Methylglyoxal in diabetes: link to treatment, glycaemic control and biomarkers of complications

2014 ◽  
Vol 42 (2) ◽  
pp. 450-456 ◽  
Author(s):  
Paul J. Beisswenger
Keyword(s):  
Glycaemic Control ◽  
Diabetic Complications ◽  
Predictive Biomarkers ◽  
Complication Rates ◽  
Specific Chemical ◽  
End Products ◽  
Carboxymethyl Lysine ◽  
Genetic And Environmental Factors ◽  
Novel Concept ◽  
The Cost

Diabetic complications are major health problems worldwide, with the cost of caring for diabetes rising to US$245 billion in 2012 in the U.S.A. alone. It is widely recognized that non-enzymatic glycation in diabetes is a major cause of damage and dysfunction of key vascular cells. MG (methylglyoxal) is directly toxic to tissues, and is a major precursor of AGEs (advanced glycation end-products). Various propensities to diabetic complications are seen among individuals with diabetes, with accelerated rates occurring in some individuals with modest hyperglycaemia, while others never progress in spite of poor glycaemic control over many years. Since production and detoxification of MG is ultimately controlled by enzymatic mechanisms, both genetic and environmental factors could regulate tissue glycation and potentially account for these variable complication rates. Activation of pathways that determine MG levels occurs in susceptible patients, indicting an important role in pathogenesis. MG leads to formation of specific AGEs, which are likely to predict propensity to diabetic complications. We have shown recently that three specific plasma AGE biomarkers [MG-H1 (MG-derived hydroimidazolones), CEL (Nε-carboxyethyl-lysine) and CML (Nε-carboxymethyl-lysine)] predict biopsy-documented fast DN (diabetic nephropathy) progression. Since two of the predictive biomarkers are MG end-products, these outcomes support a role for MG in the development of DN. Our studies on MG and its end-products have also shown anti-complication effects of the drug metformin, which binds and inactivates MG, thus reducing MG-related AGEs. We have also shown that reducing post-meal glucose decreases MG levels, as well as levels of MG-related AGEs. Our clinical outcome studies have been based on the novel concept that the unique glycation products that we can measure reflect the activity of specific chemical pathways that are selectively activated by hyperglycaemia in patients that are inherently more susceptible to diabetic complications, and can be used to solve other diabetes-related medical questions.

Role of lipids in chemical modification of proteins and development of complications in diabetes

2003 ◽  
Vol 31 (6) ◽  
pp. 1413-1416 ◽  
Author(s):  
A.S. Januszewski ◽  
N.L. Alderson ◽  
T.O. Metz ◽  
S.R. Thorpe ◽  
J.W. Baynes
Keyword(s):  
Risk Factor ◽  
Chemical Modification ◽  
Diabetic Complications ◽  
Type I ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine ◽  
Chemical Modification Of Proteins ◽  
And Oxidative Stress

Hyperglycaemia is the major risk factor for the development of complications in both Type I and Type II diabetes; however, there is growing evidence from several clinical trials that dyslipidaemia, including hypertriglyceridaemia, is a significant and independent risk factor for diabetic complications. In this paper, we propose that chemical modification of proteins by lipids may be a underlying pathogenic mechanism linking dyslipidaemia to diabetic complications. Thus the major AGEs (advanced glycation end-products) in tissues, such as carboxymethyl-lysine, carboxyethyl-lysine and hydroimidazolones, may, in fact, be ALEs (advanced lipoxidation end-products), derived from lipids. Increased lipid peroxidation and accelerated ALE formation, possibly catalysed by hyperglycaemia and oxidative stress, may be the mechanistic link between dyslipidaemia and diabetic complications. If correct, this proposal would suggest that inhibition or reversal of glycation, which is a central theme of this symposium, may not be sufficient for protection against diabetic complications.

