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Biomedical subjects

R S Gray

Publications and source records attributed to R S Gray.

At least 55 records · Page 3Linked to original sources
PubMed1983

Non-insulin-treated ICA positive and negative diabetics are equally insulin resistant.

Insulin action was assessed in 5 cytoplasmic islet cell antibody (ICA) positive non-diabetics, 8 ICA positive (type I) non-insulin-treated diabetics, 7 ICA negative insulin-treated diabetics by measurement of steady state plasma glucose (SSPG) levels during a combined intravenous infusion of propranolol, adrenaline, glucose and insulin. SPPG values of ICA positive and negative non-diabetics were similar and their combined value (4.0 +/- 0.5 mmol/l) was significantly lower (p less than 0.01 and less than 0.01) than those (11.5 +/- 1.9 and 11.3 +/- 2.2 mmol/l) of ICA positive and negative diabetics, indicating that both groups of diabetics were similarly insulin resistant. Similar correlations were observed between SSPG and HbA1 levels when considering all ICA positive subjects (r = 0.89, p less than 0.001) and all ICA negative subjects (r = 0.73, p less than 0.01). Conventional insulin treatment (2.6 months) in 4 ICA positive diabetics improved insulin action in each case with a reduction in mean SSPG concentration from 14.0 +/- 2.3 to 8.5 +/- 3.4 mmol/l. Thus, ICA positive and negative diabetics, of equivalent degree of carbohydrate intolerance, are equally insulin resistant. Insulin treatment may improve, but appears not to normalise, insulin action in ICA positive (type I) diabetics.

Adult↗
PubMed1983

Humoral immunity in type 1 diabetes mellitus: a prospective study.

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.

Adult↗
PubMed1982

Glycosylated hemoglobin and its temporal relationship to plasma glucose in non-insulin dependent (type 2) diabetes mellitus.

Total glycosylated hemoglobin (HbAI) and random plasma glucose were measured at monthly intervals for 6 mo in 33 non-insulin dependent (type 2) diabetics. The mean HbAI and mean plasma glucose in individual patients over the 6 mo showed a close correlation (p less than 0.001). A significantly higher HbAI (p less than 0.001) for a given plasma glucose was seen in those patients receiving combined chlorpropamide and metformin therapy (n = 14) than in those receiving chlorpropamide alone (n = 19). For each patient correlation coefficients were calculated between plasma glucose and HbAI with time lags of 0.1 and 2 mo. The coefficients with no time lag showed a significant tendency to be positive (p less than 0.01) whereas those with time lags of 1 or 2 mo were not significant. A constant proportional variability of both HbAI and plasma glucose over time was demonstrated, the mean coefficient of variation for HbAI being 8.4 +/- 2.7% and for plasma glucose 22.3 +/- 9.7%. We conclude that HbAI provides an index of plasma glucose control, not during the preceding few months as was previously thought but, during the previous few weeks. In terms of variability from month to month a single HbAI determination was equivalent to approximately the mean of 3 single plasma glucose values.

Blood Glucose↗
PubMed1982

Alpha 2-macroglobulin and proliferative retinopathy in type 1 diabetes.

Serum alpha 2-macroglobulin (alpha 2m) and total glycosylated haemoglobin (HbA1) concentrations were measured in 110 insulin dependent Type 1 diabetics with minimal or no fundoscopic retinopathy, referred to as non-retinopaths, and in 52 proliferative retinopaths. Proteinuria was recorded in 8 (7%) non-retinopaths and 29 (56%) retinopaths and was accompanied by elevated alpha 2m concentrations in both groups of diabetics but only significantly so in the non-retinopaths. Diabetics without proteinuria showed a significant correlation between alpha 2m concentration and duration of diabetes, HbA1 and age (being higher at extremes of age). Alpha 2m concentrations were significantly higher in retinopaths than in non-retinopaths without proteinuria when allowance was made for the influence of age and duration of diabetes on alpha 2m. This difference may be attributed to the higher HbA, levels found in retinopaths than in non-retinopaths and was no longer evident when account was taken of the prevailing HbA1 concentration in individual patients.

Adult↗
PubMed1982

HLA antigens and other risk factors in the development of retinopathy in type 1 diabetes.

