Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes

2014 ◽  
Vol 116 (8) ◽  
pp. 998-1005 ◽  
Author(s):  
Bart B. L. Groen ◽  
Henrike M. Hamer ◽  
Tim Snijders ◽  
Janneau van Kranenburg ◽  
Dionne Frijns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fiber Type ◽  
Capillary Density ◽  
Boundary Region ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.

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.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.

scholarly journals Impact of a Booklet about Diabetes Genetic Susceptibility and Its Prevention on Attitudes towards Prevention and Perceived Behavioral Change in Patients with Type 2 Diabetes and Their Offspring

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Masakazu Nishigaki ◽  
Eiko Sato ◽  
Ryota Ochiai ◽  
Taiga Shibayama ◽  
Keiko Kazuma
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Susceptibility ◽  
Behavioral Change ◽  
Behavioral Changes ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
The Patient’S View ◽  
Self Administered Questionnaire ◽  
Type 2 Diabetic

Background. Offspring of type 2 diabetic patients are at a high risk of type 2 diabetes. Information on diabetes genetic susceptibility and prevention should be supplied to the offspring.Methods. A six-page booklet on diabetes genetic susceptibility and prevention was distributed to 173 patients who ere ordered to hand it to their offspring. The patients answered a self-administered questionnaire on booklet delivery and attitudinal and behavioral changes toward diabetes and its prevention in themselves and their offspring.Results. Valid responses were obtained from 130 patients. Forty-nine patients had actually handed the booklet. Booklet induces more relief than anxiety. From the patient's view, favorable attitudinal and/or behavioral changes occurred in more than half of the offspring who were delivered the booklet.Conclusion. The booklet worked effectively on attitudes and behaviors toward diabetes and its prevention both in patients and their offspring. However, the effectiveness of patients as information deliverers was limited.

Awareness of Complications in Diabetic Patients - Study in a Tertiary Care Centre in Kerala

2021 ◽  
Vol 8 (37) ◽  
pp. 3334-3338
Author(s):  
Satish Kumar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Tertiary Care ◽  
Diabetic Patients ◽  
Tertiary Care Centre ◽  
Type 2 Diabetic Patients ◽  
Complications Of Diabetes ◽  
Type 2 Diabetic

BACKGROUND Type 2 diabetes mellitus is common in the Indian population and awareness regarding the disease and its complications is low among the patients with diabetes. There is lack of studies regarding awareness of complications of diabetes among type 2 diabetic patients. The purpose of this study was to assess the awareness of diabetic complications among type 2 diabetic patients. METHODS This is an institutional based observational study. The sample comprised of 150 adult patients with type 2 diabetes mellitus who underwent treatment in the Department of Medicine, Medical College Kottayam and the patient’s age ranged from 18 - 77 years. RESULTS Majority of patients were in the age group 38 to 57 and the sample comprised of 56 % males and 44 % female patients. Out of 150 patients involved in the study, 120 patients (80 %) were aware of the complications of diabetes mellitus. Among the male patients, 70 (83.33 %) and among females, 50 (75.75 %) were aware of the complications in diabetes. In the study sample, 92 (61.33 %) were aware of the foot problems, 120 patients (80 %) were aware of renal complications, 91 patients were aware regarding eye problems of diabetes, 38 (25.33 %) regarding development of hypertension, 62 (41.33 %) regarding heart attack, 42 (28 %) patients were aware regarding development of stroke and 78 patients (52 %) had awareness regarding occurrence of recurrent infections. CONCLUSIONS Awareness regarding diabetes and its complications is fairly good among the diabetic patients in Kerala. Awareness regarding all complications of diabetes was higher among males than females. Providing awareness to type 2 diabetic patients by various educational programs may be of further help to prevent complications and to decrease the mortality and morbidity in type 2 diabetes patients. KEYWORDS Awareness, Diabetes

scholarly journals Increased Urine IgM and IgG2Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ole Torffvit ◽  
Majid Kalani ◽  
Jan Apelqvist ◽  
Björn Eliasson ◽  
Jan W. Eriksson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Physiological Saline ◽  
Diabetic Patients ◽  
Size Selectivity ◽  
Type 2 Diabetic Patients ◽  
Once Daily ◽  
Urinary Levels ◽  
Glomerular Size ◽  
Type 2 Diabetic

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n=28), or physiological saline, (n=26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P<0.001) and serum IGFBP-1 (P<0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy.

scholarly journals A study of prevalence of microalbuminuria in recently detected type 2 diabetes and its relation to hypertension, dyslipidaemia and obesity

2020 ◽  
Vol 11 (5) ◽  
pp. 38-43
Author(s):  
Shrikrishna V Acharya
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Screening Tool ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Group 2 ◽  
Type 2 Diabetic ◽  
Group 1 ◽  
New Onset

Background: Microalbuminuria is one of the earliest markers of diabetic nephropathy, and if not recognized and treated early it may lead to diabetic nephropathy resulting in chronic renal failure. Aims and Objective: The aim of the current study was to find out the prevalence of microalbuminuria among newly detected Type 2 diabetic patients and also compare prevalence of microalbuminuria in patients with or without hypertension, dyslipidaemia and obesity. Materials and Methods: In this retrospective study, we analysed 90 patients with new onset type 2 diabetes mellitus. We divided the patients into two groups, group 1 with comorbidities like hypertension, dyslipidaemia and obesity (50 patients) and group 2 without comorbidities (40 patients). We analysed urinary microalbumin level in all patients and compared the prevalence of microalbuminuria between group 1 and group 2. Results: In our cohort of 90 patients, urinary microalbuminuria was found in 30 patients (33.3%). When we divided these nephropathy patients to group1 and group 2, we observed that group 1 with comorbidities had higher percentage of nephropathy patients i.e 24 out of 50(48%). Group 2 with 40 patients had only 6 patients with microalbiminuria ie 6 out of 40(15%). Incidence of microalbiminuria was higher in patients with hypertension, dyslipidaemia and obesity. Conclusions: We conclude that incidence of microalbiminuria is much more common in newly diagnosed type 2 diabetes. We also conclude that hypertension, obesity and hypercholesterolemia are risk factors for nephropathy and urinary microalbuminuria appears to be much more sensitive than serum creatinine as screening tool to detect diabetic nephropathy.

scholarly journals Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3405 ◽  
Author(s):  
Lubin Xu ◽  
Yang Li ◽  
Jiaxin Lang ◽  
Peng Xia ◽  
Xinyu Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Type 2 Diabetic Patients ◽  
Sglt2 Inhibition ◽  
Type 2 Diabetic

Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]). Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

2021 ◽  
Vol 8 ◽  
Author(s):  
Dan Xu ◽  
Owain Chandler ◽  
Cleo Wee ◽  
Chau Ho ◽  
Jacquita S. Affandi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Diabetic Patients ◽  
Atherosclerotic Cardiovascular Disease ◽  
Healthy Individuals ◽  
Type 2 Diabetic Patients ◽  
Sodium Glucose Cotransporter ◽  
Type 2 Diabetic

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

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