scholarly journals Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort

2021 ◽  
Author(s):  
Zhila Semnani-Azad ◽  
Philip W. Connelly ◽  
Richard P. Bazinet ◽  
Ravi Retnakaran ◽  
David J. A. Jenkins ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Total Cholesterol ◽  
Estimating Equation ◽  
Adipose Tissue Dysfunction ◽  
Increased Risk ◽  
Tnf Α ◽  
Design And Methods

<b>Aim: </b>Our objective was to determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. <div><p><b>Research design and methods</b>: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes.</p> <p><b>Results</b>: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL.</p> <p><b>Conclusion</b>: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.</p> </div> <b><br> </b>

scholarly journals Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort

2021 ◽  
Author(s):  
Zhila Semnani-Azad ◽  
Philip W. Connelly ◽  
Richard P. Bazinet ◽  
Ravi Retnakaran ◽  
David J. A. Jenkins ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Total Cholesterol ◽  
Estimating Equation ◽  
Adipose Tissue Dysfunction ◽  
Increased Risk ◽  
Tnf Α ◽  
Design And Methods

<b>Aim: </b>Our objective was to determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. <div><p><b>Research design and methods</b>: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes.</p> <p><b>Results</b>: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL.</p> <p><b>Conclusion</b>: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.</p> </div> <b><br> </b>

scholarly journals Elevated circulating follistatin associates with an increased risk of type 2 diabetes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chuanyan Wu ◽  
Yan Borné ◽  
Rui Gao ◽  
Maykel López Rodriguez ◽  
William C. Roell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Genome Wide Association Study ◽  
Regulatory Protein ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

2017 ◽  
Vol 176 (2) ◽  
pp. R67-R78 ◽  
Author(s):  
Charlotte Brøns ◽  
Louise Groth Grunnet
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cellular Localization ◽  
Future Research ◽  
Causal Mechanism ◽  
Increased Risk ◽  
Adipose Tissue Expandability

Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver.

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

scholarly journals Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

Diabetologia ◽  
2007 ◽  
Vol 50 (12) ◽  
pp. 2562-2571 ◽  
Author(s):  
P. Plomgaard ◽  
A. R. Nielsen ◽  
C. P. Fischer ◽  
O. H. Mortensen ◽  
C. Broholm ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Tnf Α

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 ◽  
Elmahdi 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 then the 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 .

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 Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

2021 ◽  
Vol 22 (12) ◽  
pp. 6444
Author(s):  
Anna Gabryanczyk ◽  
Sylwia Klimczak ◽  
Izabela Szymczak-Pajor ◽  
Agnieszka Śliwińska
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Cancer Risk ◽  
Vitamin D Deficiency ◽  
Cancer Development ◽  
Increased Risk

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

scholarly journals TheType 2 Deiodinase Thr92Ala PolymorphismIs Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaowen Zhang ◽  
Jie Sun ◽  
Wenqing Han ◽  
Yaqiu Jiang ◽  
Shiqiao Peng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Meta Analysis ◽  
Increased Risk ◽  
Design And Methods ◽  
Hba1c Levels

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

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