Carotid atherosclerosis in type 2 diabetes mellitus: potential role of endothelin-1, lipoperoxides, and prostacyclin.

Factors were studied that may initiate macroangiopathy or enhance or aggravate its pathogenesis in patients with type 2 diabetes mellitus. A total of 151 diabetics were compared with healthy controls (n=50); all patients and subjects were normotensive and without renal failure. Plasma endothelin-1 and free radical levels were measured. In addition, plasma prostacyclin levels were assessed by assaying its stable, spontaneous, breakdown product 6-keto-prostaglandin-F1a. Diabetics were divided into three groups: those with clinically evident macroangiopathy and those with early or without atherosclerosis (as determined by the carotid intima-media thickness. Plasma endothelin-1 levels were increased in all diabetics with atherosclerosis. Plasma free radical levels were increased in diabetics with macroangiopathy when compared with control subjects. The plasma levels of 6-keto-prostaglandin-F1a were slightly, but significantly, decreased in the diabetics with macroangiopathy when compared with control subjects. The carotid intima-media thickness was significantly greater in diabetics without macroangiopathy when compared with the controls. Furthermore, the intima-media thickness increased significantly in this group of diabetics but not in the controls over a 30-month follow-up period. Several factors may contribute to atherogenesis in diabetics. These include increased plasma endothelin-1 and free radical levels as well as a deficiency of prostacyclin. These factors may become targets for intervention as well as markers of disease progression.

Treatment of renal osteodystrophy with 1,25-dihydroxycholecalciferol.

Nine patients with renal osteodystrophy were tested for 6.5 to 35 months with 1,25-dihydroxycholecalciferol (1,25-DHCC). A close biochemical follow-up was performed during the first 6 months of treatment, including biweekly determinations of serum calcium, phosphorus, magnesium, alkaline phosphatase and creatinine levels. A bone biopsy, radiologic investigations and determinations of plasma levels of immunoreactive parathyroid hormone (IPTH) and intestinal absorption of calcium 47 were performed before and after the 6 months. Although the five patients with osteitis fibrosa showed a significant improvement, the four with predominantly osteomalacic lesions showed no response to treatment. These four had a normal initial plasma iPTH level, higher serum calcium levels than the other five patients, extreme sensitivity to 1,25-DHCC, with frequent episodes of hypercalcemia, and only a slightly increased serum alkaline phosphatase level, which remained unchanged during treatment. All but one of the patients, irrespective of the histologic abnormality, showed a decrease in the uptake of radionuclide by bone after treatment. The renal function of one patient, a man with long-standing stable renal failure who had not undergone dialysis, deteriorated during treatment.

Visceral calcification and the CaXP product.

The authors studied the presence of visceral calcification as evidenced by the visceral uptake of bone-seeking radionuclides during the course of a bone scan among 22 patients with terminal renal failure maintained on dialysis, nine patients with hypercalcemia secondary to malignancy, and nine patients with primary hyperparathyroidism. Uptake by the lungs or stomach was observed in 11 renal failure patients (50%) and in four of those with malignancy and hypercalcemia (44%). None of the patients with primary hyperparathyroidism had evidence of visceral calcification. The serum CaXP product was significantly higher among those with visceral calcification than those without. The results of this study indicate that a CaXP product of 60 represents the saturation product of calcium phosphate in serum above which spontaneous precipitation of this salt may occur in such viscera as stomach and lungs.

Detection and pathogenesis of visceral calcification in dialysis patients and patients with malignant disease.

Scintiscanning to detect the uptake of bone-seeking radioactive isotopes by soft tissue is a promising technique for the in vivo study of visceral calcification. Visceral uptake of such radioisotopes was studied in 40 patients: 22 undergoing long-term dialysis, 9 with malignant disease and hypercalcemia and 9 with primary hyperparathyroidism and hypercalcemia.Fifteen patients, 11 undergoing dialysis and 4 with malignant disease, had radioisotope uptake in the lungs, and 5, 3 undergoing dialysis and 2 with malignant disease, had uptake in the stomach. None of the patients with primary hyperparathyroidism had visceral uptake, nor did the patients with uptake have radiologic evidence of pulmonary or gastric calcification. The dialysis patients with visceral uptake had a mean calcium x phosphate product of 84.3 +/- 23.7 (standard deviation), which was significantly greater (P < 0.001) than that of patients without such uptake (59.2 +/- 14.0). Similarly, in patients with malignant disease and visceral uptake the Ca x P product was 72.2 +/- 6.4 - significantly greater (P < 0.005) than that of patients without such uptake (49.3 +/- 6.7).These findings indicate that scintiscanning for the visceral uptake of a bone-seeking radioisotope is a simple and effective technique for the in vivo study of visceral calcification. An elevation in the Ca x P product seems to be the single most important factor in the production of visceral calcification.