Abstracts EASD, 19th Annual Meeting, Oslo, 14–17 September 1983

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<ul><li><p>Diabetologia (1983) 25:135 207 Diabetologia 9 Springer-Verlag 1983 </p><p>Nineteenth Annual Meeting of the European Association for the Study of Diabetes </p><p>Oslo, Norway, 14-17 September 1983 </p><p>Abstracts </p><p>1. Childhood Diabetes in Tokyo and Oslo O. Aagena~s, E. Wannag and T. Kitagawa. Department of Paediatrics, Aker Hospital, Oslo, Norway In Tokyo and Oslo all newly diagnosed Type I (insulin-dependent) diabetes in children under age 15 years from 1 April 1979 to I October 1981, were studied according to a common protocol. Thirty-two chil- dren were diagnosed in Oslo (19/100,000/year) and 47 children in To- kyo (&lt; 1/100,000/year). The relative incidence in the age groups 0 5 188 6-11 188 and 12-14 188 did not differ signifi- cantly in the two towns. Average age at diagnosis in Tokyo was 8.1 years and in Oslo 8.6 years. Five (12%) of the Tokyo children were di- agnosed by routine urine glucose screening at school. This is per- formed yearly in 20% of the school-children in Tokyo. One of the Oslo children was diagnosed by routine screening. Screening is only per- formed once in first grade in Oslo. Average insulin dose after 1 year of insulin treatment was similar in Tokyo and Oslo. Forty-five percent of HLA-examined Tokyo children were DR3 or DR4 positive, while that was the case for 100% of the examined Oslo childrenAn spite of the great genetic difference and difference in incidence, the age at diagno- sis, clinical picture and clinical course in the first year are surprisingly similar in Tokyo and Oslo. </p><p>2. Efflux of Radioactive Ca z+ from Microcarrier-Attached Cloned Rat Insulinoma Cells H. Abrahamsson and P.-O. Berggren. Department of Medical Cell Bi- ology, University of Uppsala, Uppsala, Sweden Calcium metabolism was studied in cloned rat insulinoma cells (RINm5F). Under appropriate conditions these cells aggregate to form islet-like structures which contain a central necrotic zone render- ing such islets unsuitable for analyses. The problem was circumvented by attaching the tumour cells to plastic beads coated with fibronectin. This preparation allowed perifusion studies under standard condi- tions employed for.isolated islets. Addition of Ca 2+ to a Ca2+-defi- cient medium resulted in a prompt stimulation of 45Ca effiux from preloaded cells. Removal of Na + from the same type of medium in- hibited 45Ca efflux, indicating the participation of a Na+/Ca2+-ex - change in the extrusion of Ca 2+. Furthermore, the RINm5F cells reacted like normal B-cells to the ionophore A-23187. Depolarizing agents, such as high concentrations of K+and tolbutamide, stimulat- ed the 45Ca efflux in a medium containing 2.56 mmol/1 Ca 2+. Never- theless glucose failed to stimulate 45Ca efflux under the same experi- mental conditions. It is suggested that a primary defect in the RI Nm5 F cells is an inability of glucose to open the voltage-dependent Ca 2+ channels in the plasma membrane. </p><p>3. Transmission of Impaired Glucose Tolerance to Subsequent Genera- tions by Female, Not by Male, Youngsters of Experimentally Diabetic Pregnant Rats L. Aerts and F.A. Van Assche. A.Z. St Rafael-Gasthuisberg, K.U. Leuven, Belgium Intravenous injection of 30 mg/kg streptozotocin induces mild diabe- tes in pregnant rats Oqrstgeneration). Their fetuses (second generation) </p><p>show islet hyperplasia and B cell hyperactivity. These modifications of the endocrine pancreas during intra-uterine life have consequences for later adult life, which are not perceptible in basal conditions, but appear in situations stressing B cells, such as an IV glucose load or pregnancy. During pregnancy, these female youngsters of diabetic mothers (mated with