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Biomedical subjects

Rafael Carmena

Publications and source records attributed to Rafael Carmena.

At least 19 recordsLinked to original sources
PubMed2006

Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study.

AIM: To assess the prevalence of Coronary Heart Disease (CHD) and Metabolic Syndrome (MS) in patients treated with antipsychotics. METHODS: Retrospective, cross-sectional, multicenter study in which 117 Spanish psychiatrists (the CLAMORS Study Collaborative Group) recruited consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, receiving antipsychotic treatment for at least 12 weeks. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CHD events) function. MS was defined by at least 3 of the following components: waist circumference >102 (men)/>88 (women) cm; triglycerides > or =150 mg/dl; HDL-cholesterol <40 mg/dl (men)/<50 mg/dl (women); blood pressure > or =130/85; fasting glucose > or =110 mg/dl. RESULTS: 1452 evaluable patients (863 men, 60.9%), aged 40.7+/-12.2 years (mean+/-SD) were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p=0.130)]. The overall 10-year risks were 0.9+/-1.9 (SCORE) and 7.2+/-7.6 (Framingham). 8% (95%CI: 6.5-9.5) and 22.1% (95%CI: 20.0-24.3) of patients showed a high/very high risk according to SCORE (> or =3%) and Framingham (> or =10%) function. Abdominal obesity and low HDL-cholesterol were more prevalent in women: 54.5% (95%CI: 50.2-58.9) versus 34.3% (95%CI: 31.0-37.7), and 46.1% (95%CI: 41.4) versus 28.5 (95%CI: 50.8), p<0.001 in both cases. Hypertension and hypertriglyceridemia were more prevalent in men: 59.0% (95%CI: 55.7-62.3) versus 46.0% (95%CI: 41.8-50.2), and 40.7% (95%CI: 37.2-44.2) versus 32.4 (95%CI: 28.3-36.5), p<0.01 in both cases. CONCLUSIONS: CHD risk and MS prevalences among patients with schizophrenia treated with antipsychotics were in the same range as the Spanish general population 10 to 15 years older.

Adolescent↗
PubMed2006

Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study.

BACKGROUND: Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome. METHODS: The TNT study was a prospective, double blind, parallel-group trial done at 256 sites in 14 countries between April, 1998, and August, 2004, with a median follow-up of 4.9 years. 10,001 patients were enrolled aged 35-75 years with clinically evident coronary heart disease. Our analysis includes 5584 patients with metabolic syndrome based on the 2005 NCEP ATP III criteria. Patients were randomly assigned to receive either atorvastatin 10 mg per day (n=2820) or 80 mg per day (n=2764). The primary outcome measure was time to first major cardiovascular event, defined as death from coronary heart disease, non-fatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or non-fatal stroke. FINDINGS: In patients with coronary heart disease and metabolic syndrome, mean on-treatment low-density lipoprotein cholesterol concentrations at 3 months were 2.6 mmol/L (99.3 mg/dL) with atorvastatin 10 mg, and 1.9 mmol/L (72.6 mg/dL) with atorvastatin 80 mg. At a median follow-up of 4.9 years, major cardiovascular events occurred in 367 (13%) patients receiving atorvastatin 10 mg, compared with 262 (9.5%) receiving atorvastatin 80 mg (hazard ratio 0.71; 95% CI 0.61-0.84; p<0.0001). Irrespective of treatment assignment, significantly more patients with metabolic syndrome (11.3%) had a major cardiovascular event at a median of 4.9 years than those without metabolic syndrome (8.0%; hazard ratio 1.44; 95% CI 1.26-1.64; p<0.0001). This increased risk was significantly reduced by intensive therapy with atorvastatin 80 mg beyond that achieved with atorvastatin 10 mg. INTERPRETATION: These data indicate that patients with coronary heart disease and metabolic syndrome derive incremental benefit from high-dose atorvastatin therapy, irrespective of the presence of diabetes.

Adult↗
PubMed2006

[Role of atherogenic dyslipidemia in the development of metabolic syndrome].

