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Alternative therapeutic principles in the prevention of microvascular and neuropathic complications
1Diabetesforschungsinstitut an der Heinrich-Heine-Universität, Düsseldorf, Germany.
Abstract:
Since the prevention of chronic diabetic complications by near normal metabolic control is not always achievable, alternative therapeutic principles have been developed. The specific intervention at metabolic abnormalities which seem to play a key role in the pathogenesis of complications has been shown to prevent the development of microangiopathy and neuropathy in experimental diabetes, e.g. inhibition of non-enzymatic glycation by aminoguanidine, inhibition of polyol pathway activity by aldose reductase inhibitors, prevention of hypoxia and oxidative stress by vasodilators and radical scavengers such as alpha-lipoic acid. Some of these drugs should soon be available for common clinical use.
Insights
New therapeutic strategies target metabolic abnormalities to prevent chronic diabetic complications like microangiopathy and neuropathy. Drugs inhibiting non-enzymatic glycation and oxidative stress show promise for clinical use.
Area of Science:
- Endocrinology and Metabolic Diseases
- Pharmacology
- Diabetology
Background:
- Near-normal metabolic control is often insufficient for preventing chronic diabetic complications.
- Key metabolic abnormalities contribute significantly to the pathogenesis of diabetic microangiopathy and neuropathy.
Purpose of the Study:
- To explore alternative therapeutic principles targeting specific metabolic pathways in diabetes.
- To evaluate interventions aimed at preventing diabetic complications.
Main Methods:
- Inhibition of non-enzymatic glycation using aminoguanidine.
- Inhibition of the polyol pathway with aldose reductase inhibitors.
- Prevention of hypoxia and oxidative stress via vasodilators and radical scavengers like alpha-lipoic acid.
Main Results:
- Experimental diabetes models demonstrated prevention of microangiopathy and neuropathy.
- Specific interventions targeting metabolic pathways were effective in preclinical studies.
Conclusions:
- Targeting specific metabolic abnormalities offers a promising therapeutic approach for diabetic complications.
- Several drug candidates, including aminoguanidine and alpha-lipoic acid, are nearing clinical availability.