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  • 1
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 7 ( 2019-07-01), p. 1326-1332
    Abstract: Sleep disturbances and circadian misalignment (social jet lag, late chronotype, or shift work) have been associated with worse glycemic control in type 2 diabetes (T2D). Whether these findings apply to adults with prediabetes is yet unexplored. We hypothesized that self-reported short sleep, poor sleep quality, and/or circadian misalignment are associated with higher glycemia, BMI, and blood pressure (BP) in adults with prediabetes or recently diagnosed, untreated T2D. RESEARCH DESIGN AND METHODS Our cohort included 962 overweight/obese adults ages 20–65 years with prediabetes or recently diagnosed, untreated T2D who completed a 2-h oral glucose tolerance test and validated sleep questionnaires. Independent associations of sleep and circadian variables with glycemia, BMI, and BP were evaluated with regression models. RESULTS The multiethnic cohort was 55% men, with mean ± SD age 52.2 ± 9.5 years and BMI 34.7 ± 5.5 kg/m2. Mean sleep duration was 6.6 ± 1.3 h. Poor sleep quality was reported by 54% and high risk for obstructive sleep apnea by 64%. HbA1c was significantly higher in those reporting & lt;5 or & gt;8 h sleep per night. Sleep duration & gt;8 h was also associated with higher fasting glucose and & lt;6 h with higher BMI. Shift work was also associated with higher BMI. Social jet lag and delayed chronotype were associated with higher BP. CONCLUSIONS In our cohort, self-reported short and long sleep were both associated with adverse measures of glycemia, and short sleep and shift work were associated with higher BMI. Further research using objective measures of sleep is needed to better delineate the relationship between sleep and glycemia in adults with prediabetes or T2D.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 2
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 8 ( 2019-08-01), p. 1521-1529
    Abstract: We examined the relationship between habitual daily physical activity and measures of glucose tolerance, insulin sensitivity, and β-cell responses in adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS Participants included 230 adults (mean ± SD age 54.5 ± 8.5 years, BMI 35 ± 5.5 kg/m2; 42.6% women) who underwent a 3-h oral glucose tolerance test (OGTT) and hyperglycemic clamp. Wrist accelerometers worn for 7 consecutive days measured total physical activity counts (TAC) (daily mean 233,460 [∼50th percentile for age]). We evaluated whether TAC was associated with fasting plasma glucose, OGTT 2-h plasma glucose or glucose incremental area under the curve (G-iAUC), hyperglycemic clamp measures of insulin sensitivity (steady-state glucose infusion rate/insulin [M/I] ) and β-cell responses (acute C-peptide response to glucose, steady-state C-peptide, and maximal β-cell response), and OGTT C-peptide index (ΔC-peptide0–30/Δglucose0–30). RESULTS After adjustments for confounders, there was no association of TAC with fasting plasma glucose, 2-h glucose, or G-iAUC. Higher TAC was associated with higher insulin sensitivity (M/I). After adjusting for M/I, higher TAC was not associated with measures of β-cell response. CONCLUSIONS In adults with IGT or drug-naive, recently diagnosed type 2 diabetes, higher levels of habitual physical activity are associated with higher insulin sensitivity. Further studies are needed to understand why higher levels of physical activity are not associated with better β-cell response.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 3
    Online Resource
    Online Resource
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 5 ( 2019-05-01), p. 1855-1865
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 5 ( 2019-05-01), p. 1855-1865
    Abstract: Total insulin clearance is decreased in nonalcoholic fatty liver disease (NAFLD), but the relationship between liver fat and hepatic insulin extraction (HIE) is unknown. Objective This cross-sectional study addresses the hypothesis that HIE is reduced in NAFLD and investigates metabolic and/or anthropometric characteristics most closely associated with insulin clearance. Participants Nondiabetic subjects with NAFLD (n = 13) and age- and body mass index (BMI)-matched controls with normal liver enzymes (n = 15) underwent abdominal CT, dual-energy X-ray absorptiometry, oral glucose tolerance test (OGTT), and labeled two-step hyperinsulinemic-euglycemic clamps. Outcome Measurements Liver fat was estimated by the CT liver/spleen ratio. Hepatic and extrahepatic insulin clearances were modeled using clamp and OGTT data. Results Extrahepatic insulin clearance and HIE were not different between NAFLD and controls and did not correlate with liver fat. HIE was positively correlated with insulin sensitivity [rate of glucose disposal (Rd; low r = +0.7, P & lt; 0.001; high r = +0.6, P = 0.001), adiponectin (r = +0.55, P = 0.004), and insulin-mediated suppression of clamp nonesterified free fatty acid (NEFA; r = +0.67, P & lt; 0.001)] but was not associated with fasting NEFA, insulin-mediated suppression of glucose production, or measures of adiposity. Extrahepatic insulin clearance was positively associated with percent body fat (r = +0.44, P = 0.02) and subcutaneous fat (r = +0.42, P = 0.03) but not BMI, intra-abdominal fat, liver fat, Rd, adiponectin, or NEFA. Conclusions HIE is not directly associated with hepatic steatosis but is associated with muscle and adipose tissue insulin resistance. The data suggest differential regulation of insulin clearance with extrahepatic insulin clearance being associated with body fat and not insulin sensitivity.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2017
