Investigations into a trigger-based approach for initiating emergency vaccination to augment stamping out of foot-and-mouth disease in New Zealand: a simulation study.

AIMS: To investigate an adaptive management approach to the deployment of emergency vaccination as an additional measure to stamping out (SO) during simulated outbreaks of foot-and-mouth disease (FMD) in New Zealand. METHODS: A simulation modelling (n=6000 simulations) approach was used. The study population comprised all known farms in New Zealand with FMD-susceptible livestock. Each simulation started with infection seeded into a single randomly selected farm. Each outbreak was randomly assigned to one of four control strategies, comprising SO only; trigger-based vaccination (TRV) where SO was augmented with vaccination if an early decision indicator trigger operating between Days 11-35 of the response indicated a large outbreak was developing; SO plus vaccination started randomly on Days 11-35 of the response (VACr); and SO plus vaccination with a fixed start on Day 21 of the response (VACf). Other parameters, such as the number of personnel available were also varied randomly. Generalised additive models (GAM) were used to evaluate variables associated with the number of infected premises (IP) and epidemic duration. RESULTS: The mean number of IP was 29 (median 9, min 1, max 757), while epidemics lasted on average 26.9 (median 18, min 1, max 220) days. These excluded 303 extreme outbreaks larger than the UK 2001 FMD epidemic (2,030 cases). Univariable analysis of the pooled vaccination results vs. SO, showed that vaccination significantly reduced the number of IP (p<0.001) and outbreak duration (p<0.001). GAM of large outbreaks revealed that only the TRV strategy was significantly protective compared to SO alone, reducing the odds of a large outbreak by 22% (OR=0.78; 95% CI=0.63-0.96). The number of veterinarians was non-linearly associated with large outbreaks, with low numbers increasing the odds of a large outbreak, but above 200 veterinarians, the odds reduced. Time to first detection was also non-linearly associated with large outbreaks, with detections <13 days protective and longer detection times increasing the odds of a large outbreak. GAM of long outbreaks showed similar findings, except that all three vaccination strategies significantly reduced duration. Overall, the TRV strategy resulted in the smallest and shortest epidemics. CONCLUSIONS AND CLINICAL RELEVANCE: An adaptive management approach that deployed vaccination in response to a trigger when a large outbreak was developing outperformed SO and reduced the odds of large or long outbreaks more than the other two vaccination strategies, although the differences between the three vaccination strategies were statistically small. This study provides highly relevant insights into the dynamics of disease establishment and spread that will guide New Zealand's readiness for responding to highly infectious disease incursions such as FMD.

Prevalence and characterisation of wounds in sheep attributed to attacks by kea (Nestor notabilis) on high country farms in New Zealand.

Aims: To characterise and classify wounds in sheep suspected to have been caused by attacks by kea (Nestor notabilis) (kea strike), and to report the prevalence of these wounds on five high country farms in the South Island of New Zealand.Methods: Data were collected from farms between 28 August 2012 and 20 September 2013. Sheep were examined opportunistically immediately after shearing for signs of wounds caused by kea. The age and sex of sheep were also recorded. Wounds were measured and characterised as recent, healing, or healed, and the estimated true prevalence was calculated for each farm.Results: Injuries consistent with kea strike wounds were identified in 70/13,978 (0.5%) sheep examined. The estimated true prevalence varied between farms, from 0 (95% CI = 0-0.16) to 1.25 (95% CI = 0.97-1.61)%. Of the 76 wounds identified, 61 (80%) were located in the lumbar region, and 74 (97%) consisted of full-thickness ulceration of the skin, one showed evidence of injury to muscle and one to bone. The median length of the 63 wounds measured was 6 (min 1, max 23.5) cm, and 10/63 (13%) were categorised as recently healed, 47/63 (62%) as healing, and 17/63 (22%) as recent wounds.Conclusions: The results of this study show that kea strike on sheep was occurring at a low prevalence on the high country farms surveyed. The wounds identified were survivable, but the welfare impact of kea strike on sheep should be considered in balance with the conservation status of kea. There was clear variation in the prevalence of wounds attributed to kea strike between the farms but we were not able to identify the risk factors contributing to these differences. Future studies of kea strike should examine variables such as altitude, local kea density and distribution, and differences in kea strike management and husbandry practices, and should include high country farms without a history of kea strike.

