sulindac and Diabetes-Mellitus--Type-1

To study the effect of sulindac on the alteration of the blood-retinal barrier, 24 insulin-dependent diabetic patients with minimal or no retinopathy were randomly assigned to receive either oral sulindac (200 mg twice daily) or a placebo for a period of six months. All patients underwent fundus photography, fluorescein angiography, and vitreous fluorophotometry before treatment and after 1, 3, and 6 months of treatment. Vitreous fluorophotometry data showed that there were fewer alterations of the blood-retinal barrier in the sulindac group compared with the placebo group during the six-month study period.

Topics: Administration, Oral; Cell Membrane Permeability; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Double-Blind Method; Fluorescein; Fluoresceins; Humans; Indenes; Retina; Rheology; Sulindac

The purpose of this study was to define pathological abnormalities in the peripheral nerve of a large animal model of long-duration type 1 diabetes and also to determine the effects of treatment with sulindac. Detailed morphometric studies were performed to define nerve fiber and endoneurial capillary pathology in 6 control dogs, 6 type 1 diabetic dogs treated with insulin, and 6 type 1 diabetic dogs treated with insulin and sulindac for 4 years. Myelinated fiber and regenerative cluster density showed a non-significant trend toward a reduction in diabetic compared to control animals, which was prevented by treatment with sulindac. Unmyelinated fiber density did not differ among groups. However, diabetic animals showed a non-significant trend toward an increase in axon diameter (p < 0.07), with a shift of the size frequency distribution towards larger axons, which was not prevented by treatment with sulindac. Endoneurial capillary density and luminal area showed a non-significant trend toward an increase in diabetic animals, which was prevented with sulindac treatment. Endoneurial capillary basement membrane area was significantly increased (p < 0.05) in diabetic animals, but was not prevented with sulindac treatment. We conclude that the type 1 diabetic dog demonstrates minor structural abnormalities in the nerve fibers and endoneurial capillaries of the sciatic nerve, and treatment with sulindac ameliorates some but not all of these abnormalities.

Topics: Animals; Capillaries; Cyclooxygenase Inhibitors; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dogs; Microscopy, Electron; Nerve Fibers; Nerve Fibers, Myelinated; Sciatic Nerve; Sulindac

We have studied the functional importance of renal eicosanoids in renal hemodynamics of seven newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients by treatment with two structurally unrelated inhibitors of cyclooxygenase (i.e., piroxicam and sulindac). Glomerular filtration rate (GFR), renal plasma flow (RPF), daily urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of prostacyclin), and thromboxane B2 (TXB2, the stable hydrolysis product of thromboxane A2) were measured before, during, and after piroxicam (all patients) or sulindac (3 patients) treatment. Urinary excretion of 6-keto-PGF1 alpha was significantly increased (P less than .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB2 was unchanged. The baseline value of GFR was significantly (P less than .01) higher in diabetic compared with normal volunteers, whereas baseline RPF was comparable in both groups. Piroxicam (20 mg/day) reduced urinary excretion of 6-keto-PGF1 alpha and TXB2 by 65.7 +/- 26 and 64.6 +/- 33%, respectively. These biochemical changes were temporally associated with the approximately 19% decrease in GFR (P less than .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF1 alpha were still significantly (P less than .05) reduced, whereas urinary excretion of TXB2 returned to control values. In contrast, urinary excretion of eicosanoids and renal function were not affected by sulindac (0.4 g/day) treatment. No functional changes were detected in healthy subjects despite a similar suppression of renal cyclooxygenase activity when they were treated with piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Creatinine; Diabetes Mellitus, Type 1; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Piroxicam; Sulindac; Thromboxane A2