Visceral Fat Accumulation Is Related to Impaired Pancreatic Blood Perfusion and Beta-Cell Dysfunction in Obese Women.

AIMS/HYPOTHESIS: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. METHODS: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2-L5 vertebrae). RESULTS: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = -0.434, p = 0.017), WHR (r = -0.411, p = 0.024), and VAT (r = -0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = -0.401, p = 0.028) and HOMA-IR (r = -0.376, p = 0.041). DISCUSSION/CONCLUSION: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

Effect of glucagon-like peptide-1 analogue liraglutide on primary cultures of rat hepatocytes isolated from lean and steatotic livers.

Non-alcoholic fatty liver disease and its complications are frequent causes of liver-related morbidity and mortality. Incretin glucagon-like peptide-1 (GLP-1) affects liver functions and metabolism. Although GLP-1 analogues are widely used in clinical practice, information regarding their potential toxic effect on hepatocytes in vitro is missing. Therefore, we evaluated the effect of GLP-1 analogue liraglutide on activity of caspases 3/7, cell viability and oxidative stress in primary cultures of hepatocytes. Primary cultures isolated from male Wistar rats fed a standard (ST1-group, 10% energy from fat) or a high-fat diet (HF-group, 71% fat) for 10 weeks were incubated with liraglutide (0.1-1000 nmol/l) for 24 h. Activities of caspases 3/7 and cellular dehydrogenases (WST-1), lactate dehydrogenase (LDH) leakage and oxidative stress (malondialdehyde concentration and DCFDA assay) were evaluated. HF-groups vs. ST1-groups showed higher caspases activity, LDH leakage and MDA production (p < 0.001) and lower cellular dehydrogenases activity (p < 0.01). Liraglutide induced a dose-dependent decrease of caspases activity in both groups, reduction of oxidative stress in HF-animals and exerted no negative effects on other parameters. In conclusion, GLP-1 analogue liraglutide decreased activity of caspases 3/7, reduced ROS production and didn't exhibit negative effects on cell viability and oxidative stress in primary cultures of hepatocytes isolated from lean and steatotic livers.

Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells.

OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers. INTERVENTIONS: Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 µg/mL propofol for 96 hours. MEASUREMENTS AND MAIN RESULTS: Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 µg/mL of propofol, concentrations as low as 1 µg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. CONCLUSIONS: Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.

Prevalence of malnutrition risk among institutionalized elderly from North Bohemia is higher than among those in the Capital City of Prague, Czech Republic.

OBJECTIVE: The aim of the study is to assess the risk of malnutrition among institutionalized elderly individuals in North Bohemia and compare it to the risk of malnutrition in the capital city of Prague, Czech Republic. In the Czech Republic, very few studies have been conducted with the goal of describing and evaluating the nutritional status of the institutionalized elderly. METHODS: In this study, data was collected from 254 elderly individuals (aged ≥ 65) residing in retirement homes in North Bohemia and then compared with similar data for the elderly living in retirement homes in Prague (the data from Prague were previously published in 2013). The data included an Mini-Nutritional Assessment (MNA) test; anthropometric measurements - Body Mass Index (BMI), waist circumference, triceps skinfold thickness; and biochemical parameters - albumin, prealbumin, transferrin, urea, and creatinine. RESULTS: Mean BMI values were 27.4 kg/m2 for females and 26.3 kg/m2 for males. According to the MNA questionnaire, 10.4% of all tested elderly were malnourished and 50.8% were at risk of malnutrition; lager proportion of females were found to be malnourished than males. Biochemical indicators supported the MNA results. MNA categories correlated positively with independence (r = 0.56; p < 0.001), mental status (r = 0.54; p < 0.001), mobility (r = 0.46; p < 0.001), calf circumference (r = 0.42; p < 0.001), BMI, and the ability to self-feed (both r = 0.37; p < 0.001). The percentage of institutionalized elderly with malnutrition living in North Bohemia and Prague were about the same; however, the percentage of those at risk of malnutrition was higher in North Bohemia (p = 0.006). CONCLUSION: Study results confirmed that the institutionalized elderly face issues that lower their nutritional status and put them at increased risk; clearly these issues need urgent attention.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

BACKGROUND/AIMS: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). METHODS: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. RESULTS: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. CONCLUSIONS: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent.

Serum microRNA-196 and microRNA-200 in pancreatic ductal adenocarcinoma of patients with diabetes mellitus.

