Review: Obesity Induced Insulin Resistance, Type 2 Diabetes and Emerging Therapeutic Approaches.

2021 ◽  
pp. 1-22
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Obese Patients ◽  
Therapeutic Approaches ◽  
Tnf Α

There is a strong association between obesity, insulin resistance and type 2 diabetes mellitus. Abdominal obesity appears to be a major mediator of insulin resistance and hyperinsulinemia. Insulin resistance is a pathological condition in which cells fail to respond normally to the hormone insulin. leading to high blood sugar (impaired glucose uptake in peripheral tissues, particularly in skeletal muscle.) The more life-threatening problems fall into four main areas: type 2 diabetes, cardiovascular diseases (CVD), dyslipidemia and certain types of cancers and musculoskeletal disorders. There is considerable evidence that inflammation is a primary mediator of obesity induced insulin resistance and related co-morbidities, including diabetes and CVD whereby pro-inflammatory substances and other chemokines produced by adipocytes and macrophages are able to cause insulin resistance. The major inflammatory factors include pro-inflammatory interleukins (IL-1 & IL-6) and signaling intermediate-nuclear factor kappa B cells (NF-kB), chemokines and cytokines, tumor necrosis factor alpha (TNF-α), adiponectin (ADN), circulating C-reactive protein (CRP) concentrations, toll-like receptors (Tlr), free fatty acids (FFA), oxidative stress and dietary fatty acids. Considering this viewpoint, in the present review, we have selected ten well designed clinical studies with salsalates, thiazolidinediones (TZD) and TNF-α–antagonists to discuss and analyze these emerging therapeutic approaches for the treatment of obesity induced insulin resistance and type 2 diabetes mellitus. These therapeutics provide sufficient evidence of improved glycemic control post treatment in obese patients by targeting the state of chronic inflammation that characterizes obesity and resulted in improved insulin sensitivity by reducing adipocyte pro-inflammatory cytokine expression, adipose tissue macrophage content and immune cell infiltration into adipose tissue and other inflammatory markers. Even with looking at only few studies, analyzing each pathway, the hypothesis that targeting pro-inflammatory pathways in adipocytes with TZD and salicylates as a novel approach remains supported for reducing chronic inflammation-induced insulin resistance in obese patients, with TZD emerging with the strongest effects.

scholarly journals Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial

2019 ◽  
Vol 16 (4) ◽  
pp. 360-368
Author(s):  
Hani Zaidi ◽  
Rune Byrkjeland ◽  
Ida U Njerve ◽  
Sissel Åkra ◽  
Svein Solheim ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Exercise Training ◽  
Artery Disease

Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.

Acute-phase serum proteins and adipocytokines in women with type 2 diabetes mellitus: Relationships with body composition and blood glucose fluctuations

2016 ◽  
Vol 88 (10) ◽  
pp. 35-41 ◽  
Author(s):  
V V Klimontov ◽  
N V Tyan ◽  
O N Fazullina ◽  
N E Myakina ◽  
N B Orlov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Composition ◽  
Adipose Tissue ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Hs Crp ◽  
Pai 1

Aim. To estimate the relationships between the serum concentrations of acute-phase proteins (APPs) and adipocytokines, body composition (BC), and blood glucose (BG) fluctuations in women with type 2 diabetes mellitus (T2DM). Subjects and methods. A total of 165 women with T2DM and 22 with a normal body mass index (BMI) at the age of 40 to 70 years were examined. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and acid α1-glycoprotein (α1-AGP) were determined by ELISA. The levels of interleukins 6, 8, and 18 (IL-6, IL-8, IL-18), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor type 1 (PAI-1) were measured by a multiplex analysis. Dual energy X-ray absorptiometry was used to estimate BC parameters. BG fluctuations were estimated via continuous glucose monitoring. Results. The levels of hs-CRP, α1-AGP, IL-6, IL-8, IL-18, TNF-α, and PAI-1 were significantly higher in the obese women with T2DM than those in the control group. In the diabetic normal weight women, only hs-CRP, α1-AGP, and IL-8 concentrations exceeded those in the controls. The level of hs-CRP (other than α1-AGP) correlated positively with BMI, the mass of adipose tissue, body trunk (android), and gynoid fats. A multivariate regression analysis showed that adipose tissue mass and trunk fat proportion were independent predictors of hs-CRP levels. The concentrations of IL-6, IL-8, IL-18, PAI-1, and TNF-α correlated positively with waist-to-hip ratio, but demonstrated no associations with BMI and BC. Only the serum α1-AGP level showed a positive association with mean BG and its variability parameters. Conclusion. In the women with T2DM, the serum concentrations of APPs and adipocytokines correlate differently with the mass of adipose tissue, its distribution, and BG fluctuations. The findings indicate the multifactorial genesis of chronic inflammation in these patients.

