Lipid Metabolism In Type Research Articles

Aerobic Exercise and Vitamin D Supplementation are Associated with Lipid Metabolism in Type 2 Diabetes

Aerobic Exercise and Vitamin D Supplementation are Associated with Lipid Metabolism in Type 2 Diabetes

The Thioesterase ACOT1 as a Regulator of Lipid Metabolism in Type 2 Diabetes Detected in a Multi-Omics Study of Human Liver.

Type 2 diabetes (T2D) is characterized by pathophysiological alterations in lipid metabolism. One strategy to understand the molecular mechanisms behind these abnormalities is to identify cis-regulatory elements (CREs) located in chromatin-accessible regions of the genome that regulate key genes. In this study we integrated assay for transposase-accessible chromatin followed by sequencing (ATAC-seq) data, widely used to decode chromatin accessibility, with multi-omics data and publicly available CRE databases to identify candidate CREs associated with T2D for further experimental validations. We performed high-sensitive ATAC-seq in nine human liver samples from normal and T2D donors, and identified a set of differentially accessible regions (DARs). We identified seven DARs including a candidate enhancer for the ACOT1 gene that regulates the balance of acyl-CoA and free fatty acids (FFAs) in the cytoplasm. The relevance of ACOT1 regulation in T2D was supported by the analysis of transcriptomics and proteomics data in liver tissue. Long-chain acyl-CoA thioesterases (ACOTs) are a group of enzymes that hydrolyze acyl-CoA esters to FFAs and coenzyme A. ACOTs have been associated with regulation of triglyceride levels, fatty acid oxidation, mitochondrial function, and insulin signaling, linking their regulation to the pathogenesis of T2D. Our strategy integrating chromatin accessibility with DNA binding and other types of omics provides novel insights on the role of genetic regulation in T2D and is extendable to other complex multifactorial diseases.

Effects of acupoint thread-embedding therapy on serum apelin and GLP-1 in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen

To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method, with 33 cases in each group. Patients in the control group were treated with exenatide and metformin, while patients in the observation group were treated with additional acupoint thread-embedding. After 12-week treatment, the obesity-related indicators, including body mass index (BMI), waist circumference and body fat rate, the glycometabolism indicators, including fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin, and the lipid metabolism indicators, including total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), as well as serum apelin and GLP-1 levels were observed in patients of the two groups. After treatment, the BMI, waist circumference and body fat rate of patients in the two groups were all reduced (all P 0.05); the TC, TG and LDL-C levels were all significantly reduced in the observation group (all P<0.05), lower than those in the control group (all P<0.05); the serum apelin level was decreased (P<0.05) and the serum GLP-1 level was increased (P<0.05) in the observation group, statistically different from those in the control group (both P<0.05). Combined with the conventional medication, acupoint thread-embedding therapy can significantly improve the obesity-related indicators, glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. This may be achieved by regulating the serum apelin and GLP-1 levels.

Effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in type 2 diabetic mice

ObjectiveWith the prevalence of diabetes worldwide, it is urgent to find a suitable treatment. Recently, the ketogenic diet has shown beneficial effects in reducing blood glucose, but some concerns have been raised about its probable side effects, such as hyperlipidemia and hepatic steatosis. Because a low-carbohydrate diet replaces part of the fat with carbohydrates on the basis of the ketogenic diet, we would like to know whether it does better in treating type 2 diabetes. The aim of this study was to explore the possibility of a low-carbohydrate diet as a substitute for a ketogenic diet intervention in mice with type 2 diabetes. MethodsC57 BL/6 J mice with type 2 diabetes, constructed by a high-fat diet combined with streptozotocin, were fed a standard diet, a high-fat diet, a low-carbohydrate diet, or a ketogenic diet for 14 wk, respectively. Then glucose and insulin tolerance tests were conducted. At the end of the study, blood and liver samples were collected and analyzed for serum biochemical indicators, histopathologic evaluation, hepatic lipid and glycogen content, and expression levels of mRNA and protein. ResultsReduced blood glucose could be observed in both low-carbohydrate and ketogenic diets, as well as improvement in glucose tolerance and insulin sensitivity. However, the ketogenic diet decreased liver glycogen content and promoted gluconeogenesis. Mechanistically, this effect was due to inhibition of phosphorylated AMP-activated protein kinase, which could be improved by a low-carbohydrate diet. Regarding lipid metabolism, the ketogenic diet increased lipid oxidation and reduced de novo lipogenesis, but the hepatic lipid content still inevitably increased. On the contrary, the low-carbohydrate diet reduced triacylglycerols and markers of liver damage. ConclusionsCollectively, these findings suggest that both diets are effective in lowering blood glucose, improving glucose tolerance, and raising insulin sensitivity. Moreover, the low-carbohydrate diet plays a role in inhibiting hepatic gluconeogenesis and improving lipid metabolism. The results suggest that the two diets have different effects on glucose and lipid metabolism, and that the low-carbohydrate diet might have more benefits in the treatment of type 2 diabetes mellitus.

AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients

SummaryExperimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to demonstrating pharmacodynamic effects but with dose-limiting adverse events. Here we report results from a phase 1 multiple ascending dose study of AKR-001, an Fc-FGF21 fusion protein engineered for sustained systemic pharmacologic exposure, in individuals with type 2 diabetes. With a half-life of 3–3.5 days, the peak-to-trough ratio under steady-state conditions is approximately 2 following QW dosing. AKR-001 appears to demonstrate pharmacodynamic effects on serum markers of insulin sensitivity and acceptable tolerability up to and including 70 mg QW. Positive trends in lipoprotein profile, including triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, HDL-C, and apolipoproteins B and C3 are consistent with other FGF21 analogs. AKR-001’s clinical profile supports further evaluation as a treatment for metabolic diseases.

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

BackgroundMesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM).MethodsHucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting.ResultsHucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism.ConclusionsThese findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients.

Arctium lappa L. polysaccharide can regulate lipid metabolism in type 2 diabetic rats through the SREBP-1/SCD-1 axis

In the analysis of risk factors of diabetes mellitus with coronary heart disease, dyslipidemia is the most important. Previous studies have found that Arctium lappa L. polysaccharide (ALP) can regulate lipid metabolism in type 1 diabetic rats, but it has not been studied in type 2 diabetes. In this study, the regulatory effect of ALP on lipid metabolism in type 2 diabetic rats was investigated by constructing a model of type 2 diabetes. The results of blood biochemical analysis showed that ALP effectively reduced the synthesis of triglycerides and cholesterol, and reduced the risk of atherosclerosis in diabetic rats. Histopathological observation (hematoxylin and eosin, Masson, Periodic Acid-Schiff and oil red O staining) showed that it also effectively regulated lipid metabolism in the liver of diabetic rats and inhibited the process of liver fibrosis. Immunohistochemistry and Western blot analysis showed that ALP regulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of diabetic rats. In conclusion, the results of this study demonstrate that ALP can effectively regulate lipid metabolism and reduce the risk of atherosclerosis in type 2 diabetic rats through the SREBP-1/SCD-1 axis.

579-P: Dyslipidemia in Type 2 Diabetic Mice Is Improved by Targeting Smad3 with a Smad3 Inhibitor SIS3

Purpose of the Study: Dyslipidemia is one of the diabetic complications which is relevant to the disorder of interaction between glucose and lipid metabolism. In our preliminary studies, we found that Smad3 is the key pathogenic mediator in db/db mice. Metabolic symptoms in diabetes are improved in Smad3KO-db/db mice. Thus, we hypothesized that Smad3 is a therapeutic target for treatment of dyslipidemia in type 2 diabetes. Methods: db/db mice were treated with Smad3 inhibitor SIS3 at the age of 4 weeks at the dose of 2.5mg/kg bw/day by intra peritoneal injection for 8 weeks. Control group db/db mice were treated with SIS3 solvent only. Molecules and cytokines involved in lipid metabolism were examined by Realtime-PCR, Western blotting, immunohistochemistry, ELISA for in vivo and in vitro experiments. The mechanism of Smad3 signaling interfering lipid metabolism was studied by Chip-sequencing and RNA sequencing. Summary of the results: Blood high density lipoprotein (HDL) level was up regulated while low density lipoprotein (LDL) level and triglycerides were down regulated in Smad3 KO mice, which showed Smad3 is one of the main regulators in lipid metabolism. SIS3 treated mice showed significantly improved glycemia, lipidemia. Insulin sensitivity was ameliorated in SIS3 treatment group compared with control group. SIS3 treated Hepg2 cells and AML12 cells showed lower lipid absorbance than control group. RNA sequencing revealed that differentially expressed genes (DEGs) in concentrations of apolipoproteins A1 (ApoA1) was notable enriched in liver of Smad3KO mice, which also showed APOA1 has direct binding site with Smad3. We subsequently found that APOA1 was negatively regulated by Smad3 signaling therefore influence the lipid metabolism in type 2 diabetes. Conclusion: Smad3 is a pathogenic mediator of diabetic metabolism. Treatment of type 2 diabetic mice with Smad3 inhibitor SIS3 improves lipidemia by enhancing the activity of DEGs in APOA1. Disclosure H. He: None. X. Huang: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. H. Lan: None.

