Laboratorijska medicina u šećernoj bolesti: Conditio sine qua non kvalitetnog standarda zdravstvene zaštite

Harmonizirana i racionalna laboratorijska medicina utemeljena na znanstvenim dokazima jest conditio sine qua non kvalitetnog standarda zdravstvene zaštite osoba sa šećernom bolešću. U ovom pregledu prikazane su aktualne mogućnosti laboratorijske medicine u ostvarenju ciljeva Nacionalnog programa zdravstvene zaštite osoba sa šećernom bolešću 2015.-2020. Ministarstva zdravlja Republike Hrvatske te prijedlog aktivnosti za unaprjeđenje kvalitete područja nužne za svrhovito i racionalno postizanje ciljeva. S obzirom na preventivnu prirodu Nacionalnog programa, fokus pregleda je na široko zastupljenim pretragama iz područja opće medicinske biokemije. Ovaj pregled svjedoči o dugogodišnjim strukturiranim aktivnostima koje laboratorijska medicina, zalaganjem prije svega kliničkog laboratorija Referentnog centra za šećernu bolest Republike Hrvatske, u tom smislu poduzima, no problematizira i brojna područja koja još uvijek zahtijevaju značajno i žurno unaprjeđenje kvalitete. Šećerna bolest je paradigma nužnosti suradnje kliničke i javnozdravstvene medicine s laboratorijskom medicinom jer jedino zajednička nastojanja u strukturiranim programima daju optimalna rješenja. Nacionalni program predstavlja poticaj za unaprjeđenje kvalitete i daljnje usklađivanje laboratorijske prakse u Hrvatskoj s međunarodnim standardima, na dobrobit oboljelih od šećerne bolesti

Laboratorijska medicina u šećernoj bolesti: Conditio sine qua non kvalitetnog standarda zdravstvene zaštite

Harmonizirana i racionalna laboratorijska medicina utemeljena na znanstvenim dokazima jest conditio sine qua non kvalitetnog standarda zdravstvene zaštite osoba sa šećernom bolešću. U ovom pregledu prikazane su aktualne mogućnosti laboratorijske medicine u ostvarenju ciljeva Nacionalnog programa zdravstvene zaštite osoba sa šećernom bolešću 2015.-2020. Ministarstva zdravlja Republike Hrvatske te prijedlog aktivnosti za unaprjeđenje kvalitete područja nužne za svrhovito i racionalno postizanje ciljeva. S obzirom na preventivnu prirodu Nacionalnog programa, fokus pregleda je na široko zastupljenim pretragama iz područja opće medicinske biokemije. Ovaj pregled svjedoči o dugogodišnjim strukturiranim aktivnostima koje laboratorijska medicina, zalaganjem prije svega kliničkog laboratorija Referentnog centra za šećernu bolest Republike Hrvatske, u tom smislu poduzima, no problematizira i brojna područja koja još uvijek zahtijevaju značajno i žurno unaprjeđenje kvalitete. Šećerna bolest je paradigma nužnosti suradnje kliničke i javnozdravstvene medicine s laboratorijskom medicinom jer jedino zajednička nastojanja u strukturiranim programima daju optimalna rješenja. Nacionalni program predstavlja poticaj za unaprjeđenje kvalitete i daljnje usklađivanje laboratorijske prakse u Hrvatskoj s međunarodnim standardima, na dobrobit oboljelih od šećerne bolesti

Hemoglobin A1c: Standardization of the “gold standard”

