Fasting Plasma Triglyceride Concentrations Research Articles

Association of hypertriglyceridemic waist phenotype with metabolic syndrome traits and its diagnostic potential to predict metabolic syndrome in adults with excess body weight: A community-based cross-sectional study.

The hypertriglyceridemic waist (HTGW) phenotype is a simple measure to identify individuals at increased risk of metabolic syndrome (MetS) traits. The present study aimed to describe the HTGW prevalence, and its associations with MetS traits, and also determine the diagnostic potential of the mirror indices of HTGW phenotype to predict MetS and its components in community-dwelling adults with overweight or obesity in Southern, Sri Lanka. In a cross-sectional study, 300 adults with excess body weight (body mass index >23 kg/m2) were enrolled and examined for the HTGW phenotype (fasting plasma triglyceride concentration ≥1.695 mmol/L and waist circumference >90 and >85 cm in males and females, respectively). One in five adults with excess body weight had the HTGW phenotype. Phenotype-positive adults had significantly higher fasting plasma glucose (FPG) (p = 0.010), low-density lipoprotein cholesterol (HDL-C) (p < 0.001), total cholesterol (p < 0.001), atherogenic index (p < 0.001), coronary risk index (p = 0.001), triglyceride glucose index (p = 0.040), bioimpedance visceral fat (p = 0.041) and significantly lower HDL-C (p = 0.001) and cardioprotective index (p = 0.009) than those without the HTGW phenotype. Adults with excess body weight and the HTGW phenotype had an increased risk of FPG (odds ratio [OR] = 1.294; 95% confidence interval [CI] 1.051-1.594), atherogenic index (OR = 3.138; 95% CI = 1.559-6.317) and triglyceride glucose index (OR = 3.027; 95% CI = 1.111-8.249). The HTGW phenotype was strongly associated with MetS traits (OR = 16.584; 95% CI = 6.230-44.147). The cut-off values for the product of waist circumference × triglyceride, to identify the risk of having MetS and dyslipidemia among adults with excess body weight were 158.66 and 160.15 cm × mmol/L, respectively. The readily available and inexpensive measures of the HTGW phenotype could serve as a clinically useful marker to identify MetS traits in adults with excess body weight.

Triglyceride-glucose index is capable of identifying metabolically obese, normal-weight older individuals

BackgroundThe concept of metabolically obese, normal weight (MONW) has emerged to describe individuals with a normal body mass index (BMI) who are at a relatively high risk of chronic diseases. However, BMI itself is a suboptimal index for the assessment of the health risks associated with visceral fat. The triglyceride-glucose (TyG) index is considered to be a reliable and cost-effective marker of insulin resistance. Therefore, in the present study, we aimed to determine the TyG index cut-off values that could be used to define MONW in older people and to determine the usefulness of these values for the prediction of chronic diseases.MethodsA total of 4,721 participants in the Korea National Health and Nutritional Examination Survey who were ≥ 60 years of age and did not have underweight or obesity were included. MONW was defined using the criteria for metabolic syndrome (MS), and the TyG index was calculated on the basis of the fasting plasma triglyceride and glucose concentrations. Chronic diseases, including T2DM, hypertension, and non-alcoholic fatty liver disease (NAFLD), were diagnosed.ResultsThe prevalence of MS increased from the lowest to the highest TyG index tertile. The cut-off values of the TyG index for MONW were calculated as 8.88 and 8.80 for males and females, respectively. MONW, defined using these cut-off values, was associated with high odds ratios for NAFLD, T2DM, and hypertension in both males and females.ConclusionsThe TyG index cut-off values calculated in the present study can be used to discriminate individuals with MONW from other older individuals without obesity and to predict the risk of chronic diseases. These findings show that the TyG index is an effective and cost-efficient method of assessing the risk of chronic diseases in people with MONW.

New targets for treating hypertriglyceridemia.