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 312, No. 3 ( 2017-03-01), p. E175-E182
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 312, No. 3 ( 2017-03-01), p. E175-E182
    Abstract: Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) 〈 60 ml·min −1 ·1.73 m 2 ] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SI clamp ), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SI clamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8–38% lower in participants with vs. without CKD and 13–59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SI clamp did not differ significantly by CKD or obesity status. Adjusting for SI clamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD ( P = 0.09) and 36% lower in participants with vs. without obesity ( P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD ( P = 0.02) and 46% lower in participants with vs. without obesity ( P 〈 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SI clamp , but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2017
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2016
    In:  Journal of Diabetes and its Complications Vol. 30, No. 4 ( 2016-05), p. 618-622
    In: Journal of Diabetes and its Complications, Elsevier BV, Vol. 30, No. 4 ( 2016-05), p. 618-622
    Type of Medium: Online Resource
    ISSN: 1056-8727
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2006763-X
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  • 6
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-02-10)
    Abstract: NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK–T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5 -deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness. Interestingly, NLRC5 expression in T cells is required to protect them from NK-cell-mediated elimination upon inflammation. Using T-cell-specific Nlrc5 -deficient mice, we show that NK cells surprisingly break tolerance even towards ‘self’ Nlrc5 -deficient T cells under inflammatory conditions. Furthermore, during chronic LCMV infection, the total CD8 + T-cell population is severely decreased in these mice, a phenotype reverted by NK-cell depletion. These findings strongly suggest that endogenous T cells with low MHCI expression become NK-cell targets, having thus important implications for T-cell responses in naturally or therapeutically induced inflammatory conditions.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2553671-0
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  • 7
    In: Journal of Renal Nutrition, Elsevier BV, Vol. 26, No. 2 ( 2016-03), p. 93-102
    Type of Medium: Online Resource
    ISSN: 1051-2276
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 8
    In: Pediatric Diabetes, Hindawi Limited, Vol. 20, No. 8 ( 2019-12), p. 1056-1063
    Type of Medium: Online Resource
    ISSN: 1399-543X , 1399-5448
    URL: Issue
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2025536-6
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  • 9
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: High glycemic variability has been associated with increased oxidative stress and β-cell dysfunction. To test whether changes in glycemic variability impact β-cell function and oxidative stress markers in adults with prediabetes, we conducted an RCT where we provided study subjects controlled diets varying in glycemic index (GI) to experimentally manipulate post-prandial glucose excursions. After 2 weeks on a control diet (mean GI= 55-58), subjects were randomized to 1 of 3 groups for 4 weeks: low (LGI & lt;35) GI diet, high (HGI & gt;70) GI diet plus the anti-oxidant N-acetylcysteine (HGI/NAC) 600 mg BID or HGI diet plus placebo (HGI/PLAC). Subjects underwent CGMS (iPro), fasting markers of oxidative stress (GSH/GSSG and TBARS) and an IVGTT at the end of each diet. Independent t-test was used to test the intervention effect on the change in disposition index (DI), a marker of β-cell function. Fifty-two subjects (26M/26F, age 53±10 y, BMI 32.1±6.2 kg/m2) with IFG and/or IGT completed the study (18 LGI, 17 HGI/NAC, 17 HGI/PLAC). The 3 groups did not differ by sex, age, BMI, A1c, fasting or 2 h glucose (ANOVA). On the control diet, DI was inversely correlated with CGMS mean daily glucose (r=-0.33, p=0.02) and daily SD glucose (r=-0.31, p=0.03) and the GSH/GSSG ratio (r=-0.35, p=0.01), but not TBARS (r=0.13, p=0.4). Compared to LGI, HGI/PLAC increased mean CGMS glucose (change -1.4±1.9 LGI vs. 4.6±2.4 HGI/PLAC mg/dl, p=0.05) and SD (change -2.6±1.3 vs. 5.0±2.2, p=0.005). Results did not differ between HGI/PLAC and HGI/NAC. There were no significant intervention effects on DI, TBARS or GSH/GSSG ratio. Changes in CGMS mean glucose and SD and oxidative stress markers did not correlate with changes in DI. In conclusion, GI diet-induced changes in glucose concentrations and variability did not impact β-cell function or oxidative stress markers. These results suggest that glucose variability may be a consequence of β-cell dysfunction rather than a cause. Disclosure K. Utzschneider: Consultant; Self; Novo Nordisk Inc.. T.N. Johnson: None. K. Breymeyer: None. M.L. Neuhouser: None.
    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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  • 10
    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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