Incident Cancer Risk of Patients with Prevalent Type 2 Diabetes Mellitus in Hungary (Part 2).

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [ORmales: 2.76 (2.70-2.82) vs. ORfemales: 2.27 (2.22-2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [-1.79% (-2.07--1.52%), p < 0.0001] vs. -0.50% (-1.12-+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM.

Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - A nationwide database analysis from Hungary.

AIMS: Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies. METHODS: We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed. RESULTS: Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95% CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95% CI: 0.62-0.82, p < 0.0001), hospitalization for heart failure (HR 0.72, 95% CI: 0.66-0.78, p < 0.0001), cancer events (HR 0.83, 95% CI: 0.76-0.92, p = 0.0002) and all-cause mortality (HR 0.55, 95% CI: 0.49-0.61, p < 0.0001), but not for lower limb amputation (HR 1.05, 95% CI: 0.89-1.25, p = 0.5455). This association was supported by results of evaluating annual event rates and sensitivity analyses. CONCLUSIONS: This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.

[Lipid accumulation in the pancreas: clinical significance of NAFPD (non-alcoholic fatty pancreas disease)] / A nem alkoholos hasnyálmirigy-elzsírosodás klinikai jelentosége

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.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Sodium-Glucose Co-Transporter 2 Inhibitors May Change the Development of Urinary Tract and Hematological Malignancies as Compared With Dipeptidyl Peptidase-4 Inhibitors: Data of the Post-Hoc Analysis of a Nationwide Study.

BACKGROUND: In diabetes mellitus, during the last years, cancer became of equivalent importance as a cardiovascular disease in terms of mortality. In an earlier study, we have analyzed data of the National Health Insurance Fund (NHIF) of Hungary with regards all patients treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) vs. those treated with dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4is) in a given timeframe. In propensity score-matched groups of SGLT2i- vs. DPP-4i-treated patients, we found a lower incidence of cancer in general. In this post-hoc analysis, we aimed to obtain data on the incidence of site-specific cancer. PATIENTS AND METHODS: All patients starting an SGLT2i or a DPP-4i between 2014 and 2017 in Hungary were included; the two groups (SGLT2i vs. DPP-4i) were matched for 54 clinical and demographical parameters. The follow-up period was 639 vs. 696 days, respectively. Patients with a letter "C" International Classification of Diseases, 10th Revision (ICD-10) code have been chosen, and those with a known malignancy within a year before the onset of the study have been excluded from the analysis. RESULTS: We found a lower risk of urinary tract [HR 0.50 (95% CI: 0.32-0.79) p = 0.0027] and hematological malignancies [HR 0.50 (95% CI: 0.28-0.88) p = 0.0174] in patients treated with SGLT2i vs. those on DPP-4i. Risk of other types of cancer (including lung and larynx, lower gastrointestinal (GI) tract, rectum, pancreas, non-melanoma skin cancers, breast, or prostate) did not differ significantly between the two groups. When plotting absolute risk difference against follow-up time, an early divergence of curves was found in case of prostate, urinary tract, and hematological malignancies, whereas late divergence can be seen in case of cancers of the lung and larynx, the lower GI tract, and the breast. CONCLUSIONS: Urinary tract and hematological malignancies were less frequent in patients treated with SGLT2i vs. DPP-4i. An early vs. late divergence could be observed for different cancer types, which deserves further studies.

Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study.

INTRODUCTION: Mortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model. RESULTS: After propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p<0.0001) were lower in the SGLT2i population compared with DPP-4i. Risk of LLA was higher in the SGLT2i group (HR, 1.35; 95% CI 1.03 to 1.77; p=0.0315). SGLT2i in combination with DPP-4i results in lower all-cause mortality (HR, 0.46; 95% CI 0.31 to 0.67; p=0.0001), with a lower trend in stroke, LLA, HHF and cancer, but without any statistical difference. CONCLUSIONS: SGLT2i treatment leads to a lower risk of overall mortality, HHF and cancer when compared with DPP-4i treatment. Adding SGLT2i to DPP-4i instead of switching from DPP-4i to SGLT2i further lowers the risk of all-cause mortality.

