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Updated: Jul 12, 2025

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Associations between insulin-like growth factor binding protein-2 and insulin sensitivity, metformin, and mortality
Rikke Hjortebjerg1, Maja R Kristiansen2, Ivan Brandslund3
1Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark; Endocrine Research Unit, Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology, Odense University Hospital, Denmark.
Aims:
Serum insulin-like growth factor binding protein-2 (IGFBP-2) is low in persons with type 2 diabetes mellitus (T2D) and possibly regulated by metformin. Counter-intuitively, high IGFBP-2 associates with mortality. We investigated the association between IGFBP-2, metformin-treatment, and indices of insulin sensitivity, and assessed IGFBP-2 in relation to prior comorbidity and mortality during five-year follow-up.
Methods:
The study included 859 treatment-naive and 558 metformin-treated persons enrolled in the Danish Centre for Strategic Research in T2D and followed for 4.9 (3.9-5.9) years through national health registries. All proteins were determined in serum collected at enrollment.
Results:
Following adjustment for age, metformin-treated and treatment-naive persons has similar IGFBP-2 levels. Low IGFBP-2 level was associated with increased BMI, fasting glucose, and C-peptide. IGFBP-2 was higher in the 437 persons who had comorbidities at enrollment than in those with T2D only (343 (213;528) vs. 242 (169;378) ng/mL). During follow-up, 87 persons died, and IGFBP-2 predicted mortality with an unadjusted HR (95% CI) per doubling in IGFBP-2 concentration of 2.62 (2.04;3.37) and a HR of 2.21 (1.61;3.01) following full adjustment.
Conclusions:
In T2D, high IGFBP-2 associates with low glucose and insulin secretion, is unaffected by metformin treatment, and associates with risk of prior comorbidity and mortality.
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