Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes

Cabrera-Rode, Eduardo; Molina, Gisela; Arranz, Celeste; Vera, Manuel; González, Pedro; Suárez, Rolando; Prieto, Mirta; Padron, Saul Alejandro; León, Rafael; Tillán, Juana; García, Igrid; Tiberti, Claudio; Rodríguez, Olga María Rodríguez; Gutiérrez, Antonio; Fernández, Tamara; Govea, Amparo; Hernández, José Angel Flores; Chiong, Dania; Domínguez, Emma; Mario, U. Di; Díaz-Díaz, Oscar; Diaz-Horta, Oscar

doi:10.1080/08916930600738383

Cited by 20 publications

(12 citation statements)

References 45 publications

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“…Thus, oral NAM administration is thought to be a therapeutic agent for T1DM. Although small-scale clinical trials have reported the beneficial effects of NAM against T1DM [76], a large-scale randomized controlled trial demonstrated that NAM intervention in patients with confirmed anti-islet cell antibodies failed to prevent the onset of T1DM [77]. For T1DM treatment, NMN and NR are still attractive candidates because NAD-mediated SIRT1 activation augments GSIS in β-cells [78].…”

Section: Diabetesmentioning

confidence: 99%

Implications of altered NAD metabolism in metabolic disorders

et al. 2019

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Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that participates in various energy metabolism pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Besides, it is a required cofactor for post-translational modifications such as ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerases (PARPs) and sirtuins, respectively. Thus, NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response through these enzymes. Numerous studies have shown that NAD levels decrease with aging and under disturbed nutrient conditions, such as obesity. Additionally, a decline in NAD levels is closely related to the development of various metabolic disorders, including diabetes and fatty liver disease. In addition, many studies have revealed that administration of NAD precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), efficiently increase NAD levels in various tissues and prevent such metabolic diseases. These NAD precursors are contained in natural foods, such as cow milk, vegetables, and meats. Therefore, altered NAD metabolism can be a practical target for nutritional intervention. Recently, several human clinical trials using NAD precursors have been conducted to investigate the safety, pharmacokinetics, and efficacy against metabolic disorders such as glucose intolerance. In this review, we summarize current knowledge on the implications of NAD metabolism in metabolic diseases and discuss the outcomes of recent human clinical trials.

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Section: Diabetesmentioning

confidence: 99%

Implications of altered NAD metabolism in metabolic disorders

et al. 2019

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“…NAM treatment induced liver NAD + levels, which were complimented by enhanced glucose control (Yang et al, 2014). Despite NAM being suggested as a treatment for type 1 diabetes (Olmos et al, 2006), clinical trials failed to confirm this hypothesis (Cabrera-Rode et al, 2006; Gale, Bingley, Emmett, Collier, & European Nicotinamide Diabetes Intervention Trial (ENDIT) Group, 2004).…”

Section: The Choice Of Nad+ Precursor Is Criticalmentioning

confidence: 99%

Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD+-dependent SIRT1–PGC-1α–TFAM pathway

Chandrasekaran

Anjaneyulu

Choi

et al. 2019

International Review of Neurobiology

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Survival of human peripheral nervous system neurons and associated distal axons is highly dependent on energy. Diabetes invokes a maladaptation in glucose and lipid energy metabolism in adult sensory neurons, axons and Schwann cells. Mitochondrial (Mt) dysfunction has been implicated as an etiological factor in failure of energy homeostasis that results in a low intrinsic aerobic capacity within the neuron. Over time, this energy failure can lead to neuronal and axonal degeneration and results in increased oxidative injury in the neuron and axon. One of the key pathways that is impaired in diabetic peripheral neuropathy (DPN) is the energy sensing pathway comprising the nicotinamide-adenine dinucleotide (NAD+)-dependent Sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α)/Mt transcription factor A (TFAM or mtTFA) signaling pathway. Knockout of PGC-1α exacerbates DPN, whereas over-expression of human TFAM is protective. LY379268, a selective metabolomic glutamate receptor 2/3 (mGluR2/3) receptor agonist, also upregulates the SIRT1/PGC-1α/TFAM signaling pathway and prevents DPN through glutamate recycling in Schwann/satellite glial (SG) cells and by improving dorsal root ganglion (DRG) neuronal Mt function. Furthermore, administration of nicotinamide riboside (NR), a precursor of NAD+, prevents and reverses DPN, in part by increasing NAD+ levels and SIRT1 activity. In summary, we review the role of NAD+, mitochondria and the SIRT1–PGC-1α–TFAM pathway both from the perspective of pathogenesis and therapy in DPN.

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“…However, long-term NAM treatment increases NAD + levels via the NAD + salvage pathway, which likely tips the balance of the NAD + /NAM ratio such that SIRT1 is activated. Despite NAM being suggested as a treatment for type 1 diabetes (Olmos et al, 2006), clinical trials failed to confirm this hypothesis (Cabrera-Rode et al, 2006; Gale et al, 2004). More recently OLETF rats, a rodent model of obesity and type 2 diabetes, exhibited profound metabolic improvements following NAM treatment (100mg/kg for 4 weeks).…”

Section: Introductionmentioning

confidence: 99%

NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

2015

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NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.

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Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes

Abstract: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.

Cited by 20 publications

References 45 publications

Implications of altered NAD metabolism in metabolic disorders

Implications of altered NAD metabolism in metabolic disorders

Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD+-dependent SIRT1–PGC-1α–TFAM pathway

NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

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