Page 868 - Small Animal Internal Medicine, 6th Edition

840 PART VI Endocrine Disorders

neuropathy in the diabetic cat include weakness, impaired deficiency. Excessive production of ketone bodies as occurs
ability to jump, knuckling, a plantigrade posture with the in uncontrolled diabetes results in their accumulation in the
VetBooks.ir cat’s hocks touching the ground when it walks (see Fig. 49.14, circulation and development of the ketosis and acidosis of
ketoacidosis.
Video 49.1), muscle atrophy, depressed limb reflexes, and
The etiopathogenesis of DKA is complex and usually
deficits in postural reaction testing. Clinical signs may pro-
gress to include the thoracic limbs (palmigrade posture). affected by concurrent clinical disorders. Virtually all dogs
Abnormalities on electrophysiologic testing are consistent and cats with DKA have a relative or absolute deficiency of
with demyelination at all levels of the motor and sensory insulin. DKA develops in some diabetic dogs and cats even
peripheral nerves and include decreased motor and sensory though they receive daily injections of insulin, and their
nerve conduction velocities in pelvic and thoracic limbs and circulating insulin concentrations may even be increased.
decreased muscle action potential amplitudes. Electromyo- The “relative” insulin deficiency in these animals is created
graphic abnormalities are usually absent and, when identi- by concurrent insulin resistance, which in turn is created
fied, are consistent with denervation. Histologic examination by concurrent disorders such as pancreatitis, infection, or
of nerve biopsies from affected cats reveals endoneurial insulin-resistant hormonal disorder. Increased circulating
microvascular pathology, segmental demyelination, and concentrations of diabetogenic hormones, most notably
axonal degeneration in myelinated nerve fibers that culmi- glucagon, accentuate insulin deficiency by promoting
nate in loss of myelinated fibers. The pathogenesis of diabetic insulin resistance; stimulate lipolysis, leading to ketogen-
peripheral neuropathy is considered multifactorial, with esis; and stimulate hepatic gluconeogenesis, which worsens
contributions from both metabolic and vascular factors. hyperglycemia.
Currently, no specific therapy is available. Aggressive gluco- Insulin deficiency and insulin resistance, together with
regulation with insulin may improve nerve conduction and increased circulating concentrations of diabetogenic hor-
reverse posterior weakness and plantigrade posture (see Fig. mones, play a critical role in the stimulation of ketogen-
49.14). However, the response to therapy is unpredictable, esis. For the synthesis of ketone bodies to be enhanced, two
and the risks of hypoglycemia increase with aggressive major alterations in intermediary metabolism must occur:
insulin treatment. Generally, the longer the neuropathy has (1) enhanced mobilization of FFAs from triglycerides stored
been present and the more severe the neuropathy, the less in adipose tissue, and (2) a shift in hepatic metabolism from
likely it is that improving glycemic control will reverse the fat synthesis to fat oxidation and ketogenesis. Insulin is a
clinical signs of neuropathy. (See Suggested Readings for powerful inhibitor of lipolysis and FFA oxidation. A relative
more information on diabetic neuropathy in cats.) or absolute deficiency of insulin allows lipolysis to increase,
thus increasing the availability of FFAs to the liver and in
Prognosis turn promoting ketogenesis. As ketones continue to accu-
Variables that impact the prognosis are similar for diabetic mulate in the blood, the body’s buffering system becomes
cats and dogs and include owner commitment to treating the overwhelmed, and metabolic acidosis develops. As ketones
disorder, ease of glycemic regulation, presence and revers- accumulate in the extracellular space, the quantity even-
ibility of concurrent disorders, avoidance of chronic compli- tually surpasses the renal tubular threshold for complete
cations associated with the diabetic state, and minimizing resorption, and they spill into the urine, contributing to
the impact of treatment on the quality of life of the owner the osmotic diuresis caused by glycosuria and enhancing
(see p. 830). Median survival time from the time of diagnosis the excretion of solutes (e.g., sodium, potassium, calcium,
was 516 days (range, 1-3468 days) in 114 diabetic cats in magnesium). Insulin deficiency per se also contributes to
Zurich, Switzerland (Callegari et al., 2013). In our experi- excessive renal losses of water and electrolytes. The result is
ence, the mean survival time in diabetic cats is approximately excessive loss of electrolytes and water, leading to volume
3 years from the time of diagnosis. However, survival times contraction, underperfusion of tissues, and the development
are somewhat skewed because cats are usually 8 to 15 years of prerenal azotemia. The rise in blood glucose concentra-
old at the time of diagnosis, and a high mortality rate exists tion raises plasma osmolality, and the resulting osmotic
during the first 6 months because of concurrent life- diuresis further aggravates the rise in plasma osmolality by
threatening or uncontrollable disease (e.g., pancreatitis, causing water losses in excess of salt loss. The increase in
chronic kidney disease, acromegaly). In general, “younger” plasma osmolality causes water to shift out of cells, leading to
diabetic cats that survive the first 6 months can easily live cellular dehydration. The metabolic consequences of DKA,
longer than 5 years with the disease if properly treated. which include severe acidosis, hyperosmolality, obligatory
osmotic diuresis, dehydration, and electrolyte derangements,
DIABETIC KETOACIDOSIS eventually become life-threatening.

Etiology Clinical Features
Ketone bodies (i.e., acetoacetic acid, β-hydroxybutyric DKA is a serious complication of diabetes mellitus that
acid, acetone) are derived from oxidation of nonesterified occurs most commonly in dogs and cats with diabetes that
or free fatty acids (FFAs) by the liver and are used as an has gone undiagnosed. Less commonly, DKA develops in an
energy source by many tissues during periods of glucose insulin-treated diabetic dog or cat receiving an inadequate