The COVID-19 frontiers - sink or swim.

OBJECTIVES: The objective of this study is to address issues faced by doctors working in the COVID-19 units during the second phase of COVID-19 in the Czech Republic, when the country registered the highest per capita rate of new COVID-19 cases in the world. METHODS: A prospective study was designed using Google online questionnaire. Inclusion criteria were doctors from medical and surgical specialties working in COVID-19 units. The Czech Medical Association was approached in obtaining permission and helping us distribute the questionnaire with an introductory message with the aims of the study via email to the chairpersons of 18 medical and surgical Czech Societies and their respective members. The online questionnaire link was active for 31 days. Completion of a questionnaire implied consent to participate. Data was collected from the completed responses and statistical analysis was done. RESULTS: Fifteen out of eighteen invited Societies participated in the study. Out of all the transferred or volunteering doctors at the COVID units, 47.6% were from 9 medical specialties and 52.4% from 6 surgical units. The highest transfers were seen amongst male surgeons with 21 to 35 years of work experience, whilst the youngest group of doctors made the highest contribution. There was no statistical significance between the effects of COVID-19 and gender. Despite adequate medical provisions, 42% of all doctors had issues with procedural diagnostic methods, 40% tested positive for COVID-19 and 31% reported staff reduction leading to diminished patients' admissions and compromised care. Doctors from surgical departments experienced more difficulties in working in COVID-19 units. Furthermore, on contraction of COVID-19, 114 doctors asserted a lack of support and another 26% were unaware of any services. CONCLUSIONS: Our survey reiterates the relationship between factors related to occupational health and safety, standards of patient care and possibility of medicolegal consequences with the continuing COVID-19 pandemic.

Long-term impact of adalimumab therapy on biomarkers of systemic inflammation in psoriasis: Results of a 2 year study.

Psoriasis patients are at increased risk of atherosclerosis, characterized by endothelial dysfunction, linked through systemic inflammation. Anti-TNF-a therapy seems to decrease this risk. The purpose of this study was to measure the levels of serum markers associated with systemic inflammation in psoriasis patients, compared to healthy individuals and to investigate the change in their levels after 3 months and 2 years of adalimumab therapy. We investigated four biomarkers: high-sensitivity C-reactive protein (hsCRP), oxidized low-density lipoproteins (OxLDL), E-selectin, and Interleukin 22 (IL-22). These markers were measured in healthy volunteers and in 28 patients with moderate/severe psoriasis before and after 3 and 24 months of treatment with adalimumab. Psoriasis patients had increased levels of markers in comparison to the control group. After 3 months of therapy, E-selectin decreased significantly (P < .001), as well as IL-22 (P < .001). hsCRP also decreased but did not show a statistical significance, OxLDL were slightly higher than initially. After 24 months, 17 patients were still being treated with adalimumab. In these patients, hsCRP (P < .05), E-selectin (P < .001) and IL-22 (P < .001) were significantly decreased. OxLDL remained at a higher level. The stable decrease of E-selectin, hsCRP, and IL-22 after 24 months confirms that adalimumab suppresses systemic inflammation.

A summary of the EAS consensus concerning the causal relationship between low-density lipoproteins and atherosclerotic cardiovascular diseases, prepared by the Board of the Czech Society for Atherosclerosis.

This article summarised opinion of the European Society for Atherosclerosis on the causal relationship between low density lipoprotein (LDL) and the development of atherosclerosis. The fact that there is a clear causal relationship between the LDL concentration and the development of atherosclerotic cardiovascular disease (ASKVO) is evidenced by congenital lipid metabolism disorders and results of prospective epidemiological studies, Mendelian randomized trials, and randomized controlled trials. It is documented that the effect of LDL exposure on ASKVO development is cumulative; the additive effect of other risk factors is also discussed. In conclusion the facts, underlying the rational approach to the therapy of patients with dyslipidemia, are summarized. Key words: atherosclerotic cardiovascular disease - LDL - low density lipoprotein - EAS.

