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Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder.

Decrease in gall-bladder surface area, as obtained by ultrasound, was measured in 52 patients with insulin-dependent diabetes (27 with and 25 without autonomic neuropathy) 60 minutes after administration of the bile stimulant Biloptin. The post-stimulation area was 33 +/- 6% of initial value in patients with autonomic neuropathy, and 67 +/- 8% (P less than 0.0005) in those without autonomic neuropathy. Comparison with insulin-dependent chronic diabetics matched for sex, age and duration of illness, demonstrated that heart-rate variability in cholelithiasis was less than in the control subjects (P less than 0.05). It is concluded that autonomic neuropathy, measured by the occurrence of spontaneous vagotomy, in insulin-dependent diabetics is an important risk factor in the overall pathogenesis of cholelithiasis.

Antral contraction after a test meal was measured by ultrasonography in 32 insulin-dependent diabetics with and without autonomic neuropathy and in 12 control subjects. In sequence of the three groups studied the results were: frequency of contractions 3.6 +/- 2.0, 4.8 +/- 1.6, and 4.8 +/- 1.6, respectively, per two minutes; intensity of contraction 30.9 +/- 8.2, 41.4 +/- 5.2 and 57.5 +/- 8.8% of maximal antral surface decrease; and contraction velocity per sec 4.8 +/- 1.5, 8.2 +/- 1.2 and 9.95 +/- 2.8% of maximal antral surface decrease. Different from the frequency, intensity and velocity of antral contraction were reduced in diabetics (compared with normal controls) even without an autonomic neuropathy. In all diabetics, contraction velocity was positively correlated to variations in heart rate and to the postprandial blood-glucose rise. The results indicate that disorders of motility in diabetics with autonomic neuropathy can be visualized by ultrasonography and can be diagnosed early from a reduction in contraction velocity.

Gastric emptying following the ingestion of 200 ml orange juice was investigated sonographically in 24 insulin-dependent diabetics with and without autonomic neuropathy and in 11 control subjects. Furthermore, the relationship between emptying and blood glucose was determined. The duration of gastric emptying in all patients was negatively correlated with the heart rate variation (P less than 0.01) and was longer in patients with autonomic neuropathy than in control subjects or patients without autonomic neuropathy (t1/2 48 +/- 12 min vs. 20 +/- 9 min and 24 +/- 5 min, respectively, P less than 0.0005). The rise in blood glucose was positively correlated with the heart rate variation in all patients (P less than 0.01) and was slower in autonomic neuropathy (1.2 vs. 2.9 mg/dl X min, P less than 0.0005). The delayed carbohydrate absorption in autonomic neuropathy with slower gastric emptying could be important in the management of diabetic patients in whom metabolic control is difficult.

Necrotic ulcers of the feet are a dangerous complication of the diabetic foot syndrome. Besides peripheral vascular disease (PVD) peripheral neuropathy is an important factor in the pathogenesis of necroses. We examined whether the reserve of circulation during reactive hyperemia at the feet of patients with type I diabetes mellitus with abnormal blood flow (n = 17) is decreased compared with diabetic (n = 14) and nondiabetic (n = 20) controls. Further we analyzed whether there is a correlation with the oxygen supply of the foot. PVD was excluded by clinical check-up, oscillography, and Doppler ultrasound. The reserve of circulation of the foot was measured during reactive hyperemia and oxygen supply of the foot by oximetry. Abnormal blood flow of the foot was diagnosed by the pulsation index. On examination it was found that the reserve of circulation of diabetic feet with abnormal blood flow is about 52% less than in diabetic and about 50% less than in nondiabetic controls (Por = 0.005). The decreased reserve of circulation correlates with the oxygen supply of the feet; this is about 21% less compared to diabetic feet with normal blood flow and about 16% less in comparison to nondiabetic feet. The present study shows that diabetic feet suffer from disturbed circulation although there is no evidence of PVD. This disturbed circulation is correlated with a decreased oxygen supply of the feet. Hypoxia during strain could be of great importance in the pathogenesis and treatment of necrotic ulcers of diabetic feet.

