scholarly journals The ACAA-insertion/deletion polymorphism at the 3′ UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance

2006 ◽  
Vol 155 (2) ◽  
pp. 331-336 ◽  
Author(s):  
Gemma Villuendas ◽  
José I Botella-Carretero ◽  
Abel López-Bermejo ◽  
Carme Gubern ◽  
Wifredo Ricart ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mexican Americans ◽  
Receptor Gene ◽  
Diabetic Patients ◽  
Surrogate Markers ◽  
Wild Type ◽  
Deletion Polymorphism ◽  
Insulin Resistant

Objective: The IGF-II receptor gene (IGFIIR) is located at chromosome 6q26, a region that harbors a genetic marker linked to insulin-resistant traits in Mexican–Americans. In the present study conducted in Spaniards, we tested a common polymorphism in IGFIIR for association with type 2 diabetes and insulin-resistant traits. Design: Case–control association study. Methods: One hundred and forty-five type 2 diabetic patients and 217 non-diabetic controls were genotyped for the ACAA-insertion/deletion polymorphism at the 3′ UTR of IGFIIR. Phenotyping included anthropometrics and a metabolic profile, including serum lipid levels and surrogate indexes of insulin resistance whenever possible. Results: Diabetic patients were more frequently homozygous for the wild type 144 bp allele of IGFIIR compared with controls (diabetic patients 77.2%, controls 51.6%, P<0.001) suggesting a potential protective role against type 2 diabetes for the IGFIIR 140 bp variant. Carrying 140 bp alleles was associated with an odds ratio of having diabetes of 0.290 (95% confidence interval 0.109–0.770), and controls homozygous for the wild type 144 bp allele presented with lower insulin and triglyceride levels, which are proxies for insulin resistance. Conclusions: The ACAA-insertion/deletion polymorphism at the 3′ UTR of IGFIIR is associated with type 2 diabetes and influences surrogate markers of insulin resistance in non-diabetic subjects.

Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes

2014 ◽  
Vol 307 (9) ◽  
pp. C774-C787 ◽  
Author(s):  
Lubna Al-Khalili ◽  
Thais de Castro Barbosa ◽  
Jörgen Östling ◽  
Julie Massart ◽  
Pablo Garrido Cuesta ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Proteome Analysis ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.

scholarly journals Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Michael Albosta ◽  
Jesse Bakke
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Treatment Option ◽  
Primary Care Physicians ◽  
Case Series ◽  
Current Evidence ◽  
Intermittent Fasting ◽  
Diabetic Patients ◽  
Medicinal Treatment

Abstract Background Type 2 Diabetes is a metabolic disorder characterized by hyperglycemia that causes numerous complications with significant long-term morbidity and mortality. The disorder is primarily due to insulin resistance particularly in liver, skeletal muscle, and adipose tissue. In this review, we detail the hormonal mechanisms leading to the development of diabetes and discuss whether intermittent fasting should be considered as an alternative, non-medicinal treatment option for patients with this disorder. Methods We searched PubMed, Ovid MEDLINE, and Google Scholar databases for review articles, clinical trials, and case series related to type 2 diabetes, insulin resistance, and intermittent fasting. Articles were carefully reviewed and included based on relevance to our topic. We excluded abstracts and any non-English articles. Results The majority of the available research demonstrates that intermittent fasting is effective at reducing body weight, decreasing fasting glucose, decreasing fasting insulin, reducing insulin resistance, decreasing levels of leptin, and increasing levels of adiponectin. Some studies found that patients were able to reverse their need for insulin therapy during therapeutic intermittent fasting protocols with supervision by their physician. Conclusion Current evidence suggests that intermittent fasting is an effective non-medicinal treatment option for type 2 diabetes. More research is needed to delineate the effects of intermittent fasting from weight loss. Physicians should consider educating themselves regarding the benefits of intermittent fasting. Diabetic patients should consult their physician prior to beginning an intermittent fasting regimen in order to allow for appropriate oversight and titration of the patients medication regimen during periods of fasting.

scholarly journals FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 601.2-602
Author(s):  
J. Avouac ◽  
M. Elhai ◽  
M. Forien ◽  
J. Sellam ◽  
F. Eymard ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Requirement ◽  
Multivariate Logistic Regression ◽  
Biological Profile ◽  
Research Support ◽  
Insulin Resistant ◽  
Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

Mutation of the 5' untranslated region stem-loop mRNA structure reduces type I collagen deposition and arterial stiffness in male obese mice

