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  • American Diabetes Association  (12)
  • 1
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    Online Resource
    A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk
    American Diabetes Association ; 2018
    In:  Diabetes Care Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Abstract: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS & gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-0087
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1490520-6
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  • 2
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    Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
    American Diabetes Association ; 2019
    In:  Diabetes Care Vol. 42, No. 2 ( 2019-02-01), p. 192-199
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 2 ( 2019-02-01), p. 192-199
    Abstract: There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A] , and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P & lt; 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-0288
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 3
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    Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial
    American Diabetes Association ; 2020
    In:  Diabetes Care Vol. 43, No. 8 ( 2020-08-01), p. 1822-1828
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 43, No. 8 ( 2020-08-01), p. 1822-1828
    Abstract: Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14–72 years; mean HbA1c, 7.1% [54 mmol/mol]) were randomly assigned to CLC (N = 54, Control-IQ) or PLGS (N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70–180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study. RESULTS All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P & lt; 0.001). Time & gt;180 mg/dL was lower in the CLC group than PLGS group (difference = −6.0%; 95% CI −8.4%, −3.7%; P & lt; 0.001) while time & lt;54 mg/dL was similar (0.04%; 95% CI −0.05%, 0.13%; P = 0.41). HbA1c after 13 weeks was lower on CLC than PLGS (7.2% [55 mmol/mol] vs. 7.5% [56 mmol/mol] , difference −0.34% [−3.7 mmol/mol]; 95% CI −0.57% [−6.2 mmol/mol] , −0.11% [1.2 mmol/mol]; P = 0.0035). CONCLUSIONS Following 6 months of CLC, switching to PLGS reduced TIR and increased HbA1c toward their pre-CLC values, while hypoglycemia remained similarly reduced with both CLC and PLGS.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc20-0124
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 4
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    242-OR: Do GLP-1RA and SGLT2i Reduce Cardiovascular Mortality in African-American Patients with Type 2 Diabetes? A Meta-analysis
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: While patients enrolled in the cardiovascular safety trials (CVST) for GLP-1RA and SGLT2i were mostly whites, the ADA’s updated recommendations are being generalized to all races. This raises a controversial question regarding the ability to generalize CVST results to African American (AA) patients. We searched MEDLINE, EMBASE, and CENTRAL looking for CVST comparing diabetic medications to placebo in type 2 diabetes and reporting a statistically significant lower incidence of either the primary outcome of MACE or any of the pre-specified secondary outcomes. We then extracted cardiovascular outcomes for AA patients. Sensitivity and subgroup analyses were performed according to the class of diabetic medications. We included 6 trials (GLP-1RA in 4; SGLT2i in 2). While those trials enrolled 53,978 patients, only 2794 were AA. There was no significant difference in CV outcomes between diabetic medications (GLP-1RA or SGLT2i) and placebo in AA patients (RR [95% CI] = 0.97 [0.68, 1.39] ). On restricting the analysis to GLP-1RA, then to SGLT2i, results for AA patients remained non-significant. On comparing results for GLP-1RA to those with SGLT2i, there was no difference between the groups. We conclude that AA are not well represented in CVST. Because cardiovascular outcomes were not significantly improved for AA, it remains unclear whether GLP-1RA or SGLT2i would reduce cardiovascular risk in AA. Disclosure B.M. Mishriky: None. J.R. Powell: None. J.A. Wittwer: None. J.X. Chu: None. K. Sewell: None. Q. Wu: None. D.M. Cummings: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-242-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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  • 5
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    928-P: Psychosocial Factors in Diabetes-Specific Risk Taking among Adolescents with Type 1 Diabetes
