Povezanost vaskularnih komplikacija s izostankom terapijskog učinka eksenatida u bolesnika sa šećernom bolešću tipa 2

Exenatide is an incretin mimetic that acts through glucagon-like peptide 1 receptor accepted as a successful novel glucose-lowering agent in type 2 diabetes. The aim of this study was to explore the possible predictive factors for exenatide efficacy among baseline characteristics of type 2 diabetic patients. We observed basic anthropometric measurements, laboratory findings and diabetic complications in ninety-one type 2 diabetic patients starting exenatide therapy. There were forty-six (50.5%) male and forty-five (49.5%) female patients, median age 58 (31-76) years, body mass index 38.95}4.35 kg/m2, duration of diabetes 10 (1-30) years and HbA1c level 8.3}1.4%. Thirty (33%) patients stopped therapy because of glycemic dysregulation during 105 (21-390) days on therapy. These patients differed statistically significantly from those that continued therapy according to the following seven variables: higher fasting glucose blood concentration (11.5 mmol/L (5.6-20) vs. 10.2 mmol/L (5-19), higher serum creatinine concentration (93 μmol/L (44-149) vs. 72 μmol/L (44-124), more frequent diabetic complications including retinopathy (56.7% vs. 27.9%), chronic kidney disease (43.7% vs. 24.7%), coronary artery disease (53.3% vs. 31.1%) and peripheral artery disease (60% vs. 34.4%), and less often concomitant metformin and exenatide therapy (62% vs. 82%). Bivariate logistic regression identified peripheral artery disease, coronary artery disease, retinopathy, and chronic kidney disease as risk factors for glycemic dysregulation on exenatide therapy. We found reasonable to consider that a higher rate of microvascular and macrovascular complications may indicate failure of exenatide therapy in the majority of patients.Eksenatid je inkretinski mimetik koji djeluje putem receptora proteina nalik glukagonu 1, široko prihvaćen kao uspješan novi lijek u terapiji šećerne bolesti tipa 2. Svrha ovoga istraživanja bila je istražiti moguće čimbenike predviđanja učinkovitosti terapije analizom osnovnih nalaza među bolesnicima sa šećernom bolešću tipa 2. Provedena je analiza antropometrijskih obilježja, laboratorijskih nalaza i evaluacija dijabetičnih komplikacija kod 91 bolesnika koji su započeli terapiju eksenatidom. Bilo je 46 (50,5%) bolesnika muškog spola i 45 (49,5%) ženskog spola; medjian dobi bio je 58 (31-76) godina, indeks tjelesne mase 38,95}4,35 kg/m2, trajanje šećerne bolesti 10 (1-30) godina s prosječnom vrijednosti HbA1c 8,3}1,4%. Tridesetoro (33%) bolesnika prekinulo je terapiju zbog loše regulacije glikemije tijekom 105 (21-390) dana. Sedam varijabli statistički ih je razlikovalo od skupine koja je postigla zadovoljavajuću glukoregulaciju na eksenatidu: više vrijednosti glukoze natašte (11,5 mmol/L (5,6-20) prema 10.2 mmol/L (5-19), više vrijednosti kreatinina u serumu (93 μmol/L (44-149) prema 72 μmol/L (44-124), viša učestalost razvijenih dijabetičnih komplikacija: retinopatije (56,7% prema 27,9%), kronične bubrežne bolesti (43,7% prema 24,7%), koronarne arterijske bolesti (53,3% prema 31,1%) i periferne arterijske bolesti (60% prema 34,4%), te rjeđa upotreba metformina u kombinaciji s eksenatidom (62% prema 82%). Bivarijatna logistička regresija identificirala je perifernu arterijsku bolest, koronarnu arterijsku bolest, retinopatiju i kroničnu bubrežnu bolest kao statistički značajne čimbenike rizika za disregulaciju glikemije na terapiji eksenatidom. Navedeni rezultati navode na zaključak kako bi razvijene mikrovaskularne i makrovaskularne komplikacije mogle biti čimbenik koji predviđa neuspjeh glukoregulacije eksenatidom

Association between Red Blood Cell Count and Renal Function Exist in Type 1 Diabetic Patients in the Absence of Nephropathy