BACKGROUND/OBJECTIVES: Our aim was to compare expressions of 6 microRNAs (miRNAs) in patients with pancreatic ductal adenocarcinoma (PAC) and non-cancer patients, moreover according to the presence or absence of diabetes mellitus. METHODS: Expressions of miRNA-192, -196, -200, -21, -30 and -423 were measured in 77 patients with PAC and 64 non-cancer patients (34 patients with type 2 DM and 30 control persons). 60 patients with PAC (78%) had DM or prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 44 out of them. RESULTS: The expressions of all microRNAs were 1.4-3.7 times higher (significantly) in the PAC group compared to non-cancer patients. No difference was found between PAC diabetic and PAC non-diabetic patients. MicroRNA-200 was significantly higher in PAC patients with significant body weight loss against those without weight loss. Adding miRNA-196 and -200 to the current marker CA 19-9 improved the discriminative ability of the test (compared to CA 19-9 alone). CONCLUSION: MicroRNA-196 and -200 could be used as additional markers in PAC diagnosis.

[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.

[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.

Low Frequencies of Autoimmunity-Associated PTPN22 Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies.

BACKGROUND: The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. METHODS: We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). RESULTS: The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. CONCLUSIONS: MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders.

Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports.

INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome. METHODS: We searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality. RESULTS: Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose. CONCLUSION: PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late.

[miRNA as a new marker of diabetes mellitus and pancreatic carcinoma progression]. / miRNA jako nový ukazatel u diabetes mellitus a u rozvoje karcinomu pankreatu.

Pancreatic cancer is a disease with increasing incidence and high (and nearly unchanged) lethality that is caused mainly due to its late diagnosis. Risk factors for neoplastic transformation are especially chronic pancreatitis, diabetes mellitus, but also obesity and smoking. The search for suitable early markers becomes a key element of research in this area. Such markers could be microRNAs, short single-stranded RNA molecules functioning as regulators of translation. This article serves as a review of contemporary evidence of microRNA in diabetes mellitus and pancreatic cancer.

[miRNA-192, miRNA-21 and miRNA-200: new pancreatic cancer markers in diabetic patients?]. / miRNA-192, miRNA-21 a miRNA-200: nové markery karcinomu pankreatu u diabetiku?

INTRODUCTION: Newly-onset diabetes mellitus (DM) in middle-aged and older people may be an early symptom of pancreatic cancer (PC). However, sensitive markers for PC are still missing. MicroRNAs (miRNAs) play an important role in a cell response regulation. Significant changes in miRNA expressions were observed in cancers. Our goal was to compare expressions of selected miRNAs in patients with PC, DM and controls. METHODS: We enrolled 74 patients with PC (42/32, with/without DM), 29 type 2 diabetic patients and 17 controls. MicroRNA was determined in serum of all examined subjects. In 9 patients with PC the tumor was resected subsequently and after 3 months the measurements were repeated. We analyzed the expressions of 8 miRNAs that we had identified in a previous pilot study (miR-21, miR-30, miR-191, miR-192, miR-196, miR-200, miR-423, miR-454). RESULTS: MicroRNA expressions were significantly higher in patients with PC than in DM and controls: miR-192: 1.6 (1.2 to 2.0) vs 0.3 (0.2-0.4) vs 0.3 (0.2 to 0.5), p < 0.00001; miR-21: 1.4 (1.2-1.7) vs 0.3 (0.2 to 0.5) vs 0.5 (from 0.4 to 0.7), p < 0.00001, miR-200: 1.6 (1.1 to 2.3) vs 0.3 (0.3-0.4) vs 0.3 (0.2 to 0.4), p < 0.00001. No difference was observed between DM and controls, as well as between diabetic and non-diabetic patients within the PC group. There were no significant differences in miRNA expressions in 9 patients after pancreatic surgery. But there were significant interindividual differences. CONCLUSION: Our data shows that miR-21, miR-192 and miR-200 could be used as new diagnostic markers for pancreatic cancer. A dynamics of these miRNAs could serve as a prognostic marker in patients after cancer removal. Futher prospective studies with newly-onset diabetic patients with no signs of malignancy will be needed to validate if suggested miRNAs could be used as early markers as well.

Palmitate-induced cell death and mitochondrial respiratory dysfunction in myoblasts are not prevented by mitochondria-targeted antioxidants.

