Elevated insulin concentrations are independent predictors of coronary heart disease (CHD) and are related to high blood pressure, low serum HDL-cholesterol and elevated serum triglyceride. Insulin resistance is a major determinant of the plasma insulin concentration. Computer modelling of plasma glucose, insulin and C-peptide concentrations during an intravenous glucose tolerance test enables quantification of the determinants of plasma insulin concentration. The association between risk markers of CHD and model-derived measures of determinants of plasma insulin concentration in a group of healthy males has been investigated. In univariate linear regression analysis of the glucose, insulin and C-peptide data, the incremental insulin area during the second phase (10-180 min.) was found to be the strongest predictor of lipid, lipoprotein and blood pressure variables. Variations in insulin sensitivity and hepatic insulin throughput contribute to variation in the insulin response and may be secondary correlates of lipids, lipoproteins and blood pressure.

Adult↗

PubMed1992

High impedance mechanical ventilator for small animals: use of programmable controller.

We built a simple high impedance ventilator, which generates a pattern of flow largely independent of respiratory mechanics, to mechanically ventilate anaesthetized small animals. The system includes a source of compressed gas with an electronic valve and a flow controller on the inspiratory side and a second valve on the expiratory side. The two valves are driven by a programmable controller. To assess the performance of this ventilator we measured the delivered tidal volume while the ventilator was connected to an external, gradually varying resistance. This resistance was progressively increased to simulate bronchoconstriction of the respiratory system. Comparison with a volume-controlled ventilator was made. The use of a programmable controller also allows control of different patterns of mechanical ventilation, such as end-inspiratory pause or the static pressure-volume relationship, which can be used to perform lung function tests. The system is a simple, versatile device allowing both reliable mechanical ventilation and lung function assessment in small rodents and is suitable for routine use in laboratories.

Animals↗

PubMed1992

An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose.

Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age-related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides.

Adult↗

PubMed1992

Minimal models and the labelled IVGTT.

Explore the source record for details and available documents.

Blood Glucose↗

PubMed1992

The myelodysplastic hip and scoliosis.

To investigate the relationship between unilateral hip dislocation or subluxation and scoliosis, the records were examined of 31 patients aged 10 to 26 years with myelomeningocele and an initial neurosegmental level of L3 or L4. 11 patients had deteriorated neurologically over time; the remainder had stable neurological examinations, with an average follow-up of 14.3 years. Scoliosis occurred in three of the nine patients with unilateral hip instability, compared with five of the 11 remaining patients. Only two patients had the expected pattern of unilateral hip instability on the high side of an oblique pelvis, with scoliosis convex to the opposite (low) side. Several unexpected patterns were observed. The functional neurosegmental level is not stable in many patients with myelodysplasia. In neurologically stable patients, unilateral hip instability and scoliosis are comorbid factors and no causal relationship was identified.

Adolescent↗

PubMed1992

Oesophageal propulsive force and its relation to manometric pressure.

A fixed volume capsule incorporating a force transducer and a side hole for manometric measurements was constructed and calibrated. Simultaneous measurements of the propulsive (aboral) force and the manometric pressure (intraluminal pressure) were made at 5, 10, and 15 cm above the lower oesophageal sphincter and in response to dry and wet (5, 10, and 15 ml) swallows. The propulsive force and manometric pressure waves had a simultaneous onset and were of similar duration. Peak values of propulsive force for wet swallows increased significantly as measurements were made progressively more distally within the oesophagus and were greatest in the distal oesophagus. The association between manometric pressure and propulsive force is not strong (r = 0.61) suggesting that intraluminal pressure is a poor predictor of propulsive force and hence an unreliable measure of oesophageal 'function'.

Adult↗

PubMed1992

Evaluation of four mathematical models of glucose and insulin dynamics with analysis of effects of age and obesity.

Despite there being a number of mathematical models of glucose and insulin dynamics, there have been no evaluations of their operation in large groups of subjects. We have carried out intravenous glucose tolerance tests on a group of 182 healthy males, with determination of plasma glucose, insulin, and C-peptide concentrations. Parameters of glucose and insulin dynamics were determined using the minimal model of glucose disappearance, a minimal model of peripheral insulin delivery, and two different models of pancreatic insulin secretion (models I and II). Successful identifications were obtained in 96, 95, 76, and 100% of cases, respectively. The models were evaluated in terms of their ability to recover effects of obesity and aging on carbohydrate metabolism. The glucose disappearance model successfully detected the insulin resistance of both obesity and aging, whereas the peripheral insulin delivery model indicated an increased responsiveness of insulin delivery to glucose in obesity but detected no significant change associated with age. No parameter of pancreatic secretion model I exhibited a significant association with either age or obesity. Insulin secretion model II indicated that the hyperinsulinemia accompanying obesity resulted from both increased pancreatic secretion and decreased hepatic insulin uptake.

Adult↗

PubMed1992

Influence of insulin resistance, secretion, and clearance on serum cholesterol, triglycerides, lipoprotein cholesterol, and blood pressure in healthy men.

