GlycA - a new biomarker of inflammation, cancer, cardiovascular disease and a predictor of death, regardless of its causes

2017 ◽  
pp. 136-141
Author(s):  
Б.И. Кузник
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Information Processing ◽  
Cardiovascular Diseases ◽  
Speed Of Information Processing ◽  
Global Cognition ◽  
High Concentrations

В обзоре представлены данные о недавно (2015 г.) выявленном предикторе смерти, независимо от причин её вызывающих. На роль предиктора смерти претендует продукт ацетилирования гликопротеинов - GlycA (N-acetylglucosamine/galactosamine). Обсуждаются тонкие механизмы действия GlycA при воспалении, сердечно-сосудистой патологии, онкологических заболеваниях и диабете 2-го типа. Выявлены тесные корреляционные связи между содержанием GlycA и резистентностью к инсулину. С возрастом и увеличением массы тела (ИМТ) содержание GlycA повышается. Высокие концентрации GlycA обратно пропорциональны объему памяти и скорости обработки информации. This review presents data on a recently discovered (2015) predictor for death regardless of its cause, a glycoprotein acetylation product, GlycA (biomarker of protein glycan N-acetyl groups). Subtle mechanisms of GlycA action in inflammation, cardiovascular diseases, cancer, and type 2 diabetes are discussed. A strong correlation of GlycA content with insulin resistance was found. The GlycA content increases with increasing age and body weight (BWI). High concentrations of GlycA are inversely proportional to global cognition, memory, and speed of information processing.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals Effect of Arterial Hypertension on the ICAM-1, VCAM-1 and Е-selectin Level in Type 2 Diabetes Patients

2021 ◽  
pp. 43-47
Author(s):  
Liliia Mogylnytska
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Serum Level ◽  
Control Group ◽  
Regression Equations ◽  
Multifactor Regression ◽  
Diabetes Patients

Cardiovascular disease is the leading cause of death in diabetes mellitus. Endothelial dysfunction is the first step in the development of atherosclerotic vascular lesions, which underlies cardiovascular pathology, and adhesion molecules secreted by the endothelium during inflammatory changes are involved in the progression of this lesion. The objective: the serum level of adhesive molecules (ІCAM-1, VCAM-1, Е-selectin) in hypertensive and non-hypertensive type 2 diabetes patients as a marker of endothelial dysfunction and its relationship with other risk factors for cardiovascular disease was studied. Materials and methods. We examined 64 patients with type 2 diabetes, which were divided into two subgroups: the first subgroup – 41 hypertensive type 2 diabetes patients (age – 53,56±7,14 years, BMI – 32,2±87,4; HbA1c – 9,97±2,02%), the second subgroup – 23 nonhypertensive type 2 diabetes patients (age – 50,5±4,92 years, BMI – 25,4±5,22; HbA1c – 9,09±1,95%). The control group included 18 people without diabetes with normal blood pressure (age – 50,72±6,98 years, BMI – 24,71±4,88; HbA1c – 5,26±0,42%). The serum level was determined by immunoenzyme assay. The significance of the difference between the mean values was determined by the t-Student test. Multifactor regression analysis was used to assess the relationships between the studied factors. Results. We revealed an increase of serum levels of ІCAM-1, VCAM-1, Е-selectin in hypertensive (+71,62%, +68,42%, +66,95%, respectively) and non-hypertensive type 2 diabetes patients (+46,17%, +62,79%, +42,85%, respectively) compared with the control group (p<0,01). The serum concentration of ІCAM-1, Е-selectin was higher in hypertensive type 2 diabetes patients compared to non-hypertensive type 2 diabetes patients (+17,27%, +16,86%, respectively, p<0,01). There was a significant effect of Hb1Ac, lipids, insulin resistance on the serum level of ІCAM-1, VCAM-1, Е-selectin (p<0,01). The corresponding regression equations are derived. Conclusion. There is an increase of serum level of ІCAM-1, VCAM-1, Е-selectin in hypertensive and non-hypertensive type 2 diabetes patients, which indicates the development of endothelial dysfunction. Hypertension, hyperglycemia, dyslipidemia and insulin resistance contribute to the development of these changes.

