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Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: Relationship with NF-κB gene expression.
Dehghani, M, Aghaei Zarch, SM, Vahidi Mehrjardi, MY, Nazari, M, Babakhanzadeh, E, Ghadimi, H, Zeinali, F, Talebi, M
Endocrinologia, diabetes y nutricion. 2020;(7):454-460
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder whose prevalence is rising very fast across the world. Diagnosis of this disease in early stages (pre-diabetic stage) plays an important role in reducing mortality associated with this disorder. miRNAs, as key players in the pathogenesis of T2DM, have been investigated in several studies. Furthermore, their expression profile changes in the early stages of diabetes mellitus in body fluids such as serum, peripheral blood, and peripheral blood mononuclear cell (PBMC) have been studied. Due to their high stability and the presence of non-invasive sensitive methods for their measurement, such as real-time PCR, they can be used for early diagnosis of T2DM as a biomarker. In this experimental study, the expression levels of miR-181b, miR-126-5p, and NF-κB were measured in patients with T2DM, pre-diabetic subjects, and healthy controls in a Yazd population. MATERIAL AND METHOD Ninety asymptomatic subjects including 30 T2DM, 30 pre-diabetic, and 30 healthy subjects (diagnosis based on WHO criteria) were included in this study. Real-time PCR was used to measure the expression levels of miR-181b and miR-126-5p. Moreover, the NF-κB expression level was also measured to determine its relationship with these two microRNAs. RESULT In this study, the expression level of miR-181b and miR-126-p decreased gradually in pre-diabetic as well as T2DM subjects compared to healthy controls. Furthermore, our study showed a significant negative correlation between these two miRNAs and NF-κB for the first time. CONCLUSION These results introduce these anti-inflammatory miRNAs as powerful tools for early diagnosis of T2DM.
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2.
Diagnosis of Diabetes Mellitus in Older Adults.
Reddy, SSK
Clinics in geriatric medicine. 2020;(3):379-384
Abstract
In the United States, 4 out of 10 adults with diabetes are ≥65 years of age. The older adult with diabetes is very likely to be asymptomatic and also at higher risk of vascular disease. New concerns include new diagnosis of diabetes for older adults admitted to hospital and older adults in long-term care facilities. The pathophysiology for increased incidence of diabetes in older adults is multifactorial, but dominant features are increased likelihood of metabolic syndrome, dysfunctional insulin secretion, and peripheral insulin resistance. Society in general benefits from more cost-effective care of older adults with diabetes.
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Visceral Adiposity and Glucoregulatory Peptides are Associated with Susceptibility to Type 2 Diabetes: The TOFI_Asia Study.
Sequeira, IR, Yip, W, Lu, L, Jiang, Y, Murphy, R, Plank, L, Zhang, S, Liu, H, Chuang, CL, Vazhoor-Amarsingh, G, et al
Obesity (Silver Spring, Md.). 2020;(12):2368-2378
Abstract
OBJECTIVE Ethnic differences in fat deposition contribute to type 2 diabetes (T2D). Identification of biomarkers that underpin dysglycemia are needed for better-targeted prevention and treatment. METHODS The cross-sectional thin-on-the-outside-fat-on-the-inside (TOFI)_Asia study investigated adipose depots and clinical biomarkers as predictors of fasting plasma glucose (FPG) and insulin resistance (IR; assessed using the updated homeostatic model assessment of IR) in lean and overweight normo- and dysglycemic Chinese (n = 199) and Caucasian (n = 158) individuals. Multivariate least-angle regression models were used to identify predictors of FPG and IR. RESULTS At similar age and BMI, Chinese individuals had lower body weight but had a greater percentage of total abdominal adipose tissue and a greater percentage of total visceral adipose tissue (VAT) (all P < 0.005). In Chinese individuals, FPG, hemoglobin A1c , fasting insulin, and triglycerides were higher, whereas HDL cholesterol and total and high-molecular-weight adiponectin levels were lower (all P < 0.0001). Raised liver enzyme and peptide concentrations (P < 0.02) were consistent with increased T2D risk. Lean Chinese women (<25 kg/m2 ) had greater total abdominal adipose tissue (kilograms) and VAT (kilograms) than Caucasian women, exhibiting the TOFI profile, with raised FPG (P < 0.001) and IR (P = 0.01). Risk factors for elevated FPG specific to Chinese individuals included male gender, VAT, and triglycerides (R2 = 0.33), and risk factors for IR specific to Chinese individuals included amylin, C-peptide, and glucagon (R2 = 0.49). VAT, amylin, and C-peptide were predictors in Caucasian individuals. CONCLUSIONS VAT contributed to dysglycemia in both ethnicities, particularly in Chinese individuals characterized by the TOFI phenotype, as did the glucoregulatory peptides amylin and C-peptide, providing targets for T2D prevention.