Elevated fasting and postprandial plasma triglyceride concentrations are associated with an increased risk for atherosclerotic cardiovascular disease in patients on and off low-density lipoprotein (LDL) lowering therapy. This association is not mediated by triglycerides directly. Other components of triglyceride rich lipoproteins, such as cholesterol and apolipoproteins B and -CIII can directly induce and enhance atherosclerosis. In addition, an elevated concentration of triglyceride rich lipoproteins affects the concentration, composition, function, and metabolism of LDL and high-density lipoprotein (HDL), which contributes to the risk. Especially in patients with hypertriglyceridemia, apolipoprotein B and non-HDL-cholesterol (encompassing cholesterol of all atherogenic lipoproteins) predict risk better than LDL-cholesterol and/or triglycerides. Therefore, current guidelines have stated secondary goals relating to non-HDL-cholesterol and apolipoprotein B (in addition to the primary goal relating to LDL-cholesterol). These secondary goals can be achieved by further reducing LDL-cholesterol or by decreasing triglyceride rich lipoproteins. However, only further LDL reduction has so far proven to be beneficial in outcome trials. In addition, high dose eicosapentaenoic acid (EPA) can reduce atherosclerotic cardio-vascular disease risk in patients with hypertriglyceridemia, although benefit is not (or not only) related to apolipoprotein B or non-HDL-cholesterol reduction. Non-HDL-cholesterol and apoB represent novel targets for patients with hypertriglyceridemia, but achieving LDL-cholesterol targets remains the first step for cardio-vascular risk reduction.

Exposure to a mixture of benzo[a]pyrene and triclosan induces multi-and transgenerational metabolic disorders associated with decreased female investment in reproduction in Silurana (Xenopus) tropicalis

Animals must partition limited resources between their own growth and subsequent reproduction. Endocrine disruptors (ED) may cause maternal metabolic disorders that decrease successful reproduction and might be responsible for multi- and transgenerational effects in amphibians. We found that the frog Silurana (Xenopus) tropicalis, exposed to environmentally relevant concentrations of benzo[a]pyrene and triclosan throughout its life cycle, produced F1 females with delayed sexual maturity and decreased size and weight. These F1 females displayed a marked metabolic syndrome associated with decreased fasting plasma cholesterol and triglyceride concentrations and decreased gonadal development. F1 females from F0 exposed animals also had decreased reproductive investment highlighted by a decrease of oocyte lipid reserves associated with significant F2-tadpole mortality. F2 females from F0 exposed animals also displayed a marked metabolic syndrome but were able to correctly direct liver lipid metabolism to the constitution of fat bodies and oocyte yolk stores. In addition, the F2 females produced progeny that had normal mortality levels at 5 days post hatching compared to the controls suggesting a good reproductive investment. Our data confirmed that these ED, at concentrations often found in natural ponds, can induce multi- and transgenerational metabolic disorders in the progeny of amphibians that are not directly exposed. We present a hypothesis to explain the transmission of the metabolic syndrome across generations through modification of egg reserves. However, when high mortality occurred at the tadpole stage, surviving females were able to cope with metabolic costs and produce viable progeny through sufficient investment in the contents of oocyte reserves.

Vitamin A Deficiency during the Perinatal Period and First Weeks of Life Modifies Vitamin A and Lipid Postprandial Metabolism in Both Female and Male Young Rats.

The effect of vitamin A deficiency on vitamin A and lipid postprandial metabolism in young rats is addressed, considering the effect of sex. Sprague-Dawley rats are fed either 400 UI.kg-1 vitamin A diet (vitamin A-deficient (VAD) diet) or 2300 UI.kg-1 vitamin A (control diet), before being mated. Mothers receive the same VAD or control diet during gestation and lactation. Offspring receive the same diet than mothers until 8 weeks of age. VAD diet-fed female and male offspring display a severe vitamin A deficiency with no body weight or glucose tolerance defects. Fasting plasma triglyceride concentrations are decreased in VAD diet-fed animals compared to controls (p < 0.05). Retinyl ester postprandial responses after vitamin A gavage, expressed as area under the curves, are not different in VAD diet-fed and control animals, although retinyl ester postprandial peak is significantly delayed (p < 0.05) in VAD diet-fed rats. Lipids also accumulate in the distal part of the intestine after gavage and [1-13 C]-oleate postprandial response is decreased in VAD diet-fed males. Vitamin A deficiency modulates both vitamin A absorption rate and lipid postprandial metabolism, which can partly explain the altered fasting lipid status observed in VAD diet-fed offspring.

