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Biomedical subjects

R R Holman

Publications and source records attributed to R R Holman.

13 recordsLinked to original sources
PubMed1979

Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations.

The liver and beta cells function in a negative feedback loop, which appears to have a predominant role in regulating both the basal plasma glucose and insulin concentrations. The degree of basal hyperglycemia in diabetes probably provides a bioassay of both the effect of a reduction in insulin secretory capacity and the degree of insulin resistance. A mathematic model of the interaction of insulin deficiency and insulin resistance has been constructed, based on the known response characteristics of the beta cells to glucose, and of plasma glucose and insulin control of hepatic and peripherpal glucose flux. The degree to which beta cell deficiency increases basal plasma glucose reflects the hyperbolic shape of the normal insulin secretory response to different glucose concentrations. The height of basal plasma insulin is a function of the degree of insulin resistance. From the basal plasma insulin and glucose concentrations, the model provides an estimate of the degree to which both beta cell deficiency and insulin resistance contribute to diabetes. The predictions arising from the model are in accord with experimental data in man and in animals. In normal-weight diabetics who do not have increased insulin resistance, the model predicts that more than 85% of beta cell function has to be lost for the basal plasma glucose to rise to 6 mmol/liter, but a further 5%--10% loss increases the basal plasma glucose to over 10 mmol/liter. In a third of a consecutive series of 65 newly presenting, uncomplicated diabetics, both normal weight and obese, the analysis from the model suggested that insulin resistance, rather than beta cell deficit, was the predominant feature.

Blood Glucose↗
PubMed1979

Maintenance of basal plasma glucose and insulin concentrations in maturity-onset diabetes.

Normal and mildly diabetic subjects each have their own "set" of basal plasma glucose and insulin concentrations. Diabetic patients have raised basal plasma glucose, with low-normal basal plasma C-peptide concentrations. Restoring normal glucose levels in mild diabetes by an insulin infusion further reduces the C-peptide concentration, but both the plasma glucose and the C-peptide return to their "set" level when the insulin is withdrawn. These results accord with the action of beta cells and liver in a negative feedback loop that maintains basal plasma glucose and insulin concentrations.

Adult↗
PubMed1978

Home blood sampling for plasma glucose assay in control of diabetes.

Estimation of plasma glucose in home blood samples is needed to improve diabetic control. Sufficiently precise measurements on capillary blood were obtained by (a) storing Reflotest glucose-oxidase strips in a desiccant container before reading and (b) collecting blood samples into a simple vacuum bottle containing potassium fluoride (assay of sodium content indicating volume of plasma collected). The precision of the methods (+/- 1 SD) was +/-0.35 mmol/1 (+/-6.3 mg/100 ml). Clinical reliability was assessed by measuring the basal plasma glucose concentration at home on different mornings in patients with maturity-onset diabetes, the day-to-day variation (+/- 1 SD) being +/-0.73 and +/-0.92 mmol/1 (+/-13.2 and +/-16.6 mg/100 ml) respectively. The mean basal plasma glucose concentration in all 84 patients with maturity-onset diabetes from three general practices was 8 mmol/1 (144 mg/100 ml), 44 of the values exceeding 6 mmol/1 (108 mg/100 ml). Improving control by monitoring the basal plasma glucose concentration in maturity-onset diabetes might help to prevent diabetic complications.

Aged↗
PubMed1978

Basal normoglycemia attained with chlorpropamide in mild diabetes.

Sixteen adult-onset diabetics, who were thought by current criteria to be well controlled on diet alone, had substantially elevated overnight, basal plasma glucose concentrations. Chlorpropamide had a sufficiently prolonged stimulatory effect on the beta cells such that normal basal plasma glucose levels were obtained in 13 patients. Both basal plasma C-peptide levels and the C-peptide response to meals became normal, with improved postprandial glycemia. Diurnal plasma triglyceride levels were reduced. Plasma growth hormone levels were normal both before and after therapy. When diet alone is insufficient to maintain basal normoglycemia in mild diabetes, chlorporpamide is as effective as basal insulin supplements in producing normal basal plasma glucose levels.

Blood Glucose↗
PubMed1978

Serum lipids in treated diabetic children and their families.

