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A pancreaticus lipidakkumuláció – amelyet egyre gyakrabban NAFPD (non-alcoholic fatty pancreas disease) néven említenek az angol nyelvű szakirodalomban – az elmúlt néhány évben került az érdeklődés előterébe. Az elváltozást több, eltérő névvel illették korábban; a NAFPD megnevezést hazánkban még ma is csak ritkán használjuk, magyar nyelvű megfelelője sem kristályosodott ki. A pancreaticus lipidfelhalmozódást az ectopiás zsírszövet-akkumuláció egyik megjelenési formájaként tartják számon. A NAFPD felismerése képalkotó vizsgálatokkal lehetséges, a klinikai gyakorlatban leginkább az ultrahangvizsgálat és a komputertomográfia jön szóba, de a kvantifikáció még nem kiforrott. A NAFPD prevalenciája a felnőtt lakosság körében 30–35%-ra tehető, előfordulására elhízott gyermekek/serdülők körében is számíthatunk. A NAFPD érinti a pancreas endokrin és exokrin funkcióját. A NAFPD és a 2-es típusú diabetes/metabolikus szindróma összefüggését több tanulmány igazolta, a NAFPD lokális következményeiről még kevés ismerettel rendelkezünk. Adatok szólnak amellett, hogy a NAFPD-nak szerepe lehet a heveny és az idült pancreatitis, illetve a pancreascarcinoma kialakulásában, a pancreas exokrin diszfunkciójában. A NAFPD-t előnyösen befolyásolja a testsúly csökkenése, ami elhízottak körében életmód-terápiával, gyógyszeres intervencióval vagy bariátriai sebészeti beavatkozással érhető el. Fontos, hogy a 2-es típusú diabetesben szenvedő, testsúlyfelesleggel rendelkező betegek antihyperglykaemiás kezelése olyan antidiabetikumokkal történjen, amelyek a jó glykaemiás kontroll mellett testsúlyredukciót is eredményeznek. A NAFPD feltehetően gyakori, de ritkán felismert, viszonylag új klinikai entitás, amely a belgyógyászaton belül több szubspecialitás (gasztroenterológia, diabetológia, lipidológia, obezitológia), illetve a sebészet területén tevékenykedő szakemberek érdeklődési körébe esik. Orv Hetil. 2022; 163(44): 1735–1742.

Pancreatic lipid accumulation - which is known as NAFPD (non-alcoholic fatty pancreas disease) - has gained an increasing attention in the last couple of years. Previously, this alteration was mentioned using different names. Undoubtedly, the term of NAFPD is still rarely used in the Hungarian scientific literature, even the proper translation should be considered difficult. Pancreatic lipid accumulation is a clinical manifestation of ectopic occurrence of adipose tissue. NAFPD can be diagnosed by different imaging modalities. Although proper quantification of pancreatic lipid accumulation is challenging, ultrasonography and computed tomography are used in clinical practice. The prevalence of NAFPD was about 30-35% in different adult populations but a relatively higher frequency might also be observed in children and adolescents with obesity. NAFPD may influence both endocrine and exocrine functions of the pancreas. Clinical studies documented a close correlation between NAFPD and type 2 diabetes/metabolic syndrome. Local consequences of pancreatic lipid accumulation are less recognized but clinical observations suggested that NAFPD might play a role in the development of acute and chronic pancreatitis, pancreatic cancer, and pancreatic exocrine dysfunction. Therapeutically, weight loss in patients with obesity, due to life-style modification, pharmacological intervention or bariatric surgery, may reduce pancreatic lipid accumulation. Importantly, antihyperglycemic treatment of patients with type 2 diabetes should be performed by using antidiabetic drugs providing not only proper glycaemic control but even weight loss. NAFPD is a relatively new clinical entity which is rather common and probably underdiagnosed. Basic and new data about NAFPD are of importance for clinicians working in the field of different specialties and sub-specialties (internal medicine, gastroenterology, diabetology, lipidology, obesitology, surgery). Orv Hetil. 2022; 163(44): 1735-1742.

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Napjainkban a benfotiamin a neuropathiás károsodások oki kezelésének egyik alapgyógyszere. Bár mind hatásmechanizmusa, mind klinikai alkalmazási lehetőségei jól körvonalazottak, ismereteink folyamatosan gyarapszanak. A közlemény áttekinti klinikai farmakológiája és biokémiai hatásai főbb jellemzőit, valamint az adásával kapcsolatos újabb kísérletes és klinikai megfigyeléseket. Rámutat, hogy a hatóanyag kedvező mellékhatás-spektruma és sokoldalú alkalmazhatósága folytán indikációs köre várhatóan tovább bővülhet majd.

A 2-es típusú diabetes ( T2DM) prevalenciája jelentősen növekedett az elmúlt 2 évtizedben Magyarországon, ami jelentős társadalmi és egészségügyi teher kialakulásához vezetett, ezért a diabetes hatásának felmérése a magyar T2DM-es populáció halálozására mindinkább szükséges. Retrospektív tanulmányunkban a NEAK (Nemzeti Egészségbiztosítási Alap-kezelő) adatbázisa alapján felmértük a 2016-ban ismert T2DM-es betegek kor- és nemfüggő többlethalálozását a nem diabeteses populációhoz viszonyítva. A NEAK adatbázisban 2016-ban összesen 744 192 T2DM-es beteget tartottak nyilván, melynek 54,41%-a volt nő. Átlagos életkoruk 66,02 év volt. A legmagasabb T2DM-halálozást férfiaknál 70–74 éves korban (n=2721), nőknél 85 év felett találtunk (n=4525). A teljes férfi T2DM-es populációban a halálozás esélye férfiakban 42%-kal, nőknél 56%-kal volt magasabb 2016-ban, mint a magyar népesség nem diabeteses populációjában. A női T2DM-es populációban a halálozási esély majdnem minden korban magasabb volt, mint a férfiakban. Mindemellett a halálozási kockázati arány (RR) a korral fordítottan változott, míg a 35–39 éves korcsportban a T2DM-es nőknél az RR-érték 3,22, férfiaknál 2,25 (p

Az SGLT-2-gátlók kardiovaszkuláris és renális előnyeire a 2-es típusú cukorbetegek körében végzett biztonságossági vizsgálatok (EMPA-REG OUTCOME, CANVAS Program, DECLARE, VERTIS CV) eredményei hívták fel a figyelmet. Ehhez csatlakoztak később azok a vizsgálatok, amelyeket közvetlenül a szívelégtelenség, illetve az idült vesebetegség befolyásolásának megítélése érdekében terveztek (cukorbetegek és nem cukorbetegek körében). A jelenlegi közlemény az SGLT-2-gátlókkal kapcsolatos új klinikai tanulmányok eredményeit tekinti át, kitérve arra, hogy ennek nyomán hogyan újult meg a klinikai gyakorlat. Az új adatok megalapozták a szakmai irányelvek módosulását is. Napjainkban annak vagyunk szemtanúi, hogy az SGLT-2-gátlók az eredetileg csak diabetológusok által használt antihyperglykaemiás szerekből speciális kardiológiai és nefrológiai indikációval is rendelkező készítményekké válnak.

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings. ispartof: DIABETES OBESITY & METABOLISM vol:22 issue:10 pages:1705-1713 ispartof: location:England status: published

Aims: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. Methods: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. Results: Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3–64.4) at one year and 44.2% (95% CI 36.4–52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5–79.5) at six months to 52.8% (95% CI 51.6–59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1–3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. Conclusions: Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

Background and aimsNon-alcoholic fatty liver disease (NAFLD) increases cardiovascular morbidity and mortality, and carries poor long-term hepatic prognosis. Data about the role of genetic and environmental factors in the hepatic lipid accumulation are limited. The aim of the study was to evaluate the genetic and environmental impact on the hepatic lipid accumulation within a cohort of adult twin pairs.Patients and methodsWe investigated 182 twin subjects [monozygotic (MZ, n = 114) and dizygotic (DZ, n = 68) same-gender twins (age 56.0 ± 9.6 years; BMI 27.5 ± 5.0 kg/m2; females 65.9%)] who underwent computed tomography (CT) with a 256-slice scanner. Using non-enhanced CT-images, we calculated the average value of hepatic attenuation [expressed in Hounsfield unit (HU)] suggesting hepatic lipid content. Crude data were adjusted to age, sex, BMI and HbA1c values. Intra-pair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C) and unique environmental (E) components to the investigated phenotype.ResultsThe study cohort represented a moderately overweight, middle-aged Caucasian population. There was no significant difference between MZ and DZ twin subjects regarding hepatic CT-attenuation (57.9 ± 12.6 HU and 59.3 ± 11.7 HU, respectively; p = 0.747). Age, sex, BMI and HbA1c adjusted co-twin correlations between the siblings showed that MZ twins have stronger correlations of HU values than DZ twins (rMZ = 0.592, p < 0.001; rDZ = 0.047, p = 0.690, respectively). Using the structural equation model, a moderate additive genetic dependence (A: 38%, 95% CI 15–58%) and a greater unique environmental influence (E: 62%, 95% CI 42–85%) was found. Common environmental influence was not identified (C: 0%).ConclusionThe results of our classical CT-based twin study revealed moderate genetic and greater environmental influences on the phenotypic appearance of hepatic steatosis, commonly referred to as NAFLD. Favorable changes of modifiable environmental factors are of great importance in preventing or treating NAFLD.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.; METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping.; FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1577234194), there were 5119585 incident cases of type 2 diabetes, 4007064 deaths in those with type 2 diabetes, and 11854043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years).; INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes.; FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia. Copyright © 2022 Elsevier Ltd. All rights reserved.

Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes.In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR).In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources.All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes.US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Háttér: Kevés közlemény hasonlítja össze az 1-es típusú cukorbetegség szövődményeit a hasonlóan fiatal korú, 2-es típusú cukorbetegségben szenvedőkével. Vizsgálatunk célja a két cukorbetegség-típusban megfigyelhető mortalitási és morbiditási kockázat összehasonlítása volt 40 év alatti életkorúaknál. Módszerek: Azonosítottunk minden a Nemzeti Egészségbiztosítási Alapkezelő adatbázisában 2001 és 2014 között szereplő, fiatal felnőtt, 1-es típusú cukorbetegségben szenvedő beteget (n=11 863) és adataikat összehasonlítottuk egy hasonló korú, fiatal felnőtt 2-es típusú diabeteses betegcsoportéval (n=47 931). Az összes halálozás, myocardialis infarctus, stroke, bármilyen daganatos megbetegedés, diabeteses ketoacidosis és a hypoglykaemia előfordulását a cukorbetegség diagnózisától a halál bekövetkeztéig, vagy a tanulmányi időszak lezártáig követtük. Eredmények: Az összes halálozás kockázata magasabb volt 1-es, mint 2-es típusú cukorbetegségben (esélyhányados; 95%-os CI: 2,17; 1,95–2,41; p

Abstract: Type 2 diabetes – due to its natural course – should be considered as a progressive chronic disease. Owing to this fact, antihyperglycemic treatment should be continuously increased stepwise in order to achieve proper glycemic control. Lifestyle modification should be initiated immediately after manifestation, shortly followed by metformin monotherapy, and later, dual or triple combinations and, finally, injectable derivatives – only insulin in the past – should be used for appropriate glycemic control. Guidelines about treatment approach of patients with type 2 diabetes unequivocally emphasize and describe in detail the need of treatment intensification, in other words, stepwise escalation in clinical practice. In the last couple of years, evidences provided that step down therapy, simplification of complex treatment regimens should also be considered in certain cases. This approach was generally called de-escalation in antihyperglycemic treatment which should be considered in patients with type 2 diabetes 1) after bariatric (metabolic) surgery; 2) with significant weight reduction irrespective of its origin; 3) with complex insulin regimens where re-evaluation of this treatment was missed; 4) with continuously decreasing renal function; 5) among elderly patients with comorbidities; 6) in social deprivation. In this article, data about therapeutic de-escalation of antihyperglycemic treatment in patients with type 2 diabetes and first experiences with this treatment approach are summarized. Orv Hetil. 2019; 160(31): 1207–1215.