Safety of dapagliflozin in a broad population of patients with type 2 diabetes: Analyses from the DECLARE-TIMI 58 study.

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.

[De-escalation of antihyperglycemic treatment in patients with type 2 diabetes - when less is more]. / Az antihyperglykaemiás terápia deeszkalációja 2-es típusú diabetesben ­ amikor a kevesebb több.

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.

Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary.

BACKGROUND: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.

Signs of subclinical atherosclerosis in asymptomatic patients at increased risk of type 2 diabetes mellitus.

AIMS: We aimed to study carotid intima media thickness (CIMT) in asymptomatic patients with an increased risk of type 2 diabetes mellitus (T2DM) and in a pre-diabetic state. METHODS: Diabetes risk assessment was performed in 2420 participants in a voluntary screening program between 2011 and 2013. The risk of T2DM was estimated by the Findrisc scoring system (FR). A FR≥12 was considered as increased risk. HbA1c% between 5.7 and 6.4% signified a pre-diabetic state. Carotid duplex scan was performed and CIMT above 0.9 mm was regarded as pathological. Patients with T2DM or a history of cardiovascular disease were excluded. RESULTS: Overall 1475 subjects were included. Four groups were compared: "control" (normal HbA1c, FR<12), "HbA1c only" (HbA1c: 5.7-6.4%, FR<12), "Findrisc only" (normal HbA1c, FR≥12) and "combined" (HbA1c: 5.7-6.4%, FR≥12). Frequency of pathological maximal CIMT was 9.4%, 19.7%, 27.4% and 36.4% in the groups, respectively (p<0.001). Logistic regression analysis revealed that compared to control subjects, sex and risk factor-adjusted Odds Ratios for the presence of pathological maximal CIMT were 2.2 (p<0.001), 3.4 (p<0.001) and 5.1 (p<0.001) for the groups, respectively. CONCLUSIONS: Evaluation of Findrisc score and HbA1c at population level may facilitate early recognition of subclinical vascular complications even in the pre-diabetic state.

[Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in Hungary between 2001 and 2014 - results from the database analysis of the National Health Insurance Fund]. / A 2-es típusú diabetes antihyperglykaemiás kezelésének alakulása Magyarországon 2001­2014 között ­ az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének eredményei.

In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42% in this period. The most frequently used drug at first treatment initiation was metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors were newly administered in 20,362 cases while GLP1-mimetics were newly used by 4,996 patients in 2014. Five years later after initiating sulfonylurea therapy between 2010 and 2014, metformin was more frequently used as second drug (39%) than sulfonylurea in patients with previous metformin treatment (22.9%). The prescribing patterns of glucose-lowering drugs have changed over time in accordance with new guidelines. Further changes in prescribing habits can be expected in the near future. Orv Hetil. 2017; 158(20): 770-778.

Heritability of the femoral intima media thickness.

BACKGROUND: The measurement of femoral intima-media thickness (IMT) is underutilized in the clinical practice, although it is a surrogate marker of cardiovascular disease. MATERIALS AND METHODS: 388 Hungarian and Italian twins (121 monozygotic, 73 dizygotic pairs) underwent bilateral B-mode sonography of femoral arteries. IMT was measured by semiautomated software, where available, or by calipers. RESULTS: Within-pair correlation in monozygotic twins was higher than in dizygotics for each parameter. Age-, sex- and country-adjusted genetic effect accounted for 43.9% (95% confidence interval, CI 21.3%-65.2%) and 47.2% (95% CI, 31.4%-62.6%) of the variance of common and superficial femoral artery IMT, respectively, and unshared environmental effect for 56.1% (95% CI 34.6%-78.5%) and 52.8% (95% CI, 37.2%-68.5%). These results did not change significantly after correcting for body mass index or central systolic blood pressure. CONCLUSIONS: Genetic factors have a moderate role in the determination of common and superficial femoral IMT; however, the influence of environmental (lifestyle) factors remains still relevant. Environmental factors may have a role in influencing the genetic predisposition for femoral vascular hypertrophy.

