Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass
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Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass. / Bojsen-Møller, Kirstine N; Dirksen, Carsten; Svane, Maria Saur; Jørgensen, Nils B; Holst, Jens Juul; Richter, Erik A.; Madsbad, Sten.
In: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 312, No. 5, 2017, p. R797-R805.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass
AU - Bojsen-Møller, Kirstine N
AU - Dirksen, Carsten
AU - Svane, Maria Saur
AU - Jørgensen, Nils B
AU - Holst, Jens Juul
AU - Richter, Erik A.
AU - Madsbad, Sten
N1 - CURIS 2017 NEXS 156
PY - 2017
Y1 - 2017
N2 - Roux-en-Y gastric bypass (RYGB) induces weight loss and improves insulin sensitivity when evaluated by the hyperinsulinemic-euglycemic clamp (HEC). Surrogate indices of insulin sensitivity calculated from insulin and glucose concentrations at fasting or after an oral glucose tolerance test (OGTT) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared with HEC-estimated peripheral insulin sensitivity (Rd or Rd/I, depending on how the index was originally validated) and the tracer-determined hepatic insulin sensitivity index (HISI) in patients with preoperative type 2 diabetes (n=10) and normal glucose tolerance (n=10) 1 week, 3 months and 1 year postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in Rd at any visit, but were comparable to changes in HISI at 1 week. Changes in QUICKI and revised-QUICKI correlated with Rd/I after surgery. Changes in Matsuda and Gutt did not correlate with changes in Rd/I and Rd, respectively, whereas OGIS-changes correlated with Rd-changes at 1 year post-RYGB. In conclusion, surrogate measures of insulin sensitivity may not reflect results obtained with gold standard methodology after RYGB, underscoring the importance of critical reflection when surrogate endpoints are used. Fasting surrogate indices may be particularly affected by post-RYGB changes in insulin clearance, whereas the validity of OGTT-derived surrogates may be compromised by the surgical rearrangements of the gut.
AB - Roux-en-Y gastric bypass (RYGB) induces weight loss and improves insulin sensitivity when evaluated by the hyperinsulinemic-euglycemic clamp (HEC). Surrogate indices of insulin sensitivity calculated from insulin and glucose concentrations at fasting or after an oral glucose tolerance test (OGTT) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared with HEC-estimated peripheral insulin sensitivity (Rd or Rd/I, depending on how the index was originally validated) and the tracer-determined hepatic insulin sensitivity index (HISI) in patients with preoperative type 2 diabetes (n=10) and normal glucose tolerance (n=10) 1 week, 3 months and 1 year postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in Rd at any visit, but were comparable to changes in HISI at 1 week. Changes in QUICKI and revised-QUICKI correlated with Rd/I after surgery. Changes in Matsuda and Gutt did not correlate with changes in Rd/I and Rd, respectively, whereas OGIS-changes correlated with Rd-changes at 1 year post-RYGB. In conclusion, surrogate measures of insulin sensitivity may not reflect results obtained with gold standard methodology after RYGB, underscoring the importance of critical reflection when surrogate endpoints are used. Fasting surrogate indices may be particularly affected by post-RYGB changes in insulin clearance, whereas the validity of OGTT-derived surrogates may be compromised by the surgical rearrangements of the gut.
KW - Bariatric surgery
KW - Peripheral insulin sensitivity
KW - Hepatic insulin sensitivity
KW - HOMA-IR
KW - QUICKI
KW - Matsuda
KW - OGIS
U2 - 10.1152/ajpregu.00291.2016
DO - 10.1152/ajpregu.00291.2016
M3 - Journal article
C2 - 28202439
VL - 312
SP - R797-R805
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5
ER -
ID: 173508972