Next- generation sequencing is an effective method for diagnosing patients with different forms of monogenic diabetes.

AIM: Monogenic diabetes (MD) represents 5-7% of antibody-negative diabetes cases and is a heterogeneous group of disorders. METHODS: We used targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay to perform genetic and clinical characteristics of a study group of 684 individuals, including 542 patients referred from 12 Polish Diabetes Centers with suspected MD diagnosed between December 2016 and December 2019 and their 142 family members (FM). RESULTS: In 198 probands (36.5%) and 66 FM (46.5%) heterozygous causative variants were confirmed in 11 different MD-related genes, including 31 novel mutations, with the highest number in the GCK gene (206/264), 22/264 in the HNF1A gene and 8/264 in the KCNJ11 gene. Of the 183 probands with MODY1-5 diabetes, 48.6% of them were diagnosed at the pre-diabetes stage and most of them (68.7%) were on diet only at the time of genetic diagnosis, while 31.3% were additionally treated with oral hypoglycaemic drugs and/or insulin. CONCLUSIONS: In summary, the results obtained confirm the efficacy of targeted NGS method in the molecular diagnosis of patients with suspected MD and broaden the spectrum of new causal variants, while updating our knowledge of the clinical features of patients defined as having MD.

Application of polymeric membranes for the purification of solutions containing cationic surfactants.

The aim of the study was to examine physicochemical properties of three cationic surfactants and to evaluate the effectiveness of their removal with the use of polymeric membranes. The experiments were performed in a laboratory scale set-up with the use of Microdyn-Nadir® nanofiltration and ultrafiltration membranes. Cetrimonium bromide (CTAB), benzalkonium chloride (BAC) and Tequat LC90i (TEAQ) were chosen for the test. In the experiments, surfactant solutions in a wide range of concentration were treated (50-3,000 mg L-1). The experimental research included evaluation of the effect of membrane type and solution parameters (surfactant type and concentration, presence of inorganic compounds) on the process efficiency (retention coefficient and permeate flux). It was shown that surfactant removal by means of the pressure-driven membrane processes is an extensive issue and its efficiency depends on many factors. Ultrafiltration and nanofiltration membranes proved to be usable in CTAB removal (separation exceeded 90%); however, the process effectiveness was affected by surfactant concentration, membrane polymer type and membrane pore size. Separation obtained for BAC was on the lower level - the use of nanofiltration membranes brought maximum retention of 70%. TEAQ separation was very high and reached 100% with the use of ultrafiltration membranes. Mineral salt addition led to significant drop in surfactant retention.

Antioxidant action of six Trifolium species in blood platelet experimental system in vitro.

This study includes a comparative evaluation of antioxidant effects of plant extracts (1.5-50.0 µg/ml), derived from six clover (Trifolium) species: T. alexandrinum L., T. fragiferum L., T. hybridum L., T. incarnatum L., T. resupinatum var. majus Boiss., and T. resupinatum var. resupinatum L. Chemical profiles of the extracts contained three or four groups of (poly)phenolic compounds such as phenolic acids, clovamides, isoflavones, and other flavonoids. Antioxidant properties of Trifolium extracts were assessed as the efficacy to reduce oxidative and nitrative damage to blood platelets, exposed to 100 µM peroxynitrite-induced oxidative stress in vitro. Antioxidant actions of the examined extracts were determined by the following biomarkers of oxidative stress: thiol groups, 3-nitrotyrosine, lipid hydroperoxides, and thiobarbituric acid-reactive substances (TBARS). Despite the significant differences in the chemical composition (the total phenolic concentrations varied between 11.30 and 52.55 mg/g of dry mass) of Trifolium extracts, we observed noticeable protective effects of almost all tested plant preparations. The T. alexandrinum extract, containing the highest concentration of phenols, was the most effective antioxidant among the tested extracts. On the other hand, the T. incarnatum extract, which contained a comparable total phenolic content (49.77 mg/g), was less efficient in prevention of tyrosine nitration and generation of TBARS. These findings indicate on the important role of individual phenolic components of the examined clover extracts for the final antioxidative effects. Antioxidative properties of the remaining extracts were noticeably weaker.

