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  • 1
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    Serum Uromodulin (SUMOD) Inversely Correlates with Aortic Stiffness in Type 1 Diabetes (T1D) Youth
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Lower SUMOD correlates with decreasing kidney function and atherosclerosis in adults with T1D, but its relationship with markers of arterial stiffness in youth with T1D is unknown. We sought to evaluate the relationship between SUMOD and central arterial stiffness in youth with T1D. Participants (n=49, 12-21 years old, 51% female, BMI 25.2±4.6 kg/m2, mean HbA1c8.6±1.4) were enrolled in EMERALD, a randomized controlled trial of metformin in youth with T1D. Post-hoc SUMOD was measured using Euroimmun ELISA kits from serum from the baseline visit. Ascending (AA) and descending aortic (DA) stiffness (pulse wave velocity [PWV] and strain) were determined by MRI at baseline and 3 months of follow-up. SUMOD positively correlated with AA strain (r: 0.37, p=0.04) and negatively with AA PWV (r: -0.41, p=0.03). According to SUMOD tertiles, participants in the lower tertile had higher AA PWV vs. the middle and high tertiles (Figure). Lower baseline SUMOD also predicted worsening in AA PWV over 3 months (β±SE: -0.04±0.01, p=0.03) adjusting for age, sex, baseline AA PWV, treatment group (metformin vs. placebo) and estimated glomerular filtration rate. In T1D youth, decreased SUMOD is associated with increased aortic stiffness. Further research is needed in T1D youth to understand the pathogenesis of SUMOD in cardiovascular disease. Disclosure P. Wiromrat: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. C. Roncal-Jimenez: None. M. Schäfer: None. A. Baumgartner: None. L. Pyle: None. M. Cree-Green: None. Y. Garcia Reyes: None. L. Browne: None. R. Johnson: Board Member; Self; XORT Therapeutics. Stock/Shareholder; Self; Colorado Research Partners LLC. Consultant; Self; Danone Research Foundation. K.J. Nadeau: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-431-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 2
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    216-OR: Cardiovascular (CV) Impact of BMI in Youth with Type 1 Diabetes (T1D)
    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: Insulin resistance (IR) and obesity are independently associated with T1D and are known risk factors for CV disease, the leading cause of mortality in T1D. We evaluated the impact of BMI on CV outcomes in T1D youth and compared obese T1D (OT1D) youth to youth with type 2 diabetes (T2D). Pubertal youth aged 12-21 years with T1D and T2D were recruited from the RESistance to InSulin in type 1 and type 2 diabetes (RESISTANT) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with type 1 Diabetes (EMERALD) cohorts. Participants were stratified as lean (LT1D), overweight, or obese T1D or T2D (Table). CV outcomes included resting heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), leptin, hsCRP, and adiponectin. T1D participants performed bicycle ergometry for peak oxygen consumption (VO2peak), brachial artery (BA) distensibility by Dynapulse, and aortic MRI. HR, SBP, DBP, mean arterial pressure, and prevalence of hypertension were higher and BA distensibility, descending aorta oscillatory shear index, VO2peak, leptin, and hsCRP were worsened in OT1D vs. LT1D. Beyond hypertension prevalence in OT1D vs. T2D, which was worse in OT1D, T2D did not differ significantly from OT1D. Higher BMI, which is increasingly prevalent in T1D, is associated with a worsened CV profile in T1D youth, nearly approximating the CV phenotype of T2D youth. Closer attention to lifestyle management in T1D youth is needed to help reduce CV risk. Disclosure K.L. Tommerdahl: None. K.V. Baumgartner: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Baumgartner: None. L. Pyle: None. J.G. Regensteiner: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. K.J. Nadeau: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.); JDRF (11-2010-343); National Institutes of Health (1R56DK088971-01)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-216-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 3
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    183-LB: The Gut Microbiome and Puberty in Girls at Risk for Type 2 Diabetes (T2D)
