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It's time to mow the GRAS in type 1 diabetes.

Schatz DA, Levine SR, Atkinson MA - Diabetes (2011)

View Article: PubMed Central - PubMed

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Tommy (fictitious name, but a true story) did not pick a run-of-the-mill school science fair project, such as seeing whether plants grew better with Bach versus Metallica, powering a radio with a potato, or testing the absorbency of various paper towel brands... This observation some 3 years ago, combined with many other like reports over the years, has convinced us that it is time to readdress this issue of large-scale clinical testing for Generally Recognized As Safe (GRAS)-like agents in settings of type 1 diabetes... Evaluating the ability of these agents to enhance glycemic control, and/or improve anti-inflammatory/antioxidant/immunomoregulatory status, could identify a safe and cost-effective approach to improving lives and perhaps attenuate disease-associated complications... Indeed, many GRAS-like agents have been tested in type 1 diabetic patients in situations ranging from those anecdotal in design to efforts involving controlled clinical trials... Hence, reason number one to look at GRAS-like agents again: a large portion of the clinical enterprise associated with type 1 diabetes research focuses on a small minority of subjects and not the population as a whole... Second, any such listing for rationale would fall short if we failed to highlight the “S” in GRAS: safety... Fourth, we will soon be approaching the 20th anniversary of the results reporting for the NIH Diabetes Control and Complications Trial (DCCT) effort... Having contended that a GRAS-like initiative is warranted, the next obvious questions would be, “What would you test and in which populations?” We would posit that options for testing could include—but not be limited to—the following compounds, either alone or in combination: γ-aminobutyric acid, grapefruit extract, omega-3 fatty acids, vitamin D, glutathione, nitro fatty acids, Trichuris suis ova, and probiotics... Any such list could certainly be modified subject to available data suggesting potential therapeutic benefit... In the NIH's DCCT trial, a nontrivial percentage (i.e., ∼11%) of individuals with disease from 5–15 years postdiagnosis were noted to produce an appreciable quantity of C-peptide (≥0.02 pmol/mL) (Fig. 1)... Additional subject groups worth testing for the benefits of GRAS therapy would also include the aforementioned group with recent-onset disease, established type 1 diabetic patients independent of their ability to produce C-peptide, as well as those who do not yet have type 1 diabetes but are at high risk for the disease as the result of the presence of disease associated autoantibodies... Indeed, we consider testing within this later group seeking disease prevention a particularly attractive option given many of the arguments for GRAS therapies previously mentioned in this editorial (e.g., safety, cost, ease of delivery)... Although the goals and outcomes for studying each of these groups would certainly be different, we believe it remains of significant question and interest whether GRAS-like therapies would afford clinical and quality-of-life benefits to such populations.

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Effects of duration of type 1 diabetes on residual β-cell function: observations during eligibility testing for the DCCT. Stimulated C-peptide as a function of type 1 diabetes duration. Eleven percent of adults with a disease duration of greater than 5 years had a stimulated C-peptide of greater than 0.02 pmol/mL (those meeting this standard are noted in the red box; those with stimulated C-peptide above this range regardless of disease duration are noted with a gold line). Adapted from the DCCT Research Group. J Clin Endocrinol Metab 1987;65:30–36.
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Figure 1: Effects of duration of type 1 diabetes on residual β-cell function: observations during eligibility testing for the DCCT. Stimulated C-peptide as a function of type 1 diabetes duration. Eleven percent of adults with a disease duration of greater than 5 years had a stimulated C-peptide of greater than 0.02 pmol/mL (those meeting this standard are noted in the red box; those with stimulated C-peptide above this range regardless of disease duration are noted with a gold line). Adapted from the DCCT Research Group. J Clin Endocrinol Metab 1987;65:30–36.

Mentions: Having contended that a GRAS-like initiative is warranted, the next obvious questions would be, “What would you test and in which populations?” We would posit that options for testing could include—but not be limited to—the following compounds, either alone or in combination: γ-aminobutyric acid, grapefruit extract, omega-3 fatty acids, vitamin D, glutathione, nitro fatty acids, Trichuris suis ova, and probiotics. Any such list could certainly be modified subject to available data suggesting potential therapeutic benefit. As to which populations testing is warranted, one group that would certainly be of interest is the large cohort of often ignored individuals with type 1 diabetes who, based on their ability to produce C-peptide, might particularly benefit from GRAS-like therapies. In the NIH's DCCT trial, a nontrivial percentage (i.e., ∼11%) of individuals with disease from 5–15 years postdiagnosis were noted to produce an appreciable quantity of C-peptide (≥0.02 pmol/mL) (Fig. 1) (6). While this group is usually thought rare, not often considered is that by sheer number (i.e., 11% of 1.5M equates to some 165,000 persons) they eclipse the aforementioned population size of recent-onset subjects eligible for most disease reversal or islet β-cell preservation efforts. Additional subject groups worth testing for the benefits of GRAS therapy would also include the aforementioned group with recent-onset disease, established type 1 diabetic patients independent of their ability to produce C-peptide, as well as those who do not yet have type 1 diabetes but are at high risk for the disease as the result of the presence of disease associated autoantibodies. Indeed, we consider testing within this later group seeking disease prevention a particularly attractive option given many of the arguments for GRAS therapies previously mentioned in this editorial (e.g., safety, cost, ease of delivery). Although the goals and outcomes for studying each of these groups would certainly be different, we believe it remains of significant question and interest whether GRAS-like therapies would afford clinical and quality-of-life benefits to such populations.


