scholarly journals Modulation of miR-29a and ADAM12 Reduces Post-Ischemic Skeletal Muscle Injury and Improves Perfusion Recovery and Skeletal Muscle Function in a Mouse Model of Type 2 Diabetes and Peripheral Artery Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 429
Author(s):  
Victor Lamin ◽  
Joseph Verry ◽  
Isaac Eigner-Bybee ◽  
Jordan D. Fuqua ◽  
Thomas Wong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Function ◽  
Muscle Injury ◽  
Genetic Modifier ◽  
Limb Amputation ◽  
Skeletal Muscle Injury ◽  
Increased Risk

Both Type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) are associated with an increased risk of limb amputation in peripheral arterial disease (PAD). How diabetes contributes to poor PAD outcomes is poorly understood but may occur through different mechanisms in DM1 and DM2. Previously, we identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery. In an experimental PAD, we showed that ADAM12 is regulated by miR-29a and this regulation is impaired in ischemic endothelial cells in DM1, contributing to poor perfusion recovery. Here we investigated whether miR-29a regulation of ADAM12 is altered in experimental PAD in the setting of DM2. We also explored whether modulation of miR-29a and ADAM12 expression can improve perfusion recovery and limb function in mice with DM2. Our result showed that in the ischemic limb of mice with DM2, miR-29a expression is poorly downregulated and ADAM12 upregulation is impaired. Inhibition of miR-29a and overexpression of ADAM12 improved perfusion recovery, reduced skeletal muscle injury, improved muscle function, and increased cleaved Tie 2 and AKT phosphorylation. Thus, inhibition of miR-29a and or augmentation of ADAM12 improves experimental PAD outcomes in DM2 likely through modulation of Tie 2 and AKT signalling.

scholarly journals In a Mouse Model of Type 2 Diabetes and Peripheral Artery Disease, Modulation of MirR29a and ADAM12 Reduced Post -Ischemic Skeletal Muscle Injury, Improved Perfusion Recovery and Skeletal Muscle Function

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A289-A290
Author(s):  
Victor Lamin ◽  
Thomas Wong ◽  
Aya Babikir ◽  
Joseph Verry ◽  
Isaac Eigner-Bybee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Function ◽  
Muscle Injury ◽  
Hind Limb ◽  
Diabetic Mice ◽  
Skeletal Muscle Function ◽  
Skeletal Muscle Injury ◽  
Hind Limbs

Abstract Diabetes Mellitus (DM) is a major risk factor for developing peripheral arterial disease (PAD) and individuals with DM have worse PAD outcomes but the molecular mechanisms involved are poorly understood. Previously, in a hind limb ischemia (HLI) model of PAD, we identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery. Moreover, we showed that expression of ADAM12 in mouse and human tissue is regulated by miR29a. In non-diabetic mice, miR29a expression is downregulated after HLI that allows increased expression of ADAM12. However, upon HLI in high fat diet feed (HFD) mice, a model of type 2 diabetes, miR29a expression remains elevated that prevents ADAM12 increase and results in poor reperfusion recovery, increased skeletal muscle injury and decreased muscle function. Hence, we hypothesized that inhibition of miR29a or augmenting ADAM12 would improve these functional outcomes. Mice (male, 26–28 weeks old) were randomized into 3 treatment groups and their hind limbs were treated with saline (grp1), ADAM12 cDNA (grp 2) or mir29a-inhibitor (grp3), through targeted micro-bubble delivery. Mice were treated at -3 days and -1 pre-surgery, followed by post-surgery weekly boosting. HLI was achieved by unilateral ligation and excision of the femoral artery of the left hind limb. The right hind limb served as non-ischemic control. Gene expression analysis in the hind limbs 3 days post HLI showed decreased miR29a expression in normal chow fed B6, but elevated miR29a expression in HFD (B6 vs HFD; 0.5730±0.01 vs.1.02 ± 0.06, n=3–4, p= 0.001). Treatment with miR29a inhibitor decreased miR29a expression in HFD and increased ADAM12 expression compared to control untreated HFD mice (miR29a INH vs Control HFD: 0.70±0.06 vs 1.02±0.06, n= 4–5, p= 0.004) ADAM12 expression (miR29A INH vs Control: HFD 208.62±24.52 vs 11.75±4.94, n= 3–4 P<0.01). Although ADAM12 cDNA improved ADAM12 expression, miR29a inhibition increased ADAM12 expression to a greater extent (HFD vs ADAM12 vs miR29aINH; 11.75±4.94 vs 20.71±2.98 vs 208.62±24.52, n3-4, p=< 0.001). Accordingly, miR29a inhibition and ADAM12 augmentation decreased skeletal muscle injury assessed by the number of centralized nuclei/muscle fibre (Control vs ADAM12 vs miR29aINH: 0.252±0.043, vs 0.139±0.041 vs 0.040±0.012 n=4, p= 0.05), and improved skeletal muscle function assessed as maximum muscle contraction (Control vs ADAM12 vs miR29aINH: 0.17±0.06 vs 0.26±0.06, vs 0.54±0.08, n=6–7, p<0.01). It also improved perfusion recovery, (% ischemic to non-ischemic limb, control vs ADAM12 vs miR29aINH: 42.52±5.35, vs 58.45±4.87, vs 97.59±6.14, n= 5–10, p<0.01). Thus, our results show augmentation of ADAM12 and Inhibition of MiR29a improves outcomes in experimental PAD in diabetic mice but inhibiting miR29a is a more effective strategy. 2414 characters now2500 characters allowed

