• MeSH
• Albuminuria diagnosis   urine   MeSH
• Antihypertensive Agents pharmacology   therapeutic use   MeSH
• Renal Insufficiency, Chronic classification   therapy   MeSH
• Diabetic Nephropathies * diagnosis   classification   therapy   MeSH
• Diagnosis, Differential MeSH
• Dyslipidemias drug therapy   MeSH
• Glomerular Filtration Rate MeSH
• Hyperglycemia drug therapy   MeSH
• Hypertension drug therapy   MeSH
• Hypoglycemic Agents pharmacology   therapeutic use   MeSH
• Hypolipidemic Agents pharmacology   therapeutic use   MeSH
• Humans MeSH
• Diet, Protein-Restricted methods   MeSH
• Disability Evaluation MeSH
• Prognosis MeSH
• Proteinuria diagnosis   urine   MeSH
• Kidney Function Tests methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

• MeSH
• Diabetic Nephropathies * diagnosis   epidemiology   therapy   MeSH
• Diagnostic Techniques, Urological MeSH
• Renal Dialysis methods   MeSH
• Diagnosis, Differential MeSH
• Hyperglycemia therapy   MeSH
• Humans MeSH
• Renal Insufficiency therapy   MeSH
• Kidney Function Tests methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

• Publication type
• Meeting Abstract MeSH

• MeSH
• Diabetic Nephropathies * diagnosis   epidemiology   therapy   MeSH
• Diagnostic Techniques, Urological MeSH
• Renal Dialysis methods   MeSH
• Diagnosis, Differential MeSH
• Hyperglycemia therapy   MeSH
• Humans MeSH
• Renal Insufficiency therapy   MeSH
• Kidney Function Tests methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

Hlavní příčinou vzniku diabetické periferní neuropatie (DPN) je dlouhodobá hyperglykémie s navazujícími mechanismy včetně možných změn úrovně vaskulárních a nervových růstových faktorů. V rámci projektu bude u zdravých dobrovolníků, nemocných s diabetem 1. typu bez komplikací a nemocných s diabetem 1. typu před , 1 rok a 5-10 let po úspěšné transplantaci pankreatu (a ledviny) s dlouhodobou normoglykémií vyšetřena hustota epidermálních nervových vláken a exprese vaskulárních a dalších růstových faktorů v kožních biopsiích z oblasti stehna. Vyšetření hustoty epidermálních nervových vláken bude provedeno pomocí nepřímé imunofluorescence a vyšetření exprese růstových faktorů metodou qRT-PCR. Projekt by měl zhodnotit vliv navození dlouhodobé normoglykémie po transplantaci pankreatu na epidermální inervaci a expresi růstových faktorů u pokročilých forem DPN.; The pathogenesis of diabetic peripheral neuropathy (DPN) involves hyperglycemia-linked mechanisms which may include changes in the expression of growth factors. In the course of the project epidermal nerve fibre densities and expression of vascular and neural growth factors will be assessed in lower limb skin biopsies of healthy controls, patients with type 1 diabetes mellitus without complications and type 1 diabetic patients at the time of and 1 and 5-10 years after a successful pancreas (and kidney) transplantation with long-term normoglycemia. The epidermal nerve fibre densities will be assessed by indirect immunofluorescence and growth factor skin levels by quantitative RT-PCR. The grant project should evaluate the effect of reestablishment of normoglycemia on epidermal innervation and expression of growth factors in advanced DPN.

• MeSH
• Diabetes Mellitus, Type 1 MeSH
• Pancreas MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• diabetologie
• transplantologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Whether nerve fiber loss, a prominent feature of advanced diabetic neuropathy, can be reversed by reestablishment of normal glucose control remains questionable. We present 8-year follow-up data on epidermal nerve fiber (ENF) density and neurological function in patients with type 1 diabetes after simultaneous pancreas and kidney transplantation (SPK) with long-term normoglycemia. Distal thigh skin biopsies with ENF counts, vibration perception thresholds (VPTs), autonomic function testing (AFT) and electrophysiological examinations were performed at time of SPK and 2.5 and 8 years after SPK in 12 patients with type 1 diabetes. In comparison to controls, baseline ENF density, VPT and AFT results of patients indicated severe neuropathy. At follow-up, all SPK recipients were insulin independent with excellent glycemic control and kidney graft function; however, the severe ENF depletion present at baseline had not improved, with total ENF absence in 11 patients at 8-year follow-up. Similarly, no amelioration occurred in the VPT and AFT results. Numerical improvement was seen in some electrophysiological parameters; however, statistical significance was achieved only in median motor nerve conduction velocity. ENF loss and functional deficits in advanced diabetic peripheral neuropathy are rarely reversible, even by long-term normoglycemia, which underscores the importance of neuropathy prevention by early optimal glycemic control.

