The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study.

AIMS/HYPOTHESIS: The variants of transcription factor 7-like 2 (TCF7L2) gene have been proposed to be associated with latent autoimmune diabetes in adults (LADA). We sought to confirm the possible association in Europeans and to examine the interaction between one gene variant and clinical data. METHODS: The TCF7L2 rs7903146 C-to-T polymorphism was genotyped in 211 LADA, 1,297 type 2 diabetic, 545 type 1 diabetic and 1,497 control individuals from Hungary. A meta-analysis of our and previously published studies was performed to evaluate the size and the heterogeneity of the gene effect. RESULTS: The meta-analysis yielded a significant effect of TCF7L2 T allele (OR 1.28; p < 0.0001) on LADA risk without heterogeneity among Europeans. The T allele conferred equally strong susceptibility to LADA and type 2 diabetes. In the Hungarian dataset, the T allele was associated with LADA and type 2 diabetes, but not with type 1 diabetes. T allele carriers had significantly lower BMI than patients with the CC genotype in the LADA and type 2 diabetes groups (p = 0.0021 and p = 0.0013, respectively). In both diseases, the diabetes risk was significantly higher in the non-overweight than in the overweight BMI category (p = 0.0013 and p < 0.0001, respectively); susceptibility to LADA was increased by 2.84-fold in non-overweight individuals compared with overweight ones. CONCLUSIONS/INTERPRETATION: The meta-analysis demonstrates that TCF7L2 rs7903146 polymorphism is a population-independent susceptibility locus for LADA in Europeans. The effect size is similar for LADA and type 2 diabetes. The gene effect on diabetes risk may be modulated by BMI, such that the lower the BMI, the higher the gene effect.

Gallstone Ileus, Bouveret's Syndrome and Choledocholithiasis in a Patient with Billroth II Gastrectomy - A Case Report of Combined Endoscopic and Surgical Therapy.

Intestinal obstruction due to gallstone is a rare, but quite severe gastrointestinal disorder, which always requires a rapid and correct diagnosis to achieve optimal therapy. Digestive endoscopy is an important method to determine the level of the bowel obstruction and to plan an optimal therapeutic strategy. Our present case demonstrates that in a high-risk patient, a combined endoscopic and surgical therapy is the best choice to solve the obstruction of the colon, of the stomach and of the common bile duct caused by multiple gallstones.

A new distensibility technique to measure sphincter of Oddi function.

BACKGROUND: Evaluation of the biliary tract is important in physiological, pathophysiological, and clinical studies. Although the sphincter of Oddi (SO) can be evaluated with manometry, this technique has several limitations. This may explain the difficulties in identifying pathophysiological mechanisms for dysfunction of the SO and in identifying patients who may benefit from certain therapies. To encompass problems with manometry, methods such as the functional lumen imaging probe (FLIP) technique have been developed to study GI sphincters. This study set about miniaturising the FLIP probe and validating it for measurements in the SO. In order to get a better physiological understanding of the SO the aims were to show the sphincter profile in vivo and motility patterns of SO in pilot studies using volunteers that were experiencing biliary type pain but had normal SO manometry. METHODS: The SO probe was constructed to measure eight cross-sectional areas (CSA) along a length of 25 mm inside a saline-filled bag. To validate the technique for profiling the SO, six perspex cylinders with different CSAs were measured nine times to assess reproducibility and accuracy. KEY RESULTS: Reproducibility and accuracy for these measurements were good. The probe performed well in bench tests and was therefore tested in four humans. The data indicated that it was possible to make distensions in the human SO and that a geometric sphincter profile could be obtained. CONCLUSIONS & INFERENCES: The probe will in future studies be tested for diagnostic purposes related to sphincter of Oddi diseases.

The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence Finnish and the medium-incidence Hungarian populations.

