E.M. Kohner

Glucose intolerance in hypertensive patients treated with diuretics; a fourteen-year follow-up.

Abstract Glucose tolerance was studied prospectively in thirty-four hypertensive patients treated with oral thiazide diuretics without interruption for 14 years. Standard oral glucose tolerance tests were carried out before treatment and after 1, 6, and 14 years. Mean fasting blood glucose increased from 4·7±0·6 to 6·0±2·3 mmol/l and the 2 h value rose from 5·5+1·9 to 8·0±4·7 mmol/l after 14 years. Withdrawal of thiazide therapy for 7 months in ten of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2 h value.

DETERIORATION OF GLUCOSE TOLERANCE IN HYPERTENSIVE PATIENTS ON PROLONGED DIURETIC TREATMENT

Glucose tolerance was investigated in 51 hypertensive patients before and after 1 and 6 years of treatment with oral diuretics. Glucose tolerance was unchanged after 1 year but had deteriorated significantly after 6 years therapy. In a comparable group of 16 patients tested at similar intervals in which diuretic therapy had been given only for 3 of the 6 years there was no change in glucose tolerance, suggesting that prolonged oral treatment with thiazide diuretics is diabetogenic.

Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography.

Fluorescein angiography was used to study retinal microvascular perfusion in 20 patients undergoing coronary artery surgery. Colour retinal photographs and fluorescein angiograms were obtained preoperatively and at 5-14 days postoperatively. In 10 patients retinal fluorescein angiograms were also obtained intraoperatively during cardiopulmonary bypass, and all were found to have retinal microvascular occlusions after 40-160 min of extracorporeal circulation. 3 patients had in addition focal leakage of fluorescein, and 6 had foci of abnormal drainage of dye. These changes are consistent with retinal microembolism, and appeared to have resolved by the time of the postoperative study. No new pathological features appeared in the retina after surgery. Intraoperative fluorescein angiography of the retina may prove valuable for investigation of cerebrovascular microembolism in the territory of the internal carotid artery during cardiopulmonary bypass in man.

EFFECT OF DIURETIC THERAPY ON GLUCOSE TOLERANCE IN HYPERTENSIVE PATIENTS

Abstract Glucose-tolerance tests were done in 137 hypertensive patients before and after a year of therapy with one of four diuretics (clorexolone, ethacrynic acid, hydrochlorothiazide, or frusemide). The mean blood-sugar, serum-insulin, and serum-free-fatty-acid levels did not alter significantly during the year in the group as a whole or in the individual drug groups, except the frusemide group, where blood-sugar and serum-insulin both fell. Serum-potassium fell significantly during the year but was not related to changes in blood-sugar. 3 patients developed clinical diabetes. In 2 of these, diuretic therapy may have been of aetiological significance.

PLASMA-LIPIDS AND GLUCOSE/INSULIN RELATIONSHIP IN NON-INSULIN-REQUIRING DIABETICS WITH AND WITHOUT RETINOPATHY

Serum-lipid concentrations and their relationship to blood-glucose and serum-insulin were examined in non-insulin-requiring diabetics, 62 with and 45 without retinopathy. The age, sex-body-weight, and duration of known diabetes was comparable in the two groups. All were treated by diet only or diet and oral hypoglycaemic agents. Patients with retinopathy had higher fasting serumtriglyceride and serum--cholesterol levels than those without. Compared with a non-diabetic population, significantly more diabetics with retinopathy had raised derum-lipids. The lipid concentrations did not correlate with body-weight, serum-thyroid-stimulating-hormone levels, renal involvement, or fasting blood-sugar. While the blood-sugar concentrations were similiar in the two groups the absolute insulin increment and the relative insulin response to a 50 g. oral glucose load were significantly lower in those with retinopathy than in those without. The impairment of insulin response correlated significantly with the frequency of hyperlipidaemia. It is suggested that insulin deficiency with secondary hyperlipidaemia is characteristic of diabetic patients with retinopathy.

SEVERE RETINOPATHY AND MILD CARBOHYDRATE INTOLERANCE: POSSIBLE ROLE OF INSULIN DEFICIENCY AND ELEVATED CIRCULATING GROWTH HORMONE

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.

IMPORTANCE OF PITUITARY HORMONES IN ÆTIOLOGY 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.