    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: Objectives: Pediatric-onset T2D is twice as common in girls vs. boys and is tightly linked with puberty and obesity. Alterations in gut microbiota, specifically the Firmicutes:Bacteroidetes ratio (F:B), may be associated with insulin sensitivity (Si) and may play a role in the pathophysiology of T2D. We aimed to evaluate associations between gut microbiome composition and Si and insulin secretion in obese prepubertal (PP) vs. late-pubertal (LP) girls. Methods: Obese PP (N=9, age 8.5 ±0.8 year, BMIz 2.0±0.5) and LP (Tanner 4-5, N=9, age 13.0±2.0 year, BMIz 2.0±0.5) obese girls underwent stool collection and intravenous glucose tolerance testing after an overnight fast. High-throughput sequencing of the bacterial 16S rRNA gene V3-V4 region was used to profile fecal bacterial communities. Bergman's minimal model was used to estimate Si and insulin secretion (acute insulin response to glucose, AIRg) and disposition index (DI). T-tests assessed group differences in Si, AIRg and DI. Spearman’s correlation examined relationships between microbiota relative abundance (%RA) and Si, AIRg and DI. Results: PP vs. LP girls had significantly higher Si (8.0±1.0 vs. 2.0±0.5 x10-4/min-1/μIU/ml, p & lt;0.001) and DI (3,525 ± 636 vs. 1,687 ± 385 x10-4/min-1, p=0.03). AIRg was not different between PP and LP girls (568 ± 132 vs. 840 ± 174 μIU/ml, p=0.23). F:B ratio related to insulin secretion and DI, (r=-0.32, p=0.20; r=-0.39, p=0.11) but not Si. At the genus level, Si was correlated to Ruminococus and Lachnospira %RA (r=0.53, p=0.02; r=0.50, p=0.036). AIRg was correlated to Peptostreptococcaceae %RA (r=-0.48, p=0.045). DI was correlated with Prevotella and Bifidobacterium %RA (r=0.57, p=0.01; R=- 0.54, p=0.02). Conclusion: These pilot study results suggest possible relationships among the gut microbiome, glucose metabolism, and puberty in girls at risk for T2D that merit further exploration. Disclosure B. Jobira: None. D.N. Frank: None. L. Pyle: None. S. Gross: None. D. Ir: None. W. Pendleton: None. C.E. Robertson: None. K.J. Nadeau: None. M.M. Kelsey: None. Funding University of Colorado Center for Women’s Health; National Institutes of Health/Colorado Clinical Translational Science Award (UL1TR002535)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-183-LB
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 4
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    Metformin Improves Insulin Resistance (IR) and Vascular Health in Youth with Type 1 Diabetes (T1D)
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Cardiovascular disease is the leading cause of mortality in T1D and relates to IR. We demonstrated that lean and obese T1D youth have IR and that metformin improves surrogate markers of IR in obese T1D youth. Yet, little is known about vascular health in T1D youth or about the effect of metformin on directly-measured IR or vascular health. In The Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study, we hypothesized that T1D youth have impaired vascular function and that metformin decreases IR and improves vascular health. 49 T1D youth ages 12-21 years (40% with BMI ≥ 90%ile; 44% male) and 24 controls of similar age, BMI and sex underwent phase contrast MRI of the ascending (AA) and descending aorta (DA) to determine aortic pulse wave velocity (PWV) and wall shear stress (WSS). T1D youth also had carotid intima-media thickness (cIMT) by ultrasound, DXA scan, fasting labs following overnight IV glycemic control, and a hyperinsulinemic-euglycemic clamp (80 mU/m2/min insulin) to assess IR (glucose infusion rate [mg/kg/min)]/insulin or M/I). T1D youth were then randomized 1:1 to 2g of metformin or placebo daily, and all measures repeated at 3 months. At baseline, T1D youth vs. controls had elevated aortic PWV (AA: 3.7±0.2 vs. 2.5±0.4 m/s, p & lt;0.05; DA: 4.2±0.2 vs. 3.1±0.3 m/s, p=0.02) and WSS (AA: 1.1±0.04 vs. 0.9±0.N/m2, p=0.003; DA: 1.6±0.vs. 1.1±0.07 N/m2, p & lt;0.0001). Compared to the placebo group, T1D youth in the metformin group had no baseline differences but had improvement at 3 months in M/I (12.2±3.2 vs. -2.4±3.6 uIU/uL, p & lt;0.01), AA PWV (-1.1±1.1 vs. 4.1±1.6 m/s, p & lt;0.04), AA WSS (-0.03±0.04 vs. 0.2±0.N/m2, p & lt;0.03) and far wall diastolic cIMT (-0.04±0.01 vs. 0.00±0.01 mm, p=0.04) in baseline-adjusted models. T1D youth have IR and vascular dysfunction compared to controls of similar age, sex and BMI. Metformin mitigated IR and improved aortic and carotid health in T1D youth, and thus may hold promise as a cardiovascular protective intervention. Disclosure K.J. Nadeau: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. M. Sch fer: None. L. Browne: None. A. Baumgartner: None. Y. Garcia Reyes: None. A. Maniatis: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; MannKind Corporation, Dexcom, Inc., Xeris Pharmaceuticals, Inc., Bigfoot Biomedical. S. Nayak: None. L. Pyle: None. M. Cree-Green: None. J.E. Reusch: Research Support; Self; Merck & Co., Inc.. Board Member; Self; American Diabetes Association. Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-234-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 5