Hemoglobin A1c (HbA1c) je u proteklih 30 godina primjene postao "zlatnim standardom" u kliničkom praćenju šećerne bolesti. Dobra kontrola glikemije, izražena kroz koncentraciju HbA1c ≤7%, danas je klinički normativ kroz koji se procjenjuje djelotvornost terapije i rizik pojave komplikacija šećerne bolesti i glavna tema komunikacije između dijabetologa i pacijenata. Raznovrsna i nestandardizirana metodologija, varijabilnost kemijskih entiteta nastalih glikacijom molekule hemoglobina i nepostojanje primarnoga referentnog materijala značajno utječu na pouzdanost primjene HbA1c u kliničkoj praksi. Međunarodna federacija za kliničku kemiju i laboratorijsku medicinu (IFCC) je 2002. godine objavila referentnu metodu za HbA1c. Zajedno s metodom definiran je analit i proizveden primarni, specifični referentni materijal. Međutim, primjena referentne metode onemogućena je značajno nižim rezultatima HbA1c u odnosu na "konvencionalne" metode. Naime, kliničke smjernice i standardi utemeljeni su na rezultatu dugogodišnjih istraživanja, gdje se koristila precizna, ali nedovoljno specifična metodologija. Moguće snižavanje apsolutnih koncentracija HbA1c, koje bi nastalo uvođenjem IFCC-referentnog sustava, predstavlja ozbiljnu prepreku u postizanju i održavanju dobre kontrole šećerne bolesti. Stoga dijabetološka struka energično inzistira na zadržavanju postojećih standarda. Harmonizacija određivanja HbA1c ključno je pitanje kako individualne skrbi za bolesnike, tako i evaluacije kliničkih istraživanja. Međutim, njena provedba nužno podrazumijeva kombinaciju analitičkih i kliničkih standarda. Stoga je predložen "treći put", odnosno derivacija novog parametra "prosječne glikemije", koji bi sublimirao analitičke prednosti IFCC-referentnog sustava i dragocjene kliničke podatke. Cilj ovog preglednog članka jeprikazglobalnog projekta harmonizacije određivanja HbA1c, te predstavljanje aktivnosti poduzetih u tom smislu u Hrvatskoj.Hemoglobin A1c (HbA1c) has been used as a "gold standard" for clinical management of diabetes mellitus for almost 30 years. A good glycemic control, expressed as HbA1c value ≤7%, today is considered to be a clinical standard for the assessment of both therapeutic efficacy and the risk for development of diabetic complications. It is also a main subject of communication between diabetologists and patients. Variable and unstandardized methodology, different chemical entities resulting from glycation of the hemoglobin molecule, and a lack of the primary reference material significantly influenced a reliable use of HbA1c in the clinical practice. In 2002, International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has published a reference method for HbA1c. Together with the method, an analyte has been defined, and a primary, specific reference material has been produced. However, the application of the reference method has been dimmed because of the significantly lower HbA1c values, when compared to "conventional" methods. Clinical guidelines and standards have been based on the results of long-term studies where a precise, but insufficiently specific methodology was used. The possibility of lowering absolute HbA1c values, resulting from IFCC reference method implementation, has been recognized as a serious drawback in attaining and maintaining good metabolic control. Therefore, clinical diabetology has insisted vigorously in keeping existing standards. Harmonization of HbA1c determination is a key issue of both individual patient care and evaluation of clinical research results. However, a combination of both analytical and clinical standards is implicated in pursuing this goal. Thus, a "third way" has been proposed that offers a derivation of the new parameter "mean blood glucose", representing a sublimation of the analytical advantages offered by IFCC-reference system and valuable clinical data. The aim of this article was to review the global HbA1c harmonization project, and to introduce the respective activities carried out in Croatia

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

Slobodni tiroksin i trijodtironin su povezani s bubrežnom funkcijom u normoalbuminuričnih eutireoidnih bolesnika sa šećernom bolešću tipa 1

