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Biomedical subjects

M Nattrass

Publications and source records attributed to M Nattrass.

At least 73 records · Page 4Linked to original sources

Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism.

Intermediary metabolite and serum insulin concentrations have been measured during incremental intravenous low-dose insulin infusion in massively obese patients before, and 3 months and 12 months after gastroplasty. Fasting blood glucose was similar on the three occasions, but fasting serum insulin was significantly higher preoperatively and showed a progressive fall with weight loss. Significant negative linear correlations were found between serum insulin and blood glucose, plasma nonesterified fatty acids, blood glycerol and blood total ketone bodies concentrations. The insulin-glucose dose-response curve showed a significant left shift at 3 months with a further significant improvement at 12 months. No significant change in the responses for nonesterified fatty acids, glycerol, and ketone bodies was observed at 3 months, but all three showed a significant left shift at 12 months. Massively obese patients are resistant to the action of insulin on carbohydrate and fat metabolism. Weight loss following gastroplasty results in an improvement in sensitivity to insulin, which is evident earlier in carbohydrate metabolism than in fat metabolism.

Adult↗

Macrovascular disease and hyperinsulinaemia.

The evidence that hyperinsulinaemia represents an independent risk factor for cardiovascular disease is tantalizing but the hypothesis cannot be said to be proven. The inconsistencies arising from the major prospective studies require that further work be done. Hyperinsulinaemia may not carry the same implications in all subjects and its interactions with other risk factors and with blood glucose are not well described. Possible further research has been discussed and outlined at a recent meeting (Colwell, 1985). The suggestions include delineating the action of growth factors and insulin in defined serum-free tissue culture, and the use of more sophisticated culture models, such as smooth muscle covered by vascular endothelium. The choice of human or primate tissue is desirable because of the species specificity of the atherosclerotic lesions. Prospective trials of modifying peripheral insulin levels in treated diabetic patients are probably still impracticable. The case for attempting to achieve normoglycaemia in diabetes to avoid microvascular complications is strong, and current insulin treatment regimens accept peripheral hyperinsulinaemia as a consequence of achieving portal insulin concentrations sufficient to suppress hepatic glucose output. It is hard to envisage a trial to examine reduced peripheral insulin concentrations which would not give unacceptably poor blood glucose control. Current studies of different methods and degrees of control of blood glucose might be used to provide some indication of whether such a trial could ever be justified. The Diabetes Control and Complication Trial (DCCT) is a prospective multicentre study of intensive versus conventional insulin treatment in insulin-dependent diabetic patients in the USA, and the UK Prospective Study of therapies of maturity onset diabetes (UKPS) is following patients not satisfactorily controlled on diet, randomized to different treatment modalities. These may produce some evidence within the next few years, on insulin concentrations and complications (Tattersall and Scott, 1987). Should any of this change current management of non-insulin-dependent diabetes? Despite claims of enthusiasts, special treatment regimens with intensive exercise, a particular oral agent or the addition of sulphonylureas to insulin therapy are either not generally applicable or have little theoretical basis (Martin, 1986). Current 'good practice' in Europe as put forth in a consensus document (Alberti and Gries, 1988), recognizes the need to address risk factors other than diabetes in the management of the non-insulin-dependent diabetic patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteriosclerosis↗

Treatment--metformin.

The hyperglycaemia of NIDDM is associated with insulin resistance due, in part, to reduced insulin receptor binding and more especially postreceptor defects. Metformin is an antihyperglycaemic agent which can be used to ameliorate insulin resistance. It appears to act directly on insulin target cells to enhance insulin action. Although metformin may increase insulin-receptor binding, its main effect appears to be directed at the postreceptor level of insulin action. Accordingly the drug potentiates insulin-suppression of hepatic gluconeogenesis and increases insulin-mediated peripheral glucose uptake and metabolism. It does not stimulate insulin release, does not cause weight gain and does not cause clinical hypoglycaemia. The risk of lactate accumulation should be appreciated in patients with renal insufficiency, liver dysfunction and following acute illness with hypoxia, when therapy should be stopped. Although metformin is often bracketed with phenformin in the context of lactic acidosis, different pharmacodynamics and adherence to prescribing guidelines render such a comparison unwarranted.

Diabetes Mellitus, Type 2↗

Diuretics and hyperkalaemia in diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) often presents with hyperkalaemia. We investigated whether it was more likely in patients taking potassium-retaining diuretics. A retrospective survey of all patients (552 cases) presenting in DKA between 1974 and 1984 was undertaken. Initial biochemical data were compared for patients recorded as taking potassium-retaining diuretics (7 cases) at the time of presentation with those taking potassium-losing diuretics (13 cases), and age matched control groups were selected from those who presented in DKA but were not taking diuretics. There was no significant difference in initial serum potassium levels between the diuretic treated groups. The serum sodium was higher in the control group than in the potassium losing group (p = 0.045) and the serum urea significantly lower (p = 0.045). We conclude that potassium-retaining diuretics do not predispose to hyperkalaemia in diabetic ketoacidosis.

Adult↗

A comparison of arterial and non-arterialized capillary blood gases in diabetic ketoacidosis.

The results of acid-base and blood gas estimations in arterial and non-arterialized capillary blood have been compared in samples obtained simultaneously from patients presenting with diabetic ketoacidosis. Highly significant correlations were obtained for pH, pCO2 and bicarbonate measurements. Small but significant differences were observed with capillary pH slightly lower and capillary pCO2 and bicarbonate slightly higher than arterial values. These differences were of no clinical significance. Non-arterialized capillary samples are a reliable indicator of acid-base status in this form of metabolic acidosis and are preferable to repeated arterial puncture.

Acid-Base Equilibrium↗

Recurrent diabetic ketoacidosis.

In a study over 15 years, 740 episodes of diabetic ketoacidosis occurred in 505 patients. A total of 113 patients had more than one episode. The majority (90%) of recurrences were within 4 years of the initial episode. Taking a definition of recurrent ketoacidosis as three or more episodes within 4 years, 39 patients were identified. Two subgroups appeared prone to such frequent recurrences, namely girls less than 20 years of age and women more than 59 years of age. A variety of causes of recurrent episodes was noted in the young patients but in the older patients other chronic illnesses complicated the diabetes. The need for good domiciliary supervision of elderly chronic sick patients who require insulin is emphasized.

Diabetic Ketoacidosis↗

Extra-laboratory blood glucose measurement: a policy statement.

The introduction of test strips for measurement of blood glucose has led to their widespread use by medical and paramedical staff outside the central laboratory. While many users have developed ad hoc schemes of training and quality control, formal guidelines have not been presented. This paper makes recommendations on various aspects of extra-laboratory blood glucose measurement in hospitals, but not in the home, with the aim of improving the safety and reliability of results. It is recommended that: 1. a formal programme of training should be devised by staff in the laboratory together with those in the diabetes service and others as appropriate; 2. laboratory and diabetes staff should train, assess, and approve more senior users who would then take responsibility for the training and performance of more junior colleagues; 3. all users should demonstrate their competence at regular intervals; 4. there should be a quality assurance programme arranged by the laboratory which tests the performance of the operator and the equipment; 5. laboratory staff, in consultation with users, should be responsible for the selection and purchase of equipment; 6. equipment should be cleaned and maintained on a regular basis by users.

Allied Health Personnel↗

HbA1 in the diagnosis of factitious remission of diabetes.

A case of factitious remission of type I diabetes in an adolescent girl is reported. The clue to diagnosis came from an inconsistency between clinic blood glucose levels and the corresponding values of glycosylated haemoglobin. Investigations of 24 h hormone and metabolite profiles demonstrated discrepancies between insulin dose, endogenous insulin production and free insulin levels which provided confirmatory evidence of surreptitious self-administration of insulin by the patient.

Adolescent↗

Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients.

Glucose, fructose, sorbitol and myoinositol concentrations were measured in biopsies of peripheral nerve obtained at above-knee or below-knee amputation. In diabetic patients nerve glucose (median [range]) (5.09 [1.62-12.82] vs 3.12 [1.81-4.01]) p less than 0.001, fructose (0.245 [0.060-1.280] vs 0.150 [0.053-0.385]) p less than 0.05, and sorbitol (0.028 [0.012-0.496] vs 0.016 [0.007-0.059] p less than 0.02, mumol/g wet weight) were significantly higher than in non-diabetic patients. No significant difference was found in myoinositol concentration (1.95 [1.00-3.55] vs 2.09 [1.27-5.40] mumol/g wet weight). Concentrations differed markedly from previously reported values in human nerve obtained at post-mortem.

Adult↗

Metabolic effects of combined oral contraceptive preparations.

Fasting intermediary metabolite concentrations were measured in comparable groups of women either in the follicular or luteal phase of the menstrual cycle or taking low-dose estrogen combined oral contraceptive preparations. Blood total ketone bodies concentrations were significantly elevated in oral contraceptive users (p less than 0.05 v follicular and luteal groups) whilst blood alanine levels were lower (p less than 0.01 v follicular).

3-Hydroxybutyric Acid↗

Blood fuel metabolites in asthma during and after progressive submaximal exercise.

Ten male stable asthmatic subjects and 10 matched control subjects performed a progressive exercise test on a treadmill to 85% of their predicted maximum heart rate. Blood lactate, pyruvate, hydrogen ion, glucose, alanine, glycerol and total ketone body concentrations were measured at frequent intervals during and up to 60 min after exercise. Carbon dioxide production, oxygen consumption, ventilation, respiratory exchange ratio and oxygen saturation were also measured during and up to 10 min after exercise. There were no significant differences between the asthmatic and control subjects in levels of carbon dioxide production, oxygen consumption and ventilation. The respiratory exchange ratio was greater in the asthmatic subjects during recovery from exercise (P less than 0.05). No changes in oxygen saturation were observed during exercise in either group. In both asthmatic and control subjects, lactate, pyruvate, hydrogen ion, alanine and glycerol concentrations showed an increase from baseline levels, reaching maximum levels up to 10 min after exercise and returning to baseline within 1 h after exercise. Total ketone body concentrations decreased during exercise. There were no significant differences between the asthmatic and control subjects in the concentration of any metabolite over the study period. These data indicate that fuel metabolism during and after short-term progressive exercise is similar in stable asthmatic and normal subjects.

Adult↗

Residual insulin secretion in adolescent diabetics after remission.

Twenty four hour blood glucose profiles were compared in two groups of insulin dependent adolescent diabetic patients who were beyond their initial partial remission phase. In the group with persistent endogenous insulin secretion, blood glucose profiles were significantly lower but the difference was small and not reflected in average 24 hour concentrations of glucose nor glycosylated haemoglobin. Endogenous insulin secretion must be considered in studies of metabolic control after the remission period but the effect on overall glucose control is probably clinically unimportant.

Adolescent↗

Multiple aspects of insulin resistance. Comparison of glucose and intermediary metabolite response to incremental insulin infusion in IDDM subjects of short and long duration.

Glucose and intermediary metabolite responses during incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U X kg-1 X h-1) were examined in IDDM subjects with duration of diabetes of greater than 5 yr (group D5: n = 8, duration 13.5 +/- 3.9 yr, mean +/- SD) and less than 1 yr (group D1: n = 8, duration 0.3 +/- 0.1 yr) from diagnosis. Group D5 had significantly elevated basal plasma free-insulin levels (D5 27.4 +/- 9.6, D1 15.5 +/- 9.4 mU/L; P less than .05). Nonetheless, basal blood glucose (D5 13.8 +/- 4.8, D1 7.1 +/- 1.5 mM; P less than .01), plasma nonesterified fatty acid (NEFA) (D5 1.26 +/- 0.12, D1 0.89 +/- 0.10 mM; P less than .01), blood glycerol (D5 0.12 +/- 0.05, D1 0.07 +/- 0.02 mM; P less than .05), and blood ketones (D5 1.25 +/- 0.91, D1 0.26 +/- 0.20 mM; P less than .01) were higher in group D5. During insulin infusion, group D5 had significantly elevated plasma free-insulin (P less than .05) and blood glucose (P less than .01) levels. Isotopically determined glucose turnover showed metabolic clearance rates were significantly diminished in group D5 during all insulin infusions, indicating a marked impairment of peripheral glucose metabolism. In individual subjects the relationship of blood glucose, plasma NEFA, and blood total ketones (log scale) with the simultaneously occurring plasma insulin level (log scale) was linear for each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