It's time to mow the GRAS in type 1 diabetes.

Schatz DA, Levine SR, Atkinson MA - Diabetes (2011)

Effects of duration of type 1 diabetes on residual β-cell function: observations during eligibility testing for the DCCT. Stimulated C-peptide as a function of type 1 diabetes duration. Eleven percent of adults with a disease duration of greater than 5 years had a stimulated C-peptide of greater than 0.02 pmol/mL (those meeting this standard are noted in the red box; those with stimulated C-peptide above this range regardless of disease duration are noted with a gold line). Adapted from the DCCT Research Group. J Clin Endocrinol Metab 1987;65:30–36.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198084&req=5

Figure 1: Effects of duration of type 1 diabetes on residual β-cell function: observations during eligibility testing for the DCCT. Stimulated C-peptide as a function of type 1 diabetes duration. Eleven percent of adults with a disease duration of greater than 5 years had a stimulated C-peptide of greater than 0.02 pmol/mL (those meeting this standard are noted in the red box; those with stimulated C-peptide above this range regardless of disease duration are noted with a gold line). Adapted from the DCCT Research Group. J Clin Endocrinol Metab 1987;65:30–36.
Mentions: Having contended that a GRAS-like initiative is warranted, the next obvious questions would be, “What would you test and in which populations?” We would posit that options for testing could include—but not be limited to—the following compounds, either alone or in combination: γ-aminobutyric acid, grapefruit extract, omega-3 fatty acids, vitamin D, glutathione, nitro fatty acids, Trichuris suis ova, and probiotics. Any such list could certainly be modified subject to available data suggesting potential therapeutic benefit. As to which populations testing is warranted, one group that would certainly be of interest is the large cohort of often ignored individuals with type 1 diabetes who, based on their ability to produce C-peptide, might particularly benefit from GRAS-like therapies. In the NIH's DCCT trial, a nontrivial percentage (i.e., ∼11%) of individuals with disease from 5–15 years postdiagnosis were noted to produce an appreciable quantity of C-peptide (≥0.02 pmol/mL) (Fig. 1) (6). While this group is usually thought rare, not often considered is that by sheer number (i.e., 11% of 1.5M equates to some 165,000 persons) they eclipse the aforementioned population size of recent-onset subjects eligible for most disease reversal or islet β-cell preservation efforts. Additional subject groups worth testing for the benefits of GRAS therapy would also include the aforementioned group with recent-onset disease, established type 1 diabetic patients independent of their ability to produce C-peptide, as well as those who do not yet have type 1 diabetes but are at high risk for the disease as the result of the presence of disease associated autoantibodies. Indeed, we consider testing within this later group seeking disease prevention a particularly attractive option given many of the arguments for GRAS therapies previously mentioned in this editorial (e.g., safety, cost, ease of delivery). Although the goals and outcomes for studying each of these groups would certainly be different, we believe it remains of significant question and interest whether GRAS-like therapies would afford clinical and quality-of-life benefits to such populations.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Tommy (fictitious name, but a true story) did not pick a run-of-the-mill school science fair project, such as seeing whether plants grew better with Bach versus Metallica, powering a radio with a potato, or testing the absorbency of various paper towel brands... This observation some 3 years ago, combined with many other like reports over the years, has convinced us that it is time to readdress this issue of large-scale clinical testing for Generally Recognized As Safe (GRAS)-like agents in settings of type 1 diabetes... Evaluating the ability of these agents to enhance glycemic control, and/or improve anti-inflammatory/antioxidant/immunomoregulatory status, could identify a safe and cost-effective approach to improving lives and perhaps attenuate disease-associated complications... Indeed, many GRAS-like agents have been tested in type 1 diabetic patients in situations ranging from those anecdotal in design to efforts involving controlled clinical trials... Hence, reason number one to look at GRAS-like agents again: a large portion of the clinical enterprise associated with type 1 diabetes research focuses on a small minority of subjects and not the population as a whole... Second, any such listing for rationale would fall short if we failed to highlight the “S” in GRAS: safety... Fourth, we will soon be approaching the 20th anniversary of the results reporting for the NIH Diabetes Control and Complications Trial (DCCT) effort... Having contended that a GRAS-like initiative is warranted, the next obvious questions would be, “What would you test and in which populations?” We would posit that options for testing could include—but not be limited to—the following compounds, either alone or in combination: γ-aminobutyric acid, grapefruit extract, omega-3 fatty acids, vitamin D, glutathione, nitro fatty acids, Trichuris suis ova, and probiotics... Any such list could certainly be modified subject to available data suggesting potential therapeutic benefit... In the NIH's DCCT trial, a nontrivial percentage (i.e., ∼11%) of individuals with disease from 5–15 years postdiagnosis were noted to produce an appreciable quantity of C-peptide (≥0.02 pmol/mL) (Fig. 1)... Additional subject groups worth testing for the benefits of GRAS therapy would also include the aforementioned group with recent-onset disease, established type 1 diabetic patients independent of their ability to produce C-peptide, as well as those who do not yet have type 1 diabetes but are at high risk for the disease as the result of the presence of disease associated autoantibodies... Indeed, we consider testing within this later group seeking disease prevention a particularly attractive option given many of the arguments for GRAS therapies previously mentioned in this editorial (e.g., safety, cost, ease of delivery)... Although the goals and outcomes for studying each of these groups would certainly be different, we believe it remains of significant question and interest whether GRAS-like therapies would afford clinical and quality-of-life benefits to such populations.

Show MeSH
Related in: MedlinePlus