[Diabetes in the aged--senile diabetes].
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Biomedical subjects
Publications and source records attributed to V Schliack.
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Eight type I diabetic patients received a subcutaneous injection of 10 IU regular insulin, or--after a one week interval--a suppository containing 75 IU crystalline insulin, the surfactant Brij 58, and the basic mass. In all patients there was a disease in blood glucose (onset after 20 min, maximum effect after 50 min, end of the effect after 90 min), and the plasma IRI level increased. However, the effect was attenuated in relation to the control test employing s.c. administration. The ratio of subcutaneous to rectal doses required to achieve the same effect was between 1:18 and 1:26.
In view of experimental and clinical findings, it was predicted (Dörner, 1973 and 1976; Dörner and Mohnike, 1973 and 1977) that a preventive therapy of diabetes mellitus may be possible by preventing hyperinsulinism in perinatal life by means of prevention of hyperglycaemia in pregnant women and overnutrition in newborns. Meanwhile, this prediction appears to have been realized. Thus, the prevalences of diabetes mellitus in children, who were born in Berlin/GDR over the past decade, were found to be significantly decreased as compared to those born between 1962 and 1972. On the other hand, the children born in Berlin/GDR between 1962 and 1972 displayed a significantly higher prevalence of diabetes mellitus as compared to those born between 1957 and 1961. The decreasing prevalence of childhood-onset diabetes over the past decade has been apparently achieved by systematic prevention of hyperglycaemia and impaired glucose tolerance in pregnant women and overnutrition in newborns. These findings suggest that a preventive therapy of diabetes mellitus--even of insulin-dependent childhood-onset diabetes--is possible by preventing hyperinsulinism in the foetus and newborn during differentiation and maturation of the neuroendocrine central nervous-pancreatic system.
In 130 type I and II diabetics with normal serum lipids and in 98 diabetics with type IIa-V hyperlipoproteinemia (HLP), liver biopsies were performed if clinically indicated. During histological examinations of one half of the biopsy specimen lipid droplet size was classified into 4 categories, which were proved by morphometric studies, independent of the amount of fat. From the remaining part the fatty acid composition of triglycerides was analyzed by gas liquid chromatography. Moreover, the fatty acid pattern of serum triglycerides and subcutaneous adipose tissue from the abdominal wall was estimated. The percentage of eicosapentaenoic acid (EPA) in triglycerides of normal diabetic liver (no visible fat) was remarkably high (greater than 30 per cent). In adipose tissue it was low (less than 1 per cent). In serum triglycerides it remained between liver and depot fat (about 3 per cent). EPA decreased with rising lipid droplet size in hepatocytes. Liver diseases, like chronic hepatitis, had no influence on the results. One year after clofibrate treatment, the percentage of EPA in liver appeared increased. In adipose tissue, however, it remained constant. In general, EPA in liver and serum triglycerides was higher in diabetics with normal serum lipids as compared to diabetics with HLP. The decreased availability of EPA in liver and serum triglycerides of diabetics with HLP suggests a significant correlation between this fatty acid and hepatic lipid accumulation which itself is associated with diseases known as risk factors of atherosclerosis.
Only few informations exist on the effect of different oils and the transformation of these precursor fatty acids to prostaglandins in patients with hyperlipoproteinemia. Therefore we investigated the impact of linseed oil and olive oil intake resp. on serum lipoprotein levels, platelet aggregation and fatty acid pattern of serum phospholipids and triglycerides resp. in patients with primary hypercholesterolemia (HC) (n = 13) and hypertriglyceridemia (HTG) (n = 16). The probands were randomly admitted to a 4 week test period with 30 ml olive or linseed oil intake. After linseed or olive oil intake all lipid fractions did not change significantly. Olive oil significantly reduced the platelet aggregation only in patients with HTG, whereas linseed oil failed to influence aggregation. After linseed oil intake there was a significant increase in linolenic and also in eicosapentaenoic acid content of phospholipids in patients with HTG. In contrast to HTG in HC linseed oil only increased significantly the linolenic acid fraction. Our data suggest, that the response of serum lipoproteins, fatty acids and platelet aggregation on modifications in dietary fats depends on the type of lipoprotein disorder.
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The influence of an eicosapentaenoic acid rich diet containing only 6,8 g cod liver oil daily for 2 weeks in 20 type I diabetics on fatty acid pattern in serum, platelet aggregation and thiobarbituric acid-reactive substances in serum were studied. There were increases in eicosapentaenoic acid portions in triglycerides, cholesterol esters and phospholipids of serum. This was associated with an inhibition of the platelet hyperaggregation, whereas platelet hyporeactivity is shifted to normal. Hyperreactivity of platelets from diabetics may be caused by enhanced TXA2 formation in comparison to healthy humans (1). On the other hand, diets rich in eicosapentaenoic acid inhibit platelet aggregation in healthy Volunteers (2,3). Therefore we investigated the dietary effect of relatively low doses of cod liver oil in diabetics type I on the eicosapentaenoic acid/arachidonic acid balance.
We investigated the ability of platelets from two groups of diabetics type I and two groups of healthy volunteers matched of age to generate thromboxane B2 (TXB2) during spontaneous clotting of whole blood. The serum concentration of TXB2, reflecting the ability of the platelets to generate TXA2 during clotting, was measured by gas liquid chromatography. Platelets from old diabetics with more than 40 years duration of diabetes mellitus formed significantly less TXB2 than those from old healthy controls. Platelets from juvenile diabetics (9 years duration of disease) formed nearly the same amount of TXB2 as those from young healthy volunteers. The importance of these results is discussed.
