Adjustment For Homeostasis Model Assessment Research Articles

Serum Lipopolysaccharide-binding Protein Levels and the Incidence of Metabolic Syndrome in a General Japanese Population: the Hisayama Study.

The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population. 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1-4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model. At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59-5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07). In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Serum Lipopolysaccharide-Binding Protein Levels and the Incidence of Cardiovascular Disease in a General Japanese Population: The Hisayama Study.

BackgroundEpidemiological studies have reported a link between serum LBP (lipopolysaccharide‐binding protein) levels and lifestyle‐related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations.Methods and ResultsA total of 2568 community‐dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002–2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20–9.68 μg/mL; quartile 2: 9.69–10.93 μg/mL; quartile 3: 10.94–12.40 μg/mL; quartile 4: 12.41–24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow‐up period, 180 individuals developed CVD. The age‐ and sex‐adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60–1.78]; quartile 3: HR, 1.52 [95% CI, 0.92–2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17–3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high‐sensitivity C‐reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08).ConclusionsThe present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low‐grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.

The American Heart Association Ideal Cardiovascular Health and Incident Type 2 Diabetes Mellitus Among Blacks: The Jackson Heart Study.

BackgroundThe concept of ideal cardiovascular health (CVH), defined by the American Heart Association primarily for coronary heart disease and stroke prevention, may apply to diabetes mellitus prevention among blacks.Methods and ResultsOur sample included 2668 adults in the Jackson Heart Study with complete baseline data on 6 of 7 American Heart Association CVH metrics (body mass index, healthy diet, smoking, total cholesterol, blood pressure, and physical activity). Incident diabetes mellitus was defined as fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes mellitus drugs, or glycosylated hemoglobin ≥6.5%. A summary CVH score from 0 to 6, based on presence/absence of ideal CVH metrics, was derived for each participant. Cox regression was used to estimate adjusted hazard ratios. Mean age was 55 years (65% women) with 492 incident diabetes mellitus events over 7.6 years (24.6 cases/1000 person‐years). Three quarters of participants had only 1 or 2 ideal CVH metrics; no participant had all 6. After adjustment for demographic factors (age, sex, education, and income) and high‐sensitivity C‐reactive protein, each additional ideal CVH metric was associated with a 17% diabetes mellitus risk reduction (hazard ratio, 0.83; 95% CI, 0.74–0.93). The association was attenuated with further adjustment for homeostasis model assessment for insulin resistance (hazard ratio, 0.89; 95% CI, 0.79–1.00). Compared with participants with 1 or no ideal CVH metric, diabetes mellitus risk was 15% and 37% lower in those with 2 and ≥3 ideal CVH metrics, respectively.ConclusionsThe AHA concept of ideal CVH is applicable to diabetes mellitus prevention among blacks. These associations were largely explained by insulin resistance.

Development of Nephrolithiasis in Asymptomatic Hyperuricemia: A Cohort Study

Although the association between gout and nephrolithiasis is well known, the relationship between asymptomatic hyperuricemia and the development of nephrolithiasis is largely unknown. Cohort study. 239,331 Korean adults who underwent a health checkup examination during January 2002 to December 2014 and were followed up annually or biennially through December2014. Baseline serum uric acid levels of participants. The development of nephrolithiasis during follow-up. Nephrolithiasis is determined based on ultrasonographic findings. A parametric Cox model was used to estimate the adjusted HRs of nephrolithiasis according to serum uric acid level. During 1,184,653.8 person-years of follow-up, 18,777 participants developed nephrolithiasis (incidence rate, 1.6/100 person-years). Elevated uric acid level was significantly associated with increased risk for nephrolithiasis in a dose-response manner (P for trend< 0.001) in men. This dose-response association was not observed in women. In male participants, multivariable-adjusted HRs for incident nephrolithiasis comparing uric acid levels of 6.0 to 6.9, 7.0 to 7.9, 8.0 to 8.9, 9.0 to 9.9, and≥10.0mg/dL with uric acid levels< 6.0mg/dL were 1.06 (95% CI, 1.02-1.11), 1.11 (95% CI, 1.05-1.16), 1.21 (95% CI, 1.13-1.29), 1.31 (95% CI, 1.17-1.46), and 1.72 (95% CI, 1.44-2.06), respectively. This association was observed in all clinically relevant subgroups and persisted even after adjustment for homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein level. Dietary information and computed tomographic diagnosis of nephrolithiasis were unavailable. In this large cohort study, increased serum uric acid level was modestly and independently associated with increased risk for the development of nephrolithiasis in a dose-response manner in apparently healthy men.