Both hypothyroidism and hyperthyroidism affect renal function. The aim of this study was to investigate the relationship between parameters of thyroid function (TSH, free triiodothyronine (FT3), and free thyroxine (FT4)) and parameters of renal function in patients with type 1 diabetes (T1DM). The study included 272 T1DM with normoalbuminuria and estimated glomerular filtration rate (eGFR) > 60 ml/min-11.73m-2, normal thyroid function, and without antihypertensive and antihyperlipidemic therapy. TSH significantly correlated with urinary albumin excretion rate (UAE) (r=-0.15, p<0.05) and fT3 with serum creatinine (r=0.12, p<0.05). Furthermore, fT4 significantly correlated with all renal function parameters (serum creatinine, eGFR and UAE (r=-0.12, 0.34 and -0.13, respectively, for all p<0.05)). Patients in the highest quartile of fT4 had significantly higher eGFR levels compared to those in the lowest quartile (116 vs. 101 ml/min-11.73m-2, p<0.001). In logistic regression analysis, after adjustment for covariates, fT3 and fT4 were significantly associated with worsening of renal function parameters with odds ratios of 0.75 to 1.29. This study, conducted in euthyroid T1DM with normoalbuminuria and eGFR > 60 ml/min-11.73m-2 without therapeutic intervention, suggests that the thyroid function may be connected with renal function parameters even in the euthyroid range.Hipotireoza kao i hipertireoza utječu na bubrežnu funkciju. U ovoj studiji istraživali smo povezanost između TSH, slobodnog trijodtironina (sT3) i slobodnog tiroksina (sT4) s parametrima bubrežne funkcije u normoalbuminuričnih bolesnika sa tipom 1 šećerne bolesti (ŠB1). Studija je uključila 272 bolesnika sa ŠB1 i normalnom funkcijom štitnjače te prije terapije statinima, ACE-inhibitorima ili blokatorima receptora angiotenzina 2. Studija je uključila bolesnike s glomerularnom filtracijom (GF) > 60 mlmin-11.73m-2. sT4 je statistički značajno korelirao s serumskim kreatininom, GF i albuminurijom (r=-0.12, 0.34 i -0.13, za sve p<0.05), TSH je statistički značajno korelirao s albuminurijom (r=-0.15, p<0.05) a sT3 s serumskim kreatininom (r=0.12, p<0.05). Razina GF bila je značajno viša u ispitanika u najvišoj kvartili sT4 u usporedbi s onim u najnižoj kvartili (116 prema 101 ml min-1 1.73m-2, p<0.001). U logističkoj regresiji, nakon prilagodbe za dob, spol, indeks tjelesne težine, trajanje šećerne bolesti i HbA1c, sT3 i sT4 bili su statistički značajno povezani s rizikom od pogoršanja bubrežne funkcije u naših bolesnika s omjerom izgleda (odds ratios) između 0.75 i 1.29. Ova studija, provedena na eutireotičnim normoalbuminuričnim bolesnicima s ŠB1 bez terapijskih intervencija, ukazala je da je utjecaj funkcije štitnjače na parametre bubrežne funkcije prisutan već i u stanju eutireoze

Persons with latent autoimmune diabetes in adults express higher dipeptidyl peptidase-4 activity compared to persons with type 2 and type 1 diabetes

AIMS: We aimed to determine serum dipeptidyl peptidase-4 (DPP-4) activity in a group of persons with latent autoimmune diabetes in adults (LADA) and to compare it with persons with type 1, type 2 diabetes and healthy controls. ----- METHODS: DPP-4 activity measurement was performed in 67 persons (21 with type 1, 26 type 2 and 19 with LADA) and 13 healthy age and gender matched controls. ----- RESULTS: Persons with LADA showed highest DPP-4 activity among the study groups (32.71±3.55 vs 25.37±2.84 vs 18.57±2.54 vs 18.57±2.61U/L p<0.001). Mean glutamic acid autoantibody in persons with LADA was 164.32±86.28IU/mL. It correlated with DPP-4 activity (r=0.484, p=0.013). Furthermore, DPP-4 activity correlated with waist circumference (r=0.279, p=0.034) and glycated haemoglobin A1c (r=0.483, p<0.001), as well as with LDL cholesterol (r=0.854, p<0.001) and total daily insulin dose (r=0.397, p=0.001). In the multinomial regression analysis DPP-4 activity remained associated with both LADA (prevalence ratio 1.058 (1.012-1.287), p=0.001) and type 1 diabetes (prevalence ratio 1.506 (1.335-1.765), p<0.001) while it did not show an association with type 2 diabetes (prevalence ratio 0.942 (0.713-1.988), p=0.564). ----- CONCLUSIONS: Persons with LADA express higher DPP-4 activity compared to persons with both type 1 and type 2 diabetes. The possible pathophysiological role of DPP-4 in the LADA pathogenesis needs to be further evaluated