Microvascular complications are responsible for a major proportion of the burden associated with diabetes contributing to substantial morbidity, mortality, and healthcare burden in people with diabetes. Retinopathy, nephropathy, and neuropathy constitute the leading causes of blindness, end-stage renal disease, and lower-extremity amputations, respectively. Since the efficacy of causal therapies of diabetic microvascular complications is limited, especially in type 2 diabetes, there is an unmet need for adjunct treatments which should be effective despite ongoing hyperglycemia. Experimental studies have indicated that diabetic microvascular complications can be prevented or ameliorated by various biofactors in animal models by interfering with the pathophysiology of the underlying condition. Some of the findings related to biofactors, like α-lipoic acid and benfotiamine, could be translated into the clinical arena and confirmed in clinical trials, especially in those focusing on diabetic polyneuropathy. Given the micronutrient nature of these compounds, their safety profile is excellent. Thus, they have the potential to favorably modify the natural history of the underlying complication, but long-term clinical trials are required to confirm this notion. Ultimately, biofactors should expand our therapeutic armamentarium against these common, debilitating, and even life-threatening sequelae of diabetes.

Background and Objectives: In patients with diabetes mellitus, hypoglycaemic episodes, especially during night hours, carry a significant risk. Data about the occurrence of nocturnal hypoglycaemia in real-world settings are of clinical importance. The aim of our study was to evaluate the occurrence of nocturnal hypoglycaemia among patients with diabetes using self-monitoring of blood glucose (SMBG) with telemedicine support. Materials and Methods: We retrospectively analysed the central database of an internet-based supportive system between 2010 and 2020 when 8190 SMBG users uploaded nearly 10 million capillary blood glucose values. Nocturnal hypoglycaemia was defined as capillary blood glucose &lt, 3.0 mmol/L measured between 00:00 and 05:59 h. Results: The database contained 914,146 nocturnal blood glucose values from 7298 users, 24,623 (2.7%) glucose values were below the hypoglycaemic threshold and 2363 patients (32.4%) had at least one hypoglycaemic glucose value. Nocturnal hypoglycaemia was more often found in patients with type 1 vs. type 2 diabetes (n = 1890 (80.0%) vs. n = 387 (16.4%), respectively). Hypoglycaemic blood glucose values were most frequently observed in the age group of 10.0–19.9 years (n = 481 (20.4%)). Patients with nocturnal hypoglycaemia were mostly on insulin treatment (1854 (78.5%) patients with 20,727 (84.1%) hypoglycaemic glucose values). Only 356 patients (15.1%) with nocturnal hypoglycaemia performed a retest within 120 min. Within a one-day-long (1440 min) timeframe, the elapsed median time until a retest, yielding a safe blood glucose value (&gt, 3.9 mml/L), was 273 min (interquartile range: 157–300 min). Conclusions: Nocturnal hypoglycaemia should be considered as a persisting challenge to antihyperglycaemic treatment in patients living with diabetes. Continuous efforts are needed to improve both antihyperglycaemic treatment and patient education for preventing nocturnal hypoglycaemia, and to act adequately if hypoglycaemic values are detected.

Background: Several studies showed that lipid accumulation in the pancreas (NAFPD: nonalcoholic fatty pancreas disease) may lead to different pancreatic disorders, including beta-cell dysfunction. ...