[OxLDL/ß2-glycoprotein I complex as a pro-atherogenic autoantigen. Is atherosclerosis an autoimmune disease?] / Komplex oxLDL/ß2-glykoprotein I jako proaterogenní autoantigen. Je ateroskleróza autoimunitní onemocnení?

Oxidation of atherogenic low-density lipoproteins (LDL) plays a key role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interrelated and they can potentiate one another. In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma ß2-glycoprotein I (ß2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies. It has been documented that oxLDL/ß2GPI in immune complex with IgG autoantibody is internalized by macrophages through the Fcγ receptor. Increased levels of oxLDL/ß2GPI were first observed in patients with systemic lupus erythematodes (SLE) and antiphospholipid syndrome (APS), further in individuals with coronary heart disease (CHD) and type 2 diabetes mellitus (DM2T). In a prospective study, initial plasma concentrations of oxLDL/ß2GPI correlated with the number and severity of cardiovascular events in patients with chronic CHD over a 2-year period.Key words: atherosclerosis - ß2-glycoprotein I - inflammation - oxidative stress - oxLDL.

[Changes in nutritional recommendations for a healthy population and their influence on a diabetic diet]. / Posuny v nutricních doporuceních pro zdravé obyvatelstvo a jejich dopad pro diabetickou dietu.

UNLABELLED: Recently, thousands of papers brought knowledge about effects of nutrients on cellular level, in experimental animals and in human experiments on one side, the results of epidemiological studies on the other side have suggested the nutrients and foods for healthy diet and nutrients and foods, which should be consumed only in limited amount. Among foods, which should be avoided, those with higher content of trans-fatty acids. Their daily intake should not exceed 1 % of total energy intake. Similar should be limited saturated fatty acid, added sugar and salt. On the contrary, the intake of monounsaturated and polyunsaturated fatty acids in foods should be basic part of fat intake. In these conditions the amount of consumed fat could create up to 35 % of all daily energy intake. Beneficial carbohydrates are those with low glycemic index, i.e. whole grain and brown rice products and legumes. The intake of salt is necessary to limit fewer than 6 g per day and alcohol intake should not exceed 10 g per day in women and 20 g per day in men. The recommendation in last years do not limit cholesterol daily intake. The food of animal origin with high content of saturated fatty acids, i.e. meat and milk products parallel contains also cholesterol. On the other hand, the oils of vegetable origin mostly from tropical oils, which contents high amount of saturated fatty acids represents the risk? On the contrary eggs and shellfish contents high amount of cholesterol and very low amounts of saturated fatty acids. Therefore, there is no reason for their strict limitation in the diet. KEY WORDS: carbohydrate - diabetes - dietary recommendation - energy intake - fat - healthy diet - iron - cholesterol - protein.

[The common position of the Czech professional associations on the consensus of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine regarding investigation on blood lipids and interpretation of their levels]. / Spolecné stanovisko ceských odborných spolecností ke konsenzu European Atherosclerosis Society a European Federation of Clinical Chemistry and Laboratory Medicine k vysetrování krevních lipidu a k interpretaci jejich hodnot.

The aim of this opinion is to summarize and to comment the consensus of the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine, which covers two main areas: 1) whether it is necessary / required to be fasting or non-fasting before blood sampling for lipids measurement, and what are the changes in the concentration of blood lipids during the day; 2) What decision limits (cut off value) of lipids and lipoproteins should be reported from laboratories and what is the recommended procedure for people with extreme / critical blood lipid values. Following parameters are discused: total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a). This opinion should be the object of interest both for professionals in clinical laboratories and for physicians in hospitals and out-patients departments.Key words: apolipoproteins - blood collection - cholesterol - laboratory testing - lipoprotein(a) - cut off limits - triglycerides.

[PCSK9 inhibitors - new possibilities in the treatment of hypercholesterolemia: For which patients will be indicated?Czech atherosclerosis society statement]. / PCSK9 inhibitory - nové moznosti v lécbe hypercholesterolemie: U koho budou indikovány?Stanovisko Ceské spolecnosti pro aterosklerózu.