Central nesfatin-1 activates lipid mobilization in adipose tissue and fatty acid oxidation in muscle via the sympathetic nervous system.

Little is known about the influence of central nesfatin-1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin-1 regulates lipid metabolism in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high-fat diets (HFDs) and were treated twice with low-dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin-1 required the hypothalamic-sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP-activated protein kinase (AMPK) levels in skeletal muscle and hormone-sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin-1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin-1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty-acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin-1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin-1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.

Effect of gastric bypass on BMI and lipid metabolism in type 2 diabetes mellitus

To compare the clinical efficacy of gastric bypass in obese patients with T2DM with different BMI. Serum leptin, adiponectin, triglyceride (TG), cholesterol (CHOL) were measured as the indicators to show clinical efficacy after laparoscopic gastric bypass surgery (LRYGB). For patients with high BMI and patients with low BMI, the therapeutic effect of LRYGB surgical diabetes is more significant. The postoperative remission rate of diabetes in the high BMI group was not correlated with the preoperative lipid metabolism index but was positively correlated with the postoperative lipid metabolism index CHOL, TG, leptin, adiponectin. The postoperative remission rate of diabetes in the low BMI group was positively correlated with the preoperative abnormal lipid metabolism of the patients, and positively correlated with the postoperative remission of leptin and adiponectin, but was not correlated with the postoperative remission of total CHOL and TG. The increase of serum adiponectin level and the decrease of leptin resistance after LRYGB surgery restored the metabolic balance of leptin and adiponectin, improved insulin resistance (IR), and thus improved blood glucose level. Therefore, LRYGB has a definite therapeutic effect on obese patients with T2DM, and elevated adiponectin and improved leptin resistance are some of the mechanisms of surgical treatment of diabetes.

Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

Effects of Lespedeza Bicolor Extract on Regulation of AMPK Associated Hepatic Lipid Metabolism in Type 2 Diabetic Mice.

Lespedeza bicolor (LB) is one of the ornamental plants used for the treatment of inflammation caused by oxidative damage. However, its beneficial effects on hyperglycemia-induced hepatic damage and the related molecular mechanisms remain unclear. We hypothesized that Lespedeza bicolor extract (LBE) would attenuate hyperglycemia-induced liver injury in type 2 diabetes mellitus (T2DM). Diabetes was induced by a low dosage of streptozotocin (STZ) injection (30 mg/kg) with a high fat diet in male C57BL/6J mice. LBE was administered orally at 100 mg/kg or 250 mg/kg for 12 weeks. LBE supplementation regardless of dosage ameliorated plasma levels of hemoglobin A1c (HbA1c) in diabetic mice. Moreover, both LBE supplementations upregulated AMP-activation kinase (AMPK), which may activate sirtuin1 (SIRT) associated pathway accompanied by decreased lipid synthesis at low dose of LBE supplementation. These changes were in part explained by reduced protein levels of oxidative stress (nuclear factor erythroid 2-related factor 2 (Nrf2) and catalase), inflammation (nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide synthases (iNOS)), and fibrosis (α-smooth muscle actin (α-SMA) and protein kinase C (PKC)) in diabetic liver. Taken together, LBE might be a potential nutraceutical to ameliorate hepatic damage by regulation of AMPK associated pathway via oxidative stress, inflammation, and fibrosis in T2DM.

Antidiabetic Effect of Fenugreek Seed Powder Solution (Trigonella foenum-graecum L.) on Hyperlipidemia in Diabetic Patients.

