The Middle East External Quality Assessment Scheme for Clinical Chemistry: The first decade.

The Middle East External Quality Assessment Scheme for Clinical Chemistry has been operating for ten years, during which the number of participants has increased from 32 to 95 in 1990. The success of the Scheme in supporting better health care is reflected in the general improvement in performance of most laboratories. Initially linked to the United Kingdom National External Quality Assessment Scheme, it is anticipated that the Scheme will soon operate independently.

The Middle East external quality assessment scheme for clinical chemistry.

The establishment and first 7 years' operation of an external quality assessment scheme for clinical chemistry in the Middle East region are described. The scheme utilises specimens distributed previously in the UK, and the performance of participating laboratories is assessed relative to the UK consensus values, taking account of method. Variance Index scoring has been used to quantitate performance, and there has been an improvement in average scores during the operation of the scheme. There are currently 88 participants, though some laboratories which failed to return results regularly were removed from the scheme. The consensus values from the scheme itself have now been validated, and in future the scheme should operate independently.

Hormonal and metabolic responses in brittle diabetic patients during feedback intravenous insulin infusion.

Twenty-four hour profiles of blood hormones and intermediary metabolites were obtained in seven 'brittle' diabetic subjects during their usual insulin therapy and during feedback intravenous insulin infusion from an artificial pancreas (GCIIS). The results were compared to those in matched stable diabetics and normal controls. Although routine insulin doses were higher in the brittle group than in the stable group (164 +/- 32 (mean +/- SE) vs. 58 +/- 8 U/day, P less than 0.005) during routine therapy, plasma free insulin levels were equal (35 +/- 12 vs. 31 +/- 6 mU/l). In the brittle group feedback i.v. insulin infusion reduced daily requirements to normal levels (80 +/- 13 U/day, P less than 0.025; stable group 71 +/- 4 U/day, NS). On routine therapy blood glucose levels were not different in the two groups (brittle 10.5 +/- 1.6, stable 10.8 +/- 0.6 mmol/l) and were similarly corrected by the GCIIS (6.9 +/- 0.3 and 6.9 +/- 0.3 mmol/l, respectively). Blood lactate and pyruvate levels were markedly abnormal in the brittle group during routine therapy (lactate: brittle group 1.93 +/- 0.27 mmol/l, stable group 0.91 +/- 0.07 mmol/l, P less than 0.025), and this abnormality was not corrected by the GCIIS (1.75 +/- 0.32 and 0.88 +/- 0.08 mmol/l, P less than 0.005). Abnormalities were also found in profiles of blood alanine and glycerol, and serum cortisol. Blood ketone body levels did not differ between the two groups of patients. The results suggest a defect in insulin delivery from subcutaneous tissue into the plasma. These patients have a characteristic metabolic abnormality, unresponsive to short-term normoglycaemia, either as the result of long-term disturbance of diabetic control, or as a marker for the underlying hormonal or biochemical abnormality.

The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: studies with a glucose controlled insulin infusion system (artificial endocrine pancreas).

Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3 +/- 0.7 compared with 5.6 +/- 0.3 mmol/l on feedback control and 5.5 +/- 0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94 +/- 0.04 on subcutaneous insulin, 0.91 +/- 0.04 on feedback control and 0.74 +/- 0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600-1800 h) was normal on feedback control (1.41 +/- 0.20 versus 1.55 +/- 0.18 mg X kg-1 X min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04 +/- 0.09 mg X kg-1 X min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.

Acetate: inhibitor of growth hormone hypersecretion in diabetic and non-diabetic uraemic subjects.

