title: Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass.
abstract: 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 surrogates (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared with HEC-estimated peripheral insulin sensitivity (RdorRd/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 wk, 3 mo, and 1 yr postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes inRdat any visit, but were comparable to changes in HISI at 1 wk. Changes in QUICKI and revised-QUICKI correlated withRd/I after surgery. Changes in the Matsuda and Gutt indices did not correlate with changes inRd/I andRd, respectively, whereas OGIS changes correlated withRdchanges at 1 yr 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 surgical rearrangements of the gut.
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark; kirstine.bojsen-moeller@regionh.dk.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kirstine N
authors.identifier: 0000-0003-1962-5302
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Dirksen
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Svane
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nils B
authors.initials: NB
authors.lastname: Jørgensen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Nutrition, Exercise and Sports Sciences, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D015390:Gastric Bypass; D015309:Glucose Clamp Technique / Q000379:methods*; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D009767:Obesity, Morbid / Q000097:blood* / Q000175:diagnosis / Q000601:surgery*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: HOMA-IR; Matsuda; OGIS; QUICKI; bariatric surgery; hepatic insulin sensitivity; peripheral insulin sensitivity