Factors possibly influencing the development of diabetic retinopathy were studied in 112 randomly selected type 1 diabetics having no or minimal retinopathy (group A) and in 82 type 1 diabetics with known severe diabetic retinopathy. The latter comprised those with severe background retinopathy (group B, n = 17) and those having proliferative retinopathy without (group C, n = 38) and with group D, n = 27) diabetic nephropathy. Nonretinopaths (group A) were of similar sex ratio, body weight, and age at diagnosis of diabetes but had been diabetic longer (p less than 0.001) and were thus older (p less than 0.001) than retinopaths (groups B-D). The distribution of HLA antigens of the A, B, and C loci was similar in nonretinopaths and retinopaths with the exception that HLA B7 showed a reduced (p less than 0.05) prevalence in the retinopaths (6% versus 17%) and was singularly underrepresented in group D, where no patients had this antigen. Mean postprandial plasma glucose and HbA1 concentrations were higher (p less than 0.01 and p less than 0.001) and cigarette smoking was more prevalent (p less than 0.01) in the retinopathy groups B-D than in group A. Systolic and diastolic blood pressures were similar in groups A-C, with higher (p less than 0.001) values only in group D. There was no association between insulin antibody binding in the serum or measurable plasma C-peptide immunoreactivity and retinopathy status. The risk of development of diabetic retinopathy in type 1 diabetes may be related to HLA-associated genetic factors and to cigarette smoking.

Adult↗
PubMed1982

In vivo deactivation of peripheral, hepatic, and pancreatic insulin action in man.

The in vivo deactivation of insulin action has been studied in 10 lean, nondiabetic subjects using a modification of the euglycemic glucose clamp technique. Following cessation of 40- and 120-mU/m2/min insulin infusions, the serum insulin levels fell to one-half their initial values (mean +/- SE) of 126 +/- 7 and 350 +/- 14 microunits/ml in 7 +/- 1 and 8 +/- 1 min, respectively. The mean incremental glucose disposal rates (IGDR) fell more slowly following discontinuation of the 40- and 120-mU/m2/min insulin infusions, so that the time required for the IGDRs to fall to one-half their initial values (D50 IGDR) were were 42 +/- 5 and 78 +/- 1 min, respectively. Mean hepatic glucose output was totally suppressed during the 40- and 120-mU/m2/min insulin infusions, remained completely suppressed following cessation of the infusions for 50 and 80 mi, and subsequently returned to basal levels. The times required for the HGOs to return to one-half their basal levels (R50 HGO) were 59 +/- 8 and 119 +/- 6 min, respectively. The times required for insulin action to decrease to one-half the initial values in the periphery (D50 IGDR) and in the liver (R50 HGO) were correlated with the preceding steady-state glucose disposal rates in individual subjects (r = 0.75, P less than 0.001 and r = 0.58, P less than 0.05, respectively). The suppression of endogenous insulin secretion by exogenous insulin infusions was also studied in 4 subjects during a total of 5 euglycemic glucose clamps; the mean basal serum C-peptide level was 0.67 +/- 0.24 pmol/ml before administration of the exogenous insulin, fell to 0.34 +/- 0.17 pmol/ml during the steady-state phase of the study, and remained suppressed throughout the duration of the deactivation phase of the glucose clamp. Residual pancreatic insulin secretory capacity was demonstrated by a rise in the serum C-peptide level to 1.77 +/- 0.50 pmol/ml at 120 min following a standardized meal given at the conclusion of the deactivation phase of the glucose clamp. These results demonstrate that the deactivation of insulin action in the periphery, liver, and pancreas lags behind the disappearance of insulin from the plasma. The mechanisms responsible for this lag in in vivo deactivation are not known for certain, but may include slower clearance of insulin form tissue compartments than form the plasma, the necessity for the target tissues to generate specific deactivation signals, or a slow rate of decay of saturable steps in the cellular activation process.

Adult↗
PubMed1982

Effect of a glucosidase inhibitor on the metabolic response of diabetic rats to a high carbohydrate diet, consisting of starch and sucrose, or glucose.

The metabolic consequences of the addition of Bay-g-5421 to a diet whose caloric value included 67% carbohydrate, comprising wheat starch (diet A), equal quantities of wheat starch and sucrose (diet B) or glucose (diet C) were studied in lean diabetic and non-diabetic rats. BAY-g-5421 led to a significant (30%) reduction in daily food intake of diabetic and non-diabetic rats fed diets A and B, respectively. In diabetic rats fed diets A and B with Bay-g-5421, daily urinary glucose was diminished ten-fold, while the post-prandial plasma glucose excursions were almost halved. Serum cholesterol, but not triglyceride concentrations, were reduced after five days, by the addition of BAY-g-5421 to diets A or B in non-diabetic rats, and in diabetic rats when the animals fed diets A and B were combined. BAY-g-5421 did not significantly after the food intake, urinary glucose excretion, post-prandial plasma glucose excursions nor serum lipids in diabetic and non-diabetic rats fed diet C. These findings illustrate the therapeutic potential of BAY-g-5421 as an adjunct to the dietary management of diabetes mellitus.

Acarbose↗
PubMed1981

Diabetic control in patients treated with once or twice-daily insulin injections, including a comparison of conventional beef and highly purified pork insulins.

