scholarly journals Specific Metabolic Profiles and Their Relationship to Insulin Resistance in Recent-Onset Type 1 and Type 2 Diabetes

2016 ◽  
Vol 101 (5) ◽  
pp. 2130-2140 ◽  
Author(s):  
Birgit Knebel ◽  
Klaus Strassburger ◽  
Julia Szendroedi ◽  
Jorg Kotzka ◽  
Marsel Scheer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Pairwise Comparison ◽  
Plasma Metabolites ◽  
Inverse Association ◽  
Recent Onset ◽  
Detection Of Biomarkers

Abstract Context: Insulin resistance reflects the inadequate insulin-mediated use of metabolites and predicts type 2 diabetes (T2D) but is also frequently seen in long-standing type 1 diabetes (T1D) and represents a major cardiovascular risk factor. Objective: We hypothesized that plasma metabolome profiles allow the identification of unique and common early biomarkers of insulin resistance in both diabetes types. Design, Setting, and Patients: Two hundred ninety-five plasma metabolites were analyzed by mass spectrometry from patients of the prospective observational German Diabetes Study with T2D (n = 244) or T1D (n = 127) and known diabetes duration of less than 1 year and glucose-tolerant persons (CON; n = 129). Abundance of metabolites was tested for association with insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamps and related metabolic phenotypes. Main Outcomes Measures: Sixty-two metabolites with phenotype-specific patterns were identified using age, sex, and body mass index as covariates. Results: Compared with CON, the metabolome of T2D and T1D showed similar alterations in various phosphatidylcholine species and amino acids. Only T2D exhibited differences in free fatty acids compared with CON. Pairwise comparison of metabolites revealed alterations of 28 and 49 metabolites in T1D and T2D, respectively, when compared with CON. Eleven metabolites allowed differentiation between both diabetes types and alanine, α-amino-adipic acid, isoleucin, and stearic acid showed an inverse association with insulin sensitivity in both T2D and T1D combined. Conclusion: Metabolome analyses from recent-onset T2D and T1D patients enables identification of defined diabetes type-specific differences and detection of biomarkers of insulin sensitivity. These analyses may help to identify novel clinical subphenotypes diabetes.

1746-P: Obese Youth with Type 1 Diabetes (T1D) Have Worse Hepatic Insulin Resistance (IR) Than Youth with Type 2 Diabetes (T2D)

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1746-P
Author(s):  
PATTARA WIROMRAT ◽  
MELANIE CREE-GREEN ◽  
BRYAN C. BERGMAN ◽  
KALIE L. TOMMERDAHL ◽  
AMY BAUMGARTNER ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Hepatic Insulin Resistance ◽  
Obese Youth

scholarly journals Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial

2017 ◽  
Vol 14 (2-3) ◽  
pp. 301-310 ◽  
Author(s):  
Mitra Zarifkar ◽  
Sina Noshad ◽  
Mona Shahriari ◽  
Mohsen Afarideh ◽  
Elias Khajeh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Type 2 Diabetes Mellitus ◽  
Randomized Clinical Trial ◽  
Inverse Association ◽  
Orexin A

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

scholarly journals Association between breastfeeding and insulin sensitivity among young people with Type 1 and Type 2 diabetes: the SEARCH Nutrition Ancillary Study

2016 ◽  
Vol 33 (10) ◽  
pp. 1452-1455
Author(s):  
N. S. The ◽  
C. M. Shay ◽  
A. P. Lamichhane ◽  
T. L. Crume ◽  
J. L. Crandell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Young People ◽  
Ancillary Study

Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

2014 ◽  
Author(s):  
◽  
Leryn J. Boyle
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Ethnic distinctions in the pathophysiology of type 2 diabetes: a focus on black African-Caribbean populations

2019 ◽  
Vol 79 (2) ◽  
pp. 184-193 ◽  
Author(s):  
Louise M. Goff ◽  
Meera Ladwa ◽  
Olah Hakim ◽  
Oluwatoyosi Bello
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Global Public Health ◽  
Black African ◽  
African Caribbean ◽  
Black Populations ◽  
The Impact ◽  
Caribbean Populations

Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.

scholarly journals Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study

2019 ◽  
Vol 109 (3) ◽  
pp. 626-634 ◽  
Author(s):  
Christopher Papandreou ◽  
Mònica Bulló ◽  
Miguel Ruiz-Canela ◽  
Courtney Dennis ◽  
Amy Deik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Area Under The Curve ◽  
Predictive Ability ◽  
Plasma Metabolites ◽  
Incident Type ◽  
Dieta Mediterranea ◽  
Dieta Mediterránea

ABSTRACT Background Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). Objectives The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. Methods We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography–tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR–related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. Results We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. Conclusions The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.

scholarly journals Association of Vitamin D with Type 2 Diabetes in Postmenopausal Females in Saudi Arabia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Shatha Alharazy ◽  
Eman Alissa ◽  
Mohammed Ardawi ◽  
Susan Lanham-New ◽  
M. Denise Robertson
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Saudi Arabia ◽  
Insulin Sensitivity ◽  
Postmenopausal Women ◽  
Cell Activity ◽  
Study Cohort ◽  
Model Assessment

AbstractVitamin D (vitD) deficiency has been suspected as a risk factor for type 2 diabetes mellitus (T2DM). It has been reported that an inverse relationship exists between vitD status and risk of T2DM. The aim of this study was to investigate whether there is an association between vitD status and glycemic profile and other metabolic parameters among postmenopausal women with T2DM (living in Saudi Arabia). A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. One thirty six (n = 136) postmenopausal females (age ≥ 50 years) living in Jeddah city, Saudi Arabia, with T2DM were randomly recruited in this study. Anthropometric measures, blood pressure readings and fasting blood samples were obtained fro all study participants. Several biochemical parameters were estimated in fasting serum samples including total 25(OH)D, HbA1c, insulin, glucose, c-peptide and lipid profile. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment for insulin resistance and beta cell activity (HOMA-IR, HOMA-β), Quantitative insulin sensitivity check index (QUICK-I) and McAuley's index. VitD deficiency was defined as serum total 25(OH)D level below 20 ng/ml.The Mean (± SD) serum levels of total 25(OH)D were 13.8 ± 8.6 ng/ml with 79% of the study cohort being vitD deficient. Furthermore, serum total 25(OH)D levels were found to be inversely correlated with fasting insulin (r = -0.24, p = 0.029), HOMA-IR (r = -0.24, p = 0.03), and positively correlated with McAuley's index (r = 0.22, p = 0.048) and QUICK-I (r = 0.25, p = 0.024). In conclusion, vitD deficiency is highly prevalent among postmenopausal women with T2DM living in Jeddah, Saudi Arabia. VitD was found to be associated with insulin resistance. Whether vitD supplements are able to improve insulin sensitivity and other parameters in T2DM postmenopausal women should be further investigated.

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