scholarly journals The role of nonesterified fatty acids in pathogenesis of cardiovascular diseases

2010 ◽  
Vol 16 (1) ◽  
pp. 93-103 ◽  
Author(s):  
M. V. Tsvetkova ◽  
V. N. Khirmanov ◽  
N. N. Zybina
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Sudden Death

The paper reviews publications concerned the role of nonesterifi ed fatty acids (NEFA) in pathogenesis of cardiovascular diseases. NEFAs are four and more carbons chain length carbonic acids and they are presented in free form (nonesterifi ed) in human body. Plasma NEFAs are produced by the adipose tissue triglyceride lipolysis, another source are lipoproteins such as chylomicrons, very low density lipoproteins and intermediate density lipoproteins. Elevated NEFA concentrations in plasma are the risk factor of cardiovascular diseases and type 2 diabetes mellitus and the independent risk factor of hypertension and sudden death. NEFA plasma concentration is elevated in atherosclerosis, acute myocardial infarction, diabetes mellitus, obesity, hypertension, and often in metabolic syndrome. A probable cause of NEFAs accumulation in plasma may be overeating and low physical activity, which result in increase of adipose tissue mass, lipolysis intensifi cation and elevation of NEFAs concentration in plasma. The role of elevated plasma NEFA concentration in a number of conditions (abdominal obesity, atherogenic dyslipidemia, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular infl ammation, atherosclerosis, hypertension, ischemic heart disease, rhythm disturbances, sudden death) and possible ways of their correction are discussed.

scholarly journals The role of the lipotoxicity in the pathogenesis of type 2 diabetes mellitus and obesity

2014 ◽  
Vol 11 (2) ◽  
pp. 8-12 ◽  
Author(s):  
F R Abdulkadirova ◽  
A S Ametov ◽  
E V Doskina ◽  
R A Pokrovskaya
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Diabetes Mellitus Type 2 ◽  
Comorbid Conditions ◽  
Fatty Acids Metabolism

Obesity is a major risk factor for diabetes mellitus type 2, cardiovascular diseases and associated comorbid conditions. It is traditionally considered that insulin resistance is dependent on glucose metabolism. However, in recent years more and more attention is devoted to the fatty acids metabolism, the increase in concentrations of which plays a significant role in the pathophysiological mechanisms associated with insulin resistance.

scholarly journals Abnormal Non Esterified Fatty Acid Suppression After a Mixed Meal Test in Patients With Partial Lipodystrophy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1-A2
Author(s):  
Maria Cristina Foss de Freitas ◽  
Baris Akinci ◽  
Elif A Oral
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Meal Test ◽  
Mixed Meal ◽  
Partial Lipodystrophy ◽  
Mixed Meal Test

