Incidence of components of metabolic syndrome in the metabolically healthy obese over 9 years follow-up: the Atherosclerosis Risk In Communities study.

BackgroundSome obese adults are not afflicted by the metabolic abnormalities often associated with obesity (the 'metabolically healthy obese' (MHO)); however, they may be at increased risk of developing cardiometabolic abnormalities in the future. Little is known about the relative incidence of individual components of metabolic syndrome (MetSyn).MethodsWe used data from a multicenter, community-based cohort aged 45-64 years at recruitment (the Atherosclerosis Risk In Communities study) to examine the first appearance of any MetSyn component, excluding waist circumference. Body mass index (BMI, kg m-2) and cardiometabolic data were collected at four triennial visits. Our analysis included 3969 adults who were not underweight and free of the components of MetSyn at the initial visit. Participants were classified as metabolically healthy normal weight (MHNW), overweight (MHOW) and MHO at each visit. Adjusted hazard ratios (HR) and 95% confidence intervals were estimated with proportional hazards regression models.ResultsThe relative rate of developing each risk factor was higher among MHO than MHNW, with the strongest association noted for elevated fasting glucose (MHO vs MHNW, HR: 2.33 (1.77, 3.06)). MHO was also positively associated with elevated triglycerides (HR: 1.63 (1.27, 2.09)), low high-density lipoprotein-cholesterol (HR: 1.68 (1.32, 2.13)) and elevated blood pressure (HR: 1.54 (1.26, 1.88)). A similar, but less pronounced pattern was noted among the MHOW vs MHNW.ConclusionsWe conclude that even among apparently healthy individuals, obesity and overweight are related to more rapid development of at least one cardiometabolic risk factor, and that elevations in blood glucose develop most rapidly

A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes

BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study. Spijkerman AM, Henry RM, Dekker JM, Nijpels G, Kostense PJ, Kors JA, Ruwaard D, Stehouwer CD, Bouter LM, Heine RJ. Institutes for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. [email protected] OBJECTIVES: Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications. DESIGN: Cross-sectional population-based study. SETTING: Population study, primary care. SUBJECTS: Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients). Ischaemic heart disease and prior myocardial infarction were assessed by ECG recording. Peripheral arterial disease was assessed by the ankle-arm index. Intima-media thickness of the right common carotid artery was measured with ultrasound. RESULTS: A total of 195 SDM patients and 60 GPDM patients participated in the medical examination. The prevalence of MI was 13.3% (95% CI 9.3-18.8%) and 3.4% (1.0-11.7%) in SDM patients and GPDM patients respectively. The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients. The prevalence of peripheral arterial disease was similar in both groups: 10.6% (95% CI 6.9-15.9%) and 10.2% (4.7-20.5%) respectively. Mean intima-media thickness was 0.85 mm (+/-0.17) in SDM patients and 0.90 mm (+/-0.20) in GPDM patients. The difference in intima-media thickness was not statistically significant. CONCLUSIONS: Targeted screening identified patients with a prevalence of macrovascular complications similar to that of patients detected in general practice, but with a lower degree of hyperglycaemi

Changes in Body Composition Over 8 Years in a Randomized Trial of a Lifestyle Intervention: The Look AHEAD Study

Objective To determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. Methods Body composition was measured by dual‐energy X‐ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. Results At 1 year, the intervention group lost fat (5.6 ± 0.2 kg) and lean mass (2.3 ± 0.1 kg) but regained fat (∼100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 ± 0.4 vs. 2.3 ± 0.4 kg); comparison group weight loss was mostly lean mass (2.1 ± 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post‐baseline time points. Conclusions Reduced fat mass may place the intervention group at a lower risk of obesity‐linked sequelae, a hypothesis that can be tested by future studies of this cohort

Racial Differences in Exposure and Glucuronidation of the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK)

BACKGROUND; In the United States, Blacks who smoke cigarettes have a higher mean blood concentration of the nicotine metabolite cotinine than White smokers. It has not been determined whether there are racial differences in the exposure to the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and in the detoxification of NNK metabolites. METHODS; A community-based cross-sectional survey of 69 Black and 93 White smokers was conducted in lower Westchester County, New York. Information on smoking and lifestyle habits was collected and urinary concentrations of several tobacco smoke biomarkers were compared, including the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). A frequency histogram and probit plot of NNAL-Gluc:NNAL ratios were constructed to determine slow and rapid glucuronidation phenotypes. RESULTS; The mean concentrations of total NNAL, urinary cotinine, plasma cotinine, and thiocyanate were significantly higher in Black men than in White men for each cigarette smoked. In women, the only biomarker that was significantly elevated in Blacks was plasma cotinine. A higher proportion of White versus Black women was categorized as "rapid" glucuronidators (two-tailed exact test, P = 0.03). In men, there were no significant differences in NNAL-Gluc:NNAL phenotypes. CONCLUSIONS; The higher rates of lung carcinoma in black men may be due in part to a higher level of exposure to tobacco smoke carcinogens

