasing hormone (GHRH)-arginine stimulation test and high cortisol in overweight adolescents would be associated with higher regional fat, insulin resistance, and lipids. We examined the following parameters in 15 overweight and 15 bone age-matched control 12- to 18-yr-old girls: 1) body composition using dual-energy X-ray absorptiometry and MR [visceral and subcutaneous adipose tissue at L(4)-L(5) and soleus intramyocellular lipid ((1)H-MR spectroscopy)], 2) peak GH on the GHRH-arginine stimulation test, 3) mean overnight GH and cortisol, 4) 24-h urinary free cortisol (UFC), 5) fasting lipids, and 6) an oral glucose tolerance test. Stepwise regression was the major tool employed to determine relationships between measured parameters. Log peak GH on the GHRH-arginine test was lower (P = 0.03) and log UFC was higher (P = 0.02) in overweight girls. Log mean cortisol (overnight sampling) was associated positively with subcutaneous adipose tissue and, with body mass index standard deviation score, accounted for 92% of its variability, whereas log peak GH and body mass index standard deviation score accounted for 88% of visceral adipose tissue variability and log peak GH for 34% of the intramyocellular lipid variability. Log mean cortisol was independently associated with log homeostasis model assessment of insulin resistance, LDL, and HDL and explained 49-59% of the variability. Our data indicate that lower peak GH and higher UFC in overweight girls are associated with visceral adiposity, insulin resistance, and lipids.

Association of Television Viewing With Fasting and 2-h Postchallenge Plasma Glucose Levels in Adults Without Diagnosed Diabetes

We examined the associations of television viewing time with fasting plasma glucose (FPG) and 2-h postchallenge plasma glucose (2-h PG) levels in Australian adults. A total of 8,357 adults aged > 35 years who were free from diagnosed diabetes and who attended a population-based cross-sectional study (Australian Diabetes, Obesity and Lifestyle Study [AusDiab]) were evaluated. Measures of FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported television viewing time (in the previous week) was assessed using an interviewer-administered questionnaire. Homeostasis model assessment (HOMA) of insulin sensitivity (HOMA-%S) and beta-cell function (HOMA-%B) were calculated based on fasting glucose and insulin concentrations. After adjustment for confounders and physical activity time, time spent watching television in women was positively associated with 2-h PG, log fasting insulin, and log HOMA-%B and inversely associated with log HOMA-%S (P < 0.05) but not with FPG. No significant associations were observed with glycemic measures in men. The beta-coefficients across categories of average hours spent watching television per day (< 1.0, 1.0-1.9, 2.0-2.9, 3.0-3.9, and > or = 4.0) for 2-h PG in women were 0 (reference), 0.009, 0.047, 0.473, and 0.501, respectively (P for trend = 0.02). Our findings highlight the unique deleterious relationship of sedentary behavior (indicated by television viewing time) and glycemic measures independent of physical activity time and adiposity status. These relationships differed according to sex and type of glucose measurement, with the 2-h PG measure being more strongly associated with television viewing. The findings suggest an important role for reducing sedentary behavior in the prevention of type 2 diabetes and cardiovascular disease, especially in women.

Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women

There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population. Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%). Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively. Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp. Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.

Transient and Steady-State Euglycemic Clamp Validation of a Model for Glycemic Control and Insulin Sensitivity Testing

There is an urgent need for a simple and accurate measure of insulin sensitivity to diagnose insulin resistance in the general population and quantify changes due to clinical intervention. A new physiological control model of glucose and insulin metabolism is validated with the euglycemic-hyperinsulinemic clamp during steady and transient states. The data consist of n = 60 (15 lean, 15 overweight, 15 obese, and 15 morbidly obese) euglycemic-hyperinsulinemic clamp trials performed on normoglycemic insulin-resistant individuals. The glucose and insulin model is fitted using an integral-based method. Correlations between clamp-derived insulin sensitivity index (ISI) and the model's insulin sensitivity parameter (SI) are obtained during steady and transient states. Results are compared with log-homeostasis model assessment (HOMA), a widely used fasting surrogate for insulin sensitivity. Correlation between model-based insulin sensitivity, SI, and ISIG (ISI normalized by steady-state glucose) is r = 0.99 (n = 60) at steady state and r = 0.97 at transient state, respectively. Correlations did not significantly change across subgroups, with narrow 95% confidence intervals. Log-HOMA correlations are r=-0.72 to SI and r=-0.71 to ISIG for the overall population but are significantly lower in the subgroups, with wide 95% confidence intervals. The model-based insulin sensitivity parameter, SI, highly correlates to ISIG in all subgroups, even when only considering a transient state. The high correlation of SI offers the potential for a short, simple yet highly correlated, model-based assessment of insulin sensitivity that is not currently available.

Ethnic Differences in Body Composition and Other Markers of Cardiovascular Disease Risk: Study in Matched Haitian and White Subjects from Quebec*

People of African descent may be at greater risk of metabolic syndrome (MS) compared with whites. We examined the associations among MS markers, body composition, and resting metabolic rate (RMR) in black Haitians and in white subjects living in Quebec, Canada. Forty randomly selected Haitians were matched with 40 white subjects for age, sex, and BMI. Glycemic status and insulin resistance were assessed based on a 3-hour glucose tolerance test. Blood lipids, blood pressure, abdominal fat (computed tomography), and waist circumference (WC) were measured. RMR was estimated by indirect calorimetry. Triglycerides were significantly correlated with blood pressure only in Haitians and with the area under the curve for insulin only in whites. Haitians had significantly (p < 0.05) lower triglycerides and higher high-density lipoprotein-cholesterol concentrations but higher blood pressure than whites at any given WC value. General linear models showed that Haitians had less visceral adipose tissue than whites for the same WC. RMR was lower among Haitians for any given value of BMI or WC than in whites. Also, WC was more strongly associated with glucose area under the curve and to log-homeostasis model assessment in white than in Haitian subjects. The MS may be ethnospecific in its features and etiology. The standard anthropometric indices of obesity may not be as effective in populations of African descent compared with whites, unless appropriate cut-off values are defined.