Anemia is a prevalent finding in patients with type 1 diabetes, particularly in those with albuminuria or reduced re- nal function. We investigated the relationship between red blood cell count (RBC) and renal function in type 1 diabetic patients with normal or mildly impaired renal function and urinary albumin excretion rate (UAE) 60 mL min –1 1.73 m –2 , and be- fore any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. UAE was measured from at least two 24-h urine samples. Hemoglobin (Hb), hematocrit (Hct), erythrocytes (E), serum iron and ferritin levels were signifi- cantly lower in subjects in the highest quartile of serum creatinine compared to those in lowest quartile (132 vs 148 g/L, 0.39 vs 0.42 L/L, 4.5 vs 4.8x10 12 /L, 13 vs 18 µmol/L, and 25 vs 103 µg/L, respectively, for all p<0.001). Hb and Hct levels were significantly lower in subjects in the highest quartile of UAE compared to those in lowest quartile (135 vs 140 g/L, and 0.40 vs 0.41 L/L, respectively, for all p=0.03). Finally, those with mildly impaired eGFR had significantly lower lev- els of Hb, Hct and E compared to those with normal eGFR or hyperfiltrating subjects (133 vs 140 g/L, 0.38 vs 0.41 L/L, and 4.4 vs 4.7x10 12 /L, respectively, for all p=0.01). We have detected that interplay between RBC and renal function pa- rameters occurs even in type 1 diabetic patients with normal or mildly impaired renal function

Gordon Holmesov sindrom prvi put dijagnosticiran u Hrvatskoj

Prikazuje se 38-godišnja bolesnica koja se klinički prezentirala ataksijom, kognitivnom disfunkcijom i sekundarnom amenorejom, s izraženim hiperintenzivnim promjenama na magnetskoj rezonanciji mozga (MR). Klinički simptomi počeli su u dobi od 20 godina razvojem sekundarne amenoreje, nestabilnosti u hodu i kognitivnom disfunkcijom. Iako je ovakav skup povezanih simptoma ataksije, primarne/sekundarne amenoreje uslijed hipogonadotropnog hipogonadizma i kognitivne disfunkcije poznat kao Gordon Holmesov sindrom (GHS), takav do sada nije opisan u Hrvatskoj. Zbog navedenog, dotadašnja klinička dijagnostika u različitim neurološkim institucijama koja je bila u početku usmjerena primarno na ataksiju, kognitivni poremećaj te nalaz hiperintenzivnih promjena na MR-u mozga, zanemarujući sekundarnu amenoreju, bila je neuspješna. Analizom velike grupe autosomno-recesivnih cerebelarnih ataksija naša grupa uočila je podudarnost skupa kliničkih simptoma: cerebelarne ataksije, kognitivne disfunkcije i hipogonadotropnog hipogonadizma, uz karakterističan MR nalaz specifičnih subkortikalnih hiperintenzivnih promjena bijele tvari, talamusa i moždanog debla i cerebelarne atrofije, koji čine sindrom uzrokovan mutacijom gena ATM RNF216, Gordon Holmesov sindrom. Sekvencijska genomska analiza učinjena u Variantyx laboratoriju u SAD-u pokazala je u naše bolesnice složenu heterozigotnu mutaciju RNF216 što je potvrdilo dijagnozu GHS-a, prvi put dijagnosticiranog u Hrvatskoj

Glucagon-Like Peptide-1 Receptor Agonists and Dual Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity/Metabolic Syndrome, Prediabetes/Diabetes and Non-Alcoholic Fatty Liver Disease-Current Evidence

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the "cardiometabolic continuum " and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm

Ramipril and Risk of Hyperkalemia in Chronic Hemodialysis Patients

Angiotensin converting enzyme (ACE) inhibitors provide well known cardiorenal-protective benefits added to antihypertensive effects in chronic renal disease. These agents are underused in management of patients receiving hemodialysis (HD) because of common concern of hyperkalemia. However, few studies have investigated effect of renin angiotensin aldosterone system (RAAS) blockade on serum potassium in hemodialysis patients. We assessed the safety of ramipril in patients on maintenance HD. We enrolled 28 adult end stage renal disease (ESRD) patients treated by maintenance HD and prescribed them ramipril in doses of 1.25 to 5 mg per day. They underwent serum potassium concentration measurements before ramipril introduction and in 1 to 3 months afterwards. No significant increase in kalemia was found. Results of our study encourage the use of ACE inhibitors in chronically hemodialyzed patients, but close potassium monitoring is mandatory

