Glycated Protein Levels

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Serum Fructosamine and Glycosylated Hemoglobin

Serum fructosamine and glycosylated hemoglobin (HbA1c) are 2 glycated proteins commonly used for monitoring human patients. These 2 proteins are markers of mean glucose concentration, and their amount is proportional to the blood glucose concentration. The concentration of these proteins is not affected by stress; therefore they are often used by veterinary practices to diagnose and monitor cats with diabetes.

Although fructosamine and HbA1c are good tools for determining regulation, they will not identify an underlying problem, nor will they replace glucose curves done for therapy adjustments. Rather, they give an idea of glycemic control over a long period: fructosamine reflects the glycemic control for the previous 2 to 4 weeks and HbA1c for the prior 2 to 4 months.

Fructosamine is preferred over HbA1c to assess glycemic control. It is more commonly evaluated than HbA1c, because simpler, less time-consuming analytical assays are available. Also, successful monitoring and regulation can be achieved with weekly or monthly measurements of serum fructosamine.

Serum Fructosamine

The majority of animals with diabetes will not always have optimal control of blood glucose; thus, fructosamine concentrations are unlikely to lie entirely within the reference range for normal cats. Single fructosamine measurements should be interpreted in the light of clinical signs, body weight, and blood glucose concentration. In general, the closer the fructosamine concentration is to the reference range for healthy cats, the better the glycemic control.

Fructosamine reference ranges⁸

Advantages of measuring fructosamine

• Distinguishes hyperglycemic, cats without diabetes, from cats with diabetes and chronic hyperglycemia.
• Not influenced by stress hyperglycemia in cats.
• Useful in confirming diagnosis in cats.
• Helps evaluate long-term control and owner compliance with insulin treatment.
• Good tool for assessing for the presence of diabetic remission.

Limitations of fructosamine measurements

• Unable to detect short-term or transient abnormalities in the blood glucose concentration, eg, transient daily episodes of hypoglycemia. This would require serial measurement of blood glucose concentrations.
• Hyperthyroid cats with diabetes mellitus may have decreased fructosamine concentrations despite having normal serum protein concentrations. This results from an increase in the protein turnover rate (decreased protein half-life) caused by increased thyroid hormone concentrations.
• Globulin and fructosamine concentrations are correlated in cats. Hypoglobulinemia will result in decreased fructosamine concentration—consult the laboratory performing the analysis as to whether a correction is required and whether this has been done.

Glycosylated Hemoglobin (HbA1c)

HbA1c is produced by the non-enzymatic, irreversible binding of glucose to hemoglobin in erythrocytes. The glycation of hemoglobin is a gradual process and is not affected by acute or transient hyperglycemia.

Use HbA1c concentration as a screening test for diabetes mellitus, as well as to monitor glycemic control in treated animals.

Advantages of HbA1c measurements

• Unaffected by stress-related or postprandial hyperglycemia.
• Useful in long-term monitoring of animals with diabetes over the previous 2 to 3 months.

Limitations of HbA1c measurements

• Test not widely available for cats.
• Not the most effective test due to the relatively long erythrocyte lifespan (~68 days in cats).
• Less effective for short-term monitoring than fructosamine, because hyperglycemia must be present for at least 3 weeks before increased values are detectable.
• Affected by hemoglobin concentrations—may be increased or decreased due to polycythemia or anemia, respectively.

Test results and interpretation vary greatly depending on the literature consulted and the laboratory where the test is performed. So, it’s best to ask each laboratory for guidelines to help with interpretation of results.

To submit blood samples to a laboratory, use red-top serum tubes for fructosamine and EDTA, lavender-top whole-blood tubes for HbA1c. A new dried blood spot mail in test is available for testing HbA1c in cats as well.

Suggested Additional Reading

• Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction.3rd ed. St. Louis, MO: Saunders; 2004.
• Rand JS, Marshall RD. Diabetes mellitus in cats. Vet Clin North Am Small Anim Pract. 2005;35(1):211–224.

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Important Safety Information:

Vetsulin^® should not be used in dogs known to have a systemic allergy to pork or pork products. Vetsulin is contraindicated during periods of hypoglycemia. Keep out of reach of children. As with all insulin products, careful patient monitoring for hypoglycemia and hyperglycemia is essential to attain and maintain adequate glycemic control and prevent associated complications. Overdosage can result in profound hypoglycemia and death. The safety and effectiveness of Vetsulin in puppies, breeding, pregnant, and lactating dogs has not been evaluated. See package insert for full information regarding contraindications, warnings, and precautions.

References:

1. Martin GJ, Rand JS. Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy. J Feline Med Surg. 2001;3(1):23–30. 2. Vetsulin^® (porcine insulin zinc suspension) [Freedom of Information Summary]. Millsboro, DE: Intervet Inc.; 2008. 3. Data on file, Merck Animal Health. 4. Graham PA, Nash AS, McKellar QA. Pharmacokinetics of porcine insulin zinc suspension in diabetic dogs. J Small Anim Pract. 1997;38(10):434–438. 5. Martin GJ, Rand JS. Pharmacokinetic and Pharmacodynamic Study of Caninsulin in Cats with Diabetes Mellitus. 2000: Internal Study Report. 6. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis, MO: Saunders; 2004:539–579. 7. Tennant B, ed. BSAVA Small Animal Formulary. 4th ed. Gloucestershire, UK: British Small Animal Veterinary Association; 2002. 8. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis, MO: Saunders; 2004:486–538. 9. Reusch C. Feline diabetes mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed. St. Louis, MO: Saunders; 2010:1796–1816. 10. Nelson RW. Canine diabetes mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed. St. Louis, MO: Saunders; 2010:1782–1796. 11. Burgaud S, Riant S, Piau N. Comparative laboratory evaluation of dose delivery using a veterinary insulin pen. In: Proceedings of the WSAVA/FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 121. 12. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic dogs. In: Proceedings of the WSAVA/ FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 122. 13. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic cats. In: Proceedings of the WSAVA/FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 45. 14. Davison LJ, Walding B, Herrtage ME, Catchpole B. Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations. J Vet Intern Med. 2008;22:1317-1325. 15. Banfield State of Pet Health 2016 Report. p 12-13.