8 patients with severe progressive diabetic retinopathy despite continued mild carbohydrate intolerance on diet therapy alone were studied; each patient had presented initially with visual deterioration and none had experienced hyperglycaemic symptoms. By comparison with 8 carefully matched diet-treated diabetics without retinopathy, the retinopathy patients had increased circulating growth hormone levels and relative insulin deficiency. Several other factors of possible importance in the aetiology of microangiopathy, including circulating intermediary metabolites, platelet aggregation, blood viscosity, and lipids were similar in the two groups. It is possible that hypoinsulinaemia together with growth hormone excess may contribute to the development of eye disease in these patients with otherwise mild diabetes.

Adult↗

PubMed1985

Loss of diabetic control and increased protein glycosylation following minor intercurrent infections.

To investigate the effect of intercurrent infections, 30 insulin-dependent diabetics and 12 normal subjects were followed prospectively during one winter, with short-term periods of control being assessed by the degree of glycosylation of plasma proteins. Eight diabetics and 7 normal subjects developed an intercurrent infection. During stable control, the diabetics had a mean +/- 1 S.D. glycosylation of 0.90 +/- 0.06 nmol HMF/mg protein/2 hour incubation, compared with the normal subjects of 0.63 +/- 0.04 nmol HMF/mg protein/2 hour. Following infection, there was no increase in glycosylated plasma protein in the normal subjects, but the diabetics increased at 3 and 6 days to 1.07 +/- 0.17 and 1.12 +/- 0.17 nmol HMF/mg protein/2 hour respectively (p less than 0.05 and p less than 0.01). This was similar to levels (1.09 +/- 0.20 nmol HMF/mg protein/2 hour) found in 12 diabetic subjects admitted to hospital because of marked loss of control with ketonuria. The marked protein glycosylation effect of temporary loss of glucose control following 'minor' intercurrent infections suggests that more attention should be paid to diabetic control during brief illnesses.

Adult↗

PubMed1979

Acromegaly and narcolepsy.

Explore the source record for details and available documents.

Acromegaly↗

PubMed1979

Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue.

A new long-acting octapeptide analogue of somatostatin, Des AA1,2,4,5,12,13 D Try8 somatostatin, has been tested in 8 patients with pancreatic endocrine tumours. The analogue given subcutaneously suppressed the tumour-derived hormones in patients with insulinomas, glucagonomas, and gastrinomas for up to 24 h. The prolonged action appeared to be the result of slow release from the injection site. No side-effects were observed. Studies of long-term administration of this new peptide are now warranted.

Adult↗

PubMed1979

Hypotrypsinaemia in diabetes mellitus.

Plasma trypsin concentrations were measured in 403 fasting diabetics and 106 healthy controls. Basal trypsin concentrations in the normal subjects were 88 +/- 6 ng/ml (mean +/- S.E.M.). Mean plasma trypsin concentrations in diabetics treated with diet alone (n = 74) were 45 +/- 2 ng/ml, while in a group of young (less than 35 years, n = 88) insulin-dependent diabetics, they were very low at 29 +/- 2 ng/ml and these levels were inversely related to insulin dosage. The findings may help in the understanding of the pathophysiological changes in the exocrine pancreas in the diabetic state and may also shed some light on the physiological interrelationship between the endocrine and exocrine pancreas.

Adolescent↗

PubMed1979

Acromegaly and narcolepsy.

7 of 372 acromegalic patients had troublesome episodes of paroxysmal daytime sleep. Although 3 patients had complete remission of symptoms within a few days of pituitary implantation of isotopes, the cause of this increased frequency of narcolepsy among acromegalic patients is not known.

Acromegaly↗

PubMed1979

Autoimmunity in diabetics induced by hormonal contaminants of insulin.

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immunocytochemical testing showed that antibody-positive diabetic plasma reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity and naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

Adolescent↗

PubMed1979

Cushing's syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy.

Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.

17-Ketosteroids↗

PubMed1978

Importance of pituitary hormones in aetiology of diabetic ketoacidosis.

The role of pituitary hormones in the aetiology of diabetic ketoacidosis was examined by withdrawing insulin from five pituitary-ablated diabetics for a 12-hour period. The rise in blood glucose and ketone-body concentrations was markedly retarded in these patients when compared with five matched juvenile-type diabetic controls with normal pituitary function. When cortisol replacement in the pituitary-ablated patients was increased to reproduce the high plasma concentrations found in severe ketoacidosis, blood ketones and glucose were increased but were still significantly lower than in the control diabetics. It is concluded that pituitary hormones may be important in the development of diabetic ketoacidosis.

Adult↗

PubMed1978

Hormonal regulation of ketone-body metabolism in man.