BACKGROUND AND OBJECTIVE: Our goal was to know if the diagnosis of metabolic syndrome (MS) as defined by International Diabetes Federation (IDF) criteria 2005 identifies more subjects with atherogenic dyslipidemia and high cardiovascular risk than the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP-III) criteria. PATIENTS AND METHOD: Cross-sectional study in an adult population (20-70 years) of 344 subjects (158 males and 186 females), who visited an out-patient clinic in the metropolitan area of Valencia over a period of one year. Opportunistic search method was used. We studied: anthropometrics parameters, blood pressure, plasma lipids -non-high-density lipoprotein cholesterol (no-HDL-c), and total cholesterol:high-density lipoprotein cholesterol index (TC-HDL-c)-, glucose and insulin, and HOMA (Homeostasis Model Assessment) index. RESULTS: We have separated the subjects on the basis to the IDF or ATP-III criteria to define the MS. The MS define a group of subjects with important plasma lipids alterations and cardiovascular risk: increase of no-HDL-c, of TC:HDL-c index and of apolipoprotein B. The TC:HDL-c index was > or = 6 in 28.6% of the subjects with MS and only in 9.4% of the subjects without MS (p < 0.0001) by IDF criteria and in 34.6% of the subjects with MS-ATP-III, and in 8.6% without MS-ATP-III (p < 0.0001). The apolipoprotein B > or = 1.2 g/l was observed in 44% of the subjects with MS and only in 26% without MS IDF criteria (p < 0.0001), and only in 47.6% and 28.6%, respectively, by ATP-III criteria (p < 0.0001). CONCLUSIONS: The MS defined by the IDF or ATP-III criteria equally identifies subjects with atherogenic dyslipidemia, with increase of no-HDL-c, of the TC: HDL-c index and of the apolipoprotein B and, for this reason, with high cardiovascular risk.

Adult↗
PubMed2006

Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?

BACKGROUND: Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies. METHODS: Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences). RESULTS: We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60% of the variants had a frequency as low as 1%. A previously described method for detection of known sequence variations in the Spanish population by DNA array analysis allowed the identification of only approximately 50% of patients with a variant LDLR gene and approximately 40% of the screened samples. CONCLUSION: Our results indicate that the adequate procedure to identify LDLR sequence variations in outbreed populations should include screening of the entire gene.

Apolipoproteins B↗
PubMed2006

Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization.

Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) that we have used as positive mutation controls (Valencia-1 to -5). All altered exons from each rearrangement are identified. Furthermore, when families from probands carrying these large rearrangements (34 members) were analyzed, our results agreed with those obtained previously with Southern blot. We have also analyzed a sample of 110 unrelated FH probands and the method has correctly identified the two different large rearrangements present and insertions or deletions as small as 1 bp. In conclusion, the method we present allows the identification of large rearrangements affecting exons of the gene, including small insertions or deletions or complete gene deletion. In addition, it constitutes a first characterization step of rearrangements, and is easy to carry out fast, and can be applied to the analysis of any gene.

Apolipoproteins B↗
PubMed2006

Effects of a controlled program of moderate physical exercise on insulin sensitivity in nonobese, nondiabetic subjects.

OBJECTIVE: To study the effect of a moderate, aerobic physical exercise program on insulin resistance and its accompanying metabolic changes in a group of healthy, middle-age, nonobese subjects, without modifying oxygen consumption and body weight. DESIGN: The inclusion of subjects was carried out among volunteers from the health personnel of our center, who complied with the inclusion criteria. PARTICIPANTS: Twelve subjects (age 30-60 years, 5 females), nonsmokers, body mass index (BMI) <27 kg/m2 and fasting plasma glucose <6.1 mmol/L. INTERVENTIONS: Insulin resistance was assessed using the Bergmann minimal model modified with insulin, and basal and maximum metabolic rate were measured with standard methods. All subjects completed a 2-month program of aerobic exercise using the American College of Sports Medicine guidelines, consisting of aerobic exercise of moderate, regular, and continual intensity (3 times per week), with a duration of 45 to 50 minutes per session. RESULTS: Following controlled exercise, no significant differences in BMI, waist-hip ratio, blood pressure, lipids, free fatty acids, and leptin plasma values were observed. Plasma glucose and insulin values decreased significantly (-0.37 mmol/L and -16.5 pmol/L, respectively). Insulin sensitivity showed an increase of 2.1 x 10(-4) mU L(-1) min(-1) (P = 0.001). Basal and maximum metabolic rate showed no significant differences after the exercise program. CONCLUSIONS: Moderate aerobic exercise increases insulin sensitivity in nonobese, nondiabetic subjects in the absence of significant changes in weight, BMI, waist-hip ratio, lipid profile, and oxygen consumption.

Adult↗
PubMed2006

Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study.

OBJECTIVE: The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes. RESEARCH DESIGN AND METHODS: A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke. RESULTS: End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58-0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48-0.98], P = 0.037) and any cardiovascular event (0.85 [0.73-1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes. CONCLUSIONS: Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.

Aged↗
PubMed2006

[Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease].

Our aim was to investigate the relationship between metabolic syndrome and cardiovascular disease (i.e., survivors of myocardial infarction) in patients with familial combined hyperlipidemia (FCH). We compared a group of 20 male patients with FCH who had survived a myocardial infarction with two other groups matched for age and body mass index, comprising 20 individuals with FCH who had not had a myocardial infraction and 20 control subjects. Plasma lipid, glucose, and insulin levels were determined. Metabolic syndrome was judged to present on the basis of World Health Organization (WHO) and National Cholesterol Education Program-Adult treatment panel (NCEP-ATPIII) criteria. Differences between the groups were evaluated using non-parametric tests and the association between ischemic coronary disease and other parameters was assessed by logistic regression analysis. According to WHO criteria, the metabolic syndrome was present in 19 FCH patients who had survived a myocardial infarction, in 11 individuals with FCH who had not had a myocardial infraction, and in six control subject (P<.001); the difference between FCH patients with and without myocardial infarction was significant (P<.01). Presence of the metabolic syndrome, as defined by WHO criteria, is a marker of cardiovascular risk in individuals with FCH.

Case-Control Studies↗
PubMed2005

Weaning induces NOS-2 expression through NF-kappaB modulation in the lactating mammary gland: importance of GSH.

At the end of lactation the mammary gland undergoes involution, a process characterized by apoptosis of secretory cells and tissue remodelling. To gain insight into this process, we analysed the gene expression profile by oligonucleotide microarrays during lactation and after forced weaning. Up-regulation of inflammatory mediators and acute-phase response genes during weaning was found. Expression of IkappaBalpha (inhibitory kappaBalpha), a protein known to modulate NF-kappaB (nuclear factor-kappaB) nuclear translocation, was significantly up-regulated. On the other hand, there was a time-dependent degradation of IkappaBalpha protein levels in response to weaning, suggesting a role for NF-kappaB. Furthermore, we have demonstrated, using chromatin immunoprecipitation assays, binding of NF-kappaB to the NOS-2 (inducible nitric oxide synthase) promoter at the early onset of events triggered during weaning. The three isoforms of NOS are constitutively present in the lactating mammary gland; however, while NOS-2 mRNA and protein levels and, consequently, NO production are increased during weaning, NOS-3 protein levels are diminished. Western blot analyses have demonstrated that protein nitration is increased in the mammary gland during weaning, but this is limited to a few specific tyrosine-nitrated proteins. Interestingly, inhibition of GSH synthesis at the peak of lactation partially mimics these findings, highlighting the role of NO production and GSH depletion during involution.

Animals↗
PubMed2005

[Determinants of postprandial lipemia measured as diurnal triglyceride profile in non diabetic normolipidemic subjects].

BACKGROUND AND OBJECTIVE: We decided to evaluate the clinical and biochemical predictors of postprandial lipemia, measured as daylong capillarly triglycerides (TGc) profiles, in normolipidemic non diabetic subjects. PATIENTS AND METHOD: We studied 76 normolipidemic non diabetic subjects (45 premenopausal females). Accutrend was used to measure daylong TGc profiles during 3 days in 6 previously standardized points: fasting, pre and 3 h after dinner and lunch and at bedtime. The area under the curve of TGc (AUC-TGc) was determined as expression of postprandial lipemia. RESULTS: Males showed significantly higher AUC-TGc (26.20 [11.00] vs 19.12 [6.57] in females; p < 0.001). Obese showed significantly higher values of AUC-TGc (27.87 [12.47] vs 20.05 [7.04]; p < 0.01). The AUC-TGc correlated with: age (r = 0.242; p < 0.05), body mass index (r = 0.312; p < 0.01), waist circumference (r = 0.394; p < 0.01), fasting plasma triglyceride (r = 0.634; p < 0.001), fasting insulinemia (r = 0.485; p < 0.001) and fasting HOMA (r = 0.484; p < 0.001). The multivariate analysis showed that HOMA (regression coefficient: 0.352; p = 0.02) and waist circumference (regression coefficient: 0.4; p = 0.05) were independent predictors of the AUC-TGc. CONCLUSIONS: Independent determinants of postprandial lipemia were waist circumference and HOMA.