Prevalence of Candidatus Mycoplasma haemolamae, bovine viral diarrhoea virus, and gastrointestinal parasitism in a sample of adult New Zealand alpaca (Vicugna pacos).

AIM: To determine the prevalence of infection with Candidatus Mycoplasma haemolamae (Mhl), antibodies to bovine viral diarrhoea virus (BVDV), and BVDV antigen, and the prevalence of animals with elevated faecal nematode egg counts (FEC) in a sample of adult New Zealand alpaca (Vicugna pacos). METHODS: Blood samples were obtained from 175 alpaca, collected from 15 farms around New Zealand, and from 31 samples sent to a diagnostic laboratory for routine haematology. Blood smears (n=170) were examined microscopically for the presence of haemoplasma, and DNA was extracted from whole blood (n=206) for real-time PCR testing for Mhl. Packed cell volume (PCV) was determined for 193 samples. Serum samples (n=195) were tested for BVDV antibody using ELISA, and for BVDV antigen using a real-time PCR assay. Faecal samples were collected from 143 animals; FEC were measured, and samples pooled for larval culture. RESULTS: No haemoplasma organisms were present on blood smear examination. Of the 206 blood samples, two (from the same farm) were positive for Mhl by real-time PCR testing, giving a prevalence of infection with Mhl of 0.97%. Of the 195 serum samples tested, four (2.1%) were positive for antibodies to BVDV; animals with BVDV antibodies were from 3/15 (20%) farms, none of which farmed cattle. None of the serum samples were positive by PCR for BVDV antigen. The median FEC was 50 epg (min 0, max 4,700), with 55/143 (38.5%) samples having 0 epg, and 33/143 (23.1%) having ≥250 epg. Haemonchus spp. were the most common nematodes present in faecal larval cultures from the North Island. Log10 FEC was negatively associated with PCV (p=0.02), and was higher in males than females (p<0.001), and in animals that were positive compared with negative for Mhl (p=0.022). CONCLUSIONS AND CLINICAL RELEVANCE: The number of alpaca infected with Mhl was low, as was the seroprevalence of BVDV. Gastrointestinal parasitism was, however, a common finding in this sample of New Zealand alpaca.

Evaluating the benefits of vaccination when used in combination with stamping-out measures against hypothetical introductions of foot-and-mouth disease into New Zealand: a simulation study.

AIMS: To evaluate the benefits of vaccination against simulated outbreaks of foot-and-mouth disease (FMD) in New Zealand, when applied as an additional measure to stamping-out. METHODS: A simulation modelling approach was used. The study population comprised all known farms in New Zealand with FMD-susceptible livestock. Infection was seeded into three different areas of New Zealand. Transmission mechanisms included direct and indirect contacts, local spread and airborne spread. Efficacies of some of the stamping-out measures were varied. Vaccination strategies involved different start times, size and type of vaccination zone, and species vaccinated. Personnel resources for vaccination were varied as was the herd immunity profile following vaccination. Altogether, 336 models were specified, with 100 iterations conducted for each model. Generalised linear modelling and boosted regression trees were used to evaluate which variables had the biggest effect on the number of infected premises (IP), epidemic duration and area under control. RESULTS: Vaccination, when used as an adjunct to the standard stamping-out programme, significantly reduced the outbreak size. Vaccination reduced the median number of IP by 26 (95% CI=18-35), epidemic duration by 16 (95% CI=13-19) days and area under control by 474 (95% CI=250-699) km2 when there was no airborne spread; and when there was airborne spread the median reduction was 87 (95% CI=70-105) IP, 32 (95% CI=28-35) days and 898 (95% CI=665-1139) km2, respectively. Multivariable analyses showed that starting vaccination 11 days after first detection of FMD produced greater benefits than starting 16 or 21 days after detection. Increasing vaccination zones resulted in increased benefits. Boosted regression tree analyses showed that the most influential variables on the outcome measures were interval to first detection, incursion location, whether there was airborne spread or not and herd immunity profile. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that there are benefits to the use of vaccination in combination with a stamping-out policy for control of FMD outbreaks under New Zealand conditions. The optimal vaccination strategy was identified as being a 3-5 km radius suppressive vaccination zone deployed between 11-16 days after first detection. Vaccination had a greater benefit during larger outbreaks, such as when there was airborne transmission. The key factors which were identified from this study will help inform New Zealand's competent authority on how best to deploy vaccination to further strengthen its approach to FMD eradication should New Zealand ever experience an outbreak.

Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level.

AIMS: Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control. METHODS: Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies. RESULTS: One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c ). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes. CONCLUSIONS: The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of ß-cell destruction induced by causes other than autoimmune ones.

[Serious risk related to oral use of sodium phosphate solution]. / Závazná rizika spojená s uzíváním natrium-fosfátových projímadel.

Sodium phosphate solutions are commonly used to cleanse the bowel in preparation for colonoscopy, for barium enema or surgical procedures and eventually for treatment of severe constipation. Though relatively safe, these drugs must be used with caution in patients with kidney disease, small intestinal disorders, or poor gut motility and are prohibited in renal insufficiency and bowel obstruction. Especially elderly patients are at increased risk for phosphate intoxication due to decreased glomerular filtration rate, concomitant medication use, and systemic and gastrointestinal diseases. Sodium phosphate solution could induce by at-risk patients serious electrolyte abnormalities (hyperphosphatemia, hypocalcemia, hypokalemia) and acute kidney injury called acute phosphate nephropathy, which is potentially life-threatening condition with slowly progressive renal insufficiency. This article gives a report on two cases of severe adverse effects after administration of oral sodium phosphate solution: an elderly women who developed increase in serum phosphate with compensatory severe hypokalcemia with tetany; and an elderly man who developed acute phosphate nephropathy following colon preparation prior to colonoscopy and barium enema. Especially in elderly and in patients in whom sodium phosphate solution is contraindicated or should be used with caution, we recommend to use isosmotic macrogol (polyethylene glycol) solution for the bowel cleansing a for the treatment of constipation.

[Food intake regulation -  1st part]. / Regulace príjmu potravy -  I. cást.

The review article summarizes a very complex process of appetite regulation: the part focused on homeostatic regulation of food intake. The aim of homeostatic regulation is to achieve energy balance, stabile weight and optimal nutrient intake, in contrast to hedonic regulation of food intake, in which emotional and motivational factors are involved. Homeostatic regulation could be divided into shortterm and longterm regulation and comprises mainly gastrointestinal peptides, fat tissue hormones and central mechanisms localized in hypothalamus. It is a resultant of the action of orexigenic factors (increasing appetite and food intake) and anorexigenic factors (decreasing appetite and thus food intake), respectively. The anorexigenic factors include gastrointestinal peptides (e.g. cholecystokinin, glucagonlike peptide 1, bombesin, peptide YY and others), hormone of fat tissue leptin and centrally acting melanocortin system. On the contrary, orexigenic factors comprise of gastric ghrelin and centrally acting system of neuropeptide Y/ Agoutirelated peptide. Understanding the principles of the regulation of food intake is essential for comprehension of pathogenesis of eating disorders and obesity, whose prevalence has been recently increasing, and it provides potential targets for pharmacological interventions.

[Metformin: the overlap of diabetology and oncology]. / Metformin: na pomezí diabetologie a onkologie.

Type 2 diabetes moderately increases predisposition for manifestation of tumor disease. Both drugs stimulating insulin secretion (insulin secretagogues) and insulin injection therapy also moderately increases risk of tumor manifestation (OR approx 1.3). According to some reports pyoglitazon therapy could be of increased risk of bladder cancer. On the other hand, hundreds of study on isolated cells, experimental animal models and retrospective studies in patients have shown preventive effect of metformin therapy on manifestation tumors of pancreas, breast, colorectum, liver, endometrium and ovary. More over, the prognosis of diabetic cancer patients on metformin therapy seems be better, than in diabetics without metformin treatment. These data are promising for future use of metformin for prevention and therapy of some malignant tumors.

[Effects of GLP-1 (glucagon-like peptide 1) on liver]. / Úcinky GLP-1 (glucagonlike peptide 1) na játra.

