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Biomedical subjects

D R Matthews

Publications and source records attributed to D R Matthews.

At least 163 records · Page 9Linked to original sources
PubMed1985

Continuous infusion of glucose with model assessment: measurement of insulin resistance and beta-cell function in man.

Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and beta-cell function. It consists of a continuous glucose infusion 5 mg glucose/kg ideal body weight per min for 60 min, with measurement of plasma glucose and insulin concentrations. These are similar to postprandial levels, change slowly, and depend on the dynamic interaction between the insulin produced and its effect on glucose turnover. The concentrations can be interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and beta-cell function. In 23 subjects (12 normal and 11 with Type 2 (non-insulin-dependent diabetes) the insulin resistance measured by CIGMA correlated with that measured independently by euglycaemic clamp (Rs = 0.87, p less than 0.0001). With normal insulin resistance defined as 1, the median resistance in normal subjects was 1.35 by CIGMA and 1.39 by clamp, and in diabetic patients 4.0 by CIGMA and 3.96 by clamp. In 21 subjects (10 normal and 11 Type 2 diabetic) the beta-cell function measured by CIGMA correlated with steady-state plasma insulin levels during hyperglycaemic clamp at 10 mmol/l (Rs = 0.64, p less than 0.002). The CIGMA coefficient of variability was 21% for resistance and 19% for beta-cell function. CIGMA is a simple, non-labour-intensive method for assessing insulin resistance and beta-cell function in normal and Type 2 diabetic subjects who do not have glycosuria during the test.

Body Weight↗
PubMed1985

Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

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 beta-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 beta-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 beta-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 (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-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.

Adult↗
PubMed1985

The half-life of endogenous insulin and C-peptide in man assessed by somatostatin suppression.

The in-vivo half-lives of insulin and C-peptide have been assessed in normal man by a method which examines the decline of endogenously produced insulin and C-peptide after somatostatin suppression of secretion. Venous blood samples were taken each minute from seven normal subjects: i.v. glucose (0.1 g/kg ideal body weight) was given over 1 min to stimulate secretion, followed by a bolus of 250 micrograms of somatostatin-14 and an infusion of a further 250 micrograms somatostatin-14 over the subsequent 30 min. Plasma samples were analysed for C-peptide, glucose and insulin. The initial mono-exponential half-lives over 8 min were 3.9 +/- 0.3 and 10.2 +/- 0.7 min respectively (mean +/- SEM), with subsequent slower declines. Log transformed insulin and C-peptide yielded biphasic declinations which were assessed by a two-pool model. The rate constant of clearance of insulin implied avid uptake, while the kinetics of C-peptide clearance were slower, and irreversible loss might be explained by glomerular filtration alone. The somatostatin suppression method of measuring hormone kinetics could be used for newly described hormones which are not available for in-vivo studies.

Adult↗
PubMed1984

Non-uniform distribution of islet amyloid in the pancreas of 'maturity-onset' diabetic patients.

Quantitative morphometry of the pancreases of five 'maturity-onset' diabetic subjects has demonstrated more amyloid in islets of the head, body and tail (where it was found in a mean 29% of the islets occupying a mean 11% islet area) than in islets of the 'pancreatic-polypeptide-rich' lobule of the head (where amyloid was found in a mean of 3% of the islets occupying a mean of 0.7% islet area, both p less than 0.005). The non-uniform amyloid distribution may relate to the hormone content of the islet; the head and tail contained significantly more A, B and D-cells than the pancreatic-polypeptide-rich lobule in both non-diabetic subjects (n = 8) and diabetic patients (n = 5; p less than 0.005). This result is compatible with the previous suggestion that amyloid may be derived from insulin or its precursors.

Aged↗
PubMed1983

Control of pulsatile insulin secretion in man.

