Hypertriglyceridemia is a common age-related lipid disorder in miniature schnauzers that used to be considered a benign condition. Recent studies, however, have shown a link between hypertriglyceridemia and conditions such as pancreatitis and hepatobiliary disease similar to what is seen in people. Insulin resistance and subsequent development of diabetes mellitus have also been linked to hypertriglyceridemia in people, but this association has not been evaluated in dogs. Comparing serum insulin concentrations in healthy miniature schnauzers with those with hypertriglyceridemia, the authors of this study hypothesized that this condition is associated with insulin resistance.
Healthy miniature schnauzers were enrolled in the study if they were free of clinical signs of illness for at least three months before blood collection, had no history of chronic diseases that would affect lipid metabolism or insulin or glucose concentrations, and were not taking any medication that could affect lipid metabolism or insulin and glucose concentrations. The dogs were fasted for at least 12 hours before blood collection, and samples were analyzed for triglyceride, insulin, and glucose concentrations. Each dog was given a homeostasis model assessment (HOMA) score based on the following formula:
HOMA score = [basal insulin concentration (mU/L) x basal serum glucose concentration (mmol/L)]/22.5
The HOMA score is used for the early detection of insulin resistance in people and has been applied in recent studies in dogs and cats as well. Traditionally, insulin resistance is measured by using the euglycemic hyperinsulinemic clamp technique, which is very accurate but requires multiple blood samples and injections of insulin and glucose. The HOMA scoring system was chosen for this study because it requires a single blood sample and is accurate and simple to use.
Based on serum triglyceride concentrations, dogs were assigned to one of two groups. Group 1 consisted of miniature schnauzers with triglyceride concentrations above the reference range of 26 to 108 mg/dl, while group 2 consisted of those with normal triglyceride concentrations.
Fifty-nine miniature schnauzers were eligible for inclusion in the study; 28 were found to have elevated triglyceride concentrations and were allocated to group 1, while 31 had normal concentrations and were assigned to group 2. The mean age of the dogs was 8.2 and 6.7 years, respectively, for groups 1 and 2. There was a statistically significant difference in the insulin concentrations and HOMA score between the two groups but no difference in glucose concentrations. Mean insulin concentrations were 21.3 mU/L for group 1 compared with 12.5 mU/L for group 2 (reference range 8.4 to 33 mU/L), while the HOMA scores were 4.9 and 2.8, respectively, indicating an insulin-resistant state in dogs with hypertriglyceridemia.
Result analysis and implications
Insulin resistance implies a decreased sensitivity to insulin at the tissue level, which leads to overproduction of insulin by the pancreas to maintain glucose homeostasis. This is the first study, to the authors’ knowledge, to investigate the association between insulin resistance and hypertriglyceridemia in dogs. In group 1 dogs, 28.6% had insulin concentrations above the reference range, while only 6.5% of group 2 dogs had hyperinsulinemia. Although not validated as a measure of insulin resistance in dogs yet, it is interesting to note that the dogs with hypertriglyceridemia in group 1 also had higher HOMA scores than those in group 2.
In people, the presence of insulin resistance has been associated with the development of diabetes mellitus and hepatobiliary disease. While not determined in this study, the authors postulate that perhaps a predisposition to the development of hypertriglyceridemia in miniature schnauzers and subsequent insulin resistance may also be the reason behind their predisposition to develop diabetes mellitus. This also raises the question whether diabetes mellitus is more difficult to control in hypertriglyceridemic schnauzers that are insulin-resistant. In people, it is known that insulin resistance may result in hypertriglyeridemia as a result of impaired lipoprotein lipase activity and overactivation of hormone-sensitive lipase. It is possible then, the authors hypothesize, that insulin resistance may further elevate triglyceride concentrations in miniature schnauzers with primary hypertriglyceridemia and, ultimately, increase the severity of both conditions in these patients.
Previous studies have shown that insulin resistance may develop as a result of obesity, and a possible limitation of this study was the lack of information on the body condition scores of the enrolled dogs. The authors note, however, that the dogs’ weights were comparable between the two groups, suggesting that obesity was not an important factor in this study.
Other medical conditions that could contribute to hypertriglyceridemia such as hyperadrenocorticism and hypothyroidism were not specifically tested for in these dogs. Inclusion into the study, however, required that the dogs be free of any clinical signs of illness for at least three months before enrollment, which, the authors feel, makes concurrent illnesses unlikely.
The authors note that it is unclear from the present study whether insulin resistance would resolve with treatment of the hypertriglyceridemia or how much time it takes to develop insulin resistance in light of hypertriglyceridemia. While the findings in this study raise interesting questions, further studies in this area are warranted.
Xenoulis PG, Levinski MD, Suchodolski JS, et al. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011;238(8):1011-1016.
Link to abstract: http://avmajournals.avma.org/doi/abs/10.2460/javma.238.8.1011?journalCode=javma