Five diabetic and 14 non-diabetic uraemic patients on long-term haemodialysis were studied during twenty-one 24 h periods including 5 to 7 h of haemodialysis against glucose-free acetate buffered dialysis fluid. Half-hourly blood samples were collected for hormonal and metabolite analysis. In addition, blood samples were analyzed in 40 experiments covering the haemodialysis and a pre-dialysis period. Before dialysis, plasma growth hormone levels were high and fluctuating, but almost always fell to low normal values within the first 2 h of haemodialysis. In the diabetic uraemic patients, the occasional severe hypoglycaemic episodes occurring during haemodialysis did not provoke growth hormone release, and hypoglycaemic reactions were not encountered. Intravenous acetate infusion studies resulted in plasma concentrations ranging from 1.3. to 2.7 mmol, ie. about 60 per cent of the levels reached during haemodialysis and in suppression of growth hormone secretion. It is suggested that the fall in growth hormone levels and the lack of hypoglycaemic symptoms during haemodialysis is due to the use of acetate as a fuel in brain.

The metabolic response to hyperglycaemic clamping in insulin-dependent diabetes.

The metabolic and hormonal effects of stable hyperglycaemia (10-12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5-6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lactate, pyruvate, total ketone bodies, glycerol and plasma non-esterified fatty acids were similar during the period of stable glycaemia at the two glucose levels. In contrast mean blood alanine was markedly elevated during hyperglycaemic clamping (0.384 +/- 0.008 vs 0.298 +/- 0.021 mmol/l) and 3-hydroxybutyrate was slightly decreased (0.068 +/- 0.007 vs 0.084 +/- 0.008 mmol/l). Plasma glucagon levels were raised during hyperglycaemic clamping and growth hormone slightly decreased. There was a close positive correlation between mean blood alanine and mean blood glucose (r = 0.79, p less than 0.01), and a negative correlation of alanine with the amount of insulin infused (r = -0.72, p less than 0.01). It is suggested that the raised alanine results from increased peripheral glucose utilisation. In general a short period of stable hyperglycaemia is not associated with a worsening of metabolic abnormalities in insulin-dependent diabetic subjects.

Improved metabolic profiles in insulin-treated diabetic patients given an alpha-glucosidehydrolase inhibitor.

An alpha-glucosidehydrolase inhibitor (acarbose; BAY g 5421) taken with food was compared with dummy tablets in seven insulin-treated diabetic patients over eight-hour periods that included breakfast, lunch, and two snacks. Acarbose diminished the postprandial increases in blood glucose, lactate, and pyruvate concentrations and may therefore be of value in the management of insulin-dependent diabetes.

Metabolic studies during normoglycaemic clamping of insulin-dependent diabetics using a glucose-controlled insulin infusion system.

Metabolic rhythms have been studied in six insulin-dependent diabetics during subcutaneous insulin therapy, and during control of blood glucose concentration by a glucose-controlled insulin infusion system (GCIIS). In none of the subjects was blood glucose concentration consistently within the normal range during subcutaneous insulin therapy. In contrast, blood glucose concentration was within the normal range after 3.5 h of insulin delivery by the glucose-controlled insulin infusion system and remained in the normal range for the following 8 h through lunch and dinner. Mean blood glucose concentration during this time ranged from 5.31 to 7.90 mM. Following normalisation of blood glucose concentration, blood lactate and pyruvate were similar with both the GCIIS and subcutaneous insulin therapy. Post-prandial lactate peaks were delayed with the GCIIS. Alanine levels were consistently higher during control with the GCIIS compared with subcutaneous therapy, while blood ketone body and plasma NEFA levels were lower, and the premeal peaks in the lipid metabolites were delayed. It is not possible to conclude that attainment of normoglycaemia with the present generation of glucose-controlled insulin infusion systems in insulin-dependent diabetics is accompanied by total normalisation of intermediary metabolism.

Continuous monitoring in vivo of blood glucose, lactate, alanine and 3-hydroxybutyrate.

Methods are described for simultaneous continuous in vivo monitoring of blood glucose, lactate, alanine and 3-hydroxybutyrate. The methods use dialysis, immobilized enzymes and measure generated reduced pyridine nucleotides fluorimetrically. The methods are accurate, sensitive, stable, and are suitable for use in emergency situations or in clinical investigation.