Economic impact of the use of the National Surgical Quality Improvement Program

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Alvine Fansi ◽  
Angela Ly ◽  
Julie Mayrand ◽  
Maggy Wassef ◽  
Aldanie Rho ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Cost Analysis ◽  
Economic Impact ◽  
Quality Improvement Program ◽  
Economic Evaluations ◽  
Complication Rates ◽  
Improvement Program ◽  
Surgical Quality ◽  
Acs Nsqip ◽  
The Cost

Objectives The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) is a validated, risk-adjusted database for improving the quality and security of surgical care. ACS NSQIP can help participating hospitals target areas that need improvement. The aim of this study was to systematically review the literature analyzing the economic impact of using NSQIP. This paper also provides an estimation of annual cost savings following the implementation of NSQIP and quality improvement (QI) activities in two hospitals in Quebec. Methods In June 2018, we searched in seven databases, including PubMed, Embase, and NHSEED for economic evaluations based on NSQIP data. Contextual NSQIP databases from two hospitals were collected and analyzed. A cost analysis was conducted from the hospital care perspective, comparing complication costs before and after 1 year of the implementation of NSQIP and QI activities. The number and the cost of complications are measured. Costs are presented in 2018 Canadian dollars. Results Out of 1,612 studies, 11 were selected. The level of overall evidence was judged to be of moderate to high quality. In general, data showed that, following the implementation of NSQIP and QI activities, a significant decrease in complications and associated costs was observed, which improved with time. In the cost analysis of contextual data, the reduction in complication costs outweighed the cost of implementing NSQIP. However, this cost analysis did not take into account the costs of QI activities. Conclusions NSQIP improves complication rates and associated costs when QI activities are implemented.

Concomitant Osteotomy Reduces Risk of Reoperation Following Cartilage Restoration Procedures of the Knee: A Matched Cohort Analysis

Cartilage ◽  
2021 ◽  
pp. 194760352110115
Author(s):  
Jacob G. Calcei ◽  
Kunal Varshneya ◽  
Kyle R. Sochacki ◽  
Marc R. Safran ◽  
Geoffrey D. Abrams ◽  
...  
Keyword(s):  
Cohort Analysis ◽  
Reoperation Rate ◽  
Similar Rate ◽  
Osteochondral Allograft ◽  
Complication Rates ◽  
Cartilage Restoration ◽  
Chondrocyte Implantation ◽  
The Cost ◽  
Reoperation Rates

Objective The objective of this study is to compare the (1) reoperation rates, (2) 30-day complication rates, and (3) cost differences between patients undergoing isolated autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA) procedures alone versus patients with concomitant osteotomy. Study Design Retrospective cohort study, level III. Design Patients who underwent knee ACI (Current Procedural Terminology [CPT] 27412) or OCA (CPT 27415) with minimum 2-year follow-up were queried from a national insurance database. Resulting cohorts of patients that underwent ACI and OCA were then divided into patients who underwent isolated cartilage restoration procedure and patients who underwent concomitant osteotomy (CPT 27457, 27450, 27418). Reoperation was defined by ipsilateral knee procedure after the index surgery. The 30-day postoperative complication rates were assessed using ICD-9-CM codes. The cost per patient was calculated. Results A total of 1,113 patients (402 ACI, 67 ACI + osteotomy, 552 OCA, 92 OCA + osteotomy) were included (mean follow-up of 39.0 months). Reoperation rate was significantly higher after isolated ACI or OCA compared to ACI or OCA plus concomitant osteotomy (ACI 68.7% vs. ACI + osteotomy 23.9%; OCA 34.8% vs. OCA + osteotomy 16.3%). Overall complication rates were similar between isolated ACI (3.0%) and ACI + osteotomy (4.5%) groups and OCA (2.5%) and OCA + osteotomy (3.3%) groups. Payments were significantly higher in the osteotomy groups at day of surgery and 9 months compared to isolated ACI or OCA, but costs were similar by 2 years postoperatively. Conclusions Concomitant osteotomy at the time of index ACI or OCA procedure significantly reduces the risk of reoperation with a similar rate of complications and similar overall costs compared with isolated ACI or OCA.