Twenty patients were changed from a single daily injection of beef insulin (a mixture of soluble and protamine zinc insulin) to two daily injections (mixtures of soluble and isophane insulins). This was associated with a reduction, one month later, in the concentration of glycosylated haemoglobin (HbA1) and in the degree of late evening glycosuria. A reduction was shown 6 months later in antibody binding of beef and pork insulin by serum. Subsequent conversion to a twice daily regime of highly purified pork insulin was not associated with further improvement in diabetic control, but was associated after 1 month with a reduction in daily insulin dose, and after 5 months with a further reduction in antibody binding of beef and pork insulin by serum. Patients failing to show a C-peptide response to intravenous glucagon had a fall in HbA1 after conversion from a once to a twice daily insulin regime, which correlated inversely with insulin antibody binding estimated at the beginning of the study.

Adolescent↗
PubMed1981

The clinical features of diabetes with coexisting autoimmune thyroid disease.

A study was made of the clinical features of diabetics with coexisting Graves' disease (n = 117) or primary hypothyroidism (n = 98). Those with Graves' disease developed thyroid dysfunction and diabetes at an earlier age than patients with primary hypothyroidism. There was, however, no difference between the two groups in respect of sex ratio nor proportion of subjects requiring insulin treatment. In contrast to the general diabetic population, 87% of diabetics with thyroid disease were female, 56% required insulin treatment and of patients requiring insulin from diagnosis, the median age at diagnosis of diabetes was 36 years. A strong correlation was observed between age at diagnosis of diabetes and that of hyperthyroidism (r = 0.71, p less than 0.001) or hypothyroidism (r = 0.65, p less than 0.001). With increasing age at diagnosis of diabetes the interval between diagnosis of diabetes and thyroid disease diminished. The mean +/- SEM interval between diagnosis of diabetes and that of thyroid dysfunction was longer in hypothyroid (6.7 +/- 1.2 years) than in hyperthyroid diabetics (-2.4 +/- 1.2 years). Neither insulin-dependent nor non-insulin dependent diabetics with associated thyroid disease exhibited a significant seasonal variation in diagnosis or symptomatic onset of diabetes. It is conceivable that where diabetes accompanies autoimmune thyroid disease in the same patient, both conditions may share a common and coincident pathogenesis which is unrelated to acute environmental influences.

Adolescent↗
PubMed1981

Hypercholesterolemia in diabetics with clinically unrecognised primary thyroid failure.

Forty-nine diabetics with primary thyroid failure, as indicated by an elevated TSH concentration (TSH 38.0 +/- 5.4 mU/L, T4 63.0 +/- 4.0 nmol/L), without overt clinical evidence of hypothyroidism, had a higher (p less than 0.025) mean plasma cholesterol concentration (6.8 +/- 0.2 nmol/L vs 6.0 +/- 0.2 nmol/L) than 49 euthyroid diabetics (TSH 3.16 +/- 0.2 mU/L, T4 99.1 +/- 2.81 nmol/L) of equivalent age, sex, weight, diabetic treatment and duration of diabetes. No significant difference in triglyceride concentration was observed between the two groups of diabetics. Thyroxine replacement therapy in 18 diabetics with subnormal T4 concentrations was associated with a reduction (p less 0.01) in mean plasma cholesterol concentration to 5.8 +/- 0.3 nmol/L, but no significant change in triglyceride concentration. Clinically unrecognised thyroid failure may contribute to the high mortality from ischaemic heart disease observed in diabetics by virtue of accompanying, reversible hypercholesterolemia.

Cholesterol↗
PubMed1981

Relationship of glycosylated haemoglobin to C-peptide secretory status and antibody binding of insulin in insulin-dependent diabetes.

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.

Adolescent↗
PubMed1981

Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.