Doppler sonographic examination of 51 diabetic subjects showed that the macrovascular hyperemic response of the pedal blood flow was negatively correlated to the duration of the disease (p less than 0.01). In comparison with non-diabetic controls (n = 20), the response was increased by more than 210% in newly detected diabetics, but decreased by more than 20% in long-term diabetics. Vascular response was correlated also not only to the duration of the diabetes, but to peripheral neuropathy (p less than 0.001). The hyperemic response was reduced in patients with reduced nerve conduction time, or somatic neuropathy (142 + 152%, p less than 0.005), and in patients with reduced arterial pulsation, or autonomic neuropathy (152 + 88, p less than 0.005), both in comparison with non-diabetic controls (293 +/- 108%). The frequency of decreased macrovascular hyperemic response was in agreement with somatic neuropathy in 69.7% and with autonomic neuropathy in 75.8% of all patients. The results demonstrate that the macrovascular hyperemic response of blood flow in diabetic feet is already reduced at an early stage of peripheral neuropathy without peripheral vascular occlusive disease. The functional reduction of pedal blood flow may be important for the development of diabetic foot gangrene.

Fifty-four patients with angiographically confirmed peripheral vascular disease (PVD) were examined in order to find out whether the occlusive form of this disease can be better diagnosed by measuring the reappearance time and mean velocity of the blood flow during reactive hyperemia than by determining the peripheral systolic blood pressure, using Doppler ultrasound for both measurements. It was shown that the Doppler pressure was only reliable for a screening diagnosis of PVD. However, using the reappearance time of reactive hyperemia, it was possible to distinguish specific localization types of sclerosis; while reactive hyperemia already reached its half maximum in controls in 4.6 s this occurred in the stenosis type of PVD after 6.9 s, in the upper leg occlusion type after 21.6 s, in the lower leg occlusion type after 46.6 s, and in the multilevel disease after 70.1 s. The delay in the half-maximum reappearance time was significantly different, not only in comparison with controls (P

Seventy-five diabetic and 40 nondiabetic subjects who where suffering from peripheral vascular disease were studied in order to determine whether the degree of the severity of their disease can be better calculated by Doppler ultrasound examinations of the peak velocity than by the systolic pressure of the peripheral bloodstream. In 46 examinations of normal controls the mean value of the peak velocity was 13.3±3.3 cm/s with a standard deviation of 15.4%±13.2% on one day and 16.1%±15.9% on different days. Considering patients with or without diabetes mellitus the velocity was significantly decreased in correlation to an increasing degree of severity of the vascular disease (P

Severe forms of arterial occlusive diseases occurred more frequently in 11 insulin-treated diabetics with persisting hyperlipidemia than in 10 control subjects who were 11 years older. Triglycerides and cholesterol of total serum and of VLDL were 2–7 times higher (P

Bei 3 Patienten mit einem Angiokeratoma corporis diffusum wurden dunnschicht-chromatographische Lipidanalysen aus Extrakten von RES (Lymphknoten und Rachentonsillen), subcutanem Fettgewebe und Harnsediment durchgefuhrt und mit den Ergebnissen bei stoffwechselgesunden Personen verglichen. Die Analysen erbrachten den Nachweis von erheblichen Mengen von Ceramidtrihexosiden. Ceramiddi- und -monohexoside wurden nicht gefunden; statt dessen liesen sich Spuren von Substanzen abtrennen, bei denen es sich mit groser Wahrscheinlichkeit um Globoside handelt. Die quantitative Bestimmung von Ceramidtrihexosiden erfolgte durch direkte Photometrie bei 460 nm. Sie ergab, das der Gehalt an Ceramidtrihexosiden in Lymphknoten und Fettgewebe beim Angiokeratoma corporis diffusum im Vergleich zum gesunden Gewebe mindestens 20mal so stark und im Harnsediment sogar um mehr als das 100fache erhoht ist.

