Biomedical subjects

M Cassader

Publications and source records attributed to M Cassader.

At least 19 recordsLinked to original sources

PubMed2006

Should we consider gestational diabetes a vascular risk factor?

Few and contrasting data have reported vascular endothelial dysfunction and increased serum levels of endothelial dysfunction and inflammatory markers in women with previous gestational diabetes mellitus (pGDM). We aimed at evaluating 6.5 years after delivery: intimal medial thickness (IMT), and C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) levels in 82 non-pregnant pGDM and 113 control women without pGDM. A subgroup of 21 women, taken from the pGDM group, showing current normal BMI, and no metabolic abnormalities, was separately analysed. All the subjects were free of medication and non-smokers. Women with pGDM, independently by their current BMI and presence of metabolic abnormalities, showed significantly higher E-selectin, ICAM-1 and IMT values than controls. IMT proved to be significantly associated with pGDM in a regression model, after adjustments for BMI, waist circumference, blood pressure, and glucose values (beta=0.046; 95% CI 0.028-0.064). In all pGDM women, E-selectin, ICAM-1, IL-6 and hs-CRP values were significantly associated with IMT in the same model. Post-GDM women, despite being currently free from metabolic abnormalities, showed higher values of markers of endothelial dysfunction and IMT than controls, consistent with an increased future cardiovascular risk.

Adult↗

PubMed2006

Low-density lipoproteins are more electronegatively charged in type 1 than in type 2 diabetes mellitus.

Multifactorial etiology is involved in premature atherosclerosis related to diabetes. Most of the mechanisms that are responsible for the etiology in diabetes have remained unsolved so far. Type 1 diabetes is associated with a favorable lipid pattern and with microangiopathy, which is not true for type 2 diabetes, which is related to dyslipidemia and macroangiopathy. The aim of this work was to evaluate the degree of LDL modification related to the types of diabetes. The question is whether the LDL could be differently modified since the pathogenesis of type 1 and type 2 diabetes is different. Thirty-one type 1 (19 male and 12 female) and thirty type 2 (18 male and 12 female) diabetic patients were included in this study. Isolated LDL was analyzed by capillary electrophoresis for diene conjugate content and for electronegativity. LDL from type 1 diabetes subjects showed the highest electrophoretic mobility (P = 0.000). Instead, the diene conjugates contents were higher in the type 2 patients with HbA1c levels > 8% (P = 0.007). In conclusion, the increased diene content in type 2 diabetic subjects in poor glycemic control and the highest LDL mobility found in type 1 subjects show that the LDL undergoes different modifications. In type 2 patients, electronegative LDL are in a state of higher susceptibility to oxidation, whereas in type 1 subjects the finding of electronegative lipoproteins could provide an index of the relative atherogenicity of circulating LDL, especially as LDL has higher electrophoretic mobility than normal subjects.

Adult↗

PubMed2005

Comparison of two enzyme immunometric assays to measure tumor necrosis factor-alpha in human serum.

BACKGROUND: Tumor necrosis factor-alpha is a 17.5 kDa, 157 amino acid protein that is a potent lymphoid factor, which exerts cytotoxic effects on a wide range of tumor cells and other target cells. TNF-alpha has been suggested to play a pro-inflammatory role by influencing transendothelial migration of monocytes and elicits the expression of proteolytic enzymes by macrophages and smooth muscle cells within the atherosclerotic plaque. METHODS: We compared two methods for the quantitative determination of human tumor necrosis factor-alpha in serum samples. Either kit follows the same assay procedure. Serum samples do not need to be diluted before sampling. Standard is provided lyophilized and serial dilutions after reconstitution generate the standard point curves. The tests are enzyme immunometric assays based on a standard 96-well microtiter plate. The wells are coated with anti-human TNF-alpha antibody. RESULTS: The range of the standard curve is similar in both kits. It spans from 1000 through 15.6 pg/mL. The median TNF-alpha concentration in samples measured by Pierce assay (n=368) was 4.23 pg/mL, (range, 1.34-77.2 pg/mL). A very different median was obtained for the same specimen measured with the Titerzyme EIA (median, 176.96 pg/mL; range, 54.7-283.9 pg/mL; n=364). Substantial significant differences were observed between the two methods. CONCLUSION: Our results show that the two kits are unmatchable for results they can give when TNF-alpha concentrations are measured in serum samples. One reason of this disagreement could be the matrix effect or a cross-reactivity of one of the two methods. This study shows that the determination of human serum TNF-alpha needs to be standardized, especially when a comparison of results is required.

Calibration↗

PubMed2005

Apolipoprotein E polymorphism and stroke subtypes in an Italian cohort.

