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SUMMARY Aims To test the safety and effectiveness of carboxyl-methyl-cellulose dressing (AquacelTM; ConvaTec, UK) in the management of deep diabetic foot ulcers, a group of consecutive out-patients attending the foot clinic of the Department of Metabolic Diseases was studied. Methods Patients were selected according to the following inclusion criteria: a foot ulcer deeper than 1 cm for > 3 weeks, good peripheral blood supply (palpable peripheral pulses or ABPI > 0.9). Exclusion criteria were as follows: active infection, as evident from clinical signs (purulent discharge, redness, swelling, tenderness) and confirmed by culture exams, plasma creatinine > 2 mg/dl, recent episodes of ketoacidosis, malignancies, and any therapy or pathology which might interfere with the healing process. Twenty patients were enrolled in the study and having obtained their informed consent, their lesions were surgically debrided with the complete elimination of all necrotic tissue and debris up to the bleeding healthy tissue; then ulcers were staged and measured, and patients were randomly assigned to two different treatment groups. Patients in group A were dressed with saline-moistened gauze, while patients in group B were dressed with AquacelTM according to the manufacturer's instructions. All patients in both groups received special post-operative shoes (Podiabetes; Zeno Buratto, Treviso, Italy) and crutches until complete re-epithelialization. Ulcers were all left to heal by secondary intent. After 8 weeks patients were blindly evaluated for: the rate of reduction of lesional volume (RLV), rate of granulation tissue (GT), number of infective complications (IC). Intralesional (ILTC) and perilesional (PLTC) temperatures were also recorded with a thermocouple surface digital thermometer, and the difference between the two values (ΔTC) was calculated. Healing time (HT, days), was then compared between the two groups. Data were compared by analysis of variance (anova), linear regression, Kaplan–Meier survival analysis and Fisher's exact test. Results HT was significantly shorter in Group B than in Group A (P < 0.001). RLV was significantly (P < 0.01) higher in Group B patients compared with Group A, as well as GT (P < 0.05). IC were in 1/10 Group B and in 3/10 Group A (P = 0.582). In addition, both ILTC and ΔTC were higher in Group B compared with Group A ones (P < 0.01). Conclusions Carboxyl-methyl-cellulose dressings were shown to be safe, effective and well tolerated in the management of non-ischaemic, non-infected deep diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

SUMMARY Aims To report on the reproducibility of iohexol glomerular filtration rate (GFR) estimation, to compare the plasma clearance of iohexol with that of[51Cr]EDTA and to evaluate the reliability of reduced sampling schedules in estimating GFR in Type 1 and Type 2 diabetes mellitus. Methods Agreement was assessed in 15 Type 1 and 26 Type 2 diabetics with creatinine ranging from 53 to 564 μmol/l. Results The regression between multiple-sample iohexol and[51Cr]EDTA clearances was 0.999 in Type 1 and 0.987 in Type 2 diabetes (P < 0.0001 for both). A seven-sample design and the three-sample approach by Brøchner–Mortensen were validated by comparison with the full-sample schedule in 87 patients (51 Type 1, 36 Type 2). Full-sample GFR was 80.3 ± 43.8, seven-sample 79.5 ± 43.9 (r = 0.990) and three-sample 79.8 ± 45.2 ml.min-1.1.73 m-2 (r = 0.972). The coefficients of variation of GFR were 2.7 ± 1.4% and 3.8 ± 1.9% for the full-sample and the seven-sample approaches, respectively, and significantly higher for the three-sample design (6.9 ± 3.4%, P = 0.0001). Conclusions After iohexol injection, the Brøchner–Mortensen schedule does not provide an accurate estimate of GFR. The seven-sample approach gives acceptable errors and allows a good estimate of GFR throughout a wide range of renal function. [ABSTRACT FROM AUTHOR]

Objectives: Diabetic impotence is generally due to peripheral neuropathy, but a central pathway impairment has also been suggested. We evaluated somatosensory transmission in a group of impotent diabetic men to assess the role of central nervous system (CNS) involvement., Materials and Methods: Somatosensory evoked potentials (SEPs) of pudendal (pdn) and posterior tibial (ptn) nerves were recorded in 74 patients. Type and duration of diabetes, severity of sexual dysfunction, medium term metabolic control, occurrence of microangiopathic chronic complications and autonomic neuropathy were evaluated., Results: Our data show an impairment of central conduction times in pdn (25.7%) and ptn (39.2%) greater than peripheral nervous impairment (pdn 12.2%, ptn 8.1%), in impotent diabetic patients without any further major complication. Central nervous conduction delay resulted to be correlated with poor glycemic control. Significant evident autonomic dysfunction was found only in a minority of cases., Conclusion: Our data might suggest that altered conduction along CNS and somatic peripheral neuropathy might develop independently. We confirm the hypothesis of a "central diabetic neuropathy" and suggest that central sensory pathways involvement, not related to peripheral impairment, could play a role in the pathogenesis of erectile dysfunction in diabetic patients.