Background Many drugs are commercially available for use in the management of diabetes. However, their side effects and high costs underscore the need for herbal alternative drugs. Trigonella foenum-graecum is one of the medicinal plants which are important in the management of diabetes mellitus. This study investigated the effect of Trigonella foenum-graecum seed powder solution on the lipid profile of newly diagnosed type II diabetic patients. Methods A total of N = 114 newly diagnosed type II diabetic patients without any significant diabetes complication were selected. They were grouped into two groups: the treatment group (n = 57) consumed 25 g Trigonella foenum-graecum seed powder solution orally twice a day for one month and the second group is the control (n = 57) which receives metformin. Blood sample was collected from each participant by a medical technologist/technician before and after the study. Lipid profile was analyzed by using Mindray BS 200E fully automated clinical chemistry analyzer. Result By the end of the intervention period, the treatment group showed significantly lower total cholesterol level by 13.6% as compared with the baseline level (219.1 ± 35.51 vs. 189.29 ± 29.06, P < 0.001) and the control group (189.29 ± 29.06 vs. 208.2 ± 40.2, P < 0.001); triglyceride level also reduced by 23.53% compared with the baseline level (256.1 ± 15.4 vs. 195.8 ± 82.95, P < 0.001) and compared with the control group (195.8 ± 82.95 vs. 244.1 ± 96.9, P < 0.05); and low-density lipoprotein cholesterol level also reduced by 23.4% as compared to the baseline level (137.9 ± 26.9 vs. 105.6 ± 24.2, P < 0.001) and the control group (between groups) (105.6 ± 24.2 vs. 144.1 ± 23.3, P < 0.001), but the treatment group showed significantly increased high-density lipoprotein cholesterol level by 21.7% as compared to the baseline level, within group (37.8 ± 1.51 vs. 48.3 ± 11.9, P < 0.001), and the control group, between groups (48.3 ± 11.9 vs. 36.01 ± 9.5, P < 0.001). However, lipid profile levels in the control group were not significantly changed. Conclusion The present study showed that the administration of Trigonella foenum-graecum seed powder solution had pronounced effects in improving lipid metabolism in type II diabetic patients with no adverse effects. Therefore, Trigonella foenum-graecum seed may provide new alternatives for the clinical management of type II diabetes.

Adenovirus-mediated expression of SIK1 improves hepatic glucose and lipid metabolism in type 2 diabetes mellitus rats.

AimIn this study, we investigated the role and mechanism of Salt-induced kinase 1 (SIK1) in regulation of hepatic glucose and lipid metabolism in a high-fat food (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) rat model.MethodsA diabetic rat model treated with HFD plus low-dose STZ was developed and was transduced to induce a high expression of SIK1 in vivo via a tail-vein injection of a recombinant adenoviral vector. The effects on hepatic glucogenetic and lipogenic gene expression, systemic metabolism and pathological changes were then determined.ResultsIn T2DM rats, SIK1 expression was reduced in the liver. Overexpression of SIK1 improved hyperglycaemia, hyperlipidaemia and fatty liver, reduced the expression of cAMP-response element binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), pS577 SIK1, sterol regulatory element binding-protein-1c (SREBP-1c) and its target genes, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and increased the expression of SIK1, pT182 SIK1 and pS171 CRTC2 in diabetic rat livers with the suppression of gluconeogenesis and lipid deposition.ConclusionSIK1 plays a crucial role in the regulation of glucose and lipid metabolism in the livers of HFD/STZ-induced T2DM rats, where it suppresses hepatic gluconeogenesis and lipogenesis by regulating the SIK1/CRTC2 and SIK1/SREBP-1c signalling pathways. Strategies to activate SIK1 kinase in liver would likely have beneficial effects in patients with T2DM and nonalcoholic fatty liver disease (NAFLD).