Serum fibroblast growth factor 21 in human obesity: regulation by insulin infusion and relationship with glucose and lipid oxidation.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) reduces plasma glucose and triglycerides, and increases free fatty acid oxidation in animal models of diabetes. The aim of the present study was to assess the relationships of serum FGF21 with glucose oxidation (GOx) and lipid oxidation (LOx) in the baseline and insulin-stimulated conditions in lean and obese subjects. DESIGN: Cross-sectional study. SUBJECTS: Eighty-four subjects with normal glucose tolerance, 42 lean (body mass index (BMI) <25 kg m(-2)) and 42 overweight or obese (BMI between 25 and 40 kg m(-2)). MEASUREMENTS: Euglycemic hyperinsulinemic clamp and indirect calorimetry in the baseline state and during last 30 min of the clamp. The change in respiratory quotient (ΔRQ) in response to insulin was used as a measure of metabolic flexibility. Serum FGF21 was determined in the baseline state and after the clamp. RESULTS: Obese subjects had higher LOx in the baseline and insulin-stimulated conditions, lower insulin-stimulated GOx and ΔRQ (all P<0.05). Fasting serum FGF21 did not differ between the groups. Insulin infusion resulted in an increase in serum FGF21 in the obese (P=0.0001), but not in the lean group (P=0.76). Postclamp serum FGF21 was higher in the obese subjects (P=0.0007). In this group, postclamp FGF21 was related to LOx during the clamp (r=0.32, P=0.044), change in GOx and LOx in response to insulin (r=-0.44, P=0.005; r=0.47, P=0.002; respectively) and ΔRQ (r=-0.50, P=0.001). CONCLUSIONS: An increase in serum FGF21 in response to insulin in obese subjects might represent inappropriate response, possibly associated with metabolic inflexibility in obesity and insulin resistance.

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. METHODS: A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. RESULTS: A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. CONCLUSIONS/INTERPRETATION: The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.

Relationships between serum adiponectin and soluble TNF-α receptors and glucose and lipid oxidation in lean and obese subjects.

Insulin resistance might be associated with an impaired ability of insulin to stimulate glucose oxidation and inhibit lipid oxidation. Insulin action is also inversely associated with TNF-α system and positively related to adiponectin. The aim of the present study was to analyze the associations between serum adiponectin, soluble TNF-α receptors concentrations and the whole-body insulin sensitivity, lipid and glucose oxidation, non-oxidative glucose metabolism (NOGM) and metabolic flexibility in lean and obese subjects. We examined 53 subjects: 25 lean (BMI < 25 kg × m(-2)) and 28 with overweight or obesity (BMI > 25 kg × m(-2)) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese subjects had lower insulin sensitivity, adiponectin and higher sTNFR1 (all P < 0.001) and sTNFR2 (P = 0.001). Insulin sensitivity was positively related to adiponectin (r = 0.49, P < 0.001) and negatively related to sTNFR1 (r = -0.40, P = 0.004) and sTNFR2 (r = -0.52, P < 0.001). Adiponectin was related to the rate of glucose (r = 0.47, P < 0.001) and lipid (r = -0.40, P = 0.003) oxidation during the clamp, NOGM (r = 0.41, P = 0.002) and metabolic flexibility (r = 0.36, P = 0.007). Serum sTNFR1 and sTNFR2 were associated with the rate of glucose (r = -0.45, P = 0.001; r = -0.51, P < 0.001, respectively) and lipid (r = 0.52, P < 0.001; r = 0.46, P = 0.001, respectively) oxidation during hyperinsulinemia, NOGM (r = -0.31, P = 0.02; r = -0.43, P = 0.002, respectively) and metabolic flexibility (r = -0.47 and r = -0.51, respectively, both P < 0.001) in an opposite manner than adiponectin. Our data suggest that soluble TNF-α receptors and adiponectin have multiple effects on glucose and lipid metabolism in obesity.

Poland: health system review

The Health Systems in Transition (HiT) country profiles provide an analytical description of each health system and of policy initiatives in progress or under development. They aim to provide relevant comparative information to support policy-makers and analysts in the development of health systems and reforms in the countries of the WHO European Region and beyond. The HiT profiles are building blocks that can be used: to learn in detail about different approaches to the financing, organization and delivery of health services; to describe accurately the process, content and implementation of health reform programmes; to highlight common challenges and areas that require more in-depth analysis; and to provide a tool for the dissemination of information on health systems and the exchange of experiences of reform strategies between policy-makers and analysts in countries of the WHO European Region. This series is an ongoing initiative and material is updated at regular intervals.