Copeptin, Insulin Resistance, and Risk of Incident Diabetes in Older Men

Context:Prior studies suggested a role for the arginine vasopressin (AVP) system in the pathogenesis of diabetes. Prospective studies on the association between copeptin (the C-terminal fragment of AVP hormone) and incident diabetes are limited.Objective:We have examined the association between plasma copeptin and the risk of incident diabetes in older men.Design:The British Regional Heart Study was a prospective study with an average of 13 years follow-up.Setting:General practices in the United Kingdom were studied.Participants:Participants were 3226 men aged 60 to 79 years with no prevalent diabetes.Outcome:We measured 253 patients with incident diabetes.Results:Copeptin was positively and significantly associated with renal dysfunction, insulin resistance (homeostasis model assessment of insulin resistance), metabolic risk factors (waist circumference, blood pressure, triglycerides, and liver function), C-reactive protein, tissue plasminogen activator, and von Willebrand factor (endothelial dysfunction) but not with plasma glucose. The risk of incident diabetes was significantly elevated only in men in the top fifth of the copeptin distribution (>6.79 pmol/L), and this risk persisted after adjustment for several diabetes risk factors including metabolic risk factors and C-reactive protein (adjusted hazard ratio in the top fifth vs the rest = 1.78 [95% confidence interval, 1.34–2.37]). Risk was markedly attenuated although it remained significant after further adjustment for homeostasis model assessment of insulin resistance and plasma glucose (adjusted hazard ratio = 1.47 [1.11–1.97]). The increased risk was seen even when the analysis was restricted to men with no chronic kidney disease or to men with no impaired fasting glucose (<6.1 mmol/L).Conclusion:Copeptin is associated with a significantly increased risk of diabetes in older men. The association is partly mediated through lower insulin sensitivity. The findings suggest a potential role of the AVP system in diabetes.

The association between hematological parameters and insulin resistance is modified by body mass index - results from the North-East Italy MoMa population study.

ObjectiveIncrements in red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) levels are reportedly associated with higher insulin resistance (IR). Obesity may cause IR, but underlying factors remain incompletely defined, and interactions between obesity, hematological parameters and IR are incompletely understood. We therefore determined whether: 1) BMI and obesity per se are independently associated with higher RBC, hemoglobin and hematocrit; 2) hematological parameters independently predict insulin resistance in obese individuals.Design and MethodsWe investigated the associations between BMI, hematological parameters and insulin resistance as reflected by homeostasis model assessment (HOMA) in a general population cohort from the North-East Italy MoMa epidemiological study (M/F = 865/971, age = 49±1).ResultsIn all subjects, age-, sex- and smoking-adjusted hematological parameters were positively associated with BMI in linear regression (P<0.05), but not after adjustment for HOMA or waist circumference (WC) and potential metabolic confounders. No associations were found between hematological parameters and BMI in lean, overweight or obese subgroups. Associations between hematological parameters and HOMA were conversely independent of BMI in all subjects and in lean and overweight subgroups (P<0.01), but not in obese subjects alone.ConclusionsIn a North-East Italy general population cohort, obesity per se is not independently associated with altered RBC, Hb and Ht, and the association between BMI and hematological parameters is mediated by their associations with abdominal fat and insulin resistance markers. High hematological parameters could contribute to identify insulin resistance in non-obese individual, but they do not appear to be reliable insulin resistance biomarkers in obese subjects.

