Relationship among insulin resistance, growth hormone, and insulin-like growth factor I concentrations in diestrous Swedish Elkhounds

Abstract

Background: In the dog, the normal estrous cycle includes a prolonged luteal phase. Progesterone stimulates local canine mammary growth hormone (GH) production, which may act systemically and contribute to insulin resistance. Swedish Elkhounds are predisposed to progesterone-related diabetes mellitus, and the relationship among insulin resistance, GH, and insulin-like growth factor I (IGF-I) is of particular interest.

Objective: To study insulin resistance in relation to GH and IGF-I in nondiabetic Swedish Elkhounds during diestrus. We also assessed whether alterations in these hormones could predict diestrus-linked diseases and all-cause mortality.

Animals: Eighty-four privately owned female intact Swedish Elkhounds >4 years of age.

Methods: Blood sampling and clinical examination during luteal phase, with a follow-up questionnaire after 20 months. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR).

Results: In multivariable regression analysis, GH was positively associated with HOMA-IR (P = .009). An increase in GH of 1 ng/mL was associated with a 12.7% increase in HOMA-IR. Moreover, C-peptide was positively associated with IGF-I (P = .04), and an increase in C-peptide of 0.1 ng/mL was associated with a 6.9% increase in IGF-I. Structural equation modeling supported these results. Twenty-three animals were found to have previously unrecognized mammary masses and had higher GH (P < .0001) and IGF-I (P = .007) than dogs without mammary masses (n = 61). There was no association between high GH and IGF-I concentrations at sampling and future mammary masses.

Conclusion: We showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.

Figure 1

Flowchart of study design.

Figure 2

Hypothetical causal pathways in GH axis and insulin resistance in Swedish Elkhounds. The bold paths shown in the web were included in structural equation modeling.

Figure 3

Results of structural equation modeling in Swedish Elkhounds (n = 37) based on the causal web depicted in Fig 2. Significance was set to P < .2. Significant paths are bold.