BACKGROUND: Studies have indicated that apolipoprotein E (ApoE)-epsilon4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. METHODS: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. RESULTS: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-epsilon4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-epsilon4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-epsilon4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-epsilon4 allele was not significant (OR 1.25, 95% CI 0.57-2.74). CONCLUSION: Our study shows similar ApoE-epsilon4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

Adult↗

PubMed2005

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are impaired in this condition. METHODS: We performed a two-step (1.5 and 6 pmol min(-1) kg(-1)) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2H2]glucose and [2H5]glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. RESULTS: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<0.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was significantly shorter in the patients than in the control subjects (48+/-12 vs 63+/-13 min, p<0.04). Lipid oxidation was significantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. CONCLUSIONS/INTERPRETATION: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.

3-Hydroxybutyric Acid↗

PubMed2005

C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.

OBJECTIVES AND STUDY DESIGN: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM). RESULTS: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001). CONCLUSIONS: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.

Adult↗

PubMed2005

Relationships between human serum resistin, inflammatory markers and insulin resistance.

OBJECTIVE: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). SUBJECTS: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. RESULTS: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). CONCLUSIONS: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.

Biomarkers↗

PubMed2005

Does C-reactive protein identify a subclinical metabolic disease in healthy subjects?

BACKGROUND: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects. DESIGN: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia. RESULTS: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile. CONCLUSIONS: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.

Body Mass Index↗

PubMed2005

Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus.

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X +/- SD; 1782.12 +/- 518.02 vs. 2269.20 +/- 231.56 mumol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 +/- 437.68 vs. 1930.63 +/- 581.01 micromol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 +/- 118.14 vs. 2269.20 +/- 231.56 and vs. 1670.74 +/- 437.68 micromol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = -0.34, p < 0.01) and with the duration of DM (r = -0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Body Mass Index↗

PubMed2005

Plasma nitrotyrosine levels, antioxidant vitamins and hyperglycaemia.

AIMS: Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes. METHODS: In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9; 95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E. CONCLUSION: A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes.

Age Factors↗

PubMed2004

Platelet cGMP inversely correlates with age in healthy subjects.

Biochemical modifications associated with the increase in platelet activity with age are not well defined. Furthermore it is well known that the nitric oxide/cyclic 3', 5'-guanosine monophosphate (cGMP) pathway regulates platelet aggregation. The aim of the present study was to examine the relationship between platelet content of cGMP and age. 120 normal subjects, evaluating the cGMP platelet concentration, 17betaE2, IGF-I, dehydroepiandrosterone sulphate (DHEAS), insulin, plasma glucose, lipid pattern, homocysteine and PAI-I antigen, were studied. The multivariate analysis in a model with cGMP as dependent variable and with age, LDL, apolipoprotein B (ApoB), DHEAS, E2 and insulin-like growth factor (IGF)-I as independent variables shows a negative correlation between cGMP and age (p<0.01, beta=-0.388). In conclusion our data suggest that the reduced efficiency of the system constitutive nitric oxide synthase (cNOS)/guanylate cyclase represents at least one of the reasons of the increased platelet aggregability with age.

Adult↗

PubMed2004

In vivo oxidizability of LDL in type 2 diabetic patients in good and poor glycemic control.

We aimed to determine if increased non-enzymatic glycosylation of the LDL was sufficient to increase the susceptibility to in vivo oxidation of the LDL particles. Twenty-two type 2 diabetic patients (11 males and 11 females) were included in this study. They were enrolled on the basis of good [glycated hemoglobin (HbA1c) < 7%] and poor glycemic control [(HbA1c) > 8%]. LDL were isolated by sequential ultracentrifugation and analyzed by capillary electrophoresis (CE) for diene conjugate content and for electronegativity. The glyc-LDL levels were increased in all diabetic type 2 patients, peaking in the diabetic subjects in poor diabetic control (17.3 +/- 8.07%). The LDL content of diene conjugates was similar between the two groups (6.65 +/- 0.77% for the patients with good glycemic control versus 6.88 +/- 0.74% for those with poor glycemic control; P = 0.49) as was the electrophoretic mobility ((-1.14544 +/- 0.089) x 10(-4) cm2/(V s) for the patients with good glycemic control and (-1.13666 +/- 0.073) x 10(-4) cm2/(V s) for those with poor glycemic control; P = 0.80). The susceptibility to in vivo oxidation of LDL from type 2 diabetic patients in poor glycemic control did not differ from that of well-controlled diabetic patients. LDL glycosylation was not able to increase the oxidizability of LDL in the diabetic patients with poor glycemic control.

Aged↗

PubMed2004

Body fat and C-reactive protein levels in healthy non-obese men.