[Changes in features of diabetes care in Hungary in the period of years 2001-2014. Aims and methods of the database analysis of the National Health Insurance Fund]. / A cukorbeteg-ellátás mutatóinak alakulása Magyarországon 2001-2014 között. Az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének célja és módszertana.

In the last couple of years, database analyses have become increasingly popular among clinical-epidemiological investigations. In Hungary, the National Health Insurance Fund serves as central database of all medical attendances in state departments and purchases of drug prescriptions in pharmacies. Data from in- and outpatient departments as well as those from pharmacies are regularly collected in this database which is public and accessible on request. The aim of this retrospective study was to investigate the database of the National Health Insurance Fund in order to analyze the diabetes-associated morbidity and mortality in the period of years 2001-2014. Moreover, data of therapeutic costs, features of hospitalizations and practice of antidiabetic treatment were examined. The authors report now on the method of the database analysis. It is to be hoped that the upcoming results of this investigation will add some new data to recent knowledge about diabetes care in Hungary. Orv. Hetil., 2016, 157(32), 1259-1265.

[Cardiovascular safety of incretin-based antidiabetic treatment - results of completed clinical trials]. / Az inkretintengelyen ható antidiabetikumokkal végzett cardiovascularis biztonságossági tanulmányok eddigi tapasztalatai.

Several randomized, controlled clinical trials were initiated some years ago in order to evaluate the cardiovascular safety of the new antidiabetic drugs in patients with type 2 diabetes due to requirements from regulatory bodies. Four trials with incretin-based drugs (saxagliptin, alogliptin, sitagliptin and lixisenatide) have been completed so far. Based on the primary outcome endpoints of these trials no cardiovascular risks were found with incretins in patients with type 2 diabetes. As for saxagliptin, the hospitalization for heart failure was investigated as a secondary endpoint, and an increased risk was observed in the respective trial; however, this observation was widely debated later in the literature. Together with ongoing trials of other novel antihyperglycemic agents, these data will provide more robust evidence about the cardiovascular safety of incretin-based antidiabetic treatment in patients with type 2 diabetes.

[Incretin-based antidiabetic treatment and diseases of the pancreas (pancreatitis, pancreas carcinoma)]. / Inkretintengelyen ható antidiabetikumok és a pancreas betegségei (pancreatitis, pancreascarcinoma).

In the last couple of years incretin-based antidiabetic drugs became increasingly popular and widely used for treating patients with type 2 diabetes. Immediately after launching, case reports and small case series were published on the potential side effects of the new drugs, with special attention to pancreatic disorders such as acute pancreatitis or pancreatic cancer. As clinical observations accumulated, these side-effects were noted with nearly all drugs of this class. Although these side-effects proved to be rare, an intensive debate evolved in the literature. Opinion of diabetes specialists and representatives of pharmaceutical industry as well as position statements of different international scientific boards and health authorities were published. In addition, results of randomized clinical trials with incretin-based therapy and meta-analyses became available. Importantly, in everyday clinical practice, the label of the given drug should be followed. With regards to incretins, physicians should be cautious if pancreatitis in the patients' past medical history is documented. Early differential diagnosis of any abdominal pain during treatment of incretin-based therapy should be made and the drug should be discontinued if pancreatitis is verified. Continuous post-marketing surveillance and side-effect analysis are still justified with incretin-based antidiabetic treatment in patients with type 2 diabetes.

Cost-effectiveness of a risk-based secondary screening programme of type 2 diabetes.