scholarly journals Efficacy and Safety of Ertugliflozin in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease Treated With Metformin and Sulfonylurea

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A331-A331
Author(s):  
Matthew J Budoff ◽  
Timothy M E Davis ◽  
Alexandra G Palmer ◽  
Robert Frederich ◽  
David E Lawrence ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Glycemic Control ◽  
Sglt2 Inhibitor ◽  
Efficacy And Safety

Abstract Introduction: Ertugliflozin (ERTU), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus (T2DM). Aim: As a pre-specified sub-study of the Phase 3 VERTIS CV trial (NCT01986881), the efficacy and safety of ERTU were assessed in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled with metformin and sulfonylurea (SU). Methods: Patients with T2DM, established ASCVD, and HbA1c 7.0–10.5% on stable metformin (≥1500 mg/day) and SU doses as defined per protocol were randomized to once-daily ERTU (5 mg or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ERTU on HbA1c compared with placebo and to evaluate safety and tolerability during 18-week follow-up. Key secondary endpoints included proportion of patients achieving HbA1c &lt;7%, fasting plasma glucose (FPG), body weight, and systolic blood pressure. Changes from baseline at Week 18 for continuous efficacy endpoints were assessed using a constrained longitudinal data analysis model. Results: Of the 8246 patients enrolled in the VERTIS CV trial, 330 patients were eligible for this sub-study (ERTU 5 mg, n=100; ERTU 15 mg, n=113; placebo, n=117). Patients had a mean (SD) age of 63.2 (8.4) years, T2DM duration 11.4 (7.4) years, estimated glomerular filtration rate 83.5 (17.8) mL/min/1.73 m2, and HbA1c 8.3% (1.0) (67.4 [10.6] mmol/mol). At Week 18, ERTU 5 mg and 15 mg were each associated with a significantly greater least squares mean (95% CI) HbA1c reduction from baseline versus placebo; the placebo-adjusted differences for ERTU 5 mg and 15 mg were –0.7% (–0.9, –0.4) and –0.8% (–1.0, –0.5), respectively (P&lt;0.001). A higher proportion of patients in each ERTU group achieved HbA1c &lt;7% relative to placebo (P&lt;0.001). ERTU significantly reduced FPG and body weight (P&lt;0.001, for each dose versus placebo), but not systolic blood pressure. Adverse events were reported in 48.0%, 54.9%, and 47.0% of patients in the ERTU 5 mg, 15 mg, and placebo groups, respectively. Genital mycotic infections were experienced by significantly higher proportions of male patients who received ERTU 5 mg and 15 mg (4.2% and 4.8%, respectively) versus placebo (0.0%; P≤0.05) and by a numerically, but not significantly, higher proportion of female patients who received ERTU 15 mg (10.3%) compared with placebo (3.8%) (P=0.36). The incidences of symptomatic hypoglycemia were 11.0% (5 mg), 12.4% (15 mg), and 7.7% (placebo), and of severe hypoglycemia 2.0% (5 mg), 1.8% (15 mg), and 0.9% (placebo). Conclusion: Among patients with T2DM and ASCVD, ERTU (5 mg and 15 mg) added to metformin and SU for 18 weeks improved glycemic control (HbA1c and FPG) and reduced body weight, and was generally well tolerated with a safety profile consistent with the SGLT2 inhibitor class.

scholarly journals Impact of Insulin Resistance on Risk of Type 2 Diabetes and Cardiovascular Disease in People With Metabolic Syndrome

Diabetes Care ◽  
2007 ◽  
Vol 30 (5) ◽  
pp. 1219-1225 ◽  
Author(s):  
J. B. Meigs ◽  
M. K. Rutter ◽  
L. M. Sullivan ◽  
C. S. Fox ◽  
R. B. D'Agostino ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome
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