AIMS/HYPOTHESIS: The rs1990760 polymorphism (Ala946Thr) of interferon induced with helicase C domain 1 (IFIH1) has been proposed to associate with type 1 diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes was investigated in two distinct white populations, the Hungarians and Finns. METHODS: The rs1990760 polymorphism was genotyped in 757/509 Hungarian/Finnish childhood-onset cases, 499/250 Hungarian/Finnish control individuals and in 529/924 Hungarian/Finnish nuclear family trios. Disease association was tested using case-control and family-based approaches. A meta-analysis of data from 9,546 cases and 11,000 controls was also performed. RESULTS: In the Hungarian dataset, the A allele was significantly more frequent among cases than among controls (OR 1.29, 95% CI 1.10-1.52; p = 0.002). Combined analysis of Hungarian and Finnish datasets revealed a strong disease association (OR 1.235, 95% CI 1.083-1.408; p = 0.002). Furthermore, the A allele was significantly overtransmitted in both family trio datasets (p = 0.017 in Hungarians; p = 0.007 in Finns). The A allele was increased in Hungarian vs Finnish cases (64.9% vs 60.8% in Finns; p = 0.003). The meta-analysis yielded a significant effect for IFIH1 rs1990760 A allele on type 1 diabetes risk (OR 1.176, 95% CI 1.130-1.225; p = 5.3 x 10(-15)) with significant heterogeneity between effect sizes across the studied populations (p = 0.023). CONCLUSIONS/INTERPRETATION: This study represents the first independent confirmation of the association between type 1 diabetes and the IFIH1 gene in Hungarian and Finnish populations. Summarising the data published so far, a clear association between the Ala946Thr polymorphism and type 1 diabetes was detected, with an apparent difference in the contribution to disease susceptibility in different populations of European ancestry.

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.

Frequencies of genetic polymorphisms of TLR4 and CD14 and of HLA-DQ genotypes in children with celiac disease, type 1 diabetes mellitus, or both.

OBJECTIVES: Besides the central role of the adaptive immune system, a disturbance of innate immunity is also involved in the pathogenesis of celiac disease (CD). Inasmuch as CD and type 1 diabetes mellitus (T1DM) frequently coexist because of a common genetic predisposition, our aim was to study the frequency of CD14 C-260T and TLR4 A+896G single nucleotide polymorphisms (SNPs) and the distribution of HLA-DQ genotypes in children affected by CD, T1DM, or both. PATIENTS AND METHODS: TLR4 and CD14 SNPs were tested by polymerase chain reaction, followed by restriction fragment length polymorphism analysis in 80 children with T1DM, 100 children with CD, and 47 children with both CD and T1DM. Determination of HLA-DQ alleles was done by sequence-specific polymerase chain reaction. Frequencies were compared with those of healthy control children. RESULTS: The prevalence of the homozygous CD14 C-260TT genotype was significantly (P = 0.0081) lower in children with T1DM but not in those with CD and T1DM, compared with control children. No difference was found in the genotype and allele frequencies of TLR4 between the studied groups. In patients with T1DM, the frequency of the homozygous HLA-DQ8 genotype was significantly higher than in CD, whereas the frequency of homozygous or heterozygous HLA-DQ2 genotypes did not differ from that in control children. In patients with CD, both homozygous and heterozygous HLA-DQ2 genotypes were significantly more frequent than in the control and T1DM groups, and no elevation in the frequency of the HLA-DQ8 genotypes was observed. In patients with T1DM and those with CD and T1DM, the occurrence of HLA-DQ2/8 heterozygosity was significantly higher than in children with CD only and in control children. CONCLUSIONS: Our results suggest that in patients with T1DM, the CD14 C-260TT homozygous genotype increases the risk for the development of CD. The distribution of HLA-DQ genotype is different in children with CD and T1DM than in children with CD or T1DM only. Determination of the HLA-DQ genotype in children with T1DM may help in estimating the risk for the development of CD.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

Analysis of the motor function of the human sphincter of Oddi by endoscopic retrograde cinecholangiography gated by manometry--a report of a case.