α-Oxoaldehyde metabolism and diabetic complications

2003 ◽  
Vol 31 (6) ◽  
pp. 1358-1363 ◽  
Author(s):  
P.J. Beisswenger ◽  
S.K. Howell ◽  
R.G. Nelson ◽  
M. Mauer ◽  
B.S. Szwergold
Keyword(s):  
Diabetic Complications ◽  
Complex Mixture ◽  
Therapeutic Interventions ◽  
Diabetic Patients ◽  
Human Populations ◽  
Control Mechanisms ◽  
Protective Mechanisms ◽  
Glycation End Products ◽  
End Products

The factors responsible for variable susceptibility to diabetic nephropathy are not clear. According to the non-enzymatic glycation hypothesis, diabetes-related tissue damage occurs due to a complex mixture of toxic products, including α-oxoaldehydes, which are inherently toxic as well as serving as presursors for advanced glycation end-products. Protective mechanisms exist to control this unavoidable glycation, and these are determined by genetic or environmental factors that can regulate the concentrations of the reactive sugars or end-products. In diabetes these protective mechanisms become more important, since glycation stress increases, and less efficient defence systems against this stress could lead to diabetic complications. Some of these enzymatic control mechanisms, including those that regulate α-oxoaldehydes, have been identified. We have observed significant increases in production of the α-oxoaldehydes methylglyoxal and 3-deoxyglucosone in three human populations with biopsy-proven progression of nephropathy. The increase in methylglyoxal could be secondary to defects in downstream glycolytic enzymes (such as glyceraldehyde-3-phosphate dehydrogenase) that regulate its production, or in detoxification mechanisms such as glyoxalase. Other mechanisms, however, appear to be responsible for the observed increase in 3-deoxyglucosone levels. We present results of our studies on the mechanisms responsible for variable production of α-oxoaldehydes by measuring the activity and characteristics of these enzymes in cells from complication-prone and -resistant diabetic patients. New therapeutic interventions designed to control these endogenous mechanisms could potentially enhance protection against excessive glycation and prevent or reverse complications of long-term diabetes.

scholarly journals Antiglycation potential of Indigoferin a, Indigoferin B and Indigoferin C natural products from Indigofera heterantha Brandis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayesha Khan ◽  
Ajmal Khan ◽  
Manzoor Ahmad ◽  
Mumtaz Ali ◽  
Umar Farooq ◽  
...  
Keyword(s):  
Natural Products ◽  
Diabetic Complications ◽  
Inhibitory Activity ◽  
Chemical Constituents ◽  
Intramolecular Hydrogen Bonding ◽  
Glycation End Products ◽  
End Products ◽  
Serious Disease ◽  
Intramolecular Hydrogen

Abstract Background Diabetes is a long-lasting and serious disease that effect in worldwide individual lives, families, and societies. Hyperglycemia of diabetes mellitus produced Advance Glycation End Products that are associated with diabetic complications like neuropathy, nephropathy, retinopathy, and cardiovascular diseases. Methods In this study, the natural products isolated from of Indigofera heterantha Brandis, Indigoferin A (S1), Indigoferin B (S2) and Indigoferin C (S3) were evaluated for their in vitro antiglycation activity. Results The compounds exhibited a significant inhibitory activity against the formation of Advanced Glycation End-Products with IC50 values of 674.25 ± 3.2 μM, 407.03 ± 4.7 μM and 726.41 ± 2.1 μM, respectively. Here, important structure-activity relationship was observed, when the intramolecular hydrogen bonding interactions suppressed the antiglycation activity of compound S3. Thus, the study clearly demonstrates that the number and the position of substituents act as an assisting factor and directly influence the inhibitory activity of the natural product by altering the sugar or protein binding affinity. Conclusions This study explain first time the antiglycation inhibitory ability of chemical constituents isolated from I. heterantha and can be used for above late diabetic complications.

Behandeling van lumbale discushernia: open versus endoscopische discectomie?

2021 ◽  
Author(s):  
J. SYS ◽  
A. VERVAECKE
Keyword(s):  
Cost Benefit Analysis ◽  
Lumbar Disc ◽  
Length Of Hospital Stay ◽  
Cost Benefit ◽  
Complication Rates ◽  
Patient Morbidity ◽  
Endoscopic Discectomy ◽  
Theoretical Advantage ◽  
Open Versus ◽  
The Cost

Open (micro) discectomie is a routine treatment for patients with a lumbar disc hernia and incapacitating sciatica, resistant to conservative treatment. Alternatively, the full-endoscopic discectomy has been increasingly performed over the past years. While the surgical instrumentation for this approach has improved and the necessary specialized training is widely available, the technique remains challenging for the surgeon and the assumed/theoretical advantage regarding patient morbidity is still unproven. When compared to open (micro) discectomie, the existing literature fails to attribute significant decreases in length of hospital stay or complication rates to the full-endoscopic approach, therefore making the cost-benefit analysis uninteresting due to the higher associated cost. The structural lack of financing of Belgian hospitals leads to intrinsic budgetary limitations which are emphasized if the hospitals have to carry the extra costs related to endoscopic disc surgery themselves.