Pregnancy outcome and liraglutide levels in serum and umbilical vein blood of a woman with type 2 diabetes. A case report

Background: According to FDA guidelines, liraglutide should be used on the basis of careful consideration in pregnant women with Type 2 diabetes mellitus. The aim of the present study was to record the concentration of liraglutide in maternal and umbilical vein serum from a pregnant woman treated with liraglutide. Case report: The pregnant woman we present in this case report is a 28-year-old diagnosed with Type 2 diabetes mellitus for 7 years. In spite of high insulin dose her glycaemia was poorly controlled, she developed dyslipidaemia and her body weight increased; thus, her diabetologist prescribed liraglutide injections and metformin. At booking, obstetrical ultrasound confirmed intrauterine pregnancy of 8 gestational weeks. The patient was informed about all possible consequences for her foetus that might be caused by liraglutide therapy during pregnancy. She continued her treatment with liraglutide and metformin medication throughout pregnancy. Her pregnancy was terminated by elective Caesarean section at 39 gestational weeks; a healthy newborn male was delivered. The concentration of liraglutide was measured in maternal and umbilical vein serum. Conclusion: There was no significant transfer of liraglutide from the circulation of the treated mother to her fetus, at least 3.5 h after the drug application

HEMOGLOBIN A1c AND THE QUALITY OF DIABETES CARE

Globalna epidemija šećerne bolesti jedan je od najvećih izazova suvremene medicine i društva u cjelini. Hemoglobin A1c (HbA1c), biokemijski biljeg prosječne glikemije, već se više od 30 godina rabi kao klinički pokazatelj uspješnosti liječenja i rizika od razvoja komplikacija šećerne bolesti. HbA1c je nedavno preporučen i kao dijagnostički test za šećernu bolest. Redovito praćenje kontrole glikemije i prilagođavanje terapije prema odgovarajućim ciljnim vrijednostima HbA1c ključni je zahtjev svih suvremenih dijabetoloških smjernica te pokazatelj kvalitete zdravstvene skrbi brojnih nacionalnih zdravstvenih sustava. Standardizirana, dostupna i kvalitetna analitička metodologija, uz dobro poznavanje bioloških čim­benika koji mogu utjecati na nalaze testa, presudni su za sigurnu kliničku primjenu HbA1c. U ovom pregledu sažeto su prikazani ključni analitički i klinički čimbenici nužni za pouzdanu uporabu nalaza HbA1c u skrbi za oboljele od šećerne bolesti te razina usklađenosti hrvatske laboratorijske i kliničke prakse s relevantnim međunarodnim 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

Hemoglobin A1c i kvaliteta skrbi za oboljele od šećerne 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

HEMOGLOBIN A1c AND THE QUALITY OF DIABETES CARE

Globalna epidemija šećerne bolesti jedan je od najvećih izazova suvremene medicine i društva u cjelini. Hemoglobin A1c (HbA1c), biokemijski biljeg prosječne glikemije, već se više od 30 godina rabi kao klinički pokazatelj uspješnosti liječenja i rizika od razvoja komplikacija šećerne bolesti. HbA1c je nedavno preporučen i kao dijagnostički test za šećernu bolest. Redovito praćenje kontrole glikemije i prilagođavanje terapije prema odgovarajućim ciljnim vrijednostima HbA1c ključni je zahtjev svih suvremenih dijabetoloških smjernica te pokazatelj kvalitete zdravstvene skrbi brojnih nacionalnih zdravstvenih sustava. Standardizirana, dostupna i kvalitetna analitička metodologija, uz dobro poznavanje bioloških čim­benika koji mogu utjecati na nalaze testa, presudni su za sigurnu kliničku primjenu HbA1c. U ovom pregledu sažeto su prikazani ključni analitički i klinički čimbenici nužni za pouzdanu uporabu nalaza HbA1c u skrbi za oboljele od šećerne bolesti te razina usklađenosti hrvatske laboratorijske i kliničke prakse s relevantnim međunarodnim 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