Management of patients with adrenal incidentaloma – 2019 update

Zadnjih desetak godina došlo je do značajnih promjena u zdravstvenom zbrinjavanju bolesnika s incidentalomima nadbubrežne žlijezde koje su rezultirale novim preporukama za dijagnostiku i liječenje ovih bolesnika napravljenim u suradnji Europskoga endokrinološkog društva i Europske mreže za istraživanje tumora nadbubrežne žlijezde. Na temelju navedenih preporuka i višegodišnjega vlastitog iskustva Referentni centar Ministarstva zdravstva Republike Hrvatske za bolesti nadbubrežne žlijezde predlaže izmjene i dopune preporuka za dijagnostiku i liječenje ovih bolesnika objavljenih u Liječničkom vjesniku 2010. godine.In the last decade, the clinical care of patients with adrenal incidentaloma has been significantly changed which prompted the European Society of Endocrinology and European Network for the Study of Adrenal Tumors to develop an updated clinical practice guideline for the management of these patients. In accordance with the aforementioned recommendations and based on its own experience, the Croatian Referral Center for adrenal gland disorders provides an update of the previous guideline for the clinical management of patients with adrenal incidentaloma published in Liječnički vjesnik in 2010

PRECIPITATING FACTORS AND CLINICAL FEATURES OF DIABETIC KETOACIDOSIS

vod: Dijabetička ketoacidoza (DKA) jedna je od najozbiljnijih akutnih komplikacija šećerne bolesti (ŠB). Pojedina istraživanja su pokazala da su infekcije precipitirajući čimbenik u polovice ispitanika. Nekoliko novijih istraživanja naglašava da je loše pridržavanje liječenja također česti uzrok DKA. Cilj: Identifi cirati najčešće precipitirajuće čimbenike za DKA u Republici Hrvatskoj. Ispitanici i postupci: Ovo retrospektivno multicentrično istraživanje uključivalo je bolesnike sa ŠB-om tipa 1 ili tipa 2 s dijagnozom DKA između 1. siječnja 2014. i 31. prosinca 2018. i liječenih u 5 različitih središta za liječenje ŠB-a: Dubrovnik, Našice, Split, Zagreb i Osijek. U analizu je uključena samo prve epizoda DKA. Pacijenti koji boluju od steroidnog ŠB-a i ŠB-a zbog endokrinih poremećaja kao što su akromegalija i Cushingov sindrom bili su isključeni. Rezultati: Istraživanjem je obuhvaćeno 160 bolesnika (55 % muškaraca), od kojih je 68% imalo ŠB tip 1. Srednja dob ispitanika bila je 42 godine (od 18 do 89). Najčešći uzrok DKA bila je infekcija (57 %), zatim slabo kontrolirani ŠB (37 %) i prva prezentacija ŠB-a (9 %), dok je u 7% bolesnika DKA bila uzrokovana ostalim uzrocima kao što su kvar inzulinske pumpe, moždani ili srčani udar. U skupini bolesnika s infekcijama najčešće su bile infekcije mokraćnog sustava (30 %), probavne infekcije (30 %) i infekcije respiratornog trakta (19 %), dok je 21 % bolesnika imalo druge izvore infekcije. U 36 ovih bolesnika uz infekciju je bio prisutan i prethodno loše kontroliran ŠB, a u 12 % DKA uzrokovana infekcijom bila je prvo očitovanje bolesti. U bolesnika sa ŠB-om tipa 2 infekcije su češće bile uzrok DKA nego u bolesnika sa ŠB-om tipa 1 (P < 0,05). U bolesnika sa ŠB-om tipa 1, slabo regulirana glikemija je češće uzrok DKA (31%) nego u bolesnika sa ŠB-om tipa 2 (18 %). Zaključak: Najčešći precipitirajući čimbenici za razvoj DKA su infekcije i loša regulacija ŠB-a. Potrebna je bolja edukacija bolesnika o važnosti redovite primjene inzulina i korekcije terapije tijekom akutne bolesti.Introduction: Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus (DM). In some studies, infections have been found to be a precipitating factor in more than half of the subjects. On the other hand, several recent studies emphasize that poor treatment adherence is also a common cause of DKA. Objective: To identify the most common precipitating factors for DKA in Croatia. Patients and Methods: This retrospective, multicenter study included DM type 1 or DM type 2 patients diagnosed with DKA between January 1, 2014 and December 31, 2018, and treated in 5 different DM treatment centers, i.e., Dubrovnik, Našice, Split, Zagreb and Osijek. Only the fi rst episode of DKA was included in the analysis. Patients receiving steroids and DM due to endocrine disorders such as acromegaly and Cushing\u27s syndrome were excluded. Results: The study included 160 patients (55% of men), of whom 68% had DM type 1. The mean age of the respondents was 42 (18-89) years. The most common cause of DKA was infection (57%), followed by poorly controlled DM (37%) and fi rst presentation of DM (9%), while in 7% of patients DKA was due to other causes such as insulin pump failure, stroke or myocardial infarction. In the group of patients with infections, urinary tract infections (30%), gastrointestinal infections (30%) and respiratory tract infections (19%) were most common, whereas 21% of patients had other sources of infection. In 36% of these patients, the infection was associated with previously poorly controlled diabetes, and in 12% of them, DKA caused by the infection was the fi rst manifestation of the disease. In patients with type 2DM, infections were more often the cause of DKA than in patients with type 1DM (p<0.05).Poorly controlled glycemia appeared to be a more frequent cause of DKA in patients with type 1 DM (31%) than in patients with type 2 DM (18%). Conclusion: The most common precipitating factors for the development of DKA were infections and poor diabetes management. Better education of patients about the importance of regular insulin administration and correction of therapy in acute illness could reduce the risk of DKA