The main hormones involved in ketone-body metabolism are the anabolic hormone insulin and the primarily catabolic hormones, glucagon, cortisol, catecholamines and growth hormone. These hormones may regulate ketone-body metabolism at three sites: adipose tissue, by regulating fatty acid supply to the liver; the liver itself, by determining the relative activities of the re-esterification and fatty acid oxidation pathways; and the periphery, by influencing the rate of extrahepatic utilization of ketone bodies. The first two are quantitatively the most important. Insulin acts on all three regulatory sites. In adipose tissue lipolysis is inhibited and re-esterification enhanced with consequent decrease of fatty acid release. Both these processes are extremely insulin-sensitive. In the liver insulin increases fatty acid synthesis and esterification. At the same time malonyl-CoA formation is increased, which inhibits the acylcarnitine transferase system and thus decreases the transport of fatty acids into mitochondria and hence fatty acid oxidation and ketogenesis. Insulin also has a small stimulatory effect on extrahepatic ketone-body utilization. The effects of glucagon depend on whether insulin is present. In normal man glucagon stimulates insulin secretion and the predominant effect is that of insulin, i.e. decreased ketogenesis. In insulin deficiency glucagon has a mild stimulatory effect on lipolysis, increasing fatty acid supply to the liver. The main effects of glucagon are, however, on the liver. It activates the carnitine acyltransferase system through inhibition of malonyl-CoA synthesis. Fatty acid oxidation is increased and ketogenesis enhanced. The overall effect on the liver depends on the relative amounts of insulin and glucagon present. Studies with somatostatin show that glucagon can increase ketogenesis acutely when insulin secretion is inhibited in normal man, but the effects are short-lived. Cortisol has similar effects to glucagon. In the presence of insulin there is a small increase in fatty acid mobilization from adipose tissue, secondary to impaired glucose entry, and perhaps a small effect on lipolysis itself. This fatty acid is, however, directed to triacylglycerol in the liver. In insulin deficiency, again demonstrated by somatostatin infusion, the incoming fatty acidstone-body formation. The mechanism remains obscure. Catecholamines, in contrast, have their most potent effects on adipose tissue, stimulating lipolysis and fatty acid release even in the presence of insulin. They thus act mainly by enhancing precursor supply and have only minor effects on liver and no effect on peripheral utilization. Growth hormone, like glucagon, has little effect in the presence of insulin, but can enhance ketogenesis in insulin deficiency, although again the mechanism is unknown. Thus in normally fed man the effects of insulin will be overriding and little ketogenesis occurs because of limited fatty acid availability in the liver...

Adipose Tissue↗

PubMed1977

Is hyperviscosity a treatable component of diabetic microcirculatory disease?

Blood viscosity at low shear-rates was significantly higher in sixty-four patients with longstanding diabetes than in sixty-one matched non-diabetic controls. This increase was most striking in patients with either proliferative retinopathy or nephropathy, although it was present to a lesser extent in diabetic patients with evidence of myocardial or peripheral ischaemia. Erythrocyte deformability was lower in the fourteen diabetic patients with the most extensive microangiopathy than in twenty-two diabetics with slight or no complications or in controls. Hyperviscosity and reduced erythrocyte deformability may well be important and potentially treatable factors in the aetiology or progression of microcirculatory disease is diabetes.

Adult↗

PubMed1977

Ketoacidosis in pancreatectomized man.

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.

Acetoacetates↗

PubMed1977

Mechanism of pancreatic polypeptide release in man.

Pancreatic polypeptide (P.P.) is a potent hormonal peptide which has been isolated from the pancreas. Its role in human physiology and pathology is not yet established. After a standard hospital lunch the plasma concentration of P.P. showed a rapid and identical rise in 10 healthy controls, 11 duodenal-ulcer patients, and 6 post-vagotomy patients but remained undetectable in 4 totally pancreatectomised subjects. In contrast plasma-P.P. was unaffected by intravenous administration of glucose, aminoacids, or fat. However, during intravenous infusion of caerulein, a cholecystokinin analogue, P.P. rose by nearly five-fold, and an even greater rise was seen after intravenous injection of Boots secretin. In 19 duodenal-ulcer patients insulin hypoglycaemia produced a rapid rise in plasma-P.P. but this did not occur in any of the 17 patients studied after a truncal vagotomy. Thus P.P. is released by oral but not intravenous nutriments and the existence of an entero-P.P. axis is postulated. One component of this axis may be the vagal innervation but the normal postprandial rise seen after vagotomy suggests that other control mechanisms, such as the intestinal hormones, are more important.

Adult↗

PubMed1977

Persistent metabolic abnormalities in diabetes in the absence of glucagon.

In order to investigate the contribution of glucagon to the abnormalities of carbohydrate and lipid metabolism in diabetes, hormones and metabolites were measured in response to IV arginine in 5 juvenile onset (control) diabetics and 5 totally pancreatectomised subjects. In the basal state, both control diabetics and pancreatectomised patients showed abnormally elevated levels of plasma glucose, blood 3-hydroxybutyrate, glycerol and plasma free fatty acids (NEFA), although no glucagon was detectable in the plasma of the pancreatectomised subjects. Blood concentrations of the gluconeogenic precursors alanine and glycerol were higher pancreatectomised patients than in the diabetics. Following infusion of arginine, the rise in glucagon observed in the diabetics was accompanied by a significant increase in plasma glucose and a fall in blood lactate when compared to the pancreatectomised subjects. In spite of the rise in glucagon in the control diabetics, no sigficant change was found in the concentrations of ketone bodies, glycerol or NEFA. Thus glucagon does not seem to have a primary role in producing the metabolic abnormalities of diabetes.

Adult↗