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    Continuous Glucose Monitoring in Youth with Pre-Type 1 Obesity/Pre-Type 2 Diabetes and Cystic Fibrosis
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Continuous glucose monitoring abnormalities are present in the prediabetic state, but how these abnormalities compare among individuals at risk for different types of diabetes (type 1, type 2, vs. cystic fibrosis related diabetes) is unknown. We compared CGM patterns of three distinct groups of youth at risk for diabetes, all with A1c & lt;6.5%: pre-T1D (multiple islet antibody positive), obese/pre-T2D (BMI ≥85th%Ile), and cystic fibrosis (CF). None were on insulin or other medications affecting glucose metabolism. CGM was obtained for 3-7 days in our observational studies. Pre-T1D youth (A1c range 5.0-6.3%) were randomly matched 1:3 on A1c to the obese/pre-T2D and CF youth. Groups were compared using random effects models for continuous variables. Age, Sex distribution and HbA1c were not different between the groups after matching. The results are shown in the table. Of interest, youth with CF and pre-T1D had greater standard deviation, higher maximum and lower minimum glucoses than obese/pre-T2D youth. In conclusion, CGM patterns are significantly different in pre-T1D and CF compared to obese/pre-T2D, reflecting differences in pathophysiology among these disease states. Early insulin deficiency appears to manifest as greater glycemic variability—higher SD, greater peaks and lows—in pre-T1D and CF, while insulin resistance leads to increased, but less variable, glucoses in obese/preT2D youth. *pre-T1D and CF significantly different from pre-T2DCGM measure (sensor glucose) Mean (SE) (mg/dl)Pre-T1D (N=14)Pre-T2D (n=42)CF (n=42)P-valueAverage glucose117 (3)114 (2)111 (2)0.17Standard deviation (SD)26 (2)16 (1)22 (1) & lt;0.0001*Maximum223 (14)162 (5)209 (7) & lt;0.0001*Minimum62 (4)77 (2)62 (2) & lt;0.0001*% time & gt;12037 (5)31 (4)27 (2)0.24% time 14017 (4)12 (3)9 (1)0.23% time & gt;2001.3 (0.7)0.4 (0.2)0.8 (0.2)0.11 Disclosure C.L. Chan: None. A. Steck: None. T.B. Vigers: None. L. Pyle: None. F. Dong: None. J. Thurston: None. M. Rewers: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH. K.J. Nadeau: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1521-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 6
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    Longitudinal Predictors of Insulin Sensitivity and Secretion during Puberty
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: All youth experience a transient reduction in Si during puberty, but little is known about the associated physiology. We previously demonstrated cross-sectionally that insulin-like growth factor 1 (IGF-1) and leptin are associated with Si early in puberty. We now aim to evaluate longitudinal predictors of Si and acute insulin response to glucose (AIRg) during puberty. Methods: Forty-five (47% female) normal-weight (mean BMI %ile 44±22%) ethnically mixed youth entered the study in early puberty (Tanner [T] 2-3). Study visits, including an IV glucose tolerance test (IVGTT), fasting laboratory studies, and DXA, were performed at T2-3, T4, and T5, based on breast development and testicular volume. Physical activity (PA) was assessed by the 3DPAR (3-Day PA Recall). Repeated measures models were used to test if changes over time in potential predictors (IGF-1, leptin, estradiol, total testosterone, dehydroepiandrosterone-sulfate, PA, and urinary gonadotropins) were associated with changes over time in the outcomes, with and without adjustment for sex and % body fat. Results: Si (p=0.04) decreased and AIRg increased (p=0.12) from T2/3-T5. IGF-1 and leptin were the only significant predictors of change in Si and AIRg over time. IGF-1 was associated with both Si (β=-0.016, p=0.0004) and AIRg (β=1.40, p=0.002), and remained so after adjusting for sex and % fat (p=0.0007 and 0.004, respectively). Leptin was associated with Si in univariate analysis (p=0.003) and with both Si (β=-0.238, p=0.003) and AIRg (β=38.4, p=0.043) after adjustment for sex and % fat. Conclusions: This is the first study to show a longitudinal relationship between leptin and Si and AIRg during puberty independent of sex and body fat, and confirms previous reports of associations between IGF-1 and Si and AIRg. These results suggest that leptin and IGF-1 may be driving factors for changes in Si and AIRg during puberty. Knowledge of normal pubertal metabolism may contribute to understanding of diseases of pubertal onset, such as type 2 diabetes. Disclosure M.M. Kelsey: Other Relationship; Self; Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp.. L. Pyle: None. A.M. Hilkin: None. A. Johnson: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1348-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 7
