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Biomedical subjects

D A Pyke

Publications and source records attributed to D A Pyke.

At least 91 records · Page 5Linked to original sources
PubMed1979

Diabetes: the genetic connections.

Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas--in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.

Chlorpropamide↗
PubMed1978

Chlorpropamide-alcohol flushing: a dominantly inherited trait associated with diabetes.

A simple test was devised to identify people susceptible to chlorpropamide-alcohol flushing (CPAF). Subjects were given a placebo tablet, followed by sherry 12 and 36 hours later. They then received a chlorpropamide tablet and sherry again after 12 and 36 hours. This single-dose challenge test was given to non-insulin-dependent diabetics, insulin-dependent diabetics, and normal subjects. CPAF was common in the non-insulin-dependent diabetics but rare in the other groups. When the test was used in identical twins and families of affected subjects CPAF appeared to be a dominantly inherited trait. We conclude that facial flushing after alcohol in people taking chlorpropamide is related to non-insulin-dependent diabetes, especially when there is a strong family history of diabetes, but not to insulin-dependent diabetes. It is a dominantly inherited trait.

Adolescent↗
PubMed1978

Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.

The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome.

Adolescent↗
PubMed1978

Islet function in diabetics with persistent islet cell antibodies.

Seventeen (14 per cent) of 121 long-term insulin-treated diabetics were found to be positive for islet cell antibodies. Their duration of diabetes ranged between five and 45 years. Thirteen of these 17 patients were tested for the persistence of islet cell function by measurement of C-peptide. There was no detectable C-peptide in 12 patients, confirming that islet function had ceased. The significance of the persistence of islet cell antibodies in diabetes is unknown.

Adolescent↗
PubMed1976

Islet-cell antibodies in diabetes mellitus.

Islet-cell antibodies (I.C.A.) were found in 38% (319/829) of insulin-dependent diabetic patients, in 5% (6/112) of insulin-independent diabetics, and in 1.7% (3/177) of non-diabetic subjects. In the insulin-dependent group I.C.A. were found in 85% of patients immediately after the onset of symptoms and they became less common as the duration of disease increased I.C.A. were equally common in both sexes and the decline in their prevalence was independent of age. The antibodies were directed against cytoplasmic components of islet cells but not against insulin itself. The appearance of I.C.A. probably follows cell damage occurring before the onset of symptoms. By contrast, thyroid and gastric autoantibodies were more common in older patients and females. There was no correlation between the presence of these antibodies and I.C.A. in patients with either diabetes of recent onset or longstanding disease.

Adolescent↗
PubMed1976

Islet-cell, thyroid, and gastric autoantibodies in diabetic identical twins.

Sera from 54 pairs of identical twins, 29 discordant and 25 concordant for insulin-dependent diabetes, and 11 pairs of concordant non-insulin dependent identical twins were examined for pancreatic islet-cell antibodies (ICAs). ICAs were found in 10 of the 29 diabetic discordant and eight of the 50 concordant twins (difference not significant P greater than 0-05). Six out of nine twins tested within one year of onset of diabetes were positive, whereas nine out of 29 tested after one to 10 years and three out of 41 tested after 10 years were positive. Only one of the 22 non-insulin-dependent twins had ICAs. Repeat ICA testing in five pair of insulin-dependent twins and in the siblings of one pair showed that ICAs may be present in people with normal glucose tolerance' may precede clinical diabetes by several years; and may decline in titre or disappear with increasing duration of disease. Thyroid or gastric autoantibodies, or both, were found in 36 out of 108 insulin-dependent twins and three out of 22 non-insulin dependent twins (difference not significant P less than 0-05). Only four twins had both ICAs and thyrogastric antibodies. There were no significant associations between autoantibodies and HLA histocompatibility types. As ICAs are more common in the diabetic than the non-diabetic twins of the discordant pairs they must be associated with juvenile onset diabetes. ICAs may appear some years before the onset of diabetes, but their prevalence declines with increasing duration of diabetes. The factors determining the production of ICA differ from those for thyroid and gastric autoantibodies.

Adolescent↗
PubMed1975

Hemoglobin components in diabetes mellitus: studies in identical twins.

The minor components of hemoglobin which are increased in subjects with diabetes mellitus, hemoglobin Ala-c, were measured in identical twins concordant and discordant for diabetes to determine whether the observed increases represent a genetically determined abnormality. The mean values for the proportion of hemoglobins Ala-c in discordant twins differed markedly in the two members of the pair: 10.4 +/- 0.74 per cent for the diabetic twins and 6.85 +/- 0.33 for the nondiabetic twins (t = 4.3811, P less than 0.005). In concordant twins with juvenile onset diabetes, the mean proportion of Hb Ala-c was 11.4 per cent, and no marked differences were observed between members of twin pairs. Four pairs of identical twins concordant for maturity onset diabetes showed lower mean values for Hb Ala-c but did not show marked intra-pair differences. Thus, the abnormal proportions of hemoglobins Ala-c found in the presence of overt diabetes mellitus appear to be a manifestation of a metabolic abnormality of diabetes.

Adolescent↗
PubMed1975

Viruses and the aetiology of diabetes: a study in identical twins.

Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins.

Adolescent↗
PubMed1975

Histocompatibility antigens in diabetic identical twins.

84 pairs of diabetic identical twins were HL-A typed. 22 were maturity-onset diabetics (diagnosed after age 45); all were concordant and they showed no disturbance of HL-A frequencies. Of the remaining 62 pairs of juvenile-onset diabetics, 31 were discordant (only one twin diabetic) and 31 concordant (both twins diabetic). The frequency of the W15 antigen was equally increased in both the concordant and discordant pairs; HL-A8 was increased only in the concordant pairs. The fact that W15 is increased in the discordant pairs shows that there is genetic predisposition to diabetes even in these twins; the fact that HL-A8 is not increased suggests that different alleles may underlie susceptibility in the two groups of twins.

Alleles↗
PubMed1974

Treatment of diabetic coma with continuous low-dose infusion of insulin.

Thirty-eight patients in diabetic coma from four different centres were treated with a continuous low-dose intravenous infusion of insulin at an average dose of 7.2 IU/hr. All patients recovered rapidly except for one profoundly shocked patient who died. The mean fall in plasma glucose was 58% four hours after the start of insulin. Blood ketone bodies and plasma free fatty acids showed a similar response. There was no significant difference in plasma glucose response according to severity of acidosis or previous treatment with insulin. Hypokalaemia was uncommon. In the treatment of diabetic coma this technique has proved simple, safe, and effective.

Adolescent↗