PRECIPITATING FACTORS AND CLINICAL FEATURES OF DIABETIC KETOACIDOSIS

vod: Dijabetička ketoacidoza (DKA) jedna je od najozbiljnijih akutnih komplikacija šećerne bolesti (ŠB). Pojedina istraživanja su pokazala da su infekcije precipitirajući čimbenik u polovice ispitanika. Nekoliko novijih istraživanja naglašava da je loše pridržavanje liječenja također česti uzrok DKA. Cilj: Identifi cirati najčešće precipitirajuće čimbenike za DKA u Republici Hrvatskoj. Ispitanici i postupci: Ovo retrospektivno multicentrično istraživanje uključivalo je bolesnike sa ŠB-om tipa 1 ili tipa 2 s dijagnozom DKA između 1. siječnja 2014. i 31. prosinca 2018. i liječenih u 5 različitih središta za liječenje ŠB-a: Dubrovnik, Našice, Split, Zagreb i Osijek. U analizu je uključena samo prve epizoda DKA. Pacijenti koji boluju od steroidnog ŠB-a i ŠB-a zbog endokrinih poremećaja kao što su akromegalija i Cushingov sindrom bili su isključeni. Rezultati: Istraživanjem je obuhvaćeno 160 bolesnika (55 % muškaraca), od kojih je 68% imalo ŠB tip 1. Srednja dob ispitanika bila je 42 godine (od 18 do 89). Najčešći uzrok DKA bila je infekcija (57 %), zatim slabo kontrolirani ŠB (37 %) i prva prezentacija ŠB-a (9 %), dok je u 7% bolesnika DKA bila uzrokovana ostalim uzrocima kao što su kvar inzulinske pumpe, moždani ili srčani udar. U skupini bolesnika s infekcijama najčešće su bile infekcije mokraćnog sustava (30 %), probavne infekcije (30 %) i infekcije respiratornog trakta (19 %), dok je 21 % bolesnika imalo druge izvore infekcije. U 36 ovih bolesnika uz infekciju je bio prisutan i prethodno loše kontroliran ŠB, a u 12 % DKA uzrokovana infekcijom bila je prvo očitovanje bolesti. U bolesnika sa ŠB-om tipa 2 infekcije su češće bile uzrok DKA nego u bolesnika sa ŠB-om tipa 1 (P < 0,05). U bolesnika sa ŠB-om tipa 1, slabo regulirana glikemija je češće uzrok DKA (31%) nego u bolesnika sa ŠB-om tipa 2 (18 %). Zaključak: Najčešći precipitirajući čimbenici za razvoj DKA su infekcije i loša regulacija ŠB-a. Potrebna je bolja edukacija bolesnika o važnosti redovite primjene inzulina i korekcije terapije tijekom akutne bolesti.Introduction: Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus (DM). In some studies, infections have been found to be a precipitating factor in more than half of the subjects. On the other hand, several recent studies emphasize that poor treatment adherence is also a common cause of DKA. Objective: To identify the most common precipitating factors for DKA in Croatia. Patients and Methods: This retrospective, multicenter study included DM type 1 or DM type 2 patients diagnosed with DKA between January 1, 2014 and December 31, 2018, and treated in 5 different DM treatment centers, i.e., Dubrovnik, Našice, Split, Zagreb and Osijek. Only the fi rst episode of DKA was included in the analysis. Patients receiving