scholarly journals Single-use versus reusable flexible ureteroscopes: a comprehensive cost-analysis decision model

2018 ◽  
Vol 97 (3) ◽  
pp. 323-333
Author(s):  
Giovanni Scala Marchini ◽  
Fábio César Miranda Torricelli ◽  
Manoj Monga ◽  
Carlos Alfredo Batagello ◽  
Fábio Carvalho Vicentini ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Case Series ◽  
Final Analysis ◽  
Flexible Ureteroscopy ◽  
Complication Rates ◽  
Ureteral Access Sheath ◽  
Flexible Scope ◽  
Surgical Costs ◽  
Single Use ◽  
The Cost

Purpose: The significant improvements in flexible ureterorenoscopes have made flexible ureteroscopy the main treatment modality to target upper urinary pathologies. The purpose of this study was to critically evaluate all literature concerning the cost-effectiveness of flexible ureteroscopy comparing single-use with reusable scopes. Methods: A systematic online literature review was performed in PubMed, Embase and Google Scholar databases. Two separate urologists (GSM and FCT) performed the online search and reviewed all papers considered suitable and relevant for this analysis. Because of the paucity of high quality publications, not only prospective assessments but also case control and case series studies were included in the final analysis. All factors potentially affecting surgical costs or clinical outcomes were considered in the analysis. Results: 741 studies with the previously elected terms were found. Of those, 18 were duplicated and 77 were not related to urology procedures and were excluded. Of the remaining 646 studies, 59 published between 2000 and 2018 were considered of relevance to the pre-defined queries and were selected for further analysis. Stone free and complication rates were similar between single-use and reusable scopes. In special, urinary tract infection rate following flexible ureteroscopy is not inferior if a single-use device is used instead of a reusable scope. Operative time was in average 20% shorter if a digital scope was used, single-use or not. There is a suggestion that the learning curve is shorter with single-use devices but this is not consistent in the literature. Surgeon expertise impacts the longevity of the flexible scope. Reusable digital scopes seem to last longer than optic ones, though scope longevity is very variable worldwide. New scopes usually last three to four times more than refurbished ones and single-use ureterorenoscopes have good resilience throughout long cases. Both sterilization method and cleaning process impact scope longevity, the best results being achieved with Cidex and a dedicated nurse to take care of the sterilization process. The main factors that negatively impact device longevity regarding patient and disease are lower pole pathologies, large stone burden and non-use of a ureteral access sheath. Conclusions: The cost-effectiveness of a flexible ureteroscopy program is dependent of several aspects that must be considered when deciding whether to choose between a single-use and a reusable ureterorenoscope. Disposable devices are already a reality and will progressively become the standard as manufacturing price falls significantly.

scholarly journals Focus on the totally laparoscopic feeding gastrostomy tube placement operative technique

2021 ◽  
Vol 9 (1) ◽  
pp. 127-133
Author(s):  
Sorin Cimpean ◽  
Alexandre Grapotte ◽  
Nicolas Boyer ◽  
Mathilde Poras ◽  
Dario Raglione ◽  
...  
Keyword(s):  
Length Of Hospital Stay ◽  
Feeding Tube ◽  
Tube Placement ◽  
Laparoscopic Technique ◽  
Complication Rates ◽  
Readmission Rates ◽  
Gastric Lumen ◽  
Gastrostomy Tube Placement ◽  
Totally Laparoscopic ◽  
The Cost

Laparoscopic feeding gastrostomy placement is a surgical operation that allows the feeding of malnourished patients through a tube that is placed in the gastric lumen. The benefits of an improved nutritional status in terms of improving clinical outcomes are well documented in the literature and consist in a reduction of the complication rates of the surgical patients, the length of hospital stay, the readmission rates, and a reduction of the cost of health services by reducing the morbidity or mortality. We present a totally laparoscopic technique of feeding tube placement.

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