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Biomedical subjects

D R Matthews

Publications and source records attributed to D R Matthews.

At least 145 records · Page 8Linked to original sources
PubMed1988

Natural history of pancreatic islet B-cell function in type 2 diabetes mellitus studied over six years by homeostasis model assessment.

Islet B-cell function and insulin sensitivity were estimated with the aid of a mathematical model from repeated fasting plasma glucose and insulin measurements over a 6 year period in 131 patients with type 2 diabetes mellitus who could be managed satisfactorily on dietary therapy alone. They presented between the ages of 40 and 69 years, and were studied before and after one year of treatment, and then at regular intervals from 12 until 72 months later. A method of averaging the individual trends by means of a linear model regression technique was used to assess the progression of their diabetes. Dietary management over the first 12 months resulted in weight loss from 118% to 106% average body weight, and improved insulin sensitivity from 26% to 40% of normal (p less than 0.001). From 12 to 72 months, the fasting plasma glucose rose at a mean rate of 0.23 mmol/l per year (p less than 0.001) despite a rate of weight loss of 0.2% average body weight per year (p less than 0.01). The estimated islet B-cell function, expressed as a percentage of normal, decreased significantly (p less than 0.05) at a rate of 1.5% per year, with no statistically significant change in insulin sensitivity. Extrapolation suggests the reduction in B-cell function predated the departure of fasting plasma glucose from the normal range.

Adult↗
PubMed1988

An amperometric needle-type glucose sensor tested in rats and man.

An amperometric glucose-measuring 25 gauge (0.5 mm diameter) needle-type sensor has been developed using a glucose oxidase and dimethyl ferrocene paste behind a semi-permeable membrane situated over a window in the needle. Electron transfer results in direct current generation. Sensors have been tested subcutaneously in the abdomen both in anaesthetized rats (40 sensors, 11 rats) and in normal, conscious man (20 sensors, 10 subjects). In rats the blood glucose was modulated by glucose and by insulin infusion. In man the glucose concentrations were rapidly changed by use of a glucose clamp at 12 mmol/l plasma concentration for 2 h, after which the glucose returned to normal. In rats the median correlation between glucose change was 0.83 with an interquartile range from 0.70 to 0.92, and in man the median correlation was 0.80 with an interquartile range 0.67 to 0.86. Hysteresis, a measure of the accuracy on the upswing and downswing, was not a problem and cross-correlation showed no phase-lag. There were quantitative differences between in vitro calibration and the performance in vivo, reflecting the different conditions of use. The current in response to a glucose concentration was stable over 6.0 h in rats and 4.5 h in man.

Adult↗
PubMed1988

Suppression of insulin secretion by falling plasma glucose levels is impaired in type 2 diabetes.

The ability of Type 2 diabetic patients to suppress islet B-cell secretion in response to falling plasma glucose levels has been studied with two different protocols. (1) Five diet-treated diabetic patients and 6 normal subjects were studied after the termination of a hyperglycaemic clamp at 15 mmol l-1 for 150 min, with the plasma glucose levels then being allowed to fall and the glucose clamp re-established at 10 mmol l-1. The plasma insulin levels fell in normal subjects from 178 +/- 141 (+/- SD) mU l-1 at the end of the 15 mmol l-1 clamp to 147 +/- 97 mU l-1 (p less than 0.02) 20 min later, whereas in diabetic patients there was no significant change from 61 +/- 41 to 56 +/- 35 mU l-1, respectively (NS). (2) The second study was performed to assess the turn-off of islet B-cell secretion with diabetic patients and normal subjects starting at comparable plasma insulin levels. Twelve diet-treated diabetic patients and 11 normal subjects were given a continuous low-dose glucose infusion for 60 min at a rate of 5 mg kg-1 ideal body weight min-1, after which the infusion was turned off and the plasma glucose level allowed to fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Relation between height velocity and fasting insulin concentrations.

A linear relation between fasting serum insulin concentration and height velocity was found in 47 normal children. This suggests that doubling of growth velocity at puberty is accompanied by a two to threefold rise in insulin. This implies that insulin dosage should be increased by a similar magnitude in pubertal diabetic children during their growth spurt.

Adolescent↗
PubMed1988

Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.

Morphometric analysis of the endocrine and exocrine pancreas was done on immunoperoxidase stained post-mortem tissue from 15 Type 2 diabetic and 10 age-matched control subjects. Thirteen of the 15 Type 2 diabetic patients had islet amyloid deposits (mean, 6.5% islet area) in the corpus (body, tail and anterior part of the head) but not in the caput (the "pancreatic polypeptide rich" part of the head) whereas none was seen in control subjects. In the corpus in diabetic subjects, the pancreatic area density of B-cells was decreased by 24% (p = 0.005) and A-cells increased by 58% (p less than 0.001) compared with control subjects. The mean A/B-cell ratio increased in the corpus from 0.27 in control subjects to 0.57 in Type 2 diabetic patients. Positive immunoreactivity for the amyloid constituent peptide, Diabetes Associated Peptide, was demonstrated in islet amyloid of diabetic subjects and in B-cells of control and diabetic subjects. The increase in A-cells may contribute to the hyperglucagonaemia and hyperglycaemia of Type 2 diabetes. The impaired insulin secretion in Type 2 diabetes may be due to a decrease in B-cells and to disruption of the islet structure by amyloid. Exocrine fat was similar in the control and diabetic subjects with both groups having more in the corpus than the caput. Diabetic subjects had increased exocrine fibrosis in the corpus region (p less than 0.001), but not in the caput. Exocrine fibrosis may be secondary to disordered islet cell function.