The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes.

AIM: Genome-wide association studies have shown that variation in the FTO gene predisposes to obesity and related traits that are common features of polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of FTO variation on obesity, insulin sensitivity, and metabolic and hormonal profiles in PCOS. METHODS: We examined 136 PCOS women (mean body mass index [BMI]: 28.28+/-6.95kg/m(2), mean age: 25.36+/-5.48 years). Anthropometric measurement, euglycaemic-hyperinsulinaemic clamp and oral glucose tolerance tests and sex hormone assessments were performed. The study group was genotyped for the FTO rs9939609 polymorphism. RESULTS: BMI (29.0+/-6.9kg/m(2) vs 26.1+/-6.8kg/m(2); P=0.023), body weight (80.1+/-20.7kg vs 72.6+/-20.2kg; P=0.048), fat mass (29.7+/-1 6.6kg vs 24.6+/-17.7kg; P=0.045) and waist circumference (89.8+/-16.7cm vs 83.2+/-17.1cm; P=0.028) were higher in carriers of at least one copy of the A allele. Differences in these parameters were more significant when comparing AA and TT homozygotes. Women with the AA genotype also had decreased insulin sensitivity (P=0.025) and follicle-stimulating hormone (P=0.036). In logistic-regression analyses, the association of the FTO gene polymorphism with insulin sensitivity was no longer significant when BMI was included in the model. CONCLUSION: Variation in the FTO gene modifies weight, adiposity and other measures of obesity and insulin sensitivity in PCOS. The examined FTO gene variant appears to have a greater impact on obesity and related traits in PCOS than in other phenotypes. The effect on insulin sensitivity appears to be secondary to its influence on obesity and body fat.

[The effect of intragastric balloon on serum lipids level in patients with morbid obesity]. / Wplyw leczenia balonem wewnatrz-zoladkowym na stezienie lipidów w surowicy u pacjentów z otyloscia olbrzymia.

Obesity is recently considered as the twentieth first century epidemy. An excessive accumulation of adipocytes that constitute metabolically active tissue, plays an important role in lipid and carbohydrate metabolism. In the morbidly obese population dyslipidemia is common. AIM OF OUR STUDY: To determine the content of total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and triacylglicerol (TG) in obese subjects treated with the Bioenterics Intragastric Balloon (BIB). MATERIAL AND METHODS: BIB was placement for 6 months in 21 obese patients, mean age 40 (21-60), with BMI 473 +/- 5.7 kg/m2. The control group consisted of 15 morbidly obese patients treated conservatively. Plasma lipid concentration were assessed by the enzymatic methods. RESULTS: No major complications have been noted in patients with BIB. However, nearly all patients complained of discomfort, nausea and vomiting for the first few days. Over a 6-month-period, a reduction in body mass in the BIB group was 17.1 +/- 8.0 kg as compared to 3.2 +/- 6.4 kg in the control group (p = 0.00003). The biggest reduction in body mass was observed during first month. After one month, total cholesterol (TC) decreased by 17.6% (p < 0.001), triacylglycerol (TG) decreased by 25.5% (p = 0.01), low-density lipoprotein cholesterol (LDL) decreased by 27.5% (p < 0.001). In the control group, the corresponding levels of TC, TG and LDL remained unchanged. The level of HDL increased in both group. CONCLUSIONS: In patients with morbid obesity treated with BIB, weight loss is accompanied by a decrease in concentration TC, LDL and TG and increase in plasma HDL. The reduction of lipid concentration in blood serum may cut down cholesterol-lowering therapy and diminish the risk for development of coronary heart disease.

The effect of intragastric balloon on plasma ghrelin, leptin, and adiponectin levels in patients with morbid obesity.