PO-062 Acute exercise intervention combined with metformin’s influences on glucose homeostasis in T2D mice

PO-062 Acute exercise intervention combined with metformin’s influences on glucose homeostasis in T2D mice

Association of APOB and LIPC polymorphisms with type 2 diabetes in Chinese Han population

BackgroundApolipoprotein B (APOB), and hepatic lipase (LIPC) genes have been shown to play a key role in lipid metabolism in type 2 diabetes (T2D). This study aimed to investigate the association of the three polymorphisms (rs679899 in APOB and rs6078 and rs6083 in LIPC) with T2D and related clinical quantitative traits. MethodsWe conducted a case-control study in Chinese Han population, with a total of 929 T2D patients and 1044 healthy subjects in Chinese Han population. Polymorphisms were genotyped by MassARRAY Genotyping System. ResultsThe risk allele G of the polymorphism rs679899 was related to T2D (odds ratio (OR): 1.207, 95% confidence interval (CL): 1.006–1.448, P = 0.043) and the polymorphism rs679899 was associated with glutamyl transpeptidase (GGT) levels (P = 0.001). We also showed that the polymorphism rs6083 was associated with cholesterol (CHOL) levels (P = 0.012), triglyceride (TG) levels (P = 0.040), and low-density lipoprotein cholesterol (LDL) levels (P = 0.033). No significant difference in genotypic frequencies of rs6078 and rs6083 was observed between T2D patients and controls. ConclusionThis study suggests that the APOB polymorphism rs679899 is associated with type 2 diabetes and GGT levels, while the LIPC polymorphism rs6083 may influence CHOL, TG, and LDL levels in Chinese Han population.

Abnormalities in the relationship of paraoxonase 1 with HDL and apolipoprotein A1 and their possible connection to HDL dysfunctionality in type 2 diabetes

AimsLipid parameters, lipid risk indexes and lipid-related oxidative stress markers (paraoxonase 1 [PON1] and lipid peroxides [LPO]) reflect the actual status of lipid metabolism in type 2 diabetes (T2DM). We hypothesized that relationships of high-density lipoprotein cholesterol (HDL-c) with PON1 and apolipoprotein A1 (ApoA1) and/or PON1 with ApoA1 under conditions of hyperglycaemia and oxidative stress might reveal HDL functionality. We investigated relationships between PON1, LPO, and lipid risk markers in T2DM subjects and compared them with those in healthy subjects. MethodsA total of 107 Caucasian subjects, 67 T2DM outpatients (mean age 52.2 ± 6.9 years) and 40 healthy subjects (mean age 48.1 ± 7.5 years) were included in the study.Serum levels of total cholesterol (CHOL-T), HDL-c, low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apolipoprotein B (ApoB), ApoA1, LPO, and PON1 activity were measured. Non-HDL-c, ApoB/ApoA1 and non-HDL/HDL (lipid risk indexes) were calculated. ResultsHigher levels of TG, LPO (P < 0.0001), nonHDL/HDL and ApoB/ApoA1 (P < 0.001, 0.05, respectively), and lower levels of HDL-c, ApoA1, and PON1 (P < 0.0001) were observed in T2DM subjects than in controls. There is a lack of relationship among PON1, HDL-c, and ApoA1 in T2DM patients. PON1 activity positively correlated with these parameters (P < 0.0001) in controls. Strong correlations between non-HDL-c and ApoB (r = 0.956 vs. 0.756; P < 0.0001), LPO and TG (r = 0.831 vs. 0.739; P < 0.0001) were recorded in both study groups (P < 0.0001). ConclusionsImpaired anti-oxidant and anti-atherogenic HDL properties associated with weakened PON1 function and lipid peroxidation may contribute to the development of atherosclerosis-related diseases in T2DM.

Effect of curcumin on glucose and lipid metabolism, FFAs and TNF-α in serum of type 2 diabetes mellitus rat models

