Evolocumab is Initiated in Central and Eastern Europe at Much Higher LDL-C Levels Than Recommended in Guidelines: Results from the Observational HEYMANS Study.

Purpose: We examined clinical characteristics and low-density lipoprotein cholesterol (LDL-C) lowering in patients initiating evolocumab in real-world practice in a Central and Eastern European (CEE) cohort from the pan-European HEYMANS study. Methods: Patients from Bulgaria, Czech Republic, and Slovakia were enrolled at initiation of evolocumab (baseline) as per local reimbursement criteria. Demographic/clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from medical records for ≤6 months before baseline and ≤30 months after evolocumab initiation. Results: Overall, 333 patients were followed over a mean (SD) duration of 25.1 (7.5) months. At initiation of evolocumab, LDL-C levels were markedly elevated in all three countries, with a median (Q1, Q3) LDL-C of 5.2 (4.0, 6.6) mmol/L in Bulgaria, 4.5 (3.8, 5.8) mmol/L in the Czech Republic, and 4.7 (4.0, 5.6) mmol/L in Slovakia. Within the first three months of evolocumab treatment, LDL-C levels were reduced by a median of 61% in Bulgaria, 64% in the Czech Republic, and 53% in Slovakia. LDL-C levels remained low throughout the remaining period of observation. The 2019 ESC/EAS guideline-recommended risk-based LDL-C goals were attained by 46% of patients in Bulgaria, 59% in the Czech Republic, and 43% of patients in Slovakia. LDL-C goal attainment was higher in patients receiving a statin ± ezetimibe-based background therapy (Bulgaria: 55%, Czech Republic: 71%, Slovakia: 51%) compared to those receiving evolocumab alone (Bulgaria: 19%, Czech Republic: 49%, Slovakia: 34%). Conclusion: In the HEYMANS CEE cohort, patients initiated on evolocumab had baseline LDL-C levels approximately three-fold higher than guideline-recommended thresholds for PCSK9i initiation. Risk-based LDL-C goal attainment was highest in patients receiving high-intensity combination therapy. Lowering the LDL-C reimbursement threshold for PCSK9i initiation would allow more patients to receive combination therapy, thus improving LDL-C goal attainment. Trial registration: ClinicalTrials.gov (NCT02770131; registration date: 27 April 2016).

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Lipid-lowering therapy use in primary and secondary care in Central and Eastern Europe: DA VINCI observational study.

BACKGROUND AND AIMS: Central and Eastern Europe (CEE) is a largely understudied region, despite having the highest cardiovascular disease mortality in Europe. This analysis aimed to assess the proportion of patients in CEE who achieved their LDL-C goals based on individual cardiovascular risk recommended by the 2016 and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. METHODS: The DA VINCI study was a cross-sectional observational study of primary and secondary prevention patients receiving lipid-lowering therapy across Europe between June 2017 and November 2018. RESULTS: In total, 2154 patients were enrolled from the Czech Republic (n = 509), Hungary (n = 319), Poland (n = 460), Romania (n = 259), Slovakia (n = 123) and Ukraine (n = 484). At LDL-C measurement, most patients were on either moderate- or high-intensity statin monotherapy (53% and 32%, respectively). Despite this, only 44% of patients achieved risk-based LDL-C goals recommended by the 2016 ESC/EAS guidelines, ranging from 21% in Ukraine to 50% in Hungary and Romania. Only 24% of patients overall achieved the risk-based LDL-C goals recommended by the 2019 ESC/EAS guidelines, ranging from 11% in Ukraine to 32% in Poland. CONCLUSIONS: Among patients receiving lipid-lowering therapy, more than half did not achieve their 2016 LDL-C goals. In one of the first comparative analyses evaluating 2019 risk-based goal attainment among countries in CEE, three-quarters of patients did not meet their 2019 LDL-C goals, highlighting a significant gap between guidelines and clinical practice for lipid management in CEE.

Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia.

AIMS: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. RESULTS: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. CONCLUSIONS: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.

