Fasting Triglyceride Concentrations Research Articles

Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency

Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele.

Efficacy and safety profile of fenofibrate-coated microgranules 130 mg, with and without food, in patients with hypertriglyceridemia and the metabolic syndrome: An 8-week, randomized, double-blind, placebo-controlled study

Background:The limited bioavailability of certain fenofibrate formulations necessitates administration with food, raising concerns about efficacy and compliance. There is a need for new formulations that have improved bioavailability and eliminate the requirement for administration with food. Objective:The aim of this study was to assess the food-related efficacy of a new formulation of micronized fenofibrate coated on inert microgranules (FF-μG) for the treatment of hypertriglyceridemia in patients exhibiting the metabolic syndrome. Methods:This was a randomized, double-blind, placebo-controlled, double-dummy, parallel-group study in patients who had fasting triglyceride (TG) concentrations ≥300 mg/dL and <1000 mg/dL and met National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. A 6-week washout and diet lead-in period was followed by an 8-week treatment period. Eligible patients were randomized to receive either FF-μG 130 mg with food, FF-μG 130 mg without food, or placebo every day for 8 weeks. The primary end point was the mean percent change in TG levels from baseline to the end of treatment; changes in other lipid end points were also assessed. Safety profiles were assessed based on adverse-event reports, changes in clinical laboratory values and vital signs (including electrocardiography), and the findings of physical examinations. Results:One hundred forty-six patients took part in the study: 54 received FF-μG 130 mg with food, 42 received FF-μG 130 mg without food, and 50 received placebo. The groups were similar in terms of mean age (56 years), sex (59.5%–63.0% men; 37.0%–40.5% women), race (83.3%–100% white), mean body weight (92 kg), mean height (172 cm), mean fasting baseline TG concentrations (480 mg/dL), and other components of the metabolic syndrome. The 2 FF-μG groups (with and without food) showed similar improvements in the dyslipidemia associated with the metabolic syndrome: TG levels decreased a mean of 36.7% and 36.6%, respectively (P < 0.001 vs placebo). The overall frequency of adverse events was similar in the 2 FF-μG groups and did not differ significantly from placebo (63.0%, 61.9%, and 52.0%, respectively). Gastrointestinal disturbances (eg, diarrhea, dyspepsia) occurred more frequently in the 2 FF-μG groups compared with the placebo group (31.5%, 26.2%, and 12.0%; P = NS). Significant increases from baseline in alanine aminotransferase were seen in both FF-μG groups (mean [SEM], 3.77 [2.60] and 11.69 [7.42] U/L, respectively; P ≤ 0.05 vs placebo); however, these increases were considered clinically significant in only 5 cases, none of them requiring discontinuation of study drug. Conclusions:This study found no inequivalence in the TG-lowering effects of the 2 fenofibrate regimens compared with placebo. Both regimens were well tolerated. Thus, FF-μG 130 mg administered without regard to meals appears to be efficacious and well tolerated for the treatment of hypertriglyceridemia in patients exhibiting the metabolic syndrome.

Features of the Metabolic Syndrome of “Hypertriglyceridemic Waist” and Transplant Coronary Artery Disease

This study evaluated the prevalence of the atherogenic metabolic triad and the hypothesis that waist circumference and fasting triglyceride concentrations could be used as screening tools for identification of the atherogenic metabolic triad in a population of heart transplant men. It also evaluated the relationship between the atherogenic metabolic triad and coronary artery disease (CAD). In the study group of 83 consecutive male heart transplant patients having their routine annual coronarography, 23 patients (28%) were characterized by the atherogenic metabolic triad defined by the presence of elevated fasting insulin and apolipoprotein B concentrations and by small low-density lipoprotein (LDL) particles. Seventy-seven per cent of patients with waist circumference values >/= 90 cm and with elevated triglyceride levels (>/=2.0 mmol/liter) were characterized by this atherogenic metabolic triad. Patients with the atherogenic metabolic triad were at markedly increased risk of CAD (odds ratio of 25.3, 95% CI: 1.11-577.3, p < 0.04) compared to heart transplant patients without the atherogenic metabolic triad. About 30% of heart transplant patients showed the features of the atherogenic metabolic triad. Measurement and interpretation of waist circumference and fasting triglycerides could be used among heart transplant patients to early identify men characterized by the presence of elevated fasting insulin and apolipoprotein B concentrations and small LDL particles. The presence of the atherogenic metabolic triad identified patients at high risk of CAD even in the heart transplant population.

