Summary.The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from Varying degrees of/3-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient r-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and /3-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (R~=0.88, p<0.0001), the fasting insulin concentration (P~ = 0.81, p < 0.0001), and the hyperglycaemic clamp, (Rs=0.69,p< 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient/3-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (R~ = 0.61, p< 0.01) and with the estimate from the intravenous glucose tolerance test (R~ = 0.64, p < 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for/3-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.

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SUMMARYAlthough frequently unrecognized, hypoxic pulmonary vascular disease is an important cofactor in the morbidity and mortality of a wide spectrum of disease processes. The hypoxic response incorporates two distinct phases, the acute hypoxic vasoconstrictor response and vascular remodelling associated with prolonged alveolar hypoxia. Understanding of the mechanisms causing both processes has increased rapidly and may result in the near future in specific treatment aimed at correcting underlying physiological abnormalities. However, currently available therapies remain limited to correction of the hypoxaemia and generalized non-specific pulmonary vasodilatation. The recent development of inhaled NO therapy represents a significant advance in the management of the acute hypoxic pulmonary vasoconstriction occurring during critical illness.

Plasma atrial natriuretic peptide concentrations, measured in samples drawn from the pulmonary artery, were raised in nine of 17 patients with hypoxic pulmonary hypertension but normal right atrial pressures at rest. No relationship was seen between atrial natriuretic peptide concentrations and mean pulmonary artery or right atrial pressure, or calculated pulmonary or systemic vascular resistance. Patients with the most severe hypoxaemia tended to have higher plasma atrial natriuretic peptide concentrations; three patients with no past history of oedema had concentrations more than twice the upper limit of normal. Treatment with supplementary oxygen for 30 minutes reduced pulmonary vascular resistance in all patients but had no significant effect on plasma atrial natriuretic peptide concentration. These findings suggest that atrial natriuretic peptide may be a factor in the control of sodium and water balance in hypoxic cor pulmonale, where the determinants of individual susceptibility to peripheral oedema are not well understood.