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Enlargement of fat cells is known to be a factor stimulating metabolic rates in adipose tissue and thus playing a role in the pathogenesis of certain metabolic disorders. Excessive adipose-cell hypertrophy of the same degree was observed in disturbances of carbohydrate (e.g. in subclinical or maturity onset diabetes) as well as of triglyceride metabolism, despite the fact that body weight in these patient groups was lower than in control subjects (with the exception of subclinical diabetics). Significant correlations between adipocyte volumes and serum triglyceride levels are in agreement with this conception. Similar characteristics of insulin concentrations measured during an oral glucose tolerance test and adipose-cell hypertrophy of the same degree may suggest a comparable influence on the development of carbohydrate intolerance and hypertriglyceridemia. Moreover, our investigations show an increasing of the prevalence of diabetes mellitus, hypertriglyceridemia and hypercholesterolemia up to a Broca Index of 1.2. This points to an extremely high metabolic risk even in people with slight overweight provided the adipocytes are significantly enlarged. Thus, adipocyte size appears to be a good parameter to characterize metabolic impairments.

A 25-year-old woman with progressive systemic sclerosis was treated with D-penicillamine. (DPA) 30 days after starting therapy cholestatic jaundice was observed. Moreover, for two years she has taken the pill. Both drugs were discontinued, the jaundice disappeared and the laboratory findings of liver became normal. A rechallenge of D-penicillamine after 9 months induced no reaction. An underlying chronic liver disease before cholestasis could be excluded by liver biopsy. Allergic cutantests and lymphocyte transformation test with D-penicillamine and penicillin gave normal results. The frequency of cholestatic jaundice caused by DPA-therapy is discussed and the possible pathomechanism analyzed.

We investigated the influence of a PSMF on body weight, body composition, blood lipids, physical working capacity, and nitrogen balance in obese HLP patients. During 4 weeks, 12 patients were treated by PSMF (approximately 340 kcal/d) under health resort conditions. At the same time, they daily exercised on a bicycle with an intensity of 80% of their physical working capacity estimated by an exercise load. The therapeutic regimen induced a significant weight loss (10.1 kg in the mean). Evidently, the patients diminished their body fat only as could be shown by estimations of total body water. Triglycerides, total cholesterol, and LDL-cholesterol also decreased significantly, while HDL-cholesterol remained unchanged. In spite of the weight reduction, the physical working capacity significantly increased from 57.8 to 93.2 kgm. Measurements of total nitrogen excretion with urine gave evidence of the protein saving effect of the therapy. Thus, PSMF--representing an effective therapeutic procedure--can be recommended to be used in obese HLP patients, proceeded that contraindications have been taken into consideration carefully.

The intravenous fat tolerance test with Lipofundin S (0.5 ml of 20% emulsion/kg body weight) was performed in 22 male nondiabetic patients. According to their fasting triglycerides (TG), the patients were arranged into three groups: low (less than 2.8 mmol/liter), medium (2.8-5.7 mmol/liter), and high (greater than 5.7 mmol/liter) concentrations. Fractional elimination rates of injected Lipofundin S decreased from 11.08 in low TG to 4.57%/min in high TG; they were positively correlated with fasting levels of high-density lipoprotein cholesterol but negatively with those of TG. The same pattern of correlations was observed with fractional catabolic rates of endogenous TG as measured after injection of tritium-labeled glycerol. The intravenous Lipofundin S load effected transient TG and free fatty acid elevations which were delayed in high TG. The elimination mechanisms of injected Lipofundin S and of endogenous TG are compared.

The prevalence of diabetes mellitus, hypertriglyceridemia, and hypercholesterolemia rised with the weight index until Broca = 1,2; at higher degrees of obesity it remained constant or even slightly decreased Dresden Study). The subcutaneous adipose tissue of the abdomen exhibited against controls an excessive hypertrophy in subclinical diabetics, maturity onset-diabetics and hyperlipoproteinemics of types IIb, IV, and V. With this respect, between these groups there were no significant quantitative differences. Juvenile onset diabetics had abnormal small as well as large fat cells.

In non-diabetic persons whose serum triglyceride (TG) concentrations ranged from normal to very high levels, endogenous TG turnover was measured using the radioglycerol method of Farquhar and coworkers. Insulin, FFA, and glucose concentrations were estimated during an oral glucose tolerance test. Stimulated insulin levels were correlated positively to TG concentrations and absolute TG turnover rates, and negatively to fractional TG catabolic rates. FFA concentrations had similar relationships, also in non-insulin-dependent diabetics. A more detailed analysis showed that elevated insulin and FFA levels - as an expression of peripheral insulin resistance - are typical finding in the kind of patients whose fractional TG catabolic rate is low [less than or equal to 0.210 (h-1)], irrespective of actual serum TG concentration. Our data do not suggest a stimulatory role of insulin for TG production.

