William Horner Andrews (1887-1953)- first professor of physiology at Onderstepoort.

W H Andrews qualified as a veterinarian in London in 1908 and was recruited soon after, in 1909, by Sir Arnold Theiler to join the staff of the newly established veterinary laboratory at Onderstepoort. After initial studies on the treatment of trypanosomosis and on snake venoms he was deployed by Theiler in 1911 to start research on lamsiekte (botulism)at a field station on the farm Kaffraria near Christiana, where he met and married his wife Doris. After a stint as Captain in the SA Veterinary Corps during World War I he succeeded D T Mitchell as head of the Allerton Laboratory in 1918, where he excelled in research on toxic plants, inter alia identifying Matricaria nigellaefolia as the cause of staggers in cattle. When the Faculty of Veterinary Science was established in 1920 he was appointed as the first Professor of Physiology. After the graduation of the first class in 1924, and due to health problems, he returned to the UK, first to the Royal Veterinary College and then to the Weybridge Veterinary Laboratories of which he became Director in 1927. After his retirement in 1947 he returned to South Africa as a guest worker at Onderstepoort where he again became involved in teaching physiology when Prof. Quin unexpectedly died in 1950. Andrews died in Pretoria in 1953 and was buried in the Rebecca Street Cemetery.

Insulin, glibenclamide or metformin treatment for non insulin dependent diabetes: heterogenous responses of standard measures of insulin action and insulin secretion before and after differing hypoglycaemic therapy.

Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment.

Apparent elevation of serum CK-MB not due to acute myocardial infarction.

An increased serum level of the MB isoenzyme of creatine kinase (CK-MB) is a useful marker for acute myocardial infarction. Although described extensively in clinical chemistry literature, there is little information in standard medical references about false positives for this test. We report two cases where high levels of measured CK-MB activity were in fact due to another form of CK, associated with internal malignancy.

Correction of fasting hyperglycaemia with insulin or sulphonylurea lowers fasting ketone levels, but does not alter resting or post-glucose energy expenditure in non insulin dependent diabetes. Differences between the OGTT and the glucose clamp.

Sixteen non-obese non insulin dependent diabetic patients had a 75 g oral glucose tolerance test with simultaneous measurement of intermediary metabolites and of overall energy expenditure by indirect calorimetry during the test. The same patients had a 3H3 glucose infusion and hyperinsulinaemic glucose clamp procedure with glucose held at 10.0 mmol/l and insulin infused at 40 mU/m2/min. The changes in glucose and fat metabolism, in total energy balance and the fall in RQ during the glucose tolerance test did not correlate with the measures of hepatic glucose output or peripheral insulin resistance in these patients. Although the concept of insulin resistance is useful in considering the non insulin dependent diabetic state, the data derived from the body responses to a single glucose load are more relevant to the day to day fluctuation of the internal environment.

The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia.

Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 +/- 0.6 mmol.L-1, mean +/- SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 +/- 0.2 mmol.L-1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3(3H) glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU.kg-1.min-1. At identical fasting glucose concentrations (HT, 5.2 +/- 0.2; C, 5.2 +/- 0.2 mmol.L-1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 +/- 1.2; C, 4.6 +/- 0.4 mU.L-1; P = .02), and C-peptide (HT, 1.7 +/- 0.2; C, 1.1 +/- 0.1 microgram.L-1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C-peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 +/- 0.3; C, 10.9 +/- 0.7 mumol.kg-1.min-1; NS). At low insulin concentrations (HT, 20.7 +/- 1.4; C, 20.5 +/- 1.4 mU.L-1), hepatic glucose appearance was equally suppressed (HT, 9.6 +/- 0.9; C, 10.5 +/- 1.3 mumol.kg-1.min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic ketoacidosis in a district general hospital, 1981-1986.

The outcome of therapy of poorly controlled insulin-requiring cases of diabetes mellitus needing admission to a district general hospital from 1981 to 1986 was examined. There were 156 admissions to the hospital, 17 of these classified as severe diabetic ketoacidosis (serum standard bicarbonate less than 14 mmol/l). A 'low dose' insulin regimen was used in each case of severe ketoacidosis. No patient who was admitted died within a six-month period. These figures emphasise the value of a policy of direct hospital admission for poorly controlled diabetics and suggest that early diagnosis in general practice is vital to allow the application of relatively simple and standard hospital treatment.