Relationship between serum circulating insulin‐like growth factor‐1 and liver fat in the United States

Nonalcoholic fatty liver disease (NAFLD), circulating insulin-like growth factor-1 (IGF-1), and IGF-1/IGF-binding protein-3 (IGFBP-3) concentrations are associated with adiposity and insulin resistance. We aimed to determine whether serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with presence or severity of NAFLD independent of potential confounding. We performed a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988–1994, a representative sample of the United States adult population. Among participants who had a fasting blood draw and ultrasound examination, we excluded those with missing data, viral hepatitis, iron overload, excessive alcohol intake, pregnancy, or taking glucose-lowering therapy, yielding 4172 adults for this analysis. In logistic regression analyses adjusted for age, gender, and race/ethnicity, higher IGF-1 and IGF-1/IGFBP-3 quartiles were associated with lower likelihood of NAFLD and lower grade steatosis. These associations became non-significant when further adjusted for adiposity (body mass index, waist circumference) with the exception of the association between IGF-1/IGFBP-3 and severity of NAFLD which remained significant after adjustment for homeostasis model assessment for insulin resistance (HOMA-IR) (odds ratio [95% CI]: Q3: 0.71 [0.53–0.96], Q4: 0.62 [0.43–0.89]) and adiposity (Q4: 0.67 [0.47–0.96]). Full adjustment (age, gender, race/ethnicity, adiposity, HOMA-IR, A1C%) further attenuated associations between IGF-1 or IGF-1/IGFBP-3 and liver fat such that they were no longer significant. Adiposity explains much of the observed association between IGF-1 or IGF-1/IGFBP-3 and liver fat. These findings do not support a direct role for the growth hormone-IGF-1/IGFBP-3 axis in the pathophysiology of NAFLD.

Letter: association of vaspin with metabolic syndrome: the pivotal role of insulin resistance (diabetes metab j 2014;38:143-9).

Dear Editor, Vaspin is an interesting adipokine, which was isolated from visceral white adipose tissue of obese, diabetic rat model [1,2]. Because there has been reports regarding the tight link between metabolic diseases, such as obesity, diabetes, and metabolic syndrome (MS), and visceral fat, vaspin has been focused as a potential biomarker for various metabolic diseases [3,4,5]. However, different vaspin concentrations showed a large scale of standard deviation in different individuals and a lack of consistency between metabolic parameters and the levels of vaspin according to previous reports, warranting more human studies and clearer explanations. In this article entitled Association of vaspin with MS: the pivotal role of insulin resistance, Esteghamati et al. [6] also showed the association between serum vaspin concentration and the components of MS in Iranian adults [6]. They showed that vaspin is associated with the components of metabolic syndrome: high triacyglyceride (TG) level, high glucose in particular, and obesity indices. However this association was abolished after the adjustment for homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein levels. Recently, our group reported that serum vaspin concentration was higher in men with MS and in women with coronary atherosclerosis in around 400 Korean subjects [7]. Among the components of MS, body mass index (BMI), waist circumference, and TG showed independent associations with plasma vaspin levels. Although these previous Iranian study and Korean study similarly investigated the correlation between serum vaspin levels and various metabolic parameters, there are several differences. Our data did not show any significant correlation between vaspin concentration and serum glucose. Our subjects were enrolled from routine health examination center and showed relatively normal range of serum glucose levels (mean value of 94 mg/dL in normal subjects vs. 115.3 mg/dL in MS subjects). However, fasting glucose levels showed a strong correlation in the article of Iranian subjects, showing the highest odds ratio among the components of MS in both men and women. In that study, the mean value of plasma glucose level was over 140 mg/dL and the mean BMI is over 27.9 in men and over 29.07 in women. On the contrary, the data from Korean subjects showed that the mean value of BMI was around 24, which is drastically different from Iranian subjects. It is interesting to see this article considering the huge differences in anthropometry and clinical characteristics between Korean and Iranian subjects with or without MS. The higher fasting blood glucose and much higher obesity index of Iranian subjects could influence on the stronger influence of insulin resistance and chronic inflammation on serum vaspin concentration. Of note, despite these differences between two ethnical groups, hyper-TG and obesity index was a common metabolic factors, which showed significant correlation with vaspin levels in both groups. Overall, vaspin should be investigated in more detail to understand its role in humans.