In 1,126 newly manifested type II diabetics of the diabetes intervention study (628 male, 498 female) between 30 and 55 years of age by a univariate and multivariate analysis the influence of atherogenic risk factors on the development of the coronary heart disease was tested. The diagnosis coronary heart disease is based on the ECG at rest (Minnesota-code), in 796 test persons an exercise electrocardiogram was made. In a manifestation of diabetes males with coronary heart disease showed higher mean values for systolic and diastolic blood pressure, body mass index and serum triglycerides than the control group free of coronary heart disease. In females systolic and diastolic blood pressure, uric acid level and age were significantly increased. By means of multidimensional analysis of variance as to the major findings in the ECG at rest (Q/QS type) in males the diastolic blood pressure, in females the systolic blood pressure and the serum uric acid proved to be significant. Minor findings (above all disturbances of repolarisation) were in males significantly associated with the triglycerides and the diastolic blood pressure, in the females with the systolic blood pressure and the age. Test persons with a stage of coronary heart disease which is to be recognized only in the exercise ECG in the behaviour of the mean value of the atherogenic risk factors did not differ from the control group free of findings with the exception of the increased serum triglycerides in the females.

Epidemiological studies have left no doubt that moderate to vigorous physical training (PT) of endurance type decreases atherogenic lipoprotein fractions and increases vasoprotective lipoproteins. Depending on the underlying metabolic abnormality in various dyslipoproteinaemias a different response to endurance training was observed. PT is particularly effective in most forms of primary hypertriglyceridaemias. PT acts on both excessive VLDL production and fractional catabolic rate of TG--rich lipoproteins. However, improved removal seems to be of dominating importance. In primary hypercholesterolaemia LDL--cholesterol levels did not change during a 4 weeks exercise regimen with standardized isocaloric lipid lowering diet. In observational studies with hyperlipidaemic patients with stable body weight and under lipid lowering diet, during the first 4-6 weeks no significant effect on HDL was seen, whereas longterm studies clearly demonstrate an increase in HDL--cholesterol. Further beneficial effects of PT in hyperlipidaemic patients are improved glucose tolerance, down--regulation of hyperinsulinaemia, lowering of blood pressure and correction of hypercoagulability of the blood.

The index of desirable body weight is currently used for classification of patients' weights. We examined how it is related to the degree of adiposity, and whether it can serve in the prediction of body fat to the same degree as Quetelet's index. Sixty-five women and 142 men comprising a wide range of weight indices were studied. Body fat (F) was measured by the tritium dilution technique with a precision of +/- 1.26 kg. Regressions of F/W0 on the index of desirable weight W/W0 gave a correlation coefficient of 0.969 for women and 0.939 for men. Regressions of F/H2 on Quetelet's index W/H2 had correlation coefficients of the same order, i.e. 0.971 for women and 0.936 for men. Hence both indices are equally powerful for calculation of body fat within the study population. Further progress was achieved by multiple regression of F on W and W0 which yielded correlation coefficients of 0.976 for women and 0.953 for men. The residual standard deviation reflecting the mean difference between calculated and estimated fat was 3.4 kg for women and 3.8 kg for men. Despite this self-consistency, prediction of body fat for persons outside the study population is only possible within wide limits. These are given by about twice the residual standard deviation. Therefore, prediction of body fat from weight indices can only be used for detection of larger abnormalities in body composition.

Fifteen healthy young probands (nine males, six females) underwent an intravenous fat tolerance test (IVFTT) and, on the following day, a fat infusion lasting 6 hr. The emulsion tested was Lipofundin MCT 10%. One half of its triglyceride mass contains medium chain fatty acids. The IVFTT was started by injection of 0.1 g lipid per kg body weight into the fasting proband. Lipid elimination was estimated by measurement of light-scattering intensity of serum samples collected during a 60-min period. Individual fraction elimination rate constants covered a considerable range (K2 = 8.84 +/- 3.45%/min). The infusion test was performed at a rate of 0.1 g lipid per kg body weight and hr and lasted 6 hr. Serum triglyceride concentrations were determined enzymatically. They increased from 0.941 +/- 0.285 mmol/liter at the fasting state to a plateau level of 1.753 +/- 0.306 mmol/liter during infusion, and returned to initial levels 1 to 2 hr after the infusion was terminated. Individual triglyceride increments during infusion were significantly correlated with half-life periods of lipid elimination during IVFTT (r = 0.792, p less than 0.001). This relationship was derived using a model of the stationary state during infusion. We conclude that elimination kinetics of exogenous fat given either as bolus or infusion are ruled by the same fractional elimination rate constant K2. The IVFTT provides an estimate of the stationary triglyceride increment during a lipid infusion lasting several hr.

