scholarly journals Sex Differences in Biomarkers Associated With Insulin Resistance in Obese Adolescents: Metabolomic Profiling and Principal Components Analysis

2014 ◽  
Vol 99 (12) ◽  
pp. 4730-4739 ◽  
Author(s):  
Dorothee Newbern ◽  
Pinar Gumus Balikcioglu ◽  
Metin Balikcioglu ◽  
James Bain ◽  
Michael Muehlbauer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Uric Acid ◽  
Fatty Acid ◽  
Acid Oxidation ◽  
Z Score ◽  
Obese Adolescents ◽  
Metabolic Signature ◽  
Components Analysis

Objective Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. Research Design and Methods Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. Results Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R2 = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R2 = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. Conclusions BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.

scholarly journals Fatty acid metabolism in obesity and type 2 diabetes mellitus

2003 ◽  
Vol 62 (3) ◽  
pp. 753-760 ◽  
Author(s):  
E. E. Blaak
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Acid Oxidation ◽  
Acid Uptake

Disturbances in pathways of lipolysis and fatty acid handling are of importance in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that a lowered catecholamine-mediated lipolytic response may play a role in the development and maintenance of increased adipose tissue stores. Increased adipose tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high lipolytic rate may increase circulating NEFA concentrations, which may promote insulin resistance and cardiovascular complications. In addition, a disturbance of NEFA uptake by adipose tissue postprandially is also a critical determinant of plasma NEFA concentration. Furthermore, evidence is increasing that insulin-resistant muscle is characterised by a lowered ability to oxidise fatty acids. A dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a factor promoting accumulation of lipid intermediates and triacylglycerols within skeletal muscle, which is strongly associated with skeletal muscle insulin resistance. The present review describes the reported disturbances in pathways of lipolysis and skeletal muscle fatty acid handling, and discusses underlying mechanisms and metabolic consequences of these disturbances.

scholarly journals Associations between Fatty Acid-Binding Protein 4–A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 227 ◽  
Author(s):  
Marcin Trojnar ◽  
Jolanta Patro-Małysza ◽  
Żaneta Kimber-Trojnar ◽  
Bożena Leszczyńska-Gorzelak ◽  
Jerzy Mosiewicz
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Clinical Aspects ◽  
Diabetic Patients ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.

scholarly journals Relationships With Type 2 Diabetes Mellitus of the Basic Parameters of Urine Acid Metabolism With Indicators of Insulin Resistance

2020 ◽  
Vol 6 (1) ◽  
pp. 122-128
Author(s):  
I. Madyanov
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Acid Metabolism ◽  
Density Lipoprotein ◽  
Tyg Index ◽  
Insulin Dependent

Hyperuricemia (HU) occurs in one third of patients with type 2 diabetes mellitus (DM 2). The formation of HU in DM 2 is due to metabolic factors and impaired renal function. At the stage of prediabetes, GU reveals a connection with insulin resistance (IR), it is not clear to what extent this phenomenon is associated with an increase in uricemia in DM 2. Direct assessment of IR in patients with DM 2 is difficult. There are methods for indirect estimation of IR based on the calculation of indices using the results of simple laboratory tests. These indices are based on the determination of fasting plasma levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) — TG/HDL-C, TG and glucose — TyG index, as well as TG, HDL-C and glucose — MI (metabolic index). The aim of the study was to study the relationship in patients DM 2 between the main indicators of uric acid metabolism and the TG/HDL-C index, TyG index, and MI. 368 patients with DM 2 an average age of 55.8 years, and an average disease duration of 7.2 years were examined. There were 147 men, 221 women. The connection of uricemia with TG/HDL-C was established (Rs=0.2, p=0.03). In the non-insulin-dependent course of DM 2, uricemia was positively correlated with TG/HDL-C (Rs=0.21, p=0.03), negative relations of renal clearance of urates with TG/HDL-C (Rs=0.34, p=0.007) and fractional clearance of urates with TyG (Rs =−0.27, p=0.007) were recorded. In the insulin-dependent course of DM 2, a positive association of TyG with uricuria (Rs=0.44, p=0.03) and a negative correlation with GGFRT, the main enzyme for purine reuse (Rs=−0.44, p=0.03), were revealed. The results obtained do not contradict the previously established patterns of uric acid metabolism in DM 2. The conclusion is made on the feasibility of using the TG/HDL-C index as an indicator of metabolic disorders of uric acid and IR in DM 2. In the insulin-dependent course of DM2, TyG index becomes important, an increase in which is associated with increased catabolism of purines and their insufficient reutilization.