Changes in Body Weight Predict CKD in Healthy Men

Several recent prospective studies have reported that obesity is associated with an increased risk for chronic kidney disease (CKD), but it is unknown whether weight gain increases the risk for CKD if one remains within the "normal" category of body mass index (BMI). We prospectively followed a cohort of 8792 healthy men who had no known risk factors for CKD and participated in a comprehensive health evaluation program at a large worksite. During 35,927 person-years of follow-up, 427 new incident cases of CKD (estimated GFR <64 ml/min per 1.73 m(2)) developed. Cox proportional hazards modeling revealed that in both the normal-weight and overweight groups, a U-shaped association between weight change categories and development of CKD was observed after adjustment for age, baseline GFR, baseline BMI, HDL, fasting blood glucose, uric acid, and exercise habits. The lowest risk for CKD was observed among those whose weight changed -0.25 to <0.25 kg/yr (P < 0.001 for quadratic term). Weight change as a time-dependent variable was significantly related to CKD incidence. These relationships remained significant even after further adjustment for Homeostasis Model Assessment of Insulin Resistance, high-sensitivity C-reactive protein, systolic BP, diastolic BP, metabolic syndrome, incident hypertension, or incident diabetes. In summary, increases in body weight are independently associated with an increased risk for CKD, even when the BMI remains within the normal range.

Association of Plasma Resistin With Glomerular Filtration Rate and Albuminuria in Hypertensive Adults

Resistin, a recently discovered proinflammatory cytokine, has been variably associated with insulin resistance, inflammation, and renal dysfunction. We investigated the association of plasma resistin with estimated glomerular filtration rate and albuminuria in 1575 hypertensive adults without known coronary heart disease or stroke (857 blacks and 718 non-Hispanic whites). Resistin was measured by a solid phase sandwich immunoassay, estimated glomerular filtration rate was estimated from serum creatinine, and albuminuria was expressed as urine albumin:creatinine ratio. After adjustment for coronary heart disease risk factors (age, sex, body mass index, smoking history, systolic blood pressure, diabetes, and total and high-density lipoprotein cholesterol) and use of renin-angiotensin blockers and statins, higher plasma resistin levels were associated with lower estimated glomerular filtration rate in both ethnic groups (each P<0.0001); the association remained significant after further adjustment for a marker of insulin resistance (homeostasis model assessment for insulin resistance) and a marker of inflammation (plasma C-reactive protein) and was seen in subjects with and without diabetes (each P<0.0001) in both ethnic groups. Higher plasma resistin levels were associated with a higher urine albumin:creatinine ratio in black subjects with diabetes (P<0.0001) and non-Hispanic white subjects with diabetes (P=0.032), independent of coronary heart disease risk factors, hypertension medication use, and statin use; the association remained significant after additional adjustment for homeostasis model assessment for insulin resistance and C-reactive protein. In adults with hypertension, higher circulating resistin levels were associated with a lower estimated glomerular filtration rate and with increased urine albumin:creatinine ratio in the presence of concomitant diabetes. This association was independent of coronary heart disease risk factors and markers of insulin resistance and inflammation.

Decreased serum adiponectin in adolescents and young adults with familial primary hypercholesterolemia

Decreased serum adiponectin is associated with dyslipidemia. However, serum adiponectin status has never before been studied in patients with familial-related severe primary hypercholesterolemia (FRSPH). The aim of this study is to measure serum adiponectin level in a group of young patients with FRSPH and determine its correlation with insulin-resistant status. Twenty-three patients with FRSPH [average LDL-cholesterol (LDL-C) = 250.8 (190-610) mg/dL] without clinical manifestations of metabolic syndrome as well as 46 healthy (control) adolescents and young adults (<30 yr old) were included. The serum adiponectin, fasting sugar, insulin, lipids, systolic and diastolic blood pressure (SBP and DBP), and anthropometrical indices such as body mass index and waist circumference were obtained. The homeostasis model assessment (HOMA) was calculated to estimate the insulin resistant status. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7+/-1.8 microg/mL vs. 10.1+/-4.3 microg/mL, P= 0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7 +/-1.8 microg/mL vs. 10.1+/-4.3 microg/mL, P = 0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. The serum adiponectin levels are lower in young patients with FRSPH without clinical manifestations of metabolic syndrome. The mechanism of hypoadiponectinemia in patients with FRSPH is probably independent of insulin resistance.

Microalbuminuria, a parameter independent of metabolic influences in hypertensive men.

To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.

Microalbuminuria, a parameter independent of metabolic influences in hypertensive men

OBJECTIVE To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. DESIGN Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. MAIN OUTCOME MEASURES Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. RESULTS HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. CONCLUSIONS Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.