We have assessed the mechanisms involved in the pathogenesis of the insulin resistance associated with impaired glucose tolerance and Type II diabetes mellitus by exploring, by means of the euglycemic glucose-clamp technique, the in vivo dose-response relationship between serum insulin and the overall rate of glucose disposal in 14 control subjects; 8 subjects with impaired glucose tolerance, and 23 subjects with Type II diabetes. Each subject had at least three studies performed on separate days at insulin infusion rates of 40, 120, 240, 1,200, or 1,800 mU/M2 per min. In the subjects with impaired glucose tolerance, the dose-response curve was shifted to the right (half-maximally effective insulin level 240 vs. 135 microunits/ml for controls), but the maximal rate of glucose disposal remained normal. In patients with Type II diabetes mellitus, the dose-response curve was also shifted to the right, but in addition, there was a posal. This pattern was seen both in the 13 nonobese and the 10 obese diabetic subjects. Among these patients, an inverse linear relationship exists (r = -0.72) so that the higher the fasting glucose level, the lower the maximal glucose disposal rate. Basal rates of hepatic glucose output were 74 +/- 4, 82 +/- 7, 139 +/- 24, and 125 +/- 16 mg/M2 per min for the control subjects, subjects with impaired glucose tolerance, nonobese Type II diabetic subjects, and obese Type II diabetic subjects, respectively. Higher serum insulin levels were required to suppress hepatic glucose output in the subjects with impaired glucose tolerance and Type II diabetics, compared with controls, but hepatic glucose output could be totally suppressed in each study group. We conclude that the mechanisms of insulin resistance in patients with impaired glucose tolerance and in patients with Type II noninsulin-dependent diabetes are complex, and result from heterogeneous causes. (a) In the patients with the mildest disorders of carbohydrate homeostasis (patients with impaired glucose tolerance) the insulin resistance can be accounted for solely on the basis of decreased insulin receptors. (b) In patients with fasting hyperglycemia, insulin resistance is due to both decreased insulin receptors and postreceptor defect in the glucose mechanisms. (c) As the hyperglycemia worsens, the postreceptor defect in peripheral glucose disposal emerges and progressively increases. And (d) no postreceptor defect was detected in any of the patient groups when insulin's ability to suppress hepatic glucose output was measured.

Adult↗
PubMed1980

Serum alpha 2-macroglobulin levels in diabetes.

Serum alpha 2-macroglobulin levels have been determined in diabetic patients by quantitative radial immunodiffusion and compared with those observed in age- and sex-matched controls. In addition, the results in diabetics have been analysed with respect to such variables as the age and sex of the patient, the duration of disease, treatment, control, and the occurrence of retinopathy or nephropathy. The alpha 2-macroglobulin levels in diabetic patients were found to be significantly higher than in age- and sex-matched controls, thus confirming previous observations. However, these differences were most apparent in the more extreme age groups. Multiple regression analysis also revealed that the only variables contributing significantly to the regression apart from age and sex were control and retinopathy.

Adolescent↗
PubMed1980

Prevalence of subclinical thyroid failure in insulin-dependent diabetes.

A study was made of the distribution of primary thyroid failure, indicated by a raised serum TSH concentration, in 605 (294 males and 311 females) insulin-dependent (type I) diabetics, aged 21-84 yr, not previously suspected of having thyroid disease. The prevalence of a raised serum TSH concentration in females of all ages (17%) was significantly greater (P less than 0.0005) than that in males (6.1%) and increased with increasing age at onset of diabetes (P less than 0.05) and age at time of study (P less than 0.001) in females but not in males. There was no significant difference in the duration of diabetes when comparing patients with normal and raised serum TSH concentrations. The prevalence of a raised TSH concentration in late-onset insulin-dependent diabetics was no greater in patients requiring insulin within 3 months of diagnosis of diabetes than in those exhibiting secondary sulfonylurea failure, who required insulin more than 3 months after diagnosis. In type I diabetes, the prevalence of subclinical primary thyroid failure is considerably greater than has previously been suspected, with female late-onset insulin-dependent diabetics being at the greatest risk.

Adult↗
PubMed1980

Glucose and insulin responses to oral glucose in overt non-insulin-dependent diabetics with and without the islet cell antibody.

Plasma insulin, glucose, and insulin/glucose responses to a 50-g oral glucose tolerance test (OGTT) were compared in 14 islet cell antibody (ICAb) positive non-insulin-dependent diabetics (NIDDM), 14 matched ICAb negative NIDDM, and 14 ICAb negative nondiabetic controls. Both groups of NIDDM exhibited marked carbohydrate intolerance with insulinopenia. Despite having significantly higher plasma glucose concentrations during the study, the ICAb positive NIDDM had significantly lower insulin levels, and thus lower insulin/glucose ratios, than the ICAb negative NIDDM both in the fasting state and in response to the OGTT. Similarily, ICAb positive NIDDM had higher integrated glucose responses (delta G), lower integrated insulin responses (delta I), and lower delta I/delta G values than ICAb negative NIDDM. Three ICAb negative and seven ICAb positive NIDDM subsequently required insulin treatment. These findings show that ICAb positive NIDDM suffer from a greater disturbance of B-cell function than do matched ICAb negative NIDDM.

Adult↗
PubMed1979

Obstetric history of diabetics: its relevance to the aetiology of diabetes.

The birth weights of infants born to patients with insulin-dependent diabetes (IDD) and insulin-independent diabetes (IID) before the disease was diagnosed were compared. An appreciable excess of infants above the 90th centile for weight was found, the proportions being 27% of infants born to mothers with IDD and 30% of those born to mothers with IID. These findings suggest that many patients with both types of diabetes have a prolonged period of metabolic abnormality before overt symptoms of diabetes arise and that the apparent acute onset of the disease in patients who are insulin dependent is illusory.

Adult↗