Plasma insulin and glucose concentrations were examined in man in a basal state from central venous samples taken at 1-min intervals for up to 2.5 h. Normal subjects have insulin oscillations of mean period 14 min (significant autocorrelation, p less than 0.0001) with changes in concentration of 40% over 7 min. The pulsation frequency was stable through cholinergic, endorphin, alpha-adrenergic or beta-adrenergic blockade, or small perturbations with glucose or insulin. Stimulation of insulin secretion by intravenous glucose, tolbutamide or sodium salicylate increased the amplitude of the insulin oscillations while the frequency remained stable. Patients with a truncal vagotomy or after Whipple's operation had longer-term oscillations of 33 and 37 min periodicity (autocorrelation: p less than 0.0001), with insulin-associated glucose swings four times larger than those of normal subjects. Type 2 (non-insulin-dependent) diabetic patients had a similarly increased insulin-associated glucose swing of six times that seen in normal subjects. The hypothesis is proposed that the 14-min cycle of insulin production is controlled by a 'pacemaker' which assists glucose homeostasis. The longer 33-37-min oscillations, seen in those with denervation, may arise from a limit-cycle of the feedback loop between insulin from the B cells and glucose from the liver. The vagus may provide hierarchical control of insulin release.

Adult↗
PubMed1983

Pulsatile insulin has greater hypoglycemic effect than continuous delivery.

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 +/- 0.08 mmol/L (+/- SEM) versus 5.53 +/- 0.06 mmol/L (+/- SEM) for steady infusion], diverging significantly (P less than 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P less than 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.

Adult↗
PubMed1982

Pulsatile, synchronous basal insulin and glucagon secretion in man.

The basal plasma insulin, glucagon, and glucose concentrations of 28 normal subjects were measured at 1-min intervals for periods of 45-120 min. Regular plasma insulin and/or glucagon cycles were detected in 11 subjects by autocorrelation (mean periods 13.1 and 13.7 min, respectively). Individual plasma insulin cycles were defined in all subjects (mean period 10.7 min, amplitude 1.1 mU/L), and were associated, after averaging, with plasma glucagon (amplitude 5.5 pg/ml) and plasma glucose (0.02 mmol/L) cycles. There was a significant correlation between the amplitudes of simultaneous plasma insulin and glucagon cycles (r = 0.23, P = less than 0.05, N = 124). Cross-correlation demonstrated a delay of 2 min between the changes in plasma insulin and glucagon. No comparable oscillations in plasma pancreatic polypeptide were detected. The synchronous pulsatile secretion of glucagon and insulin may be a mechanism by which insulin's hepatic effects are limited, thereby maintaining hepatic glucose production but allowing sufficient peripheral insulin concentrations to inhibit excessive catabolism. The simultaneous pulses of insulin and glucagon may be stimulated by a pacemaker, with the A-B intercellular connections producing insulin and glucagon synchrony.

Adult↗
PubMed1981

Adverse reactions to foods.

1. One thousand individuals were asked whether they avoided any foods. Of the 560 replies 33% stated that they avoided one or more foods because they caused 'unpleasant physiological reactions'. 2. Adverse reactions to one of thirteen foods were reported by 1-4% of the respondents and it is suggested that this number might be regarded as a standard with which to compare reactions to novel foodstuffs. A total of sixty-seven foods were specifically mentioned as a cause of an adverse reaction.

Female↗
PubMed1981

Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man.

The basal plasma insulin and glucose concentrations of 12 diet-treated maturity-onset diabetics were measured at minute intervals for 2 h. Brief, irregular oscillations (mean period 8.8 min) in plasma insulin were superimposed on longer term fluctuations (greater than 30 min). Time series analysis demonstrated a synchronous plasma glucose oscillation (mean amplitude 0.03 mmol/L) associated with short insulin cycles. The glucose changes seen in diabetic subjects were similar to the short plasma insulin cycles (less than 10 min) observed in normal subjects. In contrast, the longer plasma insulin cycles (greater than 10 min) of normal subjects were associated with a plasma glucose oscillation that rose before the end of the cycle. The demonstration of insulin oscillations independent of preceding plasma glucose changes in both normal and diabetic subjects suggests a pancreatic oscillating mechanism of "pacemaker". The associated glucose changes may reflect the entrainment, by the insulin cycles, of glucose production or utilization.