Es wird uber chromatographische Untersuchungen der Lipide an 8 Xanthompatienten berichtet. Es handelt sich um 7 Patienten—davon 2 mit Diabetes—mit einer tuberosen Xanthomatose, und um 1 Patientin mit einer cytomykotischen Granulomatose. Die qualitative und quantitative Zusammensetzung der Xanthomlipide wird den Werten der normalen haut und des Hautoberflachenfettes gegenubergestellt.

1. Die Berechnung der Serumtriglyceride mit Hilfe der enzymatischen Glycerid-Glycerinbestimmung erfolgt ublicherweise ohne Rucksicht auf das Vorhandensein von Di- und Monoglyceriden. Die dunnschichtchromatographische Trennung einzelner Glyceridfraktionen und ihre quantitative Erfassung mit der Hydroxamsauremethode zeigt jedoch stark variable Anteile der Partialglyceride von durchschnittlich 8,5% im Nuchternserum und 18,3% (maximal bis 28,6%) 2 Std p. c. Bei der essentiellen Hyperlipamie betragt ihr Anteil im Durchschnitt weniger als 1% der Gesamtglyceride. Auf die Bedeutung der Befunde fur die Berechnung der Triglyceride aus dem Glycerid-Glycerin wird hingewiesen.

Es wird uber ein 15jahriges Madchen berichtet, das die typischen Hautveranderungen eines Angiokeratoma corporis diffusum Fabry zeigt, ohne das sich bisher Veranderungen an den inneren Organen nachweisen liesen. Die Lipoidanalyse des Urins und die histologische Untersuchung der Hautveranderungen zeigten jedoch eine Vermehrung der Ceramidhexoside (CTH, CDH und CMH) bzw. Lipoidablagerungen, so das kein Zweifel an der Lipoidthesaurimose bestehen kann. Die Befunde der Lipoidanalyse werden diskutiert. Es wurde bisher mit befriedigendem Erfolg eine Behandlung der Angiokeratome durch hochtouriges Schleifen durchgefuhrt.

The doppler-sonographic measurement of reactive hyperemia is a simple method to make a functional diagnosis of PVD. In contrast to Doppler pressure measurements the new method does not only allow a screening-diagnosis of PVD, it also fit to inform about the localisation and severity of vascular occlusions. Thus the method assist to make sure whether PVD is occlusive and whether angiographic or surgical intervention is necessary.

Insulin has an exacerbating effect on endogenous hypertriglyceridemia. Experiments were carried out in order to study the acute effects of insulin in 6 patients with endogenous hypertriglyceridemia and 6 controls. 0.1 Unit insulin/kg body weight was injected into the portal vein. Blood samples were taken from the portal and hepatic veins and analysed for FFA, glycerol, VLDL-triglycerides (VLDL-TG) and insulin. Liver blood flow was measured with cardiogreen. This technique allowed a study of the acute effect of insulin on the hepatic extraction of substrates and on the hepatic production of VLDL-TG. Under basal conditions the production of VLDL-TG in patients with endogenous hypertriglyceridemia was not statistically different from the production in controls. The results did not provide statistical proof of a correlation between the production and the hepatic uptake of VLDL-TG precursors; however, the production was negatively correlated to the hepatic clearance rate of insulin. During a one-hour observation period after the application of insulin, the production of VLDL-TG was decreased in controls and increased in patients with endogenous hypertriglyceridemia. The application of insulin was also followed by a decreased uptake of free fatty acids and glycerol, this change being similar in controls and in patients with endogenous hypertriglyceridemia. There was no correlation between the effect of insulin on the production of VLDL-TG and on the uptake of substrates by the liver. It is concluded that insulin has a direct effect on the production of VLDL-TG which is independent of substrate supply. The adverse effect of insulin in endogenous hypertriglyceridemia may reflect some type of impaired hepatic responsiveness to insulin.

