High-insulinogenic nutrition--an etiologic factor for obesity and the metabolic syndrome?

This report postulates a critical role for the quantity and quality of dietary carbohydrate in the pathogenesis of obesity and the metabolic syndrome. Significant changes in human nutrition have occurred during the last 10,000 years, culminating in the current high-glycemic/high-insulinogenic nutrition. A high insulinogenic nutrition represents a chronic stimulus to the beta cells that may induce an adaptive hypertrophy and a progressive dysregulation of the cells, resulting in postprandial hyperinsulinemia, especially in genetically predisposed subjects. Significant evidence suggests that postprandial hyperinsulinemia promotes weight gain and the development of insulin resistance/metabolic syndrome. The hypothesis is able to explain the current epidemic of obesity and the metabolic syndrome in most industrialised countries, as well as some of the genetics of obesity, including the extreme high incidence of obesity and the metabolic syndrome in certain ethnic groups.     

Is hyperhomocysteinemia an additional risk factor of the metabolic syndrome?

The aim of this study was to ascertain if hyperhomocysteinemia is associated with the metabolic syndrome. The metabolic syndrome is a cluster of cardiovascular risk factors. Hyperhomocysteinemia is an obvious independent risk factor for atheroma, and thrombosis morbidity and mortality. EPIMIL is a prospective epidemiological survey, which began with a crosssectional study of cardiovascular risk factors in a French male population, followed by monitoring for 10 years. Initial data collection, blood pressure measurement, ECG, and blood samples have been performed. For the metabolic syndrome, we used the criteria of the Third Report of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) on detection, evaluation, and treatment of high blood cholesterol in adults. Out of 2045 men aged 20-58 years (37.7 +/- 8.7 years), 185 (9%) have metabolic syndrome (at least three criteria), 587 (29%) have a plasma homocysteine level of >/=12 micromol/L, and 202 (10%) have a level of >/=15 micromol/L. Mean homocysteinemia is 10.97 +/- 5.01 micromol/L for the whole population and does not differ significantly with (11.4 +/- 6 micromol/L) or without (10.9 +/- 5 micromol/L) the metabolic syndrome, as does its value distribution. Nor does it correlate with the Body Mass Index (BMI), waist and hip measurements, or blood glucose, HbA1c, insulin resistance, and cardiovascular risk markers (CRPus, microalbuminuria). It weakly correlates with systolic and diastolic blood pressure, creatinine clearance, tobacco use, cholesterolemia, triglycerides, and free fatty acids, but not with HDL and LDL fractions, or lipoprotein(a) (Lp(a)). It contributes slightly to the 10-year vascular risk according to the Framingham equations or Score system. In this male population, homocysteinemia and the prevalence of hyperhomocysteinemia do not differ with or without the metabolic syndrome. Plasma homocysteine level does not correlate with its main criteria. Hyperhomocysteinemia is not associated with the metabolic syndrome; nevertheless, it should be monitored in high-risk cardiovascular patients.     

Uric acid: A new marker for metabolic syndrome? Results of a population-based study with adults

Background and aimsRecently, studies have shown a positive association between serum uric acid (UA) and metabolic syndrome (MS). To evaluate the predictive capacity and the association of serum UA with pre-MS and MS, by sex, in adults.Methods and resultsCross-sectional study with 932 adults, of both sexes, from Viçosa, Minas Gerais (MG), Brazil. Sociodemographic and behavioral data were obtained through a questionnaire and anthropometric, clinical, and biochemical evaluation. We used multinomial logistic regression and the area under receiver operating characteristic curve (AUC). The prevalence of pre-MS was 17.8% and of MS was 26.5%. The fitted models showed positive association of serum UA with pre-MS (OR = 1.62, 95% CI = 1.09–2.40) and MS (OR = 2.61, 95% CI = 1.99–3.42) among men. For women, similar results were found for MS (OR = 2.59, 95% CI = 1.81–3.73). The optimal cutoff points obtained by AUC for pre-MS and MS were 4.7 and 4.9 mg/dL among men and 3.1 and 3.4 mg/dL among women, respectively.ConclusionThe results point to a positive association of UA with pre-MS and MS, with no significant differences between sexes. Therefore, UA can be used as an additional marker in the screening of these conditions.     

Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome?

The outcomes of fibrate trials have varied: positive with gemfibrozil in the primary prevention Helsinki Heart Study and the secondary prevention VA-HIT trial; positive with reservations in the primary prevention WHO trial (clofibrate); and mixed with bezafibrate in the secondary prevention BIP study and with fenofibrate in the combined primary and secondary prevention FIELD study. Overall, the mixed results, combined with potential for adverse effects when given in combination with statins, have limited the use of these fibrates as cardioprotective agents. However, post hoc analyses of several of the fibrate studies have shown that people with features of the metabolic syndrome, particularly overweight people with high plasma triglyceride levels and low levels of HDL cholesterol, derive a disproportionately large reduction in cardiovascular events when treated with these agents. Thus, there is a strong case for the use of a fibrate to reduce the cardiovascular risk in overweight people with high triglyceride and low HDL-C. However, it should be noted that such people also have their cardiovascular risk reduced by statin therapy. It remains to be determined whether the combination of a fibrate plus statin reduces the risk beyond that achieved with a statin alone.     