OBJECTIVE: The objective of this study was to develop a long-term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk-based screening programme in a country specific setting. METHODS: The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units. RESULTS: The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three-yearly screening gained 0.0229 quality adjusted life years for an additional €83 per person compared with no screening and resulted an incremental cost-effectiveness ratio of €3630/quality adjusted life years. CONCLUSION: From the economic perspective introduction of the 3-yearly screening programme is justifiable and it provides a good value for money. Copyright © 2016 John Wiley & Sons, Ltd.

[Neurovascular compression of the medulla oblongata: a rare cause of secondary hypertension]. / Nyúltveloi neurovascularis kompresszió. A szekunder hypertonia ritka oka.

Compression of the rostral ventrolateral medulla oblongata is one of the rarely identified causes of refractory hypertension. In patients with severe, intractable hypertension caused by neurovascular compression, neurosurgical decompression should be considered. The authors present the history of a 20-year-old man with severe hypertension. After excluding other possible causes of secondary hypertension, the underlying cause of his high blood pressure was identified by the demonstration of neurovascular compression shown by magnetic resonance angiography and an increased sympathetic activity (sinus tachycardia) during the high blood pressure episodes. Due to frequent episodes of hypertensive crises, surgical decompression was recommended, which was performed with the placement of an isograft between the brainstem and the left vertebral artery. In the first six months after the operation, the patient's blood pressure could be kept in the normal range with significantly reduced doses of antihypertensive medication. Repeat magnetic resonance angiography confirmed the cessation of brainstem compression. After six months, increased blood pressure returned periodically, but to a smaller extent and less frequently. Based on the result of magnetic resonance angiography performed 22 months after surgery, re-operation was considered. According to previous literature data long-term success can only be achieved in one third of patients after surgical decompression. In the majority of patients surgery results in a significant decrease of blood pressure, an increased efficiency of antihypertensive therapy as well as a decrease in the frequency of highly increased blood pressure episodes. Thus, a significant improvement of the patient's quality of life can be achieved. The case of this patient is an example of the latter scenario.

Genetic and environmental factors on the relation of lung function and arterial stiffness.

BACKGROUND: An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. METHODS: 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. RESULTS: Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45-85%), 28% (95% CI: 0-67%), 68% (95% CI: 20-81%) and 45% (95% CI: 0-66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between -0.12 and -0.17. No genetic covariance between lung function and arterial stiffness was found. CONCLUSIONS: Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.

Prevalence of undiagnosed abnormal glucose tolerance in adult patients cared for by general practitioners in Hungary. Results of a risk-stratified screening based on FINDRISC questionnaire.

BACKGROUND: The prevalence of type 2 diabetes mellitus is rapidly increasing, worldwide and also in Hungary. Timely diagnosis and early treatment could be aided by targeted screening. Recognizing this, the Hungarian Diabetes Association initiated a risk-stratified screening with the involvement of primary care physicians. MATERIAL/METHODS: In the first phase of screening, the FINDRISC questionnaire was completed, followed by an oral glucose tolerance test (OGTT) for those with a score of ≥12. Between September 1, 2010 and March 31, 2011, 70,432 non-diabetic adults, who visited their general practitioners for any reason, were involved in the screening. Of these, 68,476 questionnaires proved to be suitable for processing. RESULTS: From the questionnaires, 28,077 (41.0%) had a score of ≥12. A valid OGTT was performed in 22,846 cases; of this group 3,217 subjects (14.1%) had elevated fasting glucose levels, 5,663 (24.8%) had impaired glucose tolerance, and 1,750 (7.6%) had manifest, previously undiagnosed, diabetes mellitus. Overall, from the valid OGTT group, 46.5% subjects had some degree of glucose intolerance. CONCLUSIONS: Based on the FINDRISC questionnaire, the risk-stratified screening for diabetes mellitus proved to be simple and cost-effective method for the early detection of carbohydrate metabolism disorders. Using this method, the prevalence rate of previously undiagnosed abnormal glucose tolerance was high in adult patients cared for by general practitioners in Hungary.