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.

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.

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.

N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy.

The N-acetyltransferase (NAT2) polymorphism has been suggested to be related to diabetic microvascular complications. To study the distribution of NAT2 genotypes in Caucasian type 1 diabetic patients with and without diabetic nephropathy, 214 adult type 1 diabetic patients and 53 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In addition, 75 young type 1 diabetic patients were genotyped, and 70 of them also phenotyped by caffeine. Of the adult patients, 83 had normal albumin excretion, 58 had microalbuminuria, and 73 had overt diabetic nephropathy. NAT2 allele frequencies were similarly distributed between the diabetic patients and healthy individuals: 0.29/0.2 5 (NAT2*4), 0.03/0.04 (NAT2*7B), 0.25/0.27 (NAT2*6A), and 0.43/0.44 (NAT2*5B), and within the diabetic subgroups. Because smoking is a known risk factor for diabetic nephropathy, nonsmoking and smoking patients were analysed separately. NAT2 allele frequencies differed significantly between the nonsmoking normoalbuminuric, microalbuminuric and nephropathic patients: 0.18/0.41/0.30 (NAT2*4), 0.04/0.00/0.02 (NAT2*7B), 0.35/0.18/0.17 (NAT2*6A), 0.43/0.41/0.50 (NAT2*5B), P = 0.013. In nonsmoking fast acetylators odds ratio for microalbuminuria and nephropathy was 3.1 (95% confidence interval 1.36-7.05), P = 0.007 by logistic regression. In smokers, a nonsignificant odds ratio was found [0.31 (95% confidence interval 0.08-1.2), P = 0.09]. Smoking is a strong confounding factor in relation to NAT2 analyses and diabetic nephropathy. According to our data, in nonsmoking type 1 diabetic patients fast NAT2 genotype implies an increased risk for diabetic nephropathy.

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.

Red cell sodium-lithium countertransport and blood pressure in children with insulin-dependent diabetes mellitus.

Sodium-lithium countertransport and blood pressure responses, maximal elevated plasma norepinephrine concentrations induced by acute physical work load and the carbohydrate metabolic state were analyzed in 40 children suffering from insulin-dependent diabetes mellitus (IDDM). Patients were selected according to the duration of the disease to get a horizontal insight into the progression of the diabetes. Sixteen healthy children served as controls. Sodium-lithium countertransport (Na-Li CT) was 281 +/- 64 mumol/l red blood cells (RBC) per hour in the control group. Na-Li CT was elevated in all diabetic groups (newly diagnosed: 455 +/- 48; diabetics for 5-7 years: 495 +/- 48; diabetics for 10-13 years: 470 +/- 36). Plasma norepinephrine concentration increased during physical exercise, the elevation was more pronounced in diabetic children being 13.5 +/- 10.4, 10.1 +/- 5.0 and 12.3 +/- 5.4 nmol/l in the three diabetic groups, respectively, which differed significantly from that of controls (7.94 +/- 2.9; P < 0.01). Systolic blood pressure increased significantly during physical exercise in each group. However, maximal elevated systolic blood pressure was higher in children who had diabetes for more than 10 years than in controls (158 +/- 11 vs. 137 +/- 9.7 mmHg; P < 0.001). Na-Li CT correlated positively with the maximal systolic blood pressure measured during physical exercise in those diabetic children who suffered from diabetes for more than 5 years. High activity of Na-Li CT in combination with elevated blood pressure and high plasma concentration of norepinephrine induced by acute physical exercise may represent a risk of renal/vascular complications in patients suffering from IDDM.

Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine-morphine administration.