Combined aerobic and resistance exercise training decreases peripheral but not central artery wall thickness in subjects with type 2 diabetes

Objective Little is known about the impact of exercise training on conduit artery wall thickness in type 2 diabetes. We examined the local and systemic impact of exercise training on superficial femoral (SFA), brachial (BA), and carotid artery (CA) wall thickness in type 2 diabetes patients and controls. Methods Twenty patients with type 2 diabetes and 10 age- and sex-matched controls performed an 8-week training study involving lower limb-based combined aerobic and resistance exercise training. We examined the SFA to study the local effect of exercise, and also the systemic impact of lower limb-based exercise training on peripheral (i.e. BA) and central (i.e. CA) arteries. Wall thickness (WT), diameter and wall:lumen(W:L)-ratios were examined using automated edge detection of ultrasound images. Results Exercise training did not alter SFA or CA diameter in type 2 diabetes or controls (all P > 0.05). BA diameter was increased after training in type 2 diabetes, but not in controls. Exercise training decreased WT and W:L ratio in the SFA and BA, but not in CA in type 2 diabetes. Training did not alter WT or W:L ratio in controls (P > 0.05). Conclusion Lower limb-dominant exercise training causes remodelling of peripheral arteries, supplying active and inactive vascular beds, but not central arteries in type 2 diabetes

The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

BACKGROUND: Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. METHODS: We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. RESULTS: UCP1 A-3826G was associated with AIR(g )in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). CONCLUSION: This study suggests a functional variant of UCP1 contributes to the variance of AIR(g )in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets

Higher prevalence of smoking and lower BMI, waist circumference, cholesterol and triacylglyceride levels in Prague's homeless compared to a majority of the Czech population

BACKGROUND: Homeless people have higher morbidity and mortality rates than the general population. Research has shown that cardiovascular disease is the leading cause of death in older homeless adults. This study was undertaken to describe the prevalence of cardiovascular risk factors in the homeless population in Prague. METHODS: Data was obtained from a cross-sectional study carried out in 2003. Body mass index (BMI), waist circumference (WC), total cholesterol (TC), triacylglycerides (TAG) and smoking habits were assessed. The homeless participants in the study were recruited from a homeless center run by a Prague charitable organization called Naděje ("Hope") and at Prague's main railway station. Most participants were assessed at the Naděje center (134 persons) while the rest were assessed at Prague's Bulovka University Hospital (67 persons). RESULTS: A total of 201 homeless (174 males and 27 females) aged 19 – 70 years were examined. Mean values of BMI, WC, TC and TAG in homeless men and women were within normal limits. Compared with the majority of the Czech population, the homeless had significantly lower mean levels of TC and TAG and lower BMI and WC values. When compared to the majority of the Czech population, the incidence of smoking among the homeless was significantly higher. Among smokers in both populations, no differences were found in the number of cigarettes smoked per day. CONCLUSION: Classical cardiovascular risk factors such as TC, TAG, BMI and WC, are significantly lower in Prague's homeless minority than in the majority of the Czech population. However, the prevalence of smoking is much higher in the homeless population

Utility of Atherosclerosis Imaging in the Evaluation of High-Density Lipoprotein–Raising Therapies

Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C–raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C–raising compounds are effective involve improvement of cholesterol uptake from macrophages in plaque for transport back to the liver, improvement of endothelial function, and anti-inflammatory effects. Vascular imaging can aid in the determination which HDL-C–raising compounds are effective. Ultrasound and MRI have proved suitable for assessment of structural changes of the vessel wall. Ultrasound can also be used or assessment of endothelial function. 18F-fluordeoxyglucose positron emission tomography has opened up the possibility to assess vessel wall inflammation. In this article we discuss these various imaging techniques and how they can assess efficacy as well as provide pathophysiologic information on the mechanism of action of novel HDL-C–raising drugs

INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G\u3eC, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035). Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation