26 research outputs found
Pathophysiology of the Metabolic Syndrome
ProuÄavanjem patofi zioloÅ”ke pozadine
metaboliÄkog sindroma, inzulinska rezistencija i visceralni
oblik pretilosti prepoznati su kao glavni Äimbenici. Oba su
stanja povezana s intolerancijom glukoze, Å”eÄernom boleÅ”Äu,
dislipidemijom, arterijskom hipertenzijom, poremeÄajima
koagulacije i fi brinolize te disfunkcijom endotela. Inzulinska
rezistencija oznaÄava stanje u kojem inzulin, unatoÄ
održanom luÄenju iz guÅ”teraÄe, ne može ostvariti svoje
unutarstaniÄne uÄinke.
Uzrokuju je priroÄeni ili steÄeni Äimbenici, odnosno njihova
kombinacija, koji remete bilo koju stepenicu složenoga
fi zioloÅ”kog procesa, od trenutka vezanja inzulina za staniÄni
receptor.
PriroÄeni Äimbenici ukljuÄuju mutacije gena za inzulinski
receptor, transportere glukoze i signalne proteine,
protutijela na inzulinski receptor, kao i brojna druga, do
sada neidentifi cirana stanja. MeÄu steÄenim Äimbenicima
prepoznati su neaktivnost, nezdrava prehrana, starija dob,
utjecaj nekih lijekova, glukotoksiÄnost i lipotoksiÄnost.
Osim rijetkih sluÄajeva postojanja protutijela ili mutacija
gena za inzulinski receptor koji uzrokuju poremeÄaj sinteze,
razgradnje i funkcije receptora i uzrok su rijetkih sindroma,
inzulinska rezistencija u metaboliÄkome sindromu posljedica
je poremeÄaja koji nastaju nakon vezanja inzulina na
receptor.
Iako molekularna osnova inzulinske rezistencije nije
razjaÅ”njena, njezine metaboliÄke posljedice rezultat su
interakcije inzulinske rezistencije s uÄincima kompenzatorne
hiperinzulinemije u organima koji zadržavaju normalnu
osjetljivost na inzulin. Heterogenost patoloŔkih stanja
povezanih s inzulinskom rezistencijom proizlazi iz raznovrsnih
uÄinaka inzulina, kojima regulira temeljne energetske
procese u organizmu.
Iako se debljina tradicionalno defi nira kao poveÄanje
tjelesne mase, u procjeni kardiovaskularnog rizika, važnija
je raspodjela nego koliÄina tjelesne masti. S inzulinskom
rezistencijom korelira masno tkivo u abdominalnoj Ŕupljini
(visceralno), koje je za razliku od supkutanog metaboliÄki
aktivan organ. Ono luÄi razliÄite adipocitokine, udružene
s upalom, disfunkcijom endotela i trombozom, ukljuÄujuÄi
leptin, adiponektin, PAI-1 (inhibitor aktivatora plazminogena
1), tumorski faktor nekroze alfa (TNF-alfa), interleukin 6 (IL-
6), rezistin, kojima regulira osjetljivost na inzulin.
Po nekim autorima, visceralna debljina prethodi inzulinskoj
rezistenciji generirajuÄi navedene poremeÄaje, Å”to odgovor
na pitanje koji je od dva Äimbenika primaran u patogenezi
metaboliÄkog sindroma ostavlja otvorenim. S praktiÄne
strane, njihovo razdvajanje nema veÄeg znaÄenja. Slikovito
se može reÄi da je inzulinska rezistencija srž, a debljina
najÄeÅ”Äa kliniÄka manifestacija metaboliÄkog sindroma.Although the pathophysiology of the
metabolic syndrome is extremely complex and not completely
understood, insulin resistance and central obesity have
been recognised as the most important pathogenic factors.
Both conditions are independently associated with glucose
intolerance, type 2 diabetes, dyslipidaemia, hypertension,
prothrombotic and proinfl ammatory states and endothelial
dysfunction. Insulin resistance could be defi ned as the
inability of insulin to produce its numerous actions, in
spite of unimpaired secretion from the beta cells. It could
be caused by various genetic and acquired conditions,
including insulin receptor gene, glucose transporters and
signalling proteins mutation, insulin receptor antibodies,
fat diet, inactivity, age and drug infl uence, glucotoxicity,
lipotoxicity.
Except in a few rare cases involving antibodies to the
insulin receptor or mutations in the insulin receptor gene,
the insulin resistance of the metabolic syndrome results
from impairments in cellular events distal to the interaction
between insulin and its surface receptor. The molecular
basis of this syndrome is not completely understood,
although signifi cant progress has been made in recent
years toward an understanding of the intracellular signalling
events that mediate insulin action. Metabolic abnormalities
result from the interaction between the effects of insulin
resistance located primarily in muscle and adipose tissue
and adverse impact of the compensatory hyperinsulinemia
on tissues that remain normally insulin sensitive. The
clinical heterogeneity of the metabolic syndrome can
be explained by its signifi cant role on glucose, fat and
protein metabolism, cellular growth and differentiation and
endothelial function.
Although adiposity has been traditionally defi ned as an
increase in total body mass, cardiovascular risk is associated
with visceral fat accumulation. Visceral fat, in comparison
to subcutaneous tissue, represents a metabolically active
organ, strongly related to insulin sensitivity. Moderating the
secretion of various adipocytokines like leptin, adiponectin,
PAI-1, TNF-alpha, IL-6, resistin, it is associated with the
processes of infl ammation, endothelial dysfunction and
atherogenesis.
Some controversies exist around the key central role of the
metabolic syndrome between insulin resistance and visceral
adiposity. From the practical point of view, it seems there is
no need to dissociate the two conditions. Insulin resistance
is considered to be at the core of the syndrome, while central
obesity is the most prevalent clinical manifestation
Diagnostic challenges of diabetic kidney disease
Diabetic kidney disease (DKD) is one of the most common microvascular complications of both type 1 and type 2 diabetes and the most common cause of the end-stage renal disease (ESRD). It has been evidenced that targeted interventions at an early stage of DKD can efficiently prevent or delay the progression of kidney failure and improve patient outcomes. Therefore, regular screening for DKD has become one of the fundamental principles of diabetes care. Long-established biomarkers such as serum-creatinine-based estimates of glomerular filtration rate and albuminuria are currently the cornerstone of diagnosis and risk stratification in routine clinical practice. However, their immanent biological limitations and analytical variations may influence the clinical interpretation of the results. Recently proposed new predictive equations without the variable of race, together with the evidence on better accuracy of combined serum creatinine and cystatin C equations, and both race- and sex-free cystatin C-based equation, have enabled an improvement in the detection of DKD, but also require the harmonization of the recommended laboratory tests, wider availability of cystatin C testing and specific approach in various populations. Considering the complex pathophysiology of DKD, particularly in type 2 diabetes, a panel of biomarkers is needed to classify patients in terms of the rate of disease progression and/or response to specific interventions. With a personalized approach to diagnosis and treatment, in the future, it will be possible to respond to DKD better and enable improved outcomes for numerous patients worldwide
Hepatomegalija i poviÅ”ene aminotransferaze u bolesnice s loÅ”e reguliranom Å”eÄernom boleÅ”Äu
Elevated liver function tests, right upper quadrant abdominal pain, and hepatomegaly occurring in a diabetic patient treated with high doses of insulin may point to the presence of pathologic glycogen accumulation in the liver parenchymal cells. The condition was first described in children, however, studies performed in adults have shown a condition that is similar in many aspects. A case is presented of a 41-year-old female diabetic patient with abnormal liver tests and hepatomegaly. Abdominal ultrasound confirmed liver enlargement without any signs of fatty liver. Liver biopsy revealed a picture compatible with glycogenosis. As excessive hepatic glycogen deposition occurred at an adult age and without a related family history, while the patient presented with normal mental and motor development, the diagnoses of Mauriac syndrome and hereditary were ruled out. The condition was attributed to insulin hyperdosage. The patient was recommended improved glycemic control, more appropriate diet and physical exercise. On follow-up visit 3 months of discharge from the hospital, significant hepatomegaly regression was demonstrated by palpation and ultrasonography, and was accompanied by normalization of serum aminotransferases, blood glucose and glycosylated hemoglobin. Elevated serum aminotransferases and alkaline phosphatase with hepatomegaly as a consequence of hepatocellular glycogen accumulation can occur in diabetic patients of any age who are treated with high doses of insulin, and should therefore be included in the differential diagnosis.Pojava poviÅ”enih jetrenih enzima, bolova u desnom gornjem abdominalnom kvadrantu i hepatomegalije u bolesnika sa Å”eÄernom boleÅ”Äu lijeÄenih visokim dozama inzulina može ukazivati na patoloÅ”ko nakupljanje glikogena u stanicama jetrenog parenhima. Ovo je stanje prvotno opisano u djece, a kasnije studije provedene na odraslima pokazale su jednaku kliniÄku sliku. Prikazan je sluÄaj 41-godiÅ”nje žene oboljele od Å”eÄerne bolesti s poremeÄenim jetrenim nalazima i hepatomegalijom, kod koje je ultrazvuk potvrdio poveÄanje jetre bez znakova steatoze, a biopsijom je postavljena dijagnoza glikogenoze. S obzirom na to da je izrazito nakupljanje glikogena u ovom sluÄaju nastupilo u odrasloj dobi, bez pozitivne obiteljske anamneze, a bolesnica je imala uredan psihiÄki i tjelesni razvoj, iz diferencijalne dijagnoze se je mogao iskljuÄiti Mauriacov sindrom i nasljedna glikogenoza. Uzrok ovoga stanja u ove bolesnice bilo je lijeÄenje osnovne bolesti visokim dozama inzulina. Stoga joj je preporuÄena poboljÅ”ana kontrola glikemije praÄena ispravnom dijetom i tjelesnom aktivnoÅ”Äu. Na kontrolnom pregledu nakon tri mjeseca doÅ”lo je do regresije hepatomegalije potvrÄene palpacijom i ultrazvukom, te do normaliziranja serumskih aminotransferaza, glukoze u krvi i glikoziliranog hemoglobina. PoviÅ”ene aminotransferaze i alkalna fosfataza uz hepatomegaliju mogu se naÄi kod bolesnika dijabetiÄara lijeÄenih visokim dozama inzulina, kao posljedica nakupljanja glikogena u jetrenim stanicama, pa ovo stanje treba ukljuÄiti u diferencijalnu dijagnozu
DijabetiÄko stopalo - možemo Äiniti viÅ”e
Svijet se suoÄava s pandemijom Å”eÄerne bolesti tipa 2, poveÄanom incidencijom Å”eÄerne bolesti tipa 1 i njihovim komplikacijama. Svi oboljeli imaju poveÄan rizik za razvoj komplikacija, bez obzira o kojem se tipu dijabetesa radi. Broj oboljelih od Å”eÄerne bolesti u svijetu se dramatiÄno poveÄao zadnjih 30 godina. Prema epidemioloÅ”kim studijama 1985. godine ukupno je bilo oko 30 milijuna oboljelih, a sada ih ima 13 puta viÅ”e. Projekcije za 2030. godinu predviÄaju poveÄanje na 592 milijuna oboljelih od Å”eÄerne bolesti u svijetu. Time Äe se poveÄati i broj svih komplikacija, pa tako i onih vezanih za dijabetiÄko stopalo. Jedna je od najÄeÅ”Äih i najtežih komplikacija Å”eÄerne bolesti dijabetiÄko stopalo. Termin dijabetiÄko stopalo ukljuÄuje bilo koju patologiju povezanu direktno s dijabetesom ili Ā njegovim kroniÄnim komplikacijama. Kombinacija neuropatije, poremeÄenog protoka krvi poveÄava rizik za razvoj ulkusa stopala, infekcije, a time i moguÄnost amputacije donjih ekstremiteta. Podaci o prevalenciji ulkusa dijabetiÄkog stopala variraju od 4 do 27%. Rizik za razvoj ulkusa stopala u osoba oboljelih od Å”eÄerne bolesti tijekom života iznosi 25%. LijeÄenje komplikacija ulkusa dijabetiÄkog stopala predstavlja veliki teret za oboljelog, njegovu obitelj i ogromno ekonomsko optereÄenje za druÅ”tvo. Komplikacije dijabetiÄkog stopala najÄeÅ”Äi su razlog hospitalizacije dijabetiÄkih bolesnika u zapadnim zemljama. Cijena koÅ”tanja komplikacija dijabetiÄkog stopala poveÄava se s težinom bolesti, hospitalizacijom za 41%, a amputacijom za 9%. Ranim uÄinkovitim lijeÄenjem ulkusa dijabetiÄkog stopala može se smanjiti težina komplikacija prevenirati amputacije, a moguÄe je i smanjiti smrtnost i u svakom sluÄaju poboljÅ”ati kvalitetu života. PotvrÄeno je da se do 50% amputacija i ulkusa stopala u dijabetiÄkih bolesnika može izbjeÄi uÄinkovitom identifikacijom i edukacijom, a prema nekim autorima i do 79%. Cilj je usmjeriti se na prevenciju komplikacija dijabetiÄkog stopala i spaÅ”avanje ekstremiteta
HEMOGLOBIN A1c AND THE QUALITY OF DIABETES CARE
Globalna epidemija Å”eÄerne bolesti jedan je od najveÄih izazova suvremene medicine i druÅ”tva u cjelini. Hemoglobin A1c (HbA1c), biokemijski biljeg prosjeÄne glikemije, veÄ se viÅ”e od 30 godina rabi kao kliniÄki pokazatelj uspjeÅ”nosti lijeÄenja i rizika od razvoja komplikacija Å”eÄerne bolesti. HbA1c je nedavno preporuÄen i kao dijagnostiÄki test za Å”eÄernu bolest. Redovito praÄenje kontrole glikemije i prilagoÄavanje terapije prema odgovarajuÄim ciljnim vrijednostima HbA1c kljuÄni je zahtjev svih suvremenih dijabetoloÅ”kih smjernica te pokazatelj kvalitete zdravstvene skrbi brojnih nacionalnih zdravstvenih sustava. Standardizirana, dostupna i kvalitetna analitiÄka metodologija, uz dobro poznavanje bioloÅ”kih ÄimĀbenika koji mogu utjecati na nalaze testa, presudni su za sigurnu kliniÄku primjenu HbA1c. U ovom pregledu sažeto su prikazani kljuÄni analitiÄki i kliniÄki Äimbenici nužni za pouzdanu uporabu nalaza HbA1c u skrbi za oboljele od Å”eÄerne bolesti te razina usklaÄenosti hrvatske laboratorijske i kliniÄke prakse s relevantnim meÄunarodnim standardima.Global diabetes epidemics is currently representing one of the most prominent medical and societal challenges. Hemoglobin A1c (HbA1c), a biochemical marker of an average blood glucose concentration has been used for more than 30 years as a clinical indicator of both diabetes treatment efficacy and the risk for development of complications. Recently, HbA1c was proposed as a diabetes diagnostic test as well. Regular monitoring of glycemic control and adjustment of
therapy towards the recommended HbA1c-based treatment-goals is a pivotal request of contemporary diabetes care guidelines, as well as a quality indicator proclaimed by numerous national health-care-delivery systems. Standardized and attainable analytical methodology of high-quality and a good knowledge on determinants of biological variability, able to influence test results, are crucial elements for the confident clinical use of HbA1c. In this review, essential analytical and clinical aspects necessary for the reliable use of HbA1c results in diabetes care are concisely presented, together with the degree of Croatian laboratory and clinical practice harmonization with the relevant international standards
Hepatomegalija i poviÅ”ene aminotransferaze u bolesnice s loÅ”e reguliranom Å”eÄernom boleÅ”Äu
Elevated liver function tests, right upper quadrant abdominal pain, and hepatomegaly occurring in a diabetic patient treated with high doses of insulin may point to the presence of pathologic glycogen accumulation in the liver parenchymal cells. The condition was first described in children, however, studies performed in adults have shown a condition that is similar in many aspects. A case is presented of a 41-year-old female diabetic patient with abnormal liver tests and hepatomegaly. Abdominal ultrasound confirmed liver enlargement without any signs of fatty liver. Liver biopsy revealed a picture compatible with glycogenosis. As excessive hepatic glycogen deposition occurred at an adult age and without a related family history, while the patient presented with normal mental and motor development, the diagnoses of Mauriac syndrome and hereditary were ruled out. The condition was attributed to insulin hyperdosage. The patient was recommended improved glycemic control, more appropriate diet and physical exercise. On follow-up visit 3 months of discharge from the hospital, significant hepatomegaly regression was demonstrated by palpation and ultrasonography, and was accompanied by normalization of serum aminotransferases, blood glucose and glycosylated hemoglobin. Elevated serum aminotransferases and alkaline phosphatase with hepatomegaly as a consequence of hepatocellular glycogen accumulation can occur in diabetic patients of any age who are treated with high doses of insulin, and should therefore be included in the differential diagnosis.Pojava poviÅ”enih jetrenih enzima, bolova u desnom gornjem abdominalnom kvadrantu i hepatomegalije u bolesnika sa Å”eÄernom boleÅ”Äu lijeÄenih visokim dozama inzulina može ukazivati na patoloÅ”ko nakupljanje glikogena u stanicama jetrenog parenhima. Ovo je stanje prvotno opisano u djece, a kasnije studije provedene na odraslima pokazale su jednaku kliniÄku sliku. Prikazan je sluÄaj 41-godiÅ”nje žene oboljele od Å”eÄerne bolesti s poremeÄenim jetrenim nalazima i hepatomegalijom, kod koje je ultrazvuk potvrdio poveÄanje jetre bez znakova steatoze, a biopsijom je postavljena dijagnoza glikogenoze. S obzirom na to da je izrazito nakupljanje glikogena u ovom sluÄaju nastupilo u odrasloj dobi, bez pozitivne obiteljske anamneze, a bolesnica je imala uredan psihiÄki i tjelesni razvoj, iz diferencijalne dijagnoze se je mogao iskljuÄiti Mauriacov sindrom i nasljedna glikogenoza. Uzrok ovoga stanja u ove bolesnice bilo je lijeÄenje osnovne bolesti visokim dozama inzulina. Stoga joj je preporuÄena poboljÅ”ana kontrola glikemije praÄena ispravnom dijetom i tjelesnom aktivnoÅ”Äu. Na kontrolnom pregledu nakon tri mjeseca doÅ”lo je do regresije hepatomegalije potvrÄene palpacijom i ultrazvukom, te do normaliziranja serumskih aminotransferaza, glukoze u krvi i glikoziliranog hemoglobina. PoviÅ”ene aminotransferaze i alkalna fosfataza uz hepatomegaliju mogu se naÄi kod bolesnika dijabetiÄara lijeÄenih visokim dozama inzulina, kao posljedica nakupljanja glikogena u jetrenim stanicama, pa ovo stanje treba ukljuÄiti u diferencijalnu dijagnozu
Hemoglobin A1c i kvaliteta skrbi za oboljele od Å”eÄerne bolesti [Hemoglobin A1c and the quality of diabetes care]
Global diabetes epidemics is currently representing one of the most prominent medical and societal challenges. Hemoglobin A1c (HbA1c), a biochemical marker of an average blood glucose concentration has been used for more than 30 years as a clinical indicator of both diabetes treatment efficacy and the risk for development of complications. Recently, HbA1C was proposed as a diabetes diagnostic test as well. Regular monitoring of glycemic control and adjustment of therapy towards the recommended HbA1c-based treatment-goals is a pivotal request of contemporary diabetes care guidelines, as well as a quality indicator proclaimed by numerous national health-care-delivery systems. Standardized and attainable analytical methodology of high-quality and a good knowledge on determinants of biological variability, able to influence test results, are crucial elements for the confident clinical use of HbA1c. In this review, essential analytical and clinical aspects necessary for the reliable use of HbA1c results in diabetes care are concisely presented, together with the degree of Croatian laboratory and clinical practice harmonization with the relevant international standards
Randomizirano dvostruko-slijepo ispitivanje uÄinkovitosti oktreotid acetata u sprjeÄavanju abdominalne boli nakon terapijske endoskopske retrogradne kolangiopankreatografije
Abdominal pain is a complication of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST). The aim of this trial was to investigate the effects of octreotide acetate in the prevention of abdominal pain in patients undergoing therapeutic ERCP. A double-blind study was carried out in 209 subjects who were randomly allocated to two groups (A and B). Group A (104 patients) received 0.5 mg of octreotide acetate subcutaneously one hour prior to ERCP; and group B (105 patients) were given placebo. Patients were assessed 2 and 24 hours following endoscopy for the following parameters: presence and character of abdominal pain, requirements of analgetics. Thirty-nine (18%) patients complained of post-ERCP pain, i.e. ten in group A and 29 in group B, all of them treated with analgetics. Of the ten group A patients, symptoms of acute pancreatitis were identified in four (3.85%) patients versus ten (9.52%) patients in the control group B. The results obtained in the study seem to indicate that octreotide pretreatment significantly reduced the development of post-ERCP pain.Abdominalna bol je Äesta komplikacija endoskopske retrogradne kolangiopankreatografije (ERCP) i endoskopske sfinkterotomije (EST). Cilj ovoga ispitivanja bio je istražiti uÄinke oktreotid acetata u prevenciji abdominalne boli u bolesnika podvrgnutih ERCP-u. U ovu dvostruko-slijepu studiju bilo je ukljuÄeno 209 bolesnika koji su nasumce podijeljeni u dvije skupine (A i B). Bolesnici skupine A (n=104) primili su 0,5 mg oktreotid acetata supkutano jedan sat prije ERCP-a, dok su bolesnici skupine B (n=105) dobili placebo. Procjena kliniÄkih parametara (prisutnost i težina abdominalne boli te potreba za analgeticima) provedena je u bolesnika 2 i 24 sata nakon endoskopije. Ukupno se 39 (18%) bolesnika žalilo na bol nakon ERCP-a, tj. desetoro u skupini A i 29 u skupini B, a svi su oni lijeÄeni analgeticima. Od desetoro bolesnika iz skupine A simptomi akutnog pankreatitisa zabilježeni su u Äetvoro (3,85%) bolesnika, u usporedbi s desetoro (9,52%) bolesnika u kontrolnoj skupini B. Rezultati ovoga ispitivanja pokazali su da je prethodno davanje oktreotida znaÄajno smanjilo nastup abdominalne boli nakon ERCP-a