Atherosclerosis is a major contributor to the onset and progression of cardiovascular disease (CVD). Cholesterol‐loaded foam cells play a pivotal role in forming atherosclerotic plaques. Induction of cholesterol efflux from these cells may be a promising approach in treating CVD. The reverse cholesterol transport (RCT) pathway delivers cholesteryl ester (CE) packaged in high‐density lipoproteins (HDL) from non‐hepatic cells to the liver, thereby minimising cholesterol load of peripheral cells. RCT takes place via a well‐organised interplay amongst apolipoprotein A1 (ApoA1), lecithin cholesterol acyltransferase (LCAT), ATP binding cassette transporter A1 (ABCA1), scavenger receptor‐B1 (SR‐B1), and the amount of free cholesterol. Unfortunately, modulation of RCT for treating atherosclerosis has failed in clinical trials owing to our lack of understanding of the relationship between HDL function and RCT. The fate of non‐hepatic CEs in HDL is dependent on their access to proteins involved in remodelling and can be regulated at the structural level. An inadequate understanding of this inhibits the design of rational strategies for therapeutic interventions. Herein we extensively review the structure–function relationships that are essential for RCT. We also focus on genetic mutations that disturb the structural stability of proteins involved in RCT, rendering them partially or completely non‐functional. Further studies are necessary for understanding the structural aspects of RCT pathway completely, and this review highlights alternative theories and unanswered questions. [ABSTRACT FROM AUTHOR]

Aims: Diabetes mellitus (DM) is the leading cause of chronic kidney disease. Albuminuria is associated with an increased risk of cardiovascular mortality. Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) and mineralocorticoid receptor antagonists (MRAs) protect against albuminuria; however, their combined effects on albuminuria are unclear. We performed a network meta‐analysis to investigate the effects of SGLT2‐Is, MRAs and their combination on albuminuria in type 2 DM. Methods: We systematically searched PubMed, Medline, EMBASE and the Cochrane Library from inception up to 20 November 2022. We selected randomized control and crossover trials that compared MRAs, SGLT2‐Is, MRAs + SGLT2‐Is, or a placebo in patients with type 2 DM with a urinary albumin‐creatinine ratio (UACR) ≥30 mg/g creatinine. The primary outcome was the change in the UACR. Results: This meta‐analysis analysed 17 studies with 34 412 patients. The use of combination treatment with SGLT2‐Is and MRAs was associated with lower albuminuria compared with the use of SGLT2‐Is, MRAs, or the placebo alone [mean difference (95% CI): −34.19 (−27.30; −41.08), −32.25 (−24.53; −39.97) and −65.22 (−57.97; −72.47), respectively]. Treatment with SGLT2‐Is or MRAs alone caused a significant reduction in UACR compared with the placebo [mean difference (95% CI): −31.03 (−28.35; −33.72) and −32.97 (−29.68; −36.27), respectively]. The effects of MRAs on the UACR are comparable with those of SGLT2‐Is. Sensitivity analyses showed similar results. Conclusion: Combination therapy with SGLT2‐Is and MRAs was associated with lower albuminuria in patients with type 2 DM compared with monotherapy with SGLT2‐Is or MRAs alone. [ABSTRACT FROM AUTHOR]

Background: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design., Aims: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only., Materials and Methods: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality., Results: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence., Conclusion: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged., (© 2024 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Aims: Prevention of foot ulcers in persons with diabetes is important to help reduce the substantial burden on both individual and health resources. A comprehensive analysis of reported interventions is needed to better inform healthcare professionals about effective prevention. The aim of this systematic review and meta-analysis is to assess the effectiveness of interventions to prevent foot ulcers in persons with diabetes who are at risk thereof., Materials and Methods: We searched the available scientific literature in PubMed, EMBASE, CINAHL, Cochrane databases and trial registries for original research studies on preventative interventions. Both controlled and non-controlled studies were eligible for selection. Two independent reviewers assessed risk of bias of controlled studies and extracted data. A meta-analysis (using Mantel-Haenszel's statistical method and random effect models) was done when >1 RCT was available that met our criteria. Evidence statements, including the certainty of evidence, were formulated according to GRADE., Results: From the 19,349 records screened, 40 controlled studies (of which 33 were Randomised Controlled Trials [RCTs]) and 103 non-controlled studies were included. We found moderate certainty evidence that temperature monitoring (5 RCTs; risk ratio [RR]: 0.51; 95% CI: 0.31-0.84) and pressure-optimised therapeutic footwear or insoles (2 RCTs; RR: 0.62; 95% CI: 0.26-1.47) likely reduce the risk of plantar foot ulcer recurrence in people with diabetes at high risk. Further, we found low certainty evidence that structured education (5 RCTs; RR: 0.66; 95% CI: 0.37-1.19), therapeutic footwear (3 RCTs; RR: 0.53; 95% CI: 0.24-1.17), flexor tenotomy (1 RCT, 7 non-controlled studies, no meta-analysis), and integrated care (3 RCTs; RR: 0.78; 95% CI: 0.58-1.06) may reduce the risk of foot ulceration in people with diabetes at risk for foot ulceration., Conclusions: Various interventions for persons with diabetes at risk for foot ulceration with evidence of effectiveness are available, including temperature monitoring (pressure-optimised) therapeutic footwear, structured education, flexor tenotomy, and integrated foot care. With hardly any new intervention studies published in recent years, more effort to produce high-quality RCTs is urgently needed to further improve the evidence base. This is especially relevant for educational and psychological interventions, for integrated care approaches for persons at high risk of ulceration, and for interventions specifically targeting persons at low-to-moderate risk of ulceration., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU., Methods: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed., Results: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers., Conclusions: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

