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1.
The TUDID Study - Background and Design of a Prospective Cohort.
Jaghutriz, BA, Wagner, R, Kullmann, S, Fritsche, L, Eckstein, SS, Dannecker, C, Willmann, C, Randrianarisoa, E, Lehn-Stefan, A, Hieronimus, A, et al
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2022;(1):43-48
Abstract
Prevalence of both type 1 and type 2 diabetes mellitus is growing worldwide and one major cause for morbidity and mortality. However, not every patient develops diabetes-related complications, but causes for the individual susceptibility are still not fully understood. As a platform to address this, we initiated the TUDID (TUebingen DIabetes Database) study, a prospective, monocentric, observational study that includes adults with diabetes mellitus who are treated in the inpatient clinic of a University Hospital in southern Germany. Besides a thorough clinical examination and extensive laboratory tests (with integrated biobanking), major study focuses are the kidneys, the eyes, the vasculature as well as cognition and mood where standardized investigations for early stages for diabetes complications are performed. Analyses of the data generated by this precise characterization of diabetes-related complications will contribute to our understanding of the development and course of such complications, and thus facilitate the implementation of tailored treatment options that can reduce the risk and severity of diabetes-related complications.
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2.
The signaling pathways of traditional Chinese medicine in promoting diabetic wound healing.
Zhou, X, Guo, Y, Yang, K, Liu, P, Wang, J
Journal of ethnopharmacology. 2022;:114662
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The diabetic wound is one of the common chronic complications of diabetes, which seriously affects patients' quality of life and even causes disability and death. Traditional Chinese medicine (TCM) is a unique and precious resource in China, which has a good curative effect and safety. At present, it has been found that Chinese herbal compounds and effective active ingredients can effectively promote diabetic wound healing, and its mechanism needs to be further studied. Signaling pathways are involved in the pathogenesis and progression of diabetic wounds, which is one of the main targets for the pathologic mechanism of diabetic wounds and the pharmacological research of therapeutic drugs. AIM OF THE REVIEW This study has been carried out to reveal the classical signaling pathways and potential targets by the action of TCM on diabetic wound healing and provides evidence for its clinical efficacy. MATERIALS AND METHODS "diabetic wound", "diabetic foot ulcer", "traditional Chinese medicine", "natural plant" and "medicinal plant", were selected as the main keywords, and various online search engines, such as PubMed, Web of Science, CNKI and other publication resources, were used for searching literature. RESULTS The results showed that TCM could regulate the signaling pathways to promote diabetic wound healing, such as Wnt, Nrf2/ARE, MAPK, PI3K/Akt, NF-κB, Notch, TGF-β/Smad, HIF-1α/VEGF, which maintaining inflammatory interaction balance, inhibiting oxidative stress and regulating abnormal glucose metabolism. CONCLUSION The effect of TCM on diabetic wound healing was reflected in multiple levels and multiple pathways. It is envisaged to carry out further research from precision-targeted therapy, provide ideas for screening the core target of TCM in treating diabetic wounds and create modern innovative drugs based on this target.
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3.
The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials.
Jeffrey, S, Samraj, PI, Raj, BS
Current diabetes reviews. 2021;(9):e011821190404
Abstract
Alpha-lipoic acid (ALA) is a substantial antioxidant in the prevention of diabetes and diabetes complications. It can regenerate other antioxidants like vitamin E, vitamin C, Coenzyme Q10 and glutathione and is often known as a universal antioxidant. Antioxidants play a role in diabetes treatment due to hyperglycemia-induced stimulation of the polyol pathway and formation of advanced glycation end products (AGE) and reactive oxygen species (ROS). Clinical trials examining alpha-lipoic acid supplementation on diabetic neuropathy, nephropathy, cardiomyopathy and erectile dysfunction display positive results, particularly in pain amelioration in neuropathy, asymmetric dimethylarginine reductions in nephropathy and improved oscillatory potential and contrast sensitivity in retinopathy. In diabetic cardiomyopathy (DCM), ALA offers protection through inhibition of NF-kB activation, reduction of fas-ligand and decrease in matrix metalloproteinase-2. This comprehensive review summarises and provides an understanding of the importance of alpha- lipoic acid supplementation to prevent diabetes complications.
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4.
Prediction of microalbuminuria from proteinuria in chronic kidney disease due to non-diabetic lifestyle-related diseases: comparison with diabetes.
