Sustained hyperglycemia causes glycosylation of protein groups. The first change is the nonenzymatic addition of glucose to protein amino groups to form Amadori products. These reach a steady state over time and do not accumulate further. Amadori products are formed with albumin (resulting in the fructosamine assay), hemoglobin (resulting in the glycosylated hemoglobin assay) and lipoproteins (LDL). This is a reversible change.
With time, the Amadori products get transformed by dehydration, condensation, fragmentation, oxidation and cyclization to advanced glycosylation end products (AGE). This is an irreversible change. AGE form on proteins, lipids and nucleic acids and are thought to be responsible for the side-effects associated with diabetes mellitus, including diabetic neuropathy, retinopathy and nephropathy. Therefore, it is important to maintain glucose concentrations within reference intervals when treating diabetic patients.
Any cause of hyperglycemia (transient or sustained) may result in glucosuria if glucose concentrations are high enough to exceed the renal threshold. The renal threshold for glucose is species-dependent and is reported to be 180-220 mg/dL in dogs, 280-290 mg/dL in cats (lower thresholds may occur in diabetic cats), and 150 mg/dL in horses and cattle.

• Physiologic: Physiologic hyperglycemia occurs post-prandially and in response to stress in all species. This can be mediated by epinephrine (and is transient, lasting 4-6 hours) or corticosteroids (results in a more sustained increase in glucose). Cats and cattle tend to produce marked stress hyperglycemias. In cattle, a very high glucose (> 500 mg/dL) is a poor prognostic indicator. In liver disease, a prolonged postprandial hyperglycemia may be observed.
• Therapeutic agents: Glucocorticoids, dextrose-containing fluids, thyroxine, xylazine, megesterol acetate etc.
• Disease
  Sustained increases in glucose can be seen with insulin deficiency (type II diabetes mellitus) or insulin resistance. Insulin resistance can be a result of increased concentrations of hormones (e.g. glucocorticoids, growth hormone, progesterone) or inflammatory cytokines (TNF-a) that oppose insulin release or the action of insulin on peripheral tissues. Obesity is also associated with insulin resistance, particularly in cats and likely in horses. Adipose tissue is now known to be an endocrine organ and can produce specific hormones (e.g. leptin) as well as inflammatory cytokines (TNF-a).
  
  1) Diabetes mellitus: This is inherited in Keeshonds and Golden Retrievers. It has been associated with BVD infection in cattle and paramyxovirus infection in llamas. Cats are prone to non-insulin dependent diabetes mellitus. This is thought to be associated with deposition of pancreatic amyloid (from amylin protein), which is related to pancreatic islet dysfunction. When islet destruction is widespread, cats do become insulin-dependent.
  2) Hyperadrenocorticism: In dogs and horses, hyperglycemia is due to insulin resistance.
  3) Acromegaly: Hyperglycemia is due to insulin resistance.
  4) Hyperglucagonemia: Hyperglycemia is due to insulin resistance.
  All the above produce prolonged or sustained hyperglycemia.
  5) Hyperthyroidism in cats: Increases in glucose are often transient. The exact mechanism is unknown (? defective insulin secretion, ? enhanced sensitivity to catecholamines).
  6) Acute pancreatitis: Hyperglycemia, which is usually transient, may occur due to stress, glucagon secretion and decreased insulin production.

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