Hypertriglyceridemic patients generally show a post-challenge hyperinsulinemia. In patients where carbohydrate intolerance coexists, increasing of reactive insulin is relatively diminished and delayed. In a group of 31 hypertriglyceridemic patients these characteristics of insulin increments in peripheral blood during a 50 g OGTT were constant: neither a low-fat (carbohydrate-rich) nor a high-fat (low carbohydrate) isocaloric, weight-maintaining diet had a significant influence on this parameter when compared with a standard diet (protein content unaltered throughout all diet periods). Glucose tolerance was significantly improved after the low-fat, high-carbohydrate diet. The results were neither correlated with the type of dietary inducibility of fasting triglyceride levels in individual cases nor with the sequence of diet periods prescribed. Hyperinsulinemia in hypertriglyceridemic patients is not believed to be the direct consequence of abnormal composition of the antecedent diet.

Adipose tissue biopsy and an oral glucose tolerance test (OGTT) (50 g) were performed in 17 non-hyperlipoproteinemic subjects without overt diabetes mellitus. All the persons were weight stable at the time of investigation. A significant correlation between fasting insulin concentration and the mean adipocyte size was observed, whereas no correlation was noted between the ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte sizes, the difference in insulin levels was still demonstrable. The importance of adipose cell enlargement regulating basal and stimulated insulin output is underlined.

Endogenous triglyceride turnover has been measured in patients with normotriglyceridemia or with hypertriglyceridemia using the radioglycerol labelling technique. In parallel, a 50 g oral glucose tolerance test was performed (blood glucose, serum insulin, free fatty acids). Non-diabetics, borderline diabetics, and overt diabetics were included. In the non-diabetics, insulin levels were negatively correlated with fractional catabolic rates for triglycerides, whereas no correlation with triglyceride synthesis rates existed. Patients with low fractional catabolic rates for triglycerides have significantly higher insulin and free fatty acid concentrations, pointing to an association between impairment of triglyceride removal and insulin resistance. There is no typical kinetic pattern of triglyceride metabolism in non-insulin-dependent diabetes mellitus.

The magnitude and composition of weight loss obtained in obese women on two forms of very low calorie protein-supplemented diets (Cambridge diet, Dresden drink) as well as by complete starvation has been investigated. With the VLCD, nitrogen equilibrium was reached on the 10th day of fasting, the cumulative nitrogen balance also being compensated. Nearly half of the body weight loss is due to loss of fat. In order to assess the benefit of fasting regimes, we propose to measure at least two parameters which are independent of each other, e.g., nitrogen balance and total body water. Both types of VLCD were equally effective, safe, and acceptable in achieving rapid body weight reduction.

In 35 adipose maturity-onset-diabetics (27 women, 8 men, average age 48 years) we examined the influence of a 4--5-week slimming cure on the carbohydrate and fat metabolism. A significant decrease showed the index of ideal weight, volume of adipozytes, fasting free fatty acids concentration, triglyceride content of the liver as well as systolic blood pressure. The decrease of the triglycerides, of cholesterol and of the uric acid level in the serum could not be ascertained statistically. The reduction of weight did not cause an essential change of the basal and stimulated insulin concentrations, whereas the glucose tolerance clearly improved. After an observation period of 36.5 months behaviour of weight and form of therapy are analysed.

A weight loss of about 10 kg was acheived by means of individual periods of total fasting, hypocaloric diets and physical activity in three groups of patients: maturity-onset diabetics, patients with pathological OGTT and overweight persons with normal OGTT. Adipocyte volume decreased in all groups, glucose tolerance improved. IRI curves showed a significant overall lowering and FFA concentrations during OGTT were dimished.