Insulin infusion and serum potassium in normal subjects.

Two groups of healthy males of normal body mass index underwent hyperinsulinaemic glucose clamp procedures during studies of insulin resistance. Insulin was infused for 2 consecutive 100 minute periods at 40 and 400 mU.m-2.min-1, plasma glucose being maintained by 20% dextrose infusion via a Biostator. One group received 20 mmol/l potassium chloride in the dextrose infusate, calculated to replace the extracellular potassium deficit due to the action of insulin on potassium flux. Despite this, serum potassium fell equally in both groups in response to each level of insulin infusion.

Three months energy restricted diet does not reduce peripheral insulin resistance in newly diagnosed non insulin dependent diabetics.

Sixteen newly diagnosed non insulin dependent diabetic patients were treated for 3 months with an individual energy restricted diet. The effect on weight, hyperglycaemia and insulin response to oral glucose was measured in all subjects, and in 7, peripheral insulin resistance was estimated using a hyperinsulinaemic glucose clamp at two insulin infusion rates (40 and 400 mU m-2 X min-1). After diet, fasting plasma glucose fell from 12.0 +/- 0.7 mmol/l (mean +/- SEM) to 7.4 +/- 0.5 mmol/l (P less than 0.001) and weight fell from 92.9 +/- 4.2 kg to 85.0 +/- 3.1 kg (P less than 0.001). The plasma insulin response to oral glucose was unchanged after diet therapy. Insulin induced glucose disposal (M) was also unaffected by diet at insulin infusion rates of 40 mU m-2 X min-1 (12.5 +/- 1.5 mumol X kg-1 X min-1 vs 15.7 +/- 1.6 mumol X kg-1 X min-1) and 400 mU m-2 X min-1 (49.5 +/- 2.7 mumol X kg-1 X min-1 vs 55.1 +/- 2.5 mumol X kg-1 X min-1). These results show that 3 months reduction of energy consumption with weight loss in newly diagnosed non insulin dependent diabetics improves B-cell responsiveness to glucose but has no effect on liver glucose output or on peripheral insulin action.

A comparison of the pharmacokinetics of human protamine sodium insulin with human isophane insulin following subcutaneous injection in normal subjects.

The pharmacokinetics of human protamine sodium insulin 0.6 mg% were compared with those of human isophane zinc insulin using the glucose clamp technique. The insulin preparations were administered subcutaneously at a dose of 0.5 U/kg in 7 normal subjects; a placebo injection served as control. Plasma insulin and C-peptide concentrations were then measured over 24 hours. After correction of the results to allow for endogenous insulin secretion the two insulin preparations gave similar values throughout the study except that protamine sodium insulin achieved an earlier peak in plasma insulin concentration (90 minutes) compared to isophane (120 minutes). When measured by an index of the dextrose infusion rate required to maintain euglycaemia the two insulin preparations gave similar values for the first 16 hours, maximum values being obtained during the fourth hour after administration. Using this index isophane zinc insulin gave higher values during the 17th, 19th and 21st hours following administration suggesting it may have a slightly more prolonged action than protamine sodium insulin.

One month's insulin treatment of type II diabetes: the early and medium-term effects following insulin withdrawal.

In order to see if subcutaneous insulin treatment of type II diabetes might produce lasting physiologic changes, ten patients received one month's insulin treatment under strict dietary supervision. When compared to the pretreatment period, 48 hours after discontinuing insulin treatment fasting plasma glucose had fallen (P = 0.005), fasting serum insulin had risen (P = 0.005), and fasting hepatic glucose production measured by 3H-3-glucose turnover had fallen (P = 0.008). The metabolic clearance rate of glucose measured with the glucose clamp rose significantly after treatment at insulin infusion rates of 40 mU m-2 min-1 (P = 0.015) and 400 mU m-2 min-1 (P = 0.012). The serum insulin and C-peptide responses to oral glucose improved after the treatment in association with the improvement in glucose tolerance, but the plasma glucose response was unchanged. Six other type II diabetic patients who received only dietary supervision did not show significant changes in these variables. Six weeks after discontinuing insulin, the patients' fasting hepatic glucose production was still reduced compared to pretreatment (P = 0.028) and insulin action was still improved at both the lower (P = 0.028) and the higher (P = 0.028) insulin infusion rates, but the fasting plasma glucose and insulin and C-peptide responses to oral glucose had returned to pretreatment values. The improvement in glucose tolerance and beta-cell function induced by insulin treatment seems to be of more limited duration than the improvements in basal hepatic glucose production and in insulin action.

A patient with bulimia nervosa and profound folate deficiency.

A case is reported of a young woman with bulimia nervosa who presented with profound folate deficiency. This association has not been reported before despite the increased theoretical possibility. Initially she has responded well to folic acid therapy and social support.

Insulin-resistant Na+ pump activity in adipocytes from obese humans.

Basal and maximally insulin-stimulated Na+-pump activity was measured in adipocytes from subjects with normal glucose tolerance over a range of body mass indexes (BMI). In a comparison of 13 lean (BMI less than 25) vs. 15 extremely obese (BMI greater than 40) subjects basal activities per unit surface area were similar, but the maximally insulin-stimulated activity was significantly reduced in the extremely obese group [9.2 +/- 0.6 vs. 12.1 +/- 1.0 (min X dam2)-1, P less than 0.05]. The mean percent insulin stimulation of the Na+ pump above basal activity was 48 +/- 7% for the lean compared with 14 +/- 2% for the extremely obese group (P less than 0.001). A similar relationship was observed in these subjects for glucose transport where basal activities per unit surface area again were similar but the maximally insulin-stimulated transport was reduced in the extremely obese subjects (2.2 +/- 0.3 vs 5.1 +/- 0.6 attol/um2 X s, P less than 0.001). These results indicate that alterations in Na+-pump activity may be a manifestation of the insulin-resistant state that could contribute to the development of obesity via decreased cellular thermogenesis.

Elevated in vivo insulin clearance in pima indians with non-insulin-dependent diabetes mellitus.

In vivo insulin clearance in 10 subjects with non-insulin-dependent diabetes mellitus (NIDDM) has been compared with clearance in eight equally obese nondiabetic control subjects by two different methods. The first approach consisted of determining the metabolic clearance rates of exogenously infused insulin (MCRI) during hyperinsulinemic (100 mU/m2/min) glucose clamp studies. The results indicated that mean (+/- SEM) MCRI was 1.4-fold greater in the diabetic subjects (436 +/- 22 ml/m2/min) than in the controls (325 +/- 24 ml/m2/min, P less than 0.005), resulting in a lower steady-state plasma insulin concentration in the diabetic (255 +/- 8 microU/ml) compared with the nondiabetic subjects (329 +/- 29 microU/ml, P less than 0.001). The impact of NIDDM on insulin removal rates was also estimated by a second method in which extraction of endogenously secreted insulin (EXTI) in response to an oral glucose load was calculated from the integrated area above basal of plasma insulin (IRI) and of plasma C-peptide (CPR), an estimate of beta-cell secretion. The results demonstrated that fractional extraction of endogenously secreted insulin (EXTI = 100 [(CPR - IRI)/CPR]) was also 1.2-fold greater for diabetic subjects (88.9 +/- 2.5%) than for nondiabetic controls (72.0 +/- 2.8%, P less than 0.001). Finally, these two independent measurements of in vivo insulin removal rates (MCRI and EXTI) were significantly correlated with each other (r = 0.71, P less than 0.002). These observations are consistent with the view that elevated insulin clearance may contribute to the postchallenge hypoinsulinemia of NIDDM in Pima Indians.

Insulin therapy in obese, non-insulin-dependent diabetes induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal.

The effects of rigorous insulin treatment on insulin action (insulin clamp) and secretion (plasma insulin response to glucose) were studied in 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Improvements were documented in fasting (P less than 0.0001) and postprandial (P less than 0.0001) plasma glucose concentrations, insulin secretion after oral glucose (P less than 0.001), and insulin action (P less than 0.005) after 30 days of therapy. Mean integrated plasma insulin response to glucose increased 2.5-fold after insulin therapy, but this improvement varied considerably from patient to patient. Insulin action also increased with insulin treatment and the resulting values were no longer significantly different from a weight- and age-matched group of subjects with normal glucose tolerance. However, there was considerable patient-to-patient variation in the degree to which insulin action was enhanced. The insulin-induced improvements in glucose tolerance persisted for at least 2 wk after insulin withdrawal, and were associated with continued increased insulin secretion and insulin action. In conclusion, control of hyperglycemia for 1 mo led to improvements in both insulin secretion and action in a series of obese patients with NIDDM that persisted for at least 2 wk after cessation of therapy.