Endogene Hypertriglyceridamien (HTG) und Diabetes mellitus kommen haufig gemeinsam vor (Vogelberg et al., 1977). Durch Behandlung der Hyperlipidamie kann der Diabetes nicht selten in die Latenz zuruckgedrangt werden (Bruns et al, 1974; Debry et al., 1974). Unklar ist, ob dieser Effekt auf spezifisch triglyceridsenkende Masnahmen oder eine allgemeine Gewichtsreduktion im Rahmen der Hyperlipidamiebehandlung zuruckzufuhren ist. Die Frage wurde im Laufe der Hyperlipidamiebehandlung von 100 Patienten mit HTG untersucht.

Severe forms of arterial occlusive diseases occurred more frequently in 11 insulin-treated diabetics with persisting hyperlipidemia than in 10 control subjects who were 11 years older. Triglycerides and cholesterol of total serum and of VLDL were 2-7 times higher (P less than 0.01); however, LDL-cholesterol was 2 times lower than in control subjects (P less than 0.025). HDL-cholesterol was not significantly different in either group. After insulin administration (81 U/die vs 37 U/die, P less than 0.00251), the increased lipids were only insignificantly reduced, while LDL-cholesterol and the ratio of LDL-/HDL-cholesterol was even increased (P less than 0.0025 and P less than 0.05). In contrast to control subjects, VLDL-cholesterol was positively correlated to the tolbutamide-induced insulin reserve (before insulin administration) and to the diurnal insulin dosage (after insulin administration) (P less than 0.01 and P less than 0.001). The results show that the atherosclerotic risk in diabetics with persisting hyperlipidemia is higher than in control subjects and that the risk is distinguished by increased VLDL-cholesterol in correlation with increased insulin concentrations. Since the atherosclerotic risk is even more accentuated by the fact that insulin administration increases LDL-cholesterol, insulin therapy must be observed carefully in these patients.

In a controlled study on 121 patients with peripheral vascular disease (PVD) (75 patients with primary hyperlipoproteinemia, 15 diabetics, 31 patients without metabolic disease) the relationship between risk factors (hyperlipoproteinemia, obesity, hypertension, abnormal glucose tolerance, smoking) and the degree and localisation of sclerotic lesions was investigated by angiography. The degree was directly related in all patients to the number of risk factors, in Type IIa to cholesterol levels, in diabetics and Type IV with abnormal glucose tolerance to age. The latter patients were 5-10 years older than patients with Type IIa and showed 2 or more additional risk factors. The sclerotic lesions affected in Type IIa, less in Type IIb, predominately the pelvic vessels. Diabetics and Type IV patients showed a distal arterial involvement. The difference was significant. The degree of sclerotic lesions in arteries of the pelvis and the distal lower limb was positively correlated with the cholesterol-triglyceride ratio. Smoking aggravated the pelvic lesions in Type IV. Hypertension lead to more pronounced lesions of the distal lower limb in Type II. S-shaped tortuosities of the big vessels were shown to be typical, independent of localisation or degree.

Bei der Clofibratbehandlung endogener Hypertriglyceridamien (HTG) ist wiederholt ein reaktiver Serumcholesterin- bzw. LDL-Anstieg beschrieben worden [9, 13]. In einer eigenen Studie haben wir gepruft, ob dieser unerwunschte Nebeneffekt einer Clofibratbehandlung durch die Kombination mit Phenformin vermindert werden kann.

Type III hyperlipoproteinaemias are characterized by "floating" beta-lipoproteins. In lipid electrophoresis these are present as a VLDL subfraction (beta-VLDL). They can also be detected chemically on the basis of the cholesterol/triglyceride ratio of the serum or the corresponding VLDL serum fraction. In the present work, the diagnostic value of these ratios is compared with that of E III peptide loss from VLDL-apolipoproteins, which is thought to be specific for type III hyperlipoproteinaemias. Of 42 persons with a VLDL subfraction, seven showed a loss of the peptide. In these persons, the cholesterol/triglyceride quotient was 0.94+/-0.45 for the whole serum, and 0.59+/-0.25 for the serum VLDL fraction. The quotient for VLDL cholesterol/serum triglyceride was 0.43+/-0,21, and the electrophoretic mobility of the VLDL subfraction was 0.38+/-0.04. Investigation of the VLDL-cholesterol/triglyceride quotient gave four (10%) false positives, while the quotient for VLDL-cholesterol/serum triglyceride gave ten (24%) false positives. This comparison shows that the criteria used for identification of "floating" beta-VLDL subfraction are only indirectly useful in the diagnosis of type III hyperlipoproteinaemia.