During the last four decades, development of effective immunosuppressants has significantly improved short‐term results of organ transplantation. However, long‐term results have not been satisfactory due to chronic rejection or complications caused by immunosuppressive drugs. Therefore, induction of immunological tolerance of the transplanted organ is considered essential to improve the long‐term results. Despite numerous tolerance strategies that have been successful in murine models, inducing hematopoietic chimerism through donor hematopoietic stem cell transplantation is the only method that reproducibly induces kidney allograft tolerance in nonhuman primates or humans. Combining kidney and hematopoietic stem cell transplantation to achieve allograft tolerance has now been attempted with different chimerism strategies. This review summarizes the status of current clinical trials on the induction of allograft tolerance. We also summarize recent studies to extend the chimerism approach to deceased donor transplant recipients. [ABSTRACT FROM AUTHOR]

The effectiveness of wound dressing performance in exudate management is commonly gauged in simple, non‐realistic laboratory setups, typically, where dressing specimens are submersed in vessels containing aqueous solutions, rather than by means of clinically relevant test configurations. Specifically, two key fluid–structure interaction concepts: sorptivity—the ability of wound dressings to transfer exudate, including viscous fluids, away from the wound bed by capillary action and durability—the capacity of dressings to maintain their structural integrity over time and particularly, at removal events, have not been properly addressed in existing test protocols. The present article reviews our recent published research concerning the development of clinically relevant testing methods for wound dressings, focussing on the clinical relevance of the tests as well as on the standardisation and automation of laboratory measurements of dressing performance. A second objective of this work was to compile the experimental results characterising the performance of gelling fibre dressings, which were acquired using advanced testing methods, to demonstrate differences across products that apparently belong to the same "gelling fibre" family but differ remarkably in materials, structure and composition and, thereby, in performance. [ABSTRACT FROM AUTHOR]

Background: Calcineurin inhibitors (CNIs) are often associated with abnormalities in glucose and lipid metabolism. Tacrolimus is the most potent CNI which is nowadays used almost universally as a part of triple‐drug immunosuppression after kidney transplantation. Tacrolimus can cause islet cell damage and decrease in insulin secretion which can lead to post‐transplant diabetes mellitus and rarely diabetic ketoacidosis. Although rare, acute pancreatitis has also been implicated by a few case reports to be associated with tacrolimus. However, tacrolimus‐induced acute pancreatitis has not been reported in pediatric kidney transplant recipient till date. Case Description: We report the first case of tacrolimus‐induced acute pancreatitis in association with hypertriglyceridemia and DKA in a child early after kidney transplant. The patient was managed with supportive treatment, and tacrolimus was stopped for three days and then switched to cyclosporine‐based regimen. The patient became euglycemic within 8 weeks of switching to cyclosporine and did not have any recurrence of pancreatitis. Conclusion: Tacrolimus‐induced pancreatitis is rare in the setting of kidney transplants and prompt diagnosis and management can lead to a successful outcome. [ABSTRACT FROM AUTHOR]

Aim: To investigate relationships between insulin clearance, insulin secretion, hepatic fat accumulation and insulin sensitivity in black African (BA) and white European (WE) men. Methods: Twenty‐three BA and twenty‐three WE men with normal glucose tolerance, matched for age and body mass index, underwent a hyperglycaemic clamp to measure insulin secretion and clearance, hyperinsulinaemic‐euglycaemic clamp with stable glucose isotope infusion to measure whole‐body and hepatic‐specific insulin sensitivity, and magnetic resonance imaging to quantify intrahepatic lipid (IHL). Results: BA men had higher glucose‐stimulated peripheral insulin levels (48.1 [35.5, 65.2] × 103 vs. 29.9 [23.3, 38.4] × 103 pmol L−1 × min, P =.017) and lower endogeneous insulin clearance (771.6 [227.8] vs. 1381 [534.3] mL m−2 body surface area min −1, P <.001) compared with WE men. There were no ethnic differences in beta‐cell insulin secretion or beta‐cell responsivity to glucose, even after adjustment for prevailing insulin sensitivity. In WE men, endogenous insulin clearance was correlated with whole‐body insulin sensitivity (r = 0.691, P =.001) and inversely correlated with IHL (r = −0.674, P =.001). These associations were not found in BA men. Conclusions: While normally glucose‐tolerant BA men have similar insulin secretory responses to their WE counterparts, they have markedly lower insulin clearance, which does not appear to be explained by either insulin resistance or hepatic fat accumulation. Low insulin clearance may be the primary mechanism of hyperinsulinaemia in populations of African origin. [ABSTRACT FROM AUTHOR]

Plantar ulceration is one of the leading complications for diabetic patients. To reduce the risk of plantar ulceration, people with diabetic neuropathy often used custom insoles to offload high pressures from the metatarsal. However, the current custom arch‐conforming insoles, totally contact with the foot, could affect the flow of blood and produce adverse effects on foot ulcers. This study is aimed to propose novel custom insoles for diabetic foot and to make a comparison between the traditional insoles and the proposed one. The novel pressure‐relieving insole is a layered modular insole that includes eight layers of small cushions. The results showed that the current custom insoles would increase the insole volume and squeeze the space available for the foot, and then the constrictive box of the footwear could deteriorate the blood flow of the foot and produce adverse effects on foot ulcers. The novel insoles were found to reduce the peak pressure from 208.86 to 160.02 kPa. High pressure was not observed in the sensitive locations of diabetic foot in this study, and the novel insoles fit diabetic foot better. [ABSTRACT FROM AUTHOR]

