Type 2 diabetes mellitus and hypothyroidism: the possible influence of metformin therapy.

AIMS: To evaluate the frequency with which hypothyroidism is associated with Type 2 diabetes, to examine gender and ethnic group differences, and to assess the possible impact of metformin therapy. To compare the prevalence of hypothyroidism in a cohort of people with Type 2 diabetes with a previously published cohort of people with Type 1 diabetes from the same centre. METHOD: We randomly surveyed the records of 922 people with Type 2 diabetes (576 men and 342 women) to identify diagnoses of hypothyroidism, based on current thyroxin replacement therapy (with previous biochemical confirmation). Four subjects had secondary hypothyroidism after radio-iodine therapy for primary hyperthyroidism and were excluded from the analysis. The prevalence of primary hypothyroidism was documented in the remaining 918 subjects. We assessed the association of metformin therapy with hypothyroidism. RESULTS: The overall prevalence of primary hypothyroidism was 11.8% (women: 22.5%; men: 5.4%, P < 0.001) in subjects with Type 2 diabetes. Inter-ethnic differences were noted, with the highest prevalence among white subjects. The prevalence of hypothyroidism was lower in subjects with Type 2 diabetes who were receiving metformin therapy (P < 0.01), and this difference was greater when assessing those who developed primary hypothyroidism after starting metformin therapy (P < 0.001) CONCLUSIONS: Our results support a relatively close association between diabetes and hypothyroidism. Hypothyroidism was more common in the cohort of white subjects than in other ethnic groups. The use of metformin therapy in people with Type 2 diabetes was associated with a significantly lower prevalence of diagnosed hypothyroidism.

Striving for the impossible dream: a community-based multi-practice collaborative model of diabetes management.

AIMS: In 1994 the Centre for Diabetes and Endocrinology (CDE) based in Johannesburg, South Africa established a novel community-based capitation and risk-sharing model for diabetes management. We here describe the model and present a recent survey of the performance/outcomes of this unique diabetes care programme. METHODS: Data on 17 043 patients managed by the CDE Diabetes Management Programme at its Centre and its 262 affiliated Centres were analysed from its national database. From this total cohort, 1520 Type 1 and 8026 Type 2 diabetes patients have been in the Programme for > 5 years. The 5-year outcome data on hospital admission rates, glycaemic control (HbA(1c)), and microvascular complication rates were assessed in this subgroup of patients. RESULTS: Major reductions in hospital admission rates for both acute metabolic emergencies and all causes (40% overall) were achieved in patients enrolled onto the Diabetes Management Programme. The mean HBA(1c) on enrolment was 9.2% for subjects with Type 1 and 8.8% for those with Type 2 diabetes. After 1 year, mean HbA(1c) fell to 7.6% and 7.3% for the Type 1 and Type 2 subjects, respectively. At 5 years the HbA(1c) remained similar at 7.7% for the Type 1 subjects and 7.4% for the Type 2 subjects, demonstrating sustained improvement. Progression of microvascular complications appears to have been delayed. CONCLUSIONS: This managed care model of diabetes care in the context of the South African Private Health Care System achieved long-term improvement in glycaemic control and all-cause hospital admission rates. This may be due to the cost-containment being in the hands of the treating doctor, supported by an annual training programme. This programme is based on an individualized and holistic approach encompassing intensive patient education to facilitate self-empowerment and including prompting for the management of risk factors.

Driving and diabetics on insulin therapy.

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.

A bolus/basal multiple injection regimen in type I diabetes. A multicentre trial using a new 'fountain-pen' device for short-acting human insulin as well as long-acting human insulin.

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.

Portable insulin infusion pumps as an alternative means of insulin delivery in type I diabetes. Report on 11 patients.

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.

The effect of alrestatin on alanine-stimulated release of insulin and glucagon in man.

Alrestatin, an aldose reductase inhibitor, was administered orally to 10 normal men. Its effect on basal plasma glucose, insulin and glucagon levels and on the response of glucose, insulin and glucagon to an oral alanine load was assessed and compared to that of a placebo. There was a significant suppression of both the mean basal insulin level and the mean insulin response to alanine in the group pretreated with alrestatin as compared to the placebo group (p less than 0.05 at 0 and 60 min). Glucagon levels rose slightly in both groups but tended to be lower in the alrestatin-treated subjects, and blood sugar levels fell slightly. There was a significant inverse correlation between the mean insulin and glucose levels in individual subjects. The possible significance and mechanisms of insulin suppression are discussed.

Testicular function in patients with spinal cord damage.

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.

Effects of luteinizing hormone-releasing hormone on sexual arousal in normal men.

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.

The use of glycosylated haemoglobin measurements in the control of the diabetic patient.

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.

Menstrual disturbances in chronic renal failure.

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.

Effect of renal transplantation on pituitary gonadal function.

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.

Pituitary responsiveness to thyrotropin releasing hormone in insulin-dependent diabetes mellitus.

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.

The effect of luteinizing hormone releasing hormone (LRH) on pituitary gonadotropins in male homosexuals.

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.

Luteinizing hormone-releasing hormone and serum growth hormone in insulin-dependent diabetes.

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.

Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy.

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.

Pituitary-gonadal function in men with alcoholic cirrhosis of the liver.

Fourteen adult males with alcoholic cirrhosis were studied. Gonadotrophin responses to luteinizing hormone-releasing hormone (LRH) and testosterone (T) responses to human chorionic gonadotrophin (HCG) were determined and basal 17 beta oestradiol (E2) levels were measured in each case. The mean basal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and the mean LH and FSH responses to LRH were not significantly different from a group of age-matched male controls. However, the five men with testicular atrophy all had an elevated basal FSH level and an exaggerated FSH response to LRH. The mean serum T of the cirrhotic men was significantly lower than that of the controls (P less than 0.05), while the mean E2 level was not significantly different. However, the mean E2 level in the eight patients with gynaecomastia was significantly higher than in those without gynaecomastic (P less than 0.05). All patients had a T response to HCG, including those 5 with low basal T levels. A significant negative correlation was found between the maximum rise in T after HCG (delta T) and the maximum LH response to LRH (delta LH), suggesting a mediating effect of T reserve on the LH response to LRH. These findings tend to exclude a suppressive effect of alcohol on the pituitary gland as a cause for the hypogonadism found in men with alcoholic cirrhosis. Furthermore, the evidence of some testicular T reserve despite low basal T levels, and the presence of normal basal LH levels, suggests that the low T production is not primarily due to leydig cell dysfunction.