Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.

In this patient population, the reduction in bone mineral density due to thyroxine is small. It is unlikely to be of clinical significance and should not on its own be an indication for reduction of thyroxine dose in patients who are clinically euthyroid.

The interaction between the inhibitory effect on growth hormone secretion of a 75 g oral glucose load and the stimulatory effect of human pancreatic growth hormone releasing factor 1-44 (hpGRF 1-44, 10 micrograms i.v.) has been studied in six normal subjects. hpGRF 1-44 alone induced a rise in growth hormone concentrations (maximum mean +/- SEM, 16.5 +/- 1.7 mU/l 15 min after injection) while growth hormone levels were suppressed by oral glucose alone (less than 1.5 mU/l from 45 to 135 min after glucose ingestion). When hpGRF 1-44 was injected 60 min after oral glucose, the growth hormone response was attenuated (maximum, 6.7 +/- 1.4 mU/l at 15 min, P less than 0.05). Increments of blood glucose within the physiological range diminish the growth hormone response to hpGRF 1-44 in normal man.

In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min(-1) 1.73 m(-2) year(-1) on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized.

Johnston DG, Davies RR, Turner SJ. Effects of somatostatin and SMS 201-995 on carbohydrate metabolism in normal man. Scand J Gastroenteroll986,21 (suppl119), Growth hormone (GH) is important in diabetes in view of its anti-insulin actions and its relation to the long-term complications of the disease. The suppression of G H secretion in diabetics has theoretical and possible therapeutic interest. Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones. It also has inhibitory effects on gastrointestinal motility, exocrine secretion, nutrient absorption, and splanchnic blood flow. Its therapeutic use is limited by a duration of effect of several minutes only. SMS 201-995 holds more potential than native somatostatin in view of its longer duration of action. Preliminary data suggest that 50pg SMS 201-995 subcutaneously at night inhibits the noctural rise in GH secretion in normal man, hut no effect on 24-h G H secretion is observed when SMS 201-995 is injected twice daily before meals. SMS 201-995 inhibits secretion of insulin. glucagon, and TSH in addition to growth hormone and induces carbohydrate intolerance when administered before food in normal subjects. Gastrointestinal side effects suggest additional effects on nutrient disposal, which are important when it is administered before food. Further studies are required to elucidate these effects of SMS 201-995 on endocrine and gastro-intestinal function in normal and diabetic man. upon Tyne NE2 4HH, U K 158-1 65.Scand J Gastroenterol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14For personal use only.Scand J Gastroenterol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14For personal use only.