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Comparison of the effect of Dietary Approaches to Stop Hypertension diet and American Diabetes Association nutrition guidelines on lipid profiles in patients with type 2 diabetes: A comparative clinical trial.
Hashemi, R, Mehdizadeh Khalifani, A, Rahimlou, M, Manafi, M
Nutrition & dietetics: the journal of the Dietitians Association of Australia. 2020;(2):204-211
Abstract
AIM: The present study aimed to compare the effects of the Dietary Approaches to Stop Hypertension (DASH) diet and American Diabetes Association (ADA) guidelines on the lipid profiles of patients with type 2 diabetes. METHODS In a 12-week clinical trial, 80 patients with type 2 diabetes aged 18-65 years were randomly allocated into the case (n = 40) and control (n = 40) groups. The case group received the DASH diet and the control group consumed a dietary pattern in accordance with the ADA guidelines. Fasting blood samples were measured for triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and free fatty acid (FFA). Moreover, physical activity and 24-hour dietary recall (24 hours) were assessed at baseline and end of the study. RESULTS The DASH diet and diabetic diet (in accordance with the ADA guidelines) for 12 weeks significantly decreased TG, TC and VLDL (P < 0.05). FFA showed a significant decrease in both the groups, which was greater in the cases compared with the control group (P = 0.049). CONCLUSIONS Compliance with any DASH or diabetic diet for 12 weeks in patients with type 2 diabetes had beneficial effects on cardiometabolic risks.
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CVOTs: What did the endocrinologist learn?
Valensi, P, Prévost, G
Diabetes research and clinical practice. 2020;:107947
Abstract
The recent CVOTs which tested the new glucose-lowering drugs (GLD) show that in patients with type 2 diabetes mellitus (T2DM) it is now possible to reduce cardiovascular complications including ischemic events and hospitalization for heart failure, and mortality, and, to some extent, microvascular complications of diabetes, in particular renal outcomes. Additionally CVOTs provide major informations on safety and metabolic effects for long-term use of these drugs. The benefits with GLP-1 RAs are most likely derived through the reduction of atherosclerosis-related events while SGLT-2is seem mostly to reduce heart failure-related events. Specific mechanisms independent from glucose control are involved. Based on CVOTs results it is time, as stated in the new EASD-ADA and ESC/EASD guidelines, to take into consideration such opportunities in the decision-making process when treating T2DM patients, favoring the use of drugs that have shown clear cardiovascular and renal benefits. The treatment decisions require more expertise in the evaluation of cardiovascular and renal risk which becomes a major determinant for the choice of GLD treatment, the target for lipids, the adjustment of anti-hypertensive treatments and the prescription of aspirin. In this context it is essential that endocrinologists-diabetologists communicate more with cardiologists and nephrologists and with the primary care practitioners.
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Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity.
Rutter, GA, Georgiadou, E, Martinez-Sanchez, A, Pullen, TJ
Diabetologia. 2020;(10):1990-1998
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Abstract
All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper understanding of the coupling mechanisms that link glucose metabolism in these cells to the control of insulin secretion is therefore likely to be essential to develop new therapies. Beta cells display a remarkable metabolic specialisation, expressing high levels of metabolic sensing enzymes, including the glucose transporter GLUT2 (encoded by SLC2A2) and glucokinase (encoded by GCK). Genetic evidence flowing from both monogenic forms of diabetes and genome-wide association studies for the more common type 2 diabetes, supports the importance for normal glucose-stimulated insulin secretion of metabolic signalling via altered ATP generation, while also highlighting unsuspected roles for Zn2+ storage, intracellular lipid transfer and other processes. Intriguingly, genes involved in non-oxidative metabolic fates of the sugar, such as those for lactate dehydrogenase (LDHA) and monocarboxylate transporter-1 ([MCT-1] SLC16A1), as well as the acyl-CoA thioesterase (ACOT7) and others, are selectively repressed ('disallowed') in beta cells. Furthermore, mutations in genes critical for mitochondrial oxidative metabolism, such as TRL-CAG1-7 encoding tRNALeu, are linked to maternally inherited forms of diabetes. Correspondingly, impaired Ca2+ uptake into mitochondria, or collapse of a normally interconnected mitochondrial network, are associated with defective insulin secretion. Here, we suggest that altered mitochondrial metabolism may also impair beta cell-beta cell communication. Thus, we argue that defective oxidative glucose metabolism is central to beta cell failure in diabetes, acting both at the level of single beta cells and potentially across the whole islet to impair insulin secretion. Graphical abstract.
