Independent Risk Factor For Type Research Articles

High Plasma Immunoglobulin (Ig) A and Low IgG Antibody Titers to Oxidized Low-Density Lipoprotein Are Associated with Markers of Glucose Metabolism

Plasma oxidized low-density lipoprotein (OxLDL) is known to be associated with obesity, metabolic syndrome, and diabetes. The objective of the study was to investigate the association between plasma IgA, IgM, and IgG titers to OxLDL, phosphocholine (PC), and streptococcal cell wall polysaccharide (CWPS) and markers of glucose metabolism, type 2 diabetes, and liver adiposity. A population-based cohort of middle-aged Finns (n = 1039) participated in the study. Plasma IgM, IgG, and IgA to copper oxidized LDL (CuOx-LDL) and malondialdehyde-modified low-density lipoprotein (MDA-LDL), PC, and CWPS were determined with chemiluminescent ELISA and liver adiposity with ultrasonography. IgA autoantibody titers to OxLDL and PC, but not CWPS, were positively associated with fasting blood glucose and plasma insulin levels and inversely with insulin sensitivity index. IgA to OxLDL was significantly higher (P = 0.013 for CuOx-LDL and P = 0.016 for MDA-LDL) and IgG to OxLDL significantly lower (P = 0.036 for CuOx-LDL and P = 0.001 for MDA-LDL) among the subjects with type 2 diabetes compared with subjects with normal or impaired glucose metabolism when adjusted for age, sex, body mass index, smoking, and alcohol consumption. Logistic regression analysis showed that high plasma IgA to OxLDL and low IgG to MDA-LDL were independent risk factors for type 2 diabetes. Plasma IgA titers to OxLDL demonstrated a significant association with liver adiposity (P = 0.012) and gamma-glutamyltransferase levels (P = 0.002). Plasma IgA titers to OxLDL were positively and IgG titers negatively associated with markers of glucose metabolism. High plasma IgA and low IgG to OxLDL were independent risk factors for type 2 diabetes.

Pulsatile arterial compression of cranial nerves

The authors are to be commended for their observations on patients undergoing retromastoid craniectomy with microvascular decompression of the right ventrolateral medulla (VLM) and vagus nerve for type 2 diabetes mellitus. Seven of the 10 patients observed demonstrated overall glycemic control that either improved or did not worsen at the 12-month postoperative follow-up visit. These observations point the way to further questions that need to be answered to conclude definitively that pulsatile arterial compression of the right VLM is an independent risk factor for type 2 diabetes mellitus. As stated by the authors, a neurogenic basis for various cranial nerve hyperactive syndromes has long been postulated in the literature, with the first on essential hypertension made by Dr. Jannetta in the 1970s. Animal studies confirmed the presence of a subpial catecholamine-synthesizing neuronal group (C1) in the rostral ventrolateral medulla, which produces a transient pressor response when stimulated electrically, chemically or mechanically.[3,4,7,10] Histochemical studies of human medullae obtained at autopsy showed a similar group of catecholamine neurons in the subpial regions of the retro-olivary sulcus (ROS) near the root-entry zone of the ninth and tenth cranial nerves.[1,6] Conflicting results from early studies of the association between arterial compression and essential hypertension may have been due in part to inconsistencies in the exact location of compression or the failure to identify the subgroup of hypertensive patients most likely to benefit from microvascular decompression. Later studies began to address these questions. It was hypothesized that arterial pulsatile compression may either directly stimulate the C1 neurons or disinhibit them via an effect on the caudal ventrolateral medulla resulting in elevation of central sympathetic outflow or tone.[5] In support of this hypothesis, it was found that in a group of 18 subjects, those with vascular contact along the left ROS (presumed location of the C1 neurons) had higher baseline plasma norepinephrine concentrations and greater clonidine depressor response (sympathetic dependence of blood pressure) than those without vascular contact along the left ROS.[5] To better address the question of location, electrical stimulation studies were undertaken to precisely define the location of the sympatho-excitatory and inhibitory neuronal aggregates in humans.[9,11] A defined area of hypertensive responses was found at the mid ROS, centered 6 mm rostral to the lowest nerve root. Microneurography data suggested that the observed elevation of arterial blood pressure associated with electrical stimulation of this area was due to an activation of the sympathetic system, with no conclusive evidence of lateralization.[9,11] The question of whether arterial compression acted as an independent predictor of essential hypertension (apart from other known risk factors) was addressed in larger multivariable retrospective designs.[2,8] In a case-control study of 147 patients, it was found that the odds of arterial compression among hypertensive subjects were 2.99 times the odds among normotensive subjects (P= .04), controlling for hypertension risk factors such as age, body mass index, race, diabetes and family history of hypertension. Of compressed hypertensive subjects, 56% were compressed on the left and 44% on the right.[8] Collectively, these studies are building a body of evidence to aid the selection of patients eligible for microvascular decompression, i.e., those with intractable hypertension, elevated sympathetic tone, and arterial compression in accordance with a refined map of the human ventrolateral medullary surface and its relationship to cardiovascular control. Like Dr. Jannetta’s earlier observations on essential hypertension, the observations presented in the manuscript “Type 2 Diabetes Mellitus: A Central Nervous System Etiology” are valuable starting points for questions related to the exact location of arterial compression relevant to type 2 diabetes mellitus, the best experimental measure of response, and the subset of patients most likely to benefit from microvascular decompressive surgery. The authors have made a start in this direction by observing that non-obese patients with type 2 diabetes mellitus appear to respond better to decompression than obese patients. We encourage their continued efforts and those of other researchers in addressing those questions raised by this valuable contribution to our understanding of type 2 diabetes mellitus and its treatment.

