Myeloperoxidase and paraoxonase-1 in type 2 diabetic patients

Background and aimsReduced high density lipoproteins (HDL) and increased oxidative stress are features of type 2 diabetes. Myeloperoxidase is an oxidative enzyme partly associated with HDL and causing HDL dysfunction. It is an independent risk factor for cardiovascular disease. Paraoxonase-1 is an HDL-associated enzyme that protects against cardiovascular disease and is reduced in diabetes. The present study examined if serum myeloperoxidase was (i) increased in type 2 diabetes, (ii) correlated with paraoxonase-1 activity.Methods and resultsThe study was based on cross-sectional analyses of serum myeloperoxidase and paraoxonase-1 in type 2 diabetic patients and non-diabetic participants, with and without cardiovascular disease.Serum myeloperoxidase concentrations were not increased in type 2 diabetic patients without cardiovascular disease compared to non-diabetic controls. They were significantly higher in type 2 patients and non-diabetic patients with angiographically confirmed coronary disease. HDL-associated myeloperoxidase was correlated with serum myeloperoxidase (r = 0.80, p < 0.001) but not HDL-cholesterol (r = 0.08) or apolipoprotein AI (r = 0.08). Multivariate analyses showed serum myeloperoxidase to be an independent determinant of paraoxonase activities (arylesterase, p = 0.024; paraoxonase, p = 0.026).ConclusionsMyeloperoxidase is an independent, negative determinant of paraoxonase-1 activity, which may be one mechanism by which it promotes HDL dysfunction and increases cardiovascular risk. Increased serum myeloperoxidase is not a feature of type 2 diabetes in the absence of overt cardiovascular disease. The level of HDL-associated myeloperoxidase is determined by the serum concentration of the enzyme suggesting that, in the context of reduced HDL concentrations in diabetic patients, myeloperoxidase may have a greater impact on HDL function.     

Decreased lipoprotein lipase activity and increased postprandial concentrations of triglyceride-rich lipoproteins in offspring of elderly survivors of myocardial infarction

Background and aimA family history of myocardial infarction (MI) is an independent risk factor for future coronary events. Decreased plasma lipoprotein lipase (LPL) activity is associated with delayed clearance of triglyceride-rich lipoproteins (TRL) and low fasting HDL cholesterol. The aim of the study was to investigate the relations between plasma LPL activity, postprandial TRL and HDL cholesterol in offspring of MI patients.Methods and resultsA case-control study was performed in 17 healthy middle-aged offspring of MI patients and 13 healthy age-and sex-matched controls. Fasting blood samples were collected and each subject was given a standardized oral fat load (1 g fat/kg body weight) with subsequent blood samples collected for an 8-h period. Offspring of MI patients had significantly lower postheparin LPL activity (62.9 mU/ml ± 22.8 mU/ml) (mean ± SD) than healthy controls (93.0 mU/ml ± 21.7 mU/ml) (p = 0.002). Decreased postheparin LPL activity was accompanied by significantly increased and delayed clearance of postprandial TRL and subsequent lower fasting HDL cholesterol in offspring of MI patients. Postheparin LPL activity was associated with HDL cholesterol (r = 0.40, p = 0.036) and trend analysis revealed a decrease in incremental area under the curve (AUCi) for chylomicrons with increasing LPL activity (p = 0.013).ConclusionsOffspring of MI patients had decreased postheparin LPL activity accompanied by increased postprandial TRL and subsequent decreased HDL cholesterol, an unfavourable lipid profile which may contribute to their increased risk for future coronary events.     

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.     

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

ObjectiveTo study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk.Methods and designThe lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96).ResultsHIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns).ConclusionAn already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.     

Is vitamin D status a predictor glycaemic regulation and cardiac complication in type 2 diabetes mellitus patients?

