Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.

PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. RESULTS: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. CONCLUSIONS: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

BACKGROUND: The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. METHODS: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. RESULTS: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ±â€¯3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. CONCLUSIONS: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD.

Old and new basal insulin formulations: understanding pharmacodynamics is still relevant in clinical practice.

Long-acting insulin analogues have been developed to mimic the physiology of basal insulin secretion more closely than human insulin formulations (Neutral Protamine Hagedorn, NPH). However, the clinical evidence in favour of analogues is still controversial. Although their major benefit as compared with NPH is a reduction in the hypoglycaemia risk, some cost/effectiveness analyses have not been favourable to analogues, largely because of their higher price. Nevertheless, these new formulations have conquered the insulin market. Human insulin represents currently no more than 20% of market share. Despite (in fact because of) the widespread use of insulin analogues it remains critical to analyse the pharmacodynamics (PD) of basal insulin formulations appropriately to interpret the results of clinical trials correctly. Importantly, these data may help physicians in tailoring insulin therapy to patients' individual needs and, additionally, when clinical evidence is not available, to optimize insulin treatment. For patients at low risk for/from hypoglycaemia, it might be acceptable and also cost-effective not to use long-acting insulin analogues as basal insulin replacement. Conversely, in patients with a higher degree of insulin deficiency and increased risk for hypoglycaemia, analogues are the best option due to their more physiological profile, as has been shown in PD and clinical studies. From this perspective optimizing basal insulin treatment, especially in type 2 diabetes patients who are less prone to hypoglycaemia, would be suitable making significant resources available for other relevant aspects of diabetes care.

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points for cardiovascular risk in a South European population. METHODS: We performed a cross-sectional study including 1501 subjects (770 women and 731 men) between 18 and 80 years of age. Samples were collected after 12-14 h of fasting. Cholesterol, HDL-C, triglycerides and apoB levels were measured using direct methods. LDL-C was calculated by the Friedewald formula. Non-HDL-C was calculated as total cholesterol minus HDL-C. RESULTS: The Spearman's rank correlations between apoB and LDL-C (r 0.86, p < 0.0001), and between apoB and non-HDL-C (r 0.91, p < 0.0001) were both significant. The proposed cut-off points for apoB, according to LDL-C goals (70, 100, 130 and 160 mg/dl) in our population are 70, 80, 100 and 115 mg/dl respectively. The proposed cut-off values for non-HDL-C are 100, 120, 150 and 190 mg/dl respectively. CONCLUSION: The established LDL-C cut-off values could not be accurate to estimate cardiovascular risk in subjects with mild hypertriglyceridaemia, as frequently occurs in our Mediterranean population. To take into consideration the burden of atherogenic particles and better classify patients at risk we propose cut-off values for apoB or the equivalent for non-HDL-C. Prospective trials including cardiovascular variables are needed to validate our assumption.

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia.

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39 ± 8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02 ± 6.20 mM*h/L) (P < 0.05). Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

BACKGROUND: To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. METHODS: Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA(1c) and microalbuminuria were measured using standard procedures. RESULTS: Plasma Hcy, microalbuminuria, HbA(1c) and apolipoprotein B levels were significantly higher in patients with foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin B12 and folic acid values were similar in both groups. In the logistic regression model, plasma Hcy (OR 1.09; 95% CI 1.04-1.69), microalbuminuria (OR 1,01; 95% CI 1.01-1.17) and HbA(1c) levels (OR 1.33; 95% CI 1.04-1.69) were independent risk factors for the presence of diabetic foot ulceration. CONCLUSIONS: In our study, for each micromol increase in plasma Hcy levels there was a 10% increase in the risk of diabetic foot ulceration. In addition, plasma homocysteine, HbA(1c) and microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the risk of foot ulceration.

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

BACKGROUND: Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. MATERIALS AND METHODS: Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. RESULTS: Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75.0 +/- 20.7 vs. 42.7 +/- 16.8 relative luminiscence units) and XO (0.44 +/- 0.13 vs. 0.32 +/- 0.09 mU mL(-1)) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. CONCLUSION: Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients.

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia.

BACKGROUND AND AIMS: Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR). METHOD AND RESULTS: 40 Non-related subjects with FCH and 30 control subjects were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose, insulin, uric acid, XO activity, malondialdehyde (MDA), IL-6 and hsCRP in plasma and NFkB activity in circulating mononuclear cells. Patients with FCH showed significantly higher levels of uric acid, XO activity, MDA, NFkB activity, IL-6 and hsCRP than controls. XO activity was independently related to NFkB activity with an odds ratio of 4.082; to IL-6 with an odds ratio of 4.191; and to IR with an odds ratio of 3.830. Furthermore, mean NFkB activity, IL-6 levels, and IR were highest in the highest percentile of XO activity. CONCLUSIONS: Subjects with FCH showed increased XO and NFkB activities and low grade inflammatory markers related to atherosclerosis. XO activity was correlated with higher inflammatory activity and IR. These data could explain, in part, the high cardiovascular disease risk present in these patients.