BACKGROUND AND AIM: The relationships between C-reactive protein (CRP) levels, adipose tissue and metabolic alterations have not been clearly established in healthy non-obese subjects. We investigated the relationships between body fat, CRP levels and metabolic variables in healthy, non-obese sons of patients affected by metabolic syndrome (MS). METHODS AND RESULTS: Age, CRP and interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist circumference and waist-to-hip ratio, WHR), total and regional fat content (as determined by means of dual X-ray absorptiometry, DXA), total and LDL cholesterol, and the metabolic variables related to MS (HDL-cholesterol, triglyceride, glucose and insulin levels; the fasting insulin resistance index, FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients. Linear and multiple regression analyses were used to evaluate the relationships between body fat, metabolic variables and CRP levels, and to investigate whether the association between body fat content and metabolic variables persists after adjustment for CRP levels. Body fat was associated with all of the investigated variables. CRP levels were associated with total and regional body fat, the anthropometric index of weight, age, and with some metabolic alterations (HDL-cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin and LDL-cholesterol levels). The associations between total body fat and the metabolic variables did not change after adjustment for CRP levels. Total body fat was the best predictor of CRP levels (p<0.0001). CONCLUSIONS: In healthy, non-obese sons of MS patients, total body fat is the best predictor of CRP levels, and remains closely associated with metabolic abnormalities after adjustment for CRP levels. These findings strongly support the hypothesis that body fat is the main determinant of metabolic abnormalities and a low inflammatory state, at least in healthy subjects.

Adipose Tissue↗

PubMed2003

Obesity or diabetes: what is worse for the mother and for the baby?

OBJECTIVES: The aim of the present study is to evaluate pregnancy outcomes in a cohort of Caucasian pregnant women in relation to their body mass index and glucose tolerance status; the role of central fat distribution, as indicated by waist-to-hip circumference ratio, was also considered. METHODS: Seven hundred women were studied; they had gestational diabetes or impaired glucose tolerance (250) or normoglycaemia (450). Among them 117 had pre-pregnancy overweight/obesity (44 were obese), 133 hyperglycaemia, but normal weight, and 117 hyperglycaemia and overweight/obesity (42 were obese). RESULTS: Hypertension, cesarean delivery and prevalence of large-for-gestational age babies were higher in obese (both with normoglycaemia and hyperglycaemia), mainly in those with greater gestational weight gain and central fat distribution (waist-to-hip ratio > 0.90). Normal weight hyperglycaemic women showed better outcomes than obese normoglycaemic women did. In a multiple logistic regression model, obesity (OR=10.6; 95% CI 5.00-22.54) was directly related to hypertension, and independent predictors of cesarean section were: gestational hyperglycaemia (OR=1.78; 95% CI 1.21-2.62), gestational weight gain (OR=1.06; 95% CI 1.02-1.10), and central obesity (OR=1.51; 95% CI 1.02-2.24), while obesity (OR=4.48; 95% CI 2.30-8.71) gestational weight gain (OR=1.08; 95% CI 1.03-1.12) and central fat distribution (OR=1.81: 95% CI 1.12-2.93) were directly related to delivering larger babies, after multiple adjustments. CONCLUSION: These results suggest that pre-pregnancy obesity and gestational hyperglycaemia were independent risk factors for different adverse pregnancy and neonatal outcomes, while central distribution of fat, and gestational weight gain play an additive adverse role on these outcomes.

Adult↗

PubMed2003

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.

Adult↗

PubMed2002

Higher lipoprotein (a) levels in atherothrombotic than lacunar ischemic cerebrovascular disease.

To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.

Adult↗

PubMed2002

Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima-media thickness in Italian type 2 diabetic patients.

BACKGROUND: Moderately elevated levels of homocysteine have been associated with an increased cardiovascular risk in type 2 diabetic patients. The role of methylenetetrahydrofolate reductase gene polymorphism is less clear. MATERIALS AND METHODS: We investigated the contribution of plasma homocysteine levels and the methylenetetrahydrofolate reductase gene polymorphism to the variability of carotid intima-media thickness in 124 consecutive Italian patients with type 2 diabetes mellitus. Fasting plasma homocysteine was measured by high-pressure liquid chromatography with an electrochemical detector; methylenetetrahydrofolate reductase genotypes were determined by polymerase chain reaction and restriction enzyme digestion. The carotid intima-media thickness was evaluated with high-resolution B-mode ultrasonography. RESULTS: Age, creatinine and plasma homocysteine levels showed a positive correlation with mean carotid intima-media thickness values, but only age and creatinine levels were still associated with mean carotid intima-media thickness values in the multivariate analysis. Plasma homocysteine levels were significantly higher in the patients bearing the 677T/677T genotype of the methylenetetrahydrofolate reductase polymorphism; mean carotid intima-media thickness values were not different in the three different methylenetetrahydrofolate reductase genotypes. CONCLUSION: In 124 Italian patients with type 2 diabetes mellitus, basal levels of plasma homocysteine, as well as methylenetetrahydrofolate reductase gene polymorphism, did not explain the variability of mean carotid intima-media thickness.

Aged↗

PubMed2001

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients.

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.

Adult↗