Julius Sagel

Platelet adhesion and aggregation in diabetes mellitus

Platelets from diabetic patients show both increased platelet adhesiveness and sensitivity to aggregating agents. Plasma levels of the platelet-active von Willebrand Factor and the closely related factor-VIII antigen are significantly elevated, while factor VIII procoagulant activity is not. This may reflect either intravascular coagulation or disproportionate production or degradation. Plasma factors that enhance ADP-induced platelet aggregation are found in 50% of unselected male diabetics. Activity is clearly demonstrated only when plasma is added immediately prior to adding subthreshold doses of ADP to platelet-rich plasma obtained from control subjects. Systematic investigations of the molecular nature of such factors and their interactions with platelets are in progress. In platelets obtained from diabetic subjects, we have previously found increased sensitivity to the aggregating effects of arachidonic acid, and increased synthesis of immunoreactive prostaglandin E-like material. More recent studies have shown that platelets obtained from diabetic subjects are less sensitive to the antiaggregatory effects of imidazole, a thromboxane synthetase inhibitor. These observations suggest that increased synthesis of the labile aggregating substance thromboxane A2 also occurs in platelets obtained from diabetics. Collectively, these platelet and plasma abnormalities may contribute to accelerated vascular disease of diabetes. Prospective studies using antiplatelet agents are presently underway or in the planning stages in diabetics to explore their potential beneficial effects.

Pituitary Responsiveness to Luteinizing Hormone-releasing Hormone in Insulin-dependent Diabetes Mellitus

Impaired fertility and menstrual disturbances are common in diabetes mellitus. In order to study the effect of diabetes on gonadotropin secretion by the pituitary gland, twenty premenopausal diabetic females and seven diabetic males were investigated using luteinizing hormone-releasing hormone (LH-RH). Although the gonadotropes responded to LH-RH in the patients studied, a relative impairment was apparent when compared to normal matched control groups. In the female diabetic patients there was no difference in the gonadotropin responses obtained in those with oligomenorrhea or amenorrhea when compared to those with normal menses. A significant inverse relationship was found between the maximum rise in plasma luteinizing hormone and the fasting plasma glucose. These findings suggest an influence of glucose metabolism on pituitary gonadotropin function. However, the reduced gonadotropin response is unlikely to be the sole cause of the abnormal gynecologic function.

Pituitary-gonadal function in chronic renal failure: The effect of luteinizing hormone-releasing hormone and the influence of dialysis

Sixteen adult male patients with chronic renal failure undergoing either chronic intermittent hemodialysis (HD) or chronic intermittent peritoneal dialysis (PD) were studied both before and immediately after dialysis. The gonadotropin responses to luteinizing hormone-releasing hormone (LH-RH) was determined, revealing an excessive luteinizing hormone (LH) response with a delayed return to normal in both dialysis groups. No significant alteration in follicle-stimulating hormone (FSH) kinetics was observed. There was no significant difference in the mean gonadotropin responses to LH-RH between the HD and PD groups, and dialysis had no effect on either mean LH or FSH responses. The chronic renal failure patients with testicular atrophy had an excessive FSH response to LH-RH when compared to those patients without testosterone was significantly lower than normal. Chronic renal failure effects testicular function and testicular atrophy is associated with seminiferous tubular destruction and an excessive FSH response. Poor renal clearance may play a role in the abnormal LH response observed.

Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy.

Basal LH, FSH, 17ß‐oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty‐four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration.

The role of luteinizing hormone-releasing hormone in the diagnosis of constitutional delayed puberty

The presumptive diagnosis of constitutional delayed adolescence is difficult to substantiate. Clinical examination and routine biochemical testing are not sufficient to exclude isolated gonadotrophin deficiency. Seven males are reported who presented with delayed puberty. These patients were given 100 μg luteinizing hormone-releasing hormone (LH-RH) intravenously, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses were measured. Three of four males who were completely prepubertal (Stage 1) had a normal adult male response. These three patients have progressed further into puberty several months after this diagnostic test. The fourth patient in stage 1 puberty had a prepubertal LH response. A year later the response became adult in type, and 3 months thereafter stage 2 puberty was evident. The LH response to LH-RH thus appears to have some prognostic value in the assessment of males presenting with delayed puberty.