control males) have hyperglycaemia and inade- quate adaptation of their B cells. Their fetuses (third generation) ap- pear as fetuses of diabetic mothers and, when adult, show disturbed glucose tolerance. In contrast, fetuses of growing control mothers, but with a father who was born to a diabetic mother, appear normal and show normal glucose tolerance in later life. A predisposition for the development of impaired glucose tolerance and gestational diabetes is thus transmitted from one generation to another and is induced in the developing fetus by the hyperglycaemic intra-uterine environment. Whether or not the father was born to a diabetic mother has no influ- ence on the development of the endocrine pancreas of the fetus, thus excluding genetic interference. </p><p>4. National Diabetes Programme in Malta: First Epidemiologieal Re- port I. Aganovir, G. Katona, V. Vuksan and Z. Skrabalo. Vuk Vrhovac In- stitute, Krijesnice bb, Zagreb, Yugoslavia The aim of this programme was to provide relevant information on: prevalence of diabetes and impaired glucose tolerance (1GT); charac- teristics of genetic, anthropometric and biochemical variables; com- plications related to diabetes and IGT and cardiovascular risk factors. The survey population was a sample of the Maltese population over age 15 years (2149 examinees). Participation rate was 74%. Methods and criteria recommended by WHO were followed throughout the survey (year 1981). Diabetes prevalence was 7.7% (6.1% males; 9% fe- males) and IGT prevalence was 5.6% (5.9% males; 5.4% females). High fasting blood glucose was clearly associated with high body mass index. There was no clear indication that subjects with diabetes and IGT would have more diabetes among their close relatives than non-diabetic subjects. Diabetic and IGT subjects and a control group were invited to participate in a study on diabetic complications. Re- suits: Large vessel disease was found in 25% of non-diabetic, 22% of IGT and 40% of diabetic subjects. Small vessel disease of the eye was found in 35% of male and 29% of female diabetics, 8% IGT males, 6% IGT females and in 4% and 5% of non-diabetic males and females, re- spectively. Small vessel disease of the kidney was found in 22% of male and 20% of female diabetic subjects. </p><p>5. Bacitraein Has Direct Effects on Hepatoeyte Metabolism Indepen- dent of Insulin Action L. Agius and C.Wilding. Department of Clinical Biochemistry and Metabolic Medicine, Royal Victoria Infirmary, Newcastle upon Tyne, UK Bacitracin is a proteolytic inhibitor widely used to inhibit insulin de- gradation in vitro and in studies investigating the relationship be- tween the intracellular processing of insulin and insulin action. We have examined the metabolic effects of bacitracin, at concentrations currently used in insulin studies, on hepatocytes incubated in the ab- sence of insulin. In hepatocytes isolated from fed rats, bacitracin (0.25-1.0 retool/l) increased the flux through pyruvate dehydrogen- </p></li><li><p>136 Abstracts </p><p>ase, measured with (1-14C) pyruvate by 50-70% (p </p></li><li><p>Abstracts 137 </p><p>upper range (2.9%) or mean + 5 SD (2.8%) of controls as maximal nor- mal, 18 of the diabetic children had elevated percentage binding and 36 were above 95th percentile of controls. Mean_+ SD of the 18 defi- nitely elevated diabetic children was 9.2_+ 7.1%. This insulin-binding protein is precipitated by polyethyleneglycol, has a displacement curve that is parallel and over the same concentration range as serum from long-standing Type I diabetic patients and elutes from a sephac- ryl S-300 column at the position of gamma globulin. In conclusion, in- sulin binding protein(s) are present in a large percentage of newly di- agnosed Type I diabetic children and may be a marker of autoim- mune B cell