Although the motor function of the sphincter of Oddi (SO) has been clearly identified by endoscopic SO manometry (ESOM), the physiologic role of the phasic contractions of the SO remains unsettled in humans. The aim of this study was to correlate SO motor activity measured by ESOM with bile flow characteristics determined by simultaneously recorded endoscopic retrograde cinecholangiography. We investigated a 55-year-old female patient by means of ESOM. During the station pull-through recording, the ESOM catheter was withdrawn into the SO zone and retained there for 15 min. The pressures transmitted by the external transducers and the enlarged video picture of the choledochoduodenal junction from the X-ray fluoroscopic monitor (25 digital pictures/sec) were recorded simultaneously on the computer system with a time-correlated basis. During the analysis without taking note of the cinefluoroscopic events, we selected different manometric periods manually, such as the pressure wave of the SO phasic contraction, no SO phasic activity and the first second of the beginning of the next phasic contraction. Cumulative cinecholangiographic pictures were then constructed by the computer for each period, at a frequency of one frame/sec to create representative sum-of-pictures for each manometric period. By means of the application of manometrically gated cinecholangiography, we succeeded in demonstrating an exact time correlation between the SO systolic and diastolic movements on cinecholangiography and the pressure recording detected by ESOM in humans.

Altered distribution of the debrisoquine oxidative phenotypes in children with type 1 diabetes mellitus.

OBJECTIVE: The recently observed increase in the incidence of type 1 diabetes mellitus (Type 1 DM) suggests a major role of environmental factors in the etiopathogenesis of the disease. The individual variation in cytochrome P(450)IID6 may influence the individual susceptibility to environmentally linked diseases. We aimed to evaluate the prevalence of cytochrome P(450)IID6 phenotypes in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n = 100). METHODS: Debrisoquine was administered orally and debrisoquine hydroxylation phenotype was determined as a metabolic ratio of urinary recovered debrisoquine and 4-hydroxydebrisoquine. RESULTS: Eight of the 100 healthy subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome P(450)IID6 poor metabolizer phenotype (metabolic ratio > or =12.6). CONCLUSION: Cytochrome P(450)IID6's activity may play a role in the development of Type 1 DM.

HbA1c levels and erythrocyte transport functions in complication-free type 1 diabetic children and adolescents.

Higher erythrocyte sodium-lithium countertransport activity (SLC) is implicated in the development of diabetic nephropathy. Altered glucose homeostasis and genetic susceptibility are claimed to play a role in the elevation of SLC. We aimed to test whether metabolic control or the genetic variants of G protein beta 3 (Gb3) subunits determine SLC and other erythrocyte transport activities in complication-free stage of type 1 diabetes. A total of 96 complication-free type 1 diabetic children and adolescents were enrolled. SLC, Na(+)/K(+)-ATPase (NAK) and Ca(2+)-ATPase (CA) were measured by functional assays in erythrocytes. Gb3-C825T polymorphism was determined by PCR-RFLP. Results were related to HbA(1c) and were compared to those of 97 healthy controls. SLC activity was higher in diabetics (387+/-146 vs. 280+/-65 mmol/RBC. hour) and correlated with HbA(1c) levels (y=0.004x+6.42, r=0.33, n=96, p<0.01). NAK and CA activities were unaltered. The prevalence of (825)T allele was similar in the patient and control groups (0.34 vs 0.37) and no differences in enzyme activities were observed between the (825)T allele-positive and negative subjects. Although metabolic control correlated with SLC, other membrane functions were not affected. Therefore we hypothesize that the relationship between advanced glycation and SLC elevation is not causative. Rather, a genetic susceptibility for the coexistence of poor metabolic control and higher SLC is more likely. However, the presence of Gb3-C825T variant is not likely to be a risk factor for SLC-elevation and altered metabolic control diabetes.

Recurrent nonvariceal upper gastrointestinal bleeding in a patient with gastroduodenal schistosomiasis.

In this case report, we describe the rare situation of a patient with nonvariceal upper gastrointestinal bleeding induced by gastric and duodenal involvement of Schistosoma mansoni infection. In this unique case severe, recurrent upper gastrointestinal bleeding was induced by central ulcerations of gastric pseudopolypoid and duodenal polypoid lesions. However, very atypically, there were no signs of portal hypertension, coagulopathy, or variceal bleeding, and no macroscopic evidence of lower gastrointestinal tract involvement. Neither anti-ulcer therapy nor endoscopic hemostasis methods were effective in preventing recurrent bleeding episodes. Finally, typical histological and serological tests (positive for S. mansoni hemagglutination) led to the correct diagnosis, and the patient was completely cured by specific antischistosomal therapy.

