Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial.

Importance Diabetic foot ulcers are a common complication of diabetes and require specialized treatment. Cold atmospheric plasma (CAP) has been associated with benefits in wound infection and healing in previous smaller series of case reports. Yet the effect of CAP compared with standard care therapy in wound healing in diabetic foot ulcers remains to be studied. Objective To determine whether the application of CAP accelerates wound healing in diabetic foot ulcers compared with standard care therapy. Design, Setting, and Participants A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted at 2 clinics with recruitment from August 17, 2016, to April 20, 2019. Patients were scheduled to remain in follow-up until April 30, 2024. Patients with diabetes and diabetic foot ulcers described using the combined Wagner-Armstrong classification of 1B or 2B (superficial or infected diabetic foot ulcers extending to tendon) were eligible. A patient could participate with 1 or more wounds in both groups in both intervention and control groups. Wounds were randomized separately, allowing a participant to be treated several times within the study following a 2 × 2 × 2 randomization strata considering sex, smoking status, and age (≤68 years and >68 years). Interventions Standard care treatment with 8 applications of either CAP generated from argon gas in an atmospheric pressure plasma jet or 8 applications of placebo treatment in a patient-blinded manner. Main Outcomes and Measures Primary end points were reduction in wound size, clinical infection, and microbial load compared with treatment start. Secondary end points were time to relevant wound reduction (>10%), reduction of infection, parameters of patient’s well-being, and treatment-associated adverse events. Results Of 65 diabetic foot ulcer wounds from 45 patients assessed for study, 33 wounds from 29 patients were randomized to CAP and 32 wounds from 28 to placebo, with 62 wounds from 43 patients (31 wounds per group) included for final evaluation (mean [SD] age, 68.5 [9.1] years for full sample). Four patients with 5 wounds of 31 (16.1%) wounds in the CAP group and 3 patients with 4 wounds of 31 (13%) wounds in the placebo group were active smokers. CAP therapy yielded a significant increase in wound healing, both in total mean (SD) area reduction (CAP vs placebo relative units, −26.31 [11.72];P = .03) and mean (SD) time to relevant wound area reduction (CAP vs placebo relative units, 10% from baseline, 1.60 [0.58];P = .009). Reduction of infection and microbial load was not significantly different between CAP and placebo. No therapy-related adverse events occurred during therapy; patient’s perceptions during therapy were comparable. Conclusions and Relevance In this randomized clinical trial, CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection. Trial Registration ClinicalTrials.gov Identifier:NCT04205942

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Effect of Cold Atmospheric Plasma Therapy vs Standard Therapy Placebo on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial

Die Diabetesprävalenz liegt in der Altersgruppe ab 80 Jahren bei über 30 %. Bei der Diagnostik und Therapie älterer Menschen mit Typ-1- und Typ-2 Diabetes müssen altersspezifische Besonderheiten wie funktionelle und kognitive Einschränkungen sowie Komorbiditäten und Aspekte der Polypharmazie in besonderem Maße berücksichtigt werden. Die S2k-Leitlinie der Deutschen Diabetes Gesellschaft wurde mit 6 weiteren Fachgesellschaften (Deutsche Gesellschaft für Kardiologie, Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, Deutsche Gesellschaft für Geriatrie, Deutsche Gesellschaft für Ernährungsmedizin, Deutsche Gesellschaft für Pflegewissenschaft, Deutsche Gesellschaft für Palliativmedizin) und der Patientenvertretung (DBW) erarbeitet. Therapieziele wie Erhalt der Lebensqualität und strikte Vermeidung von Akutkomplikationen wie schwere Hypoglykämien treten in den Vordergrund. HbA1c-Ziele sollten gemeinsam mit den Patienten in Abhängigkeit der individuellen Wünsche und Fähigkeiten festgelegt werden. Altersspezifische Besonderheiten einzelner Medikamente müssen insbesondere im Kontext der Multimorbidität beachtet werden. In der Leitlinie werden pflegerische Aspekte, Schnittstellenmanagement, Schmerztherapie sowie häufige Komorbiditäten bei Diabetes wie Hypertonie, Frailty, Sarkopenie, Demenz, Depression, End-of-Life Situationen ausführlich dargestellt.

Diagnostik, Therapie und Verlaufskontrolle des Diabetes mellitus im Alter

Objective
The challenges posed by people living with multiple chronic conditions are unique for people with dementia and other significant cognitive impairment. There have been recent calls to action to review the existing literature on co-occurring chronic conditions and dementia in order to better understand the effect of cognitive impairment on disease management, mobility, and mortality.

Methods
This systematic literature review searched PubMed databases through 2011 (updated in 2016) using key constructs of older adults, moderate-to-severe cognitive impairment (both diagnosed and undiagnosed dementia), and chronic conditions. Reviewers assessed papers for eligibility and extracted key data from each included manuscript. An independent expert panel rated the strength and quality of evidence and prioritized gaps for future study.

Results
Four thousand thirty-three articles were identified, of which 147 met criteria for review. We found that moderate-to-severe cognitive impairment increased risks of mortality, was associated with prolonged institutional stays, and decreased function in persons with multiple chronic conditions. There was no relationship between significant cognitive impairment and use of cardiovascular or hypertensive medications for persons with these comorbidities. Prioritized areas for future research include hospitalizations, disease-specific outcomes, diabetes, chronic pain, cardiovascular disease, depression, falls, stroke, and multiple chronic conditions.