Fasting lipid concentrations have been measured in fifty treated juvenile diabetics, their siblings and parents to determine which types of hyperlipoproteinaemia co-exist with juvenile diabetes and whether the abnormalities relate to diabetic control, or represent familial disorders. Lipid concentrations amongst the parents did not differ from adult control. Triglyceride concentrations were significantly higher in those diabetic children with fasting blood glucose concentrations greater than 10 mmol/l than those with concentrations less than 10 mmol/l. The latter group had similar triglyceride levels to non-diabetic siblings. Cholesterol concentrations were not related to fasting blood glucose and were similar in diabetic and sibling controls. Hyperlipoproteinaemia (types IIa, IIb and IV) was present in ten of the diabetic patients. Six of the nine diabetic patients with raised cholesterol had at least one parent with cholesterol in the highest quintile for the control population, whereas only six of the forty-one with lower levels had parents in this category. A similar trend for cholesterol was apparent amongst the non-diabetic siblings. However, no association was apparent between the triglyceride levels of diabetics (or their siblings) and parents. Thus although hyperlipidaemia associated with juvenile diabetes appears to be largely due to inadequate control, raised cholesterol concentrations frequently occur.

Adolescent↗
PubMed1978

betacell function during insulin or chlorpropamide treatment of maturity-onset diabetes mellitus.

Maturity-onset diabetic patients usually have raised overnight-fasting plasma glucose levels associated with "normal" basal plasma insulin levels. The basal hyperglycemia is proportional to the degree of insulin deficiency. Basal insulin or C-peptide levels become subnormal if normal fasting plasma glucose levels are attained with insulin. Basal hyperglycemia is probably a compensatory response to maintain near-normal basal insulin levels. A logical therapy of maturity-onset diabetes is to produce basal normoglycemia by means of a constant basal insulin supplement, which can be provided by ultralente insulin. The reduced insulin response of diabetics to intravenous glucose is slightly increased when basal normoglycemia is established, suggesting that the high plasma glucose levels compromise beta cell function. The insulin response to meals in a mild diabetic is not affected by mild hyperglycemia but can be depleted if gross hyperglycemia occurs. Maintenance of normoglycemia then allows beta cell "recovery". In mild diabetics (c. less than 9 mmol per liter basal plasma glucose), chlorpropamide sufficiently stimulates beta cell secretion so that basal normoglycemia can be produced. The C-peptide response to meals is improved, whereas comparable reduction of the plasma glucose with insulin does not alter the meal response. Thus basal normoglycemia can be produced by "resting" beta cells with a basal insulin supplement or by stimulating them with sulfonylurea therapy.

Blood Glucose↗
PubMed1977

Diabetes: The quest for basal normoglycaemia.

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycaemia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycaemia has been obtained with markedly reduced plasma-glucose levels during the day. Plama-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycaemia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycaemia.

Adult↗
PubMed1976

Insulin rather than glucose homoeostasis in the pathophysiology of diabetes.

Hepatic glucose efflux is very sensitive to changes in plasma-insulin and it is postulated that this provides an important feedback control of insulin secretion. In diabetes this hepatic "insulin sensor" increases the basal plasma-glucose until the impaired beta cells are sufficiently stimulated to secrete normal basal insulin concentrations. Glucose regulation thus becomes of secondary importance to the maintenance of basal insulin secretion, which is teleologically needed for the "anabolic" requirements of cell growth. This hypothesis provides an explanation for the "normal" basal plasma-insulin concentrations found in diabetes in spite of impaired beta-cell function. This maintenance of basal insulin secretion accounts for the discrepancy between the marked hyperglycaemia and minimal ketosis of maturity onset diabetic patients.

Diabetes Mellitus↗
PubMed1976

Beta-cell function improved by supplementing basal insulin secretion in mild diabetes.

Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes.

Blood Glucose↗
PubMed1975

Early life of the 'battered child'.

The obstetric histories and early lives of 28 subsequently abused children are reviewed. The youngest child, more often male, was shown to be most 'at risk' especially of the mother was pregnant. Reduced antenatal care, separation of mother and child during the neonatal peroid, illness, poor features. It is felt that these and other difficulties may be regarded as 'environmental pressures' leading to child abuse by susceptible indivisuals, early recognition of such situations could lead to preventive and supportive measures.

Age Factors↗