damage. Molecular weight and binding characteristics suggest these proteins are anti-insulin antibodies. The ease of this as- say makes this possible marker of B cell damage feasible for large scale prospective population studies. </p><p>12. Evidence of Asymptomatie Abnormalites of Left Ventricular Func- tion in Diabetes: A Non-invasive Study J. R. Attali, R. N. Sachs, F. Crepin, D. Palsky, S. Lancrenon, P. Tellier, P.Aeberhard, J. Fermanian, M.Vulpillat, J. Lanfranchi and J. Se- baoun. Paris, France 49 diabetic patients (26 insulin-dependent and 23 non-insulin de- pendent) were compared with 32 control subjects. Absence of ischae- mic cardiopathy was confirmed by routine investigations and non-in- vasive cardiovascular techniques, including an exercise ECG using 12 leads and a thallium 201 scintigraphy. Our results show: (a) a pro- longed mean isovolumetric relaxation time (IVRT) as studied by the M mode echocardiography and phonomecanography: diabetics: 0.10_+0.04; controls: 0.05_+0.02s, p</p></li><li><p>138 Abstracts </p><p>of islet cells for researching the pathogenesis of insulin-dependent diabetes. </p><p>17. A 64K Protein Immunoprecipitated from Normal Rat Islets by Anti- bodies from Spontaneously Diabetic BB Rats S. B~ekkeskov, T. Dyrberg and A. Lernmark. Hagedorn Research Lab- oratory, Gentofte, Denmark Islet cell surface antibodies are present in a majority of BB rats which demonstrate morphological and metabolic evidence of the spontane- ous diabetes syndrome. In this study, it was tested whether rat islet cell antigens could be immunoprecipitated by sera from diabetic BB rats. Wistar rat islet cell proteins were biosynthetically labelled with 35S methionine. Islets were solubilized in 1% NP40 and the lysate subject- ed to immunoprecipitation with sera from 10 diabetes susceptible BB rats (33-74 days old), seven of which developed diabetes (74-108 days of age), two had insulitis (day 157) and one impaired glucose tol- erance. Control sera were from diabetic non-susceptible BB rats and four normal Wistar rats. Sera from all 10 susceptible BB rats immuno- precipitated a Mr 64000 rat islet cell protein. This component was not detected in lysates of labelled rat spleen lymphocytes. In two animals followed prospectively, immunoprecipitating antibodies were present before diagnosis. In the control group, only serum from one non-sus- ceptible BB rat immunoprecipitated the 64K component. We con- clude that autoantibodies in sera from diabetic BB rats recognize a rat islet cell antigen of M~ similar to that previously found to be associat- ed with insulin-dependent diabetes in man. </p><p>18. Comparison of Monocomponent Human and Porcine Insulin in the Treatment of Newly Diagnosed Type I (Insulin-Dependent) Diabetic Children with Respect to Immunogenicity, Endogenous Insulin Secre- tion and Metabolic Control H. B~evre, O. Soy J. Vidnes and K.W. Wefring. Department of Pae- diatrics, University of Bergen, Norway, Department of Paediatrics, The National Hospital, Oslo, Norway and Vestfold Hospital, Tonsberg, Norway The aim of this triple-centre study was to compare monocomponent human and porcine insulins (Novo) in the treatment of newly diag- nosed Type 1 diabetic children with respect to immunogenicity, en- dogenous insulin secretion and metabolic control. Twenty-six patients (17 boys and 9 girls; mean age 8.6 years) were randomly allocated to treatment with human or porcine insulin and were monitored at 3- monthly intervals for 1 year. The two treatment groups were compa- rable with respect to patient numbers, anthropometric measurements and degree of metabolic derangement at diagnosis. At no time during the first 9 months of treatment was there any statistically significant difference between the porcine and human insulin groups in respect of degree of