The "fit but fat" concept revisited: population-based estimates using NHANES

Low cardiovascular fitness is an independent risk factor for type 2 diabetes and cardiovascular disease in adults. The "fit but fat" concept suggests that cardiovascular fitness attenuates risk of metabolic and cardiovascular disease independent of body mass index (BMI), even among the obese. However, the proportion of U.S. adults considered both fit and obese is unknown. Thus, the purposes of this short paper were to estimate the proportion of U.S. adults who are obese yet have a high cardiovascular fitness level (fit but fat), and determine the independent effect of obesity on cardiovascular fitness. The study was a secondary data analysis of 4,675 adults (20-49 years) who completed a submaximal exercise test, from the National Health and Nutrition Examination Survey (1999-2002). Cardiovascular fitness and body weight were expressed as continuous (estimated VO2max [ml.kg-1.min-1] and BMI [kg/m2]) and categorical variables (low, moderate, and high cardiovascular fitness level; normal weight, overweight, and obese), the later using sex and age-specific criteria from the Aerobics Center Longitudinal Study and standard BMI cut-points, respectively. Using these methods, the prevalence of meeting the fit but fat definition among U.S. adults was 8.9% (95% C.I. = 6.9 - 10.9%), whereas 17.4% were overweight and high fit, and 30% were normal weight and high fit. Importantly, the proportion of low, moderate, and high cardiovascular fitness differed significantly (p < 0.05) by BMI level. Using multiple regression, being obese was associated with a 9.2% lower estimated VO2max compared to being normal weight, even after controlling for age, sex, race/ethnicity, and income. These results suggest that a small percentage of U.S. adults can be considered fit but fat, and that obesity is independently associated with reduced cardiovascular fitness. The likely explanation for the low proportion of U.S. adults who can be considered fit but fat is a low level of physical activity, which constributes to both a positive energy balance and low fitness. Thus, engaging obese adults in physical activity that is sufficient to improve cardiovascular fitness may help to reduce not only body weight, but the excess health burden in this population.

C-reactive protein, gamma-glutamyltransferase and type 2 diabetes in a Chinese population

Background We studied the association of C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and type 2 diabetes in Chinese. Method A population-based cross-sectional study. Results CRP and GGT levels were significantly higher in participants with diabetes than in those without ( P < 0.001). Higher CRP levels were positively associated with prevalent type 2 diabetes after adjustment for age, sex, smoking, alcohol consumption, physical activity, family history of diabetes, body mass index, waist circumference, waist/hip ratio, education, systolic blood pressure, triglycerides, high density lipoprotein cholesterol, use of antihypertensive drugs, aspirin and lipid-lowering agents, with multivariable odds ratios (OR) of 1.55 (95% confidence interval (CI), 1.05–2.27, P trend = 0.005, comparing quartile 4 to quartile 1). However, after further adjustment for GGT, the association was completely attenuated (fourth quartile OR 1.23, 95% CI, 0.83–1.82, P trend = 0.127). Moreover, the association of CRP and prevalent type 2 diabetes was stronger in subjects with GGT values above the median than in those with GGT values below the median. Increasing serum GGT quartiles were positively associated with prevalent type 2 diabetes after adjustment for potential confounding variables ( P for trend < 0.001). Conclusion CRP may not be an independent risk factor for type 2 diabetes, at least in Chinese people.