CONTEXT: Ghrelin and leptin are hormones regulating appetite and metabolic processes. Adiponectin plays an important role in the modulation of glucose and lipid metabolism. OBJECTIVE: The objective of the study was to evaluate the levels of plasma ghrelin, leptin, and adiponectin in obese subjects treated with bioenterics intragastric balloon (BIB), low-calorie diet (1500 kcal), and physical exercise. DESIGN: BIB was placed for 6 months in 21 subjects with body mass index 47.3 +/- 5.7. The control group consisted of 15 morbidly obese subjects treated with a low-calorie diet and physical effort. Plasma hormone levels were determined by RIA. RESULTS: In the BIB group, the insertion of the balloon caused a considerable reduction in body mass over a 6-month period (17.1 +/- 8.0 kg) as compared with the control group (3.2 +/- 6.4 kg). After 1 month, the levels of ghrelin increased from 621.9 +/- 182.4 to 903.9 +/- 237 pg/ml and thereafter gradually decreased, reaching the starting level 3 months after the removal of the balloon. In the same group, the levels of leptin decreased from 61.3 +/- 36.7 to 39.9 +/- 17.5 ng/ml. In the control group, the corresponding levels of ghrelin and leptin remained relatively stable. During the observation period, in the BIB group, the levels of adiponectin remained unchanged as opposed to a transient increase noted in the control group. CONCLUSIONS: In patients with morbid obesity, weight loss induced by BIB is associated with a decrease in plasma leptin and a transient elevation of plasma ghrelin. It is likely that the changes in hormones regulating the energy balance caused by BIB can prevent an increase in adiponectin level.

Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes.

AIMS/HYPOTHESIS: Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. The aim of our study was to assess parameters of the skeletal muscle sphingomyelin signalling pathway in men at risk of developing type 2 diabetes. METHODS: We studied 12 lean (BMI < 25 kg/m(2)) men without a family history of diabetes (control group), 12 lean male offspring of type 2 diabetic patients, and 21 men with overweight or obesity comprising 12 with NGT (obese-NGT) and nine with IGT (obese-IGT). A euglycaemic-hyperinsulinaemic clamp and a biopsy of vastus lateralis muscle were performed. Ceramide, sphingomyelin, sphinganine and sphingosine levels and sphingomyelinase and ceramidase activities were measured in muscle. Muscle diacylglycerol and triacylglycerol levels were estimated in a subgroup of 27 men (comprising men from all the above groups). RESULTS: Compared with the control group, the lean offspring of diabetic patients and the men with overweight or obesity showed lower insulin sensitivity (all p < 0.005) and a greater muscle ceramide level (all p < 0.01). The obese-IGT group had lower insulin sensitivity (p = 0.0018) and higher muscle ceramide (p = 0.0022) than the obese-NGT group. There was lower muscle sphingosine level and alkaline ceramidase activity in offspring of diabetic patients (p = 0.038 and p = 0.031, respectively) and higher sphinganine level in the obese-NGT (p = 0.049) and obese-IGT (p = 0.002) groups than in the control group. Muscle sphingomyelin was lower (p = 0.0028) and neutral sphingomyelinase activity was higher (p = 0.00079) in the obese-IGT than in the obese-NGT group. Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions. CONCLUSIONS/INTERPRETATIONS: Ceramide accumulates in muscle of men at risk of developing type 2 diabetes.

Increased serum interleukin-18 concentration is associated with hypoadiponectinemia in obesity, independently of insulin resistance.