ObjectiveTo evaluate vitamin D as a predictor of glycaemic regulation in type 2 diabetes mellitus patients.Research design and methodsIn observational study 171 type 2 diabetic patients who are followed for median (range) of 10.15 (3–18) years. Mean ± SD age was 56 ± 10. Plasma 25-hydroxyvitamin D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry on baseline samples. Vitamin D deficiency was defined as a 25-OHD level of less than 20 ng/ml. Vitamin D levels between 20 and 30 ng/ml are termed ‘insufficient’. Vitamin D levels greater than 30 ng/ml are termed ‘optimal’.Results125 patients have vitamin D deficiency, 14 patients have insufficient and the others have optimal. Vitamin D levels were not associated with sex, age, BMI, HDL, LDL, kreatinin, hypertension and smoking. But vitamin D deficiency patients had more longer duration (p = 0.011), more higher uric acid (p = 0.021), fasting glucose (p = 0.037), postprandial glucose (p = 0.001) and HbA1c (p = 0.026).ConclusionsIn our study type 2 diabetic patients have 73% of vitamin D deficiency. Vitamin D deficiency predicts higher fasting and postprandial blood glucose and diabetes disregulation. Type 2 DM patients and low 25-OH vitamin D levels could increased cardiovascular disease directly or indirectly (low HDL and high uric acid in 25-OH vitamin D <20 ng/ml). Whether vitamin D substitution improves prognosis remains to be investigated.     

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

ObjectiveTo examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia.MethodsHealthy men (n = 112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min) and lunch (330 min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples.ResultsSubjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P ≤ 0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (max C) were significantly greater in men with ≥3 than <3 components (P < 0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P < 0.04). For glucose, max C after the test breakfast (0–330 min) and total AUC (0–480 min) were higher in men with ≥3 than <3 components (P ≤ 0.001).ConclusionsOur data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components.     

Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

Background and aimsPostprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue.Methods and resultsTen subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) – males, aged 26–59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6 h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188 ± 28 and 135 ± 22 mg/dl·6 h) than C (87 ± 13 mg/dl·6 h, M ± SEM, p < 0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132 ± 23 vs. 75 ± 14 mg/dl·6 h, p < 0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C.ConclusionsIn insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.     

The plasma concentration of Lpa-I:A-II particles as a predictor of the inflammatory response in patients with ST-elevation myocardial infarction

ObjectiveTo investigate the relationship between plasma HDL at admission and the extent of the inflammatory response during an ST-elevation myocardial infarction (STEMI), and to analyse structural HDL changes during STEMI as related to the extent of inflammation.Methods and resultsCRP and IL-6 were monitored for 96 h in 45 patients with STEMI. Plasma apoA-II and LpA-I:A-II levels at admission, but not HDL cholesterol or other HDL-related biomarkers, were associated with the extent of the inflammatory response during STEMI, as indicated by the positive correlations with CRP AUC (apoA-II: F = 7.44, p = 0.009; LpA-I:A-II: F = 14.29, p < 0.001), and IL-6 AUC (apoA-II: F = 6.98, p = 0.012; LpA-I:A-II: F = 6.67, p = 0.013). By multivariate analysis the plasma LpA-I:A-II level at admission was a powerful independent predictor of the inflammatory response, evaluated either as CRP AUC (F = 22.30, p < 0.001), or IL-6 AUC (F = 6.92, p = 0.012). During STEMI, the plasma concentration of LpA-I:A-II, but not LpA-I particles decreased, HDL became larger and progressively enriched in serum amyloid A; these changes occurred only in patients with a significant inflammatory response.ConclusionAn elevated plasma concentration of LpA-I:A-II particles was an independent predictor of a more severe inflammatory response in patients with STEMI.     