Ogi, M, Seto, T, Wakabayashi, Y
Clinical and experimental nephrology. 2021;(7):727-750
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Abstract
BACKGROUND To suppress increases in kidney failure and cardiovascular disease due to lifestyle-related diseases other than diabetes, early intervention is desirable. We examined whether microalbuminuria could be predicted from proteinuria. METHODS The participants consisted of adults who exhibited a urinary protein-to-creatinine ratio (uPCR) of < 0.5 g/gCr and an eGFR of ≥ 15 ml/min/1.73 m2 in their spot urine at their first examination for lifestyle-related disease. Urine was tested three times for each case, with microalbuminuria defined as a urinary albumin-to-creatinine ratio (uACR) of 30-299 mg/gCr, at least twice on three measurements. Youden's Index was used as an index of the cut-off value (CO) according to the ROC curve. RESULTS A single uPCR was useful for differentiating normoalbuminuria and micro- and macroalbuminuria in patients with non-diabetic lifestyle-related diseases. Regarding the GFR categories, the CO of the second uPCR was 0.09 g/gCr (AUC 0.89, sensitivity 0.76, specificity 0.89) in G1-4 (n = 197) and 0.07 g/gCr (AUC 0.92, sensitivity 0.85, specificity 0.88) in G1-3a (n = 125). Using the sum of two or three uPCR measurements was more useful than a single uPCR for differentiating microalbuminuria in non-diabetic lifestyle disease [CO, 0.16 g/gCr (AUC 0.91, sensitivity 0.85, specificity 0.87) and 0.23 g/gCr (AUC 0.92, sensitivity 0.88, specificity 0.84), respectively]. CONCLUSION Microalbuminuria in Japanese individuals with non-diabetic lifestyle-related diseases can be predicted from the uPCR, wherein the CO of the uPCR that differentiates normoalbuminuria and micro- and macroalbuminuria was 0.07 g/gCr for G1-3a, while that in G3b-4 was 0.09 g/gCr.
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Sex Disparities in Cardiovascular Risk Factor Assessment and Screening for Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review.
de Jong, M, Peters, SAE, de Ritter, R, van der Kallen, CJH, Sep, SJS, Woodward, M, Stehouwer, CDA, Bots, ML, Vos, RC
Frontiers in endocrinology. 2021;:617902
Abstract
BACKGROUND Insight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications. METHODS PubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias. RESULTS Overall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams. CONCLUSION Overall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes.
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Sodium-glucose co-transporter 2 inhibitors: game changers when handled with care?
Htet, ZM, Karim, M
Journal of the Royal Society of Medicine. 2021;(7):351-358
Abstract
Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.
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COVID-19's toll on the elderly and those with diabetes mellitus - Is vitamin B12 deficiency an accomplice?
Wee, AKH
Medical hypotheses. 2021;:110374
Abstract
COVID-19 exacts a disproportionate toll on both the elderly and those with diabetes; these patients are more likely to require costly intensive care, longer hospitalisation, and die from complications. Nations would thus find it extremely difficult to either lift or sustain socially, economically, and politically damaging restrictions that keep this group of people safe. Without a vaccine, there is thus an urgent need to identify potential modifiable risk factors which can help manage overall fatality or recovery rates. Case fatality rates are highly variable between (and even within) nations; nutritional differences have been proposed to account significantly for this disparity. Indeed, vitamin B12 deficiency is a common denominator between the elderly and those with diabetes. The question on hand thus lies on whether managing B12 deficiencies will impact COVID-19 fatality outcome or recovery rates. Herein, we review the latest evidence that shows that B12 deficiency associates in multiple areas very similar to where COVID-19 exerts its damaging effects: immunologically; microbiologically; haematologically; and through endothelial cell signalling-supporting the hypothesis that B12 deficiency is a potential modifiable risk factor in our fight against COVID-19.
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Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial.
