bain insulin resistance

AIMS/HYPOTHESIS: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes. METHODS: This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation...

OBJECTIVES: Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids (AAA) including tryptophan for uptake into β-cells. To explore relationships between BCAAs and tryptophan metabolism, adiposity, and glucose tolerance we compared urine metabolites in overweight/obese youth with T2D to those in non-diabetic overweight/obese and lean youth. METHODS: Metabolites were measured in 24-hr and first-morning urine samples of 56 non-diabetic adolescents with overweight/obesity, 42 adolescents with T2D, and 43 lean controls, ages 12-21 yr...

AIMS AND OBJECTIVES: The aim of the present paper is to provide a narrative review of the markers and pathways of periodontitis-associated insulin resistance (IR). MATERIALS AND METHODS: Research papers published in peer-reviewed scientific journals from 2000 to 2021 were searched systematically in Online Cochrane Library, Google Scholar, and MedLine/PubMed database. The medical subject headings (MeSH) terms used for literature search were "diabetes AND periodontal disease," "diabetes AND periodontitis," "inflammation AND insulin resistance," "Insulin resistance AND periodontal disease," and "insulin resistance AND periodontitis...

OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program. METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS...

White adipose tissue (WAT) dysfunction independently predicts cardiometabolic disease, yet there is a lack of effective adipocyte-targeting therapeutics. B3AR agonists enhance adipocyte mitochondrial function and hold potential in this regard. Based on enhanced sensitivity to B3AR-mediated browning in estrogen receptor (ER)alpha-null mice, we hypothesized that ERβ may enhance the WAT response to the B3AR ligand, CL316,243 (CL). Methods: Male and female wild-type (WT) and ERβ DNA binding domain knock-out (ERβDBD KO) mice fed high-fat diet (HFD) to induce obesity were administered CL (1 mg/kg) daily for 2 weeks...

Objective: Insulin antibody (IA)-mediated insulin resistance (IR) is a rare condition for which immunosuppressive regimens have been described. However, these raise the risk of infection, and the drugs may not be effectively metabolized in patients with liver disease. A 61-year old male with type 2 diabetes mellitus and antibody-mediated IR who required >800 units of daily insulin presented with acute decompensation of his preexisting cirrhosis from recurrent diabetic ketoacidosis...

Insulin resistance in adolescents with obesity associates with a sex-dependent metabolic 'signature' comprising branched-chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic pathways. Here, we investigated the effects of lifestyle intervention on BCAA catabolism and insulin sensitivity. We hypothesized (1) weight reduction and improved insulin sensitivity associate with enhanced BCAA catabolism; (2) baseline BCAAs and their metabolic by-products predict changes in weight and insulin sensitivity during lifestyle intervention...

OBJECTIVE: To identify circulating metabolites present at ~28 weeks' gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10-14 years later. METHODS: Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hr serum samples following a 75g glucose load at ∼28 weeks' gestation from 2,290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study...

BACKGROUND: A strong association of obesity and insulin resistance with increased circulating levels of branched-chain and aromatic amino acids and decreased glycine levels has been recognized in human subjects for decades. SCOPE OF REVIEW: More recently, human metabolomics and genetic studies have confirmed and expanded upon these observations, accompanied by a surge in preclinical studies that have identified mechanisms involved in the perturbation of amino acid homeostasis- how these events are connected to dysregulated glucose and lipid metabolism, and how elevations in branched-chain amino acids (BCAA) may participate in the development of insulin resistance, type 2 diabetes (T2D), and other cardiometabolic diseases and conditions...

Estrogen receptor  (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and systemic metabolic responses to wheel running exercise in a rodent model of menopause. Female mice lacking the ERb DNA-binding domain (ERbDBDKO, N = 20) and wild-type (WT, N = 21) littermate controls were fed high-fat diet (HFD), ovariectomized (OVX), and randomized to control (no running wheel) and exercise (running wheel access) groups and were followed for eight weeks...

We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a follow-up cohort (> 5600 days) comprising participants undergoing evaluation for possible ischemic heart disease. Lipoprotein subparticles, lipoprotein-insulin resistance (LP-IR), and GlycA were measured using NMR spectroscopy (n = 8385), while acylcarnitines and amino acids were measured using flow-injection, tandem mass spectrometry (n = 3592)...

AIMS/HYPOTHESIS: Our study aimed to integrate maternal metabolic and genetic data related to insulin sensitivity during pregnancy to provide novel insights into mechanisms underlying pregnancy-induced insulin resistance. METHODS: Fasting and 1 h serum samples were collected from women in the Hyperglycemia and Adverse Pregnancy Outcome study who underwent an OGTT at ∼28 weeks' gestation. We obtained targeted and non-targeted metabolomics and genome-wide association data from 1600 and 4528 mothers, respectively, in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai); 1412 of the women had both metabolomics and genome-wide association data...

CONTEXT: Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance. OBJECTIVE: To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns. DESIGN: Cross-sectional, observational study. SETTING: Hyperglycemia and Adverse Pregnancy Outcome study...

In this review, we highlight the specific metabolic effects of fructose consumption that are involved in the development of metabolic syndrome non-alcoholic fatty liver disease and its association with obesity. The specifics effects of fructose on the liver are particularly germane to the development of a vicious cycle that starts with liver steatosis driving insulin resistance. These effects include 1) increased de novo lipogenesis, 2) increased liver fat, 3) dyslipidemia 4) increased uric acid production which feeds back on increased fructose metabolism and, 5) increased methylglyoxal and Maillard reaction that may affect adenosyl-monophosphate-dependent kinase Fructose increases cortisol activation especially in visceral fat...

Background: Recent studies, primarily in non-Hispanic whites, suggest that dietary patterns have distinct metabolomic signatures that may influence disease risk. However, evidence in South Asians, a group with unique dietary patterns and a high prevalence of cardiometabolic risk, is lacking. Objective: We investigated the metabolomic profiles associated with 2 distinct dietary patterns among a sample of Asian Indians living in the United States. We also examined the cross-sectional associations between metabolomic profiles and cardiometabolic risk markers...

BACKGROUND: Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated. OBJECTIVES: To explore the effects of weight loss by surgical and dietary interventions on plasma metabolites using both targeted and discovery-oriented metabolomics platforms. SETTING: An academic medical center in the United States. METHODS: Improvement in homeostatic model assessment for insulin resistance (HOMA-IR), as an index of insulin resistance, was compared at 6 months in 11 patients that underwent Roux-en-Y gastric bypass against 11 patients that were matched for weight loss in the Weight Loss Maintenance (WLM) program...

BACKGROUND: Childhood obesity is associated with insulin resistance (IR), increased levels of small dense low-density lipoprotein (sd-LDL) as well as with augmented hepatic de novo lipogenesis, which implies increased triose phosphate fluxes that may lead to increased methylglyoxal (MG) and its catabolic end product D-lactate. We hypothesized that obese adolescents have increased D-lactate serum levels associated with high incidence of sd-LDL. METHODS: This is a cross-sectional study where the anthropometric characteristics, atherogenic dyslipidemia complex, sd-LDL (Lipoprint, Quantimetrix) and D-lactate (kinetic enzymatic analysis) were explored in 30 lean vs...

OBJECTIVE: We used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads. RESEARCH DESIGN AND METHODS: Targeted metabolomic assays were performed on cord blood serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American newborns (400 from each ancestry group) whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and who had anthropometric measurements at birth...

AIMS/HYPOTHESIS: Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity. METHODS: Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ∼28 weeks gestation and whose offspring had anthropometric measurements at birth...

BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization...