E.A. van der Veen

COGNITIVE CHANGES DURING GROWTH HORMONE REPLACEMENT IN ADULT MEN

The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.

Effects of recombinant human growth hormone in patients with severe sepsis

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GII) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 ± 6.4 versus controls −3.7 ± 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlikc growth factor 1, glycerol, free fatty acids, and β-hy-droxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.

Growth hormone, insulin-like growthfactor I and cognitive function in adults

This review focuses on the possible contribution of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis to cognitive function. Binding sites for GH and IGF-I are found in various areas of the brain. Their distribution suggests that GH and IGF-I contribute to the function of the hippocampus, a brain structure important for the maintenance of cognitive functions such as learning and memory. Evidence for cognitive deficits in GH-deficient individuals has been found in various studies, some of which have shown that these deficits can be reversed by GH substitution therapy. In addition to examining conditions of GH deficiency, this article reviews studies evaluating the correlation between the cognitive deficits associated with ageing and age-related decreases in GH or IGF-I secretion. Based on the available data, one might hypothesize that relative GH or IGF-I deficiency could contribute to the deterioration of cognitive functions observed in the elderly.

Fatty fish-induced changes in membrane lipid composition and viscosity of human erythrocyte suspensions

The effect of a daily supplement of 75-100 g fatty fish, providing 3 g of omega 3 fatty acids, on the lipid composition and deformability of erythrocytes was studied in six healthy male subjects. After 4 weeks of the fish supplementation the mean degree of unsaturation, expressed as double bond index, of erythrocyte phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) had increased significantly by 10% and 4%, respectively. The mean cholesterol/phospholipid ratio (C/P ratio) in the membranes had increased by 28% (p less than 0.001). No change was seen in the distribution of the four major phospholipid classes. After withdrawal of the supplement for 4 weeks the changes in PC were reversed, but the changes in PE persisted and the mean C/P ratio still was higher than basal by 16% (p less than 0.01). The effect on the C/P ratio by the fatty fish is in contrast with the previously observed lack in effect of cod-liver oil. The viscosity of erythrocyte suspensions with a packed cell volume fraction of 0.80 and measured at shear rates less than or equal to 8.11 s-1 was decreased after the fish. We suggest that the fall in the viscosity of erythrocyte suspensions, reflecting increased cell deformability, is probably due to the change in the fatty acid composition of erythrocyte PC.

Absorption kinetics and action profiles of mixtures of short- and intermediate-acting insulins.

SummaryThe effects of mixing short- and intermediate-acting insulins (lente and NPH) on plasma insulin levels and action profiles, assessed by the euglycaemic clamp technique, were studied in 10 volunteers. Four protocols were used: (1) comparison between two semi-synthetic human soluble insulins in seven subjects (0.22 IU/kg); (2) assessment of insulin levels and action profiles of lente insulin in six subjects and of NPH insulin in five subjects (0.33 IU/kg); (3) comparison between mixtures of soluble with lente insulin and soluble with NPH insulin, administered immediately after mixing, in eight subjects (0.55IU/kg, 40% short-acting); (4) same mixtures, administered 2 days after preparation, in seven subjects. No differences in insulin levels and action profiles during the first 4 h after injection were found between both short-acting insulins and the soluble + NPH insulin mixtures. After the administration of NPH insulin, plasma insulin levels rose slightly faster in comparison with lente insulin, with no significant differences between the action profiles for either insulin. Onset of action was delayed after soluble + lente insulin, both when administered immediately after mixing and to a greater extent when stored for 2 days before administration. After the latter procedure, the onset of action was markedly retarded and only slightly faster than after lente insulin alone.We conclude, therefore, that mixing soluble with NPH insulin in a ratio of 2:3 does not affect the absorption kinetics of soluble insulin, whereas the onset of action is delayed when soluble is combined in the syringe with lente insulin, even when administered immediately after mixing.