Metabolic Status and Gender Affect the Absorption and Metabolism of Red Raspberry (Poly)phenols

Abstract Objectives Red raspberries are rich in bioactive (poly)phenols, particularly anthocyanins and ellagitannins. A substantial amount of variability is observed in the bioavailability and metabolism of (poly)phenols in humans. This study aimed to investigate the potential factors, i.e., metabolic status, body mass index (BMI), age, gender and race, on (poly)phenol metabolism in individuals with different health statuses. Methods After 3-day wash-in and overnight fasting, subjects (n = 65, male: female 32:33, age 34 ± 1 years, BMI 27 ± 1 kg/m2, mean ± SEM) consumed 250 g red raspberries (2 cups equivalence). Plasma samples collected over 24 h were quantified for (poly)phenolic metabolites using an ultra-high performance liquid chromatography coupled with triple quadrupole (UHPLC-QQQ). Statistical analysis was performed using PC-SAS. Results Individuals with prediabetes and insulin-resistance (n = 45) had significantly higher bioavailability of cyanidin sophoroside (0.21 ± 0.02% vs. 0.14 ± 0.03%, P = 0.04) and cyanidin 3-O-glucoside (0.12 ± 0.01% vs. 0.09 ± 0.01%, P = 0.02), and lower area under the 24 h curve (AUC0–24h) of hippuric acid glucuronide (435 ± 123 nmol/L × h vs. 1011 ± 184 nmol/L × h, P = 0.01) compared to healthy individuals (n = 20). Females (n = 33) had significantly lower bioavailability of cyanidin 3-O-glucoside (0.09 ± 0.01% vs. 0.13 ± 0.01%, P = 0.04) compared to males (n = 32). Correlation analysis on all subjects (n = 65) identified that bioavailability of cyanidin sophoroside and cyanidin 3-O-glucoside negatively correlated with fasting plasma triglyceride and positively correlated with HOMA-IR, HOMA-β, and fasting insulin concentration (P &amp;lt; 0.05). The AUC0–24h of hippuric acid glucuronide negatively correlated with fasting plasma glucose and triglyceride concentrations. Conclusions Individuals with different metabolic status and gender have different capacity to absorb and metabolize red raspberry (poly)phenols. The data provide insight for personalized nutrition for optimal health benefits and suggest further research on possible mechanisms involved. Funding Sources This project was funded by the National Processed Raspberry Council and various donor funds to the Center for Nutrition Research, Illinois Institute of Technology.

Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice

Adiponectin has emerged as a potential therapy for type 2 diabetes mellitus, but the molecular mechanism by which adiponectin reverses insulin resistance remains unclear. Two weeks of globular adiponectin (gAcrp30) treatment reduced fasting plasma glucose, triglyceride (TAG), and insulin concentrations and reversed whole-body insulin resistance, which could be attributed to both improved insulin-mediated suppression of endogenous glucose production and increased insulin-stimulated glucose uptake in muscle and adipose tissues. These improvements in liver and muscle sensitivity were associated with ∼50% reductions in liver and muscle TAG and plasma membrane (PM)-associated diacylglycerol (DAG) content and occurred independent of reductions in total ceramide content. Reductions of PM DAG content in liver and skeletal muscle were associated with reduced PKCε translocation in liver and reduced PKCθ and PKCε translocation in skeletal muscle resulting in increased insulin-stimulated insulin receptor tyrosine1162 phosphorylation, IRS-1/IRS-2-associated PI3-kinase activity, and Akt-serine phosphorylation. Both gAcrp30 and full-length adiponectin (Acrp30) treatment increased eNOS/AMPK activation in muscle and muscle fatty acid oxidation. gAcrp30 and Acrp30 infusions also increased TAG uptake in epididymal white adipose tissue (eWAT), which could be attributed to increased lipoprotein lipase (LPL) activity. These data suggest that adiponectin and adiponectin-related molecules reverse lipid-induced liver and muscle insulin resistance by reducing ectopic lipid storage in these organs, resulting in decreased plasma membrane sn-1,2-DAG-induced nPKC activity and increased insulin signaling. Adiponectin mediates these effects by both promoting the storage of TAG in eWAT likely through stimulation of LPL as well as by stimulation of AMPK in muscle resulting in increased muscle fat oxidation.