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Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update).
Rayman, G, Vas, P, Dhatariya, K, Driver, V, Hartemann, A, Londahl, M, Piaggesi, A, Apelqvist, J, Attinger, C, Game, F, et al
Diabetes/metabolism research and reviews. 2020;:e3283
Abstract
The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. In conjunction with advice from internal and external reviewers and expert consultants in the field, this update is based on a systematic review of the literature centred on the following: the Population (P), Intervention (I), Comparator (C) and Outcomes (O) framework; the use of the SIGN guideline/Cochrane review system; and the 21 point scoring system advocated by IWGDF/EWMA. This has resulted in 13 recommendations. The recommendation on sharp debridement and the selection of dressings remain unchanged from the last recommendations published in 2016. The recommendation to consider negative pressure wound therapy in post-surgical wounds and the judicious use of hyperbaric oxygen therapy in certain non-healing ischaemic ulcers also remains unchanged. Recommendations against the use of growth factors, autologous platelet gels, bioengineered skin products, ozone, topical carbon dioxide, nitric oxide or interventions reporting improvement of ulcer healing through an alteration of the physical environment or through other systemic medical or nutritional means also remain. New recommendations include consideration of the use of sucrose-octasulfate impregnated dressings in difficult to heal neuro-ischaemic ulcers and consideration of the use of autologous combined leucocyte, platelet and fibrin patch in ulcers that are difficult to heal, in both cases when used in addition to best standard of care. A further new recommendation is the consideration of topical placental derived products when used in addition to best standard of care.
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Vascular effects of combined enriched Korean Red ginseng (Panax Ginseng) and American ginseng (Panax Quinquefolius) administration in individuals with hypertension and type 2 diabetes: A randomized controlled trial.
Jovanovski, E, Lea-Duvnjak-Smircic, , Komishon, A, Au-Yeung, F, Zurbau, A, Jenkins, AL, Sung, MK, Josse, R, Vuksan, V
Complementary therapies in medicine. 2020;:102338
Abstract
BACKGROUND Type 2 diabetes is known to abrogate the vascular response. Combination of two commonly consumed ginseng species, American ginseng (AG) and a Korean Red ginseng (KRG), enriched with ginsensoide Rg3, was shown to concomitantly improve glucemic control and blood pressure. We evaluated the hypothesis that improvements in central hemodynamics, vascular function and stiffness markers are involved in observed benefits of co-administration. METHODS In this randomized, placebo controlled, two-center trial, patients with type 2 diabetes and hypertension were assigned to either 2.25 g ginsenoside Rg3-enriched KRG&AG co-administration or a control 3 times daily for 12-weeks, treated by standard of care. The effects on central hemodynamics, pulse wave velocity (PWV) and endothelial function over the 12-week administration were analyzed. RESULTS In intent-to-treat analysis of 80 individuals, a reduction in central systolic BP (-4.69 ± 2.24 mmHg, p = 0.04) was observed with co-administration of Rg3-KRG + AG relative to control at 12-weeks, which was characterized by a decrease in end-systolic pressure (-6.60 ± 2.5 mmHg, p = 0.01) and area under the systolic/diastolic BP curve (-132.80 ± 65.1, p = 0.04, 220.90 ± 91.1, p = 0.02, respectively). There was no significant change in reactive hyperemia index (0.09 ± 0.11, p = 0.44), PWV (-0.40 ± 0.28 %, p = 0.17), and other related pulse wave analysis components. CONCLUSION Co-administration of complementary ginseng species improved central systolic BP and components of pulse waveform without a direct effect on endothelial function, when added to background pharmacotherapy in individuals with diabetes. These data support potential utility of ginseng for modest blood pressure benefit to broaden its role in diabetes management.
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Psychological interventions to improve self-management of type 1 and type 2 diabetes: a systematic review.