Rheological properties of white blood cells are changed in diabetic patients with microvascular complications

SummaryErythrocyte and white blood cell suspensions were prepared from 22 Type 1 (insulin-dependent) and 37 Type 2 (non-insulin-dependent) diabetic patients and from 57 control subjects. Cell filterability was studied with the new “St. Georges Filtrometer”, which can discriminate between cell deformability and filter occlusion. A pronounced increase of filter clogging was found in diabetic patients compared with control subjects. There was no significant difference between Type 1 and Type 2 diabetic patients, but a significantly increased clogging was found in patients with retinopathy compared with retinopathy-free patients. Considering that filter occlusion is mainly due to leucocytes, our results show a reduced filterability of white blood cells in diabetic patients. Altered white blood cell function may act as an additional factor in the impairment of microvascular circulation in diabetic patients.

myo-Inositol and sorbitol in erythrocytes from diabetic patients before and after sorbinil treatment

SummaryErythrocytes from diabetic patients before and after treatment with the aldose reductase inhibitor, sorbinil, were analyzed by a capillary gas chromatographic method for sorbitol and myo-inositol. The mean erythrocyte sorbitol level in the diabetic patients was significantly higher than in the control subjects (13.1±0.9 and 5.2±0.3 nmol/ml erythrocytes, respectively, mean±SEM, p< 0.001). The mean erythrocyte myo-inositol level in diabetic patients was not different from that in control subjects (43.2±2.9 and 40.5±1.9nmol/ ml erythrocytes, respectively). Sorbinil treatment reduced the elevated sorbitol levels in the diabetic patients to normal or slightly below normal, but did not affect the erythrocyte myo-inositol concentration. It is concluded that the erythrocyte is not a suitable model to monitor a possible effect of sorbinil on myo-inositol concentration in less accessible tissues.

The Effect of Dietary Linoleic Acid and Pectin on Lipoprotein and Apolipoprotein A1 Concentrations in Rhesus Monkeys

Medium term effects (3 months) on serum lipoprotein levels of a diet with a high P/S ratio (2.2) and a low P/S ratio (0.3) were investigated in 13 normolipoproteinemic rhesus monkeys. Both diets were studied with and without added gel-forming fibre, as pectin. Addition of pectin did not have major influences on serum lipid levels. Changing from a low to a high P/S diet resulted in a significant decrease of total cholesterol (23%) and LDL cholesterol (18%) levels, but also HDL cholesterol (23%) and apolipoprotein A1 (Apo A1; 13%) concentrations fell significantly. However, after 12 weeks on the high P/S diet, HDL cholesterol concentrations rose by 24%, not significantly different from the levels during the low P/S diet. We conclude that the medium-term effects of a high P/S diet are a decrease in LDL cholesterol with only a transient effect on HDL cholesterol.

Benefits of intensive treatment of insulin-dependent diabetes patients: The importance of patient education

In a study among 34 insulin-dependent diabetes patients the effects of a more intensive treatment by three regular specialists were examined. Compared with a matched control group (n = 34), the results showed that the intensively treated group had a better metabolic control and that they judged the relationship with their specialist more favourably. No differences were found regarding the satisfaction about the patient education, the knowledge about diabetes, the state anxiety, the general and health locus of control orientation nor the attitude towards diabetes. Also the correlations between these patient education variables and the regulation and the evaluation of the relationship with the doctor did not differ for both groups. The conclusion is stressed that patient education needs to be a part of the development of a more intensive treatment of diabetes patients.

Hepatic 123I-insulin binding kinetics in non-insulin-dependent (Type 2) diabetic patients after i.v. bolus administration

Insulin binding kinetics in the liver were studied in non insulin dependent (Type 2) diabetic patients, by i.v. bolus administration of 123I-insulin. Eight Type 2 diabetic patients were compared with six male volunteers. Uptake of 123I-insulin by liver and kidneys was measured by dynamic scintigraphy with a gamma camera during 30 min. Images of liver and kidneys appeared within 2–3 min after administration of 123I-insulin at a dose of 1 mCi (37 MBq). Peak radioactivity for the liver was found 7.5±0.2 and 6.9±0.3 min after injection for the healthy and the diabetic subjects, respectively (N.S.). The percentage 123I-insulin hepatic uptake was not significantly different for the diabetic and the healthy subjects.Although a large variation exists for maximal uptake of radioactivity within both groups, the data suggest that binding differences in the liver in Type 2 diabetic patients, as compared to healthy subjects, may not account for hepatic insulin resistance.