OBJECTIVE: Interleukin-18 (IL-18) is a cytokine with proinflammatory and proatherogenic properties, which might be associated with the development of insulin resistance. In contrast, adiponectin, a protein secreted by adipose tissue, might exert insulin-sensitizing and antiatherogenic effects. The aim of the present study was to analyze the association between serum IL-18 and adiponectin in lean and obese subjects, in relation to insulin resistance. DESIGN: Cross-sectional study. SUBJECTS: One hundred and thirty individuals, 62 lean (body mass index (BMI)<25 kg/m(2), 30 men and 32 women) and 68 with overweight or obesity (BMI>25 kg/m(2), 24 men and 44 women), with normal glucose tolerance and without concomitant diseases. MEASUREMENTS: Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, serum concentrations of IL-18, IL-6, soluble tumor necrosis factor-alpha receptors and adiponectin. RESULTS: Obese subjects had lower insulin sensitivity (M value, P=0.00029) and serum adiponectin (P=0.01) and higher levels of serum IL-18 (P=0.00055). Circulating IL-18 was negatively related to adiponectin (r=-0.31, P=0.00027) and insulin sensitivity (r=-0.33, P=0.00012). Subgroup analysis revealed that these associations were present in the obese (adiponectin, r=-0.38, P=0.0014; M, r=-0.29, P=0.016), but not in lean individuals (r=-0.17, P=0.18 and r=-0.20, P=0.12, respectively). Association of IL-18 with adiponectin remained significant after adjustment for other estimated parameters, including insulin sensitivity. Also, relationship between IL-18 and insulin sensitivity was independent of other estimated parameters. CONCLUSION: Serum IL-18 is inversely related to serum adiponectin, independently of insulin resistance. The relationships of IL-18 with adiponectin and insulin sensitivity are influenced by the presence of overweight/obesity.

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin.

AIMS/HYPOTHESIS: Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. MATERIALS AND METHODS: We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model. RESULTS: Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation. CONCLUSIONS/INTERPRETATION: These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

Plasma adiponectin and E-selectin concentrations in patients with coronary heart disease and newly diagnosed disturbances of glucose metabolism.

PURPOSE: Adiponectin is a fat derived hormone, which enhances insulin sensitivity. In experimental studies adiponectin was shown to have antiatherogenic properties by suppressing endothelial expression of adhesion molecules. Therefore, the aim of the study was to evaluate plasma adiponectin and E-selectin concentrations in patients with coronary artery disease and impaired glucose metabolism and evaluation of their relationship with selected anthropometric, biochemical and clinical parameters. MATERIAL AND METHODS: The study group consisted of 62 patients with coronary heart disease, without previous diagnosis of diabetes mellitus (mean age 48.6 +/- 6.0 years; mean BMI 28.6 +/- 3.13 kg/m2). In the studied group the OGTT with glucose and insulin estimation was performed and insulin resistance index (HOMA-IR) was calculated. In the fasting state, the plasma adiponectin, soluble form of E-selectin, HbA1c and lipid parameters were estimated. RESULTS: Adiponectin concentration was not different in patients with type 2 diabetes mellitus and impaired glucose tolerance (n = 36) in comparison to the group with normal glucose tolerance (n = 26). There was also no difference in adiponectin concentration in relation to atherosclerosis progression. There was no significant correlation between adiponectin and calculated insulin resistance index, while there was marked inverse correlation between adiponectin and BMI (r = -0.30; p = 0.018), body weight (r = -0.33; p = 0.008), E-selectin (r = -0.263; p = 0.039), TG concentration (r = -0.27; p = 0.036), duration of coronary heart disease (r = -0.33; p = 0.009) and borderline significance with ejection fraction (r = -0.268; p = 0.06). CONCLUSIONS: Our study supports the hypothesis that adiponectin could be recognised as a protective protein for the development of atherosclerosis.

Homocysteine concentrations and vascular complications in patients with type 2 diabetes.

OBJECTIVE: Hyperhomocysteinemia is a well known risk factor for the diseases of the cardiovascular system, which seem to be the main cause of increased mortality in patients with type 2 diabetes. The aim of the study was to evaluate the levels of homocysteine in patients with type 2 diabetes in respect to the regimen of diabetes treatment as well as the presence of diabetic complications. METHODS: The investigation was carried out in the group of 64 patients with type 2 diabetes and in 18 healthy subjects from the control group. Clinical examination and measurements of homocysteine, folic acid, vitamin B12, glycosylated hemoglobin concentration and evaluation of parameters of the lipid metabolism, microalbuminuria and creatinine were done in both groups. RESULTS: Homocysteine concentration was significantly higher in the group of patients with diabetes in comparison to the control group (p = 0.0007). Diabetic patients had significantly lower concentrations of folic acid (p = 0.028) and HDL cholesterol (p = 0.025) together with higher levels of systolic blood pressure (p = 0.007). In the group of patients with diabetes no differences in homocysteine levels were found in respect to diabetes treatment. Diabetic patients with coronary artery disease had significantly higher homocysteine concentration in comparison to the group with diabetes without history of coronary artery disease (p = 0.0097). Homocysteine levels correlated significantly with incidence of ischaemic heart disease (r = 0.44, p = 0.001) and microalbuminuria (r = 0.26, p = 0.019). Negative correlation was noticed in HDL concentrations (r = -0.30, p = 0.013) and the levels of folic acid (r = -0.30, p = 0.008). CONCLUSION: Our results suggest that hyperhomocysteinemia in diabetic patients may contribute to the development of chronic complications. The influence of diabetes treatment on Hcy levels requires further observations.

