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Biomedical subjects

D A Pyke

Publications and source records attributed to D A Pyke.

At least 55 records · Page 3Linked to original sources
PubMed1984

Pathogenesis of insulin-dependent diabetes: a role for activated T lymphocytes.

Expression of HLA DR antigens on T lymphocytes indicates that these cells are actively involved in an immune response. Raised levels of activated T lymphocytes were found in 14 of 15 recently diagnosed but in only 7 of 28 long-standing insulin-dependent diabetics. 9 of the recently diagnosed patients retested 6 months later still had high levels of activated T lymphocytes. Even long-standing insulin-dependent diabetics had significantly higher levels of activated T lymphocytes than non-insulin-dependent diabetics and healthy controls. 5 of 7 unaffected co-twins of recently diagnosed insulin-dependent diabetics had high levels of activated T cells; this increase persisted in 2 retested 6 months later, when mildly impaired glucose tolerance had developed. These results confirm that there is an active cellular immune reaction in newly diagnosed insulin-dependent diabetics which may precede the disease and persist for at least 6 months after its appearance.

Adolescent↗
PubMed1984

The role of endogenous opioids in the chlorpropamide alcohol flush.

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Administration, Oral↗
PubMed1983

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs.

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.

Adolescent↗
PubMed1983

Metabolic studies in chlorpropamide-alcohol flush positive and negative Type 2 (non-insulin dependent) diabetic patients with and without retinopathy.

Serum insulin and blood metabolite responses to oral glucose with and without intravenous naloxone were measured in 24 chlorpropamide-alcohol flush positive and negative Type 2 (non-insulin dependent) diabetic patients with and without retinopathy. In the chlorpropamide-alcohol flush positive patients with retinopathy, fasting blood glucose was increased greater than 40% and the serum triglycerides were increased over twofold compared with each of the other three groups. Following oral glucose (50 g), the chlorpropamide-alcohol flush positive diabetic patients with complications had a lower serum insulin and higher blood glycerol than the other three groups. Thus, chlorpropamide-alcohol flush positive subjects with retinopathy showed distinct metabolic differences from the other three groups. There was no evidence that opiate-receptors influenced the metabolic response to oral glucose in the Type 2 diabetic patients since the infusion of intravenous naloxone produced no effect on the serum insulin or blood metabolites.

Aged↗
PubMed1983

Hyperglycaemia, a morphine-like effect produced by naloxone in the cat.

In unanaesthetized cats the pronounced hyperglycaemia produced by intravenous morphine (5 mg/kg) was inhibited by naloxone. However, naloxone itself produced hyperglycaemia when given in doses slightly larger than those required to produce inhibition. These two effects of naloxone were obtained when it was injected intravenously, into a lateral cerebral ventricle, or into the cisterna magna. The hyperglycaemia produced when naloxone or morphine was injected into a lateral cerebral ventricle or into the cisterna magna was not inhibited by intravenous naloxone. Hyperglycaemia was not the only morphine-like effect of naloxone. It also reproduced some of the behavioural effects of morphine.

Animals↗
PubMed1983

Muscle capillary basement membrane in identical twins discordant for insulin-dependent diabetes.

Although hereditary factors clearly modulate susceptibility to develop diabetes, their role as determinants of vascular complications associated with diabetes remains unclear. These studies were undertaken to further assess the extent to which capillary basement membrane thickening (CBMT) is governed by metabolic derangements associated with relative or absolute insulin deficiency versus genetic determinants of vascular disease closely linked to but independent of those modulating susceptibility to develop relative or absolute insulin deficiency. Quadriceps muscle capillary basement membranes obtained by needle biopsy were examined in eight pairs of identical twins discordant for insulin-dependent diabetes (IDD) for 11-29 yr. Biopsy material from one of the diabetic twins was technically unsuitable for study. The average CBM width of the IDD twins was found to be significantly thicker than that of their nondiabetic (ND) twin mates (t = 2.50, P less than 0.025). Three IDD, but none of the ND twins, had basement membrane width values in excess of 95% upper tolerance intervals for age- and sex-matched controls with no family history of diabetes. The absence of CBMT in all of the ND twins and in four of the IDD twins with diabetes of 15-24 yr duration argues against the existence, in this group of subjects, of hereditary determinants of diabetic vascular disease linked to those governing susceptibility to develop diabetes. In addition, the absence of CBMT in four subjects with IDD of 15-24 yr duration is consistent with evidence from other studies indicating that diabetic microangiopathy is not an inevitable consequence of the diabetic milieu.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Diabetic retinopathy in identical twins.

The prevalence and features of diabetic retinopathy have been examined in 95 pairs of identical twins, 31 concordant for insulin-dependent diabetes (IDD), 27 discordant for IDD, and 37 concordant for non-insulin-dependent diabetes (NIDD). Optic fundi were examined after pupillary dilatation and retinopathy was classified as nil, background, or severe. In the NIDD twins, 35 of the 37 pairs were in the same category including all but one of the 15 pairs with the same duration of diabetes. However, in insulin-dependent diabetic pairs the situation was quite different; only 21 of 31 pairs were in the same retinopathy category, and of the 10 pairs of co-twins with the same duration of diabetes 5 pairs showed a striking difference for retinopathy. There was no significant difference in the prevalence of retinopathy in the concordant and discordant IDD twin pairs. Diabetic retinopathy was not observed in 32 unaffected co-twins of diabetics. We conclude that genetic factors may be important in the etiology of retinopathy in non-insulin-dependent diabetes but that nongenetic factors must be important in the pathogenesis of retinopathy in insulin-dependent diabetes.

Diabetic Retinopathy↗
PubMed1982

Opiate receptors and the metabolic response to intravenous glucose.

The role of opiate receptors in the metabolic response to an intravenous glucose load was determined in eight non-diabetic subjects (four of whom showed a positive chlorpropamide alcohol flush response and four who did not). Subjects were studied in a double blind randomised fashion receiving either a saline control or the specific opiate receptor antagonist, naloxone (0.4 mg/min), as an infusion for 5 minutes before and 20 minutes after an intravenous bolus of glucose (0.5 g/kg body weight). Naloxone decreased the early plasma glucose peak in all subjects by increasing the distribution volume but did not alter the fractional glucose clearance. Insulin and glucagon responses to glucose were not altered by naloxone. Naloxone delayed the normal post-glucose rise in the levels of the gluconeogenic precursors alanine, lactate, pyruvate and glycerol suggesting a delay in the usual inhibition in gluconeogenesis following a glucose load. There was no difference in the metabolic response between those subjects who were liable to chlorpropamide alcohol flushing and those who were not either with or without naloxone. We conclude that opiate receptors may influence distribution volume and gluconeogenesis but do not play a major role in either insulin or glucagon secretion or in glucose disposal following an intravenous glucose load.

Alanine↗
PubMed1981

Blood concentrations of acetaldehyde during chlorpropamide-alcohol flush.

To test the suggestion that chlorpropamide-alcohol flushing (CPAF) resembles the disulfiram effect and might be mediated by acetaldehyde, the initial metabolite of alcohol, blood concentrations of acetaldehyde were measured after a drink of alcohol in controls and diabetics positive and negative for CPAF. The CPAF-positive diabetics had significantly greater blood acetaldehyde concentrations after alcohol than the CPAF-negative diabetics both with a single dose of chlorpropamide and after two weeks' chlorpropamide treatment. Concentrations in the CPAF-positive group after chlorpropamide were also significantly greater than after a placebo tablet. There was also a clear separation in the increase in facial temperature after two weeks of chlorpropamide between the CPAF-positive and CPAF-negative groups (although there was some overlap after a single tablet). There was no difference in plasma chlorpropamide or alcohol concentrations between CPAF-positive and CPAF-negative diabetics. These findings show that CPAF is distinct from alcohol flushing and that the acetaldehyde concentration in the blood provides an objective measure of CPAF. The difference between flushing and non-flushing diabetics cannot be accounted for by differences in blood concentrations of chlorpropamide or alcohol.

Acetaldehyde↗
PubMed1981

Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics.

Forty-eight out of 53 non-insulin-dependent diabetic identical twin pairs were concordant for diabetes. In the five discordant pairs the diabetic twin had only recently been diagnosed. Oral glucose tolerance tests were carried out on the unaffected twins of the five pairs and on matched controls. Fasting concentrations of blood glucose (5.5 +/- 0.6 v 3.7 +/- 0.3 mmol/l; 99.1 +/- 10.8 v 66.6 +/- 5.4 mg/100 ml), haemoglobin A1 (mean 9.1%, range 8.8-9.2% v mean 7.9%, range 7.4-8.4%), lactate, alanine, and glycerol (0.090 +/- 0.017 v 0.045 +/- 0.008 mmol/l); and the lactate: pyruvate ratio were significantly higher in the twins than controls. After glucose challenge blood glucose, lactate, alanine, and glycerol concentrations and lactate: pyruvate ratio were increased in the twins. Insulin response was severely impaired, being almost absent in four of the five twins. The non-diabetic members of the discordant non-insulin-dependent diabetic pairs showed noticeable metabolic abnormalities which would later presumably deteriorate to frank diabetes. These findings, taken with the high concordance rate for non-insulin-dependent diabetic twins, suggest that non-insulin-dependent diabetes is predominantly, possibly entirely, inherited.

Adult↗