AIMS/HYPOTHESIS: Monogenic diabetes is estimated to account for 1-6% of paediatric diabetes cases in primarily non-consanguineous populations, while the incidence and genetic spectrum in consanguineous regions are insufficiently defined. In this single-centre study we aimed to evaluate diabetes subtypes, obtain the consanguinity rate and study the genetic background of individuals with syndromic and neonatal diabetes in a population with a high rate of consanguinity. METHODS: Data collection was carried out cross-sectionally in November 2021 at the paediatric diabetic clinic, Dr Jamal Ahmad Rashed Hospital, in Sulaimani, Kurdistan, Iraq. At the time of data collection, 754 individuals with diabetes (381 boys) aged up to 16 years were registered. Relevant participant data was obtained from patient files. Consanguinity status was known in 735 (97.5%) participants. Furthermore, 12 families of children with neonatal diabetes and seven families of children with syndromic diabetes consented to genetic testing by next-generation sequencing. Prioritised variants were evaluated using the American College of Medical Genetics and Genomics guidelines and confirmed by Sanger sequencing. RESULTS: A total of 269 of 735 participants (36.5%) with known consanguinity status were offspring of consanguineous families. An overwhelming majority of participants (714/754, 94.7%) had clinically defined type 1 diabetes (35% of them were born to consanguineous parents), whereas only eight (1.1%) had type 2 diabetes (38% consanguineous). Fourteen (1.9%) had neonatal diabetes (50% consanguineous), seven (0.9%) had syndromic diabetes (100% consanguineous) and 11 (1.5%) had clinically defined MODY (18% consanguineous). We found that consanguinity was significantly associated with syndromic diabetes (p=0.0023) but not with any other diabetes subtype. The genetic cause was elucidated in ten of 12 participants with neonatal diabetes who consented to genetic testing (homozygous variants in GLIS3 [sibling pair], PTF1A and ZNF808 and heterozygous variants in ABCC8 and INS) and four of seven participants with syndromic diabetes (homozygous variants in INSR, SLC29A3 and WFS1 [sibling pair]). In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes. CONCLUSIONS/INTERPRETATION: This unique single-centre study confirms that, even in a highly consanguineous population, clinically defined type 1 diabetes is the prevailing paediatric diabetes subtype. Furthermore, a pathogenic cause of monogenic diabetes was identified in 83% of tested participants with neonatal diabetes and 57% of participants with syndromic diabetes, with most variants being homozygous. Causative genes in our consanguineous participants were markedly different from genes reported from non-consanguineous populations and also from those reported in other consanguineous populations. To correctly diagnose syndromic diabetes in consanguineous populations, it may be necessary to re-evaluate diagnostic criteria and include additional phenotypic features such as short stature and hepatosplenomegaly.
- MeSH
- diabetes mellitus 1. typu * epidemiologie genetika MeSH
- diabetes mellitus 2. typu * epidemiologie genetika diagnóza MeSH
- dítě MeSH
- kohortové studie MeSH
- lidé MeSH
- mutace genetika MeSH
- nemoci novorozenců * genetika MeSH
- novorozenec MeSH
- pokrevní příbuzenství MeSH
- proteiny přenášející nukleosidy genetika MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Irák MeSH
BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.
- MeSH
- diabetes mellitus 1. typu * MeSH
- diabetes mellitus 2. typu * MeSH
- diabetická noha * diagnóza etiologie terapie MeSH
- lidé MeSH
- neuropatická artropatie * komplikace diagnóza MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).
- MeSH
- chronická renální insuficience * diagnóza epidemiologie terapie MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- diabetes mellitus * farmakoterapie MeSH
- kardiovaskulární nemoci * diagnóza epidemiologie prevence a kontrola MeSH
- krevní glukóza MeSH
- ledviny MeSH
- lidé MeSH
- obezita komplikace MeSH
- selfmonitoring glykemie MeSH
- srdeční selhání * komplikace MeSH
- tepový objem MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
Tirzepatid – duální agonista receptorů pro glukagon-like peptid-1 (GIP) a glukózo-dependentní inzulinotropní polypeptid (GIP) je účinným antidiabetikem s významným efektem na redukci hmotnosti, u kterého je předpokládaný potenciál ovlivnit i kardiovaskulární riziko pacientů. Tento přehled se věnuje jeho vlivu na lipidové spektrum, srovnává jej s účinky selektivních agonistů GLP-1 receptoru a poskytuje pohled na vývoj dalších inkretinových agonistů a jejich metabolické působení.
Tirzepatide - a dual agonist of receptors for glucagon-like peptide-1 (GIP) and glucose-dependent insulinotropic polypeptide (GIP) is an effective antidiabetic drug associated with significant weight loss, which is expected to have the potential to influence the cardiovascular risk of patients. This review focuses on its effects on the lipid spectrum, compares it to the effects of selective GLP-1 receptor agonists, and provides insight into the development of other incretin agonists and their metabolic actions.
- Klíčová slova
- tirzepatid,
- MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- dyslipidemie farmakoterapie MeSH
- hmotnostní úbytek účinky léků MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- obezita farmakoterapie MeSH
- receptor pro glukagonu podobný peptid 2 terapeutické užití MeSH
- žaludeční inhibiční polypeptid farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
V populaci diabetiků 2. typu je častěji než v běžné populaci diagnostikováno jak srdeční selhání, tak i chronické onemocnění ledvin (CKD). Screening CKD musí směřovat k časnému záchytu onemocnění s cílem zvrátit, nebo alespoň významně zpomalit jeho průběh a oddálit přechod do selhání ledvin s nutností chronické dialyzační anebo transplantační léčby. Finerenon je nesteroidní, selektivní antagonista mineralokortikoidního receptoru. Efekty finerenonu u nemocných s diabetem 2. typu byly zkoumány ve velkých registračních klinických studiích fáze III FIDELIO-DKD, FIGARO-DKD a následně v jejich sdružené analýze FIDELITY. Na základě výsledků publikovaných prospektivních randomizovaných kontrolovaných studií s finerenonem je jeho použití u pacientů s CKD a diabetem 2. typu zmíněno v několika recentních doporučeních. Zástupci expertního panelu zahrnujícího Českou nefrologickou společnost, Českou diabetologickou společnost ČLS JEP, Českou internistickou společnost ČLS JEP a Českou kardiologickou společnost v souladu s recentními mezinárodními doporučeními považují finerenon za jeden z pilířů léčby pacientů s chronickým onemocněním ledvin a diabetem 2. typu pro jeho nefroprotektivní a kardioprotektivní účinky.
Both heart failure and chronic kidney disease (CKD) are detected more often in the type 2 diabetic population than in the general population. CKD screening should focus on its early detection to reverse, or at least significantly slow down its course and delay stage 5 CKD with the need for chronic dialysis or transplant treatment. Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist. The effects of finerenone in patients with type 2 diabetes were investigated in the large registration phase III clinical trials FIDELIO-DKD, FIGARO-DKD and subsequently in their pooled analysis FIDELITY. Based on the results of published prospective randomized controlled trials with finerenone, its use in patients with CKD and type 2 diabetes is mentioned in several recent recommendations. Representatives of an expert panel including the Czech Nephrological Society, the Czech Diabetological Society, the Czech Internal Medicine Society and the Czech Cardiology Society, in accordance with recent international recommendations, consider finerenone to be one of the pillars of the treatment of patients with chronic kidney disease and type 2 diabetes for its nephroprotective and cardioprotective effects.
- Klíčová slova
- finerenon,
- MeSH
- chronická renální insuficience * farmakoterapie prevence a kontrola MeSH
- diabetes mellitus 2. typu * farmakoterapie komplikace MeSH
- dialýza ledvin MeSH
- komplikace diabetu farmakoterapie MeSH
- lidé MeSH
- naftyridiny farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
Ačkoliv již uplynulo více než 100 let od objevení inzulinu, je tento tělu vlastní hormon i lék základním pilířem v léčbě diabetu a pomocí moderních postupů se snažíme jeho podávání co nejvíc uzpůsobit jeho fyziologickému působení. K tomu nám pomáhá jednak pozměněná farmakokinetika krátkodobých inzulinových analog, které více kopírují fyziologickou křivku uvolnění inzulinu po příjmu stravy, jednak prodloužení účinku bazálních inzulinových analog a jejich plošší farmakokinetický profil. Díky těmto modifikacím jsme schopni léčbu diabetiků individualizovat, dosáhnout lepší kompenzace a ovlivnit riziko akutních i pozdních diabetických komplikací.
Although more than 100 years have passed since the discovery of insulin, this body's own hormone and drug is still widely used in the treatment od diabetes. With the help of modern procedures we try to adapt its administration to the physiological state as much as possible. The changed pharmacokinetics of rapid-acting insulin analogs, which closely copies the physiological curve of insulin release after food intake, helps us. And we also add prolonged effect of basal insulin analogs and theirs flatter pharmacokinetic profile. Thanks to these modifications, we are able to individualize the treatment of diabetes, archieve better compensation and lower the risk of late diabetic complications.