Cigarette smoking is an independent risk factor for type 2 diabetes: a four‐year community‐based prospective study

We investigated the association between smoking and its additive effects with insulin resistance and beta-cell function on the incidence of type 2 diabetes in a prospective population-based cohort study. A total of 10 038 subjects were recruited from rural and urban areas. All subjects underwent 75 g oral glucose tolerance tests and full biochemical assessments at baseline and during 4-year follow-up period. The final analysis was limited to 4041 men due to the low smoking rates in women. The ex- and heavy current smokers had the highest incidence of diabetes of 12.5% and 11.1% respectively, compared with never-smokers (7.9%) during 4 years. After multivariate adjustment by Cox-proportional hazard model, ex- and current smokers reveal a relative risk of 1.60 (95% CI: 1.07-2.39), 2.06 (1.35-3.16, for <20 cigarettes/day) and 2.41 (1.48-3.93, for > or =20 cigarettes/day) respectively compared with never smokers. The risk of new onset diabetes was the highest in those with low homeostasis model assessment for beta cell function (HOMA-beta) and high homeostasis model assessment for insulin resistance (HOMA-IR) group in both smokers and never smokers. Smoking is an independent risk factor for type 2 diabetes mellitus and showed synergistic interaction with the status of low insulin secretion and high insulin resistance for developing diabetes. Given the high rates of smoking and growing burden of diabetes in the world, cessation of smoking should be considered as one of the key factors for diabetes prevention and treatment programmes.

Changes in racial/ethnic disparities in the prevalence of Type 2 diabetes by obesity level among US adults

Objective. Ethnic minority status and obesity are two independent risk factors for Type 2 diabetes (T2D). There is no clear understanding of how they may have interacted and influenced disparities in T2D prevalence over time. This study examined the trends in racial/ethnic disparities in the prevalence of T2D by weight status among US adults. Methods. We used nationally representative data from the National Health and Nutrition Examination Surveys I (1971–1975), II (1976–1980), and III (1988–1994), and 1999–2004 among 49,574 adults aged 20–74 years. The prevalences of diagnosed and undiagnosed T2D were estimated by race/ethnicity groups (non-Hispanic White, non-Hispanic Black, and Mexican American) and body mass index (BMI) groups (normal, 18.5–24.9; overweight, 25–29.9; obese, 30–34.9; severely obese, ≥35). We used logistic regression controlling for age, gender, and education to estimate the odds ratio of T2D across race/ethnicity and BMI groups. Results. Trends in racial/ethnic disparities in prevalence of diagnosed T2D varied by BMI. Normal weight group saw increasing racial disparities. In the overweight group, ethnic disparities worsened as diabetes prevalence increased 33.3% in Whites, compared to 60.0% in Blacks, and 227.3% in Mexican Americans. Minimal racial/ethnic disparities were observed in obese and severely obese groups over time. In contrast to diagnosed diabetes, overall racial/ethnic disparities in undiagnosed T2D declined in all BMI groups. Conclusions. Racial/ethnic disparities in diabetes prevalence have become most pronounced among normal and overweight groups. Eliminating racial/ethnic disparities in diabetes will require prevention efforts not only in obese minority individuals, but also in normal and overweight minority individuals.

Sleep Duration as a Risk Factor for Incident Type 2 Diabetes in a Multiethnic Cohort

We evaluated the association between sleep duration and type 2 diabetes in a multiethnic cohort, considering insulin sensitivity (S(I)) and secretion (acute insulin response [AIR]), two important diabetes risk factors. Among 900 diabetes-free persons, 146 developed incident type 2 diabetes. At baseline, sleep duration was assessed by self-report and S(I) and AIR by a frequently sampled intravenous glucose tolerance test. Among non-Hispanic whites and Hispanics, short sleep (<or=7 hours: odds ratio [OR] 2.36; 95% confidence interval [CI] 1.21-3.79 compared to 8 hours) was associated with increased odds of diabetes, adjusting for age, sex, glucose tolerance, clinical site, hypertension, family history of diabetes, smoking, education, and body mass index. Adjustment for S(I) and AIR did not affect short sleep (2.36; 1.11-5.00), but further attenuated the already non-significant association with long sleep (2.15; 0.50-9.30). In African Americans, an opposing pattern was observed, but none of the associations reached statistical significance. Our study supports the role of short sleep as an independent risk factor for type 2 diabetes in whites and Hispanics. While insulin sensitivity and secretion may explain previously reported associations of long sleep duration with diabetes risk, they do not seem to mediate the effects of short sleep on diabetes.