The management of diabetic foot ulcers (DFU) remains a challenge, and there is continuing uncertainty concerning optimal approaches to wound healing. The International Working Group of the Diabetic Foot (IWGDF) working group on wound healing has previously published systematic reviews of the evidence in 2008, 2012 and 2016 to inform protocols for routine care and to highlight areas which should be considered for further study. The working group has now updated this review by considering papers on the interventions to improve the healing of DFU's published between June 2014 and August 2018. Methodological quality of selected studies was independently assessed by a minimum of two reviewers using the recently published 21-point questionnaire as recommended by IWGDF/European Wound Management Association, as well as the previously incorporated Scottish Intercollegiate Guidelines Network criteria. Of the 2275 papers identified, 97 were finally selected for grading following full text review. Overall, there has been an improvement in study design and a significant rise in the number of published studies. While previous systematic reviews did not find any evidence to justify the use of newer therapies, except for negative pressure wound therapy in post-surgical wounds, in this review we found additional evidence to support some interventions including a sucrose-octasulfate dressing, the combined leucocyte, fibrin and platelet patch as well as topical application of some placental membrane products, all when used in addition to usual best care. Nonetheless, the assessment and comparison of published trials remains difficult with marked clinical heterogeneity between studies: in patient selection, study duration, standard of usual care provision and the timing and description of the clinical endpoints. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Offloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers.Methods: We updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient-reported measures, and cost-effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non-controlled studies were summarised on a narrative basis.Results: We identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta-analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non-controlled studies. Five meta-analyses and 12 RCTs provided high-quality evidence for non-removable knee-high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non-removable knee-high walkers were shown to be equally effective. Moderate-quality evidence exists for removable knee-high and ankle-high offloading devices being equally effective in healing, but knee-high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low-quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non-plantar ulcers, and neuropathic ulcers with infection or ischemia.Conclusion: Strong evidence supports the use of non-removable knee-high offloading devices (either TCC or non-removable walker) as the first-choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee-high or ankle-high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high-quality controlled studies are needed in these areas. [ABSTRACT FROM AUTHOR]

Background: Prevention of diabetic foot ulcers is important. Preventative treatment mostly targets and aims to improve modifiable risk factors of foot ulceration. While effectiveness of interventions in ulcer prevention has been systematically reviewed, their effectiveness in improving modifiable risk factors is unknown.Methods: The available medical scientific literature in PubMed, Excerpta Medica Database, and the Cochrane database was searched for original research studies on six interventions to treat modifiable risk factors for diabetic foot ulceration (ie, education for patients; education for professionals; self-management; pre-ulcer treatment; orthotic interventions; and foot- and mobility-related exercises). We assessed interventions for eight outcomes (ie, patients' knowledge; treatment adherence; professionals' knowledge; pre-ulcers; mechanical stress; neuropathy symptoms; foot/ankle joint mobility; and foot function). Both controlled and noncontrolled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers and extracted and presented in evidence and risk of bias tables.Results: We included 72 publications (26 with a controlled study design and 46 noncontrolled). We found that structured education may improve foot self-care behaviour of patients, yearly foot examinations, and foot disease knowledge of health care professionals. Callus removal reduces peak plantar pressure. Custom-made therapeutic footwear can be effective in reducing plantar pressure and may reduce callus. Foot- and mobility-related exercises may improve neuropathy symptoms and foot and ankle joint range of motion, while they do not seem to reduce peak plantar pressure; evidence for their effect on foot strength is conflicting.Conclusions: Structured education for patients and health care professionals, callus removal, custom-made therapeutic footwear, and foot- and mobility-related exercises may be beneficial for improving modifiable risk factors for foot ulceration. However, we generally found low quality of evidence for interventions targeting modifiable risk factors for ulceration in persons with diabetes, with frequently inconsistent or limited results available per intervention and outcome. [ABSTRACT FROM AUTHOR]

Pancreatic islet transplantation is a promising alternative to whole‐pancreas transplantation as a treatment of type 1 diabetes mellitus. This technique has been extensively developed during the past few years, with the main purpose of minimizing the complications arising from the standard protocols used in organ transplantation. By using a variety of strategies used in tissue engineering and regenerative medicine, pancreatic islets have been successfully introduced in host patients with different outcomes in terms of islet survival and functionality, as well as the desired normoglycemic control. Here, we describe and discuss those strategies to transplant islets together with different scaffolds, in combination with various cell types and diffusible factors, and always with the aim of reducing host immune response and achieving islet survival, regardless of the site of transplantation. Several aspects of islet transplantation have been extensively developed during the last years to improve long term islet survival and function. In this review, Perez‐Basterrechea and coauthors describe and discuss about tissue engineering strategies used in this field. [ABSTRACT FROM AUTHOR]

Aims: Lisinopril is an angiotensin‐converting‐enzyme inhibitor that is largely administered for off‐label uses. This study aims to provide a comprehensive review of off‐label uses of lisinopril to aid physicians to make evidence‐based decisions. Methods: The following bibliographic databases were searched from inception up to 30 March 2017: PubMed, EMBASE, the Cochrane Library, Cochrane Central Register of Controlled Trials, Scopus, Ovid and Proquest. This systematic review sought all randomized trials conducted on adult individuals comparing lisinopril on its off‐label uses with alternative drugs or placebos and reported direct or alternative clinical outcomes. Risk of bias assessment by using the Cochrane Collaboration risk‐of‐bias tool and quality evaluation took place. Results: Included studies demonstrated significant positive effects of lisinopril on proteinuric kidney disease; however, lisinopril caused a slight reduction of glomerular filtration rate (GFR) especially for patients with GFR < 90 ml min–1. Lisinopril offered better outcomes in comparison to other standard treatments of diabetic nephropathy. Other studies showed positive effects of lisinopril for migraine, prevention of diabetes, myocardial fibrosis, mitral valve regurgitation, cardiomyopathy in patients with Duchenne muscular dystrophy, oligospermia and infertility, and diabetic retinopathy. Conversely, the studies reported that lisinopril was ineffective for five other off‐label uses. Conclusions: The identified studies showed that lisinopril was highly effective for proteinuric kidney disease with a minor but inconsiderable decrease in GFR. Positive effects of lisinopril were demonstrated in seven other off‐label uses; however, lisinopril cannot be recommended as the first choice for these until further clinical trials confirm these positive effects. This study provides a comprehensive review of off‐label uses of lisinopril to aid physicians to make evidence‐based decisions. [ABSTRACT FROM AUTHOR]