The large increase in incidence of Type I diabetes mellitus in Poland.

AIMS/HYPOTHESIS: A rising incidence of Type I (insulin-dependent) diabetes mellitus in different countries in Europe during the last decade has been recently reported. However, in the early 1990s, Poland was reported to have a stable low incidence of this disease. This study aimed to estimate the annual incidence of Type I diabetes in a north-eastern region of Poland (Bialystok region) and investigate if it is associated with age, sex, urban rural differences and the season of disease onset. METHODS: A register of patients with Type I diabetes using two independent sets of data sources was established in 1994 as part of the EURODIAB TIGER programme. The primary data sources were paediatric and internal medicine divisions of the hospitals in the Bialystok province and the secondary were outpatient diabetic clinics in the region. The degree of ascertainment was 98.5 % for the combinated data sources. RESULTS: We found a significant rising trend in the incidence of Type I diabetes in children under 15 years of age (in 1998 the incidence was approximately twice as high as in 1994). Increasing incidence rates were observed in the rural areas but not in urban populations. Seasonal variation in the incidence was also found, with a peak in winter and nadir in summer. CONCLUSIONS/INTERPRETATION: These results show that the north-eastern region of Poland is an area with a moderate rather than a low risk of Type I diabetes. Our observations confirm the important role of environmental and socio-economic factors or both in the pathogenesis of Type I diabetes.

Changes in tumor necrosis factor-alpha system and insulin sensitivity during an exercise training program in obese women with normal and impaired glucose tolerance.

OBJECTIVE: Tumor necrosis factor-alpha (TNFalpha) plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. Plasma levels of the soluble (s) fractions of TNFalpha receptors, especially sTNFR2, are good indicators of TNFalpha system activation in obesity. The aim of the present study was to assess the effect of exercise training on the TNFalpha system and to evaluate the relationship with changes in insulin sensitivity. DESIGN AND METHODS: Sixteen obese women (body mass index (BMI)>27.8 kg/m(2)), 8 with normal (NGT) and 8 with impaired glucose tolerance (IGT), participated in an exercise training program which lasted for 12 weeks and included exercise performed on a bicycle ergometer at an individual intensity of 70% maximal heart rate, for 30 min, 5 days a week. Anthropometrical measurements and blood biochemical analyses were performed, and plasma TNFalpha, sTNFR1 and sTNFR2 levels were assessed. Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique (insulin infusion: 50 mU x kg(-1)xh(-1)). RESULTS: At baseline, despite similar anthropometrical parameters, IGT subjects were markedly more insulin resistant and had higher TNFalpha and sTNFR2 concentrations. Exercise training increased insulin sensitivity and decreased TNFalpha and sTNFR2 levels, while sTNFR1 remained unchanged. The decrease in sTNFR2 was significantly related to the increase in insulin sensitivity; that relationship remained significant after adjustment for the concurrent changes in BMI, waist circumference, percentage of body fat, plasma glucose, insulin and free fatty acids. CONCLUSIONS: Regular physical exercise decreases TNFalpha system activity and that decrease may be responsible for the concurrent increase in insulin sensitivity.

[Evaluation of lipid peroxidation and acid-base status in cord blood of newborns after diabetes in pregnancy]. / Ocena peroksydacji lipidów i równowaga kwasowo-zasadowa u noworodka z ciazy powiklanej cukrzyca.