Carlin, JL, Lieberman, VR, Dahal, A, Keefe, MS, Xiao, C, Birznieks, G, Abell, TL, Lembo, A, Parkman, HP, Polymeropoulos, MH
Gastroenterology. 2021;(1):76-87.e4
Abstract
BACKGROUND & AIMS Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis. METHODS We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018. Participants were randomly assigned to groups given oral tradipitant 85 mg (n = 77) or placebo (n = 75) twice daily for 4 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. The primary outcome from the intent-to-treat analysis was change from baseline to week 4 in average nausea severity, measured by the Gastroparesis Core Symptom Daily Diary. RESULTS Patients receiving tradipitant had a significant decrease in nausea score (reduction of 1.2) at week 4 compared with placebo (reduction of 0.7) (P = .0099) and a significant increase in of nausea-free days at week 4 (28.8% increase on tradipitant vs 15.0% on placebo; P = .0160). Patients with nausea and vomiting at baseline (n = 101) had an even greater decrease in nausea in when given tradipitant (reduction of 1.4) compared with those given placebo (reduction of 0.4) (P < .0001), as well as an increase in nausea-free days at week 4 (32.3% improvement on tradipitant vs 7.6% on placebo; P = .0003). The average nausea score was 1 or less at week 4 in 32.9% of patients given tradipitant compared with 11.8% of patients given placebo (P = .0013). A greater than 1-point improvement in Gastroparesis Cardinal Symptom Index score was observed in 46.6% of patients given tradipitant compared with 23.5% of patients given placebo (P = .0053). CONCLUSIONS Tradipitant resulted in statistically and clinically meaningful improvements in nausea and reduced vomiting, compared with placebo, in patients with idiopathic or diabetic gastroparesis. ClinicalTrials.gov, Number: NCT02970968.
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Diabetes and acute bacterial skin and skin structure infections.
Falcone, M, Meier, JJ, Marini, MG, Caccialanza, R, Aguado, JM, Del Prato, S, Menichetti, F
Diabetes research and clinical practice. 2021;:108732
Abstract
Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical needs in this area. Pathogenetic mechanisms underlying the increased risk of ABSSSIs in diabetes mellitus are multifactorial: high glucose levels play a crucial pathogenetic role in the tissue damage and delayed clinical cure. Moreover, the presence of diabetes complications (neuropathy, vasculopathy) further complicates the management of ABSSSIs in patients with diabetes. Multidrug resistance organisms should be considered in this population based on patient risk factors and local epidemiology and etiological diagnosis should be obtained whenever possible. Moreover, drug-drug interactions and drug-related adverse events (such as nephrotoxicity) should be considered in the choice of antibiotic therapy. Reducing unnecessary hospitalizations and prolonged length of hospital stay is of primary importance now, more than ever. To achieve these objectives, a better knowledge of the interplay between acute and chronic hyperglycemia, multidrug resistant etiology, and short and long-term outcome is needed. Of importance, a multidisciplinary approach is crucial to achieve full recovery of these patients.
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Systematic review of diabetic eye disease practice guidelines: more applicability, transparency and development rigor are needed.
Gyawali, R, Toomey, M, Stapleton, F, Zangerl, B, Dillon, L, Ho, KC, Keay, L, Alkhawajah, SMM, Liew, G, Jalbert, I
Journal of clinical epidemiology. 2021;:56-68
Abstract
OBJECTIVES To assess the quality of diabetic eye disease clinical practice guidelines. STUDY DESIGN AND SETTING A systematic search of diabetic eye disease guidelines was conducted on six online databases and guideline repositories. Four reviewers independently rated quality using the Appraisal of Guidelines, Research, and Evaluation (AGREE II) instrument. Aggregate scores (%) for six domains and overall quality assessment were calculated. A "good quality" guideline was one with ≥60% score for "rigor of development" and in at least two other domains. RESULTS Eighteen guidelines met the inclusion criteria, of which 13 were evidence-based guidelines (involved systematic search and grading of evidence). The median scores (interquartile range (IQR)) for "scope and purpose," "stakeholder involvement," "rigor of development," "clarity of presentation," "applicability" and "editorial independence" were 73.6% (54.2%-80.6%), 48.6% (29.2%-71.5%), 60.2% (30.9%-78.1%), 86.6% (76.7%-94.4%), 28.6% (18.0%-37.8%) and 60.2% (30.9%-78.1%), respectively. The median overall score (out of 7) of all guidelines was 5.1 (IQR: 3.7-5.8). Evidence-based guidelines scored significantly higher compared to expert-consensus guidelines. Half (n = 9) of the guidelines (all evidence-based) were of "good quality." CONCLUSION A wide variation in methodological quality exists among diabetic eyecare guidelines, with nine demonstrating "good quality." Future iterations of guidelines could improve by appropriately engaging stakeholders, following a rigorous development process, including support for application in clinical practice and ensuring editorial transparency.