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Effects of ponalrestat, an aldose reductase inhibitor, on neutrophil killing of Escherichia coli and autonomic function in patients with diabetes mellitus
- Source :
- Diabetes. 42(2)
- Publication Year :
- 1993
-
Abstract
- In diabetic subjects, polyol pathway activity might inhibit neutrophil function and cause nerve damage. The effects of ponalrestat, an aldose reductase inhibitor, were assessed on neutrophil intracellular killing of Escherichia coli and on autonomic function in diabetic subjects in a randomized double-blind, placebo-controlled, crossover trial. We studied 31 diabetic subjects with autonomic dysfunction and 21 age- and sex-matched control subjects. During two 12-wk treatment periods, the diabetic subjects took either 600 mg of ponalrestat or matching placebo once daily. Neutrophil killing of E. coli was measured by a microbiological assay technique. Kmax by neutrophils from the diabetic subjects was lower than in the control group (Kmax of diabetic subjects 54.5 ± 26.4 vs. control subjects 67.3 ± 16.3, P = 0.045). Ponalrestat significantly increased bacterial killing in the diabetic subjects (Kmax of ponalrestat 75.1 ± 16.5 vs. placebo 58.2 ± 20.8, P = 0.003) so that there was no longer any significant difference in Kmax between the control subjects and the diabetic subjects on active treatment. Ponalrestat had no significant effect on a range of standard cardiovascular autonomic nerve function tests. We conclude that neutrophil killing of E. coli is impaired in diabetic subjects with autonomic dysfunction. This is restored to normal by ponalrestat.
- Subjects :
- Male
medicine.medical_specialty
Free Radicals
Neutrophils
Valsalva Maneuver
Endocrinology, Diabetes and Metabolism
Blood Pressure
Granulocyte
Biology
Placebo
Autonomic Nervous System
Polyol pathway
Diabetic Neuropathies
Double-Blind Method
Phagocytosis
Aldehyde Reductase
Heart Rate
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Escherichia coli
Humans
Wakefulness
Analysis of Variance
Autonomic nerve
Middle Aged
medicine.disease
Crossover study
Aldose reductase inhibitor
Autonomic nervous system
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Phthalazines
Female
Sleep
medicine.drug
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 42
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....28dfb7ffecea491901633d09bf164f07