scholarly journals Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Do Kyeong Song ◽  
Young Sun Hong ◽  
Yeon-Ah Sung ◽  
Hyejin Lee
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Serum Creatinine ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Increased Risk

Abstract Background Reduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. Methods We analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated. Results In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Conclusions Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

scholarly journals Association of Serum Creatinine Levels and Risk of Type 2 Diabetes Mellitus in Korea: A Case Control Study

2021 ◽  
Author(s):  
Do Kyeong Song ◽  
Young Sun Hong ◽  
Yeon-Ah Sung ◽  
Hyejin Lee
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Serum Creatinine ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Increased Risk

Abstract Background: Reduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea.Methods: We analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated.Results: In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose.Conclusions: Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Subsequent Development ◽  
Asian Population ◽  
Gstm1 Null Genotype ◽  
Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

Epidemiology of Hypertension and Diabetes Mellitus in Latin America

2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Latin America ◽  
Cardiovascular Diseases ◽  
Latin American ◽  
Premature Mortality ◽  
Increased Risk ◽  
And Control

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.

scholarly journals Risk of Depression among Early Onset Type 2 Diabetes Mellitus Patients

2021 ◽  
pp. 1-11
Author(s):  
Baizid Khoorshid Riaz ◽  
Shahjada Selim ◽  
Megan Neo ◽  
Md Nazmul Karim ◽  
M. Mostafa Zaman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Early Onset ◽  
Tertiary Care ◽  
Positive Family History ◽  
Depression Symptoms ◽  
Mixed Effect ◽  
Increased Risk

<b><i>Methodology:</i></b> Biochemically confirmed type 2 diabetes mellitus (T2DM) patients (<i>n</i> = 1,114) were recruited from the outpatient department of 2 tertiary care hospitals in Dhaka, Bangladesh. Face-to-face interview was conducted using a semi-structured questionnaire containing sociodemographic parameters and relevant information about depression and diabetes. Biochemical test results and treatment-related information were taken from patients’ records. The Hospital Anxiety and Depression Scale (HADS) was used to screen all patients for psychiatric manifestation. Those diagnosed by HADS were subsequently reassessed using structured clinical interview for DSM-5 Disorders – Clinician Version. T2DM diagnosed at age &#x3c;40 years were considered as early onset T2DM. Association between age of onset category and depression was assessed using multivariable mixed-effect logistic regression adjusting for random variation of the area of residence and plausible confounders. <b><i>Results:</i></b> Around a third of the participants (32.5%) were diagnosed with T2DM before the age of 40 years. Early onset T2DM patients were found to have 57% increase in the risk of developing depression (OR 1.57; 95% CI 1.13–2.28; <i>p</i> = 0.011) in comparison to those with usual onset T2DM (≥40 years). Among other factors a positive family history for diabetes (OR 1.33; 95% CI 1.03–1.78; <i>p</i> = 0.038), poor glycemic control (OR 1.31; 95% CI 1.03–1.68; <i>p</i> = 0.028), presence of 1, or more diabetic complications (OR 1.37; 95% CI 1.03–1.78; <i>p</i> = 0.011) also showed increased risk of depression. <b><i>Conclusion:</i></b> Early onset T2DM patients are at greater risk of developing depression. The finding is likely to help in setting preventive strategies aiming to reduce the presence of concomitant depression symptoms among diabetes.

scholarly journals Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Ahmadizar ◽  
K Wang ◽  
F Mattace Raso ◽  
MA Ikram ◽  
M Kavousi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Arterial Stiffness ◽  
Wall Stress ◽  
Lipid Lowering ◽  
Circumferential Wall Stress ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose.  Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.

scholarly journals Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

2021 ◽  
Vol 22 (12) ◽  
pp. 6444
Author(s):  
Anna Gabryanczyk ◽  
Sylwia Klimczak ◽  
Izabela Szymczak-Pajor ◽  
Agnieszka Śliwińska
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Cancer Risk ◽  
Vitamin D Deficiency ◽  
Cancer Development ◽  
Increased Risk

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

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