Conclusions
This review summarizes that living with significant cognitive impairment or dementia negatively impacts mortality, institutionalization, and functional outcomes for people living with multiple chronic conditions. Our findings suggest that chronic-disease management interventions will need to address co-occurring cognitive impairment. Copyright © 2017 John Wiley & Sons, Ltd.

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Dementia and co-occurring chronic conditions: a systematic literature review to identify what is known and where are the gaps in the evidence?

We aimed to evaluate the link between severe hypoglycaemia and domain-specific cognitive decline, smaller brain volumes and dementia in adults with type 2 diabetes, which so far has been relatively poorly characterised. We included participants with diagnosed diabetes from the community-based Atherosclerosis Risk in Communities (ARIC) study. At the participants’ fifth study visit (2011–2013), we examined the cross-sectional associations of severe hypoglycaemia with cognitive status, brain volumes and prior 15 year cognitive decline. We also conducted a prospective survival analysis of incident dementia from baseline, visit 4 (1996–1998), to 31 December 2013. Severe hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency department visits and ambulance records. Prior cognitive decline was defined as change in neuropsychological test scores from visit 4 (1996–1998) to visit 5 (2011–2013). At visit 5, a subset of participants underwent brain MRIs. Analyses were adjusted for demographics, APOE genotype, use of diabetes medication, duration of diabetes and glycaemic control. Among 2001 participants with diabetes at visit 5 (mean age 76 years), a history of severe hypoglycaemia (3.1% of participants) was associated with dementia (vs normal cognitive status): OR 2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain MRI (n = 580), hypoglycaemia was associated with smaller total brain volume (−0.308 SD, 95% CI −0.612, −0.004). Hypoglycaemia was nominally associated with a 15 year cognitive change (−0.14 SD, 95% CI −0.34, 0.06). In prospective analysis (n = 1263), hypoglycaemia was strongly associated with incident dementia (HR 2.54, 95% CI 1.78, 3.63). Our results demonstrate a strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting a need for discussion of appropriate diabetes treatments for high-risk older adults.

/pdf/severe-hypoglycaemia-mild-cognitive-impairment-dementia-and-dbjs35d5em.pdf

Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study.

Aims To analyze the performance of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG), and CG calculated with ideal bodyweight (CG-IBW) equations to estimate glomerular filtration rate (eGFR) based on serum creatinine in a large diabetic population. Methods 24,516 adults with type-1-diabetes or type-2-diabetes from the multicenter diabetes prospective follow-up registry DPV were analyzed. We compared eGFR and measured GFR (mGFR) based on 24-h urine collection by calculating mean bias (difference), precision (SD of this difference), accuracy (proportion of eGFR within ±10% of mGFR), Bland-Altman-plots. Results CG overestimates, whereas MDRD, CKD-EPI, and CG-IBW underestimate. Smallest mean bias and highest accuracy (75.3%) were observed for MDRD compared to the other equations ( p Conclusion In this large diabetic cohort, smallest bias and highest accuracy were observed for the MDRD.

Comparison of MDRD, CKD-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes.

High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry.

AIMS The diabetic foot syndrome (DFS) is a serious complication in patients with diabetes increasing the risk for minor/major amputations. This analysis aimed to examine differences in diabetes patients with or without DFS stratified by type 1 (T1D) or type 2 diabetes (T2D). MATERIAL AND METHODS Adult patients (≥20y of age) with diabetes from the German/Austrian diabetes patients follow-up registry (DPV) were included. The cross-sectional study comprised 45 722 subjects with T1D (nDFS  = 2966) and 313 264 with T2D (nDFS  = 30 904). In DFS, minor/major amputations were analysed. To compare HbA1C , neuropathy, nephropathy, cardiovascular disease risk factors, and macrovascular complications between patients with or without DFS, regression models were conducted. Confounders: age, sex, diabetes duration. RESULTS In patients with DFS, a minor amputation was documented in 27.2% (T1D) and 25.9% (T2D), a major amputation in 10.2% (T1D) and 11.3% (T2D). Regression models revealed that neuropathy was more frequent in subjects with DFS compared with patients without DFS (T1D: 70.7 vs 29.8%; T2D: 59.4% vs 36.9%; both P < 0.0001). Hypertension, nephropathy, peripheral vascular disease, stroke, or myocardial infarction was more common compared with patients without DFS (all P < 0.0001). In T1D with DFS, a slightly higher HbA1C (8.11% vs 7.95%; P < 0.0001) and in T2D with DFS a lower HbA1C (7.49% vs 7.69%; P < 0.0001) was observed. CONCLUSIONS One third of the patients with DFS had an amputation of the lower extremity. Especially neuropathy or peripheral vascular disease was more prevalent in patients with DFS. New concepts to prevent DFS-induced amputations and to reduce cardiovascular risk factors before the occurrence of DFS are necessary.

/pdf/diabetic-foot-syndrome-in-patients-with-diabetes-a-1d427n28kj.pdf

Peter Fasching

Papers

Comparison of MDRD, CKD-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes.

High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry.

Diabetic foot syndrome in patients with diabetes. A multicenter German/Austrian DPV analysis on 33 870 patients.

Clinical inertia among patients with type 2 diabetes mellitus treated with DPP-4i and/or SGLT-2i.