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The use of nicotinamide in the prevention of type 1 diabetes
R B Elliott1, C C Pilcher, A Stewart
1Department of Pediatrics, School of Medicine, University of Auckland, New Zealand.
Abstract:
Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.
Insights
Nicotinamide shows promise in protecting against diabetes in NOD mice and at-risk humans by reducing islet inflammation. While not primarily through PARP inhibition, its safety and potential to increase NAD levels suggest therapeutic value.
Area of Science:
- Immunology
- Endocrinology
- Nutritional Science
Background:
- Type 1 diabetes involves islet inflammation and autoimmunity.
- Nicotinamide (vitamin B3) has shown potential in preclinical models of diabetes.
Purpose of the Study:
- To investigate the protective effects of nicotinamide against diabetes in NOD mice and at-risk humans.
- To explore the mechanisms underlying nicotinamide's protective action, including PARP inhibition and NAD levels.
Main Methods:
- Administration of nicotinamide to NOD mice and human subjects with islet cell antibodies.
- In vitro studies on isolated islets exposed to toxic agents.
- Measurement of islet inflammation, PARP activity, and intracellular NAD levels.
Main Results:
- Nicotinamide provided early protection against diabetes in NOD mice, with effects waning over time and reduced islet inflammation.
- Similar protective effects were observed in at-risk human populations.
- In vitro, nicotinamide protected islets but required high doses for significant PARP inhibition.
- Human-achieved nicotinamide levels were too low for significant PARP inhibition, suggesting alternative mechanisms like NAD+ synthesis or free radical scavenging.
Conclusions:
- Nicotinamide demonstrates a protective effect against diabetes development in preclinical and human studies.
- The protective mechanism in humans is likely related to increased NAD levels or antioxidant effects, rather than significant PARP inhibition.
- Nicotinamide appears safe for use in the studied doses for diabetes prevention.