Is sleep-disordered breathing an additional risk factor for the metabolic syndrome in obese children and adolescents?

Sleep-disordered breathing is highly prevalent in childhood obesity. Two recent cross-sectional studies have demonstrated an independent association between the severity of sleep-disordered breathing and the metabolic syndrome. A limited number of studies have also addressed the correlation between sleep-disordered breathing and insulin resistance, the core factor of the metabolic syndrome. Cross-sectional reports in modestly obese children are in favor of an association between sleep apnea and insulin resistance. However, these findings were not confirmed in studies of normal-weight children and of morbidly obese children. Only one out of three treatment studies before and after adenotonsillectomy confirmed the association between sleep apnea and insulin resistance, but only in obese children. Although statistical power issues and differences in patient characteristics might partially explain these contradicting results, the evidence to date is far from establishing a causal link between sleep-disordered breathing and insulin resistance. Longitudinal studies and randomized control trials are therefore warranted to investigate a possible causal link between sleep-disordered breathing and insulin resistance.     

Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?

Insulin-like growth factor (IGF) binding proteins (IGFBPs) moved on to contain both IGF high- and low-affinity binders, exerting mitogenic and metabolic actions through its complex interplay between IGF/insulin and its IGF/insulin-independent manner. Progress on the metabolic-related function of IGFBPs has been rapid in recent years. A wealth of studies in 3T3-L1 adipocytes and the transgenic mice models demonstrated that IGFBPs played important roles in the pathogenesis of obesity and insulin resistance. Studies conducted in humans demonstrated the close relation between IGFBPs and the components of the metabolic syndrome. Abnormal expression of IGFBP was detected in various states of the metabolic disorders, suggesting that it could be used as a convenient and sensitive marker of insulin resistance, identification of insulin-resistant individuals at high cardiovascular risk, and may be an earlier marker of the metabolic syndrome. These exciting findings bring us new insight into the elucidation of the metabolic syndrome, which may have important clinical implications.     

How many doses of diphtheria toxoid are required for protection in adults? Results of a case-control study among 40- to 49-year-old adults in the Russian Federation

During the Russian diphtheria epidemic of the 1990s, adults had an unexpectedly high rate of disease. A retrospective, matched case-control study was done to measure the effectiveness of one, two, or three or more doses of diphtheria toxoid against diphtheria among 40- to 49-year-old Russians. Thirty-nine diphtheria case-patients and 117 controls were studied. Previous vaccinations were included if one dose was received within the previous 10 years. Five cases (13%) and 33 controls (28%) had received three or more doses of vaccine. The matched odds ratio was 0.3 (95% confidence interval, 0.1-0.9) for three or more doses compared with no doses, which was a vaccine effectiveness of 70% (95% confidence interval, 10-90). A trend existed toward milder disease with increasing doses (chi2 test for trend, P=.02). The results suggest that Russian adults, who were unlikely to have acquired immunity to diphtheria through immunization or natural infection, required at least three doses of diphtheria toxoid for reliable protection against disease.     

Low-carbohydrate or low-fat diets for the metabolic syndrome?

This report discusses a variety of considerations and reviews recent clinical trial data relevant to the question of which dietary approach is optimal for treatment and prevention of the metabolic syndrome. Special emphasis is given to the question of whether the degree to which metabolic syndrome features are observed in an individual patient should correspond to the degree to which carbohydrate restriction should be recommended. Short-term metabolic studies lend support to this concept, but longer-term effectiveness trials suggest the degree of dietary adherence and associated weight losses, rather than diet type, are the key predictors of metabolic cardiac risk factor reduction.     

Is metabolic syndrome a risk factor for carotid atherosclerosis in normotensive and prehypertensive individuals?

AIM: We have investigated whether metabolic syndrome is a risk factor for carotid atherosclerosis also in normotensive or prehypertensive individuals. METHODS: We analyzed the data from 851 subjects who had a blood pressure of less than 140/90 mmHg and were not taking antihypertensive medication. Metabolic syndrome was defined according to three different criteria: Japan criteria (Japan-MetS); those of the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) (NCEP-MetS); and modified NCEP-ATP III criteria in which body mass index was used as a surrogate for waist circumference (modified NCEP-MetS). RESULTS: Japan-MetS, NCEP-MetS, and modified NCEP-MetS were found, respectively, in 1%, 4%, and 4%, of women, and in 10%, 5%, and 9%, of men. After the adjustment for gender and age, the association between MetS and carotid atherosclerosis did not reach statistical significance. CONCLUSION: Although the number of enrolled subjects was relatively small, these data may further support the importance of controlling blood pressure within the optimal range for the purpose of preventing atherosclerosis in individuals with metabolic syndrome.