2021 ◽  
Author(s):  
Francisco I. Ramirez-Perez ◽  
Makenzie L. Woodford ◽  
Mariana Morales-Quinones ◽  
Zachary I. Grunewald ◽  
Francisco J Cabral-Amador ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Arterial Stiffness ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Wild Type ◽  
Stem Loop ◽  
Arterial Stiffening

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden. A major contributor to arterial stiffening is increased collagen deposition. In the 5' untranslated regions of mRNAs encoding for type I collagen, an evolutionally conserved stem-loop (SL) structure plays an essential role in its stability and post-transcriptional regulation. Here, we show that feeding a high fat/high sucrose (HFHS) diet for 28 weeks increases adiposity, insulin resistance, and blood pressure in male wild-type littermates. Moreover, arterial stiffness, assessed in vivo via aortic pulse wave velocity, and ex vivo using atomic force microscopy in aortic explants or pressure myography in isolated femoral and mesenteric arteries, was also increased in those mice. Notably, all these indices of arterial stiffness, along with collagen type I levels in the vasculature, were reduced in HFHS-fed mice harboring a mutation in the 5'SL structure, relative to wild-type littermates. This protective vascular phenotype in 5'SL-mutant mice did not associate with a reduction in insulin resistance or blood pressure. These findings implicate the 5'SL structure as a putative therapeutic target to prevent or reverse arterial stiffening and CVD associated with obesity and type 2 diabetes.

Cardiovascular events in patients with type 2 diabetes

2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S4-S8
Author(s):  
Erland Erdmann
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Adverse Effects ◽  
Cardiovascular Events ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Increased Risk

Diabetes is a common risk factor for cardiovascular disease. Coronary heart disease and left ventricular dysfunction are more common in diabetic patients than in non-diabetic patients, and diabetic patients benefit less from revascularisation procedures. This increased risk can only partly be explained by the adverse effects of diabetes on established risk factors; hence, a substantial part of the excess risk must be attributable to direct effects of hyperglycaemia and diabetes. In type 2 diabetes, hyperinsulinaemia, insulin resistance and hyperglycaemia have a number of potential adverse effects, including effects on endothelial function and coagulation. Risk factor modification has been shown to reduce the occurrence of cardiovascular events in patients with diabetes; indeed, diabetic patients appear to benefit more in absolute terms than non-diabetic patients. There is thus a strong case for intensive treatment of risk factors, including insulin resistance and hyperglycaemia, in patients with type 2 diabetes.

scholarly journals The Correlation between Vitamin D and Clinical Implications for Obesity-Related Type 2 Diabetes Mellitus

2020 ◽  
Vol 14 (1) ◽  
pp. 39-45
Author(s):  
Noor Thair Tahir ◽  
Hind SH. Ahmed ◽  
Rasha K. Hashim ◽  
Teba D. Soluiman
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Lipoprotein Cholesterol ◽  
Diabetic Patients ◽  
Clinical Implications ◽  
Vitamin D Levels

Background: Obesity and type 2 diabetes have both rapidly raised during the last periods and are ongoing to increase at a disturbing rate universal. Several clinical and epidemiological researches demonstrated a reverse association between circulating vitamin D levels, central adiposity and the progress of insulin resistance and diabetes. Objective: The target of this work was to elucidate the complex role of vitamin D and the clinical implications of diabetes on metabolic defects related with obesity. Subjects and Methods: This study encompassed 90 diabetic patients (45 obese and 45 non obese) who were attending the National Diabetic Center/ Al-Mustansiriyah University during the period from June 2019 to January 2020; their age range was (35-60) years. All participant underwent clinical and biochemical examinations. Results: A substantial rise (p= 0.01) in waist/hip ratio, body mass index, fasting serum glucose, total cholesterol, triacylglycerol, and low density lipoprotein cholesterol in obese diabetic patients as paralleled to non-obese group. Moreover, there was an elevation in glycated hemoglobin, serum insulin, and homeostasis model assessment for insulin resistance in obese group, but it was not significant. A substantial decrease (p= 0.01) in serum high density lipoprotein cholesterol and vitamin D3 were detected in obese diabetic patients as paralleled to non-obese group.       Also, obese diabetic patients had the higher percent (61%) of D3 deficiency as paralleled to non-obese patients. Conclusions: In the present study, it is found that there is significant increase in blood sugar in the individuals with decreased vitamin D levels, which was related with insulin resistance, decreased β-cell function, and obesity.  

scholarly journals Association of insulin resistance and leptin receptor gene polymorphism in type 2 diabetes mellitus

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Usha Adiga ◽  
Nandit Banawalikar ◽  
Sriprajna Mayur ◽  
Radhika Bansal ◽  
Nafeesath Ameera ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Receptor Gene Polymorphism

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.

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