Doses - INSULIN INJECTION, REGULAR, INSULIN, ISOPHANE SUSPENSION (NPH), INSULIN, PROTAMINE ZINC SUSPENSION (PZI), INSULIN, ZINC SUSPENSION, EXTENDED (ULTRALENTE)
Note: The reader is strongly encouraged to refer to the original referenced materials for the dosesbelow, for more thorough discussions on the treatment of diabetes.Dogs:
For adjunctive therapy (must also correct dehydration, electrolyte & acid/base imbalances, identify and treat precipitating factors (e.g., infection), and provide a carbohydrate substratewhen necessary) for diabetic ketoacidosis:
a) Regular insulin: Loading dose of 0.2 U/kg IM, repeat IM doses of 0.1 U/kg hourlyuntil blood glucose drops below 250 mg/dl. Monitor blood glucoses every hour.
Attempt to reduce blood glucose by 50 - 100 mg/dl/hr. When blood glucose reaches250 mg/dl, begin concomitant IV dextrose 5% and maintain fluid therapy. Then regularinsulin 0.5 U/kg IM (or SQ if hydration is normal) q4-6h.
Insulin may be diluted with normal saline, sterile water or special diluent (not availablecommercially; obtained from Eli Lilly Co.) if necessary. Once animal is eating, alert, notreceiving IV fluids, and relatively stable, may switch to either PZI or NPH insulin usingthe protocol listed under "Insulin treatment for uncomplicated diabetes mellitus", below. (Nelson and Feldman 1988)
b) Low dose regular insulin infusion method: Add 1 Unit of regular insulin for each 100ml of IV fluid. Administer at a rate so that animal receives between 0.5 - 1 Unit per houror 0.025 - 0.05 Units/kg/hour. Use the lowest dose in small dogs.
Low dose IM method: Initially, 2 Units of regular insulin for dogs less than 10 kg and0.25 Units/kg for dogs over 10 kg of body weight. Thereafter, 1 Unit IM every hour fordogs <10 kg and 0.1 Unit/kg IM every hour for dogs >10 kg.
With either method blood glucose should be monitored hourly and the insulin dosagesoutlined above stopped when blood glucose is between 200-250 mg/dl. Then, eitherinfuse glucose and insulin to promote ketone utilization or convert to conventionaltherapy.
To promote ketone utilization infuse glucose (2 - 3 mg/kg/min) and regular insulin(about 0.035 U/kg/hr) until animal is eating without vomiting. Alternatively, beginconventional therapy by following the guidelines outlined below: "Insulin treatment ofuncomplicated diabetes mellitus". (Schall 1985)
Insulin treatment of uncomplicated diabetes mellitus:
a) Begin NPH at 1 Unit/kg for smaller dogs (<15 kg) and 0.5 Units/kg for larger dogs(>25 kg). Determine blood glucose once or twice an afternoon for the first 2-3 days oftreatment to determine if dose is too high. Animal should preferably be hospitalizedduring the this period. Begin dietary therapy at this time; multiple (3-4) small mealsthroughout the day, beginning with the insulin dose is best. After this initial equilibration period, serial blood glucose measurements (every 1-2 hours) should be taken over the course of the day. Adjust feeding times, frequency of insulin administration, insulin dosage, insulin type (PZI, if once daily NPH doesn't adequately cover and twicea day NPH is not feasible) so that the lowest blood glucose level occurs about 10-12hours after injection with a range of 80-120 mg/dl. At no time should the blood glucoseget below 80 mg/dl. The highest acceptable blood glucose is 180 - 200 mg/dl 24 hourspost-injection. (Nelson and Feldman 1986)
b) Begin PZI at 1 Unit/kg body weight once daily, usually in the morning. Initially, monitor urine glucose (at home) every AM. If there is deviation from the desired 100 - 250 mg/dl urine glucose, increase/decrease insulin by 5-10% accordingly. Feed 1/2 of daily ration in the morning and the remainder in the late afternoon or evening. If theanimal refuses food in the AM, give only 1/2 the scheduled dose.
Alternatively, use NPH at same dosage as PZI, but most animals will require twice dailyinjections to obtain adequate 24 hour control. (Schall 1985)
For adjunctive treatment of hyperkalemia:
a) Regular insulin 5 Units/kg/hr IV combined with glucose at 2 grams per Unit of insulingiven. Onset of action approximately 30 minutes and effects may last for several hours.(Senior 1989)
b) For hyperkalemia associated with hypoadrenocorticism: Regular insulin IV bolus at 0.5
Units/kg. Follow with 1.0 - 1.5 grams of dextrose per unit of insulin administered.
Dextrose should be added to IV fluids and administered over 4-6 hours. (Feldman,
Schrader, and Twedt 1988)
Cats: Because at the present time PZI insulin is unavailable, most veterinarians are substitutingultralente insulin initially on a unit for unit basis, although some recommend reducing insulin doseby 25%, particularly when switching to r-DNA human ultralente. Animals should be carefullymonitored during this intial phase ideally with glucose-response curves, but at a minimum for signsof hyper- or hypoglycemia.
