BackgroundIn 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.ObjectiveTo 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.AnimalsEighty‐four privately owned female intact Swedish Elkhounds >4 years of age.MethodsBlood 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).ResultsIn 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.ConclusionWe showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.