Relating oxygen partial pressure, saturation and content: the haemoglobin-oxygen dissociation curve.

The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (S O2 ) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin-oxygen dissociation curve, a graphical representation of the relationship between oxygen satur-ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979.

The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population-based study.

Background: Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population.

Migration is associated with lower total, but not free testosterone levels in South Asian men.

Objective: Serum testosterone measurement is an integral part of the endocrine assessment of men. Little is known about its variation in relation to migration. We examined within a South Asian group the effect of migration to the UK on androgen levels.

Change in pancreatic B-cell function (HOMA-B) varies in different populations with similar genetic backgrounds but different environments.

Objective: To determine whether pancreatic B-cell function varies in different populations with similar genetic backgrounds but different environments.

Research Design/methods: We compared a specific migrant Gujarati community in the UK (n = 205) with people still resident in the same villages of origin in Gujarat, India (n = 246). Pancreatic B-cell function (HOMA-B) was determined and the influence of age, migration and other factors was explored.

Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.

Aims/hypothesis: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk.

Investigation into possible causes of interference in serum testosterone measurement in women.

Background: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women.

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

Background: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.

Objective: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.

Design, Subjects And Setting: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246).

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India.

Aims/hypotheses: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system.

Materials And Methods: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246).

Screening for insulin resistance in women with polycystic ovarian syndrome.

Introduction: Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant.

Genetic testing for Gilbert's syndrome: how useful is it in determining the cause of jaundice?

Gilbert's syndrome is a benign condition causing hyperbilirubinemia, which is also a symptom of liver or hemolytic disease. A genetic test may be possible for Gilbert's syndrome because an associated gene defect has been isolated. Here we present a mathematical analysis of the use of this test in excluding harmful causes of hyperbilirubinemia.

Infant emmetropization: longitudinal changes in refraction components from nine to twenty months of age.

Rapid emmetropization is described in pediatrically normal infants from 9 months of age during the following year. The infants, obtained from various categories of the Cambridge population screening program, provided a broad range of refractive errors. The large group of 254 nonanisometropic infants studied allowed the mean rate of change and dependence on the initial refraction value to be determined.

The use of a microcomputer to automate measurement of action potential duration for both transmembrane and monophasic action potentials.

Measurement of action potential duration is made more valuable if it can be made simultaneously with other variables, to which it may be related. We have developed a microcomputer-based system which allows measurement of action potential duration, both for transmembrane action potentials and for monophasic action potentials. The system allows simultaneous recording and analysis of action potentials and intraventricular pressures.

Understanding "insulin resistance": both glucose resistance and insulin resistance are required to model human diabetes.

A mathematical model of normal glucose/insulin homoeostasis has been based on the known, experimentally determined responses of the liver and periphery to different glucose/insulin concentrations. Different defects of glucose resistance and insulin resistance have been applied to the model to investigate the degree to which these abnormalities could successfully predict the range of fasting glucose and insulin values found in normal, obese, and diabetic subjects. Modeling glucose resistance or insulin resistance at the liver or the periphery alone did not increase the plasma glucose to levels observed in diabetes, even when associated with marked deficiency of beta-cell function.

Simple empirical assessment of beta-cell function by a constant infusion of glucose test in normal and type 2 (non-insulin-dependent) diabetic subjects.

The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg.kg ideal body weight-1.min-1 provides Beta-cell assessment comparable to more intensive methods.

Application of structural model of glucose-insulin relations to assess beta-cell function and insulin sensitivity.

A structural mathematical model of glucose-insulin relationships based on known quantitative responses of the major organs involved with glucose metabolism has been computed. Different degrees of beta-cell function and insulin sensitivity can be included, and the effect of their interaction assessed (i) in a steady state, basal homeostasis after an overnight fast and (ii) in response to a glucose infusion. By comparing a patient's basal plasma glucose and insulin (or C-peptide) concentrations with the predictions of a basal homeostatic model, the degree of impairment of beta-cell function and insulin sensitivity can be assessed.

Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy.

To characterize the abnormal B-cell response to glucose in type II diabetes, five diet-treated diabetic and six weight-matched non-diabetic subjects were studied using the hyperglycemic clamp technique on three separate days at glycemic levels of 7.5, 10 and 15 mmol/L for 150 minutes with assessment of plasma insulin and C-peptide responses. To reduce possible secondary effects of hyperglycemia, diabetic subjects on a weight-maintaining diet were chosen who had only a slight elevation of the fasting plasma glucose, mean 6.

The glucose stimulus-response curve of the beta-cell in physically trained humans, assessed by hyperglycemic clamps.

In order to examine the effect of habitual exercise on beta-cell responses over a wide range of plasma glucose levels, plasma insulin and C-peptide responses to 2 1/2-hour hyperglycemic clamps at 7.5, 10, and 15 mmol/L glucose were assessed in six trained athletes and six age- and weight-matched sedentary controls. Athletes were significantly fitter than controls (estimated maximal oxygen uptake [VO2 max] mean 44 v 30 mL.

The beta cell glucose stimulus-response curve in normal humans assessed by insulin and C-peptide secretion rates.

Insulin and C-peptide secretion rates have been measured and compared in 12 nondiabetic subjects to characterize the glucose stimulus-response of B cell secretion in man. On three different days, glucose concentrations were clamped for 150 minutes at 7.5, 10, and 15 mmol/L, respectively.

Pathogenesis of NIDDM--a disease of deficient insulin secretion.

Type 2 diabetes is a familial disease and studies of both Caucasian and Japanese families have raised the possibility that a major susceptibility gene is involved. The majority of patients have both beta cell dysfunction and impaired insulin sensitivity but studies of relatives of Type 2 diabetic patients suggest that beta cell dysfunction is an early feature of the disease. Impaired insulin sensitivity, from acromegaly, Cushing's disease or steroid therapy, induces diabetes only in a small proportion of the population, and they may be those who have an inherited cell defect.