Aim: To test the hypothesis that men of black (West) African ethnicity (black African men [BAM]) with early type 2 diabetes (T2D) would have greater insulin secretory deficits compared with white European men (WEM), following prediabetic hypersecretion. Methods: In 19 BAM and 15 WEM, matched for age, body mass index and duration of diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test). Results: With similar post‐challenge glucose responses, BAM had lower second‐phase C‐peptide responses to intravenous glucose (BAM 70.6 vs WEM 115.1 nmol/L/min [ratio of geometric mean 0.55, 95% confidence interval {CI} 0.37, 0.83]; P = .006) and to oral glucose (BAM 65.4 vs WEM 88.5 nmol/L/min [mean difference −23.2, 95% CI −40.0, −6.3]; P = .009). Peripheral insulin response in BAM to oral glucose was preserved (BAM 47.4 vs WEM 59.4 nmol/L/min [ratio of geometric mean 0.89, 95% CI 0.59, 1.35]; P = .566), with relative reductions in insulin clearance (BAM 506.2 vs WEM 630.1 mL/m2 BSA/min [mean difference −123.9, 95% CI −270.5, 22.6]; P = .095), associated with enhanced incretin responses (gastric inhibitory polypeptide incremental area under the curve: BAM 46.8 vs WEM 33.9 μg/L/min [mean difference 12.9, 95% CI 2.1, 23.7]; P = .021). Conclusions: In early T2D, BAM had significantly lower insulin secretory responses to intravenous and oral stimulation than WEM. Lower insulin clearance, potentially driven by increased incretin responses, may act to preserve peripheral insulin concentrations. Tailoring early management strategies to reflect distinct ethnic‐specific pathophysiology may improve outcomes in this high‐risk population. [ABSTRACT FROM AUTHOR]

Objective Associations between maternal glucose levels and increased foetal growth are well established, and independent relationships with maternal weight, weight gain and insulin resistance are also observed. The relative roles of lipolysis and glucose production in the determination of these observations remain unclear. Design We examined, through detailed physiological studies, the relationship between maternal late gestational energy substrate production (glucose and glycerol), maternal weight and weight gain, and estimated foetal size in the third trimester. Patients Twenty-one nulliparous pregnant women, without gestational diabetes ( GDM) assessed at 28 weeks with oral glucose tolerance test, were recruited. Measurements Rates of hepatic glucose production ( GPR) and rates of glycerol production (reflecting lipolysis) using [13C6]-glucose and [2H5]-glycerol were measured at 34-36 weeks of gestation. Respiratory quotient was assessed by indirect calorimetry and body composition by measurements of total body water (TBW; H218O) and body density ( BODPOD). Foetal weight was estimated from ultrasound measures of biparietal diameter, femoral length and abdominal circumference. Results At 34-36 weeks, bivariate analyses showed that GPR and lipolysis correlated with estimated foetal weight ( r=.71 and .72, respectively) as well as with maternal weight, fat mass and fat-free mass, but not maternal weight gain. In multivariate analyses, rates of both glucose production ( r=.42) and lipolysis ( r=.47) were independently associated with foetal size explaining 63% of the variance. Conclusions Both maternal rates of lipolysis and hepatic glucose production in late gestation are strongly related to estimated foetal weight. [ABSTRACT FROM AUTHOR]

Aims/Introduction The objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients. Materials and Methods A total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4-week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t-test, analysis of variance and chisquare-test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide. Results After the therapy, fasting plasma glucose decreased significantly from 11.2 ± 2.7 mmol/L to 8.0 ± 2.2 mmol/L ( P < 0.001). Patients with AC/ CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively). Conclusions The present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Macroencapsulation technology has been an attractive topic in the field of treatment for Type 1 diabetes due to mechanical stability, versatility, and retrievability of the macro-capsule design. Macro-capsules can be categorized into extravascular and intravascular devices, in which solute transport relies either on diffusion or convection, respectively. Failure of macroencapsulation strategies can be due to limited regenerative capacity of the encased insulin-producing cells, sub-optimal performance of encapsulation biomaterials, insufficient immunoisolation, excessive blood thrombosis for vascular perfusion devices, and inadequate modes of mass transfer to support cell viability and function. However, significant technical advancements have been achieved in macroencapsulation technology, namely reducing diffusion distance for oxygen and nutrients, using pro-angiogenic factors to increase vascularization for islet engraftment, and optimizing membrane permeability and selectivity to prevent immune attacks from host's body. This review presents an overview of existing macroencapsulation devices and discusses the advances based on tissue-engineering approaches that will stimulate future research and development of macroencapsulation technology. Biotechnol. Bioeng. 2016;113: 1381-1402. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence-based recommendations for clinical judgments by incorporating various viewpoints. [ABSTRACT FROM AUTHOR]