The Impact of the International Cooperation On Familial Hypercholesterolemia Screening and Treatment: Results from the ScreenPro FH Project.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is often perceived and described as underdiagnosed and undertreated, though effective treatment of FH is available. Owing to the mentioned facts, it is ever more imperative to screen and treat FH patients. Subsequent to the identification of patients, the project focuses on the improvement of their prognoses. The ScreenPro FH project was established as a functional international network for the diagnosis, screening, and treatment of FH. Individual countries were assigned goals, e.g., to define the actual situation and available treatment. With "central support," more centers and countries participated in the project. Subsequently, individual countries reported the results at the beginning and end of the project. Collected data were statistically evaluated. RECENT FINDINGS: The increasing number of patients in databases, from 7500 in 2014 to 25,347 in 2018, demonstrates the improvement in overall effectiveness, as well as an increase in the number of centers from 70 to 252. Before all, LDL-C decreased by 41.5% and total cholesterol by 32.3%. As data from all countries and patients were not available at the time of the analysis, only those results from 10 countries and 5585 patients at the beginning of the project and at the time of writing are included. Our data are quite positive. However, our results have only limited validity. Our patients are far from the target levels of LDL-C. The situation can be improved with the introduction of new therapy, PCSK9-i, evolocumab, and alirocumab. International cooperation improved the screening of FH and finally led to an improvement in cardiovascular risk.

Therapeutic plasma exchange in secondary prevention of acute pancreatitis in pregnant patient with familial hyperchylomicronemia.

INTRODUCTION: Hormone changes during pregnancy lead to increased plasma lipid levels. When there is added disorder of lipid metabolism, this otherwise physiological change can cause extremely high triglyceride levels with potentionally life-threatening complications, such as non-biliary acute pancreatitis. MATERIALS AND METHODS: We present a case report of a 27-year-old pregnant woman with familial hyperchylomicronemia and a history of 7 hypertriglyceridemia-induced acute pancreatitis attacks. Three attacks occured during her first pregnancy with the last one leading to its termination at 33 weeks owing to the death of the fetus. During her second pregnancy, standard treatment was not able to lower the triglyceride levels sufficiently and she suffered another acute pancreatitis attack. Therapeutic plasma exchange was therefore chosen as the treatment method. RESULTS AND CONCLUSION: Plasma exchange was succesful in the secondary prevention of acute pancreatitis attack and she delivered a healthy baby at 36 weeks of gestation. Treatment was very well tolerated by the mother and the fetus and this supports the use of apheresis as a safe and efficient method in tackling gestational hypertriglyceridemia.

Treatment pattern of familial hypercholesterolemia in Slovakia: Targets, treatment and obstacles in common practice.

BACKGROUND AND AIMS: Maximal doses of potent statins are the cornerstone of treatment of familial hypercholesterolemia (FH). Despite this, a substantial proportion of FH patients are either under-treated or not treated at all. The aim of this work was to evaluate, in a retrospective study, the treatment of FH patients, the proportion of FH patients reaching low-density lipoprotein cholesterol (LDL-C) goals, and reasons for not reaching LDL-C goals, in 8 lipid clinics in Slovakia dealing with FH patients. METHODS: 201 heterozygous FH patients (50.8 ±â€¯14.9 years, 55% females) who attended the lipid clinics at least three times were included in the study. RESULTS: At the first visit, 31.3% of patients were treated with statins and the most common dose was 20 mg of atorvastatin, rosuvastatin and simvastatin. At the third visit, 78.1% of patients were treated with statins and 24.4% with ezetimibe. The majority of patients were treated with atorvastatin (75.8%) and rosuvastatin (18.5%) and 31.3% of all patients were treated with atorvastatin 80 mg or rosuvastatin 40 mg with/without ezetimibe. However, only 11.9% of patients with the LDL-C goal level <2.5 mmol/l and 6.9% with the goal <1.8 mmol/l reached the level. Reasons for not reaching the goal levels were evaluated by physicians in each patient. Insufficient LDL-C lowering effect of treatment, side-effects of therapy and non-compliance of patients were responsible for 46%, 18% and 30% of cases, respectively. CONCLUSIONS: Referral of FH patients to lipid clinics in Slovakia leads to improvement in the treatment; however, almost 22% of the patients are still without statin treatment and the majority of patients do not reach the LDL-C goal level.

Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry.

BACKGROUND AND AIMS: Despite the high prevalence of familial hypercholesterolemia (FH) and available effective lipid-lowering therapy, most of the individuals with this disorder remain undiagnosed and undertreated. The aim of the PLANET registry was to assess the real-life attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic target level in patients with heterozygous FH, to characterize prescribed lipid-lowering therapy with assessment of its efficiency according to the attainment of the target LDL-C level, and to characterize cardiovascular events observed in this patient population again in relation to LDL-C target level attainment. METHODS: PLANET registry was designed as a non-interventional, retrospective, cross-sectional, multicentre disease registry for adult patients with heterozygous FH in the Czech Republic and Slovakia. RESULTS: Overall, 1755 patients were enrolled at 32 sites specialized in FH treatment. 15.4% of patients attained the target LDL-C value. The proportion of patients with LDL-C goal achievement increased to 17.3% in the subgroup of patients receiving high-intensity statin therapy (54.6% of study population). Out of 55 patients receiving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), 61.8% reached the LDL-C treatment goal. Of all cardiovascular events reported, 14.0% occurred in patients attaining the LDL-C goal, while it was 86.0% in the not-at-target group. It was documented (p=0.004) that the longer is the patient in care at the specialized FH centre, the higher is the probability that he/she will attain the target LDL-C level. CONCLUSIONS: Although target LDL-C level attainment remains relatively low, the likelihood of LDL-C goal attainment increases with duration of specialized care.

Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis.

OBJECTIVE: Lower production of adrenal androgens has been confirmed in females with rheumatoid arthritis (RA); however, the mechanisms of this finding are not completely understood. The aim of our study was to assess the contribution of genetic factors associated with variability of dehydroepiandrosterone sulfate (DHEAS) levels to lower DHEAS in female RA patients. METHODS: 448 RA and 648 healthy controls were genotyped for single-nucleotide polymorphisms (SNPs) in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306), and ARPC1A (rs740160). Serum DHEAS concentrations were measured in 112 RA patients and 91 healthy women. RESULTS: The allele frequencies in DHEAS-related loci were similar in RA and controls. RA patients had significantly lower serum DHEAS concentrations compared to healthy women. The cumulative number of alleles associated with lower DHEAS within genes ZKSCAN5, SULT2A1, HHEX, and ARPC1A present in each individual negatively correlated with DHEAS levels in RA patients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RA patients but not in the control group. CONCLUSION: Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Rationale and Design.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Basic Epidemiology.

INTRODUCTION: Despite great recent progress, familial hypercholesterolemia (FH) is still underestimated, under-diagnosed and thus undertreated worldwide. We have very little information on exact prevalence of patients with FH in the Central, Eastern and Southern Europe (CESE) region. The aim of the study was to describe the epidemiological situation in the CESE region from data available. METHODS: All local leaders of the ScreenPro FH project were asked to provide local data on (a) expert guess of FH prevalence (b) the medical facilities focused on FH already in place (c) the diagnostic criteria used (d) the number of patients already evidenced in local database and (e) the availability of therapeutic options (especially plasma apheresis). RESULTS: With the guess prevalence of FH around 1 : 500, we estimate the overall population of 588 363 FH heterozygotes in the CESE region. Only 14 108 persons (2.4 %) were depicted in local databases; but the depiction rate varied between 0.1 % and 31.6 %. Only four out of 17 participating countries reported the the LDL apheresis availability. CONCLUSION: Our data point to the large population of heterozygous FH patients in the CESE region but low diagnostic rate. However structures through the ScreenPro FH project are being created and we can hope that the results will appear soon.Key words: diagnosis - epidemiology - familial hypercholesterolemia - screening.

Genetic testing of familial hypercholesterolemia in a real clinical setting.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by strikingly elevated low-density lipoprotein (LDL) cholesterol levels and premature atherosclerosis. For individuals with a definite or probable diagnosis of FH, molecular genetic testing is recommended. This can be justified in countries where genetic testing is broadly available and covered. On the other hand, in countries with limited access to genetic testing, it can be argued whether it is necessary and cost-effective to perform genetic testing in patients with a proven clinical diagnosis of FH. This article presents a family with FH where different family members manifested different phenotypes and discusses situations where genetic diagnosis can crucially help physicians in clinical decision-making on how to approach and treat patients.

A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study.

INTRODUCTION: The aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA). METHODS: A total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA. RESULTS: HLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA. CONCLUSIONS: The association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.

[Diabetes and dyslipidemia: Why are they so closely related?] / Diabetes a dyslipidémia: preco majú k sebe tak blízko?

Diabetes mellitus is a group of metabolic diseases that are characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The cause of premature death among patients with diabetes predominantly involves cardiovascular diseases. The risk of death from cardiovascular complications is so high that diabetes mellitus is considered a risk equivalent to a manifest atherosclerotic disease. High cardiovascular risk is also determined by dyslipidemia which is present in a large number of patients with diabetes. The review is devoted to the pathogenesis of dyslipidemia in type 1 and type 2 diabetes with an emphasis on atherogenic dyslipidemia. It describes the strategy of therapeutic procedures and their effect on cardiovascular morbidity and mortality.Key words: atherogenic dyslipidemia - fibrates - statins - type 2 diabetes mellitus.

Genetic determinants of quantitative traits associated with cardiovascular disease risk.

