Plasma proinsulin, C-peptide and insulin in diagnostic suppression tests for insulinomas.
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Biomedical subjects
Publications and source records attributed to R C Turner.
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1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3-month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine.
Diurnal plasma insulin and glucose concentrations were studied in six diabetic patients, each treated with five different insulin regimes. Subcutaneous soluble insulin was too slow and long acting for physiological replacement of the normal insulin response to meals, but the peak insulin levels were higher than the postprandial levels of normal subjects. Intramuscular insulin, though absorbed more quickly than subcutaneous insulin, was not clinically advantageous. Three rather than two injections of soluble insulin gave improved blood glucose control but two combined injections of short and medium acting insulins gave nearly as good results. A long acting insulin was needed to prevent raised plasma glucose levels overnight.
Plasma glucose, insulin and triglyceride changes in response to a standard breakfast and an oral glucose tolerance test have been studied in normal, obese and diabetic subjects. Mild diabetics with an abnormal oral glucose tolerance test may have normal or near-normal incremental glucose responses to a standard breakfast. A raised fasting plasma glucose is the predominant day-to-day glucose abnormality of mild diabetes. Diabetics have decreased insulin responses to oral glucose compared with the meal, and the deficient insulin response to glucose probably accounts for both the raised fasting plasma glucose levels and the abnormal oral GTT. The initial insulin response to a meal is normal in mild diabetics, and is probably stimulated by secretogogues other than glucose. The oral glucose tolerance test is apposite for the diagnosis of diabetes in view of the impaired insulin response to glucose, but accurate measurement of the basal plasma glucose may be of equal value. The diabetic and obese subjects had normal triglyceride levels, and there was no detectable impairment of disposal of the exogenous triglyceride following the breakfast.
The hormonal and metabolic response to the first feed of breast milk was studied in 12 infants at 4-6 hours of age. After the feed there was an increase in blood glucose concentration but no changes in the concentrations of lactate, pyruvate, alanine, or ketone bodies. The feed was followed by an increase in the concentrations of plasma insulin, growth hormone, gastrin, and enteroglucagon, but no change in levels of plasma glucagon or gastric inhibitory peptide. Several hormone systems are functionally active at birth and are stimulated by the first feed of milk.
Mothers who have had gestations diabetes (latent diabetics-LD), as well as those who have produced a large-for-dates baby (LFD) but who were not known to have been diabetic, have raised fasting plasma glucose levels, and these may induce fetal overnutrition. The increased birthweight of babies of obese mothers may also be due to their raised fasting plasma glucose levels. LD and LFD have normal or raised fasting plasma insulin levels even though they have both decreased insulin secretion to small changes in plasma glucose and normal or increased insulin sensitivity. The high fasting plasma glucose probably results from the decreased insulin-secretory response to glucose. Normal subjects have little day-to-day variation of their fasting plasma glucose, whereas subjects with a high fasting plasma glucose have less precise control. Although LD and LFD had abnormal insulin responses, they have normal plasma glucagon concentrations that do not correlate with glucose tolerance or insulin sensitivity. The reported abnormalities of glucagon in diabetes are probably a secondary, not a primary event.
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Hepatic glucose efflux is very sensitive to changes in plasma-insulin and it is postulated that this provides an important feedback control of insulin secretion. In diabetes this hepatic "insulin sensor" increases the basal plasma-glucose until the impaired beta cells are sufficiently stimulated to secrete normal basal insulin concentrations. Glucose regulation thus becomes of secondary importance to the maintenance of basal insulin secretion, which is teleologically needed for the "anabolic" requirements of cell growth. This hypothesis provides an explanation for the "normal" basal plasma-insulin concentrations found in diabetes in spite of impaired beta-cell function. This maintenance of basal insulin secretion accounts for the discrepancy between the marked hyperglycaemia and minimal ketosis of maturity onset diabetic patients.
Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes.
The decrease in insulin secretion in normal subjects in response to hypoglycemia provides a basis for suppression tests for diagnosing insulinomas. The majority of patients with insulinomas have hypoglycemia after an overnight fast, and inordinatley raised plasma insulin levels are diagnostic. A prolonged fast is a means of enhancing hypoglycemia. Fish insulin can be used to induce hypoglycemia over a short period, and provides a simple, dynamic suppression test which appears to give good diagnostic discrimination. A normal endogenous insulin response to fish-insulin-induced hypoglycemia, together with clinical assessment and a few simple investigations, virtually excludes the diseases which cause fasting hypoglycemia in adults.
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