steroids and DM due to endocrine disorders such as acromegaly and Cushing\u27s syndrome were excluded. Results: The study included 160 patients (55% of men), of whom 68% had DM type 1. The mean age of the respondents was 42 (18-89) years. The most common cause of DKA was infection (57%), followed by poorly controlled DM (37%) and fi rst presentation of DM (9%), while in 7% of patients DKA was due to other causes such as insulin pump failure, stroke or myocardial infarction. In the group of patients with infections, urinary tract infections (30%), gastrointestinal infections (30%) and respiratory tract infections (19%) were most common, whereas 21% of patients had other sources of infection. In 36% of these patients, the infection was associated with previously poorly controlled diabetes, and in 12% of them, DKA caused by the infection was the fi rst manifestation of the disease. In patients with type 2DM, infections were more often the cause of DKA than in patients with type 1DM (p<0.05).Poorly controlled glycemia appeared to be a more frequent cause of DKA in patients with type 1 DM (31%) than in patients with type 2 DM (18%). Conclusion: The most common precipitating factors for the development of DKA were infections and poor diabetes management. Better education of patients about the importance of regular insulin administration and correction of therapy in acute illness could reduce the risk of DKA

LYSOSOMAL ACID LIPASE DEFICIENCY IN CHILDREN: OUR EXPERIENCE AND A NOVEL POSSIBILITY OF ENZYME REPLACEMENT THERAPY

Manjak lizosomske kisele lipaze autosomno je recesivno nasljedna bolest s dva klinička fenotipa. Wolmanova bolest počinje u ranoj dojenačkoj dobi i brzo je progresivna. Zbog masivnog nakupljanja kolesterolskih estera i triglicerida u crijevima, jetri, slezeni i drugim stanicama monocitno-makrofagnog reda dolazi do malapsorpcije, hepatosplenomegalije, zatajenja jetre i smrti u prvoj godini života. Bolest nakupljanja kolesterolskih estera može se očitovati od rane dječje do kasne odrasle dobi, varijabilna je tijeka i progresije. Glavna su obilježja različito izražena jetrena bolest, uključujući cirozu i zatajenje jetre, hiperkolesterolemija i rana ateroskleroza. Karakterističan je patohistološki nalaz mikrovezikularne steatoze i fibroze, a patognomoničan je ultrastrukturni nalaz kristala kolesterolskih estera. Dijagnozu potvrđuju mjerenje enzimske aktivnosti i/ili analiza gena. Liječenje je donedavno bilo suportivno i simptomatsko. Klinička istraživanja enzimskoga nadomjesnog liječenja pokazuju vrlo ohrabrujuće rezultate. Prikazujemo dojenče s Wolmanovom bolešću i dvoje djece s bolešću nakupljanja kolesterolskih estera s ciljem skretanja pozornosti na bolesti zbog manjka lizosomske kisele lipaze i što ranijeg početka optimalne skrbi.Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early