metabolic control, insulin dose or C-peptide response to a standard meal. Values-+ SD at 9 months were: post-prandial blood glucose (human 15.7 +_ 7.2, porcine 16.2 9.2 retool/l); insulin dose (human 16.5 + 5.9 IU/24 h; porcine 16.2 7.6 IU/24 h); C-peptide (human 0.15 _+ 0.17 pmol/ml; porcine 0.14_+ 0.09 pmol/ml). In two of the 13 patients on porcine insulin relatively high antibody levels were observed (0.8 mU/ml at 1 year and 2.3 mU/ml at 9 months), but with- out leading to any statistically significant difference in mean insulin antibody levels between the two treatment groups. </p><p>19. Adrenaline is Anti-ketogenic in the Fasted Rat M. Bahnsen and K.G.M.M.Alberti. Department of Clinical Bio- chemistry and Metabolic Medicine, Royal Victoria Infirmary, New- castle upon Tyne, UK Catecholamines stimulate lipolysis and ketogenesis in fed and over- night-fasted man, an important component of the stress response. It is not known, however, whether the major effect of ketogenesis is on the liver or is secondary to increased fatty acid precursor supply. We have therefore used a primed continuous infusion of (3-~4C)-3-hydroxybut - yrate in 48h starved rats to study ketone body production and utilisa- tion. Adrenaline (0.2 gmol/h) was infused for 2h alone, or with soma- tostatin (10 gg/100 g body weight per h) to remove any influence of glucagon and insulin. Adrenaline infusion, with or without somato- statin, caused a 30-40% fall in blood ketone body concentrations. He- patic ketone body production declined by the same magnitude with- out any change in metabolic clearance rate. Plasma insulin was unchanged after adrenaline alone but decreased by 50% when soma- tostatin was infused. Adrenaline -+ somatostatin increased blood ala- nine (+ 105-170%), lactate (+ 105-170%) and glucose (+ 130-132%), (p &lt; 0.05). Lipolysis was stimulated, reflected by a 70% increase in glycerol concentrations, but plasma non-ester fatty acids were not altered, suggesting increased re-esterification. Thus in the rat, </p><p>adrenaline is anti-ketogenic rather than ketogenic after 48 h starva- tion. The anti-ketogenic effect could be due to increased intrahepatic oxaloacetate due to increased lactate and pyruvate delivery at a time when delivery of non-ester fatty acid substrate is unchanged. </p><p>20. Recent Data on the Metabolic Action of Gliclazide M.I. Balabolkin, L.I. Levitskaya, T.P. Morozova, L.V. Nodosugova and L.I. Gavriluk. Department of Endocrinology, Moscow Medical Stomatology Institute, Moscow, USSR We have studied 47patients suffering from non-insulin-dependent diabetes (20 patients were treated with glibenclamide and 27 with gliclazide). Before and after treatment for 6-8 weeks, all patients were submitted to oral fructose and glucose tolerance tests. The blood glu- cose level decreased significantly after treatment with gliclazide (p &lt; 0.05) compared with treatment with glibenclamide. Furthermore, af- ter 6 months of treatment with gliclazide, we found significant de- creases in serum immunoreactive insulin, C-peptide and STH levels. The number of insulin receptors on monocytes was decreased before treatment: type I receptors 407 with K affinity (2.17_+ 0.28)x109mol/1; normal 645_+98.6/cell with K affinity (4.41 _+ 0.87) x 109 mol/1; type II receptors 2532 276/cell with K af- finity (1.61 -+ 0.28) x 108 mol/l; normal 6 750 + 767/cell with K affinity (1.62-+ 0.53)x 10 a mol/1. After 2 months of treatment with gliclazide, the number of type I receptors was increased to 667 _+ 61.7/cell with K affinity (4.3 + 0.13) x 109 mol/1 and type II receptors to 6799-+ 454/cell with K affinity (2.15 + 0.29) x 108 mol/1. </p><p>21. Effect of Fetal Hypoinsulinaemia on Rat Placental and Fetal Liver Glycogen Metabolism V. Barash, A.Gutman and E. Shafrir. Department of Bi...</p></li></ul>