Ultrasound examination of ten insulin-dependent diabetics with neuropathic gastroparesis demonstrated that gastric motility can be increased by intravenous injection of both cisapride and metoclopramide (Paspertin) (P less than 0.05 to less than 0.0005). During a one-hour period of observation stimulation lasted longer after cisapride than metoclopramide, but there were no qualitative differences between them. Compared with healthy subjects the frequency of antral contractions was increased after both drugs (P less than 0.05 and less than 0.025, respectively). Intensity and speed of contraction was less in patients than in the control subjects, but this effect was significant only for speed of contraction 20 min after injection of the drugs (P less than 0.05). The results indicate that ultrasonography makes it possible to monitor drug treatment of abnormal gastric emptying in diabetics by measurement of both frequency and degree of antral contraction.

Decrease in gall-bladder surface area, as obtained by ultrasound, was measured in 52 patients with insulin-dependent diabetes (27 with and 25 without autonomic neuropathy) 60 minutes after administration of the bile stimulant Biloptin. The post-stimulation area was 33 +/- 6% of initial value in patients with autonomic neuropathy, and 67 +/- 8% (P less than 0.0005) in those without autonomic neuropathy. Comparison with insulin-dependent chronic diabetics matched for sex, age and duration of illness, demonstrated that heart-rate variability in cholelithiasis was less than in the control subjects (P less than 0.05). It is concluded that autonomic neuropathy, measured by the occurrence of spontaneous vagotomy, in insulin-dependent diabetics is an important risk factor in the overall pathogenesis of cholelithiasis.

The increments in serum lactate and ketone bodies induced by biguanides in 11 diabetics were decreased by a combined treatment with clofibrate and phenformin. Lactate concentration was nearly the same on a placebo or on the combined drug treatment. While-body weight reduction in subjects was without influence on the clofibrate-induced lowering of lactate it inhibited a decrease of ketone bodies. The effect of clofibrate on lactate was directly correlated to its serum triglyceride lowering effect. The decrease in lactate points to an improved lactate utilization. A combined clofibrate-biguanide treatment is only indicated in selected patients, predominantly in diabetics with endogenous hypertriglyceridemia, however, contraindications of both drugs have to be observed.

Primare Hyperlipoproteinamien (HLP) sind als Risikofaktoren der peripheren arteriellen Verschluskrankheit (PVK) noch wenig untersucht worden. Nach vor liegenden Untersuchungsergebnissen kommen HLP bei 25 bis 74 % aller Patienten mit einer PVK vor [5]. Auffallig ist, das neben Typ IIa vor allem Typ IV HLP beobachtet worden sind [1, 3, 5]. Uber das spezielle Arterioskleroserisiko einer bestimmten HLP ist jedoch nichts bekannt. In eigenen Untersuchungen ist die Beziehung bestimmter HLP-Typen zur Lokalisation und Auspragung der PVK gepruft worden. Zu diesem Zweck wurden die angiographischen Befunde von 121 Patienten mit einer PVK ausgewertet und die Haufigkeit bestimmter HLP-Typen und anderer Risikofaktoren mit jener von Kontrollpersonen verglichen.

The apoprotein composition of the main lipoprotein fractions (VLDL, LDL-1, LDL-2 and HDL) was studied initially in 15 patients with Broad-β disease. Analytical isoelectric focusing of urea-soluble apo-VLDL and apo LDL-1 demonstrated a variant pattern of the polymorphic Apoprotein E with a deficient Apo E-III band in all patients. The Apo E-III deficiency pattern was seen in only six out of 304 hyperlipidaemic controls. These six Apo E-III deficient controls had characteristic signs of Broad+ disease, and thus represented patients not previously recognized as having the disorder. The Apo E focusing patterns were constant on repeated examinations and were stable under different metabolic conditions. The data show that Apo E-III deficiency in VLDL is a specific qualitative marker for Broad-β disease, allowing an unequivocal diagnosis that had not been possible previously. Indirect evidence suggests that Apo E-III deficiency is the basic lipoprotein abnormality underlying the familial dyslipoproteinaemia.