[Cardiovascular risk in subjects with high probability of metabolic syndrome and insulin resistance. DESIRE study]. / Riesgo cardiovascular en sujetos con alta probabilidad de síndrome metabólico y resistencia a la insulina. Estudio DESIRE

INTRODUCTION AND OBJECTIVES: The metabolic syndrome is an association of closely related alterations. The main objective of this study is to know the frequency of the metabolic syndrome and insulin resistance, and their role as cardiovascular risk indicators in an adult population assigned to Primary Care centers in Spain. METHODS: Subjects > or = 45 years with basal glycemia > or = 90 mg/dl and abdominal circumference > or = 94 cm (men) or > or = 80 cm (women). ATP III modified-criteria were used for the metabolic syndrome and HOMA index > 3.29 was used for insulin resistance. Cardiovascular risk was estimated by the Framingham and SCORE models. RESULTS: A total of 2,341 subjects (62 +/- 10 years; 44.6% males) were included. Frequency of metabolic syndrome and insulin resistance was 54.6% (52.5; 56.8) and 56.6% (54.5; 58.7) respectively. Metabolic syndrome was associated to a higher cardiovascular risk score with both Framingham (16 [15; 16] vs 11 [11; 12] p < 0.0001) and SCORE (2.7 [2.4; 3] vs 2.4 [2.1; 2.8]; p = 0.006) models. The results were similar for the presence of insulin resistance. CONCLUSIONS: Metabolic syndrome and insulin resistance are cardiovascular risk predictors. Early identification of metabolic syndrome by the use of simple clinical measures (basal glycemia and waist circumference) would make the intervention on the different disorders of metabolic syndrome possible.

Absence of cardiovascular autonomic dysfunction and vagal pancreatic impairment in idiopathic achalasia of the oesophagus.

Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 +/- 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 +/- 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing, standing, Valsalva) and sympathetic function (postural decrease of systolic blood pressure, Handgrip test) were assessed. Statistical comparison of basal and increase levels of PP and parasympathetic/sympathetic cardiovascular parameters was performed between groups. Basal levels of PP were similar in controls and patients and maximum increase of PP during sham feeding test. A similar rate of abnormal cardiovascular tests was found between groups (P > 0.05). E/I ratio was the mostly impaired parameter (patients: 36.7% vs controls: 20%, P = 0.15, chi-squared test). Autonomic cardiovascular tests and pancreatic response to vagal stimulus are not impaired in patients with primary achalasia of the oesophagus.

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy.

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.

[Effect of gender and obesity on postprandial lipemia in non-diabetic normolipidemic subjects and subjects with familial combined hyperlipidemia]. / Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada.

INTRODUCTION: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH). MATERIAL AND METHODS: We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week. RESULTS: In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese. DISCUSSION: Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.

Effects of marathon running on plasma total homocysteine concentrations.

AIMS: There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24h before and after a marathon race. METHODS AND RESULTS: Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23-49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed. RESULTS: Changes in plasma folate and plasma vitamin B12 concentrations were not detected post-race, but a significant increase in plasma tHcy concentrations was demonstrated. Plasma tHcy increased 19% 24h after the race. Before the race 20% of the subjects had a plasma tHcy concentration > 10 micromol/l (cut-off point for ischaemic heart disease risk), while after the race 50% had plasma tHcy concentrations> 10 micromol/l. CONCLUSION: An increase in plasma tHcy concentrations was observed after a marathon race in non-professional not well-trained male athletes performing strong physical activity. The potential physiological or pathological implications of this finding are unknown.

Daylong triglyceridaemia in healthy Mediterranean and northern European subjects.

BACKGROUND: A Mediterranean eating pattern and diet enriched in monounsaturated fatty acids may result in a favourable daylong lipid profile. METHODS: 19 Spanish males (aged 32 +/- 8 years) and 28 females (34 +/- 8 years) were matched to Dutch subjects on the basis of fasting capillary triglycerides (TGc), gender and age. TGc were self-measured at six fixed time points over three days. Daylong TGc profiles were calculated as areas under the curve (TGc-AUC). RESULTS: Anthropometric parameters and fasting plasma lipids were comparable between Spanish participants and Dutch subjects. Insulin sensitivity (expressed as HOMA) was highest in the Dutch females (1.41 +/- 1.09 vs. 2.09 +/- 1.23 in the Spanish females, p < 0.05). Daylong TGc values were not different between Spanish and Dutch participants. Male Spanish subjects showed the largest daylong TGc increase after lunch, while in the Dutch males, the largest TGc increase was seen after dinner. Total daytime dietary energy and total fat intake were comparable when analysed by gender. However, the Spanish participants had a higher intake of monounsaturated and polyunsaturated fatty acids as percentage of energy. CONCLUSION: There are no major differences in daylong triglyceridaemia between Dutch and Spanish subjects, despite different eating habits and a diet enriched in monounsaturated and polyunsaturated fat in the latter.

[Plasma lipoprotein (a) values in familial defective ligand apo B 100 in a South European population]. / Estudio de los valores plasmáticos de Lp(a) en el defecto familiar de unión de la apo B 100 en una población mediterránea del sur de Europa.