Background: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment.Methods: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006.Results: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches.Conclusions: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas. [ABSTRACT FROM AUTHOR]

Purpose: To assess the relationship between diabetic polyneuropathy (DPN) and the risk of diabetic retinopathy (DR). Methods: From 1997 to 2010, we identified 5031 newly diagnosed DPN patients and 20 124 controls matched for sex, age, and index year. Cox proportional hazards regression analyses were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of DR between the DPN patients and the non-DPN group. The adjusted hazard ratio was calculated and adjusted for age, sex, duration of diabetes and comorbidities of hypertension, cardiovascular disease and diabetic nephropathy. Results: The incidence rate of DR was 5.87-fold higher in the DPN patients than in the non-DPN group (44.0 vs. 7.22 per 1000 person-years), with an adjusted HR of 5.41(95% CI = 4.92-5.94). The DPN-to-non-DPN DR incidence rate ratio decreased with age (adjusted HR = 6.63 for subgroup younger than 65 years and adjusted HR = 3.91 for subgroup aged 65 years or older). Compared with the non-DPN group, the DPN patients had a 5.63-fold risk of non-proliferative DR (adjusted HR = 5.63, 95% CI = 5.11-6.21) and a 3.67-fold risk of proliferative DR (adjusted HR = 3.67, 95% CI = 2.57-5.23). Conclusion: The patients with DPN had an increased risk of developing DR and advanced DR compared with the non-DPN group, particularly among the subgroup aged younger than 65 years. [ABSTRACT FROM AUTHOR]

Background: Prevention of diabetic foot ulcers is important. Preventative treatment mostly targets and aims to improve modifiable risk factors of foot ulceration. While effectiveness of interventions in ulcer prevention has been systematically reviewed, their effectiveness in improving modifiable risk factors is unknown., Methods: The available medical scientific literature in PubMed, Excerpta Medica Database, and the Cochrane database was searched for original research studies on six interventions to treat modifiable risk factors for diabetic foot ulceration (ie, education for patients; education for professionals; self-management; pre-ulcer treatment; orthotic interventions; and foot- and mobility-related exercises). We assessed interventions for eight outcomes (ie, patients' knowledge; treatment adherence; professionals' knowledge; pre-ulcers; mechanical stress; neuropathy symptoms; foot/ankle joint mobility; and foot function). Both controlled and noncontrolled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers and extracted and presented in evidence and risk of bias tables., Results: We included 72 publications (26 with a controlled study design and 46 noncontrolled). We found that structured education may improve foot self-care behaviour of patients, yearly foot examinations, and foot disease knowledge of health care professionals. Callus removal reduces peak plantar pressure. Custom-made therapeutic footwear can be effective in reducing plantar pressure and may reduce callus. Foot- and mobility-related exercises may improve neuropathy symptoms and foot and ankle joint range of motion, while they do not seem to reduce peak plantar pressure; evidence for their effect on foot strength is conflicting., Conclusions: Structured education for patients and health care professionals, callus removal, custom-made therapeutic footwear, and foot- and mobility-related exercises may be beneficial for improving modifiable risk factors for foot ulceration. However, we generally found low quality of evidence for interventions targeting modifiable risk factors for ulceration in persons with diabetes, with frequently inconsistent or limited results available per intervention and outcome., (© 2020 John Wiley & Sons Ltd.)

ABSTRACT Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next-generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management of chronic wounds. [ABSTRACT FROM AUTHOR]

Background The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus ( HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma ( HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. Aim To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. Methods A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor ( CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). Results Patients switched to sirolimus had improved survival ( P < 0.001) and slower progression to cirrhosis ( P = 0.001). In patients with HCC ( n = 91), sirolimus duration rather than strategy was an independent predictor of survival ( P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes ( P = 0.03). Conclusion These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome. [ABSTRACT FROM AUTHOR]

Background Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women. Methods For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22-30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group. Results Amodest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r=0.093, p=0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p=0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chisquared= 13.015, p=0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p=0.03, OR=2.156 (95% CI, 1.077-4.318). Conclusion We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L. [ABSTRACT FROM AUTHOR]

Although transplantation of microencapsulated islets has been proposed as a therapy for the treatment of diabetes mellitus, limited retrievability of the cells has impeded its medical usage. To achieve retrieval of microencapsulated islets, capsules were attached to polydimethylsiloxane ( PDMS) with a biocompatible adhesive. Because the hydrophobic nature of the PDMS surface prevents attachment, surface modification is essential. Alginate microcapsules were attached to modified PDMS sheets, and the mechanical stability of the resulting constructs was determined. Acrylic acid ( AA) and acrylamide ( AM) mixtures were grafted on the surfaces of PDMS sheets using a two-step oxygen plasma treatment ( TSPT). TSPT- PDMS was characterized according to water contact angle and zeta-potential measurements. The contact angle was altered by changing the ratio of AM to AA to generate hydrophilic surface. Evaluation of the surface charge at pH 2, 7, and 12 confirmed the presence of polar groups on the modified surface. Microcapsules were attached to TSPT- PDMS using Histoacryl® and shown to be in a monolayered and half-exposed state. The shear stress resistance of alginate capsules attached to the PDMS sheet indicates the possibility of transplantation of encapsulated cells without scattering in vivo. This method is applicable to retrieve microencapsulated porcine islets when required. [ABSTRACT FROM AUTHOR]