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Background: Diabetes-specific risk taking (DSRT) refers to unhealthy, risky behaviors that put someone with diabetes at increased risk for suboptimal health outcomes (e.g., drinking alcohol with others who are unaware you have T1D). DSRT is associated with less engagement in T1D management and higher HbA1c. This study set out to determine if lower levels of parental involvement in T1D care and higher levels of diabetes distress, also associated with less optimal T1D outcomes, were associated with DSRT among adolescents with T1D. Methods: Participants were 104 adolescents with T1D (Mage = 13.50 years, SDage = 1.69 years, 53.8% female, MHbA1c = 8.74%, SDHbA1c = 1.24%) who enrolled with their caregivers in a randomized controlled trial integrating psychologists and dietitians into T1D care visits (35% enrollment). Adolescents completed baseline measures of parental involvement, diabetes distress, and DSRT; caregivers reported demographics; and HbA1c was collected from the electronic medical record. Hierarchical linear regression was used to examine whether parental involvement and diabetes distress predicted DSRT after controlling for participants’ sex, race, ethnicity and HbA1c. Results: The full model was statistically significant and accounted for 29.7% of the variance in diabetes-specific risk taking (F(2, 91)= 19.1, p & lt; .001). Neither HbA1c, sex, race nor ethnicity were statistically significant predictors of DSRT. Higher levels of diabetes distress (β = .23, p = .01) and lower parental involvement (β = -.44, p & lt; .001) predicted more frequent DSRT. Conclusions: Adolescents with more diabetes distress and less collaborative parental involvement in T1D management reported more diabetes-specific risk taking. While causality cannot be asserted, these results can inform targeted behavioral interventions to help youth who are more likely to take risks in their T1D care. Future research should consider other factors contributing to diabetes-specific risk taking. Disclosure C. Thomas: None. T. Wysocki: None. M. A. Alderfer: None. P. Enlow: None. R. M. Wasserman: None. A. Milkes: None. J. Pierce: None. S. Gurnurkar: None. M. Carakushansky: None. D. A. Doyle: None. J. S. Pendley: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK113235)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-928-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 6
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    Novel Human Insulin Isoforms and Cα-Peptide Product in Islets of Langerhans and Choroid Plexus
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. 12 ( 2021-12-01), p. 2947-2956
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. 12 ( 2021-12-01), p. 2947-2956
    Abstract: Human insulin (INS) gene diverged from the ancestral genes of invertebrate and mammalian species millions of years ago. We previously found that mouse insulin gene (Ins2) isoforms are expressed in brain choroid plexus (ChP) epithelium cells, where insulin secretion is regulated by serotonin and not by glucose. We further compared human INS isoform expression in postmortem ChP and islets of Langerhans. We uncovered novel INS upstream open reading frame isoforms and their protein products. In addition, we found a novel alternatively spliced isoform that translates to a 74–amino acid (AA) proinsulin containing a shorter 19-AA C-peptide sequence, herein designated Cα-peptide. The middle portion of the conventional C-peptide contains β-sheet (GQVEL) and hairpin (GGGPG) motifs that are not present in Cα-peptide. Islet amyloid polypeptide (IAPP) is not expressed in ChP, and its amyloid formation was inhibited in vitro more efficiently by Cα-peptide than by C-peptide. Of clinical relevance, the ratio of the 74-AA proinsulin to proconvertase-processed Cα-peptide was significantly increased in islets from type 2 diabetes mellitus autopsy donors. Intriguingly, 100 years after the discovery of insulin, we found that INS isoforms are present in ChP from insulin-deficient autopsy donors.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-0198
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 7
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    32-LB: Interstitial Glucose Levels during Exercise in Persons with and without Type 1 Diabetes
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-32-LB
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 8
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    730-P: At-Home Randomized Crossover Comparison of Automated Insulin Delivery vs. Conventional Therapy with Scheduled Meal Challenges
