scholarly journals Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus

2020 ◽  
Vol 7 ◽  
Author(s):  
Xinyun Gu ◽  
Mohammed Al Dubayee ◽  
Awad Alshahrani ◽  
Afshan Masood ◽  
Hicham Benabdelkamel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
High Performance ◽  
Isotope Labeling ◽  
Normal Weight ◽  
Increased Risk

Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.

scholarly journals The impact of persistent milk consumption in the pathogenesis of type 2 diabetes mellitus

2019 ◽  
Vol 9 (10) ◽  
pp. 629
Author(s):  
Bodo Melnik
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
Branched Chain Amino Acids ◽  
Milk Consumption ◽  
Increased Risk ◽  
Branched Chain

Background: Milk and sugar are excessively consumed in a Western diet. There is increasing epidemiological evidence that the intake of unfermented pasteurized cow´s milk is associated with an increased risk of type 2 diabetes mellitus (T2D). It is the intention of this review to provide translational biochemical evidence for milk´s diabetogenic mode of action. Milk proteins provide the highest amounts of branched-chain amino acids (BCAAs) and thus contribute to total BCAA intake, which enhances BCAA plasma levels associated with increased risk of T2D. The consumption of pasteurized milk raises plasma levels of miRNA-29b, which is a diabetogenic miRNA promoting insulin resistance (IR). miRNA29b inhibits the activity of branched-chain-keta acid dehydrogenase, the rate limiting enzyme of BCAA catabolism, which is impaired in patients with IR and T2D. Milk consumption stimulates mTORC1 activity and increases insulin synthesis. -cell mTORC1 is overactivated in T2D patients resulting in impaired autophagy which enhances endoplasmic reticulum (ER) stress associated with a greater risk of early -cell apoptosis, the pathogenic hallmark of T2D. Chronic insulinotropic action of milk-derived BCAAs, IR-promoting mTORC1 overactivity, and miRNA-29b signaling combined with excessive glucose-mediated insulin secretion overburden -cell insulin homeostasis. Epidemiological and translational evidence identifies continued milk intake as a promoter of T2D, the most common metabolic disease of Western civilization. Keywords: Branched-chain amino acids, branched-chain-keto acid dehydrogenase, diabetes mellitus type 2, insulin resistance, milk, miRNA-29b, mechanistic target of rapamycin complex 1.

scholarly journals Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus—a prospective population-based cohort study

2017 ◽  
Vol 32 (4) ◽  
pp. 968-968 ◽  
Author(s):  
M.M. Ollila ◽  
S. West ◽  
S. Keinänen-Kiukaaniemi ◽  
J. Jokelainen ◽  
J. Auvinen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cohort Study ◽  
Population Based ◽  
Normal Weight ◽  
Increased Risk

scholarly journals Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Nabajyoti Deka ◽  
Swapnil Bajare ◽  
Jessy Anthony ◽  
Amrutha Nair ◽  
Anagha Damre ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
High Plasma ◽  
Insulin Sensitizers ◽  
Increased Risk

Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPARγ ligand and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here we report synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives as an alternate remedy for insulin resistance.

scholarly journals Investigation of leucinuria as a marker of progression of type 2 diabetes mellitus

2019 ◽  
Vol 8 (1) ◽  
pp. 32-36
Author(s):  
Kabita Khaniya Pokharel ◽  
Santosh Pradhan
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Performance ◽  
Cross Sectional Study ◽  
Chromatography Method ◽  
Cross Sectional ◽  
Ethical Approval

Background: The prevalence of diabetes is increasing worldwide leading to an extreme burden in healthcare system. Insulin resistance plays a major role in the pathogenesis of type 2 diabetes mellitus. A number of studies have been done to investigate the role of leucine in insulin resistance. These studies have elucidated raised serum leucine level in type 2 diabetes mellitus. Objectives: The objective of this study was to determine leucine in random urine of type 2 diabetes mellitus and to assess the association of urine leucine with the progression of the disease. Methodology: An analytical cross-sectional study was carried out in 187 participants after ethical approval. Patients already diagnosed with chronic kidney disease were excluded from the study. Urine microalbumin level was determined by nephelometry technique, HbA1c test was done by high performance liquid chromatoghrapy and urine leucine was detected by thin layer chromatography method. Results: The mean age of the case population was 55.7±11.6 years and that of control population was 49.98±13.7 years. Out of 105 cases, 15 (14.3%) of them had leucine in random urine where as only 3 (3.6%) of them from control showed the presence of leucine in their urine. There was a significant association observed between diabetic patient and urinary leucine excretion, P = 0.014. Conclusion: This study indicates an association of type 2 diabetes and urinary leucine excretion. However, presence of leucine in urine does not suggest the progression of the disease.

