Tuesday, November 13, 2012

Diabetes and Insulin Resistance in Miniature Schnauzers

Association of Hypertriglyceridemia with Insulin Resistance
in Healthy Miniature Schnauzers

Panagiotis G. Xenoulis, Melinda D. Levinski, Jan S. Suchodolski,
and Jörg M. Steiner

Primary (idiopathic) hypertriglyceridemia is common in the Miniature Schnauzer breed. A recent study revealed hypertriglyceridemia in almost a third of 192 healthy Miniature Schnauzers in the United States (1). The prevalence of this condition appears to be age-related, with over 75% of older Miniature Schnauzers (> 9 years) suffering from hypertriglyceridemia.

In humans, severe hypertriglyceridemia can induce insulin resistance and may lead to the development of diabetes mellitus (2-5). The Miniature Schnauzer is one of the breeds known to be at risk for developing diabetes (6,7), but the mechanism for why this breed is predisposed to become diabetic has not been investigated.

The purpose of the present study by Xenoulis et al (8) was to determine whether hypertriglyceridemia in Miniature Schnauzers is associated with insulin resistance. To this end, serum glucose and insulin concentrations were measured in two groups of Miniature Schnauzers — one with hypertriglyceridemia and the other without hypertriglyceridemia.

Hypothesis— The hypothesis of this study was that primary or idiopathic hypertriglyceridemia in clinically healthy Miniature Schnauzers is associated with a state of insulin resistance.

Objective—To determine whether hypertriglyceridemia in Miniature Schnauzers is associated with insulin resistance.

Design—Case-control study.

Animals—28 Miniature Schnauzers with hypertriglyceridemia  (study dogs) and 31 Miniature Schnauzers with normal serum triglyceride concentrations (control dogs).

Procedures—All dogs were considered healthy and were not receiving any medications known to affect lipid metabolism or serum insulin concentration. Food was withheld from each dog for ≥ 12 hours; a 5- to 10-ml blood sample was collected and then allowed to clot to obtain serum. Serum insulin and glucose concentrations were measured, and the homeostasis model assessment (HOMA) score was calculated.

Results—Median serum insulin concentration was significantly higher in hypertriglyceridemic Miniature Schnauzers (21.3 mU/L) than it was in the control dogs (12.5 mU/L). The percentage of dogs with high serum insulin concentrations was significantly greater in the hypertriglyceridemic group (28.6%) than it was in the control group (6.5%).

The median HOMA score for hypertriglyceridemic Miniature Schnauzers (4.9) was also significantly higher than that for control dogs (2.8).

Conclusions and Clinical Relevance—Results indicated that hypertriglyceridemia in Miniature Schnauzers is often associated with insulin resistance. Further studies are needed to determine the prevalence and clinical importance of insulin resistance in hypertriglyceridemic Miniature Schnauzers.

My Bottom Line

The results of the present study indicate that Miniature Schnauzers with hypertriglyceridemia often have evidence of insulin resistance, as indicated by higher basal (fasting) serum insulin concentrations and higher HOMA scores.

The HOMA score has been extensively used for the assessment of insulin resistance in humans (9) and has recently also been applied for studies in dogs and cats (10,11). The HOMA score has proven to be very useful for the early detection of insulin resistance in population-based studies and clinical practice because it is simple to determine, accurate, and only requires analysis of a single blood sample.

It is well known that Miniature Schnauzers are at increased risk for the development of diabetes mellitus (6,7). Whether this predisposition of Miniature Schnauzers to diabetes mellitus is associated with the fact that this breed also frequency develops primary hypertriglyceridemia remains to be determined.  However, based on the result of this study, it is certainly plausible that their hypertriglyceride-induced insulin resistance contributes to the glucose intolerance and overt diabetes in these dogs.

In addition, once overt diabetes has been diagnosed, these Miniature Schnauzers are typically difficult to regulate with insulin therapy. As shown in this present study (8), this is likely due to the exogenous insulin resistance that is present in these dogs as a result of their persistent, primary hypertriglyceridemia.

In addition, it is well-established, at least in humans, that insulin resistance itself can lead to secondary hyperlipidemia through the impairment of lipoprotein lipase activity and overactivation of the hormone-sensitive lipase (12). This could also be very important in these dogs because the insulin resistance in hypertriglyceridemic Miniature Schnauzers might contribute to, or worsen, the already present hyperlipidemic state, resulting in an escalation in severity of both conditions (i.e., insulin resistance and hyperlipidemia) in these Miniature Schnauzer dogs.

When most veterinarians see a diabetic dog with suspected insulin resistance, their top list of differentials generally includes hyperadrenocorticism or Cushing's syndrome (13,14). While secondary hypertriglyceridemia, as well as insulin resistance, can develop as a result of hyperadrenocorticism, very few of the "problem diabetic" Miniature Schnauzer dogs that I see have underlying Cushing's syndrome (14).  In fact, I consider hyperadrenocorticism to be a rather uncommon endocrine disorder in the Miniature Schnauzer. One must always remember that we must use caution and be careful not to make a misdiagnosis of Cushing's syndrome in these dogs, which is a common diagnostic problem in any dog with moderate to severe nonadrenal illness (16,17).

  1. Xenoulis PG, Suchodolski JS, Levinski MD, et al. Investigation of hypertriglyceridemia in healthy Miniature Schnauzers. J Vet Intern Med 2007;21:1224–1230. 
  2. Ascaso JF, Real JT, Merchante A, et al. Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia. Metabolism 2000;49:1627–1631. 
  3. Sane T, Taskinen MR. Does familial hypertriglyceridemia predispose to NIDDM? Diabetes Care 1993;16:1494–1501. 
  4. Mingrone G, DeGaetano A, Greco AV, et al. Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids. Diabetologia 1997;40:599–605. 
  5. Mingrone G, Henriksen FL, Greco AV, et al. Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency. Diabetes 1999;48:1258–1263. 
  6. Feldman EC, Nelson RW. Canine diabetes mellitus. In: Feldman EC, Nelson RW, eds. Canine and feline endocrinology and reproduction. St Louis: Saunders, 2004;486–538.
  7. Hess RS, Kass PH, Ward CR. Breed distribution of dogs with diabetes mellitus admitted to a tertiary care facility. J Am Vet Med Assoc 2000;216:1414–1417. 
  8. Xenoulis PG, Levinski MD, Suchodolski JS, et al. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011;238:1011-1016.
  9. McAuley KA, Williams SM, Mann JI, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001;24:460–464.
  10. Serisier S, Leray V, Poudroux W, et al. Effects of green tea on insulin sensitivity, lipid profile and expression of PPARalpha and PPARgamma and their target genes in obese dogs. Br J Nutr 2008;99:1208–1216.
  11. Appleton DJ, Rand JS, Sunvold GD. Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats. J Feline Med Surg 2005;7:183–193. 
  12. Ascaso JF, Real JT, Carmena R. Insulin resistance and familial dyslipidaemias. Diabetes Obes Metabol 1999;1:323–330.
  13. Melián C, Pérez-Alenza D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010; pp. 1816-1840.
  14. Peterson ME. The difficult diabetic: Acromegaly, Cushing’s, and other causes of insulin resistance. North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings. pp. 873-879.
  15. Kaplan AJ, Peterson ME, Kemppainen RJ. Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs. Journal of the American Veterinary Medical Association 1995;207:445-451.
  16. Kaplan A, Peterson ME. Effects of nonadrenal disease on adrenal function tests In: Bonagura JD (ed): Current Veterinary Therapy XIII. Philadelphia, WB Saunders Co., 2000; pp 362-363.

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