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Title: Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

Author
item SJAARDA, LINDSEY - University Of Pittsburgh Medical Center
item LEE, SOJUNG - University Of Pittsburgh Medical Center
item TFAYLI, HALA - American University Of Beirut
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item BERTOLET, MARNIE - University Of Pittsburgh
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2012
Publication Date: 6/1/2013
Citation: Sjaarda, L., Lee, S., Tfayli, H., Bacha, F., Bertolet, M., Arslanian, S. 2013. Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice? Diabetes Care. 36(6):1607-1612.

Interpretive Summary: Typically two research methods are utilized to evaluate insulin production: a hyperinulinemic-euglycemic clamp is used to measure the body’s insulin sensitivity and a hyperglycemic clamp is used to measure the body's insulin production. In this study we investigated whether both measures (insulin sensitivity and insulin secretion) can be derived from a single study (the hyperglycemic clamp) and how the indexes obtained from one study compare to the indexes derived from two studies. We evaluated the data in 330 youth: 73 with normal weight, 168 obese with normal glucose tolerance, 57 obese with impaired glucose tolerance, and 32 obese with type 2 diabetes. The agreement between the measures obtained from two clamp studies versus the hyperglycemic clamp study alone were examined. We concluded that beta cell function relative to insulin sensitivity (insulin production needed by the body to maintain normal sugar levels) could be accurately evaluated from a single hyperglycemic clamp study.

Technical Abstract: To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcDI). Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth: 73 normal weight, 168 obese with normal glucose tolerance, 57 obese with impaired glucose tolerance, and 32 obese with type 2 diabetes. The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined. Insulin sensitivity and first-phase insulin from hcDI showed a hyperbolic relationship. The hcDI correlated significantly with 2cDI in the groups combined (r = 0.85, P < 0.001) and within each group separately (r >= 62, P < 0.001). Similar to 2cDI, hcDI showed a declining pattern of beta-cell function across the glucose-tolerance groups. Overall, hcDI values were 27% greater than 2cDI, due to the hyperglycemic versus euglycemic conditions, reflected in a positive bias with Bland-Altman analysis. Beta-cell function relative to insulin sensitivity could be accurately evaluated from a single hyperglycemic clamp, obviating the need for two separate clamp experiments, when lessening participant burden and reducing research costs are important considerations.