• MeSH
• Diabetes Mellitus, Type 1 surgery   MeSH
• Diabetic Nephropathies etiology   pathology   MeSH
• Glomerular Filtration Rate MeSH
• Skin innervation   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Nerve Fibers pathology   MeSH
• Postoperative Complications MeSH
• Graft Survival MeSH
• Prognosis MeSH
• Graft Rejection etiology   pathology   MeSH
• Risk Factors MeSH
• Kidney Transplantation adverse effects   MeSH
• Pancreas Transplantation adverse effects   MeSH
• Kidney Function Tests MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Během posledních 30 let se transplantace pankreatu stala rutinním postupem, který je zvláště vhodný pro pacienty s diabetem 1. typu, kteří současně podstupují transplantaci ledviny. Zlepšuje kvalitu života a v porovnání s transplantací samotné ledviny zlepšuje dlouhodobé přežívání. Poskytuje nezávislost na inzulinu s téměř normální glukózovou tolerancí, uvolnění diety, klid od hypoglykemií a možnost zastavení postupu nebo dokonce regresi mikroangiopatických komplikací. Samostatně se transplantace pankreatu provádí zejména u vybraných pacientů s rekurentními epizodami těžkých hypoglykemií při syndromu porušeného vnímání hypoglykemie nebo jako následný výkon u příjemců s funkčním štěpem ledviny od zemřelého či žijícího dárce. 5leté přežívání funkce štěpu pankreatu činí při kombinované transplantaci, transplantaci samotného pankreatu či transplantaci pankreatu následně po ledvině více než 75, 50 a 62 %. V rozporu se zlepšujícími se výsledky je určitá stagnace počtu výkonů v některých evropských zemích a v USA. Ačkoliv se na tom podílí také horší kvalita dárců, zavádění ostrůvkové transplantace jako méně invazivní procedury a naděje v technologická řešení, hlavní příčina spočívá v nedostatečném povědomí o současné úspěšnosti a menším počtu pacientů na čekací listině. ČR se v oblasti transplantační léčby diabetu tradičně řadí k nejaktivnějším zemím. Pro pacienty jsou s ohledem na klinickou potřebu k dispozici různé varianty včetně transplantace Langerhansových ostrůvků.

During the past 30 years pancreas transplantation evolved into a routine procedure especially suitable for type 1 diabetic recipients undergoing simultaneously kidney transplantation significantly improving quality of life and life expectancy as compared with kidney only recipients. It provides insulin independence with near-normal glucose control without special dietary restriction, freedom from hypoglycemia and chance for halting or regression of microangiopathic diabetes complications. As a separate procedure, pancreas transplantation is carried out mainly in selected subjects suffering from severe hypoglycemic episodes and impaired hypoglycemia awareness or as a subsequent procedure in type 1 diabetic kidney recipients from both cadaveric or living donors. Five-year insulin independence rate following combined pancreas and kidney, pancreas only and pancreas after kidney procedures currently exceed 75, 50 and 62 %, respectively. Though the outcomes still continue to improve, the rate of pancreas transplants has reached a plateau in several European countries or even declines in the United States. Main reasons for that include fewer referrals from diabetes specialist, decreased donor quality, introduction of islet transplantation as a less invasive procedure but probably most of all probably insufficient information on the latest progress and trends achieved in this area. In the area of transplant therapy of diabetes Czech Republic traditionally ranks to the most active countries providing different transplant options according to individual clinical needs including islet transplantation.

• Keywords
• kombinovaná transplantace,
• MeSH
• Diabetes Mellitus, Type 1 surgery   MeSH
• Diabetes Mellitus * surgery   MeSH
• Diabetic Nephropathies surgery   prevention & control   MeSH
• Hypoglycemia surgery   MeSH
• Diabetes Complications prevention & control   MeSH
• Humans MeSH
• Survival Rate MeSH
• Treatment Failure MeSH
• Graft Survival MeSH
• Graft Rejection diagnosis   MeSH
• Kidney Transplantation * MeSH
• Pancreas Transplantation * methods   statistics & numerical data   MeSH
• Patient Selection MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Two different methods of graft venous drainage are used in pancreas transplantation: portal (PVD) and systemic (SVD). PVD is considered to be more physiologic due to its similarity to venous outflow of the native pancreas. The aim of our study was to compare glucose metabolism in Type 1 diabetic recipients of kidney and pancreatic grafts with PVD versus SVD by intravenous glucose tolerance test (IVGTT). We examined 28 insulin-independent patients after simultaneous pancreas and kidney transplantation: 14 recipients with PVD of the pancreatic graft and 14 with SVD after a mean post-transplant period of 1 year. All recipients had stable good function of the kidney graft. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA1c), and standard IVGTT with coefficient of glucose assimilation (KG) calculation were assessed. Insulin sensitivity and production were evaluated using the homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR], homeostasis model assessment of B-cell function [HOMA-B]). Total C-peptide and insulin secretions were calculated as areas under the curves (AUCs) from the serum levels during the IVGTT. PVD and SVD groups did not differ in age, body mass index (BMI) and duration of post-transplantation period (P ≥ .05). We did not find any significant difference in fasting glycemia, HbA1c, KG, HOMA-IR, parameters of C-peptide level, fasting insulin level, and response during IVGTT. HOMA-B and AUC of insulin level were higher in the SVD group (45.1 ± 35.1 versus 19.8 ± 15.5, P =.03 and 1075 ± 612 versus 1799 ± 954 mIU/L/60 minutes, P < .03, respectively). In the PVD group, 1 patient had an abnormal response to the glucose stimulus, 8 patients had an impaired glucose tolerance, and 5 patients had a normal glucose tolerance. In the SVD group, an abnormal response was present in none, impaired glucose tolerance in 4, and normal glucose tolerance in 10 recipients. Athough this was not a prospectively randomized trial, we conclude that the change of surgical technique from SVD to PVD did not lead to any substantial change in terms of glucose tolerance.

• MeSH
• C-Peptide blood   MeSH
• Diabetes Mellitus, Type 1 metabolism   MeSH
• Adult MeSH
• Glucose metabolism   MeSH
• Glucose Tolerance Test MeSH
• Glycated Hemoglobin analysis   MeSH
• Homeostasis MeSH
• Insulin blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• B-Lymphocytes, Regulatory immunology   MeSH
• Kidney Transplantation * MeSH
• Pancreas Transplantation * MeSH
• Portal Vein MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Publication type
• Meeting Abstract MeSH

BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

• MeSH
• Diabetes Mellitus, Type 2 complications   diagnosis   urine   MeSH
• Diabetic Nephropathies diagnosis   etiology   urine   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Peptidomimetics urine   MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Proteomics methods   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Validation Study MeSH