No abstract

This review examines some interesting 'new' histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition. It reviews the history of GH abuse that antedates by many years the awareness of endocrinologists to its potent anabolic actions. Promising methods for detection of GH abuse have been developed but have yet to be sufficiently well validated to be ready for introduction into competitive sport. So far, there are two promising avenues for detecting GH abuse. The first uses immunoassays that can distinguish the isomers of pituitary-derived GH from the monomer of recombinant human GH. The second works through demonstrating circulating concentrations of one or more GH-sensitive substances that exceed the extremes of normal physiological variability. Both methods require blood rather than urine samples. The first method has a window of opportunity lasting about 24 h after an injection and is most suitable for 'out of competition' testing. The second method has reasonable sensitivity for as long as 2 weeks after the last injection of GH and is uninfluenced by extreme exercise and suitable for post-competition samples. This method has a greater sensitivity in men than in women. The specificity of both methods seems acceptably high but lawyers need to decide what level of scientific probability is needed to obtain a conviction. Both methods need further validation before implementation. Research work carried out as part of the fight against doping in sport has opened up a new and exciting area of endocrinology.

A non-invasive Doppler ultrasound technique, based on the measurement of pulse wave velocity along the aorta, has been used to deduce aortic compliance in 25 Type 1 and 25 Type 2 diabetic patients. Thirteen of the Type 1 diabetic group had their compliance measured within 1 year of diabetes first being clinically diagnosed. All compliance values were normalized for age and sex variations using data previously obtained from over 600 normal, non-diabetic subjects (mean normalized compliance +/- SD; 100 +/- 15%). The results show that Type 1 diabetic patients have significantly more distensible aortas (132 +/- 26%) than their age- and sex-matched non-diabetic counterparts (100 +/- 12%) (p less than 0.01), while Type 2 diabetic patients have significantly stiffer aortas (74 +/- 21%) than their age- and sex-matched non-diabetic counterparts (100 +/- 18%) (p less than 0.01). The young Type 1 diabetic patients measured within 1 year of diagnosis have aortas ranging up to 78% more distensible (151 +/- 15%) than their age- and sex-matched non-diabetic controls (100 +/- 11%) (p less than 0.001). These results support findings by other groups that adult diabetic patients have less distensible arteries than normal, but contradict reports in the literature dating back over 20 years that diabetic children have stiffer arteries than normal children.

Resonances for the ketone bodies 3-D-hydroxybutyrate, acetone and acetoacetate are readily detected in serum, plasma and urine samples from fasting and diabetic subjects by 1H n.m.r. spectroscopy at 400 MHz. Besides the simultaneous observation of metabolites, the major advantage of n.m.r. is that little or no pretreatment of samples is required. N.m.r. determinations of 3-D-hydroxybutyrate, acetoacetate, lactate, valine and alanine were compared with determinations made with conventional assays at six 2-hourly intervals after insulin withdrawal from a diabetic subject. The n.m.r. results closely paralleled those of other assays although, by n.m.r., acetoacetate levels continued to rise rather than reaching a plateau 4h after insulin withdrawal. The 3-D-hydroxybutyrate/acetoacetate ratio in urine during withdrawal gradually increased to the value observed in plasma (3.0 +/- 0.2) as determined by n.m.r. The acetoacetate/acetone ratio in urine (17 +/- 6) was much higher than in plasma (2.5 +/- 0.7). Depletion of a mobile pool of fatty acids in plasma during fasting, as seen by n.m.r., paralleled that seen during insulin withdrawal. These fatty acids were thought to be largely in chylomicrons, acylglycerols and lipoproteins, and were grossly elevated in plasma samples from a non-insulin-dependent diabetic and in cases of known hyperlipidaemia.