Background The clinical significance of myocardial bridging (MB) on the left anterior descending artery (LAD) is debated. We aimed to assess the association between MB and LAD plaque volumes/compositions in a case-control set up. Methods In our retrospective analysis we investigated 50 cases with incidentally recognized LAD MB and 50 matched controls without LAD MB on coronary computed tomography angiography. We quantified plaque volumes proximal to the MB and beneath it in patients with MB and in the corresponding coronary segments in patients without MB. Results In total, we have included 100 patients (mean age 60.6 ± 10.8 years, males: 80%). Plaque volume was similar in the LAD segments proximal to the MB in cases vs. controls (150.0 mm3 [IQR: 90.7–194.5 mm3] vs. 132.8 mm3 [IQR: 94.2–184.3 mm3], respectively; p = 0.95) while the plaque volume was smaller beneath LAD MB vs. control segment (16.2 mm3 [IQR: 12.6–25.8 mm3] vs. 21.1 mm3 [IQR: 14.0–42.4 mm3], respectively; p = 0.002). No significant differences were found regarding different plaque components in segments proximal to the MB while fatty plaque and necrotic core volumes were smaller or negligible in coronary segment beneath MB than in controls (0.07 mm3 [IQR: 0.005–0.27 mm3] vs. 12.7 mm3 [IQR: 7.4–24.4 mm3] and 0.00 mm3 [IQR: 0.00–0.04 mm3] vs. 0.06 mm3 [IQR: 0.03–2.8 mm3], respectively (p Conclusion Comparing patients with MB vs. matched controls without it, MB was not associated with increased plaque volumes in LAD segment proximal to MB and plaque quantity was smaller in the MB segment. Our data are supportive of benign nature of incidentally recognized LAD MB.

T2DM is associated with a higher risk of all-cause mortality; however, detailed analyses of age- and gender-specific subgroups are rare. The aim of the study was to analyze the changes of age- and gender-specific all-cause mortality rates and ratios (excess risk) in T2DM subjects (aged >40 years) in Hungary between 2001 and 2016. We used the central database of the National Institute of Health Insurance Fund. Annual all-cause mortality rates and ratios (T2DM/non-T2DM) were determined in males/females and in different age-groups (41-50, 51-60, 61-70, >71 years). Age-adjusted values were used for evaluating standardized mortality rates. Among pharmacologically treated T2DM subjects we found 117,700 and 329,845 males, 232,143 and 391,382 females in 2001 and 2016, respectively. Standardized all-cause mortality rate was higher in males than females in 2001 (4540/100,000 vs. 3365/100,000) which decreased to 4125/100,000 in males (change: -11.8%, p Disclosure G. Jermendy: None. Z. Kiss: None. G. Rokszin: None. I. Fábián: None. I. Wittmann: None. P. Kempler: None. Funding Hungarian Diabetes Association (2019)

Aims To evaluate comprehensively the safety of dapagliflozin in patients with type 2 diabetes (T2DM), with emphasis placed on potential safety concerns related to the sodium-glucose co-transporter-2 inhibitor class. Methods In the Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) study, 17 160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evaluated in 17 143 patients receiving at least one dose of study drug. Results Acute kidney injury occurred less frequently with dapagliflozin, and adverse events suggestive of volume depletion were balanced between treatment groups, both irrespective of baseline estimated glomerular filtration rate, blood pressure, diuretic or loop diuretic use (interaction P values >0.05). Fractures and malignancies were balanced between the groups, irrespective of sex, diabetes duration or smoking (interaction P values >0.05) and fewer cases of bladder cancer occurred in the dapagliflozin versus the placebo group. Diabetic ketoacidosis was very rare, but more frequent with dapagliflozin versus placebo (27 vs. 12 patients with events; P = 0.02), yet signs, symptoms and contributing factors were similar in the two groups. Major hypoglycaemia occurred less frequently with dapagliflozin versus placebo, regardless of baseline use of either insulin or sulphonylureas (interaction P values >0.05). There were more adverse events of genital infections leading to discontinuation of study drug in the dapagliflozin versus the placebo group, but serious genital infections were few and balanced between treatment groups. Urinary tract infections, acute pyelonephritis and urosepsis were also balanced between treatment groups. Conclusions Dapagliflozin was well tolerated. The long duration and large number of patient-years in DECLARE-TIMI 58 comprehensively addressed previous safety questions, confirming the robust safety profile of dapagliflozin.

Abstract: Introduction: Being entitled for no patient co-payment, the Hungarian reimbursement condition of analogue insulins as part of basal-bolus treatment in type 2 diabetes mellitus (T2DM) requires that two HbA1c levels should achieve 1c >9.0%). Method: This one-year, non-interventional study included patients with T2DM inadequately controlled (HbA1c >9.0%) on previous human basal-bolus treatment. The main outcomes were the proportion of patients who achieved the adequate glycaemic control (defined by the reimbursement rules) and the proportion of patients who achieved reimbursement rules defined HbA1c 1c value 1c measurements had not met the reimbursement requirements in a significant part of patients. Orv Hetil. 2018; 159(50): 2122–2128.

Introduction Adequate persistence to antidiabetic treatment is highly important to achieve proper glycemic control. In this study we evaluate the persistence to treatment with dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists in a nationwide cohort of patients with type 2 diabetes. Methods Using a central database in Hungary, we analyzed the persistence to the treatment with dipeptidyl peptidase-4 inhibitors (n = 59,900), sodium-glucose co-transporter-2 inhibitors (n = 26,052), and glucagon-like peptide-1 receptor agonists (n = 17,332) at treatment intensification between 2014 and 2016. We also compared the persistence of dipeptidyl peptidase-4 inhibitors (n = 9163) and sodium-glucose co-transporter-2 inhibitors (n = 1257) in initial therapy to that of metformin (n = 79,305) or sulfonylureas (n = 29,057). The rates of persistence to treatment and risk of non-persistence are reported. Results The persistence rates of dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists at treatment intensification were 69.6%, 67.8%, and 66.3% at year 1 which decreased to 57.3%, 56.8%, and 52.1% by year 2, respectively. The risk of non-persistence was higher by 6.6% (95% CI 3.6–9.6) for sodium-glucose co-transporter-2 inhibitors and by 8.3% (95% CI 5.0–11.5) for glucagon-like peptide-1 receptor agonists as compared to dipeptidyl peptidase-4 inhibitors. Novel oral antidiabetic drugs in fixed versus free add-on combinations with metformin had higher persistence. The persistence to treatment with novel oral antidiabetic drugs in initial therapy was better (dipeptidyl peptidase-4 inhibitors, 59.6% and 47.6%; sodium-glucose co-transporter-2 inhibitors, 61.9% and 47.0%) than that of initial monotherapy with metformin (47.0% and 39.1%) or sulfonylureas (52.4% and 41.8%) at years 1 and 2, respectively. Conclusion Analysis of persistence of treatment with novel glucose-lowering medications revealed differences between drug classes, favoring dipeptidyl peptidase-4 inhibitors vs. sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Persistence data of novel antihyperglycemic agents may be useful for guiding the decision at initiation of antidiabetic treatment. Funding Hungarian Diabetes Association. Plain Language Summary Plain language summary available for this article.

Abstract: The effect of antihyperglycaemic (antidiabetic) treatment on the late diabetic complications is one of the most important research areas in clinical diabetology. The relationship between glycaemic control and late micro- and macrovascular complications was highlighted by the results of the DCCT (Diabetes Control and Complications Trial) with type 1 and by the UKPDS (United Kingdom Prospective Diabetes Study) with type 2 diabetic patients. In these studies, observational follow-up investigations were also performed after the close-out of the randomized phase of the trial. In addition to these landmark studies, other randomized, controlled efficacy trials were also performed with observational follow-up investigations resulting in the development of the concept of metabolic memory or metabolic legacy. In this article, the main results of the studies are summarized. Orv Hetil. 2018; 159(15): 575–582.

Abstract: Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615–619.

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.