Incorporating Milk Protein Isolate into an Energy-Restricted Western-Style Eating Pattern Augments Improvements in Blood Pressure and Triglycerides, but Not Body Composition Changes in Adults Classified as Overweight or Obese: A Randomized Controlled Trial.

Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m2, mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.

Prolonged standing reduces fasting plasma triglyceride but does not influence postprandial metabolism compared to prolonged sitting.

Prolonged periods of sedentary behavior are linked to cardiometabolic disease independent of exercise and physical activity. This study examined the effects of posture by comparing one day of sitting (14.4 ± 0.3 h) to one day of standing (12.2 ± 0.1 h) on postprandial metabolism the following day. Eighteen subjects (9 men, 9 women; 24 ± 1 y) completed two trials (sit or stand) in a crossover design. The day after prolonged sitting or standing the subjects completed a postprandial high fat/glucose tolerance test, during which blood and expired gas was collected immediately before and hourly for 6 h after the ingestion of the test meal. Indirect calorimetry was used to measure substrate oxidation while plasma samples were analyzed for triglyceride, glucose, and insulin concentrations. Standing resulted in a lower fasting plasma triglyceride concentration (p = 0.021) which was primarily responsible for an 11.3% reduction in total area under the curve (p = 0.022) compared to sitting. However, no difference between trials in incremental area under the curve for plasma triglycerides was detected (p>0.05). There were no differences in substrate oxidation, plasma glucose concentration, or plasma insulin concentration (all p>0.05). These data demonstrate that 12 h of standing compared to 14 h of sitting has a small effect the next day by lowering fasting plasma triglyceride concentration, and this contributed to a 11.3% reduction in postprandial plasma triglyceride total area under the curve (p = 0.022) compared to sitting.

Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain.

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

Tpcn2 Knock‐Out Mice Have Improved Insulin Sensitivity and Are Protected Against High‐Fat Diet Induced Weight Gain.

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two‐pore channel 2 (Tpcn2) knock‐out mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared to wild type mice. We tested the hypothesis that improved insulin sensitivity inTpcn2 knock‐out mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knock‐out (KO), heterozygous (Het) and wild‐type (WT) mice were fed a low fat (LF) or high fat (HF) diet for 24 weeks. HF diet significantly increases body weight in WT mice relative to those on the LF diet, whereas HF diet consumption does not significantly affect body weight in Het or KO mice. We confirm that male KO mice have improved insulin sensitivity relative to WT mice. Unfortunately, because HF diet does not lead to insulin resistance in any of the mice, we are unable to claim a direct relationship between diet‐induced protection from insulin resistance and weight gain in the KO mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet‐fed mice where there is increased cholesterol and triglycerides across all genotypes. Fasting glucose, insulin and glucose tolerance levels do not differ by genotype or diet in male mice. In contrast, females consuming the HF diet exhibit glucose intolerance and hyperinsulinemia relative to females on the LF diet, but these effects are independent of genotype. These data demonstrate that male KO mice have improved insulin sensitivity and both male and female KO mice are protected against diet‐induced weight gain independent from changes in glucose tolerance or lipid levels.Support or Funding Informationby R01 DK088975, R01 DK106386, Department of Pediatrics at the Medical College of WisconsinThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intrauterine growth-restricted Yucatan miniature pigs experience early catch-up growth, leading to greater adiposity and impaired lipid metabolism as young adults.