Lipid metabolism, exercise and insulin action

2006 ◽  
Vol 42 ◽  
pp. 47-59 ◽  
Author(s):  
Arend Bonen ◽  
G. Lynis Dohm ◽  
Luc J.C. van Loon
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Insulin Signalling ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Severely Obese

Skeletal muscle constitutes 40% of body mass and takes up 80% of a glucose load. Therefore, impaired glucose removal from the circulation, such as that which occurs in obesity and type 2 diabetes, is attributable in large part to the insulin resistance in muscle. Recent research has shown that fatty acids, derived from adipose tissue, can interfere with insulin signalling in muscle. Hence, insulin-stimulated GLUT4 translocation to the cell surface is impaired, and therefore, the rate of glucose removal from the circulation into muscle is delayed. The mechanisms provoking lipid-mediated insulin resistance are not completely understood. In sedentary individuals, excess intramyocellular accumulation of triacylglycerols is only modestly associated with insulin resistance. In contrast, endurance athletes, despite accumulating large amounts of intramyocellular triacylglycerols, are highly insulin sensitive. Thus it appears that lipid metabolites, other than triacylglycerols, interfere with insulin signalling. These metabolites, however, are not expected to accumulate in athletic muscles, as endurance training increases the capacity for fatty acid oxidation by muscle. These observations, and others in severely obese individuals and type 2 diabetes patients, suggest that impaired rates of fatty acid oxidation are associated with insulin resistance. In addition, in obesity and type 2 diabetes, the rates of fatty acid transport into muscle are also increased. Thus, excess intracellular lipid metabolite accumulation, which interferes with insulin signalling, can occur as a result of impaired rates of fatty acid oxidation and/or increased rates of fatty acid transport into muscle. Accumulation of excess intramyocellular lipid can be avoided by exercise, which improves the capacity for fatty acid oxidation.

scholarly journals Study on Association of Serum Uric Acid and Calcium with Insulin and its Resistance in Newly Diagnosed Type 2 Diabetes Mellitus Patients

2021 ◽  
Author(s):  
Saffalya Nayak ◽  
Roma Rattan ◽  
Manmath Kumar Mandal ◽  
Debjyoti Mohapatra
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Serum Insulin ◽  
Model Assessment ◽  
Newly Diagnosed

Introduction: Type 2 Diabetes Mellitus (T2DM) is a multifactorial pathological condition associated with insulin resistance and insulin deficiency. Uric acid and calcium have shown inconsistent association with occurrence of diabetes. Aim: To evaluate the role of uric acid and calcium in development of T2DM. Materials and Methods: This was a case-control study conducted in Department of Biochemistry from March to November 2019 in Sriram Chandra Bhanja, Medical College and Hospital, Cuttack, Odisha, India. A 180 subjects undertaken with the objective of finding any association of serum uric acid and calcium with insulin and its resistance in newly diagnosed T2DM cases. Newly diagnosed T2DM patients were taken as cases. Age and sex matched healthy individuals were taken as controls. Fasting Plasma Glucose (FPG), serum insulin, serum uric acid and ionised calcium were measured in autoanalyser and insulin resistance was calculated using Homeostasis Model Assessment for Insulin Resistance (HOMA- IR). Other confounding risk factors for T2DM like Body Mass Index (BMI), family history was taken into account. Results: A significant positive correlation of serum uric acid with serum insulin (p=0.029) and its resistance (p=0.032) in cases. Serum calcium was negatively associated with insulin and its resistance in both cases and controls. Regression models showed serum uric acid as a strong independent risk factor for levels of insulin and its resistance. Conclusion: The findings of the study showed that regular evaluation of serum uric acid and calcium should be done in those who are at risk of developing T2DM. Larger prospective studies will be required for definite assessment.