Objective Hypertension is characterized by microvascular remodeling resulting in increased wall/lumen ratio and elevated microvascular stiffness. Aiming to transform the measurement of macrovascular stiffness into a microvascular environment we introduce a noninvasive method to assess rPWV. rPWV alterations in early hypertension are investigated in detail. The developed methodology is compared with its possible computational alternatives. Methods Time dependent alterations of retinal arterial diameter were assessed noninvasively by the DVA in 65 male normoalbuminuric normotensive to mildly hypertensive subjects (age: 28.7 ± 6.0 years). rPWV was computed using three different methods. 'Method 1' used filtration at HR, 'Method 2' filtered at higher HR multiples, and 'Method 3' used in addition, linear fit for data averaging. Results 'Method 2' and 'Method 3' applying filtration at high HR multiples showed strong associations with systolic BP throughout the cohort ( r = 0.49, r = 0.63, p < 0.001). Based on the highest association, 'Method 3' was proposed to characterize rPWV. Hypertensive patients showed higher rPWV (1243 ± 694 RU/sec) than subjects with high-normal BP (786 ± 486 RU/sec, p < 0.01) or normotensive subjects (442 ± 148 RU/sec, p < 0.001). Conclusions rPWV demonstrated a strong association with BP and can discriminate between optimal, high-normal, and mildly hypertensive BP values. rPWV may add detailed insights into early microvascular pathophysiology, potentially beyond microalbuminuria. [ABSTRACT FROM AUTHOR]

The salivary proteome consists of thousands of proteins, which include, among others, hormonal modulators of energy intake and output. Although the functions of this prominent category of hormones in whole body energy metabolism are well characterized, their functions in the oral cavity, whether as a salivary component, or when expressed in taste cells, are less studied and poorly understood. The respective receptors for the majority of salivary metabolic hormones have been also shown to be expressed in salivary glands (SGs), taste cells, or other cells in the oral mucosa. This review provides a comprehensive account of the gastrointestinal hormones, adipokines, and neuropeptides identified in saliva, SGs, or lingual epithelium, as well as their respective cognate receptors expressed in the oral cavity. Surprisingly, few functions are assigned to salivary metabolic hormones, and these functions are mostly associated with the modulation of taste perception. Because of the well-characterized correlation between impaired oral nutrient sensing and increased energy intake and body mass index, a conceptually provocative point of view is introduced, whereupon it is argued that targeted changes in the composition of saliva could affect whole body metabolism in response to the activation of cognate receptors expressed locally in the oral mucosa. [ABSTRACT FROM AUTHOR]

Free-catch urine samples were collected from forty-one clinically normal domestic rabbits of various ages, breeds and both sexes. The Test γ GT Liquid-0018257640 was used for the in vitro quantitative determination of γ-Glutamyl-transferase (GGT) and reference intervals for γ-glutamyl transferase (γ-glutamyl transpeptidase, γ-GT, GGT) and GGT index (γ-glutamyl transferase to creatinine ratio) were established in fresh urine samples. Possible correlations of GGT and GGT index with sex and age were also explored. The stability of GGT after storage at +4°C for one week and -20°C for one month was investigated. The GGT and the GGT index reference intervals in fresh urine samples of healthy domestic rabbits were found to be 2.7-96.5 IU/l and 0.043-1.034, respectively. The urine GGT activity and the GGT index did not differ significantly between sexes in fresh urine samples. Nevertheless, a statistically significant difference was found in the GGT index with neutered status. Short-term storage at 4°C did not alter the enzyme stability, whereas, freezing did. Further investigations are needed to determine whether these parameters may be useful for early detection of renal tubular damage in rabbits, and in enabling better clinical management of affected animals. [ABSTRACT FROM AUTHOR]

Background: Education is one of the pivotal aspects of diabetes care. The impact of education has been found to be efficacious in the short term, but tends to lose efficacy in the long term. The hypothesis tested here was that one-to-one education would confer knowledge that would be reflected in metabolic improvement in this group of participants with diabetes. Methods: Thirty-nine patients with type 2 diabetes mellitus and poor diabetes control attended a one-to-one diabetic and dietetic education session with a diabetic specialist nurse and a diabetes specialist dieticican. Glycemic control was assessed by measuring serum glycosolated hemoglobin (HbA1c) measurements before the session and at 6 and 12 months afterwards. Results: The HbA1c levels fell significantly in the whole group to 8.0 ± 0.5% ( P < 0.05) at 6 months and to 8.3 ± 0.7% ( P < 0.05) at the final visit from a baseline of 9.2 ± 0.5%. Compared to female patients, male patients had a similar drop in HbA1c at 6 months of 1.1%, which persisted until the final visit, when the drop was -1.3% vs 0.3% ( P < 0.05). Conclusions: A single episode of one-to-one diabetic and dietetic education to subjects with poor diabetic control is effective in improving short- and long-term diabetic control for up to 1 year. Male patients were found to have a better response than female patients. [ABSTRACT FROM AUTHOR]