Effects of glucagonlike peptide 1 (GLP1) on liver cells are very intensively studied. In the metabolism of saccharides GLP1 stimulates synthesis of glycogen and reduces glucose production -  thus acting like insulin. In the lipid metabolism it enhances fatty acid oxidation and lipid transport from hepatocytes while reducing de novo lipogenesis -  effects more similar to glucagon action. Some studies suggest beneficial effects of GLP1 on oxidative stress, endoplasmic reticulum stress, production of inflammatory mediators and dysfunction of biliary secretion. Current results suggest that drugs affecting incretin system could be used in the treatment of certain liver diseases (e.g. NAFLD and NASH) in the future. In the following article we mention the known effects of GLP 1 on liver functions and liver metabolism and we point out its possible future therapeutic use in the treatment of liver diseases.

[Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes]. / Chronický mírný zánet spojuje obezitu, metabolický svndrom, aterosklerózu a diabetes.

Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

A multinational, multi-centre, observational, cross-sectional survey assessing diabetes secondary care in Central and Eastern Europe (DEPAC Survey).

AIMS: The objective of this study was to assess diabetes care in outpatient diabetes clinics in the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia and Slovenia. METHODS: Questionnaires for each randomly enrolled patient were completed by an endocrinologist or diabetologist. Data concerning age, sex, diabetes duration, diabetes type, treatment type, glycated haemoglobin (HbA(1c)), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), blood pressure (BP) and short- and long-term diabetes complications were recorded. Questionnaires were analysed centrally for each country and stratified for Type 1 diabetes (T1D), Type 2 diabetes (T2D) and other types of diabetes. RESULTS: Data on 10 950 individuals were analysed (mean population age 56.2 years; females 52%; T1D 22.9%; T2D 75.3%; mean time from diagnosis 11 years). Patients with HbA(1c) within target (< 6.5%): T1D 13.1%, T2D 21.4%; for TC levels (< 4.5 mmol/l): T1D 37%, T2D 20%; for TG levels (< 1.7 mmol/l): T1D 78%, T2D 44%; for HDL-C (> 1.1 mmol/l): T1D 81%, T2D 60%; for LDL-C (< 2.5 mmol/l): T1D 36%, T2D 23%; for BP (< 130/80 mm Hg): T1D 42%, T2D 9%. The prevalence of severe hypoglycaemia (within the last 6 months) was 12% in T1D and 2% in T2D. Prevalence of diabetic ketoacidosis was 0.3-6.6%, blindness 0.15-1.3% and diabetic nephropathy 19-42%. CONCLUSIONS: The data show the current quality of care and potential areas for improvement. The quality of care is generally comparable with that in Western Europe.

HLA DRB1, DQB1 and insulin promoter VNTR polymorphisms: interactions and the association with adult-onset diabetes mellitus in Czech patients.

Both the human leucocyte antigen (HLA) DRB1 and the HLA DQB1 gene loci play a role in the development and progression of autoimmune diabetes mellitus (T1DM). Similarly, the insulin promoter variable number tandem repeats (INS-VNTR) polymorphism is also involved in the pathogenesis of diabetes mellitus (DM). We studied the association between each of these polymorphisms and DM diagnosed in patients older than age 35 years. Furthermore, we analysed possible interactions between HLA DRB1/DQB1 and INS-VNTR polymorphisms. Based on C-peptide and GADA levels we were able to distinguish three types of diabetes: T1DM, latent autoimmune diabetes in adults (LADA) and T2DM. INS-VNTR was genotyped indirectly by typing INS-23HphI A/T polymorphism. The genotype and allele frequencies of INS-23HphI did not differ between each of the diabetic groups and group of healthy subjects. We did, however, observe an association between the INS-23HphI alleles, genotypes and C-peptide secretion in all diabetic patients: A allele frequency was 86.2% in the C-peptide-negative group vs. 65.4% in the C-peptide-positive group (P(corr.) < 0.005); AA genotype was found to be 72.4% in the C-peptide-negative group vs. 42.6% in the C-peptide-positive groups (P(corr.) < 0.01). The HLA genotyping revealed a significantly higher frequency of HLA DRB1*03 allele in both T1DM and LADA groups when compared to healthy subjects: T1DM (25.7%) vs. control group (10.15%), odds ratio (OR) = 3.06, P < 0.05; LADA (27.6%) vs. control (10.15%), OR = 3.37, P < 0.01. The simultaneous presence of both HLA DRB1*04 and INS-23HphI AA genotype was detected in 37.5% of the T1DM group compared to only 9.2% of the healthy individuals group (OR = 5.9, P(corr.) < 0.007). We summarize that in the Central Bohemian population of the Czech Republic, the INS-23HphI A allele appears to be associated with a decrease in pancreatic beta cell secretory activity. HLA genotyping points to at least a partial difference in mechanism, which leads to T1DM and LADA development as well as a more diverse genetic predisposition in juvenile- and adult-onset diabetes. The simultaneous effect of HLA and INS-VNTR alleles/genotypes predispose individuals to an increased risk of diabetes development.