OBJECTIVE: In this study the effect of glyceryl trinitrate on the prostigmine-morphine-induced sphincter of Oddi spasm was evaluated in nine female patients with sphincter of Oddi dyskinesia. METHOD: Sphincter of Oddi spasm was induced by prostigmine-morphine administration (0.5 mg prostigmine intramuscularly and 10 mg morphine subcutaneously) and visualized by quantitative hepatobiliary scintigraphy. The entire procedure was repeated during glyceryl trinitrate infusion (Nitrolingual 1 microg/kg/min for 120 min). RESULTS: Prostigmine-morphine provocation caused significant increases in the time to peak activity (Tmax) over the hepatic hilum (HH: 34.33 +/- 5.05 vs. 22.77 +/- 3.26) and the common bile duct (CBD: 60.44 +/- 5.99 vs. 40.0 +/- 2.88) and in the half-time of excretion (T1/2) over the liver parenchyma (LP: 120.04 +/- 16.01 vs. 27.37 +/- 2.19), HH (117.61 +/- 14.71 vs. 31.85 +/- 3.99) and CBD (158.11 +/- 9.18 vs. 40.1 +/- 6.24), indicating a complete spasm at the level of the sphincter of Oddi. Glyceryl trinitrate infusion completely normalized the prostigmine-morphine-induced alterations in these quantitative parameters (TmaX over the LP: 11.33 +/- 1.13; over the HH: 18.88 +/- 1.48; and over the CBD: 36.22 +/- 1.92; and T1/2 over the LP: 28.21 +/- 1.83; over the HH: 33.42 +/- 3.10; and over the CBD: 41.66 +/- 6.33), suggesting an effective sphincter-relaxing effect of glyceryl trinitrate. CONCLUSION: These results provide the first evidence of the effectiveness of glyceryl trinitrate on the morphine-induced sphincter of Oddi spasm in humans. Since glyceryl trinitrate is able to overcome even the drastic effect of morphine, it might be of relevance in the treatment of sphincter of Oddi dyskinesia.

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.

The effects of somatostatin and octreotide on the human sphincter of Oddi.

OBJECTIVE: Somatostatin acts at different sites in the human gastrointestinal tract and generally inhibits the release and effects of many gastrointestinal hormones and neuropeptides. Together with its long-acting analogue octreotide, somatostatin is widely used in the treatment of hormone-producing tumours, variceal bleeding, etc., but multi-centre trials have failed to prove a beneficial effect in the treatment of acute pancreatitis or in the prevention of post-ERCP pancreatitis (pancreatitis following endoscopic retrograde cholangiopancreatography). The aim of the present work was to study the effects of somatostatin and octreotide on the human sphincter of Oddi by means of quantitative hepatobiliary scintigraphy (QHBS). METHOD: Fifteen cholecystectomized patients were enrolled in the study, six in the somatostatin group and nine in the octreotide group. QHBS was performed initially with a standard protocol (baseline data), then repeated after 0.1 mg octreotide or a 250 microg bolus + 250 microg/h somatostatin administration. In the 60th min of QHBS, 0.5 mg glyceryl trinitrate (GTN) was administered sublingually. RESULTS: QHBS demonstrated that both somatostatin and octreotide caused a marked impairment in the bile flow: the half-time of excretion (T1/2) over the common bile duct was significantly prolonged compared with baseline data (somatostatin group: common bile duct T1/2 180 min versus 59.7+/-31 min; octreotide group: common bile duct T1/2 140.9+/-60.5 min versus 30.7+/-11.7 min). Glyceryl trinitrate administration accelerated the transpapillary bile flow, with significant decreases in the elevated T1/2 in both groups. CONCLUSION: Increased transpapillary flow induced by glyceryl trinitrate may be beneficial in the treatment of acute or post-ERCP pancreatitis.

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.

Reproducibility of erythrocyte sodium-lithium countertransport activity and ambulatory blood pressure measurements in type 1 diabetes mellitus.

We aimed to study the reproducibility of sodium-lithium countertransport [SLCT] activity and ambulatory blood pressure monitoring [ABPM] in type 1 diabetes. We did this by performing repeated measurements of SLCT activity and ABPM in 11 recent-onset diabetic children and in 11 patients with longer duration of diabetes. Both parameters were related to microalbuminuria. In the older group of diabetic children a significant correlation [r = 0.78; P<0.005] in SLCT activity between the first and second study was observed [514.3+/-186.4 vs 491.0+/-148.0 micromol/l erythrocytes/h]. Diurnal systolic and diastolic blood pressure were comparable at both time points within the same group of diabetic children [in group 1: 102.6+/-6.1 vs 108.6+/-7.6 mmHg N.S.; in group 2: 113.4+/-10.6 vs 114.0+/-7.8 mmHg N.S. Diastolic blood pressure in group 1: 57.4+/-4.8 vs 65.7+/-6.9 mmHg N.S., in group 2: 70.6+/-9.1 vs 68.5+/-5.3 mmHg N.S.]. Moreover, there was a significant correlation in both diurnal and nocturnal systolic blood pressure between the first and second study in the whole diabetic population. Both SLCT activity and blood pressure values obtained by ABPM were found to be reproducible individual characteristic markers in type 1 diabetic children.

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.

Comparison of the dynamics of bile emptying by quantitative hepatobiliary scintigraphy before and after cholecystectomy in patients with uncomplicated gallstone disease.

PURPOSE: Quantitative hepatobiliary scintigraphy, a noninvasive method frequently used to diagnose several biliary tract disorders, shows abnormalities in bile secretion and outflow. It is well known that there are wide variations in the normal pattern of bile emptying, but the effect of cholecystectomy on the bile flow has not yet been investigated. The goal of the current study was to examine the dynamics and normal variations of bile flow by quantitative hepatobiliary scintigraphy before and after cholecystectomy in a group of patients with uncomplicated gallstone disease. METHODS: Twenty patients were evaluated before and after cholecystectomy through cholecystokinin octapeptide-augmented quantitative hepatobiliary scintigraphy, and quantitative parameters of bile emptying (Tmax: time to peak activity, T1/2: half-emptying time before and after cholecystokinin octapeptide and duodenum appearance time) were determined and then compared. RESULTS: Before operation, the bile outflow displayed wide variations, with a moderately delayed common bile duct emptying time in some patients. After cholecystectomy, the T1/2 of the common bile duct decreased significantly when compared with the preoperative status, with only minor patient-to-patient variation, indicating uniformly faster bile emptying (common bile duct T1/2 before and after operation: 30.5 +/- 14.8 and 18.8 +/- 2.6 min, respectively). Cholecystokinin octapeptide administration caused rapid bile outflow from the common bile duct, with a significant decrease in the T1/2 parameters before and after cholecystectomy. CONCLUSIONS: In patients with their gallbladders in situ, the bile emptying rate showed wide variations and may be moderately slow without distal common bile duct obstruction. After cholecystectomy, the rate of bile emptying accelerated and showed only minor variations, thereby increasing the sensitivity of quantitative hepatobiliary scintigraphy for showing partial biliary obstruction.

[Connection between microalbuminuria and subclinical cardiovascular autonomic neuropathy in diabetic children]. / A microalbuminuria és a szubklinikai cardiovascularis autonom neuropathia összefüggésének vizsgálata diabeteses gyermekekben.

Cardiovascular tests were investigated in 16 microalbuminuric, in 20 normoalbuminuric diabetic children and a control group of 20 healthy children. Comparing to the control group, in both of two diabetic groups a similar increase in resting heart rate (74.5 +/- 2.5/min vs. 87.8 +/- 3.5/min, p less than 0.01, and 83.6 +/- 3.2/min, p less than 0.05) and a decrease in hyperventilatory arrhythmia (32.3 +/- 1.2/min vs. 20.1 +/- 0.8/min, p less than 0.01, and 17.2 +/- 0.8/min, p less than 0.01) was observed. In the diabetic group with microalbuminuria in comparison with both the control group and the normoalbuminuric group there was a lower standing/lying heart rate ratio (1.02 +/- 0.03 vs. 1.30 +/- 0.05, p less than 0.01, and 1.22 +/- 0.05, p less than 0.05), a pronounced orthostatic decrease in blood pressure (15.1 +/- 0.3 mmHg vs. 2.0 +/- 0.1 mmHg, p less than 0.001, and 5.0 +/- 0.2 mmHg, p less than 0.01) and a diminished increase in blood pressure during sustained handgrip (6.3 +/- 0.2 mmHg vs. 14.0 +/- 0.3 mmHg, p less than 0.01, and 12.2 +/- 0.3 mmHg, p less than 0.05). The occurrence of cases with distinct autonomic dysfunction (3 or more abnormal cardiovascular tests) proved to be more frequent in the group with microalbuminuria than in the diabetic group with normal albumin excretion (6/16 vs. 1/20, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Correlation of autonomic neuropathy and retinal microangiopathy in diabetic children]. / Az autonóm neuropathia és retinális microangiopathia összefüggésének vizsgálata diabeteses gyermekekben.