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    1603-P: Fasting Metabolomic Profiles Are Altered by Three Days of Standardized Diet and Restricted Physical Activity
    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: Metabolomics has been used to identify biomarkers of diabetes development and progression and to investigate pathophysiological mechanisms; however, metabolomics profiles can be affected by diet and physical activity. We evaluated the effects of acute diet and physical activity on metabolomics profiles in a cohort of obese adolescent girls. Obese adolescents (n=21, 14.2 ± 1.6 years, BMI %ile 98.0 ± 1.7) were studied. At the first study visit (fasting visit), participants fasted for 12 hours prior to sample collection. Prior to the second visit (controlled visit), participants were provided a 3-day standardized isocaloric weight maintenance diet, and were asked to avoid exercising for 3 days, and samples were drawn after 12 hours of fasting. Untargeted metabolomics was performed in plasma samples. Multilevel sPLS-DA was used to identify compounds that discriminated between fasting and controlled visits. The sPLS-DA analysis showed excellent discrimination (Figure 1) between the fasting and controlled samples, resulting in 0% misclassification error. In ROC analysis, the AUROC of the sPLS-DA model was 1.00 (p & lt;0.0001). Acute diet and physical activity affect fasting metabolic profiles, and differences identified between samples may not be a result of underlying metabolism. Caution should be used in interpreting fasting metabolomics unless diet and physical activity are controlled. Disclosure L. Pyle: None. A. Carreau: Advisory Panel; Self; Pfizer Inc. H. Rahat: None. Y. Garcia Reyes: None. K.J. Nadeau: None. M. Cree-Green: None. Funding National Institutes of Health; University of Michigan
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1603-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 8
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    1342-P: Development of Type 2 Diabetes (T2D) in Obese Adolescent Girls with Polycystic Ovary Syndrome (PCOS)
    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: PCOS is a common endocrine disorder that starts in adolescence and, when accompanied by obesity, is associated with a 4-fold risk of T2D. Adolescent onset of T2D carries significant morbidity and decreased life expectancy; rates of T2D are 12.5 cases/100,000/year in the general youth population. The incidence and prevalence of T2D in teen girls with PCOS and obesity are unknown. We conducted a retrospective chart review at a large tertiary care center. Using ICD9/10 codes for PCOS, girls aged 11-21 years with clinic visits between 7/1/2013-8/15/2018 and a BMI %ile & gt; 85th were identified. Diagnosis of PCOS and T2D were confirmed using Endocrine Society and ADA guidelines, respectively. Key demographic and diagnostic information, including time of T2D diagnosis relative to PCOS diagnosis, was extracted. Prevalence of T2D in the PCOS cohort was calculated 1) from the entire T2D cohort and 2) only the incident T2D cases, as our site may have excess new T2D diagnosis referrals. We identified 600 cases of PCOS (15.2 ± 1.8 years, BMI %ile 96.2 ± 12.1) and 54 of these also had T2D, of whom 23 were diagnosed with PCOS prior to T2D (incident cohort). The prevalence of T2D in girls with PCOS and overweight/obesity was 4% including only incident cases and 9% with inclusion of all T2D. The incidence of T2D among adolescents with obesity and PCOS is 129 cases/1000/year and T2D presents 26 ± 19 months after PCOS diagnosis. Girls with T2D were more likely to be Hispanic (67% vs. 49%; p & lt;0.0001) have obstructive sleep apnea (32% vs. 17%; p=0.01) and a 1st-degree relative with T2D (56% vs. 22%; p & lt;0.001) than those who didn’t develop T2D. Girls with PCOS and obesity are at high-risk for developing T2D in adolescence, with 1 in 23 developing T2D within 2 years of diagnosis with PCOS. Girls at higher risk include those with a strong family history of T2D and Hispanic ethnicity. Further work is needed to confirm these rates in the overall adolescent population and to develop strategies for prevention of T2D in these high-risk youth. Disclosure J. Hudnut-Beumler: None. J. Kaar: None. L. Pyle: None. M.M. Kelsey: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. M. Cree-Green: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K23DK107871)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1342-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 9
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    Valine Metabolism Is Altered in Obese Adolescents with Polycystic Ovary Syndrome and Relates to Insulin Sensitivity