Short-term dietary intake of C18:1 trans fatty acids decreases the function of cellular immunity in healthy young men.

AIM: In this study, we tested the impact of short-term intake of increased amounts of C18:1 trans fatty acids (TFAs) on parameters of cellular and humoral immunity in healthy young men. METHODS: Twenty-seven healthy young men were subsequently exposed to a standard diet for 7 days and an experimental TFA-enriched diet for 4 days. The mean energy content of these diets was 2,453 and 2,455 kcal/day, with 10, 35 and 55% of energy from proteins, fats and carbohydrates, respectively. Standard diet contained about 0.8 g and experimental diet 10.4 g TFAs. Plasma levels of C18:1 TFAs and immunological parameters were measured. RESULTS: The 4-day increased consumption of C18:1 TFAs led to a significant decrease in mitogen-induced CD69 expression on CD8+ T cells as well as decreased phagocytic activity on neutrophils. After returning to the participants' habitual diet (1 week after the end of the experimental diet), we observed a significant decrease in the mean level of circulating immune complexes. Concentrations of plasma immunoglobulins remained unchanged throughout the study. CONCLUSIONS: Acute impact of higher dietary C18:1 TFA intake on phagocytosis and cell-mediated immunity seems to be suppressive. This finding differs from results describing proinflammatory effects associated with long-term exposure to TFAs.

Higher content of C18:1 trans fatty acids in early human milk fat of Roma breast-feeding women.

AIM: The purpose of our study was to determine the content of trans fatty acids in early human breast milk as an indicator of dietary exposure in a sample of Roma breast-feeding women and in a sample of women from the general Czech population. METHODS: We collected samples of early human milk from 43 Prague women from the general population and 21 Roma women. After lipid extraction, the fatty acids were converted into methyl esters (FAMEs). Finally, gas chromatography with flame ionization detector (GC-FID) analysis on a CP-Sil 88 column was used to determine C18:1 trans monoenic fatty acid levels and total trans isomers fatty acid levels in human milk. RESULTS: A significantly higher content of C18:1 trans fatty acid isomers was detected in human milk fat from Roma mothers than in women of the general population (2.73 vs. 2.09%, p < 0.05). Both groups monitored did not differ in the representation of total fatty acid trans isomers. Differences in the frequency of consumption of certain TFA sources (butter, fried crisps) were established. CONCLUSIONS: The study proved a higher fatty acid trans isomers content in Roma breast-feeding mothers in the Czech Republic, and this is probably related to their bad eating habits.

KCNJ11 E23K polymorphism and diabetes mellitus with adult onset in Czech patients.

In this work, we studied the association of the E23K polymorphism of the Kir6.2 ATP-sensitive potassium channels in 212 Czech patients with diabetes mellitus who were diagnosed after the age of 35. Patients were classified into T1DM, LADA and T2DM groups based on C-peptide and GADA levels. Carriers of the predisposing Kir6.2 E23K K allele showed no increased risk of either type of diabetes mellitus development. On the other hand, we found a correlation between E23K SNP of the KCNJ11 gene and C-peptide levels, which may be considered a measure of pancreatic beta-cell activity, although this correlation was not statistically significant. In conclusion, we failed to confirm the Kir6.2 E23K as a genetic marker for T1DM, LADA and T2DM in the Central Bohemian population of the Czech Republic.