Association between G-308A polymorphism of the tumor necrosis factor-alpha gene and 24-hour ambulatory blood pressure values in type 1 diabetic adolescents.

Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine, which also influences blood pressure (BP). The G-308A polymorphism of the TNF-alpha gene is associated with altered TNF-alpha production. The prevalence of the TNF-alpha-308A allele is reportedly higher among patients with type 1 diabetes mellitus (T1DM) than in the healthy population. In this study we investigated whether this genetic polymorphism might correlate with BP values in diabetic adolescents. Ambulatory BP monitoring (ABPM) was performed in 126 adolescents with T1DM (mean age: 14 +/- 2.4 years). The TNF-alpha G-308A genotype was determined by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methodologies. ABPM results were related to healthy reference values and are given as standard deviation score (SDS). The prevalence of the -308A allele was higher in diabetic adolescents than the Hungarian reference population (0.26 vs 0.14, p < 0.01). TNF-alpha genotype was associated both with systolic and diastolic BP values (p < 0.01 and p < 0.01, respectively). In patients with TNF-alpha-308GG and -308GA/AA genotypes, the 24-h systolic BP average values were 0.37 +/- 1.33 and -0.38 +/- 1.28 SDS, while 24-h diastolic BP average values were 0.09 +/- 1.30 and -0.67 +/- 1.31 SDS. Hence, the TNF-alpha-308A allele carrier state appears to be associated with lower systolic and diastolic BP values.

Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus.

The aim of this study was to investigate the amounts and epitope specificity of antibodies against heat shock protein 60 (hsp60) in the sera of type 1 diabetic and healthy children. Antibodies specific for peptide p277 of human hsp60 and of M. bovis as well as for human hsp60, M. bovis hsp65 proteins were measured by ELISA. Other autoantibodies (islet cell antibodies, glutamate decarboxylase antibodies and IA-2 antibodies) were also determined. A total number of 83 serum samples from children with type 1 diabetes mellitus and 81 samples of control children were investigated. Epitope scanning of the hsp60 for linear antibody epitopes was carried out using synthetic peptides attached to pins. The antibody levels specific for peptide p277 of human- and of M. bovis origin were significantly (human: P=0.0002, M. bovis: P=0.0044) higher in the diabetic children group than in the healthy children. We could not find significant difference in the antibody levels to whole, recombinant hsp proteins among the examined groups of children. Antibodies to two epitope regions on hsp60 (AA394-413 and AA435-454) were detected in high titres in sera of children with diabetes mellitus. The first region similar to the sequence found in glutamate decarboxylase, whereas the second one overlaps with p277 epitope to a large extent. Presence of antibodies to certain epitopes of hsp60 (AA394-413-glutamic acid decarboxylase-like epitope; AA435-454-p277-like epitope) in diabetic children may reflect their possible role in the autoimmune diabetogenic process of the early diabetes.

[High prevalence of islet cell and glutamate decarboxylase antibodies in healthy young adults born with low birth weight]. / Szigetsejt-citoplazma és glutaminsav-dekarboxiláz elleni antitestek kis súllyal született fiatal felnóttekben.

Low birth weight is an independent risk factor for several chronic adult diseases. The authors determined the prevalence of islet cell cytoplasmatic antibody (ICA), glutamic acid decarboxylase antibody (GADA) and tyrosine phosphatase antibody (IA2) in 41 women and 34 men born with a birth weight under 2500 grams. ICA and/or GADA positivity was detected in 32% of the subjects tested. Both antibodies were present in 11% of the subjects. IA2 positivity was not found in any of the enrolled subjects. The cause of the high prevalence of autoantibodies is still unclear. Further studies are needed to elucidate whether this phenomenon might have a role in the development of metabolic disturbances in late adulthood.

[Prognostic significance of retinal microaneurysm number and localization in type-1 diabetes mellitus]. / Retinalis microaneurysmák számának és lokalizációjának prognosztikai jelentósége 1-es típusú diabetes mellitusban.

