Nutrition, Metabolism & Cardiovascular Diseases

Editorial Board

2010-03-01

Metabolic toxicity of the heart: Insights from molecular imaging

P. Iozzo — 2009-12-23

Abstract: There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure.The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion.The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity.

A composite scoring of genotypes discriminates coronary heart disease risk beyond conventional risk factors in the Boston Puerto Rican Health Study

2009-06-08

Abstract: Background and aims: Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs).Methods and results: We studied 11 SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1unit (high-risk allele homozygous), 0.5units (heterozygous) and 0units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements.The mean score was higher in participants with prior CHD than those CHD-free (P=0.015), and the OR for CHD with a GPS>5 was 2.90 (P<0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (≤5) were protected against CHD even if they were smokers (OR=0.44), heavy drinkers (OR=0.43), displayed low physical activity (OR=0.35), had hypertension (OR=0.52) or hyperlipidemia (OR=0.34) (P values ranging from 0.004 to 0.023).Conclusion: A simple genetic score of 11 polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors.

Metabolic syndrome and its association with white blood cell count in children and adolescents in Korea: The 2005 Korean National Health and Nutrition Examination Survey

Y.-J. Lee, Y.-H. Shin, J.-K. Kim, J.-Y. Shim, D.-R. Kang, H.-R. Lee — 2009-07-21

Abstract: Background and aims: To estimate the prevalence of metabolic syndrome (MS) and determine its association with white blood cell (WBC) count as a marker of low-grade systemic inflammation in children and adolescents in Korea.Methods and results: We investigated the prevalence of MS and its association with WBC count in 928 children and adolescents. MS was defined as having 3 or more conditions based on the modified criteria of the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP III). The odds ratios (ORs) for MS were also calculated using multivariate logistic regression analysis across WBC count quartiles (Q1, <5200; Q2, 5200–6100; Q3, 6200–7200; and Q4, ≥7300cells/μL for boys; Q1, <5200; Q2, 5200–6000; Q3, 6100–7000; and Q4, ≥7100cells/μL for girls). The prevalence of MS in children and adolescents in Korea was 6.7% (8.5% in boys, 4.5% in girls, P<0.001). MS was more prevalent in overweight and obese children and adolescents in both boys and girls. The mean WBC counts continuously increased with each additional component of MS in both boys and girls. The ORs (95% CIs) for MS in each WBC quartile were 1.00, 1.56 (0.43–5.67), 4.47 (1.42–14.07), and 5.25 (1.71–16.07) in boys and 1.00, 1.05 (0.15–7.61), 2.89 (0.55–15.17), and 7.47 (1.61–36.67) in girls after adjusting for age, household income, and residential area.Conclusion: In summary, this study shows that a substantial number of children and adolescents in Korea have MS, and elevated WBC count may be a surrogate marker for MS.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: A MONET study

2009-06-08

Abstract: Background and aims: The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women.Methods and results: This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7±4.8 yrs; body mass index: 32.4±4.6kg/m2; body fat: 38.6±9.2kg). Insulin sensitivity was determined by the euglycaemic–hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SIis) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15–28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15–17% of the variance.Conclusion: The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.

Interleukin-20 circulating levels in obese women: Effect of weight loss

2009-06-01

Abstract: Background and aims: Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight.Methods and results: Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P=0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r=0.35; P=0.02) and visceral fat (waist–hip ratio; r=0.32; P=0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153)pg/ml (median and 25%/75%; P=0.03), and it was positively associated with changes in body mass index and waist–hip ratio.Conclusion: In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist–hip ratio, and are reduced by weight loss.

Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people

2009-06-08

Abstract: Background and aim: The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form.Methods and results: Fifteen healthy individuals (12 M/3 F), mean age 54.5±7.6years, BMI 27.4±3.0kg/m2 (mean±SD), participated in a randomized sequential crossover study. After 2weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8g/day). After the two treatment periods (each lasting 3weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (−4.3%; p<0.03) and LDL (−4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting.Conclusions: Consumption of wholemeal wheat foods for 3weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Effects of a low glycemic load diet versus a low-fat diet in subjects with and without the metabolic syndrome