In 87 patients (74 males, 13 females; age 43 +/- 9.2 years) covering a wide range of triglyceride (TG) concentrations (8.8 to 80.7 mmol/l) the turnover of total serum TG has been measured using the technique of labelling endogenously synthesized TG with 3H-glycerol. In parallel, lipoprotein lipase activity in adipose tissue and the adipose-tissue lipase activity in post-heparin plasma have been assessed following an oral 50 g glucose load. Despite the well-recognized function of this enzyme for intravascular lipolysis no direct relationship between lipase activities and fractional catabolic rates (FCR), reflecting TG removal processes, was found. On the other hand, relative enzyme activities (per TG moles) are positively correlated with the FCR. However, a detailed analysis of this relationship revealed that only in HTG patients whose FCR are below 0.210 h-1 a rate-limiting influence of a relative lipase deficit can be shown. In these patients, a statistically significant elevation of concentrations of free fatty acids is supposed to contribute to the impairment of the TG removal.

Two intravenous fat tolerance tests (IVFTT) were performed in 16 healthy volunteers and 8 patients suffering from hypertriglyceridemia (HTG). We compared Lipofundin S (Braun, Melsungen) with Intralipid (Kabi Vitrum, Stockholm), using both 10- and 20% concentrations. Time intervals between the tests were 1 h for the volunteers and 2 h for the patients with HTG, respectively. Fractional elimination rates were obtained from light scattering intensity of serum samples. They were significantly higher for Lipofundin S (9.61%/min for healthy men and 12.48%/min for healthy women) compared to Intralipid (7.09%/min for healthy men and 9.41%/min for healthy women). This difference occurred independently of (1) serum triglyceride concentrations and sex of the volunteers, (2) concentrations of lipid emulsions (10 vs. 20%), and (3) the test sequence (Lipofundin S or Intralipid first). This means that the elimination kinetics during an IVFTT are not influenced by a foregoing test. Similar features of both emulsion types were: (1) Faster elimination in women compared to men, and in healthy volunteers compared to HTG patients; (2) inverse correlation between fractional elimination rates and serum triglyceride concentrations. Fractional elimination rates of Lipofundin S and Intralipid were closely interrelated. Obviously there exists an intra-individually characteristic elimination capacity for exogenous triglycerides.

In 26 male patients with primary hypertriglyceridemia (HTG) the radioglycerol labelling technique was used to assess triglyceride production rates and fractional catabolic rates pertaining to the rapidly turning-over compartment of endogenously produced triglycerides (TG). On the basis of these data the patients were allotted to 3 groups: group I with predominating TG overproduction, group II with predominating disturbances of TG removal from the bloodstream, and group III with a combination of both dysfunctions. All patients were examined prior to and after 4 weeks of drug intake at the metabolic ward. Each group got a medical treatment aiming at removing the pathogenetic cause of the HTG. Biguanides used in group I decreased TG production rates without affecting fractional catabolic rates. In group II an anabolic steroid (chlormethyltestosterone) proved to be able to improve TG removal, but this improvement was accompanied by a significant lowering of HDL cholesterol and an increase in LDL cholesterol. In contrast, clofibric acid influenced both overproduction and removal impairment in group III. Our results give an insight into mechanisms of action of certain lipid-lowering drugs providing a basis for future improvements in the elimination of the risk factor HTG.

Medium chain triglycerides (MCT) are supposed to be advantageous on account of rapid energy supply in parental nutrition. However, data on the elimination rate of MCT-containing emulsions during an intravenous fat-tolerance test (IVFTT) are scarce. We performed this test (0.1 g lipid/kg body weight) in 18 young healthy volunteers (nine females and nine males) using Lipofundin MCT 10% (50% MCT; egg phospholipids as emulsifier). Our results indicate that both elimination and metabolization of the emulsion are fast: a prompt decrease of light-scattering index and of triglyceride concentrations in serum, an immediate appearance of post-load fatty acids and of beta-hydroxybutyrate were observed. This was in good agreement with the findings obtained during 6-hr infusions in the same probands. Fractional elimination rates k2 obtained from light-scattering indices are 7.29 +/- 2.73%/min in males and 11.59 +/- 3.38%/min in females, indicating a higher removal capacity in women. In the same subjects, the corresponding k2 values for Lipofundin S 10% (containing only long chain triglycerides) were higher, reflecting an elimination rate that is faster due to the use of soya bean phospholipids as emulsifier. In comparison, k2 values based on the course of the triglyceride concentrations are generally lower.

In 17 non-selected, non-hyperlipoproteinemic subjects without overt diabetes both adipose tissue biopsy and an oral glucose tolerance test (50 g) were performed. All persons were weight-stable at the time of investigation. A significant correlation between fasting insulin concentration and mean adipocyte volume was observed, whereas no correlation existed between ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated basal insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte volumes, the difference in insulin levels was still demonstrable. This study underlines the importance of adipose-cell enlargement regulating basal and stimulated insulin output.