Additive Effects of the PPARγ, APOE, and FABP-2 Genes in Increasing Daylong Triglycerides of Normolipidemic Women to Concentrations Comparable to Those in Men

Fasting and postprandial triglyceride (TG) concentrations vary considerably among individuals. TG metabolism is more efficient in women than in men, which may partly explain why females are protected against atherosclerosis. Our aim was to identify gender-specific genetic influences on fasting and postprandial TG concentrations under typical living conditions in healthy, lean, normolipidemic women. We studied 40 women and 48 men. Diurnal capillary TG profiles were calculated as the integrated area under the capillary TG curve averaged over 3 days. Genotypes of the FABP-2, HL, LPL, APOE, and PPARgamma genes and the APOC-III, APOC-III/A-IV intergenic region were determined. Three genes (FABP-2, APOE, and PPARgamma) had a significant additive effect only in women. Mean TG concentrations were fourfold higher in women carriers of the PPARgamma wild-type allele (P = 0.044), threefold higher in carriers of the rare FABP-2 allele (P = 0.006), and fivefold higher in carriers of the E2 allele of the APOE gene (P = 0.037) than in noncarriers. None of these effects was observed in men. The presence of two or more of these adverse alleles increased TG concentrations in a dose-dependent manner. Women carriers of three adverse alleles had postprandial TG values comparable to those for men. An adverse combination of common alleles of the FABP-2, APOE, and PPARgamma genes in women increases their TG concentrations to values comparable to those seen in men. Although this influence is not appreciable when studying fasting plasma TGs, it becomes apparent with use of a more sensitive index such as measurements made throughout the day.

Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia

To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.

Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men

We investigated whether a session of prior exercise could ameliorate postprandial endothelial dysfunction. Endothelial function is impaired after fat ingestion, and this may be related to rises in triglyceride concentrations. Exercise reduces postprandial triglyceride concentrations. Ten lean (waist <90 cm) and 10 centrally obese (waist >100 cm) middle-aged men each underwent two oral fat tolerance tests (blood taken fasting and for 8 h after a high-fat meal containing 80 g fat and 70 g carbohydrate). On the afternoon before one test, subjects performed a 90-min treadmill walk (exercise); no exercise was performed before the control test. Endothelium-dependent and -independent microvascular function was assessed using laser Doppler imaging in the fasted state and at two hourly intervals during the 8-h postprandial period. Exercise reduced both fasting and postprandial triglyceride concentrations by 25% in both the lean and centrally obese groups (p < 0.0005). For all subjects taken together, exercise improved fasting endothelium-dependent function by 25% (p < 0.05), and, although there was a significant postprandial decrease in both endothelium-dependent and -independent function in both the control and exercise trials (p < 0.01), postprandial endothelium-dependent and -independent function were 15% and 20% higher, respectively, in the exercise trial than the control trial (both p < 0.05). A session of prior exercise improves fasting and postprandial vascular function in middle-aged men. This may be one mechanism by which exercise influences cardiovascular risk.

Sustained Weight Loss in Obese Subjects Has Benefits That Are Independent of Attained Weight

To explore the hypothesis that sustained weight loss in severely obese patients may have benefits that are independent of their attained BMI. We conducted a comparison of two weight-stable groups with BMI in the 30 to 35 kg/m(2) range. Subjects (n = 79) were selected obese patients 3 years after laparoscopic adjustable gastric band surgery, and controls (n = 79) were obese patients seeking weight loss therapy. Subjects were selected in a de-identified manner from our database to best match the control group. A range of clinical, biochemical, and questionnaire measures were obtained to assess obesity-related health status Subjects maintained a mean weight loss of 32.8 +/- 18 kg after surgery. The weight loss subjects had significantly lower fasting plasma glucose, insulin, and triglyceride concentrations, along with higher high-density lipoprotein-cholesterol levels and better indirect measures of insulin sensitivity when compared with controls (p < 0.05 for all). In addition, aminotransferase levels, neutrophil counts, and globulin levels were also significantly lower in weight loss subjects. All differences in laboratory variables remained significant after controlling for BMI. The subjects also reported better health-related quality of life, fewer symptoms of depression, and greater satisfaction with their appearance than controls. These findings suggest that the post-weight loss state conveys benefits that are greater than predicted by the attained BMI. These findings may have important implications regarding the expectations of weight loss therapy, and mechanisms for this effect should be carefully sought.

Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses.

Maternal dietary Fe restriction reduced fasting plasma cholesterol and triglyceride (TG) concentrations in the fetuses, as well as decreased plasma TG levels in the adult offspring. To investigate how maternal Fe restriction was affecting fetal lipid metabolism, we investigated whether there were changes in liver lipid metabolism in the full-term fetuses. There was a approximately 27% (P < 0.05) increase in cholesterol but approximately 29% reduction (P = 0.01) in TG concentrations in the liver of the Fe-restricted fetuses. Hepatic mRNA levels of cholesterol 7alpha hydroxylase and liver X receptor-alpha (LXRalpha) were reduced by approximately 50% (P < 0.01) and approximately 34% (P < 0.01), respectively. As LXRalpha regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an approximately 43% (P < 0.001) reduction in mRNA levels of SREBP-1c and its response genes, including acetyl-CoA carboxylase by approximately 35% (P = 0.01), fatty acid synthase by approximately 18% (P = 0.05), and diacylglycerol acyltransferase by approximately 19% (P = 0.03). Furthermore, protein levels of CD36 were reduced by approximately 27% (P = 0.02) in Fe-restricted fetuses. In conclusion, changes in liver cholesterol and TG concentrations in Fe-restricted fetuses may be coordinated through reduced expression of heme-containing cholesterol 7alpha hydroxylase and its regulator LXRalpha, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.

Atazanavir—A Once-daily HIV Protease Inhibitor That Does Not Cause Dyslipidemia in Newly Treated Patients: Results from Two Randomized Clinical Trials

Protease inhibitor (PI) treatment can result in dyslipidemia in a significant proportion of patients. Atazanavir (ATV) is a once-daily PI that has not been associated with clinically relevant increases in total cholesterol (TC), fasting low-density lipoprotein cholesterol (LDL-C), or fasting triglyceride (TG) concentrations. The objectives of this paper were to evaluate lipid profiles in untreated patients, and investigate the frequency and severity of dyslipidemia in the same individuals after treatment with ATV or nelfinavir (NFV) for 48 weeks. Two multinational, randomized, active-controlled, blinded trials compared the safety and efficacy of ATV and NFV in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in antiretroviral (ARV)-naive patients. Serum lipid concentrations were analyzed in patients who had available measurements both at baseline and at week 48. Patients who had missing data at either time point were not included. Lipid levels remained within baseline ranges at week 48 with ATV treatment, whereas clinically relevant elevations in TC, fasting LDL-C, and fasting TG concentrations occurred with NFV treatment. Mean changes from pre-treatment baseline in fasting LDL-C ranged from -6 percent to +6 percent in the ATV-treatment groups, and from +27 percent to +31 percent in the NFV-treatment groups. After 48 weeks, there was a substantive increase in the proportion of NFV-treated patients who would be recommended for lipid-lowering treatment by National Cholesterol Education Program (NCEP) guidelines, whereas a lesser proportion of ATV-treated patients would be recommended for lipid-lowering treatment. Atazanavir does not lead to dyslipidemia in ARV-naive patients, and may limit the need for lipid-lowering strategies to reduce the risk of cardiovascular disease.

An observational study of Yasmin® in the management of women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is the commonest endocrine disturbance affecting women in the reproductive age group and encompasses signs of hyperandrogenism, menstrual cycle disturbances and obesity. Some of the symptoms...

Association of plasminogen activator inhibitor-1 4G/5G gene polymorphism with variations in the LDL particle size in healthy Japanese men

Background: Several studies have supported the association between a predominance of small, dense low-density lipoprotein (LDL) and the risk of coronary artery disease. As another potentially atherogenic factor, impaired fibrinolytic activity due to increased plasminogen activator inhibitor-1 (PAI-1) concentrations has been shown. In addition, the 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene is reported to be associated with the atherogenic lipid profile. We investigated the relation between the PAI-1 gene polymorphism and LDL particle size. Methods: A total of 156 healthy Japanese male subjects were recruited. The diameter of LDL particles was determined at their peak size using polyacrylamide gels using fresh plasma samples. Results: Fasting insulin and triglyceride concentrations were found to be significantly higher, and the LDL particle size was smaller in the homozygotes for the 5G allele than in the carriers of the 4G allele. An analysis of covariance (ANCOVA) adjusting for insulin and triglyceride concentrations showed a consistently significant difference in LDL particle size between the two groups. In the forward stepwise multiple regression analysis, triglycerides, insulin, and the PAI-1 5G/5G genotype remained in the model as independent and significant predictors capable of influencing the LDL particle size. Conclusions: Our findings suggest that the 4G/5G polymorphism of the PAI-1 gene might be associated with LDL particle size in healthy Japanese males.