BACKGROUND/AIMS: Deleterious effects of saturated fatty acids in skeletal muscle cells are well known but their impact on mitochondrial respiration has not been well studied. Mitochondrial oxidative damage has been implicated to play a role in their effect. The purpose of this study was to evaluate viability, mtDNA integrity and mitochondrial respiration in C2C12 myoblasts and myotubes exposed to palmitate and to test the effect of mitochondria-targeted antioxidants MitoQ and MitoTEMPOL in preventing palmitate-induced damage. METHODS: Cells were treated with tested compounds, mtDNA damage was detected by quantitative PCR and mitochondrial respiration was measured using an extracellular flux analyzer XF24. RESULTS: Palmitate caused mtDNA damage, which was associated with reduced mitochondrial respiration and cell death in myoblasts but not in myotubes. MitoTEMPOL was able to prevent palmitate-induced mtDNA damage in myoblasts but failed to prevent cell death. MitoQ did not show any protective effect and both compounds markedly inhibited mitochondrial respiration. CONCLUSION: Our results indicate that skeletal muscle progenitor cells could be the first target of the deleterious action of palmitate, as myoblasts appeared to be more sensitive to its effects than myotubes possibly in part due to a lower spare respiratory capacity in the former. Only MitoTEMPOL prevented palmitate-induced mtDNA damage but neither antioxidant was able to prevent cell death and both antioxidants had a marked negative effect on respiration.

[Food intake regulation - 2nd part]. / Regulace príjmu potravy - II. cást.

The review article summarizes the principles of hedonic regulation of food intake which represents the food intake independent on the maintenance of homeostasis. The theory describing hedonic regulation, so called Incentive Salience Theory, comprises three major processes: liking (positive attribution to food stimulus), wanting (motivation to gain it) and learning (identification of these stimuli and distinguishing them from those connected with aversive reaction). Neuronal reward circuits are the anatomical and functional substrates of hedonic regulation. They react to gustatory and olfactory (or visual) stimuli associated with food intake. A food item is preferred in case its consumption is connected with a pleasant feeling thus promoting the behavioural reaction. The probability of this reaction after repetitive exposure to such a stimulus is increased (learned preference). On the contrary, learned aversion after repetitive exposure is connected with avoidance of a food item associated with a negative feeling. Main mediators of hedonic regulation are endocannabinoids, opioids and monoamines (dopamine, serotonin). Dopamine in dorsal striatum via D2 receptors generates food motivation as a key means of survival, however in ventral striatum (nucleus accumbens) is responsible for motivation to food bringing pleasure. Serotonin via its receptors 5-HT1A a T-HT2C decreases intake of palatable food. It plays a significant role in the pathogenesis of eating disorders, particularly mental anorexia. There, a food restriction represents a kind of automedication to constitutionally pathologically increased serotonin levels. Detailed understanding of processes regulating food intake is a key to new pharmacological interventions in eating disorders.

[Osteoporosis and bone alterations in celiac disease in adults]. / Osteoporóza a metabolické kostní zmeny u celiakie v dospelosti.

Both celiac disease and osteoporosis are common diseases which are considered an emerging problem in medicine. Celiac disease is a condition at high risk for secondary osteoporosis. Osteoporosis or osteopenia are typically present in untreated adult symptomatic celiac disease with an overt malabsorption syndrome, but is found in about 50 % in suboptimally treated celiac patients, subclinical patients and asymptomatic adult celiac patients, too. Etiology of pathologic bone alteration in celiac disease is multifactorial; however, two main mechanisms are involved: intestinal malabsorption and chronic inflammation. The evaluation of bone mineral metabolism (total calcium/albumin, 25-OH vitamin D3 and parathormone levels in serum) and bone mineral density (densitometry) is recommended in the clinical management of celiac patients. Many studies have demonstrated that bone mineral density values in adults show a good improvement in the first period after the institution of gluten-free diet, the improvement is then unsatisfactory and treatment with a mineral-active drug should probably be considered.

[Effect of the liquid milk nutritional supplement with enhanced content of whey protein on the nutritional status of the elderly]. / Vliv podávání tekutého mlécného nutricního doplnku se zvýseným obsahem syrovátkových bílkovin na nutricní stav senioru