Adult↗
PubMed2005

Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for correcting the lipid imbalance.

Type 2 diabetes is an important cardiovascular risk factor. A significant component of the risk associated with type 2 diabetes is thought to be because of its characteristic lipid "triad" profile of raised small dense low-density lipoprotein levels, lowered high-density lipoprotein, and elevated triglycerides (TGs). Trials of statins and fibrates have included substantial numbers of patients with diabetes and indicate that lipid lowering reduces cardiovascular event rates in these patients. However, statins alone do not always address all the lipid abnormalities of diabetes. Fibrates, which have low affinity for peroxisome proliferator-activated receptor alpha (PPARalpha), improve most aspects of the atherogenic dyslipidemia of diabetes. Chronic elevations of free fatty acids (FFA) induce insulin resistance and contribute to the lipid triad of diabetes. Therefore, reducing their levels is likely to ameliorate insulin resistance and improve the lipid triad of diabetes. PPARs are intimately involved in the regulation of FFA: PPARalpha modulation increases FFA catabolism and PPARgamma agonism (eg, by thiazolidinediones) increases TG lipolysis, FFA transport, conversion of FFA to TGs, and safe storage of FFA. Integrating potent PPARalpha and PPARgamma activity may deliver greater improvement of the diabetic dyslipidemic profile and its attendant risks than selective PPAR activation.

Cardiovascular Diseases↗
PubMed2005

Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after treatment with 20 mg of atorvastatin daily during 6 weeks. The variant was analysed by polymerase chain reaction amplification and single-strand confirmation polymorphism. Treatment reduced LDL-C, total cholesterol and TGs. Baseline fasting TGs and very-low-density lipoprotein cholesterol levels were lower in female T allele carriers (TG: 111+/-51 mg/dl GG, 89+/-35 mg/dl GT, 83+/-26 mg/dl TT, P=0.022; very-low-density lipoprotein cholesterol: 24+/-13 mg/dl GG, 16+/-5 mg/dl GT, 17+/-5 mg/dl TT, P=0.018). Triglyceride response to atorvastatin was modulated by this polymorphism in men (P=0.009), but not in women, although differences between genotypes were maintained after treatment. In conclusion, the MTP -493 GT polymorphism modulates pre- and post-treatment plasma TG values of FH in Spanish subjects in a gender-specific way. Other environmental and genetic factors likely also modulate this response.

Alleles↗
PubMed2004

[Clinical and biochemical characteristics of familial ligand-defective apo B-100 in a South European population].

BACKGROUND AND OBJECTIVE: To compare the lipoprotein phenotype between FDB and heterozygous familial hypercholesterolemia (FH); to study the prevalence and possible founder effect of familial ligand-defective apo B100 (FDB) in a Mediterranean population, and to analyze the clinical and biochemical characteristics of FDB patients. SUBJECTS AND METHOD: We studied 19 heterozygous FDB subjects (8 males) from 12 related families, carriers of the R3500Q mutation on the apo B gene, and 57 heterozygous FH (24 males) genetically characterized, randomly selected from a total of 213 FH. The genetic diagnosis was established with Southern blot analysis, PCR-SSCP analysis and automatic sequencing. In all subjects, plasma lipids and apolipoprotein levels were determined with standard procedures. RESULTS: We demonstrated a founder effect for the R3500Q mutation in a geographically isolated rural area from our community. The prevalence of FDB in this area is high: 4/350. Heterozygous FDB subjects showed a statistical significantly lower prevalence of xanthomas and coronary heart disease, plasma concentrations of total and LDL cholesterol, HDL cholesterol, apo B and apo A-I values than heterozygous FH subjects. CONCLUSIONS: A founder effect for the R3500Q mutation was found in a rural population with a high prevalence of FDB. In our population, FDB patients showed a mild clinical expression and lipoprotein phenotype compared with FH patients.

Adult↗
PubMed2004

Atherogenic lipoprotein particles in atherosclerosis.

The importance of low-density lipoprotein (LDL) cholesterol in the development of atherosclerosis has long been recognized, and LDL cholesterol remains the primary target of therapy for the prevention of coronary heart disease. Nevertheless, increasing research attention over the past decade has been devoted to the heterogeneity of LDL particles and the atherogenicity of lipids and lipoproteins other than LDL. Particularly atherogenic forms of LDL include small, dense LDL particles and oxidized LDL. All lipoproteins that contain apolipoprotein B, such as LDL, very-low-density lipoprotein, and intermediate-density lipoprotein, tend to promote atherosclerosis; however, these particles differ in their apolipoprotein and triglyceride content. High levels of plasma triglycerides increase the risk of acute coronary events. Lipoprotein(a) is now considered an independent risk factor in both men and women. Ultimately, better understanding of the roles of these lipid particles and subfractions in the initiation and progression of atherosclerosis may affect treatment decisions.

Arteriosclerosis↗
PubMed2004

Statins and diabetes.

Lipid abnormalities play an important part in raising the cardiovascular risk in diabetic subjects. The main components of diabetic dyslipidemia are increased plasma triglycerides, low concentration of high-density lipoprotein cholesterol, preponderance of small, dense low-density lipoprotein, and excessive postprandial lipemia. Small, dense low-density lipoprotein, the elevation in remnant triglyceride-rich lipoprotein particles, and the low high-density lipoprotein are the most powerful atherogenic components. The coexistence of these three factors strongly aggravates the lipid accumulation in the arterial wall and the formation of atherosclerotic plaques. The position of diabetes in cardiovascular risk assessment has been recently reviewed in the Harmonized Clinical Guidelines on Prevention of Atherosclerotic Vascular Disease. In general, patients with diabetes carry a high risk for cardiovascular disease, but the absolute risk varies depending on the type of diabetes, age, and population baseline risk. The Adult Treatment Program III (ATP III) and the American Heart Association have designated diabetes as a high-risk condition and recommended intensive risk-factor management. Concerning therapeutic targets, both ATP III and the American Diabetes Association (ADA) guidelines have identified low-density lipoprotein cholesterol as the first priority of lipid lowering, and the optimal level was set at less than 2.6 mmol/L (100 mg/dL). There is strong evidence, coming from landmark secondary prevention studies, that LDL lowering in people with diabetes is associated with significant clinical benefits. The benefits of statin therapy in type 2 diabetics can no longer be questioned. Ongoing clinical trials will help clarify the question of whether increasing high-density lipoprotein cholesterol with fibrates in the presence of low low-density lipoprotein levels (lower than 3.4 mmol/L, or 130 mg/dL) will be more beneficial than statin therapy alone. The new paradigms in risk-reduction therapies for type 2 diabetic subjects are focused on cardiovascular disease prevention, rather than only on glucose or lipid control. Therapeutic lifestyle changes are considered primary therapies for hyperglycemia and coexisting metabolic syndrome, which can be diagnosed in more than half of type 2 diabetes subjects. New perspectives of lipid management in type 2 diabetes should take into account that insulin resistance, increased lipolysis, and overproduction of large, buoyant, very low density lipoprotein particles are at the base of diabetic dyslipidemia. Accordingly, drugs acting in the regulatory steps of very low density lipoprotein assembly should be developed. Activation of peroxisome proliferator activated receptor alpha (PPARalpha), as occurs with fibrates, lowers free fatty acids (FFAs) and triglyceride levels. PPARgamma agonism, as demonstrated by the thiazolidinediones, increases triglyceride lipolysis, FFA transport, and conversion of FFAs to triglycerides. As separate activation of PPARalpha and PPARgamma improves lipid metabolism, the development of new drugs integrating PPARalpha and PPARgamma activity (PPAR-alpha/gamma agonists) is a promising line that may further improve insulin resistance, FFA metabolism, and consequently, atherogenic diabetic dyslipidemia.

Cardiovascular Diseases↗
PubMed2003

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

BACKGROUND: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). METHODS: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25-65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. RESULTS: The prevalence of IR was 39.6%. Subjects were divided into groups according to WC. A 'normal' WC was defined as below 88 cm in women and below 102 cm in men; 'AO' was defined as a WC equal to or above 88 cm in women and equal to or above 102 cm in men. The prevalence of IR was 31.7% in the group with normal WC and 54.6% in the AO group (P<0.001). The percentage of subjects with the MS (high BP, dyslipemia or abnormal glucose tolerance) significantly increased (P<0.001) in subjects with AO (48.4 vs. 18.8% in normal WC subjects). AO is an indicator of IR with an odds ratio of 2.59 (95% CI 1.55-4.29). CONCLUSIONS: AO, expressed as WC, appears to be a good indicator of risk for IR and the MS, particularly in non-obese subjects (BMI<30). The main independent parameters of risk for IR are WC and TG, whereas those for the MS are IR, WC, and age.

Journal Article↗