In the diabetes population of the GDR by means of the dispensary network of the consulting points 159 diabetics with a duration of the disease of at least 40 years were recognized and investigated on the basis of a standardized documentation material. 23 diabetics had survived their disease for longer than 50 years. The number of benign long-term courses in males was absolutely and relatively higher. The following frequencies of normal findings were stated: 55 per cent good general condition, 78 per cent normal weight/or underweight, 33 per cent no retinopathy, 65 per cent no proteinuria, 49 per cent normal ECG in rest. A proliferating retinopathy was found in 10 per cent, creatinine increases in 10 per cent, coronary infarctions in 32 per cent, gangrene and amputations, respectively, in 9 per cent. There was no striking longevity of the parents. In the majority of cases disciplined patients with a well-balanced metabolic condition were concerned. The partly existing atherogenic factors of risk (hypertension, smoking habits) speak for complex causes of the favourable course, including vasoprotective factors up to now not yet clarified.
In a multinational study, fasting plasma glucose values in 3583 diabetic patients, aged 34-56 years, were related to the characteristics of these subjects and to the presence and severity of microangiopathy as ascertained by standardised methods. The patients were from nine different populations and ranged in number from 193 to 686 per population (London, Warsaw, Berlin (FRG), New Delhi, Tokyo, Havana, Oklahoma Indians, Arizona Pima Indians, and a national sample in Switzerland). In the total group, mean fasting plasma glucose was 8.1 mmol/l for those on diet alone, 9.7 mmol/l for those on oral agents, and 12.7 mmol/l for insulin-treated patients, of whom 25% had values exceeding 16.5 mmol/l. Since many variables were measured in each patient, it was possible to take into account many confounding factors in evaluating the relationship of plasma glucose levels to retinopathy and nephropathy.
In 228 patients with diabetes mellitus (130 diabetics without and 98 diabetics with hyperlipoproteinaemia) percutaneous liver punctures after Menghini as well as biopsies of the subcutaneous fatty tissue were carried out. From the biopsy specimens and from serum the fatty acid pattern of triglycerides was estimated. In 87 patients with chronic aggressive hepatitis and 37 patients with fibrosis no differences in the fatty acid composition could be found. According to the present findings there was no evidence of alterations in the supply of individual fatty acids caused by chronic hepatitis per se. However, it is to be taken into consideration that simultaneous liver steatosis can provoke marked changes in the fatty acid pattern of liver triglycerides. The best reference seems to be the size of the fat droplet in the hepatocytes. Its rise is associated with an increase of palmitic and oleic acid, whereas the percentage of arachidonic and eicosapentaenoic acid is decreased. It must be clarified by further studies, whether this reveals a general pathophysiological phenomenon or is restricted to diabetic subjects.
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Simultaneous biopsies of liver and subcutaneous adipose tissue have been carried out in 228 patients with diabetes mellitus. In liver triglycerides a marked variability of the fatty acid pattern in relation to fatty degeneration of liver parenchyma has been confirmed. In adipose tissue fatty acid pattern was relatively constant. The most striking finding was a high content of eicosapentaenoic acid in normal liver and its decrease with the rise of lipid droplet size in the hepatocytes. No correlation with the quantity of liver fat or inflammatory liver diseases could be ascertained. When diabetes was associated with hyperlipoproteinemia (HLP) the percentage of eicosapentaenoic acid was significantly less. From the results the suggestion is obvious that a diminution of eicosapentaenoic acid in hepatic triglycerides is associated with lipid accumulation in the liver cells. A local mechanism, possibly the antilipolytic potency of prostaglandins, may be responsible for the creation of lipid droplets in liver cells of patients with metabolic disturbances. The alterations of eicosapentaenoic acid should be considered in view of recent data on the antiaggregatory effect of this fatty acid and its possibly preventive role for atherosclerosis.
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The triglyceride fatty acid pattern [TFAP] in arterial wall, adipose tissue and serum has been estimated in diabetic subjects by gas-liquid chromatography simultaneously. The samples were taken shortly before or during femoral amputation performed under halothane anaesthesia. In addition, in some probands the fatty acids of cholesterol esters of vascular walls have been obtained. The following differences in the TFAP of the tissues under study were discovered. In arterial wall compared to serum, lauric, myristic, myristoleic, palmitoleic, stearic, oleic and linolenic acid were increased; palmitic and linoleic acid were decreased, whereas eicosatrienoic, arachidonic and eicosapentaenoic acid were at the same level. In arterial wall compared to adipose tissue, myristic, palmitic and nervonic acid were decreased; eicosatrienoic, arachidonic and eicosapentaenoic acid were increased. Most differences concern the TFAP of adipose tissue compared to serum: lauric, myristic, myristoleic, palmitoleic, oleic, linolenic, lignoceric and nervonic acid were elevated in the former; palmitic, linoleic, eicosatrienoic, arachidonic and eicosapentaenoic acid were increased in the latter. In consideration of different content of fatty acids in the tissues studied the authors conclude that certain fatty acids have distinct metabolic positions such as depot fatty acids and precursors of prostaglandins.