The authors studied whether central retinal microaneurysm count predicts further progression of background retinopathy in juvenile onset type-1 diabetes mellitus. 94 patients (49 females and 45 males) were followed up longitudinally (8-17.5, mean 10 years) by evaluating fluorescein angiograms. Age at last examination was 17-32 years (mean age 22.4 years) and duration of diabetes was 8-22 years (mean duration 13.7 years). Microaneurysm counts and location were determined with the help of a grid consisting of three concentring circles and four radial lines (nine subfields) centered for the macula. 82% of the all microaneurysms were found inside the circle with 1500 micron radius. Participants were divided into three groups: those with no microaneurysms (1st group, n = 28) and those with 1-4 (2nd group, n = 35) and those with 5 or more microaneurysms (3rd group, n = 31) in the central circle with 600 micron radius at least one time during the whole follow up. Background retinopathy was found in 3 of 28 cases (approximately 10%) in the first group, 8 of 35 (approximately 23%) in the second group and in all the 31 patients (100%) in the third group. Proliferative retinopathy was found in the third group only. The authors suggest that the appearance of 5 or more microaneurysms in the macular area in type-1 diabetes mellitus may be sensitive indicator of the development of severe background and proliferative retinopathy. Study describes the importance of central microaneurysm count predicting further progression of background retinopathy could not be found in the available literature.

[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin]. / A lassan kialakuló felnóttkori autoimmun diabetes (LADA): az autoimmun eredetú 1-es típusú cukorbetegség klinikai spektrumának része.

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.

Gallbladder hypomotility in diabetic polyneuropathy.

This study was performed to evaluate the gallbladder motility in long-standing diabetes mellitus. The gallbladder function of diabetic patients was measured by means of quantitative hepatobiliary scintigraphy, and the severity of the associated autonomic and sensory polyneuropathy was determined. The presence of a marked gallbladder hypomotility was established, and a positive correlation was observed between the severity of the autonomic disturbance and the contractile disorder. This study underlines the important role of the neuropathy in the development of gallbladder hypomotility accompanying long-term diabetes mellitus.

Quantitative hepatobiliary scintigraphy and endoscopic sphincter of Oddi manometry in patients with suspected sphincter of Oddi dysfunction: assessment of flow-pressure relationship in the biliary tract.

OBJECTIVE: In the present study, the diagnostic efficacy of quantitative hepatobiliary scintigraphy (QHBS) was compared with that of endoscopic sphincter of Oddi (SO) manometry (ESOM) in patients with a suspected SO dysfunction (SOD) of biliary type II or III. METHODS: Twenty cholecystectomized patients with SOD biliary types II and III were investigated by QHBS and by ESOM. Twenty asymptomatic cholecystectomized patients served as controls for scintigraphy. ESOM was performed by applying the station pull-through method. Then SO basal pressure and phasic contraction characteristics were determined. During QHBS, time-activity curves were generated, and the time-to-peak (Tmax), the half-time of excretion (T(1/2)), the duodenal appearance time (DAT) and the hilum-to-duodenum transit time (HDTT) were then calculated. At the 60th minute of QHBS, 5 ng/kg body weight/min caerulein was administered. RESULTS: In patients with SOD and elevated SO basal pressure (> 40 mmHg), QHBS parameters, such as Tmax and T(1/2) calculated from regions of interest over the hepatic hilum and common bile duct, HDTT and DAT proved to be significantly increased compared to controls: 28.7 +/- 4.3 versus 21.1 +/- 4.6 min, 39.7 +/- 15.4 versus 18.8 +/- 2.6 min, 9.0 +/- 3.6 versus 2.3 +/- 1.3 min and 27.1 +/- 4.9 versus 16.6 +/- 3.0 min, respectively. In contrast, in patients with SOD and normal SO basal pressure, QHBS parameters did not differ significantly from the controls. For the pooled data on the symptomatic patients with SOD, a statistically significant linear correlation was found between the SO basal pressure and the QHBS parameters. Although HDTT was the most sensitive scintigraphic parameter (89%), the combined sensitivity and specificity of Tmax and T(1/2) of the common bile duct reached 100%. No scintigraphic sign of a paradoxical response to cholecystokinin was detected. CONCLUSIONS: QHBS is a useful non-invasive diagnostic method for the selection of SOD patients with an elevated SO basal pressure. A significant correlation has been established between the trans-papillary bile flow measured by QHBS and the SO basal pressure determined by ESOM.