Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia.

BACKGROUND: Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS: A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX. RESULTS: Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance. CONCLUSION: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.

[Correlation between plasma concentrations of homocysteine and diabetic polyneuropathy evaluated with the Semmes-Weinstein monofilament test in patients with type 2 diabetes mellitus]. / Correlación entre las concentraciones plasmáticas de homocisteína y la polineuropatía diabética evaluada con la prueba del monofilamento de Semmes-Weinstein en pacientes con diabetes tipo 2.

BACKGROUND AND OBJECTIVE: Few modifiable risk factors are known to be associated with the presence and progression of diabetic polyneuropathy (DPN). MATERIAL AND METHOD: We have analyzed in 405 type 2 diabetic (T2DM) subjects (169 women) the association of plasma homocysteine with the presence of DPN measured with the Semmes-Weinstein (SW) monofilament test. A score below 4 was considered an altered SW monofilament test. Plasma homocysteine, vitamin B12 and folic acid were measured using standard procedures (ELISA). RESULTS: Patients with T2DM with altered SW test have significantly higher age, evolution of disease, HbA1c and lower creatinine clearance values. In addition, plasma homocysteine values were independently and significantly higher in T2DM with DPN measured as altered SW test (13.64 ± 4.93 vs. 12.22 ± 4.48 µmol/l, P<.01) with similar vitamin B12 and folic acid values comparing the 2 groups. CONCLUSION: Plasma homocysteine and HbA1c values are the 2 modifiable biological factors associated with the presence of DPN evaluated as an altered SW monofilament test in T2DM subjects.

[Subclinical carotid atherosclerosis in patients with familial combined hyperlipidemia. Two years follow-up after treatment with high doses of atorvastatin]. / Arteriosclerosis carotídea subclínica en pacientes con hiperlipidemia familiar combinada. Evolución tras dos años de tratamiento con dosis altas de atorvastatina.

BACKGROUND AND OBJECTIVE: Familial combined hyperlipidemia (FCH) is a genetic model of atherogenic dyslipidemia with insulin resistance and early coronary disease. Our objective was to evaluate the presence of carotid alterations as a marker of systemic atherosclerosis in subjects with FCH and assess the effect of 80 mg of atorvastatin per day in carotid plaque thickness after 2 years. SUBJECTS AND METHODS: 100 non diabetic subjects with FCH in primary prevention were consecutively included. Clinical and biochemical parameters and carotid ultrasonography were performed. Subjects with carotid plaque started treatment with 80 mg of atorvastatin per day for 2 years. RESULTS: 29% of subjects had carotid plaques. We did not find significant differences in any of the parameters between subjects with presence or absence of carotid plaques. Twenty subjects with carotid plaques accepted/agreed to participate in the interventional study. Two years follow-up showed a significant reduction in LDLc (30%) and carotid plaque thickness (10%). CONCLUSION: Carotid ultrasonography is useful to detect subclinical atherosclerosis in high risk cardiovascular patients such as subjects with FCH. Treatment with high doses of atorvastatin induces the regression of carotid plaque thickness after 2 years follow-up. Our results suggest that intensive treatment with atorvastatin could be useful to reduce the development of cardiovascular disease in this group of patients.

Misclassification of subjects with insulin resistance and associated cardiovascular risk factors by homeostasis model assessment index. Utility of a postprandial method based on oral glucose tolerance test.