Relations between serum lipids, lipoproteins, blood pressure, and insulin metabolism were investigated in 158 healthy men aged 19-77 years and with body mass indexes (BMIs) of 19-41 kg.m-2. Mathematical modeling analysis of glucose, insulin, and C-peptide concentrations during an intravenous glucose tolerance test was used to measure parameters of insulin metabolism. In univariate analysis, both fasting and postglucose insulin concentrations showed significant positive associations with fasting serum triglyceride levels (r = 0.33 and 0.38, respectively) and systolic (r = 0.22 and 0.26) and diastolic (r = 0.21 and 0.24) blood pressure and negative associations with high density lipoprotein subfraction 2 cholesterol (HDL2; r = -0.21 and -0.25). In multivariate analysis, the associations between insulin and HDL2 cholesterol concentrations were found to depend on triglyceride levels. Insulin resistance and basal pancreatic insulin secretion showed significant positive associations with serum triglycerides, which were independent of the effects of age, BMI, and fat distribution. Hepatic insulin throughout was independently associated with HDL2 cholesterol. Associations of insulin-related variables with blood pressure were generally dependent on age and BMI. These results underline the importance of insulin sensitivity and insulin concentrations as determinants of triglyceride metabolism. They also indicate a close relation between hepatic insulin handling and HDL2 concentration that is independent of triglyceride metabolism.

Adult↗

PubMed1992

Insulin resistance, secretion, and metabolism in users of oral contraceptives.

Studies of insulin employing the oral glucose tolerance test demonstrate marked differences between the effects of different oral contraceptives, but provide little insight into the underlying disturbances. We investigated the metabolic basis of these disturbances by computer modelling of iv glucose tolerance test glucose, insulin, and C-peptide concentration profiles. Insulin resistance, secretion, and metabolism were evaluated in 296 oral contraceptive users and 95 nonusers. Four estrogen/progestin combinations, with similar estrogen but differing progestin contents, and 1 progestin-only formulation were studied. Effects on iv glucose tolerance test glucose, insulin, and C-peptide concentrations varied according to progestin content, with levonorgestrel-containing combinations having the greatest effect, followed by desogestrel and norethindrone. However, these formulations increased insulin resistance to a similar extent. The progestin-only formulation did not affect insulin resistance. Levonorgestrel combinations increased second phase pancreatic insulin secretion by 60-90%, but did not affect the insulin half-life. The desogestrel combination increased the insulin half-life by 28%, but did not affect insulin secretion. The effects of different combined oral contraceptives on glucose tolerance test glucose, insulin, and C-peptide concentration profiles appears to be due to a combination of estrogen-induced insulin resistance and progestin-associated changes in insulin half-life.

Adolescent↗

PubMed1992

Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men.

The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion.

Adipose Tissue↗

PubMed1992

Inverse relationship between serum Lp(a) levels and first-phase insulin secretion.

Relationships between serum Lp(a) levels and insulin metabolism were investigated in 147 healthy nonobese men attending an executive health-screening program. Each subject received an IVGTT with measurement of plasma levels of glucose, insulin, and C-peptide. An inverse relationship was seen with the first-phase plasma insulin response when subjects were stratified into quartile ranges of the serum Lp(a) distribution. This relationship was supported by mathematical modeling analyses of these data, which revealed an inverse relationship between serum Lp(a) levels and first-phase pancreatic insulin secretion and plasma insulin responsiveness to glucose.

Blood Glucose↗

PubMed1991

The ward atmosphere of a child psychosomatic unit: a ten-year follow-up.

Using the Ward Atmosphere Scale, we reassessed the ward atmosphere of a psychosomatic unit for children and adolescents that has been operating successfully for 10 years. There was remarkable stability in essential treatment program characteristics despite the complete turnover in patients and a 60% turnover in staff. There was substantial correlation between patient and staff perceptions in 1988 and across time (Spearman's rho: 0.951-0.660, all p values less than 0.05). Patients and staff subgroups differed somewhat in their relative emphases on certain program dimensions but, overall, the program still correlated highly with the therapeutic community cluster described by Moos (Spearman's rho: 0.660-0.809, all p values less than 0.05). This stability was achieved despite multiple health care changes, most notably shortened length of stay. Stability was probably due to high staff/patient ratio, continuity of the medical direction, and focus on milieu maintenance in staff meetings.

Adolescent↗

PubMed1991

Caring for the cognitively impaired. Reconceptualizing disability and rehabilitation.

Rehabilitative interventions must be based on remaining cognitive and physical abilities while recognizing the presence of disabilities. Rehabilitation goals should be to provide the least restrictive environment using the least restrictive intervention, thus promoting independence. The use of behavioral strategies that support remaining abilities and compensate for cognitive deficits is recommended as a rehabilitative approach. The behavioral approach requires an assessment of the ADL steps, the range of activities a person is able to complete, and the kinds of caregiver assistance needed.

Activities of Daily Living↗

PubMed1991

The myelodysplastic hip and scoliosis.

Explore the source record for details and available documents.

Child↗