Incident type 2 diabetes is associated with HDL,but not with its anti-oxidant constituent - paraoxonase-1: The prospective cohort PREVEND study

ObjectiveHigh-density lipoprotein cholesterol (HDL-C) is an established risk marker for cardiovascular disease and consistently associated with type 2 diabetes risk. Serum paraoxonase-1 (PON-1) - an anti-oxidant constituent of HDL - is inversely associated with cardiovascular disease risk, but its relationship with incident type 2 diabetes is uncertain. We aimed to investigate the prospective association between PON-1 and type 2 diabetes risk.MethodsPON-1 was measured as its arylesterase activity at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective study of 5947 predominantly Caucasian participants aged 28–75 years with no pre-existing diabetes, that recorded 500 type 2 diabetes cases during a median follow-up of 11.2 years.ResultsSerum PON-1 was positively correlated with HDL-C (r = 0.17; P < 0.001). In analyses adjusted for conventional diabetes risk factors, the hazard ratio (95% CI) for type 2 diabetes per 1 standard deviation increase in PON-1 was 1.07 (0.98 to 1.18; P = 0.13), which remained non-significant (1.02 (0.93 to 1.12) P = 0.65) after additional adjustment for potential confounders. The association was unchanged on further adjustment for HDL-C (1.05 (0.96 to 1.15; P = 0.29). However, in subsidiary analyses in the same set of participants, serum HDL-C concentration was inversely and independently associated with risk of type 2 diabetes.ConclusionsIncident type 2 diabetes is associated with HDL cholesterol but not with its anti-oxidant constituent - PON-1 - in a large cohort of apparently healthy men and women. The current data question the importance of PON-1 activity for the development of diabetes.     

Hypertension strengthens δ-ALA-D activity inhibition and increases it reactivation index in type 2 diabetic patients

AimsTo assess the effect of hypertension on δ-aminolevulinate dehydratase (δ-ALA-D) activity of type 2 diabetic patients (T2DM).Methodsδ-ALA-D activity and reactivation index, as well as markers of oxidative stress, biochemical and anthropometrics parameters were determined in T2DM (n = 23), type 2 diabetic patients with hypertension (T2DM/HT) (n = 30) and controls (n = 30).ResultsT2DM/HT presented a greater inhibition of δ-ALA-D activity, a higher reactivation index (p < 0.05) and a greater depletion of plasma protein thiol groups (P-SH) when compared to T2DM. Moreover, δ-ALA-D activity was positively associated with SH groups and negatively associated with serum protein carbonyl (PC) while its reactivation index was negatively associated with SH groups and positively associated with PC.ConclusionsThese results point out that there is a possible interference of hypertension on the mechanism of the δ-ALA-D activity suggesting that this condition aggravated the oxidative stress of diabetes mellitus.     

Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia

BackgroundOmega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia. However, a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published.MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Fifty patients in each group were given placebo, omega-3 fatty acids 2 g (most commonly used dosage in Korean patients), or fenofibrate 160 mg, respectively daily for 2 months.ResultsOmega-3 fatty acids therapy decreased triglycerides by 21% and triglycerides/HDL cholesterol and improved flow-mediated dilation (P < 0.01), however, did not significantly change insulin, plasma adiponectin levels, and insulin sensitivity (determined by QUICKI) relative to baseline measurements. Fenofibrate therapy decreased total cholesterol, triglycerides by 29%, and triglycerides/HDL-cholesterol (all P < 0.01) and improved flow-mediated dilation when compared with baseline. When compared with placebo and omega-3 fatty acids, fenofibrate therapy decreased non-HDL cholesterol (P < 0.001) and triglycerides/HDL cholesterol (P = 0.016) while increasing HDL cholesterol (P < 0.001) and apolipoprotein AI (P = 0.001). Of note, when compared with omega-3 fatty acids, fenofibrate therapy decreased fasting insulin (P = 0.023) and increased plasma adiponectin (P = 0.002) and insulin sensitivity (P = 0.015).ConclusionsOmega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation. However, fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia.     