AIM: The aim of this study was to evaluate the effect of long-term administration of liquid nutritional supplement with increased amounts of whey protein and reduced amounts of lactose, produced in accordance with a new recipe "Nutrisen" on the elderly living in institutionalized care. METHODS: The study was carried out from May to July, 2013, on 47 retirement home residents, living in Prague, all of which were 65 years or older. Supplemented group (n = 23) consumed (200 ml) milk drinks with three different flavours on a daily basis for eight weeks. The reference group was on a normal diet. There was no significant difference in baseline characteristics between participants in both groups. Anthropometric and biochemical indicators of nutritional status and tolerance of the nutritional supplement during long-term use were evaluated. RESULTS: Both compliance (daily intake program) and tolerance of the nutritionally defined supplement were very good. For the supplemented group, there was an average weight increased of 700 grams after the 8 week nutritional supplement test period. Average levels of albumin and prealbumin increased significantly (from the beginning to the end of the program), 35.5 ± 4.52 g/l vs 36.19 ± 4.1 g/l and 0.160 ± 0.05 vs 0.174 ± 0.04 g/l (p < 0.05), vitamin D levels increased from 31.2 ± 16.4 nmol/l to 36.8 ± 17.7 nmol/l (p < 0.001) and HDL-cholesterol levels increased from 1.29 ± 0.33 mmol/l to 1.35 ± 0.35 mmol/l (p < 0.001). CONCLUSION: The specific nutritionally defined milk drink (Nutrisen), used in this study, was well tolerated by the elderly study participants, over the eight-week clinical study. We observed a positive effect on the participants weight, serum albumin, prealbumin, vitamin D and HDL-cholesterol.

[Factors causing damage and destruction of beta-cells of the islets of Langerhans in the pancreas]. / Faktory vedoucí k poskození a destrukci B-bunek Langerhansových ostruvku pankreatu.

Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area.Key words: pancreatic islet beta-cells of Langerhans - factors damaging or destroying beta-cells - insulin secretion.

Should the negativity for islet cell autoantibodies be used in a prescreening for genetic testing in maturity-onset diabetes of the young? The case of autoimmunity-associated destruction of pancreatic ß-cells in a family of HNF1A-MODY subjects.

It was recently suggested that routine islet cell autoantibody testing should be performed to discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes mellitus (T1DM). This is the first report ever to describe the familial manifestation of T1DM autoimmunity in nonobese HNF1A-MODY subjects and the presence of islet antigen-2 (IA-2) antibodies in MODY subjects. Three nonobese subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p. Arg159Gln mutation). All the tested subjects had detectable (but varying) levels of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or IA-2) in the absence of other T1DM characteristics. They displayed long-term expression of intermediate fasting C-peptide levels, ketoacidosis was absent even in periods of spontaneous insulin withdrawal, and full dependence on externally administered insulin was not detected in any of them although better glycemic control was achieved when insulin was supplemented. The course of the disease was similar to that of the autoantibody-negative HNF1A-MODY subjects. The case questions the selectivity of autoantibodies as a marker of T1DM or late-onset autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of autoantibodies as a universal negative marker of MODY in an effort to decrease the cost of health care, as it may eventually lead to the wrong diagnosis and thus to the incorrect treatment. Further research should involve examination of the autoantibody titers and prevalence in large and geographically diverse cohorts of MODY subjects selected for genetic testing (regardless of their autoantibody titers) as well as determination of the islet cell autoantibody kinetics in the course of MODY onset and progression.

Central dopaminergic activity influences metabolic parameters in healthy men.

BACKGROUND/AIMS: Central dopaminergic activity is probably linked to regulation of glucose and lipid metabolism and weight maintenance. The aim of our study was to evaluate the relationship between central dopaminergic activity measured using the apomorphine challenge test and metabolic parameters in healthy men. METHODS: Forty-two healthy men (average age 43.5 ± 7.4 years, body mass index, BMI, 27.4 ± 5.7) were examined anthropometrically and biochemically (glycemia, lipids, glycated hemoglobin). Central dopaminergic activity was assessed as the area under the curve (AUC) of prolactin (PRL) and growth hormone (GH) responses to the apomorphine challenge test after sublingual administration of apomorphine in a dose of 0.033 mg/kg. Insulin resistance was quantified by calculation of glucose disposal and metabolic clearance rate during a euglycemic hyperinsulinemic clamp on two insulin levels (1 and 10 mIU/kg/min). Linear regression was used for statistical analysis. RESULTS: Hormonal responses correlated negatively with age (for AUC/GH r = -0.33; p = 0.031) and BMI (AUC/GH r = -0.41; p = 0.007). After adjustment for age and BMI, a statistically significant negative correlations between AUC/PRL and total cholesterol (r = -0.41; p = 0.007), AUC/GH and HbA1c (r = -0.37; p = 0.016) and AUC/GH and HOMA (homeostasis model assessment; r = -0.345; p = 0.025) were observed. CONCLUSION: Central dopaminergic activity declines with age and BMI. Higher total cholesterol, glycated hemoglobin and insulin resistance parameters are connected with lower central dopamine tone.

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.