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Glucose tolerance tests performed in 15 patients (10 males and 5 females, age range 6–34 years, mean 16 years) with transfusional iron overload revealed fasting and subsequent blood glucose concentrations within the normal range in all except one patient who was overtly diabetic. However, in all patients except one, blood glucose concentration at 2 hours was higher than the respective fasting glucose concentration. All but two of the patients (one of whom was diabetic) showed fasting and post glucose hyperinsulinism. All the patients had hepatic dysfunction of varying severity. It is hence suggested that the initial disturbance of carbohydrate metabolism in transfusional siderosis is insulin resistance, similar to that found in chronic liver disease. Overt diabetes is probably a later event, occurring when sufficient damage to pancreatic cells has occurred and appropriate hyperinsulinaemia cannot be sustained.

The relative roles of hepatic lipase and lipoprotein lipase in the pathogenesis of uremic lipid abnormalities were studied in 92 hemodialysis patients. Fasting serum cholesterol, triglyceride, and HDL-cholesterol concentrations were measured. Plasma lipoprotein electrophoretic patterns were determined in all patients. Hepatic lipase and lipoprotein lipase activities were selectively measured in post-heparin plasma in 59 patients. Hemodialysis patients had higher serum triglyceride and lower HDL-cholesterol concentrations than did their age and sex-matched control subjects. Both hepatic and lipoprotein lipase activities were reduced in hemodialysis patients. An inverse relation between lipoprotein lipase activities and serum triglyceride concentrations emerged. Lipoprotein lipase activities correlated with in vivo post-heparin fractional clearance rates of Intralipid. A positive correlation between lipoprotein lipase activities and HDL-cholesterol concentrations probably reflected impaired catabolism of triglyceride-rich lipoproteins being responsible for the low HDL-cholesterol concentrations. Hemodialysis patients (41.3%) had an abnormal lipoprotein (the 'mid-band'). While hepatic lipase activities did not correlate with any parameters of lipid metabolism, patients with 'low' hepatic lipase activities had a significantly higher prevalence of 'mid-bands' than did those with 'normal' activities. No evidence was developed to prove that the 'mid-band' lipoproteins were remnant particles.

It has recently been established that the rate of progression of chronic renal failure in man can be slowed by restricting dietary protein. Consequently, the short term and long term effects of a low protein diet on the course of different chronic nephropathies were studied in an attempt to delineate the factors that determine the response to such a diet. When a low protein diet was given for six months renal function improved significantly in nine patients with chronic tubulointerstitial nephritis (p <0 025); the diet had a marginally beneficial effect in 12 patients with chronic glomerulonephritis (p <0 05) and no effect in nine with hypertensive nephrosclerosis. The heterogenous functional response in the patients with chronic glomerulonephritis correlated closely with the effect of the diet on these patients' proteinuria (r=0 76, p <0 01). In a short term study (four weeks) of 12 patients with chronic renal failure changes in renal plasma flow were proportional to dietary protein intake. Renal vascular resistance fell during a high protein diet and increased when dietary protein was restricted. The changes in renal plasma flow during the low protein diet correlated well with the patients' long term functional response to the diet (r-0076, p <0 01).It is concluded that the response to a low protein diet in chronic renal failure is determined, firstly, by the nature of the underlying nephropathy, with maximal benefit being observed in non-glomerular disorders;

Lipoprotein(a) (Lp(a)) has recently been recognized to be a risk factor for coronary heart disease. Lp(a) median values in the absence of renal disease are around 10 mg/dl. Higher levels (greater than or equal to 30 mg/dl) correlate with the occurrence of coronary heart disease, particularly in the presence of elevated cholesterol. We have studied Lp(a) in 76 adults with proteinuria. Fifty had glomerular diseases and 26 non-glomerular diseases, with renal function varying from normal to advanced chronic renal failure. Lp(a) values were shifted to the right, with a median of 21.0 mg/dl, and 25% of patients had values of 30 mg/dl or more. Lp(a) did not correlate with cholesterol, age, lipoprotein subclasses, apoproteins A-I or B-100, albumin, creatinine, or creatinine clearance. Median Lp(a) values did not differ significantly comparing men versus women, or glomerular versus non-glomerular disease. Lp(a) may inhibit fibrinolysis, and is deposited in atherosclerotic lesions. Although the cause of these elevated Lp(a) levels is uncertain, we propose that they contribute to the increased risk of coronary heart disease in the nephrotic syndrome, and may play a role in progressive renal disease.

DiscussionThis patient showed a combination of proximal muscle weakness and a great excess of triglyceride in type 1 muscle fibres. He did not develop muscle pain on exercise, his plasma lipid concentrations were normal, and he could produce ketones on fasting. This syndrome accords with previous descriptions of the clinical features of the lipid storage myopathy associated with carnitine deficiency.8 12 Spontaneous remissions have been reported in this condition,'2 but in view of our patient's 12-year history of continuous profound muscle weakness with persistently raised activities of creatine kinase and lactate dehydrogenase it seems unlikely that treatment with propranolol coincided with a spontaneous remission in his case.The mode of action of propranolol, however, is a mystery. Fasting plasma concentrations of non-esterified fatty acids, triglycerides, and cholesterol were not appreciably altered by the drug in this patient. Its effect, therefore, is unlikely to reside in altering the amount of circulating long-chain fatty acids available for muscle metabolism. Changes in numbers of mitochondria in rabbit ventricuiar myocardium after exposuie to proprano1ol have been reported,1' and possibly the action of the drug is directly on the muscle mitochondria and has nothing to do with beta-adrenergic blockade.

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