Aged↗
PubMed1988

Time series analysis in endocrinology.

Many hormones are secreted in pulses or oscillations. If deductions about amplitude or frequency of these oscillations are to be made, then the oscillatory attributes must be analysed. The method of doing this is known as time series analysis. Samples for such analysis need to be properly spaced, taken for a sufficient period of time and de-trended. The techniques of pulse counting, autocorrelation or Fourier transformation may then be applied to demonstrate dominant features in groups of subjects. The advantages and disadvantages of these methods are discussed.

Growth Hormone↗
PubMed1987

The relationship between height velocity and growth hormone secretion in short prepubertal children.

We have performed 24 h growth hormone (GH) profiles in 50 short prepubertal children aged between 5.2 and 12.9 years, growing with height velocity standard deviation scores (SDS) between 0.4 and -3.9. There was an asymptotic relationship between height velocity and spontaneous GH secretion described by the equation: height velocity SDS = A-B(e-cx), where A, B and C are constants and x is a measure of spontaneous GH secretion. We considered GH pulse amplitude to be the better description of spontaneous GH secretion as duration of the GH pulse (the time component of area under the curve) contributed little to the relationship between height velocity and area under the pulse. The distribution of GH secretion was continuous and there was no dividing point between GH insufficiency and sufficiency. Similar overlap was observed when the results of GH responses to insulin induced hypoglycaemia were considered; 14% of slowly growing children (height velocity SDS less than -0.8), had a response greater than 15 mU/l. Likewise serum IGF-I concentrations could not clearly separate slowly growing children from normal individuals. We conclude that height velocity, which ultimately determines height achieved, is controlled predominantly by GH pulse amplitude. The findings suggest that short normal children growing along or parallel to the third height centile could be made to grow faster by the administration of exogenous GH.

Body Height↗
PubMed1987

A soluble-phase proinsulin radioimmunoassay and its use in diagnosis of hypoglycaemia.

A soluble-phase proinsulin assay has been developed which does not require solid-phase antibody-binding. A human proinsulin standard curve is prepared in insulin-free and proinsulin-free plasma for comparison with unknown plasma samples. Proinsulin and insulin are bound with excess anti-insulin antiserum, and free C-peptide is removed by charcoal adsorption. The supernatant is then assayed using a routine C-peptide radioimmunoassay which utilises anti-C-peptide antiserum. The sensitivity of the assay (2 standard deviations above zero) is 9 pmol/L using 200 microL plasma sample. The assay is free from insulin cross-reactivity up to 100 mU/L and C-peptide up to 2000 pmol/L. Between-assay CV is 13% at 100 pmol/L. The assay has been used in subjects with hypoglycaemia of various aetiologies and has shown that a raised plasma proinsulin in the presence of hypoglycaemia can occur in sulphonylurea-induced and reactive hypoglycaemia as well as in insulinomas. After hyperglycaemic clamps at 7.5, 10 and 15 mmol/L glucose, type II diabetics both on and off sulphonylurea, were found to have lower proinsulin concentrations compared with normal subjects, commensurate with the diabetics' lower insulin responses.

Adult↗
PubMed1987

Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses.

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

Animals↗
PubMed1987

Pancreatic islet amyloid and elevated proinsulin secretion in familial maturity-onset diabetes.

Quantitative morphometry of immunostained pancreatic islet cells in a surgical specimen from a maturity-onset diabetic (MOD) patient (A) has been combined with a study of beta-cell secretion in him and his MOD son (B). The morphometry showed intra-islet amyloid deposits in 24% of islet sections which is a similar distribution to that found in 7 other MODs, (median 24%, range 0-95%). The distribution of islet cells in the pancreas from A was similar to the 7 MODs and 9 age matched non-diabetic subjects (mean beta-cell area per exocrine area, A, 2%; MODs, 1.45%; controls 1.8%). There was a significantly smaller percentage beta-cell area per islet area in A and the other MODs compared to the controls. Beta-cell secretion was studied by an intravenous glucose infusion, 5 mg/kg ideal body wt. min-1 in A and B and 4 other MODs on sulphonylurea or diet therapy. Fasting plasma glucose was high in both A and B (16 and 7.6 mmol/l respectively) in spite of sulphonylurea therapy. Similarly, A and B had elevated fasting plasma levels of insulin, (0.055 and 0.13 pmol/ml respectively) and C-peptide (0.573 and 1.39 pmol/ml respectively). Plasma proinsulin formed a higher percentage of the immunoreactive insulin in fasting plasma samples of both A (36%) and B (43%) than in less hyperglycaemic MODs on diet alone (26%) or sulphonylurea therapy (17%) and the glucose stimulated proinsulin content was even higher (A, 50%; B, 53%; MODs, diet, 19%; sulphonylureas, 16%). Elevated proinsulin levels in a patient with islet-amyloid is consistent with the hypothesis that amyloid may be derived from abnormal beta-cell secretion.

Amyloid↗