Different methods are available for assessing insulin sensitivity in the fasting state. However, insulin resistance (IR) is initially a postprandial disturbance; and usually, when basal (fasting) disturbance appears, the process has been in progress for some time. Our aim was to investigate if a postprandial measurement, performing an oral glucose tolerance test (OGTT), is more sensitive than fasting values. We wished to identify early IR states in healthy, nonobese individuals and ascertain if this situation was associated with other cardiovascular risk factors. A total of 90 nonobese, nondiabetic, and nonsmoker individuals were studied. They were divided into 3 groups according to IR state--group 1: non-IR--homeostasis model assessment of IR (HOMA(IR)) and insulin sensitivity index of Matsuda-De Fronzo (ISI-Mat) were normal (HOMA(IR) <3.2 and ISI-Mat >4.0); group 2: with IR post-OGTT (ISI-Mat ≤4.0 and HOMA(IR) <3.2); and group 3: subjects with IR in basal conditions (HOMA(IR) ≥3.2). An intravenous glucose tolerance test to compare both indices was also performed. In 14.4% of subjects, the fasting HOMA(IR) values failed to identify IR (false-negative results). The ISI-Mat values were better correlated than HOMA(IR) (r = 0.875, P = .0001 and r = -0.631, P = .0001, respectively) with insulin sensitivity index obtained with intravenous glucose tolerance test. Subjects with IR had higher prevalence of a cluster of cardiovascular risk factors than non-IR subjects. These data show that that a significant percentage of subjects were misclassified with HOMA(IR). Early identification of IR by OGTT was associated with other cardiovascular risk factors. The OGTT is a simple method that could be applied to accurately identify IR subjects in the general population.

Classical cardiovascular risk factors according to fasting plasma glucose levels.

BACKGROUND: To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG). METHODS: We have studied 344 subjects between 20-70 years of age, recruited in a Primary Care Clinic. Subjects were divided into four groups according to their fasting plasma glucose (FPG) values: normal plasma glucose (NG) when FPG < 5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPG > or = 7 mmol/L or previous diagnosis of diabetes. Cardiovascular risk factors (hypertension, TC/HDL-C index and Apo B values), presence of the MetS and indirect measure of insulin resistance (HOMA) were analyzed. RESULTS: Subjects with FPG2 have a prevalence of classic CVRF and MetS similar to that observed in subjects with type 2 diabetes mellitus (T2DM). The TC:HDL-C index > or = 5 in 56% and 57%, Apo B > or = 1.2 g/L in 59% and 57%, hypertension in 60% and 54% of FPG2 and T2DM subjects, respectively. MetS was diagnosed in 79% of FPG2 and 80% of T2DM. We found significant differences with FPG1 group who presented low CVRF and MetS proportion. CONCLUSION: In our population FPG2 and T2DM subjects show a similar cardiovascular risk profile. On the other hand, such risk is significantly lower in subjects with FPG between 5.6-6.0 mmol/L. These results might have practical implications.

[Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease]. / Hiperlipidemia familiar combinada, síndrome metabólico y enfermedad cardiovascular.

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.

Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism.

OBJECTIVE: To identify a reliable yet simple indirect method for detection of insulin resistance (IR). RESEARCH DESIGN AND METHODS: A total of 65 subjects (44 men and 21 women aged 30-60 years) were selected by a simple random sampling method. Inclusion criteria were voluntary participation from staff and hospital personnel, absence of abnormal glucose tolerance, and normal results of lipid profile and basic blood chemistry. A blood sample was taken after a 12-h overnight fast to determine plasma lipid, glucose, and insulin levels. An intravenous glucose tolerance test with administration of insulin after 20 min and extraction of multiple blood samples for glucose and insulin measurements and calculation of the minimal model approximation of the metabolism of glucose (MMAMG) S(i) value were performed. Three indirect indexes used to predict insulin sensitivity or IR were calculated, and metabolic syndrome was diagnosed using the Adult Treatment Panel III (ATP III) criteria. All results were correlated with those of the MMAMG. RESULTS: The 75th percentile value as the cutoff point to define IR corresponded with a fasting plasma glucose level of 12 mU/l, a homeostasis model assessment of 2.6, a 25th percentile for S(i) value of 21, and QUICKI (quantitative insulin sensitivity check index) and McAuley indexes of 0.33 and 5.8, respectively. The S(i) index correlated (P < 0.001) with all the indirect indexes and parameters of the metabolic syndrome. CONCLUSIONS: When compared with the S(i) index, the most sensitive and specific indirect method was the score proposed by McAuley et al. (specificity 0.91, sensitivity 0.75, 9.2 probability ratio of a positive test), followed by the existence of metabolic syndrome (specificity 0.91, sensitivity 0.66, 7.8 probability ratio of a positive test).