Association of lower total bilirubin level with statin usage: the United States National Health and Nutrition Examination Survey 1999-2008

ObjectiveA low circulating level of bilirubin is associated with increased cardiovascular risk. As statins can stimulate heme oxygenase-1 (HO-1), which increases bilirubin production, we investigated whether statins in routine use increase total bilirubin levels in subjects at high cardiovascular risk.MethodsData from 3290 subjects with self-reported history of hypercholesterolemia, diabetes, or cardiovascular diseases in the United States National Health and Nutrition Examination Survey (NHANES) 1999–2008 were analyzed.ResultsSubjects taking statins (n = 1156) had lower total bilirubin levels than those not taking any lipid-lowering medication (n = 2134) after adjusting for age, sex, race/ethnicity, and survey period (adjusted mean = 0.699 vs 0.729 mg/dl respectively, P = 0.001). The association remained significant after adjusting for more covariates (P = 0.002), but was attenuated after further adjusting for glycosylated hemoglobin, insulin resistance index, and low-density lipoprotein (LDL) cholesterol (P = 0.043). The use of lovastatin, rosuvastatin, and cerivastatin was associated with lower total bilirubin levels in the full adjustment model (P < 0.05).ConclusionThe use of statins was associated unexpectedly with lower total bilirubin levels. This could be explained at least partly by the effect of statins on glycemia and LDL cholesterol. Our results do not suggest that the anti-oxidant and anti-inflammatory effects of statins are due to HO-1 induction and increased serum bilirubin levels.     

Urine α-Glutathione S-transferase, systemic inflammation and arterial function in juvenile type 1 diabetes

BackgroundDespite marked improvement in therapy and monitoring of patients with insulin-dependent (type 1) diabetes, diabetic nephropathy remains a serious complication, with subsequent end-stage renal disease in about 20% of cases.ObjectiveTo investigate in young patients with type 1 diabetes whether urine α-Glutathione S-transferase to creatinine ratio (α-GST:crea) relates to markers of systemic inflammation and subclinical vasculopathy.DesignChildren and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type 1 diabetes screened in a previous study for proximal tubular (urine α-GST:crea ratio) and renal (plasma creatinine, cystatin C glomerular filtration rate (GFR), and timed urine albumin excretion rate (AER)) function were, within the same timeframe, also investigated for vascular (blood pressure, carotid artery intima–media thickness (IMT) and compliance (CAC), brachial artery flow-mediated dilatation (FMD) and plasma cyclic guanosine monophosphate (cGMP) and inflammatory (C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α)) profiles. Exposure to environmental tobacco smoke (ETS) was assessed through questionnaire (n = 67 respondents).ResultsNone of the patients (n = 69) had overt renal insufficiency. AER correlated with age (p = 0.01, r = 0.3), diabetes duration (p = 0.02, r = 0.3), FMD (p = 0.04, r = ? 0.3, n = 52), CAC (p = 0.03, r = ? 0.3, n = 62) and cGMP (p = 0.01, r = ? 0.3, n = 59). α-GST:crea was lower (p = 0.03) in patients than in controls. α-GST:crea appeared to be particularly lower in older patients (p = 0.004, r = ? 0.34 vs age), in those with worse diabetic control (p = 0.03, r = ? 0.26 vs HbA1c), and in those with lower carotid artery elasticity (p = 0.017, r = 0.3 vs CAC). Although ETS had no direct significant impact on α-GST:crea, α-GST:crea correlated with FMD only in patients with ETS (r = 0.5, p = 0.009, n = 13). α-GST:crea showed positive association with TNF-α (p = 0.01, r = 0.3).ConclusionIn children and adolescents with type 1 diabetes, lower levels of urine excretion of α-GST:crea appear to be associated with decreasing elasticity and endothelial vasomotor function of peripheral arteries, especially in patients with ETS. In contrast, higher levels of α-GST:crea are more common in patients with elevated markers of systemic inflammation. Large scale prospective studies are needed to clarify the meaning and mechanisms of this association.     

Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy

ObjectiveTo evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway.MethodsThe capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0–8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl).ResultsThe larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner.ConclusionCETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia.     

