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Sibutramine and Orlistat are suitable "supporting drugs" for use in patients trying to lose weight. Orlistat reduces the absorption of fat from the intestine by about one-third. Over the long term too, the weight loss achieved under Orlistat (9%) has been greater than that seen under placebo (6.5%). Increased fat losses via the stools are associated with side effects and abandonment of treatment. Sibutramine inhibits the uptake of serotonin and noradrenaline in the synaptic gap, thus enhancing the CNS effects of these two transmitters, and prolonging the sensation of satiety. The most common side effects of sibutramine are dry mouth, headache and fatigue. The effects of sibutramine on weight reduction are similar to those of orlistat. For both drugs, the indications have been defined, and in the case of sibutramine, interactions with other medications have to be taken into account.

Objective: To investigate whether obesity influences cardiac autonomic nerve function., Design: Comparing two groups of subjects with different degrees of obesity to normal weight controls., Subjects: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2)., Measurements: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position)., Results: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001)., Conclusion: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.

Basic Remarks: The frequency of overweight, together with the associated increase in morbidity--in particular coronary heart disease--means that such patients often require intensive care., Main Points Discussed: The particular features of intensive care of obese patients are the increased risk of aspiration pneumonia (in the presence of lowered pH and elevated gastric juice volume), respiratory insufficiency caused by a reduction in expiratory reserve volume, and a greater incidence of thrombosis and embolism. Ventricular hypertrophy and dilatation results in a reduced cardiac reserve. A clinically unrecognized insulin resistance may become manifest during intensive care. Digoxin, theophylline and aminoglycosides, commonly with a low therapeutic spectrum, when administered on the basis of weight, may lead to dangerously high serum concentrations in the overweight., Conclusions: At a weight of more than about 100 kg, it must generally be expected that the compensatory mechanisms of the body are exhausted and that there will be an increased susceptibility to additional disorders of homeostasis.

Obesity and an android body fat distribution are related to metabolic disorders. We investigated the interdependences between metabolism, overweight, and body fat distribution in 40 moderately obese men before and after weight-loss. Correlations between metabolic parameters and body mass index (BMI) or waist to hip ratio (WHR) were much weaker in this exclusively obese population than in subjects of all weight categories, but the association between BMI and glucose tolerance (r = -.46, P less than .01) increased significantly after weight-loss. The improvement of metabolic parameters was much stronger in men who achieved normal weight (BMI less than 27 kg/m2) than in those who remained obese (BMI greater than 30 kg/m2, P less than .05). The WHR decreased during the diet (P less than .001), and this decrease and the extent of weight-loss were significantly correlated to an increase in insulin sensitivity (r = -.41, P less than .01) and a decrease in glucose area after an oral glucose load (r = .34, P less than .05). The decrease in apolipoprotein B, total cholesterol, and low-density lipoprotein (LDL) cholesterol was significantly correlated only to the extent of weight-loss (r = .34, .31, and .39, respectively; P less than .05). We conclude that it is best to reach normal weight for the normalization of metabolic aberrations. The reduction of cholesterol appears to be dependent on the extent of weight-loss, while the improvement in insulin sensitivity and glucose tolerance apparently is related to both the extent of weight-loss and to a change toward a less android body fat distribution.

It is speculated that endogenous opioid peptides are involved in glucose metabolism and that their homeostasis might be disturbed in obesity. Despite a different response of the pancreatic beta-cells after beta-endorphin and naloxone injections between obese patients and normal weight controls, there is little knowledge concerning the direct influence of a glucose load on beta-endorphin plasma levels, especially with respect to various nutrition states. During exploration of this topic we gained further insight on the difference of basal beta-endorphin plasma levels between normal and overweight persons. We compared beta-endorphin plasma levels during an oral glucose load in 60 obese, non-diabetic patients and in 20 normal weight controls. We also studied 40 of the obese patients after a weight reduction of 2.1 kg/m2. The following results were obtained: (1) Normal weight females have significantly lower (P less than 0.05) basal beta-endorphin levels compared to the male controls. This difference in gender is abolished in obesity where female and male patients do not differ in basal beta-endorphin plasma levels. Therefore, the difference between normal and overweight persons in beta-endorphin plasma levels was restricted to the subgroup of females. We suppose that former neglect of this difference in gender explains most of the so far reported discrepant results. (2) During the oral glucose tolerance test the beta-endorphin plasma values remained constant in the obese group. Despite improved insulin sensitivity after weight reduction there was still no change of beta-endorphin plasma levels both during the OGTT and when compared to the values before weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

The connection of body fat distribution (BFD) and the risk of developing mammary, cervical, endometrial or ovarian carcinoma was ascertained for 163 patients with carcinoma (mean age 49.9 [19-78] years) and 489 controls of comparable age and body-mass index. BFD was expressed as the ratio of waist and hip circumference (T/H ratio of 0.822 vs 0.781 and 0.826 vs 0.789, respectively; P less than 0.01). In premenopausal women with mammary or cervical carcinoma and in all postmenopausal women BFD was similar to that in the control subjects. A common cause of android obesity and ovarian or endometrial carcinoma may be a reduction of sex-hormone-binding globulins with an elevated serum level of free androgens and oestrogens.

Lipoprotein (a) is believed to be an independent risk factor for atherosclerosis. Fat modified diets or lipid lowering drugs seem to have little effect on Lp(a) serum levels. We tested the possibility of lowering Lp(a) by weight reduction and examined the correlation between Lp(a) serum levels, other lipoproteins, body weight and body fat distribution in 53 obese patients. Weight reduction by a 4000 kJ protein enriched diet for four weeks led to a mean 19 percent reduction of Lp(a) serum levels in men (P less than 0.01) and a mean 30 percent reduction in premenopausal women (P less than 0.001). Significant correlations could neither be demonstrated between Lp(a) and other lipoproteins nor between initial Lp(a), overweight and body fat distribution. This implies that an intraindividual interdependence between Lp(a) and body weight seems to be possible although an interindividual correlation can not be shown.