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Polycystic Ovarian Syndrome (PCOS) is common and associated with insulin resistance (IR). The mechanism of IR in PCOS is unclear, likely multifactorial, and may relate to branched-chain amino acids (BCAA) and mitochondrial metabolism. We quantitated differences in BCAA and BCAA breakdown product short chain (C3-C5) acylcarnitines in response to hyperinsulinemia in obese girls with and without PCOS, and assessed the relationship to IR and hyperandrogenism. Obese girls with PCOS [n=15, 14.5 ± 1.6 years, BMI %ile 98.5 ± 1.0] and without PCOS [n=6; 13.2 ± 1.2 years, BMI %ile 98.0 ± 1.1] were studied. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp and a testosterone panel obtained. Nontargeted metabolomics were performed in plasma samples obtained before and after the clamp. T-tests were used for group comparisons, with the Benjamini-Hochberg procedure (false discovery rate (FDR) set to 0.05) to control for multiple testing. Spearman’s correlation coefficient was calculated for BCAA vs. glucose infusion rate (GIR) and free androgen index (FAI). The groups had similar demographic, physical activity, diet attributes, HbA1c and lipids. Girls with PCOS had higher FAI and worse IR than controls. FAI related negatively to short chain acylcarnitines C4 (r = -0.74, p=0.0002) and C3 (r=-0.60, p =0.007). During hyperinsulinemia, girls with PCOS had higher valine (FDR-adjusted p=0.04) and lower valine breakdown product C4 butyrylcarnitine (FDR-adjusted p=0.01). End-clamp valine correlated with GIR (r= -0.59, p= 0.006) as did C4 butyrylcarnitine (r=0.44, p=0.04). Under hyperinsulinemia, a metabolomic signature was revealed in obese girls with PCOS, distinct from that in uncomplicated obesity. Valine was higher in girls with PCOS, while C4 acylcarnitine, its direct mitochondrial metabolite, was lower. Further work is needed to determine if BCAA metabolism is a modifiable target to improve insulin sensitivity or simply a useful biomarker. Disclosure A. Carreau: None. H. Rahat: None. Y. Garcia Reyes: None. L. Pyle: None. K.J. Nadeau: None. M. Cree-Green: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1338-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 10
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    Late Reactive Hypoglycemia (RHG) as a Common Early Sign of Glycemic Dysfunction in Obese Adolescent Girls
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Many obese adolescent girls describe symptoms of hypoglycemia, but this has not been systematically assessed. Due to pubertal insulin resistance (IR), hormonal responses to an oral glucose tolerance test (OGTT) may occur beyond the typical 2h sampling interval. We sought to determine how often reactive hypoglycemia (RHG) occurs in these girls. 56 girls aged 12-20 years, BMI percentile ≥ 90th, were enrolled in a study including fasting metabolic labs and a 6h OGTT with frequently sampled glucose, C-peptide, insulin, GLP-1 and glucagon. RHG was defined as a blood glucose (BG) & lt; 70 mg/dL with a ≥ 20 mg/dL drop from the previous sample. Comparisons between those with and without RHG were performed with a Student’s t-test. 50% of girls had BG & lt;70mg/dL (mean nadir was 62 mg/dL); 18% were & lt;65 mg/dL and 12% & lt; 60 mg/dL. The median time for lowest BG was 240 min (range 210-360 min) after the glucose load. Girls with RHG were slightly younger (15.1±1.8 vs. 16.2±1.5 years; p=0.02). The groups had similar BMI percentile (97.8 vs. 96.8) and percent fat mass, but tended to have more visceral fat (10.1% vs. 8.1%; p=0.08). Fasting glucose and insulin were not different between groups, but HOMA-IR tended to be higher in RHG (7.0±5.4 vs. 4.9±2.2, p=0.07). The area under the curve of insulin and glucose for the first 180 min of the OGTT was higher in RHG (p=0.01 and p=0.04, respectively), with impaired glucose tolerance tending to be more frequent in RHG (63% vs. 40%; p=0.08). The mean insulin peak for the RHG was at 150 min, vs. 30 min post-drink in the normal group. At 240 min, glucagon tended to be higher in RHG (81 vs. 67 pg/ml; p=0.06). RHG defined as a BG & lt;70 mg/dL following a rapid drop, is common in girls with obesity in response to liquid sugar, and occurs later than detectable with a standard 2h OGTT. RHG appears to be secondary to an overly robust, late insulin response. This pattern is likely related to IR, may precede further dysglycemia and may be severe enough to cause a counter regulatory response, arguing to avoid consuming liquid sugar in isolation. Disclosure A. Carreau: None. H. Rahat: None. Y. Garcia Reyes: None. L. Pyle: None. K.J. Nadeau: None. M. Cree-Green: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1361-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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