Sleep duration as a risk factor for the development of type 2 diabetes or impaired glucose tolerance: Analyses of the Quebec Family Study

Objective To examine the long-term relationship between sleep duration and type 2 diabetes or impaired glucose tolerance (IGT). Methods Body composition measurements and self-reported sleep duration were determined in a longitudinal sample of 276 individuals aged 21 to 64 years followed for a mean of 6 years. Risk factors of type 2 diabetes/IGT over the follow-up were determined and relative risks (RRs) calculated for the development of type 2 diabetes/IGT by sleep duration group. Results Independent risk factors of type 2 diabetes/IGT over the follow-up included age, obesity, sleep duration, and glucose/insulin homeostasis indicators. Using adults with 7-8 h of sleep as a reference, the adjusted RR for the development of type 2 diabetes/IGT was 2.78 (1.61-4.12) for those with ⩽6 h of sleep and 2.54 (1.42-3.53) for those with ⩾9 h of sleep. These elevated RRs remained significant after adjustment for body mass index, waist circumference or percent body fat. Conclusion Short and long sleeping times are associated with a higher risk of developing type 2 diabetes/IGT, independent of several covariates. These results suggest that sleep duration may represent a novel risk factor for type 2 diabetes/IGT.

Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis

We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies. We analysed a case-control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis. In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03-2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum gamma-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66-1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54-1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I (2) = 52.8%, p = 0.007). Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.

Smoking habits and the risk of type 2 diabetes: A case-control study

Aim The objective of the study was to assess the relationship between smoking and the risk of type 2 diabetes. Subject and methods This case-control study included 234 cases with newly confirmed diagnoses of type 2 diabetes and 468 controls who were free of the disease in 2001. Cases and controls were matched by gender and age (±5 years). A questionnaire was used to collect information on the possible risk factors of type 2 diabetes. Clinical measurements were taken in accordance with the recommendations of the WHO. Fasting plasma glucose and triglycerides were also measured, and the glucose tolerance test was performed in the controls. The odds ratios (OR) and 95% confidence intervals (CI) for type 2 diabetes were calculated using conditional logistic regression. Results The diabetes cases had significantly less education, more first-degree relatives with a positive family history of diabetes and higher body mass index (BMI) scores compared with the controls. Also, after adjusting for possible confounders, an increased risk of type 2 diabetes was determined for current smokers (OR = 2.41; 95% CI 1.07–5.44) vs. non-smokers. In addition, there was an association between the disease and duration of smoking (OR = 2.47; 95% CI 1.03–5.93 for 40 years or more) vs. non-smokers, and those who had been smokers for 10 or more pack-years had twice the risk of diabetes (OR = 2.17; 95% CI 1.07–4.40) vs. non-smokers. There were no significant associations found between the risk of type 2 diabetes and number of cigarettes smoked per day or stopping smoking. Conclusion Our data confirms that smoking may be an independent risk factor for type 2 diabetes.

Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes

OBJECTIVE—The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study.RESEARCH DESIGN AND METHODS—A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions.RESULTS—Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32–2.31]; RR for 10 μg/ml 1.04 [1.03–1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 μg/ml 1.03 [1.01–1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, γ-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 μg/ml full adjusted model 1.05 [1.02–1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.CONCLUSIONS—Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model☆

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

Uric Acid Indicates a High Cardiovascular Risk Profile but Is Not Closely Associated With Insulin Resistance in Obese Adolescents

We comment on a recent study by Dehghan et al. (1), who identified high serum uric acid as an independent risk factor for type 2 diabetes in adults. We investigated serum levels of uric acid in a large cohort of obese adolescents ( n = 355; mean ± SD age 13.1 ± 4.1 years and age range 10–22 years) and normal-weight control subjects ( n = 200) of …