Winkley, K, Upsher, R, Stahl, D, Pollard, D, Kasera, A, Brennan, A, Heller, S, Ismail, K
Health technology assessment (Winchester, England). 2020;(28):1-232
Abstract
BACKGROUND For people with diabetes mellitus to achieve optimal glycaemic control, motivation to perform self-management is important. The research team wanted to determine whether or not psychological interventions are clinically effective and cost-effective in increasing self-management and improving glycaemic control. OBJECTIVES The first objective was to determine the clinical effectiveness of psychological interventions for people with type 1 diabetes mellitus and people with type 2 diabetes mellitus so that they have improved (1) glycated haemoglobin levels, (2) diabetes self-management and (3) quality of life, and fewer depressive symptoms. The second objective was to determine the cost-effectiveness of psychological interventions. DATA SOURCES The following databases were accessed (searches took place between 2003 and 2016): MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, PsycINFO, EMBASE, Cochrane Controlled Trials Register, Web of Science, and Dissertation Abstracts International. Diabetes conference abstracts, reference lists of included studies and Clinicaltrials.gov trial registry were also searched. REVIEW METHODS Systematic review, aggregate meta-analysis, network meta-analysis, individual patient data meta-analysis and cost-effectiveness modelling were all used. Risk of bias of randomised and non-randomised controlled trials was assessed using the Cochrane Handbook (Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928). DESIGN Systematic review, meta-analysis, cost-effectiveness analysis and patient and public consultation were all used. SETTING Settings in primary or secondary care were included. PARTICIPANTS Adolescents and children with type 1 diabetes mellitus and adults with types 1 and 2 diabetes mellitus were included. INTERVENTIONS The interventions used were psychological treatments, including and not restricted to cognitive-behavioural therapy, counselling, family therapy and psychotherapy. MAIN OUTCOME MEASURES Glycated haemoglobin levels, self-management behaviours, body mass index, blood pressure levels, depressive symptoms and quality of life were all used as outcome measures. RESULTS A total of 96 studies were included in the systematic review (n = 18,659 participants). In random-effects meta-analysis, data on glycated haemoglobin levels were available for seven studies conducted in adults with type 1 diabetes mellitus (n = 851 participants) that demonstrated a pooled mean difference of -0.13 (95% confidence interval -0.33 to 0.07), a non-significant decrease in favour of psychological treatment; 18 studies conducted in adolescents/children with type 1 diabetes mellitus (n = 2583 participants) that demonstrated a pooled mean difference of 0.00 (95% confidence interval -0.18 to 0.18), indicating no change; and 49 studies conducted in adults with type 2 diabetes mellitus (n = 12,009 participants) that demonstrated a pooled mean difference of -0.21 (95% confidence interval -0.31 to -0.10), equivalent to reduction in glycated haemoglobin levels of -0.33% or ≈3.5 mmol/mol. For type 2 diabetes mellitus, there was evidence that psychological interventions improved dietary behaviour and quality of life but not blood pressure, body mass index or depressive symptoms. The results of the network meta-analysis, which considers direct and indirect effects of multiple treatment comparisons, suggest that, for adults with type 1 diabetes mellitus (7 studies; 968 participants), attention control and cognitive-behavioural therapy are clinically effective and cognitive-behavioural therapy is cost-effective. For adults with type 2 diabetes mellitus (49 studies; 12,409 participants), cognitive-behavioural therapy and counselling are effective and cognitive-behavioural therapy is potentially cost-effective. The results of the individual patient data meta-analysis for adolescents/children with type 1 diabetes mellitus (9 studies; 1392 participants) suggest that there were main effects for age and diabetes duration. For adults with type 2 diabetes mellitus (19 studies; 3639 participants), baseline glycated haemoglobin levels moderated treatment outcome. LIMITATIONS Aggregate meta-analysis was limited to glycaemic control for type 1 diabetes mellitus. It was not possible to model cost-effectiveness for adolescents/children with type 1 diabetes mellitus and modelling for type 2 diabetes mellitus involved substantial uncertainty. The individual patient data meta-analysis included only 40-50% of studies. CONCLUSIONS This review suggests that psychological treatments offer minimal clinical benefit in improving glycated haemoglobin levels for adults with type 2 diabetes mellitus. However, there was no evidence of benefit compared with control interventions in improving glycated haemoglobin levels for people with type 1 diabetes mellitus. FUTURE WORK Future work should consider the competency of the interventionists delivering a therapy and psychological approaches that are matched to a person and their life course. STUDY REGISTRATION This study is registered as PROSPERO CRD42016033619. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 28. See the NIHR Journals Library website for further project information.
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Emerging science on benefits of whole grain oat and barley and their soluble dietary fibers for heart health, glycemic response, and gut microbiota.
Tosh, SM, Bordenave, N
Nutrition reviews. 2020;(Suppl 1):13-20
Abstract
The aim of this work is to review the major mechanisms by which consumption of whole grain oats and barley, and β-glucans, reduces the risk of coronary heart disease, type 2 diabetes, and other noncommunicable chronic conditions. These effects have been predominantly explained by the role of soluble dietary fibers and smaller bioactive compounds, such as phenolic compounds, in oats and barley. These help to reduce the level of serum low-density lipoprotein cholesterol, decreasing postprandial blood glucose and modulating gut microbiota. In the present review, the role of viscosity development of the intestinal content by β-glucans in these mechanisms is discussed, as well as the impact of processing conditions altering the composition or the physicochemical characteristics of β-glucans.