First line drug for the treatment of hypercholesterolemia are statins, which reduce LDL-cholesterol up to 50 %; such reduction is sufficient for most patients to achieve the target values. The exceptions are patients with familial hypercholesterolemia and patients with statin intolerance. To achieve target LDL-cholesterol in these two groups of patients will be possible with new drugs - PCSK9 inhibitors, which decrease LDL-cholesterol by an additional 50-60 %. The first two PCSK9 inhibitors (alirocumab and evolocumab) already had been approved for clinical use by European regulatory authorities. The primary indication for combination statin with PCSK9 inhibitor should be undoubtedly patients with a confirmed diagnosis of familial hypercholesterolemia, who are treated in the Czech Republic primarily in specialized centers of MedPed project. Furthermore, this treatment should be available for other patients at very high risk of cardiovascular diseases, who cannot achieve target LDL-cholesterol (eg. for statins intolerance).

[Annual monitoring of side effects of administering sitagliptin in patients with type 2 diabetes mellitus]. / Rocní sledování vedlejsích úcinku podávání sitagliptinu u pacientu s diabetes mellitus 2. typu.

UNLABELLED: We present the results of an independent, drug company-unsupported follow-up of patients with type 2 diabetes mellitus (T2DM) treated with the dipeptidyl peptidase 4 inhibitor sitagliptin. 29 patients (16 men, 13 women) used sitagliptin 100 mg daily for one year as an add-on to their chronic antidiabetic therapy. 16 type diabetic patients formed a control group - they used their chronic antidiabetic therapy without sitagliptin. 10 additional patients (6 men and 4 women) were enrolled in the study and treated with sitagliptin for one month. Body weight, BMI, glycaemia, glycated hemoglobin (HbA1c), cholesterolemia, triacylglycerolemia and serum amylases were determined and abdominal ultrasonography was performed. Because significant changes in immunological tests had been found especially after one month of treatment, 10 additional patients (6 men and 4 women) were enrolled in the study and treated with sitagliptin for one month. Sitagliptin treatment led to a significant body weight loss of 1 kg per year. In the control group, no significant change was observed. Similar results were noticed in HbA1c level and fasting glycaemia - mild but statisticaly significant reduction in the sitagliptin group both after one month and one year (not in HbA1c), no difference in the control group. There was no change in cholesterolemia, or in triacylglycerolemia. In 33% of patients in the sitagliptin group, the level of liver steatosis decreased by ultrasonographic evaluation. This was not found in any of the patients case in the control group. The serum amylase levels increased slightly over the upper limit in two sitagliptin treated patients. In the other sitagliptin treated patients serum amylase remained within the laboratory limits, but slight, statistically significant elevation of serum amylases was observed in the intervened group. This result was not found in the control group. There were not differences in the frequency between occurence of mild respiratory infections in the sitagliptin and control group. Marginally significant decrease was observed in the intervened group. KEY WORDS: sitagliptin - type 2 diabetes mellitus - side effects.

[Evolocumab and PROFICIO Project: Initial Results]. / Evolokumab a projekt PROFICIO: první výsledky.

The PROFICIO project includes 20 clinical studies evaluating the effect of evolocumab on the incidence of cardio-vascular disease including its safety profile and tolerance. Most of the included studies follow the average proportional decrease of LDL-cholesterol concentrations over 10 and 12 weeks of administering evolocumab as compared to the input values. The first results were announced at the congress of the European Society of Cardiology (ESC) in London at the end of August and beginning of September 2015. This subanalysis comprised 3146 patients, who underwent one of the selected studies of phase 3 clinical testing and who were administered a dose of 140 mg s.c. evolocumab once in 2 weeks, or 420 mg s.c. once in 4 weeks. LDL-cholesterol levels decreased after evolocumab by 56.5-74.9% in the individual studies as compared to placebo and by 36.9-44.9% compared to ezetimib. The incidence of adverse effects did not differ from the group which used placebo.