Established risk factors for cardiovascular diseases (CVD) may be moderated by genetic variants. In 2403 unrelated individuals from general practice (mean age 40.5 years), we evaluated the influence of 15 variants in 12 candidate genes on quantitative traits (QT) associated with CVD (body mass index, abdominal obesity, glucose, serum lipids, and blood pressure). Prior to multiple testing correction, univariate analysis associated APOE rs429358, rs7412 and ATG16L1 rs2241880 variants with serum lipid levels, while LEPR rs1137100 and ATG16L1 rs2241880 variants were linked to obesity related QTs. After taking into account confounding factors and correcting for multiple comparisons only APOE rs429358 and rs7412 variants remained significantly associated with risk of dyslipidemia. APOE rs429358 variant almost tripled the risk in homozygous subjects (OR = 2.97; 95% CI 1.09-8.10, p < 0.03) and had a lesser but still highly significant association also in heterozygous individuals (OR = 1.67; 95% CI 1.24-2.10; p < 0.001). Associations with hypertension, diabetes mellitus, and metabolic syndrome were not significant after Bonferroni correction. The influence of genetic variation is more evident in dyslipidemia than in other analyzed QTs. These results may contribute to strategic research aimed at including genetic variation in the set of data required to identify subjects at high risk of CVD.

An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog.

Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements.

Insulin detemir results in less weight gain than NPH insulin when used in basal-bolus therapy for type 2 diabetes mellitus, and this advantage increases with baseline body mass index.

OBJECTIVE: Weight gain during insulin therapy can be a challenging problem in already overweight type 2 diabetes mellitus patients, affecting treatment compliance and long-term prognosis. The analogue insulin detemir has been reported to have a weight-sparing effect compared with other basal insulins. This pooled analysis investigated whether this potential advantage is related to body mass index (BMI) when insulin detemir is used as the basal component of basal-bolus therapy. METHODS: Data were pooled from two randomised, parallel group trials of 22 and 24 weeks' duration, in which 900 insulin-treated patients with type 2 diabetes mellitus had their treatment intensified to basal-bolus therapy. Patients received once- or twice-daily insulin detemir or neutral protamine Hagedorn (NPH) insulin in conjunction with insulin aspart or human soluble insulin at meal times. RESULTS: Patients treated with insulin detemir had minimal weight gain (mean <1 kg), regardless of their BMI at entry (estimated slope -0.032), whereas, in patients treated with NPH insulin, weight gain increased as baseline BMI increased (estimated slope 0.075, p = 0.025). Indeed, NPH insulin-treated patients with the largest BMI (>35 kg/m(2)) gained the most weight (mean of ~2.4 kg). In contrast, insulin detemir-treated patients with a BMI >35 kg/m(2) lost weight (mean of ~ -0.5 kg). Glycaemic control was similar with the two treatments. CONCLUSION: Insulin detemir may provide a clinical advantage in terms of reduced weight gain in the treatment of overweight patients with type 2 diabetes.

Familial defective apolipoprotein B-100 in Slovakia: are differences in prevalence of familial defective apolipoprotein B-100 explained by ethnicity?

The objective of this study was to examine frequency of familial defective apo-B-100 (FDB, R3500Q mutation) in probands with the phenotype of familial hypercholesterolemia (FH) and in the general population of 40-year-old subjects in Slovakia and to characterize their lipid and clinical criteria and to compare the frequency of FDB with other populations. We identified 35 patients with FDB among 362 probands with clinical diagnosis of FH and two cases of FDB in the 40-year-old cohort of 2323 subjects from general Slovak population. Probands with FDB differed from those with FH only in plasma triglyceride concentrations (1.84+/-1.4 mmol/l versus 1.45+/-0.98 mmol/l, respectively, p<0.01). Evaluation of personal history of premature atherosclerosis did not show any differences (11.4% in FDB versus 20% in FH, p<0.16). The FDB patients had similar manifestation of xanthomatosis as the FH patients (17.1% versus 8.25%, p<0.25). The frequency of FDB of 9.7% found in the FH patients is among the highest of those reported to date. The frequency of R3500Q mutation of 0.09% found in Slovak 40-year-old subjects did not differ significantly from published population molecular data. Our comparison of estimated FDB frequencies with those which were found by DNA analysis demonstrated that estimated frequencies were not only wider in range, but also significantly higher than those which were assessed by the analysis. The definitive answer to the prevalence of FDB and its biochemical and clinical characteristics requires screening of unbiased samples of the general population from different ethnic groups based on molecular genetic methods.