Variation in the lamin A/C gene: associations with metabolic syndrome.

Metabolic syndrome is associated with increased risk for cardiovascular disease and type 2 diabetes mellitus (T2DM). The lamin A/C (LMNA) gene, mutations of which cause rare syndromes of severe insulin resistance and dyslipidemia, is located on chromosome 1q21-q24, a region linked to T2DM in several genome wide scans, including in the Old Order Amish. To determine whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and its constituent components. We performed DNA sequence analysis of LMNA. Six single-nucleotide polymorphisms (SNPs) were identified: c.141889C>T (intron 3), c.141906G>T (intron 3), A287A (c.141253T>C; exon 5), c.140353G>A (intron 6), c.139418C>T (intron 8), and H566H (c. 138747C>T; exon 10). In 971 participants from the Amish Family Diabetes Study, the H566H polymorphism of LMNA was associated with metabolic syndrome diagnosed according to National Cholesterol Education Program ATP III criteria and also higher mean fasting triglyceride and lower mean high-density lipoprotein-cholesterol concentrations. However, no differences in allele frequencies were observed for any SNP among participants with T2DM or impaired glucose homeostasis (IGH) and normoglycemic controls. Haplotype analysis showed that >87% of individuals carried 1 of 2 common LMNA haplotypes. There were no significant differences in haplotype frequencies among subjects with metabolic syndrome T2DM, IGH, and controls. Sequence variation in LMNA may confer modest susceptibility for development of metabolic syndrome and dyslipidemia in the Amish. To determine whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and its constituent components, we performed DNA analysis of polymorphisms in LMNA. The H566H polymorphism was associated with metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the Old Order Amish.

Apolipoprotein C-III SstI Genotypes Modulate Exercise-Induced Hypotriglyceridemia

To investigate whether the efficacy of exercise as an antitriglyceridemic treatment was dependent on the apolipoprotein (apo) C-III SstI gene polymorphism. A subgroup of 100 Korean men, who were prescreened by genotypes (S1S1 = 40, S1S2 = 40, S2S2 = 20), participated in a 6-d moderate-exercise intervention using either a motor-driven treadmill or a cycle ergometer. Height and weight for body mass index and waist circumference were measured. Fasting total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and insulin were measured. Univariate analysis of variance and ANCOVA followed by Bonferroni post hoc tests were used to compare the preintervention values and the pre- to postexercise change (delta) scores in the measured variables across the genotypes, respectively. Multivariate linear regressions were carried out with age, smoking, waist circumference, body mass index, and genotype as independent variables and lipids, glucose, and insulin as dependent variables. Subjects with the S2S2 genotype had a significantly higher preintervention TG concentration than subjects with the S1S1 genotype (P = 0.022). Waist circumference and genotype were the only significant predictors for the preintervention TG (P < 0.001). With respect to the delta scores, the subjects with the S2S2 genotype had a greater reduction in TG than the subjects with the S1S1 genotype, adjusted for the preintervention difference (P = 0.047). This study suggests that the apo C-III SstI gene polymorphism might be useful for determining who is most susceptible to intervention by exercise in lowering fasting TG concentration.

Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality. Although it was previously assumed that this was due to its relation with obesity, recent data suggest that OSA is independently associated with the cardiovascular risk factors that comprise metabolic syndrome, including hypertension, insulin resistance, impaired glucose tolerance, and dyslipidaemia. However, as previous studies have only considered these variables individually, it has not been possible to determine the overall association of OSA with this syndrome. We recruited 61 male subjects with OSA and 43 controls. Glucose, insulin, lipids, and blood pressure (BP) were measured following an overnight fast. Insulin resistance was estimated using homeostasis model assessment (HOMA). Metabolic syndrome was diagnosed according to National Cholesterol Education Program (NCEP) criteria. Subjects with OSA were more obese, had higher BP and fasting insulin, were more insulin resistant, had lower HDL cholesterol, and an increased incidence of metabolic syndrome (87% vs. 35%, p<0.0001). In order to determine whether these associations were independent of obesity and other known covariates, a regression analysis adjusted for age, BMI, smoking, and alcohol consumption was performed. This demonstrated that OSA was independently associated with increased systolic and diastolic blood pressure, higher fasting insulin and triglyceride concentrations, decreased HDL cholesterol, increased cholesterol:HDL ratio, and a trend towards higher HOMA values. Metabolic syndrome was 9.1 (95% confidence interval 2.6, 31.2: p<0.0001) times more likely to be present in subjects with OSA. OSA is independently associated with an increase in the cardiovascular risk factors that comprise the metabolic syndrome and its overall prevalence. This may help explain the increased cardiovascular morbidity and mortality associated with this condition.

W12.289 PPARγ activation lowers postprandial but not fasting triglyceride concentrations in type 2 diabetes: An investigation of tissue-specific mechanisms in humans

The present study was conducted to determine whether alimentary lipemia alters platelet activity in vivo. Normolipidemic volunteers were given a fatty meal and platelet function was assessed before, and 3 and 6 h after the meal. Platelet aggregability and secretion was determined using whole blood flow cytometry (expression of platelet P-selectin and fibrinogen binding), filtragometry ex vivo (reflecting platelet aggregability in vivo) and by measurements of platelet specific products in plasma (β-thromboglobulin and platelet factor 4). Plasma triglycerides increased from 0.8 (0.6:1.1; median, 25th and 75th percentiles) to 1.7 (1.0:2.3) mmol/l at 3 h and returned to baseline after 6 h (P<0.001, one-way ANOVA). Apo B-100 and apo B-48 were both markedly increased 3 h postprandially in the Sf 60–400 fraction (large VLDLs, P<0.001 for both), whereas the Sf 20–60 (small VLDLs) and Sf 12–20 fractions (IDL) did not change. The platelet function assessments revealed that the percentage of platelets expressing P-selectin increased by 40% (5%; 64%) after 3 h and by 51% (−7%; 85%) 6 h postprandially in unstimulated samples (P<0.05 for both). In samples stimulated by ADP in vitro P-selectin expression increased by 45% (6%; 58%) after 3 h and by 30% (12%; 58%) (P<0.01 for both) after 6 h at 0.1 μM. Platelet P-selectin expression was less influenced at higher ADP concentrations. The plasma levels of β-thromboglobulin (≈20 ng/ml) and platelet factor 4 (≈0.3 ng/ml) were not affected by the fat load. Flow cytometric analyses of fibrinogen binding and filtragometry measurements also failed to reveal any postprandial alterations. The present finding of enhanced platelet P-selectin expression suggests that platelets are mildly sensitized postprandially. Whether this is of importance for thrombus formation and atherosclerosis needs to be studied further.

W12.289 PPAR$gamma; activation lowers postprandial but not fasting triglyceride concentrations in type 2 diabetes: An investigation of tissue-specific mechanisms in humans

W12.289 PPAR$gamma; activation lowers postprandial but not fasting triglyceride concentrations in type 2 diabetes: An investigation of tissue-specific mechanisms in humans

The Combined Effect of β2- and β3-Adrenergic Receptor Genotypes on Hyperglycemic Risk in the Korean Population

Adrenergic receptors play a major role in thermogenesis and lipolysis in brown and visceral adipose tissues, and have been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of β2-adrenergic receptor (β2AR) and β3-adrenergic receptor (β3AR) genotypes on hyperglycemia and obesity in the Korean population. A representative sample consisting of 530 Korean men and women were measured for height, weight, BMI, WHR, obesity index and body composition. The genotypes of β2AR polymorphism in codon 27 and β3AR polymorphism in codon 64 were analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, total cholesterol, HDL cholesterol and triglyceride were determined. The frequencies of β2AR and β3AR genotype were: both wild type, 62.5%; only β2AR variant type, 12.8%; only β3AR variant type, 18.8%; and both variant type, 5.8%; the frequency of E and R alleles were 0.098 and 0.137, respectively. Among the physiological parameters, fasting glucose level was significantly higher in subjects with both variant type compared with the three other types (p＜0.05). Subjects with both variant type had 12%, 12% and 9.3% increases in serum glucose levels compared with wild type, only β2AR variant type, and only β3AR variant type, respectively. When logistic regression analysis was conducted to estimate the risk for hyperglycemia, the subjects were selected for fasting blood glucose concentrations of more than 6.105 mmol/L (110 mg/dL), and the odds ratios were 1.215 (p=0.636) for only β2AR variant type, 1.659 (p=0.089) for only β3AR variant type, and 3.078 (p=0.011) for both variant type. These results suggest that the interaction of β2AR and β3AR variant genotypes has a strong association with increased glucose levels, and might be a significant risk factor for hyperglycemia among Korean subjects.

Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration

Background Hyperinsulinemia/insulin resistance and elevated plasma free fatty acids (FFA) levels are involved in the hypertension and cardiac sympathetic overactivity. Metformin improves insulin action and lower plasma FFA concentrations. We investigate the possible effect of metformin on arterial blood pressure (BP) and cardiac sympathetic nervous system. Methods One hundred twenty overweight type 2 diabetic patients were treated by placebo ( n = 60) + diet or metformin (850 mg twice daily) ( n = 60) + diet for 4 months, to evaluate the effect of metformin treatment on the cardiac autonomic nervous system. Insulin resistance was measured by the Homeostasis Model Assessment (HOMA) index. Heart rate variability (HRV) assessed cardiac sympathovagal balance. Results Metformin treatment, but not placebo treatment, was associated with a decrease in fasting plasma glucose ( P < .05), insulin ( P < .05), triglyceride ( P < .05), and FFA ( P < .03) concentrations and HOMA index ( P < .03). Metformin treatment was also associated with a significant improvement in cardiac sympathovagal balance but not in mean arterial BP. Furthermore, in a multivariate analysis, delta change in sympathovagal balance index (LF/HF ratio) were associated with delta change in plasma FFA concentrations and HOMA index independently of gender and delta change in plasma triglyceride and HbA1c concentrations. Conclusions Our study demonstrated that metformin treatment might be useful for improving cardiac sympathovagal balance in obese type 2 diabetic patients.

The effect of high-fat and high-fructose diets on glucose tolerance and plasma lipid and leptin levels in rats.

High-fat and high-fructose diets are usually used to induce animal model diabetes mellitus. The purposes of this research were to compare the abnormalities of glucose metabolism caused by high-fructose diet and a high-fat diet and the effects of the high-fructose diet and high-fat diet on plasma leptin. In this research, 24 Sprague-Dawley rats were used as the experimental animals, which were divided into three groups: chow diet (control group), high-fructose diet (60% fructose w/w) and high-fat diet (20% lard w/w). They were fed for a period of 8 weeks, during which an oral glucose tolerance test was conducted in the seventh week, and after completion of the eighth week, the abdominal adipose tissue and liver of the rats were excised and weighed, and the plasma cholesterol, triglyceride, insulin and leptin concentrations were assayed. The high-fat diet group presented a fasting blood glucose concentration that was higher than that of the control group. Furthermore, after 2 h of glucose challenge, the rats in the high-fat and high-fructose diet groups all presented higher plasma glucose concentrations than did the control group. The high-fat diet group showed higher body weight, higher relative liver weight, a higher plasma cholesterol concentration and higher amylase activity than did the other groups, whereas the high-fructose diet group showed higher fasting insulin and triglyceride concentrations. As for adipose tissue, the high-fat diet group presented an amount that was higher than that of the high-fructose and control groups, but the plasma leptin concentration of the high-fructose group was higher than that of the control group. It can be concluded from the above-mentioned experimental results that a high-fructose diet can cause hyperinsulinaemia, while a high-fat diet can result in impaired pancreatic function of insulin secretion and glucose intolerance, indicating that high-fructose diet and a high-fat diet may exert divergent effects on glucose metabolism in rats.

Low fasting low high-density lipoprotein and postprandial lipemia

BackgroundLow levels of high density lipoprotein (HDL) cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG) postprandially in respect to serum HDL cholesterol levels.ResultsFifty two Greek men were divided into 2 main groups: a) the low HDL group (HDL < 40 mg/dl), and b) the control group. Both groups were further matched according to fasting TG (matched-low HDL, and matched-control groups). The fasting TG concentrations were higher in the low HDL group compared to controls (p = 0.002). The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p < 0.001, respectively). The matched-low HDL group revealed higher TG only at 8 h postprandially (p = 0.017) compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p < 0.001).ConclusionsThe delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.