Biomedical subjects
Publications and source records attributed to L A Distiller.
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Patients with diabetes mellitus who require insulin therapy have always been thought to be at high risk of motor vehicle accidents, primarily because of the possibility of hypoglycaemic events while driving. There are, however, no specific guidelines in South Africa that allow for a rational decision as to when a diabetic is medically fit to drive. The Road Traffic Ordinance simply states that 'Patients with uncontrolled diabetes should be forbidden to drive'. No guidelines are given as to what constitutes 'uncontrolled diabetes'. The situation is not much clearer internationally, where various countries have different laws in this regard. Diabetics on insulin therapy are not restricted from driving private vehicles in any country, but the laws regarding commercial vehicle driving by diabetics on insulin are widely disparate. The actual increased risk of motor vehicle accidents incurred by diabetic drivers on insulin is also uncertain, there being wide variations in the risk rate in different publications. Literature review does suggest, however, that diabetics are probably at a slightly increased risk of traffic violations and accidents compared with the general population, but that this increased overall risk is slight and probably acceptable. There are, however, no known actual statistics for South Africa and any rational guidelines on driving for diabetics on insulin in this country will need to be based on international experience, mostly gleaned from the USA and Western Europe. The decision as to whether a diabetic on insulin should be allowed to drive (either a private vehicle or, more often, a commercial vehicle) is frequently left to the attending doctor. Appropriate guidelines, based on international experience, are suggested.
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A trial was undertaken to ascertain the effect and acceptability of a multiple insulin injection regimen (MII) in patients with insulin-dependent diabetes mellitus using short-acting monocomponent human soluble insulin (Actrapid HM; Novo) for pre-meal bolus injections with the NovoPen injection device (Novo) and long-acting human insulin (Ultratard HM; Novo) at bedtime. Fifty-four patients, all previously on twice-daily short/intermediate-acting human insulin (Monotard HM; Novo) and Actrapid HM, were randomly selected. There was a significant overall improvement in diabetic control over the 12 weeks of the trial, the glycosylated haemoglobin (Hb A1) dropping from a mean of 9.8 +/- 2.2% to 8.6 +/- 1.7% (P less than 0.05). MII, using the NovoPen, was found to be more convenient than conventional insulin administration by 92% of the subjects. It is concluded that the NovoPen is a useful and convenient means of administering pre-meal boluses in an MII regimen, with a very high rate of acceptance by patients of all ages.
In many cases of type I diabetes it is extremely difficult to maintain adequate long-term diabetic control. Over the last decade a better understanding has been gained of the relationship between hyperglycaemia and the onset of diabetic microvascular disease. Because of this new techniques are being developed to improve diabetic control; one of these is the use of portable 'open loop' insulin infusion pumps. The results achieved in the first 11 patients to use the Auto-Syringe AS-6C insulin infusion pump on an outpatient basis for longer than 4 months are described. A highly significant improvement in fasting blood glucose levels, 2-hour postprandial blood glucose levels, mean blood glucose levels, glycosylated haemoglobin levels and mean glycaemic excursions was noted in all patients. No cutaneous complications developed despite the use of indwelling subcutaneous needles for up to 4 days at a time. Patient acceptability was excellent and none of the patients had any problems in adapting to 24-hour pump use. The importance of correct patient selection and continuous home blood glucose monitoring is stressed. Insulin infusion pumps can provide an alternative and highly efficacious means of maintaining excellent diabetic control in a select group of type 1 diabetics. However, it is essential that the physician be trained in the use of these pumps and that adequate back-up services are available.
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Glycosylated haemoglobin (HbA1c) has recently been used as an indicator of long-term diabetic control. This study compares the efficacy of HbA1c measurements and postprandial blood glucose estimations in assessing diabetic control in 51 diabetic patients. It was found that the HbA1c levels reflected overall diabetic control significantly better than did a single postprandial blood glucose estimation. HbA1c measurements give considerable aid in the assessment of the longitudinal blood sugar control in the diabetic, and may be a useful indicator of the efficacy of diabetic treatment.
Six normal adult male subjects were administered either luteinizing hormone-releasing hormone (LRH, 500 micrograms, intramuscularly injected) or a saline placebo 10 min before a 40-min laboratory session in which they were exposed to erotic stimuli; subjects attended four such sessions, twice receiving LRH and twice the placebo in a balanced, double-blind, crossover design. Sexual arousal was inferred from degree of tumescence, with penile circumference measured by a mercury-in-rubber strain gauge. Heart rate was monitored continuously, and blood samples were taken periodically and assayed for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T). Rapidity of onset of erection, maximum degree of erection obtained, and overall levels of tumescence were consistently greater following LRH administration than following saline placebo; however, the differences were not statistically significant. The anticipated LH and FSH response to LRH was noted as well as a small increment in LH levels following erotic stimulation. No significant alteration in serum testosterone was observed within the time sampled. There were no significant correlations between hormonal data and any measurement of penile tumescence. In view of the results, further investigation of the behavioral effects of LRH appears justified.
Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.
Vaying degrees of testicular dysfunction are found in men with traumatic spinal cord damage. Eighteen paraplegic men have been studied and the gonadotropin response to luteinizing hormone-releasing hormone (LRH) measured. Basal serum testosterone estimations were made and in eight of the patients testicular testosterone reserve was assessed by the testosterone response to human chorionic gonadotropin (HCG). Testicular biopsies were performed in seven cases. In three of these patients, the testicular biopsies were abnormal. Five of the patients had elevated Follicle stimulating hormone levels and abnormalities of Luteinizing hormone kinetics were found in the same five patients. There was no significant difference between the plasma testosterone levels of the paraplegic patients when compared to the control group. In all the patients tested, there was an adequate testosterone reserve, and this included the three patients with the abnormal testicular biopsies. No relationship was found between the level of cord lesion and any of the hormonal parameters measured. This study confirms the primary nature of the seminiferous tubular damage which occurs in some patients with paraplegia.
Twelve adult male patients who had undergone successful renal transplantation were investigated. The gonadotropin responses to 100 microgram luteinizing hormone-releasing hormone (LRH) were studied, and basal serum testosterone and prolactin assayed. Significantly elevated mean basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found, associated with a correspondingly excessive LH and FSH response to LRH. Mean basal serum testosterone levels in the posttransplant patients were significantly lower than in normal controls, while the mean basal prolactin levels were similar in the two groups. The results were not influenced by the varying degrees of renal function found in the posttransplant patients.
The pituitary responses to the intravenous administration of 200 mg of Thyrotropin Releasing Hormone were investigated in 14 poorly controlled insulin dependent diabetic males and in nine matched controls. The mean TSH and prolactin responses in the two groups were similar although both tended to be lower in the diabetics. There was a small FSH rise in 11 of the 23 subjects.
Basal serum LH and FSH values were found to be within normal limits in 9 homosexual men. The mean LH and FSH responses following the intravenous administration of 100 microgram of LRH were not significantly different from that of heterosexual controls. In addition, the mean basal plasma serum testosterone was similar in the two groups. There is thus no definite implication of endocrine factors in the genesis of male homosexuality.
Growth hormone (GH) responses were studied in 26 insulin-dependent diabetics after the intravenous administration of 100 microgram of synthetic luteinizing hormone-releasing hormone (LH-RH). Although the mean basal GH concentration was significantly higher than that of 20 matched non-diabetic controls, no significant increment occurred after the LH-RH injection. (The controls also showed no rise in GH.) It seems that the GH hypersecretion of insulin-requiring diabetics does not, as is frequently noted in acromegaly, respond to the injection of LH-RH.
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Basal LH, FSH, 17 beta-oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty-four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration. The mean basal testosterone and 17 beta-oestradiol values in the lepromatous group were significantly lower than those of the tuberculoid and control groups. The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated. The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17 beta-oestradiol values). This is compatible with the lack of gonadal involvement in these patients.
Conventional insulins, even if recrystallised many times, are found to contain several peptides on gel electrophoresis and are immunogenic. Antibody formation, insulin allergy, fat atrophy, fat hypertrophy and insulin bumps are thought to be largely caused by the impurities rather than by the insulin itself. 'Monocomponent' insulin has recently been prepared in the laboratories of Novo industries Ltd. Theoretically, this insulin should not cause the above complications. A combined clinical trial of monocomponent insulin has been carried out in Johannesburg and Cape Town on 24 patients with diabetes of diverse aetiology, who required insulin. The results of the trial may be summarised as follows: Monocomponent insulin appears to be very effective in patients with insulin allergy, adipopathy, and possibily in some patients in whom diabetes is not controlled with large doses of insulin. The monocomponent insulins deteriorate on storage at room temperature and yield monodesamido insulin. This de-amidation may be associated with persistent circulating antibodies to insulin and pro-insulin and with failure to reduce insulin requirements, but does not interfere with improvement in allergy or adipopathy. Long-standing diabetic patients, who are qell controlled with conventional insulin, are unlikely to gain therapeutic benefit from monocomponent insulin, and may even deteriorate or lose smooth metabolic control.
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