Reduced diurnal variation of blood pressure in non-insulin-dependent diabetic patients with microalbuminuria.

In essential hypertension reduced diurnal blood pressure (BP) variation is associated with an increased prevalence of target organ damage. We have examined diurnal BP variation in 25 microalbuminuric (MA) and 19 normoalbuminuric (NMA) patients with non-insulin-dependent diabetes and related albumin excretion rate (AER) to diurnal BP variation in the microalbuminuric group. There were no significant differences in age, body mass index (BMI), renal function, diabetic control, clinic or daytime ambulatory BP between the groups. Night-time SBP was higher (MA 145 mm Hg (137-153), NMA 132 mm Hg (125-139); P = 0.019) in the microalbuminuric group while the diurnal variation as assessed by the day-night dip in BP was significantly reduced in the microalbuminuric group (systolic: (mean (95% confidence intervals) MA 4.7% (1.7-7.7), NMA 12.8% (9.5-16.0), p = 0.001; diastolic: MA 6.5% (3.0-10.0), NMA 14.5% (10.2-18.8), P = 0.007). Within the microalbuminuric group, the systolic dip in BP was inversely related to the AER (r = -0.48, P = 0.015). Reduced diurnal BP variation and high night-time BP may contribute to target organ damage in diabetes.

Lithium inhibits the action of fludrocortisone on the kidney.

A patient with autoimmune Addison's disease treated with hydrocortisone and fludrocortisone became mineralocorticoid-deficient whilst taking lithium carbonate for a bipolar illness. During an in-patient metabolic balance study she required 1.0 mg fludrocortisone daily and dietary sodium supplementation to make plasma renin activity and serum potassium normal, and to abolish postural hypotension. We present data to suggest that lithium carbonate inhibits the action of fludrocortisone on the distal renal tubule.

Relation between the urinary cortisol:creatinine ratio and hypoglycaemia.

The relationships between (i) urinary free cortisol and urinary creatinine concentrations and (ii) the urinary cortisol/creatinine ratio (UCCR) and various glycaemic levels were studied in three groups--normal, insulin-stressed and insulin-treated diabetic subjects. In non-hypoglycaemic subjects, there was a significant positive linear correlationship between urinary free cortisol and urinary creatinine excretion, but in the presence of hypoglycaemia, this relationship was lost. The highest mean urinary cortisol/creatinine ratio (UCCR) was found in subjects after an insulin tolerance test (ITT). The mean post-ITT UCCR was significantly greater than the mean for the pre-ITT samples. There was a significant negative correlation between capillary blood glucose levels at 03.00 and the UCCR of the overnight urine samples of insulin-treated diabetic subjects. We conclude that there is a definite increase in the UCCR after hypoglycaemia in subjects with adequate adrenocortical response to hypoglycaemia and that determination of the UCCR could be helpful in the detection of nocturnal hypoglycaemia.

Plasma insulin, C-peptide and glucagon concentrations in patients with insulin-independent diabetes treated with chlorpropamide.

The effect of chlorpropamide on blood glucose, plasma insulin, C-peptide and glucagon levels was studied in 21 patients with insulin-independent diabetes. A metabolic profile of these parameters was obtained throughout a normal day in seven newly-diagnosed diabetic patients (group A), before, and 3 to 8 weeks after treatment with chlorpropamide was established, and in 14 patients on longterm therapy with chlorpropamide (seven taking less than 250 mg. chlorpropamide--group B; seven taking 250-375 mg.--group C), before, and two weeks after withdrawal of the drug. In group A, correction of hyperglycaemia was not accompanied by a significant rise in the mean plasma insulin and C-peptide levels but a fall was observed in the mean plasma pancreatic glucagon concentrations. In groups B and C, withdrawal of chlorpropamide produced no significant change in plasma insulin, C-peptide or glucagon levels, although the mean blood glucose increased. This study supports an extrapancreatic effect of chlorpropamide to lower blood glucose after prolonged administration. In the short-term, it is possible that chlorpropamide may influence the secretion of pancreatic glucagon.

Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics.

Glycosylated haemoglobin (HbA1) was measured in seven insulin-dependent diabetic patients before, during, and after a seven-day period of monitored poor control. There was considerable individual variation in the pattern and degree of change in HbA1 concentration induced by poor control and the time when it occurred. Greater increases in HbA1 were seen during the period of metabolic derangement than in the subsequent two months. More information is required before HbA1 estimations are widely used clinically to monitor control in individual diabetics.

Hypothalmic-pituitary adrenal responsiveness to dexamethasone-insulin tolerance test in acromegalic patients before and during treatment with bromocriptine.

Insulin tolerance tests were carried out in 10 acromegalic patients after 1 mg dexamethasone had been given the previous evening (DEX-ITT). Nine patients showed a rise in plasma 11-OHCS and four patients showed a rise in plasma growth hormone (GH) levels. These responses were unaltered after treatment with bromocriptine 10 mg daily for two months. Basal plasma GH levels fell in 6 of the patients and the mean plasma GH levels of the 10 patients during an oral glucose tolerance test (OGTT) fell from 63.2 +/- 25.5 ng/ml before treatment to 53.0 +/- 27.1 ng/ml (mean +/- sem; p less than 0.05). These data fail to confirm a previous report of abnormal hypothalmic-pituitary-adrenal suppressibility during a DEX-ITT in acromegalic patients. They also indicate that bromcriptine does not alter the responses of plasma 11-OHCS and plasma GH to the DEX-ITT despite lowering plasma GH levels.

Effect of propranolol on glucose tolerance in hyperthyroidism.

Glucose tolerance tests were performed on six hyperthyroid patients in the morning and afternoon before, and at the end of treatment with propranolol for 2 weeks. All six subjects showed normal glucose tolerance with a normal diurnal rhythm before treatment and this remained normal in five during treatment with propranolol, while one patient developed abnormal glucose tolerance and the diurnal variation was abolished. No change in insulin levels was noted in any of the patients either before or during treatment. Propranolol may cause deterioration in glucose tolerance in some subjects with hyperthyroidism and this possibility should not be overlooked.

Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.