Abstract Elevated levels of non-esterified fatty acids (NEFA) have been observed in individuals with several clinical scenarios of insulin resistance, such as in diabetes mellitus and lipodystrophy. Insulin is a well-known stimulator of de novo lipogenesis. Despite the reduction of adipose tissue mass, paradoxically elevated circulating NEFA concentrations have been observed in patients with different lipodystrophy syndromes. Aiming to understand the behavior of NEFA in lipodystrophy versus common Type 2 diabetes mellitus during feeding, we compared NEFA kinetics during a mixed meal test in patients with partial lipodystrophy (PL) and Type 2 diabetes mellitus (DM). We reviewed data from 17 PL patients (13F/4M, ages 12–64) matched by gender and BMI to 20 DM patients (13F/7M, ages 24–72). All patients were evaluated during fasting state and then underwent a mixed meal test (MMT). Blood samples were collected before (fasting) and at 30, 60, 90, 120, and 180 minutes post-meal to measure glucose, insulin, non-esterified free fatty acids (NEFA), and triglyceride levels. Adipose tissue insulin resistance (ADIPO-IR) and homeostatic model of insulin resistance (HOMA-IR) were calculated from the fasting measurements, and the area under the curve (AUC) and maximum percentage of change from baseline were calculated from the MMT data. Fasting insulin and triglyceride (Tg) levels were lower in the DM group compared to the PL group (Insulin: 24.4±13.7 vs. 68.0±67.2 pmol/L, p=0.003 and Tg: 168.0±107.7 vs. 1378.3±1927.3 mg/dL, p<0.001). HOMA-IR was significantly higher in the PL group compared to the DM group (6.0±2.1 vs. 3.3±1.5, p=0.005), as well as ADIPO-IR (297.0±241.1 vs. 115.3±80.1, p=0.03). NEFA, glucose and triglyceride AUC were significantly higher in the PL group compared to the DM group. Patients with PL had higher glucose and triglyceride levels throughout the MMT at all-time points. Interestingly, NEFA levels were similar in both groups at baseline, but the PL group suppressed NEFA less than DM group (54.9±13.3% vs. 69.2±11.1%, p=0.002) despite higher insulin levels. Additionally, we divided the PL group according to the presence of a pathogenic variant in the lamin A gene (n=8) versus those without mutations in this gene (n=9), but there were no notable differences among these subgroups with respect to NEFA levels at baseline or during the meal. These findings support the need to better understand and address the origins of abnormal NEFA kinetics and adipose tissue insulin resistance in PL patients.

scholarly journals Association of Serum Adipokines Levels with Glycemic Control and Metabolic Dyslipidemia in Sudanese Patients with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Halima Babiikir Eltahir ◽  
Elmahadi Mohamed Ali ◽  
Abdelrahim Osman Mohamed
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Glycemic Control ◽  
Total Cholesterol ◽  
Pearson Correlation ◽  
P Value

Abstract Background:The pathogenesis of type 2 diabetes mellitus is due to two major abnormalities including insulin resistance and dysfunction, which lead to the inability to regulate blood glucose level. Adiponectin is a hormone secreted by the adipose tissue and it takes part in glucose metabolism with insulin-sensitising properties. Low levels of adiponectin leads to reduction of fatty acid oxidation decreased glucose uptake in skeletal muscle cells and increased level of free fatty acids leading to insulin resistance. Leptin is another adipokine produced by adipose tissue involved in the control of food intake via its action on the hypothalamus, suppressing appetite and stimulating energy expenditure. Leptin plays a critical role in pathophysiology of type 2 diabetes mellitus.The aim of the study was to investigate the association of serum adipokines levels with glycemic control and metabolic dyslipidemia in Sudanese patients with type 2 diabetes mellitus.Methods: This was a case control study. 202 patients with type 2 diabetes and 102 non-diabetic controls participated after signing written consent. Weight (kg) and height (m) were measured thenthe body mass index (kg/m2) was determined. Blood samples were collected after an overnight fasting. FBG, HbA1c and lipid profiles were measured using enzymatic methods. Adiponectin and leptin were measured using sandwich ELISA.Results: Adiponectin concentrations was significantly lower in patients with type 2 diabetes compared with the controls (p<0.001) and it was inversely correlated with HbA1c (Pearson Correlation -.160, P value = 0.005), total cholesterol and LDL levels (P = 0.05) and direct correlated HDL levels (P = 0.05). Leptin concentrations was significantly higher in patients with type 2 diabetes compared with the controls (p<0.002) and it was positively correlated with HbA1c (Pearson Correlation .155, P value = 0.02), total cholesterol and LDL levels (P = 0.05), there were no correlation with HDL and TG levels. Patients had significantly higher fasting blood glucose, HbA1c levels, total cholesterol and LDL levels compared with the controls. Conclusion: Patients with type 2 diabetes mellitus had decreased levels of serum adiponectin, high levels of serum leptin. There were significant correlations found between adiponectin and leptin levels with glycemic control and metabolic dyslipidemia

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