- MeSH
- diabetes mellitus 1. typu farmakoterapie MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- inzulin * analogy a deriváty farmakologie terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- Dapagliflozin,
- MeSH
- chronická renální insuficience * farmakoterapie MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- glifloziny * farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- srdeční selhání farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
The majority of cases of chronic kidney disease (CKD) worldwide are driven by the presence of type 2 diabetes (T2D), resulting in an increase in CKD rates over the past few decades. The existence of CKD alongside diabetes is associated with increased burden of cardiovascular disease and increased risk of death. Optimal glycaemic control is essential to prevent progression of CKD, but achieving glycaemic targets in people with CKD and diabetes can be challenging because of increased risk of hypoglycaemia and limitations on glucose-lowering therapeutic options. This review considers the challenges in management of T2D in people with impaired kidney function and assesses evidence for use of basal insulin analogues in people with CKD.
- MeSH
- chronická renální insuficience * komplikace farmakoterapie chemicky indukované MeSH
- diabetes mellitus 2. typu * komplikace farmakoterapie chemicky indukované MeSH
- hypoglykemie * chemicky indukované prevence a kontrola komplikace MeSH
- hypoglykemika terapeutické užití MeSH
- inzulin terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM. METHODS: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured. SAT obtained by needle biopsy was used to analyze adipocyte size, lipidome, mRNA expression, and inflammatory markers. Primary cultures of adipose precursors were analyzed for adipogenic capacity and metabolism. RESULTS: Compared with control individuals, FDR individuals had lower IS and a higher amount of visceral fat. However, SAT-derived adipose precursors did not differ in their ability to proliferate and differentiate or in metabolic parameters (lipolysis, mitochondrial oxidation). In SAT of FDR individuals, lipidomic and mRNA expression analysis revealed accumulation of triglycerides containing polyunsaturated fatty acids and increased mRNA expression of lysyl oxidase (LOX). These parameters correlated with IS, visceral fat accumulation, and mRNA expression of inflammatory and cellular stress genes. CONCLUSIONS: The intrinsic adipogenic potential of SAT is not affected by a family history of T2DM. However, alterations in LOX mRNA and polyunsaturated fatty acids in triacylglycerols are likely related to the risk of developing T2DM independent of obesity.
- MeSH
- diabetes mellitus 2. typu * genetika metabolismus MeSH
- inzulinová rezistence * genetika MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita genetika metabolismus MeSH
- podkožní tuk metabolismus MeSH
- průřezové studie MeSH
- triglyceridy metabolismus MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Důsledná metabolická kompenzace je zásadní pro úspěšný průběh těhotenství žen s pregestačním i gestačním diabetem. Na rozdíl od období mimo těhotenství jsou však farmakologické možnosti léčby diabetu těhotných žen značně omezené. V porovnání s inzulinem přináší metformin řadu praktických výhod, jako je perorální způsob podání, nenáročná edukace pacientek a nízká finanční náročnost léčby. Přestože prochází placentou, není patrně jeho užívání spojeno s rizikem poškození plodu v časném období těhotenství. Velké randomizované studie naznačují několik pozitivních metabolických důsledků užívání metforminu v těhotenství, jako je nižší přírůstek hmotnosti matky, nižší výskyt hypertenzních poruch těhotných žen nebo menší počet hypertrofických novorozenců. Na druhou stranu je však metformin také spojován s možným rizikem růstové restrikce plodů a předčasného porodu. Ve srovnání s inzulinem nevedl metformin ke snížení rizika závažných novorozeneckých komplikací. V neposlední řadě je zkoumáno možné intrauterinní ovlivnění metabolismu plodu, které může vést ke zvýšenému riziku metabolických poruch v pozdějším životě dětí.
Excelent metabolic control is essential for the successful course of pregnancy in women with both pregestational and gestational diabetes. However, in contrast to the non-pregnancy period, pharmacological options for the treatment of diabetes are limited. Compared with insulin, metformin offers a number of practical advantages, such as an oral route of administration, easy training and the low price. Although it crosses the placenta, its use is probably not associated with a risk of fetal harm in early pregnancy. Large randomized trials suggest several positive metabolic consequences of metformin use in pregnancy. These include lower maternal weight gain, lower incidence of hypertensive disorders in pregnant women, or fewer hypertrophic newborns. On the other hand, metformin is also associated with a possible risk of fetal growth restriction and preterm birth. Compared with insulin, metformin does not reduce the incidence of serious neonatal complications. Finally, the possible intrauterine influence on fetal metabolism, which may lead to an increased risk of metabolic disorders in later life in children, is being investigated.
- MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- gestační diabetes farmakoterapie MeSH
- hodnocení léčiv MeSH
- hypoglykemika MeSH
- inzulin terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- metformin * farmakologie terapeutické užití MeSH
- těhotenství při diabetu * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