During the past years the improved methods in discerning the disorders of lipid metabolism have shown that, besides beta lipoproteins, prebeta lipoproteins are also risk factors in the development of peripheral vascular disease (PVD) (Greenhagen et al., 1971; Kremer et al., 1973; Wollenweber et al., 1971). In order to get detailed informations of the relation between severity and localization of sclerotic lesions in PVD and lipid disorders we studied hyperlipoproteinemias (HLP) in 74 patients in whom angiography had been performed because of PVD of the lower limbs.

Die Therapie primarer Hyperlipoproteinamien vom Typ IIa und b erfordert haufig neben einer Diat, zusatzliche lipidsenkende Medikamente. Besonderes Interesse haben dabei hochgereinigtes (L-Anteil geringer als 0,2%) DT4 [1], DT3, die Kombination von DT4+ DT3 sowie DL-α-Methylthyroxin-ethylester gefunden. Nicht geklart waren dabei zum Teil der optimale Dosisbereich, der lipidsenkende Effekt von DT3 sowie einer Kombination von DT4+ DT3 und das Verhalten dieser Medikamente verglichen am selben Patienten.

Forty-nine diabetics (aged 50-69 yr, with a pulse deficit in 54 legs) were examined for peripheral vascular disease (PVD). In relation to pulse deficits PVD was proved by oscillography in 24 (44%), by qualitative Doppler velocity measurements in 19 (51%) and by quantitative Doppler in 28 (35%) cases. The overall rate of the agreement in the diagnosis between the two Doppler techniques and oscillography was 76.8% and 73.5% respectively. The differences in the PVD frequency detected by Doppler sonography were not significant. However, a comparison of Doppler deficits and pulse deficits showed that PVD was more frequently found by the qualitative Doppler technique (76.0% vs 35.2%, p less than 0.0005). Also in 94.7% of all cases PVD could be detected by the qualitative examination of only one artery. The quantitative Doppler results were directly correlated to localized findings in the foot in PVD. Thus, it can be concluded that in comparison to oscillography the qualitative Doppler velocity measurements are simpler and more time-saving for a screening diagnosis of PVD, while the quantitative technique is useful for evaluating the severity of evident PVD.

Gastric emptying following the ingestion of 200 ml orange juice was investigated sonographically in 24 insulin-dependent diabetics with and without autonomic neuropathy and in 11 control subjects. Furthermore, the relationship between emptying and blood glucose was determined. The duration of gastric emptying in all patients was negatively correlated with the heart rate variation (P less than 0.01) and was longer in patients with autonomic neuropathy than in control subjects or patients without autonomic neuropathy (t1/2 48 +/- 12 min vs. 20 +/- 9 min and 24 +/- 5 min, respectively, P less than 0.0005). The rise in blood glucose was positively correlated with the heart rate variation in all patients (P less than 0.01) and was slower in autonomic neuropathy (1.2 vs. 2.9 mg/dl X min, P less than 0.0005). The delayed carbohydrate absorption in autonomic neuropathy with slower gastric emptying could be important in the management of diabetic patients in whom metabolic control is difficult.