The authors investigated the preclinical signs of autonomic neuropathy (resting heart rate, hyperventilatory arrhythmia, heart rate on standing/lying, orthostatic blood-pressure decrease) in 15 type I diabetic children with negative FLAG as well as a control group of 10 healthy children. In the diabetic group with negative FLAG as compared to control children the mean resting heart rate was significantly higher, the mean values of cardiovascular reflexes did not show significant differences, however in a third of these patients the narrowing of hyperventilatory arrhythmia was demonstrable. The differences of mean values of all the four investigated parameters in the group with positive FLAG comparing with the control group proved to be significant. According to their results the initial disturbances of the autonomic nervous system in childhood diabetes may appear relatively early--before the preclinical stage of retinal microangiopathy--showing the untimely dysfunction of the parasympathetic nervous system, on the other hand the signs relating to disturbance of the sympathetic nervous system (heart rate ratio on standing/lying, orthostatic blood-pressure decrease) become only in preclinical retinopathic children positive.

[Incidence of childhood diabetes in Hungary]. / A gyermekkori diabetes mellitus incidenciája Magyarországon.

A retrospective epidemiological study using primary data sources and external validation was made to assess the incidence of childhood diabetes (0-14 yr) over a ten-year period. The degree of ascertainment was 96.2 per cent. Age-specific incidence rates increased until puberty with peak incidence in girls at 10 year and in boys at 13 year. There was a seasonal variation of onset with peaks in autumn and winter. The yearly incidence rates showed an increasing trend, the incidence in 1987 (8.7/100,000) was 2.3 times higher than in 1978. The rise in incidence was not continuous, incidence rates were similar in the years 1978-79, 1980-84 and 1985-87, but relatively sharp increases could be observed in 1980 and in 1985 which were mainly due to increases in incidence of the age group 5 to 9 years. Dynamic changes have taken place in the incidence of childhood diabetes in Hungary between 1978 and 1987, but it is not known whether the increases can be regarded as epidemics or parts of a discontinuous trend.

[Retinal microangiopathies in diabetic children and adolescents, occurring in cases of pubertal and prepubertal onset of diabetes]. / Cukorbeteg gyermekek és fiatalok retinalis microangiopathiájának alakulása prepubertális és pubertális betegségkezdet esetén.

The prevalence and development of retinal microvascular complications in pre-puberty and puberty onset insulin-dependent diabetes mellitus were studied in 109 young patients with an average follow-up of 6 years. The data suggest that the earlier childhood the diabetes began, the later the microvascular abnormalities could be found by fluorescein angiography. First signs of background retinopathy were seen in average 20--22 years of age, almost independently the age at onset of diabetes. Rapid progression of retinal vascular damage occurred mainly in postpubertal but not pubertal subjects. Diabetes with puberty onset meant worse prognosis in the respect of retinal vascular complications than pre-puberty onset. Good glycemic control would be achieved more difficult in subjects with puberty onset diabetes added to a changing hormonal balance. The authors suggest that psychological factors (altered behavior during and after puberty) and other problems of adolescents (changes in social, familial and working conditions) may also contribute to poor glycemic control. Though the effect of prepubertal duration on the risk of retinal complications appears to be smaller than later years, the attendant work in prepubertal years is as important as later.

[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.