Glucagon-like peptide-1 analogues exenatide and liraglutide exert inhibitory effect on the early phase of liver regeneration after partial hepatectomy in rats.

Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats. Animals were submitted either to PHx or laparotomy and received 3 doses of either GLP-1 analogues (Exenatide - 42 microg/kg b.w., Liraglutide - 0.75 mg/kg b.w.) or saline intraperitoneally. We analyzed body and liver weight, liver bromodeoxyuridine incorporation, liver content of DNA, triacylglycerols and cholesterol and biochemical serum parameters. Bromodeoxyuridine labeling was significantly lower in hepatectomized rats receiving either type of GLP-1 analogues when compared to hepatectomized controls. This effect was more pronounced in the Liraglutide group compared to Exenatide (p<0.001). In addition, liver DNA content was lower in hepatectomized rats receiving Liraglutide than in hepatectomized control rats (p<0.001). In conclusion, GLP-1 analogues Exenatide and Liraglutide significantly inhibited an early phase of liver regeneration after PHx in rats. This inhibitory effect was more pronounced in rats receiving Liraglutide.

The assessment of the serum C-peptide and plasma glucose levels by orally administered whey proteins in type 2 diabetes mellitus.

A personalized antidiabetic therapy is not yet part of the official guidelines of professional societies for clinical practice. The aim of this study was to evaluate the serum C-peptide and plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) after oral administration of whey proteins. Sixteen overweight T2DM Caucasians with good glycemic control and with preserved fasting serum C-peptide levels (>200 nmol/l) were enrolled in this study. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were administered for assessing serum C-peptide and plasma glucose levels in each participant. Both oral tests induced similar pattern of C-peptide secretion, with a peak at 90 min. The serum C-peptide peak concentration was 2.91+/-0.27 nmol/l in OWIST, which was 22 % lower than in OGTT. Similarly, the C-peptide iAUC(0-180) were 32 % lower in the OWIST than in the OGTT (p<0.01). Contrary to OGTT the OWIST did not cause a significant increase of glycemia (p<0.01). Our study showed that the OWIST represents a useful tool in estimation of stimulated serum C-peptide levels in patients with T2DM.

Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

BACKGROUND/OBJECTIVES: Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. SUBJECTS/METHODS: Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. RESULTS: Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. CONCLUSIONS: Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

[Glibenclamide instead of insulin: a new chance for MODY 3 type diabetes patients: case report]. / Glibenklamid místo inzulinu: nová sance pro pacienty s diabetem MODY 3: kazuistika.

MODY 3 belongs to monogenic forms of diabetes mellitus and is caused by monoallelic mutation in gene for transcription factor HNF-1alpha, essential for regulation of beta-cell function. Clinical presentation of MODY 3 is similar to that of type 1 diabetes. Although MODY 3 patients are not threatened by ketoacidosis, tight metabolic control is important for prevention of chronic diabetic complications. In the sibbling pair diabetes was manifested by osmotic symptoms resulting from hyperglycaemia at the age of 18 years (brother) resp. 15 years (sister) and both of them started being treated with intensified insulin treatment. Metabolic control of the brother was very tight with HbA1c 3.3 % but frequent hypoglycaemias occured. On the contrary metabolic control of the sister was very poor due to her non-compliance (HbA1c 10.9 %, IFCC). Molecular-genetic testing proved HNF-1alpha gene mutation (Arg200Gly). In accordance with the references treatment with sulphonylurea derivate glibenclamide was initiated [at the doses 1.25 (brother) resp. 7.5 (sister) mg/day] and insulin treatment was discontinued. The treatment change led to better quality of life and metabolic control in both the patients and suprisingly to the lower frequency of the hypoglycaemias in the brother (HbA1c decreased from 3.3 % to 2.8 % in three months in the brother resp. from 10.9 % to 10.0 % in two months in the sister). Molecular-genetic testing enables the change of treatment leading to better quality of life and metabolic control, although its longterm safety and efficacy will have to be confirmed.

Excess of free fatty acids as a cause of metabolic dysfunction in skeletal muscle.

Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA.