Treatment of Diabetes Mellitus in Dogs and Cats by gxr14046

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									complications                                                                                                                                                                                                                                                   ENDOCRINOLOGY




Thomas Schermerhorn,VMD, Diplomate ACVIM, Kansas State University




Treatment of Diabetes Mellitus
in Dogs and Cats
                                                                                                                     Acute complications are those directly related to                                                                    can cause significant morbidity and may be fatal
Diabetes mellitus results                                                                                            insulin administration and can occur in new and                                                                      in some patients.2 In some poorly regulated dia-
                                                                                                                     established diabetics. Chronic complications                                                                         betic patients, chronic subclinical hypoglycemia
when insulin production is                                                                                           occur when diabetes therapy is in the mainte-                                                                        or episodic bouts of clinical hypoglycemia may
                                                                                                                     nance phase and usually result from poorly con-                                                                      occur. The latter situations largely reflect prob-
reduced or abolished (secretory                                                                                      trolled diabetes.                                                                                                    lems with diabetic management that require
                                                                                                                                                                                                                                          reevaluation of the insulin therapy protocol.
defect) or when insulin action                                                                                       Acute complications
                                                                                                                     Hypoglycemia: Insulin-induced hypoglycemia                                                                           Hypophosphatemia: In diabetic dogs and
at target tissues is impaired                                                                                        is a severe and potentially life-threatening com-                                                                    cats, hypophosphatemia usually develops after
                                                                                                                     plication of diabetes treatment. Under some cir-                                                                     insulin treatment has begun and is caused by
(insulin resistance).                                                                                                cumstances, insulin therapy can precipitate                                                                          rapid insulin-mediated cellular uptake of phos-
                                                                                                                     hypoglycemia as well as exacerbate or promote                                                                        phorus. Severe hypophosphatemia (phospho-
The metabolic defects of diabetes primarily                                                                          hypophosphatemia, hypokalemia, and hypov-                                                                            rous levels < 1.0 mg/dl) causes hemolysis,
include hyperglycemia and hyperlipidemia,                                                                            olemia. Hypoglycemia in established diabetics                                                                        which can be life-threatening. Decreased serum
although electrolyte abnormalities, dehydration,                                                                     may occur after pharmacologic insulin doses or                                                                       phosphorus impairs adenosine triphosphate
ketosis, and metabolic acidosis may develop                                                                          accidental insulin overdose. In any circum-                                                                          generation and reduces 2,3-diphosphoglycerate
with severe insulin deficiency when treatment is                                                                     stance, unrecognized or untreated hypoglycemia                                                                       concentrations in red cells, which leads to red
delayed. Prompt and effective treatment of dia-                                                                                                                                                                                           cell fragility and reduced oxygen delivery. Mas-
betes is necessary to prevent catastrophic meta-                                                                                                                                                                                          sive hemolysis can develop when serum phos-
bolic complications, but treatment of diabetes is
                                                                                                                           Table 1.
                                                                                                                                                                                                                                          phate falls below the critical level needed to
associated with complications as well, some of                                                                             Complications of Treatment
                                                                                                                                                                                                                                          maintain red cell integrity. Hypophosphatemia
which can be life-threatening.                                                                                             of Diabetes Mellitus                                                                                           may also cause varying degrees of rhabdomyoly-
                                                                                                                           Acute                                                                                                          sis, ileus, and encephalopathy.3
Types of Complications                                                                                                            Hypoglycemia
The complications associated with diabetes mel-                                                                                                                                                                                           Hypokalemia and hypomagnesemia:
                                                                                                                                  Hypophosphatemia
litus fall into two general categories: those that                                                                                                                                                                                        These may be noted at diagnosis or develop dur-
arise from untreated diabetes and those that                                                                                      Hypokalemia                                                                                             ing the treatment of ketoacidosis and other
develop during treatment for diabetes (Table                                                                                      Hypovolemia                                                                                             complicated forms of diabetes. Total-body potas-
1). The emergency management of complicated                                                                                                                                                                                               sium and magnesium may be depleted in diabet-
                                                                                                                           Chronic
diabetes has been reviewed in detail1 and is not                                                                                                                                                                                          ics because of reduced dietary intake and
addressed here. This article focuses on the                                                                                       Persistent hyperglycemia                                                                                increased renal and gastrointestinal losses. Dur-
causes and treatments of complications that                                                                                       Cataracts                                                                                               ing diabetes treatment, fluid diuresis promotes
develop in dogs and cats during treatment of                                                                                      Neuropathy                                                                                              renal loss of potassium and magnesium, and
diabetes mellitus.                                                                                                                                                                                                                        insulin treatment can precipitate or exacerbate
                                                                                                                                  Weight gain
                                                                                                                                                                                                                                          hypokalemia and hypomagnesemia by promot-
Complications associated with diabetes treat-                                                                                     Episodic hypoglycemia                                                                                   ing cellular water and solute uptake.4,5
ment may be classified as acute or chronic.                                                                                       Susceptibility to infection
                                                                                                                                                                                                                                                                                                                      c o n t i n u e s


co m p l i c at i o n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . N AV C c l i n i c i a n’s b r i e f . j a n u a r y . 2 0 0 8 . . . . . 3 5
complications                                                              CONTINUED




Chronic complications                                                                                                polyneuropathy has been described in diabetic
Persistent hyperglycemia: Persistent hyper-
glycemia may be one of the most prevalent com-
                                                                                                                     dogs and cats. Clinically, the pelvic limbs are
                                                                                                                     more commonly affected than the thoracic
                                                                                                                                                                                                                                                 2
plications of diabetes. When due to ineffective                                                                      limbs. Affected animals demonstrate pelvic limb
insulin therapy, it is associated with persistent                                                                    weakness, abnormal postural reactions, and
clinical signs of diabetes. Chronic hyperglycemia                                                                    depressed tendon reflexes.7 Diabetic cats with
places the patient at risk for glucose toxicity and                                                                  polyneuropathy assume a plantigrade stance
other chronic diabetic complications, such as                                                                        characterized by dropped tarsi and gait abnor-
cataract formation, neuropathy, malnutrition,                                                                        malities. The pathophysiology that underlies the
and susceptibility to infection. Additionally,                                                                       development of neuropathy is unknown but may
patient quality of life may be perceived as unac-                                                                    involve altered polyol metabolism and glucose
ceptable, leading to premature or unnecessary                                                                        toxicity.                                                                                                             A portion of an abdominal radiograph showing
euthanasia. Ineffective insulin therapy in estab-                                                                                                                                                                                          emphysematous cystitis in a diabetic dog. The uri-
                                                                                                                                                                                                                                           nary bladder has a mixed air and soft-tissue density
lished diabetics causes poor glycemic control                                                                        Susceptibility to infection: Evidence sug-                                                                            due to the accumulation of air within the bladder
and can lead to the development of severe meta-                                                                      gests that diabetes causes immune suppression                                                                         wall. Urinary culture confirmed infection with
bolic complications, such as ketoacidosis.                                                                           in dogs and cats, as it does in humans. Several                                                                       Escherichia coli, which is a common organism associ-
                                                                                                                                                                                                                                           ated with this disorder in dogs.
                                                                                                                     studies have identified diabetes as a risk factor
Cataract formation: Diabetic cataract forma-                                                                         for bacterial and fungal urinary tract infections
tion is common in dogs, and may be more com-                                                                         in dogs and cats.8,9 Emphysematous cystitis                                                                           vation with instructions to report the appearance
mon in cats than previously believed (Figure                                                                         caused by infection with gas-forming bacteria                                                                         of clinical signs or other concerns to the veteri-
1). Cataracts result from deranged glucose                                                                           occurs more often in diabetic dogs (Figure 2).                                                                        narian. A more involved program might involve
metabolism in the diabetic lens. Chronic hyper-                                                                      Similarly, many clinicians feel that diabetic ani-                                                                    having the owners perform urine monitoring for
glycemia impairs glycolytic pathways and leads                                                                       mals have a higher incidence of urinary, repro-                                                                       glucose and ketones or keep a diary of pertinent
to increased sorbitol and fructose production in                                                                     ductive, and skin infections than nondiabetics                                                                        details about the pet. Several recent studies
the lens. Sorbitol and fructose exert osmotic                                                                        and that infections may be more difficult or take                                                                     showed the feasibility of at-home blood glucose
forces that draw water into the lens, causing                                                                        longer to clear in diabetic patients.                                                                                 monitoring for companion animals, which has
swelling and rupture of the lens filaments and                                                                                                                                                                                             led to alternative strategies for at-home glucose
ultimately cataract formation.6 Secondary lens-                                                                      Prevention of Complications                                                                                           monitoring for certain pets.10,11
induced uveitis is an additional ocular complica-                                                                    Prevention of complications in treated diabetics
tion of cataract formation.                                                                                          is facilitated by anticipation of common prob-                                                                        Recommendations for veterinary monitoring
                                                                                                                     lems and a close veterinarian–pet owner rela-                                                                         also vary. Most diabetic dogs and cats should be
Peripheral neuropathy: Distal symmetric                                                                              tionship. Regular veterinary care that includes                                                                       evaluated by a veterinarian at least twice a year,
                                                                                                                     careful monitoring of glycemic control and                                                                            although 3 to 4 times per year may be appropri-

      1                                                                                                              proper dietary management is essential to mini-
                                                                                                                     mize or prevent diabetic complications, but the
                                                                                                                                                                                                                                           ate for some patients. Physical and laboratory
                                                                                                                                                                                                                                           assessments are performed at each visit. Labora-
                                                                                                                     vital role of client education for prevention of                                                                      tory evaluations helpful for assessing diabetic
                                                                                                                     diabetic complications cannot be understated.                                                                         control include the serum fructosamine level
                                                                                                                                                                                                                                           and glucose curve assessment.
                                                                                                                     Maintain adequate glycemic control:
                                                                                                                     Chronic hyperglycemia is associated with the                                                                          Client education: Client education is an
                                                                                                                     development of diabetic complications. Thus,                                                                          essential part of diabetes therapy. For successful
                                                                                                                     adequate control of blood glucose is probably                                                                         management, owners must be taught the basic
                                                                                                                     the single most important goal for prevention of                                                                      principals of glucose control and insulin admin-
                                                                                                                     chronic diabetic complications. Proper blood                                                                          istration. It is important that they also be taught
Cataract in a dog: Cataracts are a common and frus-                                                                  glucose control requires close patient monitor-                                                                       to look for clinical signs of poor glucose control
trating complication of diabetes, especially in dogs.
In many dogs, cataracts are present when diabetes is
                                                                                                                     ing by the owner at home and by periodic vet-                                                                         and insulin overdose and learn to perform dia-
diagnosed. In others, cataracts form after insulin                                                                   erinary evaluations. Diabetic monitoring can                                                                          betic “first aid” should an adverse complication
therapy is initiated. Unfortunately, although glycemic                                                               take many forms depending on the patient, the                                                                         arise. Properly educated and motivated owners
control minimizes cataract formation, even dogs with
reasonably well-controlled diabetes often develop
                                                                                                                     owner, and the veterinarian. A simple at-home                                                                         can help prevent or reduce morbidity associated
cataracts that interfere with vision.                                                                                monitoring program might be limited to obser-                                                                         with diabetic management.

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Treatment of Complications                                                                                           Hypophosphatemia: Phosphorous deficiency
Hypoglycemia: Clinical signs of hypoglycemia                                                                         is treated with intravenous phosphorous supple-                                                                            Table 2.
after insulin administration are a relatively com-                                                                   mentation. Potassium phosphate, which contains                                                                             Intravenous Potassium
mon adverse effect of diabetes treatment and                                                                         3 mmol phosphate/ml, is added to compatible                                                                                Chloride Supplementation
often occur while the patient is at home with the                                                                    intravenous fluids. The recommended dose for
owner.12 Feeding the pet a small meal or rub-                                                                        phosphorous supplementation is 0.01 to 0.03                                                                                Serum Potassium                                       Potassium
bing corn syrup on the gingiva can be done at                                                                        mmol/kg per hour, although higher replacement                                                                                   Level                                             Chloride
                                                                                                                     rates are needed in some dogs and cats.3                                                                                       (mEq/L)                                             to Add
home by the owner and may be all that is need-                                                                                                                                                                                                                                                          (mEq/L)
ed to treat mild hypoglycemia. Moderate or
severe hypoglycemia usually requires veterinary                                                                      Hypokalemia: In hospitalized patients,                                                                                                   > 3.5                                             20
attention. Intravenous infusion of a 50% glu-                                                                        hypokalemia is corrected by the addition of                                                                                            3.0–3.5                                             30
cose solution (0.5 g glucose/ml) is the emer-                                                                        potassium chloride to intravenous fluids. Intra-                                                                                       2.5–3.0                                             40
gency treatment of choice. Glucose is                                                                                venous supplementation of potassium chloride
                                                                                                                                                                                                                                                            2.0–2.5                                             60
administered at 0.5–1.0 g/kg body weight (1–2                                                                        should be based on the serum potassium level
ml/kg of the 50% solution). The 50% solution                                                                         (Table 2), and the rate of potassium supple-                                                                                             < 2.0                                             80
is typically diluted 1:4 (to make a 10% solu-                                                                        mentation should not exceed 0.5 mEq/kg per
tion) before injection to minimize the discom-                                                                       hour. Contraindications for potassium supple-
fort associated with intravenous injection of                                                                        mentation include hyperkalemia of any cause,                                                                         caused by an inappropriate choice of insulin.
concentrated glucose.12                                                                                              and it should be avoided in cases of acute renal                                                                     Determining the cause of persistent hyper-
                                                                                                                     failure where urine production is subnormal.                                                                         glycemia may be more difficult if the problem is
Persistent hypoglycemia is best addressed by                                                                         Occasionally, hypokalemia will persist in diabet-                                                                    due to true insulin resistance, which is typically
constant-rate glucose infusion or by administra-                                                                     ic dogs and cats, especially those with concur-                                                                      suspected when the patient is receiving at least
tion of glucagon. A constant-rate infusion of glu-                                                                   rent chronic renal failure. Chronic hypokalemia                                                                      2.2 U/kg of insulin per dose. An algorithm for
cose is prepared by adding 5% to 10% glucose                                                                         in stable patients can be treated by using oral                                                                      approaching persistent hyperglycemia is pre-
to a balanced electrolyte solution. After an initial                                                                 potassium supplements added to daily meals.1                                                                         sented in the Diagnostic Tree on page 39.
bolus injection to restore euglycemia, the glu-
cose infusion is initiated at 10 to 20 ml/kg per                                                                     Hypomagnesemia: Available magnesium sup-                                                                             Cataracts: The preferred treatment for
hour. The infusion rate may have to be titrated                                                                      plements for intravenous use include magne-                                                                          cataracts is surgical removal of the affected lens.
to reach the desired endpoint of euglycemia.                                                                         sium chloride (9.25 mEq Mg2+/g) and                                                                                  If lens-induced uveitis is present, ocular inflam-
The total dose of glucose needed before eug-                                                                         magnesium sulfate (8.13 mEq Mg2+/g). Magne-                                                                          mation should be controlled by using topical
lycemia is restored is difficult to predict. In a                                                                    sium-containing solutions must be diluted in 5%                                                                      glucocorticoid or nonsteroidal antiinflammatory
study of dogs and cats with insulin overdose,                                                                        dextrose in water (D5W solution; maximum                                                                             drug preparations before lensectomy.7 If retinal
median values have been reported to be greater                                                                       concentration 20%) for intravenous administra-                                                                       pathology is present, electroretinography should
than 1 g glucose/kg, but individual patients                                                                         tion. The dosage is up to 1 mEq/kg per day                                                                           be performed before cataract removal.7 Cataract
required as much as 20 g/kg.12                                                                                       given by constant-rate infusion. Care must be                                                                        removal is a highly specialized procedure, and
                                                                                                                     taken to ensure that the magnesium solutions                                                                         referral to a veterinary ophthalmologist or quali-
Glucagon infusion has been reported as an                                                                            are compatible with any crystalloid fluid prepa-                                                                     fied veterinary surgeon is recommended.
effective therapy for hypoglycemia caused by                                                                         rations and drugs the patient may be receiving.14
canine insulinoma but may also be helpful in                                                                                                                                                                                              Neuropathy: Unfortunately, there is no specific
cases of insulin overdose.13 A constant-rate infu-                                                                   Persistent hyperglycemia: No single treat-                                                                           treatment for diabetic neuropathy. Clinical
sion of glucagon is prepared by first reconstitut-                                                                   ment strategy will be effective for all cases of                                                                     improvement in nerve function, posture, and
ing 1 mg of injectable glucagon with the diluent                                                                     persistent hyperglycemia.15 Often, persistent                                                                        gait is observed in some affected animals when
supplied by the manufacturer and adding it to 1                                                                      hyperglycemia results from ineffective insulin                                                                       strict glucose control is imposed, suggesting that
L 0.9% sodium chloride (final concentration of                                                                       replacement therapy, but physiologic insulin                                                                         glucose toxicity may play a role in the develop-
infusion solution is 1000 ng/ml). The initial                                                                        resistance is responsible in some cases. Regard-                                                                     ment of neuropathy.7 s
constant-rate infusion is set at 5 to 10 ng/kg per                                                                   less of cause, the treatment goal is to reestablish
minute, although the rate can be titrated as                                                                         blood glucose control. Glycemic control may be                                                                       See Aids & Resources, back page, for
needed.                                                                                                              readily reestablished if the problem is due to a                                                                     references, contacts, and appendices.
                                                                                                                     compliance or management problem or is                                                                               Article archived on www.cliniciansbrief.com



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