Postprandial hyperlipidemia in overt and subclinical hypothyroidism

Background and aimsLipid alterations in overt hypothyroidsm (OH) were well known, but its changes in subclinical hypothyroidism (SCH) and postprandial period were not clear. The aim of this study is to evaluate postprandial lipemia by oral lipid tolerance test (OLTT) in patients with OH and SCH.Materials and methodologyTwenty-five OH and 27 SCH, totally 52 hypothyroid patients [mean age 38.3 ± 12.8 year, body mass index (BMI): 29.0 ± 5.8 kg/m²] and 23 BMI- and age-matched healthy controls (mean age 36.7 ± 11.9 years; BMI: 27.1 ± 6.9 kg/m²) were included to the study. Anthropometric measurements and HOMA-IR levels were measured. Basal and postprandial lipid profile at 2nd, 4th, 6th and 8th hours were determined by oral lipid tolerance test.ResultsThere were not any statistical differences among three groups (control, OH and SCH) in terms of mean fasting levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride. On the contrary, mean triglyceride levels at postprandial 8th hour in both OH and SCH patients were higher than control subjects (p = 0.017 and p = 0.049, respectively). Again mean postprandial 8th hour VLDL-cholesterol levels in OH group were also higher than control subjects (p = 0.05). In addition mean HOMA-IR value of SCH and OH patients was similar with control subjects (1.5 ± 1.4 in OH; 1.3 ± 0.8 in SCH; 2.2 ± 2.2 in control group).ConclusionsAlthough total, LDL and VLDL-cholesterol, and triglyceride levels were not different from healthy controls, triglyceride and/or VLDL-cholesterol levels apparently increased with OLTT in both OH and SCH patients. Decreased lipid clearance may be responsible for this result.     

Effects of short-term low- and high-carbohydrate diets on postprandial metabolism in non-diabetic and diabetic subjects

Background and aimLow-fat high-carbohydrate diets raise plasma triacylglycerol (TG) concentrations. To test whether the nature of the carbohydrate affects metabolic responses, we conducted a randomized cross-over study using a short-term, intensive dietary modification.Methods and resultsEight non-diabetic subjects and four subjects with diet-controlled type 2 diabetes participated. They followed three isoenergetic diets, each for 3 days: high-fat (50% energy from fat), high-starch and high-sugar (each 70% energy from carbohydrate). Normal foods were provided. We measured plasma TG and glucose concentrations, fasting and after a standard test meal, on day 4 following each dietary period. Fasting TG concentrations were greatest following the high-sugar diet (mean ± SEM for all subjects 1900 ± 420 μmol/l) and lowest following high-fat (1010 ± 130 μmol/l) (P = 0.001); high-starch (mean 1500 ± 310) and high-fat did not differ significantly (P = 0.06). There was a greater effect in the diabetic subjects (diet × diabetes status interaction, P = 0.008). Postprandial TG concentrations were similarly affected by prior diet (P < 0.001) with each diet different from the others (P ≤ 0.01). The elevation of fasting TG on the high-sugar versus high-fat diet was strongly related to the average fasting TG concentration (P = 0.01 across both diabetic and non-diabetic subjects). Fasting glucose concentrations were not affected by prior diet but postprandial glucose concentrations were (P = 0.018), with significantly higher values after the high-fat than the high-sugar diet (P = 0.03).ConclusionsThe short-term TG-raising effect of a very low-fat diet is dependent upon the nature of the carbohydrate, with a greater effect of a sugar-rich than a complex-carbohydrate-rich diet.     

SHBG levels correlate with insulin resistance in postmenopausal women

BackgroundOverweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated.Methods229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n = 125) and postmenopausal women (n = 104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured.ResultsNo significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p = 0.866).In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI.In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL.SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol.ConclusionsObesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women.These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.     

Glycated apolipoprotein B and myocardial infarction

AimsTo evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes.MethodsThe design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data.ResultsApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P = 0.009 and P = 0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95 % CI 0.93–4.33) in non-diabetic and 2.88 (0.85–9.68) in diabetic subjects (chi-square test for trend; non-diabetics P = 0.03, diabetics P = 0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P > 0.10).ConclusionApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.