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  • 1
    Online Resource
    Online Resource
    Precision and accuracy of hyperglycemic clamps in a multicenter study
    American Physiological Society ; 2021
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 320, No. 4 ( 2021-04-01), p. E797-E807
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 320, No. 4 ( 2021-04-01), p. E797-E807
    Abstract: Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and 〉 450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements. Clamp operators received initial and repeated training with ongoing feedback based on surveillance of clamp performance. The precision and accuracy of the achieved stage-specific glucose targets were evaluated, including differences by study center. We also evaluated robustness of the method to baseline physiologic differences and on-study treatment effects. The RISE approach produced high overall precision (3%–9% variance in achieved plasma glucose from target at various times across the procedure) and accuracy (SD 〈 10% overall). Statistically significant but numerically small differences in achieved target glucose concentrations were observed across study centers, within the magnitude of the observed technical variability. Variation of the achieved target glucose over time in placebo-treated individuals was low ( 〈 3% variation), and the method was robust to differences in baseline physiology (youth vs. adult, IGT vs. diabetes status) and differences in physiology induced by study treatments. The RISE approach to standardization of the hyperglycemic clamp methodology across multiple study centers produced technically excellent standardization of achieved glucose concentrations. This approach provides a reliable method for implementing glucose clamp methodology across multiple study centers. NEW & NOTEWORTHY The Restoring Insulin Secretion (RISE) study centers undertook hyperglycemic clamps using a simplified methodology and a decision guidance algorithm implemented in an easy-to-use spreadsheet. This approach, combined with active management including ongoing central data surveillance and routine feedback to study centers, produced technically excellent standardization of achieved glucose concentrations on repeat studies within and across study centers.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00598.2020
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp
    American Physiological Society ; 2017
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 312, No. 3 ( 2017-03-01), p. E175-E182
    Details
    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
    URL: Article
    DOI: 10.1152/ajpendo.00394.2016
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2017
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice
    American Physiological Society ; 2005
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 289, No. 4 ( 2005-10), p. E703-E709
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 289, No. 4 ( 2005-10), p. E703-E709
    Abstract: Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and β-cell dysfunction. Islet amyloid is associated with reduced β-cell mass and function and develops in the majority of our C57BL/6J × DBA/2J (F 1 ) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J × DBA/2J F 1 mice ( n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F 1 : 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6: 14 ± 3%, F 1 : 44 ± 8%, DBA2: 49 ± 9%, P 〈 0.05) and severity (%islet area occupied by amyloid; BL6: 0.03 ± 0.01%, F 1 : 9.2 ± 2.9%, DBA2: 5.7 ± 2.3%, p ≤ 0.01) were significantly lower in BL6 than F 1 and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F 1 ( r 2 = 0.75, P 〈 0.001) and DBA2 ( r 2 = 0.87, P 〈 0.001) mice but not BL6 mice ( r 2 = 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes (F 1 and DBA2 mice) being more susceptible to amyloid deposition that replaces β-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00471.2004
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2005
    detail.hit.zdb_id: 1477331-4
    SSG: 12
    Location Call Number Limitation Availability
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