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Glargine versus regular insulin protocol in feline diabetic ketoacidosis

Zeugswetter FK, Luckschander-Zeller N, Karlovits S, Rand JS. Glargine versus regular insulin protocol in feline diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio). 2021 Jul;31(4):459-468. doi: 10.1111/vec.13062. Epub 2021 May 4. PMID: 33945208; PMCID: PMC8360016. 

Diabetes ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus (DM), where up to a 50% mortality rate has been documented in cats. Treatment recommendations for feline patients have been modeled after human and canine data as there is a lack of studies in cats. The major premises of treatment include hydration therapy, correction of electrolyte abnormalities, and insulin therapy. Different insulin protocols include intravenous continuous rate infusion (CRI), intermittent intramuscular (IM) administration, and combination of subcutaneous (SC) and IM injections.

Glargine, a common long-acting insulin analog used in cats, is an effective subcutaneous at-home therapy, and in humans, has comparable effects to regular insulin when given intravenously or intramuscularly. Glargine has been successfully used as a subcutaneous-intramuscular combination (basal-bolus) in cats in DKA in a previous study. However, there have been no comparison studies between basal-bolus glargine with the more traditional regular IV insulin protocol in treatment of feline DKA. This prospective randomized clinical trial aimed to compare these two protocols, with a summary of the data and results presented here:

Primary Outcome Measure: Time (hours) to resolution of ketonemia (plasma Beta-hydroxybutrate (Beta-OHB) concentration < 2.55 mmol/L)

Secondary Outcome Measures: Time (hours) to 1) improvement of hyperglycemia and ketonemia, 2) blood glucose < 250 mg/dl, 3) resolution of acidosis (pH < 7.27), 4) first meal, 5) discharge from hospital Patient Selection: 20 cats were block-randomized to either the regular insulin CRI group (n=10) or basal-bolus SC and IM glargine protocol (n=10). Cats considered for inclusion had a history of diabetes mellitus, at least 2 clinical signs of DKA (mentation score > 1, vomiting, or anorexia), blood glucose > 270 mg/dl, blood Beta-OHB concentration > 2.55 mmol/L, and metabolic high anion gap (AG) acidosis (pH < 7.27, and AG > 20.6 mmol/L).

Exclusions: IRIS Chronic Kidney Disease (CKD) stage > 3 (serum Creatinine > 4.9 mg/dl), congestive heart failure (CHF), mentation score 4 (unable to stand, unresponsive), and if the attending clinician did not follow protocol.

Diagnostic Monitoring: Physical examination, blood collection, and abdominal ultrasound were performed in all cases. Blood Glucose (every 2 hours), venous Beta-OHB (every 6 hours), venous blood gas (every 6 hours), and phosphorus concentrations (every 24 hours) were monitored. If possible, urine was collected by cystocentesis. In cases of refractory hypokalemia, blood magnesium concentration was measured. Thoracic radiographs were taken at clinician’s discretion.

Standard Treatments: 0.9% NaCl IV Fluids (fluid deficits, maintenance, and estimate ongoing losses), Potassium added to fluids based on blood results, Phosphorus IV supplementation based on blood results, antiemetics (Maropitant) and gastric protectants (Esomeprazole)

Non-standard Treatments as Required: Additional fluid stabilization/boluses to improve hydration state, Antimicrobials, Analgesic (opioids), Bicarbonate therapy (with pH < 6.9); Nasoesophageal feeding tubes placed in cats with inappetance greater than 3 days. Cats were fed a liquid diet (Royal Canin Recovery) at standard daily resting energy requirement.

Insulin Therapies: The primary aim of both protocols was to achieve a blood glucose concentration < 250 mg/dl.

1. CRI-group: 1.1 u/kg Regular Insulin added to 250 ml bag of 0.9% saline (first 50 ml drained to allow insulin absorption by plastic tubing); Initiated 2 hours after rehydration at a constant rate of ~0.05 units/kg/hr. Adjusted every 2 hours to achieve an ideal 36-54 mg/dl decrease in blood glucose level.

2. Glargine-group: All cats received 2 units SC bolus regardless of body weight concurrently with starting of rehydration, and 1 unit/cat IM in 2 hours; Additional 1 unit/cat IM every 4 hours if glucose was greater than 250 mg/dl, and then SC Glargine every 12 hours at 0.25 unit/kg.

All Cats Switched to SC Glargine Therapy when: adequately hydrated, eating spontaneously, and blood Beta-OHB concentration < 2.55 mmol/L.

Patients Discharged when: cat was eating, no vomiting, blood Beta-OHB concentration < 2.55 mmol/L, and cat’s condition was assessed by attending clinician as suitable to be sent home.

Highlight Results of the Study:
– 17 cats survived to discharge (80% in CRI-group, 90% in Glargine-group). However, any patients that were euthanized or died were as a result of a non-diabetic condition (i.e. liver failure).
– Median time to blood Beta-OHB concentration < 2.55 mmol/L was comparable in both groups and not statistically significant – Glargine-group had statistically significant shorter median times to first improvement of hyperglycemia (>1.6% decrease from baseline). Glargine-group was 2 hours, CRI-group was 6 hours.
– Glargine-group had a statistically significant shorter median time to discharge from the hospital. Glargine-group was 140 hours, CRI-group was 174 hours.
– Resolution of acidosis, time to first meal, and blood glucose < 250 mg/dl were not statistically significant between groups.
– The major limitation in this study was the small sample size of patients as this may not represent the entire spectrum of cats who present in DKA.

What knowledge can be gained from this study’s results?

It appears that both regular insulin IV CRI therapy and basal-bolus glargine therapy are effective options in treatment of DKA in feline patients, which offers flexibility to veterinarians. From these results, advantages of using glargine therapy would include being less labor intensive for hospital staff, and a shorter hospitalization time which would likely be less stressful for cats and decrease the financial burden on clients. Further studies are still needed to determine the benefits and disadvantages of IM bolus vs CRI-therapy.  ~BJP


For further reading:

Gallagher B, Mahony OM, Rozanski EA, et al. A pilot study comparing a protocol using intermittent administration of glargine and regular insulin to a continuous rate infusion of regular insulin in cats with naturally occurring diabetic ketoacidosis. J Vet Emerg Crit Care. 2015;25:234-239.

Marshall RD, Rand JS, Gunew MN, et al. Intramuscular glargine with or without concurrent subcutaneous administration for treatment of feline diabetic ketoacidosis. J Vet Emerg Crit Care. 2013;23:286-290.

Sparkes AH, Cannon M, ChurchD, et al. ISFM Consensus guidelines on the practical management of diabetes mellitus in cats. Journal of Feline Medicine and Surgery. 2015;17:235-250.