ObjectiveTo investigate how curcumin affects the glucose and lipid metabolism in type 2 diabetes mellitus (DM) rat models, and to explore its effect on the free fatty acid (FFA) and tumor necrosis factor α (TNF-α) in serum.MethodsSuccessfully established type 2 DM rats were divided into three groups, i.e. the normal control group, model group and curcumin group, and received the medication for consecutive 8 weeks. Thereafter, we detected the level of fasting blood glucose (FBG), and the blood glucose at 30 min, 60 min and 120 min; besides, we also carried out the insulin tolerance tests to measure the levels of fasting serum insulin (FINS) and blood glucose at 40 min and 90 min; additionally, we also detected the levels of TC, TG, HDL-C, LDL-C, FFA and TNF-α in serum. The results were expected to discover the mechanism of curcumin in decreasing the blood glucose level in DM rats.ResultsCompared with the model group, AUCs of FBG, blood glucose at 30 min, 60 min and 120 min, and glucose were decreased in varying degrees in the curcumin group, and the differences had statistical significance (p < .05). After subcutaneous injection of insulin, we found that the blood glucose at 40 min and 90 min in the curcumin group was decreased, while AUC of glucose level was also decreased (p < .05 or .01). Eight weeks after medication, compared with the rats in the normal group, the levels of HDL-C, LDL-C, TC and TG in rats of the model group and the curcumin group were obviously increased (p < .05). In comparison with the model group, the level of LDL-C in rats of the curcumin group was also decreased significantly (p < .05). In comparison with the normal control group in the same period, we found that the content of FFAs and TNF-α in serum of rats of the model group were elevated significantly, and the differences had statistical significance (p < .05 or .01); the levels in the curcumin group were significantly decreased in comparison with the model group in the same period, and the difference had statistical significance (p < .05 or .01).ConclusionTreatment with curcumin can significantly improve the metabolic disorder of glucose and lipid, enhance the sensitivity to the insulin, and ameliorate the resistance to insulin of the type II DM rats. Meanwhile, this treatment method can also significantly decrease the level of FFA and TNF-α in serum of type II DM rats. Thus, we inferred that the mechanism of curcumin to improve the insulin resistance might be correlated with the decreases of FFA and TNF-α in serum.

Effects of a liquid high-fat meal on postprandial lipid metabolism in type 2 diabetic patients with abdominal obesity

BackgroundPostprandial lipemia and lipoprotein lipase (LPL) activity play crucial roles in the pathogenesis of accelerated atherosclerosis. This study aimed to evaluate the postprandial lipid metabolism after the ingestion of a liquid high-fat meal in type 2 diabetic patients with abdominal obesity, and determine if the PvuII polymorphisms of LPL influence their postprandial lipid responses.MethodsSerum glucose, insulin, triglycerides (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured in fasting and postprandial state at 0.5, 1, 2, 4, 6 and 8 h after a liquid high-fat meal in 51 type 2 diabetic patients with abdominal obesity, 31 type 2 diabetic patients without abdominal obesity and 39 controls. Their PvuII polymorphisms of LPL were tested in fasting.ResultsType 2 diabetic patients with abdominal obesity had significantly higher postprandial areas under the curve (AUC) of glucose [least square mean difference (LSMD) = 30.763, 95% confidence interval (CI) = 23.071–38.455, F = 37.346, P < 0.05] and TC (LSMD = 3.995, 95% CI = 1.043–6.947, F = 3.681, P < 0.05) than controls. Postprandial AUCs for insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and TG were higher (LSMD = 86.987, 95% CI = 37.421–136.553, F = 16.739, P < 0.05; LSMD = 37.456, 95% CI = 16.312–58.600, F = 27.012, P < 0.05; LSMD = 4.684, 95% CI = 2.662–6.705, F = 26.158, P < 0.05), whereas HDL-C AUC was lower (LSMD = −1.652, 95% CI = −2.685 – -0.620, F = 8.190, P < 0.05) in type 2 diabetic subjects with abdominal obesity than those without abdominal obesity. In type 2 diabetic patients with abdominal obesity, postprandial TG AUC was lower in P−/− than in P+/− (LSMD = −4.393, 95% CI = −9.278 – -0.491, F = 4.476, P < 0.05) and P+/+ (LSMD = −7.180, 95% CI = −12.319 – -2.014, F = 4.476, P < 0.05) phenotypes. Postprandial AUCs for glucose, insulin, HOMA-IR, TC and HDL-C were not different according to PvuII phenotypes.ConclusionsAbdominal obesity exacerbates the postprandial lipid responses in type 2 diabetic patients, which partly explains the excess atherogenic risk in these patients. In addition, the presence of P+ allele could contribute to a greater postprandial TG increase in type 2 diabetic patients with abdominal obesity.Trial registrationChiCTR-IOR-16008435. Registered 8 May 2016.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

BackgroundIt has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs).Material/MethodsAn up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level.ResultsA total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], −0.38; confidence interval [CI], −0.62 to −0.14, P=0.002; I2=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, −0.38; CI −0.59 to −0.18, P=0.0003; I2=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, −0.99; CI −1.52 to −0.47, P=0.0002; I2=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous.ConclusionsThis meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.