The frequency, intensity and velocity of antral contractions were measured by ultrasonography in 32 patients with insulin-dependent diabetes mellitus and in 12 controls before and up to 60 min after a test breakfast. The examination showed that motility was lower in the diabetics with autonomic neuropathy than in those without and in the non-diabetic controls. The frequency of contractions was determined in the 3 groups as follows: 3.6 +/- 2.0 vs. 4.8 +/- 1.7 vs. 4.8 +/- 1.6 contractions per 2 min (p less than 0.0025); the intensity of contractions was 30.9 +/- 8.2 vs. 41.4 +/- 5.2 vs. 57.5 +/- 8.8 delta % of antral area (p less than 0.025, resp. p less than 0.0005); the velocity of contractions was 4.8 +/- 1.5 vs. 8.2 +/- 1.2 vs. 9.95 + 2.8 delta % of antral area/sec (p less than 0.0125 resp. p less than 0.005). There was a significant difference in the intensity and velocity of contractions between the patients without autonomic neuropathy and the non-diabetic controls (p less than 0.0025 resp. p less than 0.025). 10 min after the test breakfast the motility indices reached a maximum and then decreased continuously towards the end of the test period (p less than 0.01). 20 min after the test meal this decrease was significantly faster in the patients with autonomic neuropathy than in those without and in controls. In all the diabetics the velocity was positively correlated to the coefficient of the variation from beat to beat of the heart, and also positively correlated to the increase of blood glucose concentrations (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of chronic insulin resistance in 3 adipose diabetics is reported. The clinical course shows that the actual success of the treatment of resistance depends less on weight reduction than on a short interruption of the insulin therapy and withdrawal of nutriment at the same time. After breaking off nourishment and insulin supply, the efficacy of the insulin therapy could be regained, at least partially, in all patients, and the diabetic metabolic state improved. In addition to the reduction in hyperinsulinism, physical activity and specific effects of diet are also probably important for the success of the treatment.

Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder.

Diabetes mellitus (Diabetes) und Hyperlipoproteinamie (HLP) gehoren zu den haufigsten Stoffwechselerkrankungen des Erwachsenenalters. Beide Erkrankungen kommen getrennt voneinander vor, werden aber haufig auch gleichzeitig beobachtet. Auf das gemeinsame Vorkommen von Diabetes und HLP wurde bereits vor mehr als 150 Jahren hingewiesen (Mariet, 1799). In der Vor-Insulin- Ara wurde die masige Trubung des Serums oft als Komplikation eines Terminalstadiums des Diabetes beschrieben (Fischer, 1903; Allen, 1917). Als man bald nach der Entdeckung des Insulins erkannte, das sich die HLP bei einer Ketoazidose nach Insulinzufuhr rasch zuruckbildete, schien es klar, das diese Fettstoffwechselstorung Ausdruck eines schweren Insulinmangels sei (Blix, 1926; Schmidt u. Saatschian, 1927; Lewin, 1935).

22 outpatients with primary hyperlipoproteinemia type IIb and IV were treated in periods of eight weeks as follows: placebo; 0,15 g phenformin/day; 0,15 g phenformin + 1,5 g clofibrate/day; 1,5 g clofibrate/day; placebo. Compared to the first placeboperiode the serumtriglycerides were significantly lowered by phenformin (about 26%), by the combined treatment with phenformin + clofibrate (60%) and by clofibrate (51%) after eight weeks of treatment. The serumcholesterol was significantly lowered by phenformin (10%) and by the combined treatment with phenformin and clofibrate (14%), but not significantly by clofibrate (8%). After eight weeks of treatment with phenformin alone or in combination with clofibrate the body weight decreased significantly (1,9% or 1,4%). These changes in body weight were not related to changes in blood lipids. In conclusion, the combined treatment with 0,15 g clofibrate/day was more effective in lowering increased serum lipids than the treatment with phenformin or clofibrate alone.

Combined treatment with clofibrate and phenformin increased the lipid-lowering effect of clofibrate monotherapy in 15 patients with endogenous hypertriglyceridaemia significantly by ca. 10%. The therapeutic success was shown by a reduction in LDL-cholesterol and an additional reduction in VLDL-triglycerides. A clofibrate-induced rise in LDL-cholesterol could not be observed during the combined treatment. Thus combined treatment could be particularly advantageous in the prophylaxis of arteriosclerotic complications of endogenous hypertriglyceridaemia, provided that contra-indications of either of the preparations are excluded.