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  • ISMAIL-BEIGI, FARAMARZ  (3)
  • 2015-2019  (3)
  • 1
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: In nondiabetic subjects a biphasic (rise, fall, rise) vs. monophasic (rise then fall) glucose pattern on OGTTs has been associated with better metabolic parameters, but data in T2DM are limited. We categorized the shape of the glucose curve from baseline OGTTs performed in the Glycemia Reduction Approaches in Diabetes Study (GRADE) into monophasic, biphasic or continuous rise and analyzed their relationship with metabolic parameters. GRADE eligibility included T2DM & lt;10 y, HbA1c 6.8-8.5% with metformin treatment alone. OGTT glucose and insulin were measured at 0, 15, 30, 60, 90 and 120 minutes (n=5047 adults: age 57.2±10 y, 63.6% male, HbA1c 7.5±0.5%, duration T2DM 4.2±2.8 y). Most glucose profiles were monophasic. HbA1c did not differ between groups. Those with a monophasic shape were more likely to be men, had higher BMI, fasting glucose and incAUC glucose, and lower HOMA-S and disposition index (Table). Compared to the monophasic group, those with a continuous rise shape had lower fasting glucose and higher HOMA-S, but the highest 2 h glucose. Those with a biphasic pattern had intermediate insulin sensitivity, but the highest disposition index. Thus, a biphasic glucose pattern reflects better β-cell function, similar to that observed in nondiabetic subjects. Whether glucose patterns predict response to GRADE interventions will be determined on study completion.Table. Phenotypic and metabolic characteristics by OGTT glucose curve shapeMonophasicBiphasicContinuousP valueN (%)3212 (64.0)283 (5.6)1523 (30.4)Sex (%male)70.359.750.2 & lt;0.001Age (years)56.5±9.958.0±10.558.5±9.9 & lt;0.001BMI (kg/m2)35±732±633±7 & lt;0.001HbA1c (%)7.5±0.57.5±0.57.5±0.50.6Fasting glucose (mmol/L)8.5±1.78.4±1.68.3±1.7 & lt;0.0012 hour glucose (mmol/L)15.4±2.915.8±3.117.1±3.0 & lt;0.001incrementalAUC0-120 glucose (mmol/L)6.4±1.55.3±1.75.7±1.5 & lt;0.001HOMA-S (mU.mmol/L-2)0.22±0.230.25±0.210.28±0.41 & lt;0.001δInsulin/δGlucose0-30 (mU/mmol)5.3±4.46.5±5.65.1±6.10.002Disposition index (mmol/L-1)0.34±0.640.46±0.430.38±0.370.005Mean±SD. 23 had missing data and 6 were excluded with a triphasic pattern. Disposition index = δI/δG0-30 x HOMA-S. Disclosure K. Utzschneider: Consultant; Self; Novo Nordisk Inc. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc. J.I. Barzilay: Stock/Shareholder; Self; AbbVie Inc., AstraZeneca, Celgene Corporation, DuPont, Merck & Co., Inc., Teva Pharmaceutical Industries Ltd.. E.V. Gonzalez: None. F. Ismail-Beigi: None. K.J. Mather: Research Support; Self; Merck & Co., Inc., Sanofi-Aventis, Novo Nordisk A/S, Abbott. Advisory Panel; Self; Merck & Co., Inc. P. Raskin: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., GlaxoSmithKline plc.. N. Younes: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. G. Research Group: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute. Other Relationship; Self; Bristol-Myers Squibb Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis, Roche Diagnostics Corporation, Becton, Dickinson and Company, Centers for Disease Control and Prevention, National Diabetes Education Program.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Little data exist on the relationship between glycemic variables, insulin sensitivity and insulin and C-peptide responses in subjects with T2DM. We assessed these relationships using baseline OGTT data from the Glycemia Reduction Approaches in Diabetes, A Comparative Effectiveness study (GRADE) cohort. Eligibility included T2DM & lt;10 y, HbA1c 6.8-8.5% treated with metformin alone. Glucose, insulin and C-peptide were measured at 0, 15, 30, 60, 90 and 120 minutes in 5047 OGTTs. Insulin sensitivity was measured by HOMA-S and insulin and C-peptide responses were estimated using δhormone/δglucose0-30 and incremental area under the curve (incAUC) hormone/glucose0-120. Subjects were 63.6% men, 57.2±10 y old (mean±SD), with HbA1c 7.5±0.5% and T2DM duration 4.2±2.8 y. Insulin and C-peptide responses were inversely associated with HOMA-S in a curvilinear manner (p & lt;0.001 for all). Glycemic variables were all inversely associated with HOMA-S and insulin and C-peptide responses (Table, p & lt;0.001 for all). The weakest association was between HbA1c and HOMA- S and the strongest between 2h glucose and incAUC C-peptide. Even in established diabetes there is measurable β-cell function and these measures remain proportional to glycemic responses. We plan to use these baseline measures of β-cell function as potential determinants of treatment outcomes in GRADE. Table: Adjusted Regression DataHOMA-SδI/δG0-30δCP/δG0-30incAUC I/G0-120incAUC CP/G0-120Fasting glucose-0.28-0.20-0.21-0.28-0.322hr glucose-0.18-0.25-0.27-0.34-0.44incAUC-G0-120-0.10-0.16-0.16-0.16-0.18HbA1c-0.07-0.10-0.09-0.13-0.15Regression models are presented as signed R2 adjusted for sex, age, race, BMI, T2DM duration, eGFR and metformin dose. I = insulin, G = glucose, CP = C-peptide Disclosure K. Utzschneider: Consultant; Self; Novo Nordisk Inc. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc. J.I. Barzilay: Stock/Shareholder; Self; AbbVie Inc., AstraZeneca, Celgene Corporation, DuPont, Merck & Co., Inc., Teva Pharmaceutical Industries Ltd.. E.V. Gonzalez: None. F. Ismail-Beigi: None. K.J. Mather: Research Support; Self; Merck & Co., Inc., Sanofi-Aventis, Novo Nordisk A/S, Abbott. Advisory Panel; Self; Merck & Co., Inc. P. Raskin: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., GlaxoSmithKline plc.. N. Younes: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. G. Research Group: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute. Other Relationship; Self; Bristol-Myers Squibb Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis, Roche Diagnostics Corporation, Becton, Dickinson and Company, Centers for Disease Control and Prevention, National Diabetes Education Program.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 3
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Factors associated with β-cell dysfunction in type 2 diabetes (T2D) are not well understood. We examined the association between OGTT-derived estimates of insulin sensitivity, insulin/C-peptide responses and β-cell function with baseline phenotypic characteristics in the GRADE cohort. The cohort comprised 5,047 adults with T2D & lt;10 y, treated with metformin alone. Subjects were 63.6% men, 57.2±10 y/o (mean±SD), with BMI 34.3±6.8 kg/m2, weight 99.9±22.3 kg, waist circumference (circ) 112.3±15.8 cm, HbA1c 7.5±0.5% and T2D duration 4.2±2.8 y. Racial composition was 66% white, 20% African Americans, 4% Asian, 3% American Indian, and 7% Other. Insulin sensitivity did not differ between men and women, but women had higher insulin/C-peptide responses and disposition index (DI) (p & lt;0.001 for all). The associations between insulin sensitivity, insulin/C-peptide responses and DI with age, BMI, weight, waist circ and T2D duration are provided in Table 1. Insulin sensitivity, insulin/C-peptide responses and DI differed by racial category (p & lt;0.001 for all). In summary, among GRADE participants, sex, race and obesity are associated with β-cell function. Although statistically significant, the associations of insulin sensitivity and β-cell responses with age and T2D duration are not as strong.Table 1- The Spearman correlation (upper line) and p value (lower line) between baseline phenotypic characteristics and insulin sensitivity, insulin/C-peptide responses and DI.AgeWeightBMIWaist circT2D DurationMatsuda Index0.07 & lt;0.001-0.40 & lt;0.001-0.46 & lt;0.001-0.45 & lt;0.0010.08 & lt;0.001HOMA-S Index0.12 & lt;0.001-0.47 & lt;0.001-0.50 & lt;0.001-0.49 & lt;0.0010.09 & lt;0.001Insulin responseδinsulin 0-30/δglucose 0-300.04=0.010.26 & lt;0.0010.32 & lt;0.0010.29 & lt;0.001-0.13 & lt;0.001C-peptide responseδC-peptide 0-30/δglucose 0-300.07 & lt;0.0010.14 & lt;0.0010.19 & lt;0.0010.18 & lt;0.001-0.08 & lt;0.001Disposition Index(δinsulin 0-30/δglucose 0-30)/fasting insulin0.13 & lt;0.001-0.13 & lt;0.001-0.11 & lt;0.001-0.13 & lt;0.001-0.03=0.09 Disclosure N. Rasouli: Consultant; Self; AstraZeneca, Intarcia Therapeutics, Inc. R.M. Cohen: Stock/Shareholder; Self; Bristol-Myers Squibb Company. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc. S. Inzucchi: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Sanofi, Lexicon Pharmaceuticals, Inc.. Consultant; Self; VTV Therapeutics. Other Relationship; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc., Alere Inc.. F. Ismail-Beigi: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. K. Utzschneider: Consultant; Self; Novo Nordisk Inc. J. Lachin: Board Member; Self; AbbVie Inc., Celgene Corporation. N. Younes: None. G. Research Group: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute. Other Relationship; Self; Bristol-Myers Squibb Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis, Roche Diagnostics Corporation, Becton, Dickinson and Company, Centers for Disease Control and Prevention, National Diabetes Education Program.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
    Location Call Number Limitation Availability
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