Dose-, IGF-I- and sex-dependent changes in lipid profile and body composition during GH replacement therapy in adult onset GH deficiency.

OBJECTIVE: Patients with GH deficiency of adult onset (GHDA) exhibit dyslipidaemia and increased cardiovascular morbidity. GH replacement potently reduces body fat and serum lipids in GHDA. In recent years, lower GH doses have been introduced. The purpose of this analysis was to explore the response relationship between GH doses, lipids and body composition. DESIGN: Two consecutive, randomized 12-month GH replacement studies covering placebo and three different doses of GH (0.5, 1.0 and 1.7 IU/m(2) per day). Low and intermediate doses were IGF-I titrated. PATIENTS: Fifty-eight patients with severe GHDA, not previously treated with GH and stably substituted for other endocrine deficiencies, were included in the study. METHODS: Serum lipoproteins, serum IGF-I and body composition analysis by dual energy X-ray absorptiometry (DXA) were used. RESULTS: Fifty-seven percent of patients exhibited low density lipoprotein (LDL) cholesterol levels above 4.16 mmol/l, corresponding to the American Heart Association threshold of 160 mg/dl. GH treatment resulted in significant decreases in total and LDL cholesterol, with no significant change in high density lipoprotein cholesterol or triglycerides. The low dose induced no significant changes in lipid levels, whereas the medium dose reduced LDL cholesterol and the high dose decreased both LDL and total cholesterol. The effects depended significantly on the GH dose and the level of IGF-I obtained, but not on gender. GH replacement induced dose-dependent reductions in fat mass and sex-dependent increases in lean mass. CONCLUSIONS: GH given for 1 year at a dosage between 0.5 and 1.7 IU/m(2) per day reduced fat mass in a dose-dependent manner, increased lean body mass and lowered total and LDL cholesterol in patients with severe GHDA. Low dose GH treatment with normal IGF-I levels induced smaller changes compared with high dose therapy, and may need a longer treatment time.

Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies.

OBJECTIVE: To establish the optimum GH dose for restoring bone mineral density (BMD) in adult-onset GH deficiency (GHDA). DESIGN: Two separate randomized, controlled clinical trials. PATIENTS: Fifty-eight adults aged 45.1 (20-64) years with severe GHDA were followed in two 12-month studies. In the first study, patients were randomized to placebo or GH 1.7 IU/m2/day and in the second study GH 0.5 IU/m2/day or 1.0 IU/m2/day. MEASUREMENTS: BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C-terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months. RESULTS: Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo-treated patients, spinal BMD declined by 2.5%. At the low and medium doses, BMD increased by 2.4 and 3.1%, respectively, while a nonsignificant 0.2% decrease was seen with high dose. Forearm BMD decreased by 4.9% (P < 0.05) with high-dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose-response relationship was similar in males and females. CONCLUSION: A GH dose of 0.5-1.0 IU/m2/day (4-9 micro g/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1.7 IU/m2/day congruent with 15 micro g/kg/day) was associated with initial declines in forearm and whole-body BMD.

Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus.

Diabetic nephropathy is one of the leading causes of end-stage renal disease. We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate (GFR), and whether any effect was associated with the ACE genotype. In a prospective double-blind randomized study, normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril, an ACE inhibitor. Urine albumine/creatinine ratio (ACR), mean blood pressure (MBP) and index of glomerular filtration rate (GFR) based on S-creatinine were determined. ACE genotype was determined by electrophoresis. ACR was higher in the placebo group than in the perindopril group after 4 months, and continued to increase during the study period. After 36 months of observation, ACR in the placebo group was 1.7+/-1.1 mg/mmol, and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group (p<0.001, Mann-Whitney test). During treatment, a significant increase in ACR in the placebo group (p=0.007), Wilcoxon matched paired test) was observed. There were no differences between the groups regarding MBP or GFR. The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype (II, ID, DD).

[Autoimmune insulin syndrome. The first Danish case report]. / Autoimmunt insulinsyndrom. Forste danske tilfoelde.

This is the first case published in Denmark of autoimmune insulin syndrome (mb. Hirata). The patient, a 53 year old female suffering from a rheumatoid systemic disease, demonstrated high concentrations of autoimmune insulin antibodies in serum, a diabetic glucose tolerance test and recurrent postprandial hypoglycaemic attacks.

[75 diabetic pregnancies 1984-1991]. / Femoghalvfjerds diabetiske graviditeter 1984-1991.

During the period 1984-1991, out-patient control of 75 pregnancies of diabetic women or women who developed diabetes during their pregnancy was performed. The controls were arranged prospectively so as to investigate the patients' metabolic status in relation to malformations and the perinatal mortality. The frequency of malformations was calculated as 8% and the perinatal mortality as 6.6%. The results show that the patients began the controls at a quite advanced stage of their pregnancies and that very few were well-regulated prior to conception (6%). Under out-patient control, the patients achieved an improvement in their metabolic status which is comparable to that of other centres. It is concluded: 1) That there is a need for optimal metabolic status before conception which requires special treatment of the group of fertile diabetic women and 2) that controls can be performed under an out-patient regime.

Preventive effect of levothyroxine in patients operated for non-toxic goitre: a randomized trial of one hundred patients with nine years follow-up.

OBJECTIVE: Earlier reports have shown different effects of levothyroxine in the prevention of recurrence of non-toxic goitre after operation. These studies have been either retrospective or of short-term follow-up. This study was designed to evaluate the efficacy of long-term Eltroxin treatment (levothyroxine 0.1 mg daily) in the prevention of post-operative recurrence of non-toxic goitre. DESIGN: Randomized prospective non-placebo controlled study with 9 years follow-up. Group A (n = 40) received levothyroxine and group B (n = 60) did not. PATIENTS: One hundred patients consecutively operated for non-toxic goitre. All clinically and biochemically euthyroid and none taking any thyroid and/or antithyroid medication. MEASUREMENTS: T3, T4, TSH, thyroid antibodies (microsomal/thyroglobulin), weight and neck circumference were measured and thyroid palpation were done preoperatively, 3 and 12 months after surgery and thereafter yearly up to 9 years. RESULTS: Sixty-nine patients completed 9 years follow-up. Incidence of recurrence in group A vs group B was 14.5 vs 21.8% (P < 0.05) irrespective of type of operation, pathoanatomical diagnosis, removed amount or remnant size of the thyroid gland and level of TSH. CONCLUSION: No preventive effect on incidence of recurrence of goitre by Eltroxin 0.1 mg daily in patients operated for non-toxic sporadic goitre was observed.

High-dose dietary myo-inositol supplementation does not alter the ischaemia phenomenon in human diabetics.

Five diabetic patients and 3 non-diabetics were subjected to a dietary supplement of 20 g per day of myo-inositol (40 X the normal ingestion) for 14 days. This amount neither produced toxic side-effects nor changed the peripheral nervefunction expressed by motor conduction velocity or resistance to ischaemia.

The effect of an aldose reductase inhibitor (Sorbinil) on diabetic neuropathy and neural function of the retina: a double-blind study.

37 patients with diabetic neuropathy were randomized into 2 equal groups and given daily doses of 200 mg or 50 mg of Sorbinil - a potent aldose-reductase inhibitor - in a double-blind 4-week period between 2 periods on placebo. The purpose was to assess the role of the drug on various neurophysiological parameters and its clinical effect. No difference was shown either in the placebo periods compared to Sorbinil treatment or between the 2 groups on the neurophysiological parameters but there was a statistically significant effect on overall subjective well-being. The drug had no side-effects in the present study.

Oral supplementation of myoinositol: effects on peripheral nerve function in human diabetics and on the concentration in plasma, erythrocytes, urine and muscle tissue in human diabetics and normals.

28 young diabetics with short disease duration participated in a double-blind study by taking 6 g of myoinositol or placebo daily for 2 months. The aim was to demonstrate a possible beneficial effect of this compound on subclinical diabetic neuropathy. Measurement of vibratory perception threshold, motor and sensory conduction velocity and amplitude of nerve potential did not disclose any effect of the myoinositol given. In accordance with this, no indication for a lack of myoinositol in human diabetic blood or tissue could be found. The concentration of myoinositol in the plasma and erythrocyte of 4 human diabetics was normal or high, even though the loss of urinary myoinositol was greater than in the case of 4 normals. Further, an analysis of the content of free and lipid-bound myoinositol in muscle biopsies taken from the 4 diabetics did not give any indication of deficiency. The content of myoinositol in their muscle tissue remained uninfluenced by oral supplementation of myoinositol.

Gas chromatographic mass spectrometric determination of myo-inositol in humans utilizing a deuterated internal standard.

The isotopic dilution technique was used for determining the content of myo-inositol in human urine, plasma and haemolysed erythrocyte samples. A deuterated myo-inositol, synthesized from inosose-2 by base-catalysed exchange of hydrogens by deuterium, followed by reduction of the inosose with 2H2, was added as internal standard to the samples at an early stage in the analytical procedure. After separation and derivatization to the hexa-acetate, the gas chromatographic mass spectrometric analysis was carried out. A 25 m fused silica capillary column coated with methyl silicone was used, and the ions selected for monitoring were m/z 210 and m/z 214, which are characteristic and abundant fragment ions from unlabelled and hexadeuterated myo-inositolhexa-acetate, respectively. Calibration curves from water, urine, plasma and haemolysed erythrocytes show parallel, linear responses in the ratio between analyte and internal standard in the area of interest (0.2-2.0).

Post partum haemolytic-uraemic syndrome treated with antithrombin-III.

A 34-year-old woman with a family history of pregnancy-associated thrombotic disease developed pre-eclampsia in her 8th month of pregnancy. A severe haemolytic-uraemic syndrome (HUS) developed within 24 h after spontaneous delivery. Because the plasma antithrombin-III (AT-III) was only 15% of the normal concentration, an AT-III concentrate was given intravenously. When the normal level of plasma AT-III was reached, the clinical and biochemical signs of the syndrome disappeared. Renal function and biopsy were normal within 10 days. Because complete recovery is unusual in patients with post partum HUS and no previous reports have described a rapid recovery, the case reported here suggests that infusion of an AT-III concentrate should be tried when plasma AT-III is significantly decreased.

Myoinositol and function of peripheral nerves in human diabetics. A controlled clinical trial.

Fifty-nine diabetic patients participated in a double-blind study in order to evaluate the efficiency of myoinositol to improve the function of peripheral nerves. Myoinositol in the amounts given was not able to change motor conduction velocity or vibratory perception threshold. No change in retinopathy and several biochemical parameters was observed.

A family with dominantly inherited mild juvenile diabetes.

A family of 53 members is described in which mild diabetes in young, non-obese subjects is transmitted through four generations from parents to children, the ratio diabetic/non-diabetic offspring of diabetic parents being 3:2 and all affected individuals having a diabetic parent. In this family, mild juvenile diabetes thus appears to be inherited as an autosomal Mendelian dominant.