T.O. Klemsdal, I. Holme, H. Nerland, T.R. Pedersen, S. Tonstad — 2009-06-08

Abstract: Background and aim: Although many studies report benefits of low glycemic diets, the clinical effects as a whole are mixed. The study aim was to compare a low glycemic load (LGL) diet versus a low-fat diet in a trial with a moderately intense dietary intervention in subjects with varying degrees of metabolic syndrome.Methods and results: Men and women aged 30–65 years, with a BMI of 28–40kg/m2 (28–35 for women) and at least one criterion of metabolic syndrome were randomized to the two diets. A total of 202 subjects were included, of which 126 (62%) had metabolic syndrome (≥3 criteria). The completion rate was 81%. At 3 months, weight loss was greater in the LGL group (−4.8±3.9kg versus −3.8±3.5kg; P=0.06) compared to the low-fat group. At 1 year, however, weight loss was similar in both groups (−4.0±5.5kg versus −4.3±6.2kg; n.s.), but waist circumference reduction was less in the LGL group (−3.9±5.3cm versus −5.8±6.8cm; P=0.03). In contrast, diastolic blood pressure decreased significantly more in the LGL group (−4.0±8.7mmHg versus −1.1±8.5mmHg; P=0.02). We also observed a significant interaction between the presence of the metabolic syndrome and the effect of the two diets on waist circumference, with a less favorable effect of the LGL diet in subjects without the syndrome (P=0.039).Conclusion: After 12 months, both diets reduced body weight and the metabolic disturbances similarly, but the LGL diet appeared more suitable for subjects with metabolic syndrome, and was less effective in those without it.

Study of the effects of transoral gastroplasty on insulin sensitivity and secretion in obese subjects

2009-06-08

Abstract: Background and aims: Transoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion.Methods and results: Nine glucose normo-tolerant obese subjects (age:41±6years; BMI:42.49±1.03kg/m2) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution.Three months after surgery, a significant (P=0.008) reduction of BMI to 35.65±0.65kg/m2, with a decrease of FM and FFM from 57.22±2.19 to 41.46±3.02kg (P=0.008) and from 59.52±1.36 to 56.67±1.10kg (P=0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45±20.08 vs. 421.18±20.84ml/min/m2, P=0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05±27.50 to 124.77±14.50nmol/min/m2, P=0.021). Total ISR correlated with weight, BMI and FM (r=0.522, P=0.028; r=0.541, P=0.020; r=0.463, P=0.049, respectively). BMI represented the most powerful predictor of ISR decrease (R2=0.541, P=0.020).Conclusion: Transoral gastroplasty allows a significant weight loss 3months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy

2009-11-27

Abstract: Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance.Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function.In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents.A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

The high-molecular weight (HMW) form of adiponectin is a significant surrogate marker for the prediction of type 2 diabetes mellitus in the Japanese population

Hiroki Satoh, Satoshi Fujii, Hiroyuki Tsutsui — 2009-08-20

Decreased plasma adiponectin levels have a substantially high risk for the occurrence of type 2 diabetes mellitus (DM) . Adiponectin was present in serum as a hexamer of relatively low molecular weight and a larger meltimeric structure of high-molecular weight (HMW) . Mutations in the adiponectin gene such as G84R and G90S mutants are associated with type 2 DM and do not form HWW adiponectin , suggesting that alternations in HWW adiponectin levels might be more relevant in the occurrence of type 2 DM than those in plasma total adiponectin levels. Indeed, low HMW adiponectin levels are significantly associated with undiagnosed impaired glucose tolerance or type 2 DM in coronary artery disease patients . Pajvani et al demonstrated that the ratio of the plasma level of HMW adiponectin to that of the total adiponectin level (HMW adiponectin ratio, HMWR) is significantly more useful for the improvement of insulin sensitivity in response to thiazolidinedions in type 2 DM .

Abdominal subcutaneous adipose tissue morphology in a patient with a dominant-negative mutation (P467L) in the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARG) gene

R. Boiani, S. Cinti, D.B. Savage, A. Vidal-Puig, S. O'Rahilly — 2010-02-15

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear hormone receptor that works as transcription factor in a variety of tissues . It is known to be involved in adipocyte differentiation, lipid and glucose metabolism, cellular energy homeostasis, inflammation and carcinogenesis . The fact that PPARγ is required for adipogenesis was initially demonstrated in vitro and later confirmed by observations in PPARγ-deficient and hypomorphic mouse models . In addition to its pivotal role in promoting adipocyte differentiation, PPARγ is also a modulator of insulin sensitivity; in fact it is the biological target of synthetic agonists (thiazolidinediones) which are prescribed for their ability to improve insulin sensitivity in type 2 diabetic patients . The link between adipogenesis and insulin sensitivity regulated by PPARγ, in humans, was supported by the characterization of the metabolic syndrome resulting from dominant-negative mutations in PPARG .