scholarly journals Uric Acid Levels in Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 3 (2) ◽  
pp. 83-89
Author(s):  
Linda Ramadhanti ◽  
Devi Etivia Purlinda
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Acid Value ◽  
Cross Sectional ◽  
Type 2 Dm ◽  
Exercise Activity

Type 2 diabetes mellitus accounts for about 90% of all diabetes cases worldwide. Type 2 DM is caused by the body's inability to respond well to insulin or called insulin resistance. Insulin resistance causes hyperglycemia and hyperinsulinemia which results in decreased uric acid excretion function in the kidney tubules, so that there will be an increase in uric acid in the blood or hyperuricemia. Type of research including descriptive with cross sectional approach. The examination was carried out at Dr. Adhyatma, MPH. The research respondents were 24 people, uric acid levels were examined with a TMS 50i Superior device. The data obtained is processed and presented in the form of diagrams and percentages. Type 2 DM respondents numbered 24 people. The highest hyperuricemia is based on the characteristics of the respondents, those are above 55 years old (25%), female sex (25%), high blood pressure (25%), and exercise activity 1x / day (21%). Of the 24 respondents, 14 people (58.3%) had normal uric acid levels and 10 people (41.6%) had hyperuricemia, with an average female uric acid value of 5.54 mg / dL and men of 6,48 mg / dL.

scholarly journals Prevalence of insulin resistance in obese adolescents

2013 ◽  
Vol 53 (3) ◽  
pp. 167 ◽  
Author(s):  
Aman B. Pulungan ◽  
Ardita Puspitadewi ◽  
Rini Sekartini
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Family History ◽  
Model Assessment ◽  
Obese Adolescents ◽  
History Of

Background Childhood obesity is a global health problem, withthe prevalence is differed in each country and affected by manyfactors, such as lifestyle and physical activity. Insulin resistance(IR) as a basic mechanism of several metabolic diseases in obesity,is related with metabolic syndrome (MetS) along with its longterm complications, such as type 2 diabetes mellitus (T2DM).Several factors are known to be associated with IR, and thepresence of acanthosis nigricans (AN) has an important meaningin predicting IR.Objectives To assess the prevalence of IR, MetS in obeseadolescents and its potentially associated factors, such as gender,signs of AN, and family history of metabolic diseases.Methods A cross-sectional study was performed in obeseadolescents, aged 12-15 years, over a two-month period. Fastingblood glucose, insulin, and lipid profiles were measured. Obesitywas defined using body mass index (BMI). Insulin resistancewas quantified by the homeostasis model assessment for IR(HOMA-IR) . Metabolic syndrome was defined according to theInternational Diabetes Federation (IDF) 2007 criteria.Results Of92 obese adolescents, IR was found in 38% of subjects,with females predominating (57.2%). Signs of AN were seen in71. 4% of subj ects and a positive family history of metabolic diseaseswas found in 82.8% of subjects, including family history of obesity,type 2 diabetes mellitus (T2DM), and hypertension. Less than10% of subjects were considered to be in a prediabetic state, andnone had T2DM. No statistical significance was found betweengender, family history, or signs of AN and IR (P>0.05). Metabolicsyndromes was found in 19.6% of subjects, with the fo llowingprevalences for each component: 34.8% for hypertension, 78.3%for central obesity, 8.7% for impaired fasting glucose (IFG), 22.8%for low levels of HDL, and 2 1. 7% for high triglyceride levels. Astrong correlation was found between IR and IFG with OR= 5 .69(95%CI 1.079 ~ 29.993, P= D.04).Conclusion We find a high prevalence ofIRin obese adolescents,and IR increases the risk of prediabetes. Thus, prevention strategies are needed to overcome the long term impact of obesity on health.

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