AIMS: 1) to study lipoprotein (a) (Lp(a)) plasma values in subjects with familial ligand-defective apo B 100 (FDB). METHODS: We studied 19 heterozygous FDB subjects (8 males) from 12 families, carriers of R3500Q mutation on apo B gene and 90 controls (34 males). The genetic diagnosis was established with PCR-SSCP analysis and automatic sequencing. In all subjects plasma lipids, apolipoprotein B and Lp(a) levels were determined with standard procedures. RESULTS: Subjects carriers of R3500Q mutation on apo B gene have significantly higher plasma Lp(a) and log transformed Lp(a) values and prevalence of Lp(a) > 30 cut point for coronary heart disease than controls. CONCLUSIONS: Subjects with FDB showed higher Lp(a) plasma values than controls, although the mechanism and the clinical consequences of these result are not known.

[Risk factors associated to hospitalization in diabetic patients with foot ulcers]. / Factores asociados con el ingreso hospitalario de pacientes diabéticos con ulceración en el pie.

BACKGROUND: To analyse the risk factors associated with admissions of diabetic patients with foot ulcers, in order to prevent hospitalization. In-patient care supposes the greatest cost of the diabetic foot care. SUBJECTS AND METHOD: We studied 108 diabetic patients (male n = 59, mean age 68 [11] years, 100 type 2 diabetics, disease duration 16.4 [10.3]) who attended the diabetic foot unit between January 1996 and September 1997. Clinical and biochemical risk parameters were recorded in a clinical protocol. Patients were followed up for a mean period of 200.2 (121.3) days. Admission was needed for 30 diabetic patients (28%). RESULTS: Risk factors for hospitalization were: higher ulcer diameter (1.9 [1.6] vs 3.4 [2.3] cm, p < 0.05), higher ulceration grade according to Wagner's classification (p = 0.005), presence of > 2 cm cellulitis (p < 0.001), worse metabolic control (HbA1c 7.6 [1.3] vs 8.6 [1.1], p < 0.05), and greater degree of retinopathy (p < 0.005). Odds ratios (OR) for admission were: advanced diabetic retinopathy: OR 1.9 (CI 95% 1.3-2.9; p = 0.02); presence of moderate to severe polyneuropathy: OR 1.6 (CI 95% 1.3-2.1; p = 0.05); upper HbA1c tertile: OR 2.4 (CI 95% 1.2-4.2; p = 0.004). In the logistic regression model, both foot ulcer diameter and advanced diabetic retinopathy were significantly independent. CONCLUSIONS: In diabetic subjects with foot ulcers, hospitalization is independently related to the diameter of the ulcer and the degree of diabetic retinopathy. Therapeutic and preventive approaches should be strengthened in this subgroup of diabetic patients to prevent their hospitalization.

[Insulin resistance quantification by fasting insulin plasma values and HOMA index in a non-diabetic population]. / Cuantificación de insulinorresistencia con los valores de insulina basal e índice HOMA en una población no diabética.

BACKGROUND: Our goal was to determine the prevalence of insulin resistance (IR) by means of fasting insulin plasma values and the HOMA index,and to analyse the relation of these parameters with other components of the metabolic syndrome. SUBJECTS AND METHOD: We studied 292 non-diabetic individuals, aged between 20 and 65 years, randomly selected from subjects attending an outpatient care center (Valencia-Spain-metropolitan area). 97 subjects who lacked clinical and biological criteria of IR were selected. In addition to calculating the HOMA index, anthropometric parameters, plasma lipids values, fasting glucose and insulin plasma levels were measured by standard methods in all subjects. RESULTS: In the subgroup of 97 subjects without clinical and biological criteria of IR, we established a diagnosis of IR when the fasting plasma insulin value was >= 16.7 mU/l or the HOMA index was >= 3.8. Cut-off points of the percentil 90th of this subgroup were taken into account. In the whole group,the prevalence of IR (HOMA >= 3.8) was 31.8%, with a higher frequency in men compared to women. CONCLUSIONS: In addition to fasting plasma insulin values and HOMA index, the best clinical and biochemical indicators of IR were fasting plasma glucose levels, BMI and triglycerides (TG) plasma values. Thus, the odds ratio for insulin resistance was 5.9 for a glycemia >= 110 mg/dl, 2.6% for BMI >= 25 kg/m(2) and 2.2 for triglycerides >= 150 mg/dl.

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause.

OBJECTIVE: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). METHODS: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). RESULTS: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels were found in the apo E2/E3 group (P<0.0001). After HRT, women with phenotype E3/E4 showed higher levels of TC and TC/HDL-C ratio (P<0.0001 and P<0.006, respectively). The apo E2/E3 phenotype group showed increased levels of TG (P<0.0001). In the multivariant analysis the changes of TG after HRT were related to the type of treatment used (P<0.001), age (P=0.05) and the apo E phenotype (E2/E3). CONCLUSION: Women with phenotype E2/E3 have higher plasma TG levels and show a significant post HRT increase compared with the other phenotypes. Other factors with a lower impact on TG levels are age and progestagen association.