The roles of apo E genotype, gender and adipokines in blood plasma lipids in Caucasians with well-controlled type 2 diabetes

2010 ◽  
Vol 18 (2) ◽  
pp. 49-54
Author(s):  
Douglas E. Barre D.E. ◽  
Kazimiera A. Mizier-Barre K.A. ◽  
Odette Griscti O. ◽  
Kevin Hafez K.
Keyword(s):  
Type 2 Diabetes ◽  
Blood Plasma ◽  
Plasma Lipids ◽  
Apo E ◽  
Apo E Genotype ◽  
In Blood Plasma

scholarly journals Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1260
Author(s):  
Daria Shunkina (Skuratovskaia) ◽  
Alexandra Komar ◽  
Maria Vulf ◽  
Hung Vu Quang ◽  
Egor Shunkin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Blood Plasma ◽  
Tumor Necrosis ◽  
Greater Omentum ◽  
Obese Patients ◽  
Tnf Superfamily ◽  
In Blood Plasma

Interactions between receptors and ligands of the tumor necrosis factor superfamily (TNFSF) provide costimulatory signals that control the survival, proliferation, differentiation, and effector function of immune cells. All components of the TNF superfamily are associated with NF-kB functions that are not limited to cell death and may promote survival in the face of adipose tissue inflammation in obesity. Inflammation dysfunction of mitochondria is a key factor associated with insulin resistance in obesity. The aim of the study was to analyze the relationship of soluble forms of receptors and ligands of the TNF superfamily in blood plasma with mitochondrial dynamics in adipose tissue (greater omentum (GO) and subcutaneous adipose tissue (Sat)) of obese patients with and without type 2 diabetes mellitus (T2DM). Increased plasma sTNF-R1, sTNF-R2, sTNFRSF8 receptors, and ligands TNFSF12, TNFSF13, TNFSF13B are characteristic of obese patients without T2DM. The TNF-a levels in blood plasma were associated with a decrease in MFN2 gene expression in GO and IL-10 in blood plasma. The TNFSF12 levels contributed to a decrease in glucose levels, a decrease in BMI, and an increase in IL-10 levels by influencing the MFN2 gene expression in GO, which supports mitochondrial fusion.

Plasma Lipids, Lipoprotein Metabolism and HDL Lipid Transfers are Equally Altered in Metabolic Syndrome and in Type 2 Diabetes

Lipids ◽  
2014 ◽  
Vol 49 (7) ◽  
pp. 677-684 ◽  
Author(s):  
Vanessa M. Silva ◽  
Carmen G. C. Vinagre ◽  
Luis A. O. Dallan ◽  
Ana P. M. Chacra ◽  
Raul C. Maranhão
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Plasma Lipids ◽  
Lipoprotein Metabolism

scholarly journals Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator

2019 ◽  
Vol 11 (475) ◽  
pp. eaau3441 ◽  
Author(s):  
Adrian Vella ◽  
Jennifer L. R. Freeman ◽  
Imogene Dunn ◽  
Kit Keller ◽  
John B. Buse ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Lipids ◽  
Regulatory Protein ◽  
Density Lipoprotein ◽  
Loss Of Function ◽  
Therapeutic Success ◽  
Double Blind ◽  
Glucokinase Activator ◽  
Clinically Significant

The therapeutic success of interventions targeting glucokinase (GK) activation for the treatment of type 2 diabetes has been limited by hypoglycemia, steatohepatitis, and loss of efficacy over time. The clinical characteristics of patients with GK-activating mutations or GK regulatory protein (GKRP) loss-of-function mutations suggest that a hepatoselective GK activator (GKA) that does not activate GK in β cells or affect the GK-GKRP interaction may reduce hyperglycemia in patients with type 2 diabetes while limiting hypoglycemia and liver-associated adverse effects. Here, we review the rationale for TTP399, an oral hepatoselective GKA, and its progression from preclinical to clinical development, with an emphasis on the results of a randomized, double-blind, placebo- and active-controlled phase 2 study of TTP399 in patients with type 2 diabetes. In this 6-month study, TTP399 (800 mg/day) was associated with a clinically significant and sustained reduction in glycated hemoglobin, with a placebo-subtracted least squares mean HbA1c change from baseline of −0.9% (P < 0.01). Compared to placebo, TTP399 (800 mg/day) also increased high-density lipoprotein cholesterol (3.2 mg/dl; P < 0.05), decreased fasting plasma glucagon (−20 pg/ml; P < 0.05), and decreased weight in patients weighing ≥100 kg (−3.4 kg; P < 0.05). TTP399 did not cause hypoglycemia, had no detrimental effect on plasma lipids or liver enzymes, and did not increase blood pressure, highlighting the importance of tissue selectivity and preservation of physiological regulation when targeting key metabolic regulators such as GK.

scholarly journals Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (9) ◽  
pp. 2329 ◽  
Author(s):  
Alena Soboleva ◽  
Gregory Mavropulo-Stolyarenko ◽  
Tatiana Karonova ◽  
Domenika Thieme ◽  
Wolfgang Hoehenwarter ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Plasma ◽  
Plasma Proteins ◽  
Linear Discriminant ◽  
Slow Development ◽  
Specificity And Sensitivity ◽  
Blood Plasma Proteins

Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels. Moreover, due to a large variation in the half-life times of plasma proteins, a generalized biomarker, based on multiple glycation sites, might provide comprehensive control of the glycemic status across any desired time span. Therefore, here, we address the patterns of glycation sites in highly-abundant blood plasma proteins of T2DM patients and corresponding age- and gender-matched controls by comprehensive liquid chromatography-mass spectrometry (LC-MS). The analysis revealed 42 lysyl residues, significantly upregulated under hyperglycemic conditions. Thereby, for 32 glycation sites, biomarker behavior was demonstrated here for the first time. The differentially glycated lysines represented nine plasma proteins with half-lives from 2 to 21 days, giving access to an integrated biomarker based on multiple protein-specific Amadori peptides. The validation of this biomarker relied on linear discriminant analysis (LDA) with random sub-sampling of the training set and leave-one-out cross-validation (LOOCV), which resulted in an accuracy, specificity, and sensitivity of 92%, 100%, and 85%, respectively.

scholarly journals Novel lipid species for detecting and predicting atrial fibrillation in patients with type 2 diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Yow Keat Tham ◽  
Kaushala S. Jayawardana ◽  
Zahir H. Alshehry ◽  
Corey Giles ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Plasma Lipids ◽  
Lipid Analysis ◽  
Logistic Regression Models ◽  
Lipid Species ◽  
Patients With Diabetes

The incidence of atrial fibrillation (AF) is higher in patients with diabetes. The goal of this study was to assess if the addition of plasma lipids to traditional risk factors could improve the ability to detect and predict future AF in patients with type 2 diabetes. Logistic regression models were used to identify lipids associated with AF/future AF from plasma lipids (n=316) measured from participants from the ADVANCE trial (n=3,772). To gain mechanistic insight, follow-up lipid analysis was undertaken in a mouse model which has an insulin-resistant heart and is susceptible to AF. Sphingolipids, cholesteryl esters and phospholipids were associated with AF prevalence, whereas two G<sub>M3</sub> ganglioside species were associated with future AF. For AF detection and prediction, addition of 6 and 3 lipids, respectively, to a base model (12 conventional risk factors) increased the C-statistics (detection:0.661 to 0.725; prediction:0.674 to 0.715), and categorical net reclassification indices. GM3(d18:1/24:1) was lower in patients who developed AF, improved the C-statistic for the prediction of future AF, and was lower in the plasma of the mouse model susceptible to AF. This study demonstrates that plasma lipids have the potential to improve both the detection and prediction of AF in patients with diabetes.

Effects of three months' diet after diagnosis of Type 2 diabetes on plasma lipids and lipoproteins (UKPDS 45)

2000 ◽  
Vol 17 (7) ◽  
pp. 518-523 ◽  
Author(s):  
◽  
S. E. Manley ◽  
I. M. Stratton ◽  
C. A. Cull ◽  
V. Frighi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Lipids ◽  
Lipids And Lipoproteins

Abstract P233: Plasma essential fatty acids and type 2 diabetes risk: the Hoorn Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Marjan Alssema ◽  
Mieke Cabout ◽  
Giel Nijpels ◽  
Coen D Stehouwer ◽  
Peter L Zock ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Plasma Lipids ◽  
Essential Fatty Acids ◽  
Saturated Fatty Acids ◽  
Alpha Linolenic Acid ◽  
Cross Sectional ◽  
Prospective Analyses

Background: A high consumption of the polyunsaturated fatty acids linoleic acid (LA) and alpha-linolenic acid (ALA) instead of saturated fatty acids is known to reduce CHD risk, but data on the relation between LA and ALA intake and Type 2 Diabetes Mellitus (T2DM) risk are limited and inconsistent. Plasma levels of LA and ALA provide a relatively accurate reflection of the intake over several weeks or months, because of the essential nature of these fatty acids. Objective: To investigate the association of the percentage of LA and ALA in plasma lipids with fasting plasma glucose (FPG), post-load glucose (PLG) and glycated hemoglobin (HbA1c) as markers of T2DM risk. Methods: The study population included 667 Dutch men and women, aged 50-75 years from the population-based Hoorn Study. Baseline data for the current study were collected between 2000 and 2001, with follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses. Results: In cross-sectional analyses, plasma LA (per %) was significantly and inversely associated with FPG ( B = -0.022 [-0.044, 0.000]) and PLG ( B = -0.096 [-0.155, -0.036]), but not with HbA1c ( B = 0.000 [-0.014, 0.014]), after adjustment for age, gender, total energy intake, BMI, waist-to-hip ratio, physical activity, fiber, dietary saturated fat intake, alcohol intake and education level. In prospective analyses, plasma LA was not significantly associated with FPG, PLG or HbA1c after adjustments for baseline glucose. In addition, no significant associations were found between plasma ALA and markers of T2DM risk in cross-sectional or prospective analyses. Conclusion: Plasma LA, but not ALA, was inversely associated with fasting and post-load glucose levels in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of plasma LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.

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