O bjectives: Hypoglycaemia is a common cause of morbidity in dogs with congenital portosystemic shunts but the aetiology is unknown. The hypothesis of this study was that dogs with congenital portosystemic shunts would have significantly higher insulin concentrations than dogs without congenital portosystemic shunts. The main objective of the study was to compare peripheral glucose and insulin concentrations between dogs with congenital portosystemic shunts and dogs without congenital portosystemic shunts. M ethods: Peripheral serum insulin and plasma glucose concentrations were measured in dogs with congenital portosystemic shunts and without congenital portosystemic shunts and compared both between groups as well as to reference intervals derived from healthy dogs. R esults: Congenital portosystemic shunts were diagnosed in 41 dogs. Forty-eight dogs hospitalised with other conditions acted as controls. Serum insulin concentrations were mildly elevated (Ä40 μU/mL) in seven dogs and were markedly elevated in two dogs with congenital portosystemic shunts, yet mild hypoglycaemia (3·3 mmol/L) was detected in only one of these dogs. Four dogs with congenital portosystemic shunts showed fasting hypoglycaemia, yet insulin concentrations were within or below the reference interval in three. There was no difference between the median insulin concentration of dogs with congenital portosystemic shunts and without congenital portosystemic shunts. C linical S ignificance: Hyperinsulinaemia is infrequently observed in dogs with congenital portosystemic shunts. The aetiology of hypoglycaemia in dogs with congenital portosystemic shunts merits further investigation. [ABSTRACT FROM AUTHOR]

Objectives. To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) andtotal mortality in the general population. Background. Epidemiologically, risk of IHD is inversely related to HDL cholesterol levels. Mutations in apolipoprotein (apo) A-I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHDandearlydeath. Design. We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial infarction (MI) and mortality in 10 440 individuals in the prospective Copenhagen City Heart Study followed for 31 years. Results were validated in an independent case-control study (n = 16 035). Additionally, we determined plasma ratios of mutant to wildtype (WT) apoA-I in human heterozygotes and functional effects of mutations in adenovirus-transfected mice. Results. We identified a new mutation, A164S (1 : 500 in the general population), which predicted hazard ratios for IHD, MI and total mortality of 3.2 [95% confidence interval (CI): 1.6-6.5], 5.5 (95% CI: 2.6- 11.7) and 2.5 (95% CI: 1.3-4.8), respectively, in heterozygotes compared with noncarriers. Mean reduction in survival time in heterozygotes was 10 years (P < 0.0001). Results for IHD and MI were confirmed in the case-control study. Furthermore, the ratio of mutant S164 to WT A164 apoA-I in plasma of heterozygotes was reduced. In addition, A164S heterozygotes had normal plasma lipid and lipo protein levels, including HDL cholesterol and apoA-I, and this finding was confirmed in adenovirus- transfectedmice. Conclusions. A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality without low HDL cholesterol levels. [ABSTRACT FROM AUTHOR]

An estimated 15% of patients with diabetes mellitus will develop a foot ulcer during their lifetime. Debridement is included in multiple guidelines and algorithms for the care of patients with diabetic neuropathic foot ulcers, and it has long been considered an essential step in the protocol for treating diabetic foot ulcers. In addition to altering the environment of the chronic wound, debridement is a technique aimed at removing nonviable and necrotic tissue, thought to be detrimental to healing. This is accomplished by removing abnormal wound bed and wound edge tissue, such as hyperkeratotic epidermis (callus) and necrotic dermal tissue, foreign debris, and bacteria elements known to have an inhibitory effect on wound healing. While the rationale for surgical debridement seems logical, the evidence for its role in enhancing healing is deficient. In this paper, we systematically review five published clinical trials, which met the criteria and investigated surgical debridement of diabetic foot ulcers to enhance healing. Most existing studies are not randomized clinical trials optimized to test the relationship between debridement of diabetic foot ulcers and wound healing. Therefore, a focused, well-designed study is needed to elucidate the effect of surgical debridement on the healing status of chronic wounds. [ABSTRACT FROM AUTHOR]

Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, “uremic” GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N-methyl-d-aspartate receptors by GSA, concomitant inhibition of γ-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins. [ABSTRACT FROM AUTHOR]

Gonadotrophin-releasing hormone (GnRH) is a hypothalamic decapeptide with an undisputed role as a primary regulator of gonadal function. It exerts this regulation by controlling the release of gonadotrophins. However, it is becoming apparent that GnRH may have a variety of other vital roles in normal physiology. A reconsideration of the potential widespread action that this traditional reproductive hormone exerts may lead to the generation of novel therapies and provide insight into seemingly incongruent outcomes from current treatments using GnRH analogues to combat diseases such as prostate cancer. [ABSTRACT FROM AUTHOR]

Management of diabetic foot ulcers presents a major clinical challenge. The response to treatment is often poor and the outcome disappointing, while the costs are high for both healthcare providers and the patient. In such circumstances, it is essential that management should be based on firm evidence and follow consensus. In the case of the diabetic foot, however, clinical practice can vary widely. It is for these reasons that the International Working Group on the Diabetic Foot has published guidelines for adoption worldwide. The Group has now also completed a series of non-systematic and systematic reviews on the subjects of soft tissue infection, osteomyelitis, offloading and other interventions designed to promote ulcer healing. The current article collates the results of this work in order to demonstrate the extent and quality of the evidence which is available in these areas. In general, the available scientific evidence is thin, leaving many issues unresolved. Although the complex nature of diabetic foot disease presents particular difficulties in the design of robust clinical trials, and the absence of published evidence to support the use of an intervention does not always mean that the intervention is ineffective, there is a clear need for more research in the area. Evidence from sound clinical studies is urgently needed to guide consensus and to underpin clinical practice. It is only in this way that patients suffering with these frequently neglected complications of diabetes can be offered the best hope for a favourable outcome, at the least cost. [ABSTRACT FROM AUTHOR]