Dogs: Monitoring and controlling diabetes mellitus

Glycated protein levels

Fructosamine and glycosylated hemoglobin

Fructosamine and glycosylated hemoglobin (GHb) are two glycated proteins commonly used for monitoring diabetic human patients. These two 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 ideal for monitoring stressed, diabetic dogs.

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

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

Fructosamine

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

Fructosamine reference ranges

Dogs
Fructosamine values (micromol/L)
Normal non-diabetic dog
225-365
Newly diagnosed diabetic dog
320-850
Treated diabetic dogs:
Excellent control
350-400
Good control
400-450
Fair control
450-500
Poor control
>500

(Reference: Feldman EC, Nelson RW (2004) Canine diabetes mellitus. In Canine and Feline Endocrinology and Reproduction. 3rd edition. Saunders, St Louis, USA p.510)

Advantages of measuring fructosamine

  • Distinguishes hyperglycemic, non-diabetic animals from diabetics with chronic hyperglycemia.
  • Does not appear to be influenced by transient hyperglycemia.
  • Useful in evaluating longer-term control and owner compliance with insulin treatment.

Limitations of fructosamine measurements

  • Unable to detect short-term or transient abnormalities in the blood glucose concentration, e.g. transient daily episodes of hypoglycemia. This would require serial measurement of blood glucose concentrations.
  • Albumin and fructosamine concentrations are highly correlated in dogs. Dogs with hypoalbuminemia also have a decreased fructosamine concentration (false negative) – the laboratory performing the analysis should be consulted as to whether a correction is required and whether or not this has been done.

Glycosylated Hemoglobin

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

Glycosylated (glycated) hemoglobin concentration can be used as a screening test for diabetes mellitus, as well as for the monitoring of glycemic control in treated diabetic animals.

Advantages of GHb measurements

  • Unaffected by stress-related or post-prandial hyperglycemia.
  • Useful in long-term monitoring of diabetic animals over the previous 2−4 months.

Limitations of GHb measurements

  • Test not widely available for dogs.
  • Not the most effective test due to the relatively long erythrocyte lifespan (approximately 110 days in dogs).
  • 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. Therefore, it is recommended to ask each laboratory for the guidelines for the purposes of interpretation.

To submit blood samples to the lab, tubes for serum (red-top tubes) must be used for fructosamine; and tubes for whole blood (EDTA tubes, lavender-top tubes) for GHb.

Suggested additional reading:

  1. Canine and Feline Endocrinology and Reproduction. 3rd edition, Feldman & Nelson, 2004.
  2. The Veterinary Clinics of North America, May 1995.