Early nutrition has critical influences on cardiovascular disease risk in adulthood. The study objectives were to evaluate the impact of low birth weight on fasting and postprandial lipid metabolism and endothelium function in Yucatan miniature pigs. Intrauterine growth-restricted (IUGR) piglets (n = 6; 3 days old, 0.73 ± 0.04 kg) were paired with normal-weight (NW) same-sex littermates (n = 6; 1.11 ± 0.05 kg) and fed milk replacer ad libitum for 4 weeks. Thereafter, all pigs were fed a standard diet ad libitum for 5 h/day with growth, intakes, and blood samples collected for 8 months. At 9 months old, pigs were surgically fitted with venous catheters and an oral fat tolerance test was performed. At 10 months old, pigs were killed and endothelium-dependent and -independent vasodilations of isolated coronary arteries were measured using wire-myographs. IUGR pigs demonstrated catch-up growth (P < 0.05) in body weight and abdominal circumference prior to sexual maturity (<7 months old) and had more (P < 0.05) subcutaneous fat at 10 months old compared with NW pigs. IUGR pigs had consistently higher fasting plasma triglyceride concentrations from 5 to 10 months old and higher liver triglyceride and total cholesterol concentrations at 10 months old (P < 0.05). The fat tolerance test revealed delayed postprandial triglyceride clearance in IUGR pigs, but no differences in plaque formation or vascular reactivity. To conclude, IUGR and early postnatal catch-up growth are associated with increased overall body fat deposition and altered triglyceride metabolism in adult Yucatan miniature swine.

Family history of type 2 diabetes, abdominal adipocyte size and markers of the metabolic syndrome.

Background/ObjectivesA major risk factor of type 2 diabetes mellitus (T2DM) is a positive family history of diabetes. First degree relatives (FDR) of patients with T2DM are more insulin resistant and are reported to have larger abdominal subcutaneous adipocytes than adults without a family history. Our objectives were to assess whether a family history of T2DM is associated with larger abdominal adipocytes independent of age, sex, and abdominal subcutaneous fat and to assess whether FDR of T2DM is also independently related to femoral adipocyte size, as well as visceral fat and fasting plasma triglyceride (TG) concentrations.MethodsWe extracted adipocyte size, body composition, plasma TG and demographic data of non-diabetic research participants of previous studies conducted in our laboratory. We ascertained the family history of T2DM from the electronic medical records. Multivariate regression analysis was used to assess whether FDR of T2DM are more likely to have other risk factors after adjusting for known covariates.ResultsOf 604 participants, 148 were a FDR of T2DM. Although abdominal and femoral adipocyte size was greater in FDR of T2DM than those without a family history (0.74 ± 0.33 vs 0.63 ± 0.33 µg lipid/cell, P < 0.001; 0.81 ± 0.29 vs 0.72 ± 0.33 µg lipid/cell, P=0.01, respectively), this was confounded by FDR of T2DM being older, having greater BMI’s and percent body fat. A family history of T2DM was a significant predictor of abdominal adipocyte size after adjustment for age and body fat distribution parameters in females (total R2=0.5, p < 0.0001), but not in males. A family history of T2DM was not independently predictive of femoral adipocyte size, visceral fat area or TG.ConclusionsFDR of T2DM females have larger abdominal, but not femoral, adipocytes, even after accounting for age and body fat distribution.

Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study

Background/Objective:Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy).Subjects/Methods:Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15–18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or ⩾2% post intervention).Results:Nine participants were stratified to DHA⩾2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with ⩾2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of 13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05).Conclusions:The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment ⩾2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy. ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosis.