Elevated liver enzymes in women with a family history of diabetes

Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9 kg/m 2 vs. 23.4 kg/m 2; p = 0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67 mmol/L vs. 5.22 mmol/L; p < 0.001), asparate aminotransferase (AST: 20.0 IU/L vs. 19.2 IU/L; p = 0.049), alanine aminotransferase (ALT: 18.4 IU/L vs. 16.7 IU/L; p = 0.004), gamma-glutamyltranspeptidase (GGT: 24.1 IU/L vs. 20.5 IU/L; p < 0.001), and triglycerides (TG: 1.09 mmol/L vs. 1.00 mmol/L; p = 0.011) for FHDM subjects, when adjusted for age and BMI. Multiple linear regression analysis revealed that FHDM, age, BMI, FPG, and TG were correlated with GGT ( p = 0.004 for FHDM; p < 0.001 for age, BMI, FPG, and TG). Elevated liver enzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.

Potential of Adiponectin as a Cardioprotective Agent

In this review, we focus on the role of adiponectin as a cardioprotective agent in several pathological heart conditions. Obesity is closely associated with Type 2 diabetes, hypertension and heart disease. Adiponectin is an adipose tissue-derived hormone whose concentration is downregulated in subjects with obesity-related diseases. Hypoadiponectinemia has been identified as an independent risk factor for Type 2 diabetes, coronary artery disease, acute coronary syndrome and hypertension. More recent experimental findings have shown that adiponectin directly affects signaling in cardiac myocytes and has beneficial effects on several pathological heart conditions, including cardiac hypertrophy and myocardial infarction. The favorable effects of adiponectin are associated with attenuated inflammatory response, decreased myocyte death, decreased hypertrophic response, maintained ischemia-induced angiogenesis and reduced interstitial fibrosis. Therefore, adiponectin could represent a molecular target for treating obesity-linked cardiac diseases.

Hepatitis C is associated with type 2 diabetes mellitus in HIV‐infected persons without traditional risk factors

Hepatitis C virus (HCV) monoinfection has been linked to type 2 diabetes mellitus (DM). We evaluated the effect of HCV on risk of DM in relation to traditional risk factors such as age, body mass index (BMI) and family history of DM in an HIV-infected population. This was a retrospective, cross-sectional study of 1529 HIV-infected out-patients. An adjusted multivariate logistic regression was performed to assess the effect of HCV seropositivity on DM stratified by low and high propensity for DM based on age, BMI and family history. Race, age, BMI, family history and HCV were associated with DM. Use of protease inhibitors (PIs) was not associated with DM, but HIV/HCV-coinfected patients were less likely to be on PIs than those with HIV infection alone. In a multivariate analysis controlled for race, the association between HCV and DM was stronger in lean, young patients without a family history of DM; the low-risk group. No association between HCV and type 2 DM was seen in patients who were older or overweight or had a family history of DM; the high-risk group. PI use did not affect the association between HCV and DM. Hepatitis C is an independent risk factor for type 2 diabetes in young, lean, HIV-infected patients. HIV-infected patients with HCV infection, regardless of whether they are on PIs, should be carefully screened for DM even if traditional risk factors for DM are not present.

Chemerin, a Novel Adipokine That Regulates Adipogenesis and Adipocyte Metabolism

Obesity is an alarming primary health problem and is an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Although the pathologic mechanisms linking obesity with these co-morbidities are most likely multifactorial, increasing evidence indicates that altered secretion of adipose-derived signaling molecules (adipokines; e.g. adiponectin, leptin, and tumor necrosis factor alpha) and local inflammatory responses are contributing factors. Chemerin (RARRES2 or TIG2) is a recently discovered chemoattractant protein that serves as a ligand for the G protein-coupled receptor CMKLR1 (ChemR23 or DEZ) and has a role in adaptive and innate immunity. Here we show an unexpected, high level expression of chemerin and its cognate receptor CMKLR1 in mouse and human adipocytes. Cultured 3T3-L1 adipocytes secrete chemerin protein, which triggers CMKLR1 signaling in adipocytes and other cell types and stimulates chemotaxis of CMKLR1-expressing cells. Adenoviral small hairpin RNA targeted knockdown of chemerin or CMKLR1 expression impairs differentiation of 3T3-L1 cells into adipocytes, reduces the expression of adipocyte genes involved in glucose and lipid homeostasis, and alters metabolic functions in mature adipocytes. We conclude that chemerin is a novel adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism.

Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue

During our study of the reversal of seasonal obesity in Siberian hamsters, we found an interaction between receptors for the pineal hormone melatonin and the sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT). This ultimately led us and others to conclude that the SNS innervation of WAT is the primary initiator of lipid mobilization in these as well as other animals, including humans. There is strong neurochemical (norepinephrine turnover), neuroanatomical (viral tract tracing), and functional (sympathetic denervation-induced blockade of lipolysis) evidence for the role of the SNS in lipid mobilization. Recent findings suggest the presence of WAT sensory innervation based on strong neuroanatomical (viral tract tracing, immunohistochemical markers of sensory nerves) and suggestive functional (capsaicin sensory denervation-induced WAT growth) evidence, the latter implying a role in conveying adiposity information to the brain. By contrast, parasympathetic nervous system innervation of WAT is characterized by largely negative neuroanatomical evidence (viral tract tracing, immunohistochemical and biochemical markers of parasympathetic nerves). Functional evidence (intraneural stimulation and in situ microdialysis) for the role of the SNS innervation in lipid mobilization in human WAT is convincing, with some controversy regarding the level of sympathetic nerve activity in human obesity.

Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans

Hypoadiponectinemia has emerged as an independent risk factor for type 2 diabetes and cardiovascular disease. Although associations of adiponectin with central obesity and insulin resistance have been reported, very little data are available from studies using detailed measures of insulin sensitivity (S(I)) and/or body fat distribution in ethnic groups at high risk for metabolic disease. The aim of the study was to identify the correlates of adiponectin in 1636 nondiabetic Hispanics and African-Americans. A cross-sectional analysis of participants in the Insulin Resistance Atherosclerosis Family Study was conducted. S(I) was determined from frequently sampled iv glucose tolerance tests with minimal model analysis. Subcutaneous and visceral adipose tissues (SAT, VAT, respectively) were determined with computed tomography. Triglyceride, high-density lipoprotein, C-reactive protein, and adiponectin were measured in fasting samples. Generalized estimating equation (GEE) models were used to identify factors associated with adiponectin concentration. A multicenter study using a family-based design was conducted. A total of 1636 nondiabetic Hispanic and African-American subjects participated. Circulating adiponectin concentration was measured. Age, female gender, high-density lipoprotein, SAT, and S(I) were positive independent correlates of adiponectin, whereas glucose, CRP, and VAT were negative independent correlates (all P < 0.05). Ethnicity was not an independent correlate of adiponectin in this model (P = 0.27); however, an ethnicity by VAT interaction term was retained, indicating a stronger negative association of VAT with adiponectin in African-Americans compared with Hispanics. Directly measured S(I), VAT, and SAT were independently correlated with adiponectin in Hispanic and African-American subjects. The inverse association of VAT with adiponectin was stronger in African-Americans compared with Hispanics, a finding that suggests possible ethnic differences in the effects of visceral obesity.

Birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults

To investigate the association between birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults. Nine hundred and seventy-three individuals from a population-based cross-sectional survey for the prevalence of type 2 diabetes conducted in Shanghai in 2002 were enrolled and followed up to 2004 with yearly examination. Birth weight was classified into four categories: <2500, 2500-2999, 3000-3499 and >or=3500 g. In this study, there were 373 males and 600 females, with a mean age of 46.2+/-9.9 years. Fasting plasma glucose was higher in subjects with the lowest birth weight (<2500 g) compared with those with the highest birth weight. Waist circumference and systolic blood pressure showed U-shaped relationships with birth weight. Birth weight was found to be an independent risk factor for type 2 diabetes, abdominal obesity and hypertension. For type 2 diabetes, the crude odds ratio (95% confidence interval) was 3.17 (1.48-6.78) in the lowest birth weight category when compared with that in the highest birth weight category (>or=3500 g) and the ratio increased to 3.97 (1.71-9.22) after adjustment for related variables. The highest prevalence of type 2 diabetes (34.5%) was observed among those with the lowest birth weight and abdominal obesity. Birth weight is inversely associated with the risk of type 2 diabetes. Subjects with the lowest or the highest birth weight were associated with a high risk of developing abdominal obesity and hypertension. Low birth weight coupled with abdominal obesity is a strong predictor of type 2 diabetes.