scholarly journals Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus—a prospective, population-based cohort study

2016 ◽  
Vol 32 (2) ◽  
pp. 423-431 ◽  
Author(s):  
M.-M.E. Ollila ◽  
S. West ◽  
S. Keinänen-Kiukaanniemi ◽  
J. Jokelainen ◽  
J. Auvinen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cohort Study ◽  
Population Based ◽  
Normal Weight ◽  
Increased Risk

scholarly journals Exploration of Insulin Sensitivity, Insulin Resistance, Early Insulin Secretion and β-cell Function, and Their Relationship with Glycated Hemoglobin Level in Normal Weight Patients with Newly Diagnosed Type 2 Diabetes Mellitus

2020 ◽  
Vol 70 (12) ◽  
pp. 4217-4223 ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Normal Weight ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Β Cell Function

When discussing insulin resistance and insulin sensitivity, data from literature focuses on obese and overweight patients. In our study on, 110 patients with normal body-mass index with newly diagnosed type 2 diabetes mellitus, with the help of glucose tolerance test, we explored insulin resistance, sensitivity, early insulin secretion and β-cell function assessed by using the following indexes: HOMA-IR, ISI, IGI and HOMA-β. We compared the results from our reference group with a control group of 109 overweight patients with newly diagnosed type 2 diabetes mellitus. Normal weight patients had a statistically significant lower HOMA-IR index than overweight patients (2.65 vs. 3.55, p<0.01), however in both groups HOMA-IR was above the cut-off value of 2.5. HOMA-β was statistically significant lower in normal weight patients than in overweight patients (55.08 vs 65.36, p<0.01). ISI index was in an inverse proportional relationship with HOMA-IR, statistically significant higher in normal weight individuals (5.97 vs.3.48, p<0.01). IGI index was not statistically significant lower in normal weight patients (3.63 vs.3.95, p=0.07). It is important to observe that although they have a normal BMI these patients are insulin-resistant confirming the hypothesis of metabolic obese normal weight patients that develop type 2 diabetes mellitus. The indexes that correlate with HbA1c in normal weight patients, predicting glucose status, are HOMA-β (negative correlation), ISI (positive correlation) and IGI index (negative correlation). Keywords: insulin, β-cell, glycated hemoglobin, type 2 diabetes mellitus

scholarly journals Early-life Programming of Type 2 Diabetes Mellitus: Understanding the Association between Epigenetics/Genetics and Environmental Factors

2019 ◽  
Vol 20 (6) ◽  
pp. 453-463 ◽  
Author(s):  
Fatma Z. Kadayifci ◽  
Sage Haggard ◽  
Sookyoung Jeon ◽  
Katie Ranard ◽  
Dandan Tao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Public Health Problem ◽  
Increased Risk

Type 2 Diabetes Mellitus is an increasing public health problem that poses a severe social and economic burden affecting both developed and developing countries. Defects in insulin signaling itself are among the earliest indications that an individual is predisposed to the development of insulin resistance and subsequently Type 2 Diabetes Mellitus. To date, however, the underlying molecular mechanisms which result in resistance to the actions of insulin are poorly understood. Furthermore, it has been shown that maternal obesity is associated with an increased risk of obesity and insulin resistance in the offspring. However, the genetic and/or epigenetic modifications within insulin-sensitive tissues such as the liver and skeletal muscle, which contribute to the insulin-resistant phenotype, still remain unknown. More importantly, a lack of in-depth understanding of how the early life environment can have long-lasting effects on health and increased risk of Type 2 Diabetes Mellitus in adulthood poses a major limitation to such efforts. The focus of the current review is thus to discuss recent experimental and human evidence of an epigenetic component associated with components of nutritional programming of Type 2 Diabetes Mellitus, including altered feeding behavior, adipose tissue, and pancreatic beta-cell dysfunction, and transgenerational risk transmission.

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