Blood Glucose↗
PubMed1979

Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings.

In a study of whether oscillations in plasma glucose and insulin occur in human beings, plasma samples were taken at one-minute intervals from 10 normal subjects for periods lasting between one and two hours. In five subjects the basal plasma insulin concentrations cycled regularly, with a mean period of 13 minutes and mean amplitude of 1.6 mU per liter (11.5 pmol per liter). A concurrent plasma glucose cycle was demonstrated, with a mean amplitude (after averaging to minimize random error) of 0.05 mmol per liter (1 mg per decliter). The average plasma glucose cycle was two minutes in advance of the plasma insulin. In the subjects with less regular plasma insulin cycles, a similar plasma glucose rise was demonstrated two minutes before the insulin rise. These phase relations are compatible with the presence of a negative-feedback loop between the liver and pancreatic beta cells that regulates both basal plasma insulin and glucose concentrations, although the cyclic beta-cell secretion could be independent of plasma glucose.

Adult↗
PubMed1972

On the existence in human auditory pathways of channels selectively tuned to the modulation present in frequency-modulated tones.

1. The sensitivity of detecting modulation in a test tone sinusoidally frequency-modulated at a rate varphi(test) is diminished after exposure to a conditioning tone more deeply frequency-modulated at a rate varphi(cond) provided that varphi(cond) is not very different from varphi(test), the sound amplitude being kept constant for each tone at a comfortable hearing level 40-45 dB above threshold.2. When varphi(cond) = varphi(test) the frequency deviation in the modulated test tone must be increased to about three times the unconditioned threshold magnitude to be detectable immediately after exposure to the conditioning tone. Detection sensitivity returns to normal in about one minute.3. At low modulation frequencies the conditioning effects are tuned, being much diminished when varphi(cond) differs from varphi(test) by a few cycles per second.4. Comparing monaural with contra-aural conditioning demonstrates a considerable interaural transfer of about 60-80% of the effect, indicating that the conditioning and its selectivity are predominantly central phenomena.5. The magnitude of the deterioration in detection sensitivity after conditioning is about 3 x at modulation frequencies between about 3/sec and 30/sec. It diminishes at lower and higher modulation frequencies and is effectively absent at 100/sec modulation. The bandwidth of the effect increases from a few cycles per second at the lower end of this range, to some tens of cycles per second at the upper end.6. For the same modulation frequency, the conditioning is relatively insensitive to the mean ;carrier' audiofrequency, f(0). The band width in terms of carrier frequency is at least as wide as ;critical bands'. With a test signal f(0) = 250 Hz, varphi(test) = 8/sec, conditioning is still appreciable for a conditioning tone of varphi(cond) = 8/sec but centred upon f(0) = 150 Hz or = 350 Hz. Conditioning is thus not explicable in terms of coincidences between particular spectral components in the conditioning and test tones.7. Whereas the sensitivity of detecting 8/sec amplitude modulation in a tone is conditioned by prior exposure to either amplitude- or frequency-modulated tones, in contrast the detectability of 8/sec frequency-modulated signals is conditioned only by prior exposure to frequency-modulated tones and not by amplitude-modulated conditioning tones. This underlines the special place of frequency modulation in human audition and emphasizes that the operative stimulus cannot be some aspect common to amplitude modulation and frequency modulation, like identical periodicity or coincident positioning of bands in the integrated spectra of the tones, but points to the instantaneous frequency-modulated wave form as the adequate stimulus.8. These findings strongly suggest that the human auditory pathways contain ;channels' in their organization which determine a final response selectively tuned to particular frequency-modulations. Periodicity coding alone cannot adequately explain this effect which may well only be understood in terms of a ;place' theory of frequency selectivity.9. This organization is well suited to subserve the recognition of frequency-modulation patterns in acoustic signals rather independently of the mean audiofrequency that carries the frequency modulation.

Acoustic Stimulation↗