The purpose of our study was to evaluate lipid peroxidation products and scavenging enzyme activity in placenta and cord blood as well as the estimation of acid-base status and blood gases. Seventy five pregnant patients and their newborns were investigated. Twenty eight had pre-gestational diabetes mellitus (PGDM) and 19 gestational diabetes mellitus (GDM). The following parameters were measured: malondialdehyde (MDA) concentrations, glutathione (GSH) levels, the activity of CuZn dismutase (SOD) (Bioxytech, France). Base excess, pO2, pCO2 and pH were measured in arterial and venous samples. Statistical analysis was performed using Mann-Whitney U test. MDA levels and GSH content increased significantly, while SOD activities declined in diabetic group. Newborns of PDGM mothers had essentially diminished pH and rised both, pCO2 and base deficit. There were no any significant differences in parameters of acid-base balance in newborns of patients with GDM as compared with healthy patients. Our results suggest, that in diabetic patients the fetuses are exposed to increased oxidative stress. The evaluation of antioxidant defence and lipid peroxidation, apart from routine measurement of acid-base balance, might serve as a useful marker of fetal distress in diabetic patients.

Lipid peroxidation, antioxidant defence and acid-base status in cord blood at birth: the influence of diabetes.

Pregnancy complicated by poor control of diabetes is associated with a higher risk of embryopathies, spontaneous abortions and perinatal mortality. A number of authors suggest an involvement of reactive oxygen species (ROS) in diabetic pregnancy. Determining lipid peroxidation products (LP), scavenging enzyme activities and the umbilical cord blood's acid-base balance may contribute to an adequate diagnosis of the neonate at birth. Nevertheless, such measurements seem to have limited value in practical clinical routine. The present study evaluates LP, antioxidant defence and acid-base status related to diabetic pregnancy. Twenty-eight women with type 1 diabetes (PGDM), 19 with gestational diabetes (GDM) and 13 control cases were investigated. An additional control group consisted of 15 healthy patients with negative diabetic history; all women underwent vaginal delivery. Immediately after delivery cord blood samples and placental tissue were collected for malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) determination. Additionally, pH, pCO2, pO2 and base excess were measured in both vessels and compared to identify and exclude double venous samples. MDA levels in both cord blood and placental homogenates were significantly higher in both pregestational and gestational diabetic groups, but SOD activity was significantly diminished. Cord blood GSH was markedly elevated in PGDM and GDM. We have also shown significant differences in acid-base parameters in infants of PGDM group. Statistical analysis was performed using the Mann-Whitney U-test. These findings indicate an excessive oxidative stress in pregnancy complicated by diabetes mellitus. Evaluating LP products and scavenging enzyme activities may be valuable, sensitive indexes of fetal/neonatal threat in diabetic pregnancy in humans. Since oxidative stress is an important pathway for fetal injury, we believe that obtaining adequate measurements at the time of birth would contribute to clarifying the fetal/neonatal status in a medical and legal context and might be of value in altering therapy in newborn infants.

Insulin, leptin, IGF-I and insulin-dependent protein concentrations after insulin-sensitizing therapy in obese women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, hormonal and biochemical effect of 4-5 months of insulin-sensitizing therapy (hypocaloric diet+metformin) in obese patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. METHODS: Twenty-three obese patients with PCOS, 19 obese patients without menstrual disturbances and 11 healthy control women were recruited from the Department of Endocrinology and Endocrine Gynecology, Medical Academy, Bialystok, Poland. Obese patients received 500 mg metformin together with hypocaloric diet three times daily for 4-5 months, after baseline study. The clinical parameters, menstrual pattern and serum concentrations of insulin, leptin, IGF-I, insulin-dependent proteins (sex hormone-binding protein (SHBG), insulin-like growth factor-binding protein-1 (IGFBP-1)), gonadotropins and sex steroids were determined before and after treatment. RESULTS: In the baseline study, obese patients with PCOS had significantly higher insulin, testosterone and LH concentrations in comparison with the other groups. The serum leptin, IGF-I, IGFBP-1 and SHBG were not different between the two groups of obese patients, but there was a significant difference in comparison with the control group. After metformin therapy a significant reduction in BMI, % of body fat and leptin concentration were observed in both groups of obese patients. Fasting insulin, testosterone and LH concentrations decreased significantly only in the PCOS group. Six out of 11 patients in the PCOS group had more regular menstrual cycles; two patients conceived. CONCLUSIONS: Insulin-sensitizing therapy could be considered as an additional therapeutic option in obese women with PCOS.