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: Automated Insulin Delivery (AID) hybrid closed-loop systems have not been well studied in the context of prescribed meals. We evaluated our interoperable artificial pancreas system (iAPS) with scheduled meal challenges in a randomized crossover trial in an at-home setting. Ten adults with type 1 diabetes completed two weeks of AID-based control and two weeks of conventional therapy (sensor-augmented pump/predictive low-glucose suspend) at home in random order. During each period, subjects consumed pasta or white rice as part of a complete dinner meal on six different occasions (each meal three times in random order). The AID system increased time in range 70-180 mg/dL from 70.6 to 74.0% (3.4, 95% CI -2.3 to 9.1, p=0.22), while sensor time & lt;70 mg/dL significantly decreased from 3.5 to 2.3% (-1.2, 95% CI -2.1 to -0.2, p=0.02). Postprandial glucose AUC difference between meals in conventional therapy was 10,919.0 mg/dL x min (95% CI 3,190.5 to 18,648.0, p=0.009) while for AID it was 6,522.1 mg/dL x min (p=0.24), highlighting the ability of AID to minimize glycemic excursions postprandially. The AID system decreased insulin delivery at 0-2h by 0.45 units (p=0.001) for pasta, while it increased at 2-4h by 0.47 units (p=0.18) for white rice (Table 1). The AID system improved postprandial glucose control over conventional therapy in the handling of challenging meals in the at-home setting. Disclosure J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. S. Deshpande: None. M. Church: None. M. Piper: None. C.C. Andre: None. J.S. Massa: None. F.J. Doyle: Research Support; Self; DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Mode AGC. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. D.M. Eisenberg: Consultant; Self; Barilla Center For Food and Nutrition, Italy. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. Funding Barilla Center for Food & Nutrition Foundation; National Institutes of Health (DP3DK104057, DP3DK113511); Harvard Accelerator; Dexcom, Inc. (IIS-2018-019)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-730-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 9
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    779-P: Comparative Effects of Two Types of Pasta vs. White Rice on Postprandial Glucose Levels in Adults with Type 1 Diabetes
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Background: Food choices are essential to successful glycemic control in persons with diabetes. Methods: Twelve adults with type 1 diabetes (T1D) (age 58.7±14.2 years, HbA1c 7.5±1.3%) completed an in-clinic double-blinded crossover study comparing the glycemic response to higher protein pasta (10 grams protein/serving), regular pasta (7 grams protein/serving), and white rice. All meals contained 42 grams carbohydrate, were served with homemade tomato sauce, green salad and balsamic dressing, and were repeated in random order. Linear mixed effects models assessed the 5 h postprandial glycemic response. Results: Compared to white rice, peak glucose levels were significantly lower for higher protein pasta (-32.6 mg/dL; 95% CI -48.4, -17.2; p & lt;0.001) and for regular pasta (-43.2 mg/dL, 95% CI -58.7, -27.7; p & lt;0.001). The difference between the two types of pastas did not reach statistical significance (-11 mg/dL; 95% CI -24.1, 3.4; p=0.17). Total glucose area under the curve for the 5 h postprandial period was significantly higher for white rice compared to both pastas (p & lt;0.001) (Table 1). Conclusions: There is a significant difference in postprandial glycemic response in persons with T1D between rice and both types of pasta when consumed in equal amounts of carbohydrate. Persons with T1D need to be aware of the relative impact of commonly consumed carbohydrates in the setting of real-life meals. Disclosure J.E. Pinsker: Research Support; Self; Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, LifeScan, Inc., Roche Diabetes Care, Tandem Diabetes Care. Speaker's Bureau; Self; Tandem Diabetes Care. S. Zavitsanou: Employee; Self; Novo Nordisk A/S. J.S. Massa: None. S. Deshpande: None. M. Church: None. C.C. Andre: None. F.J. Doyle: Consultant; Self; ModeAGC. Other Relationship; Self; Insulet Corporation. A. Michelson: None. J. Creason: None. E. Dassau: Consultant; Self; Eli Lilly and Company, Insulet Corporation. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Ltd., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; Roche Diabetes Care. Other Relationship; Self; ModAGC. D.M. Eisenberg: Advisory Panel; Self; Barilla Center for Food & Nutrition Foundation. Consultant; Self; Campus for H (Japan), Infinitus (China) Company LTD., Nutrition Development Group, LLC. Funding Barilla Center for Food & Nutrition Foundation
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-779-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 10
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    Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet
    American Diabetes Association ; 2013
    In:  Diabetes Vol. 62, No. 10 ( 2013-10-01), p. 3500-3513
    Details
    In: Diabetes, American Diabetes Association, Vol. 62, No. 10 ( 2013-10-01), p. 3500-3513
    Abstract: Eating a “Westernized” diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6–1, NKX2–2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db13-0266
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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