Hypertriglyceridemia: A simple approach to identify insulin resistance and enhanced cardio-metabolic risk in patients with prediabetes

AimsPrediabetes (PreDM) is a metabolically heterogeneous condition, differing in degree of insulin resistance and risk of type 2 diabetes mellitus and coronary heart disease (CHD). This study was initiated to evaluate the hypothesis that a fasting plasma triglyceride (TG) concentration ⩾1.7mmol/L can aid in identifying the subset of individuals with PreDM who are most insulin resistant and at greatest risk to develop CHD as well as type 2 diabetes mellitus. MethodsIn this cross-sectional study, measurements were made of: (1) steady-state plasma glucose (SSPG) concentration during the insulin suppression test to ascertain degree of insulin resistance and (2) conventional CHD risk factors in 587 apparently healthy individuals with normal fasting plasma glucose (NFG, n=370) or PreDM (n=217). ResultsSubjects with PreDM were significantly (P<0.001) more insulin resistant (higher SSPG concentrations) and had a more adverse CHD risk profile than those with NFG. A TG concentration ⩾1.7mmol/L identified a subset of individuals with PreDM (38%) who had a higher mean SSPG concentration (11.3±3.5mmol/L vs. 9.3±3.9mmol/L, P<0.001), were more likely to be insulin resistant (66% vs. 39%, P<0.001), and had a more adverse CHD risk factor profile. ConclusionsMeasurement of fasting TG concentration in individuals with PreDM may provide a simple clinical approach to identify those who are insulin resistant, at enhanced risk of CHD, and more likely to develop type 2 diabetes mellitus.

The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides.

IntroductionApolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.MethodsIn 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.ResultsCompared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms.ConclusionWe conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.

The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.

Polymorphisms in adiponectin receptor genes are associated with lipodystrophy-related phenotypes in HIV-infected patients receiving antiretroviral therapy.

Adiponectin is a circulating peptide secreted by mature adipocytes that may act as a regulator of glucose and lipid metabolism. This study aimed to investigate the association between genetic variability in the adiponectin receptor genes ADIPOR1 (adiponectin receptor 1) and ADIPOR2 and lipodystrophy and its related anthropometric and metabolic phenotypes in HIV-infected patients on highly active antiretroviral therapy (HAART). We studied six single nucleotide polymorphisms (SNPs) in the adiponectin receptor genes ADIPOR1 (rs1342387 and rs10920533) and ADIPOR2 (rs11061925, rs10773983, rs929434 and rs767870) and their association with adiponectin plasma levels, lipodystrophy subtypes and other parameters linked to glucose and lipid metabolism involved in the lipodystrophic syndrome. The genotypes of 407 HIV-infected patients receiving HAART were investigated using real-time polymerase chain reaction. Mean biochemical and anthropometrical parameters were compared between the different genotypes using analysis of variance. Two ADIPOR2 SNPs (rs11061925 and rs929434) were associated with fasting plasma triglyceride concentrations in the entire sample. Stronger significant associations were found between these SNPs and biochemical parameters (levels of triglycerides, total cholesterol, adiponectin and glucose) in men. We did not find any significant associations with ADIPOR1 gene variants. SNPs in the ADIPOR2 gene appear to be involved in the metabolic alterations in HIV-infected men receiving HAART.

Fasting plasma triglyceride concentration: A possible approach to identify increased risk of statin-induced type 2 diabetes.

To evaluate the hypothesis that measurement of fasting plasma triglyceride concentration identifies individuals at enhanced risk of statin-induced type 2 diabetes mellitus. A retrospective analysis of data collected from routine health examinations in non-diabetic, East Asian individuals (n = 5790) with low-density lipoprotein cholesterol concentrations of ⩾3.4 mmol/L. Subjects were stratified into those with or without a triglyceride concentration of ⩾1.7 mmol/L, and comparisons made of risk factors for type 2 diabetes mellitus. Approximately 40% of men and 20% of women with elevations of both low-density lipoprotein cholesterol and triglyceride concentrations were more insulin resistant (homeostatic model assessment of insulin resistance), associated with higher plasma concentrations of HbA1c, glucose and insulin. Apparently, healthy, non-diabetic East Asian men and women with combined elevations of low-density lipoprotein cholesterol and triglyceride concentrations are glucose intolerant and insulin resistant, and thereby at enhanced risk of type 2 diabetes mellitus. Measurement of plasma triglyceride concentration can identify within a hypercholesterolemic population a subset of individuals at enhanced risk of statin-induced type 2 diabetes mellitus.