Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Composite image to demonstrate a pituitary mass typical of cats with acromegaly.

<p>Transverse (left) and saggital (middle) CT images showing a contrast enhancing pituitary mass (>4mm height) in a cat with acromegaly. Without treatment, the cat was euthanised some months later and post-mortem examination demonstrated the large pituitary mass (right). Histopathology was consistent with an acidophil adenoma.</p

Echocardiographic and plasma IGF-1 measurements before and after treatment of acromegaly.

<p>Echocardiographic and plasma IGF-1 measurements before and after treatment of acromegaly.</p

Population characteristics of cats enrolled in the echocardiographic study.

<p>Normally distributed data are represented mean (±standard deviation) and compared using a one-way ANOVA. Non-normally distributed data are represented median (range) and compared using a Kruskal-Wallis test. Categorical variables are represented as percentages and compared using a Chi squared test.</p

Box and whisker plot to illustrate the difference in maximum left ventricular (LV) wall thickness between the three groups of cats at enrolment.

<p>DM, diabetes mellitus; HS, hypersomatotropism.</p

Population characteristics of cats whose myocardial tissue was analysed in the histopathologic study.

<p><i>HCM</i>, <i>hypertrophic cardiomyopathy; HW</i>, <i>heart weight; BW</i>, <i>body weight; RVFW</i>, <i>right ventricular free wall thickness; IVS</i>, <i>interventricular septal thickness; LVFW</i>, <i>left ventricular wall thickness</i>.</p

Box and whisker plots to illustrate the difference in left atrial size between groups at enrolment.

<p>DM, diabetes mellitus; HS, hypersomatotropism.</p

Echocardiographic measurements of all cats enrolled in the study.

<p>Normally distributed data are represented mean (±standard deviation) and compared using a one-way ANOVA. Non-normally distributed data are represented median (range) and compared using a Kruskal-Wallis test. Categorical variables are represented as percentages and compared using a Chi squared test.</p

Box plot to show the proportion of cats affected by myocardial inflammatory cell infiltrate in each group.

<p>Box plot to show the proportion of cats affected by myocardial inflammatory cell infiltrate in each group.</p