The oxidized low-density lipoprotein/ß2-glycoprotein I complex is associated with abdominal obesity in healthy middle-aged men.

BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) in complex with ß2-glycoprotein I (ß2GPI) has been associated with autoimmune diseases, diabetes mellitus, chronic renal disease and coronary atherosclerosis. The aim of our study was to determine whether plasma levels of oxLDL/ß2GPI complexes are associated with insulin resistance, inflammation and markers of endothelial damage in obese middle-aged men and, if so, whether oxLDL/ß2GPI correlates better with insulin resistance parameters than oxLDL, advanced oxidation protein products (AOPP) or thioredoxin. METHODS: A total of 72 healthy men were recruited (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as the criterion for abdominal obesity. RESULTS: The obese men demonstrated higher oxLDL/ß2GPI levels (p < 0.001), homeostasis model assessment of insulin resistance (p < 0.01) and intima-media thickness of the common carotid artery (p < 0.01). oxLDL/ß2GPI correlated with more insulin resistance parameters compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/ß2GPI was associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001) and negatively with interleukin-8 (r = -0.297, p < 0.05). CONCLUSIONS: In summary, oxLDL/ß2GPI reflects the criterion for abdominal obesity and markers of insulin resistance in our study. The independent positive correlation with PAI-I indicates that oxLDL/ß2GPI may serve as an early marker of low-grade inflammation and atherosclerosis initiation.

Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention.

BACKGROUND: The aim of our study was to assess the impact of increased iron stores on the presence of asymptomatic atherosclerosis in a cohort of healthy men. We anticipated that higher iron stores would be associated with higher soluble cluster of differentiation 163 (sCD163) concentrations, elevated markers of oxidative stress, inflammation and higher common carotid intima-media thickness, independently of traditional risk factors of atherosclerosis. METHODS: In this cross-sectional study that included 72 healthy men, we measured the ultrasonography of common carotid intima-media thickness (IACC), the ratio of plasma-circulating transferrin receptors concentration to plasma ferritin concentration, certain inflammatory and oxidative stress markers, insulin sensitivity, plasma lipids and markers of endothelial dysfunction. RESULTS: The plasma-circulating transferrin receptor concentration to plasma ferritin concentration ratio (TfR/F) showed significant association with IACC (r=-0·310, P=0·008 vs. r=0·295, P=0·012). Multivariate analysis confirmed that the correlation of TfR/F with IACC is independent of traditional risk factors of atherosclerosis. The TfR/F ratio correlated with other indicators of atherosclerotic process fibrinogen (r=-0·292, P=0·013), von Willebrand factor (vWf; r=0·284, P=0·017), sCD163 (r=0·239, P=0·043) and IL-8 (r=0·233, P=0·049). In multivariate analysis, TfR/F independently correlated with haemoglobin (ß=-0·220, P=0·047), fibrinogen (ß=-0·290, P=0·009), IL-8 (ß=0·227, P=0·039) and sCD163 (ß=0·244, P=0·025); however, when vWf was added, significant independent correlation was seen only with fibrinogen (ß=-0·301, P=0·007) and IL-8 (ß=0·219, P=0·047). In addition, we demonstrated the independent correlation of sCD163 with vWf (ß=0·240, P=0·040). CONCLUSIONS: Our study showed a clear association of body iron stores expressed by the TfR/F ratio with asymptomatic carotid atherosclerosis. TfR/F further exhibited an independent positive correlation with fibrinogen and a negative correlation with sCD163 and IL-8.

Not Just a 'Breath of Death': Indirect Consequences of Working in a COVID-19 Unit.

We carried out a survey in the Czech Republic between January and February 2021 to evaluate the impact of COVID-19 on doctors working in the COVID-19 unit. A rise in 250,000 cases were seen in the Czech Republic during the time of the survey. The indirect impact of the disease on doctors working in COVID-19 units and strategies to control the situation in the Czech Republic were evaluated here. About 35% doctors were concerned with health issues, 40% had tested positive for SARS-CoV-2 antigen, 51% reported lack of support for those who had contracted COVID-19 and 163 agreed that medical, psychological counselling and financial services should be provided. Most doctors experienced moderate and severe degrees of psychological impact. Doctors with the least working experience and those with at least 21 to 35 years were most affected. Mental fatigue was the most common reported psychosomatic effect. The effects were higher in doctors who were more concerned about working in COVID-19 units. Around 87% agreed that the best strategy in controlling the situation in the Czech Republic would be 'preventive measures in combination with vaccination'. History shows us that pandemics can occur in multiple waves. Subsequent waves, inadequate support as well as unparalleled workload can lead to a serious rise in psychological disorders amongst HCWs worldwide.

Relationship between increased body iron stores, oxidative stress and insulin resistance in healthy men.

AIM: The aim of our cross-sectional study was to assess the relationships between body iron stores, oxidative stress, impaired insulin sensitivity and carotid atherosclerosis in a cohort of healthy men in primary prevention of cardiovascular disease. METHODS: We examined 151 volunteers, aged 35- 60 years. Anthropometric parameters, markers of metabolic syndrome, insulin resistance, inflammatory markers, parameters of oxidative stress and intima-media thickness of common carotid artery were measured. RESULTS: Ferritin correlated positively with waist circumference, body mass index, impaired insulin sensitivity, plasma triglycerides and inversely with high-density lipoprotein cholesterol. We observed positive correlations between ferritin, oxidized lowdensity lipoprotein and advanced oxidation protein products after adjustment for age, waist circumference, body mass index and measured inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-alpha). There were no significant associations between ferritin and intima-media thickness or markers of endothelial dysfunction. In a stepwise multiple regression analysis, triglycerides, waist circumference and elevated transaminases were independent determinants of the serum ferritin level. CONCLUSION: Our results provide evidence for a relationship between plasma ferritin and oxidative modification of lipids as well as proteins in vivo. Higher body iron stores may contribute to impaired insulin sensitivity through increased oxidative stress in a cohort of healthy men.

Long-term donors versus non-donor men: Iron metabolism and the atherosclerotic process.

BACKGROUND AND AIMS: The increased iron level and the labile iron pool (LIP) in circulating monocytes are connected to a higher frequency of cardiovascular events. METHODS: The study investigates the relationship between LIP in circulating monocytes and markers of iron metabolism and atherosclerosis (inflammation, oxidative stress, endothelial dysfunction and arterial elasticity) in long-term blood donors and non-donor volunteers. RESULTS: We found that donors had significantly higher LIP values than the control group (1.89 ±â€¯0.47 µM vs. 1.50 ±â€¯0.41 µM, p = 0.007). Despite the observed tendency for the donor group to have higher blood pressure, cholesterol, glucose and HOMAR-IR (homeostasis model assessment of insulin resistance), the groups did not differ in inflammatory markers, markers of endothelial dysfunction and markers of impaired arterial elasticity. The donor group had significant changes in iron metabolism (higher serum Fe, ceruloplasmin, and TfR/Ft ratio (transferrin receptor/ferritin ratio) and lower hepcidin, ferritin, and CD163), indicating depletion of body iron stores and activation of iron turnover. CONCLUSIONS: LIP seems to be a good marker of iron turnover activity in these individuals despite the lack of a decrease in the hemoglobin concentration. We did not find a significant correlation between LIP levels and atherosclerosis progression in the two groups. However, further studies are needed to assess long-term donorship as a protective factor against atherosclerosis.

Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study.

Psoriasis is a chronic systemic immune-mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti-tumor necrosis factor (TNF)-α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C-reactive protein (measured high sensitively, hsCRP), oxidized low-density lipoproteins (oxLDL), oxLDL/ß-glycoprotein I complex (oxLDL/ß2GPI), vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin and interleukin (IL)-22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL-ß2GPI complex (P < 0.05), E-selectin (P < 0.001) and IL-22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM-1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E-selectin (P < 0.001) and IL-22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF-α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E-selectin and IL-22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.

Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes.

Epidemiological studies have established that a high level of iron body stores is associated with increased risk of acute coronary heart disease. To explain this association, it has been proposed that iron catalyzes the production of highly reactive forms of free oxygen species, and thus, promotes low-density lipoprotein (LDL) oxidation, a lipoprotein that plays a critical role in atherogenesis. However, few studies have provided evidence to support this hypothesis. In the present study, we determined the effect of iron loading of THP-1 mononuclear phagocytes on LDL metabolism. We demonstrated that iron loading of THP-1 cells stimulated conjugated diene formation in LDL in the culture medium. In addition, iron loading of THP-1 cells significantly increased cholesteryl ester accumulation in cells exposed to native LDL, suggesting that during the incubation of the cells with native LDL, the LDL became oxidized and was taken up by the cells. We further demonstrated that the degradation of 125I-oxidized LDL was significantly increased in iron-loaded THP-1 cells. Lastly, we demonstrated that iron loading of THP-1 cells stimulated scavenger receptor expression in these cells. In conclusion, this study demonstrates that loading of mononuclear phagocytes with iron leads to oxidization of LDL, increased cellular cholesterol accumulation and scavenger receptor expression, and supports the hypothesis that increased macrophage iron levels promote atherogenesis.

Renal risk associated with sodium phosphate medication: safe in healthy individuals, potentially dangerous in others.

INTRODUCTION: Sodium phosphate purgatives are used for bowel preparation before endoscopic or radiologic examination and occasionally for treatment of severe obstipation. Generally, they are well tolerated and effective; however, safety concerns exist regarding serious renal injury and electrolyte disturbances after administration of these drugs. AREAS COVERED: The review presents complications associated with the use of agents containing sodium phosphate with regard to electrolyte disorders and renal impairment, namely acute phosphate nephropathy (APhN). This paper discusses the pathophysiology, histopathological findings, clinical symptoms, diagnosis and treatment of APhN. Additionally, it examines the epidemiology of adverse renal events and the safety of using sodium phosphate preparations prior to colonoscopy. EXPERT OPINION: Because of safety concerns, sodium phosphate purgatives are not recommended for routine bowel cleansing. Despite some serious and even fatal adverse events associated with these drugs when used with at-risk patients, available data suggest that administration of sodium phosphate purgatives is relatively safe in nonrisk individuals(i.e., in adequately hydrated, otherwise healthy adults, younger than 55 years with evidence of normal renal function).

Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima-Media Thickness.

Aim. GCK-MODY is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia. The risk of macrovascular complications is considered low, but studies are limited. We, therefore, investigated the carotid intima-media thickness (CIMT) as an indicator of macrovascular complications in a group of patients with GCK-MODY. Methods. Twenty-seven GCK mutation carriers and 24 controls recruited among their first-degree relatives were compared, all aging over 35 years. The CIMT was tested using a high-resolution B-mode carotid ultrasonography. Medical history, anthropometry, and biochemical blood workup were obtained. Results. The mean CIMT was 0.707 ± 0.215 mm (mean ± SD) in GCK mutation carriers and 0.690 ± 0.180 mm in control individuals. When adjusted for age, gender, and family status, the estimated mean difference in CIMT between the two groups increased to 0.049 mm (P = 0.19). No difference was detected for other characteristics, with the exception of fasting blood glucose (GCK-MODY 7.6 mmol/L ± 1.2 (136.4 mg/dL); controls 5.3 mmol/L ± 0.3 (95.4 mg/dL); P < 0.0001) and glycated hemoglobin HbA1c (GCK-MODY 6.9% ± 1.0%, 52 mmol/mol ± 10; controls 5.7% ± 0.4%, 39 mmol/mol ± 3; P < 0.0001). The frequency of myocardial infarction and ischemic stroke did not differ between groups. Conclusion. Our data indicate that the persistent hyperglycemia in GCK-MODY is associated with a low risk of developing diabetic macrovascular complications.

Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease.

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.