For adjunctive therapy (must also correct dehydration, electrolyte & acid/base imbalances, identify and treat precipitating factors (e.g., infection), and provide a carbohydrate substratewhen necessary) for diabetic ketoacidosis:
a) Regular insulin: Loading dose of 0.2 U/kg IM, repeat IM doses of 0.1 U/kg hourlyuntil blood glucose drops below 250 mg/dl. When blood glucose reaches 250 mg/dl, begin concomitant IV dextrose 2.5 - 5% and maintain fluid therapy until cat can begineating. Then regular insulin 0.5 U/kg SQ q6h; adjust in increments of 0.5 - 1 units tomaintain blood glucose between 100-250 mg/dl.
Insulin may be diluted 1:10 with normal saline or special diluent (not available commercially; obtained from Eli Lilly Co.) if necessary. Monitor blood glucose frequently(every 1-2 hours until patient stabilizes). Once cat is eating and relatively stable, mayswitch to either PZI or NPH insulin using the protocol listed under "Insulin treatmentfor uncomplicated diabetes mellitus". (Peterson and Randolph 1989)
Insulin treatment of uncomplicated diabetes mellitus:
a) Patients on NPH insulin should receive doses every 12 hours. PZI insulin may be usedonce daily. Begin at 0.25 - 0.5 U/kg/day and slowly increase dose as needed. Feed one-half of daily caloric allotment at the time the morning injection is given (both NPH &
PZI) and the other half 12 hours later (with 2nd NPH injection, if used). If diluted withsterile water or isotonic saline when using very low dosages, discard unused insulinafter 2 months.
During first 1-2 weeks of therapy the owner should monitor urine glucose and ketonelevels 1-2 times per day, if possible. Dosage should be adjusted by 0.5 - 1 Unit increments every 3-4 days if necessary (based on serial urine glucose, clinical symptomatology). Dosage should not be adjusted based on a single urine glucose value. Frequentblood glucose measurements (over the course of day, preferable at 1-2 week intervalsuntil stable) are a better method of monitoring therapy and adjusting dosage. (Petersonand Randolph 1989)
b) Begin PZI at 0.5 Unit/kg body weight once daily, usually in the morning. Initially, monitor urine glucose (at home) every AM. If there is deviation from the desired 100 - 250 mg/dl urine glucose, increase/decrease insulin by 5-10% accordingly. Feed 1/2 of daily ration in the morning and the remainder in the late afternoon or evening. If the animal refuses food in the AM, give only 1/2 the scheduled dose.
Alternatively, use NPH at same dosage as PZI, but most animals will require twice dailyinjections of NPH to obtain adequate 24 hour control. (Schall 1985)
For adjunctive treatment of hyperkalemia:
a) Regular insulin 0.5 Units/kg IV combined with glucose at 2 grams per Unit of insulingiven. Onset of action is approximately 30 minutes and effects may last for severalhours. (Senior 1989)
b) For hyperkalemia associated with hypoadrenocorticism: Regular insulin IV bolus at 0.5
Units/kg. Follow with 1.0 - 1.5 grams of dextrose per unit of insulin administered.
Dextrose should be added to IV fluids and administered over 4-6 hours. (Feldman,
Schrader, and Twedt 1988)Cattle:
For hyperglycemia:
a) Adult cow:150 - 200 Units SQ every 36 hours (type of insulin not specified; PZI?).(Howard 1986)Horses:
For diabetes mellitus:
a) True diabetes mellitus rarely occurs in horses. Most cases are a result of pituitary tumors that cause hyperglycemia secondary to excessive ACTH or Growth Hormone. A case is cited where an animal received 0.5 - 1.0 Unit/kg of PZI insulin and the hyperglycemia was controlled. Patients with hyperglycemia secondary to a pituitary tumor are apparently insulin-resistant. (Merritt 1987)
b) PZI insulin 0.15 U/kg IM or SQ bid (Robinson 1987)Birds:
For diabetes mellitus:
a) NPH (U-40) insulin: 0.002 - 0.1 Units IM. Insulin should be diluted 1:1000 yielding aconcentration of 0.04 Units/ml. At this concentration, initially give 0.05 ml/30 gramsbody weight IM. Adjust dosage by monitoring urine glucose. When urine glucosereaches 1+, recheck blood glucose. Generally takes 1-2 weeks to regulate the dosage.(Stunkard 1984)
b) If urine glucose exceeds 0.5 per cent, check serum glucose. If it is > 1000 mg/dl, beginempiric insulin therapy. If serum glucose levels are between 600 - 1000 mg/dl; repeattest in 24 hours and start insulin if repeat test is the same or elevated.
Dilute 0.3 ml of insulin (U-40) with 2.7 ml of lactated Ringer's for larger birds, yielding a solution containing 4 Units/ml. For smaller birds, further dilute 0.1 ml (0.4
Units) of this solution with an additional 0.9 ml of lactated Ringer's to yield a 0.04
Units/0.1 ml solution. Diluted insulin may be stored in the refrigerator for 3-4 months.
Dosages of insulin are extremely variable. Smaller birds generally require more insulinper gram of body weight than larger birds. Reported dosages for budgerigars rangefrom 0.000067 - 0.00333 Units per gram of body weight. Bird should have free accessto food. Twice a day therapy is recommended with monitoring of droppings to maintaina slightly positive glucose level in the urine. (Lothrop et al. 1986)
Monitoring Parameters - 1) Blood glucose; 2) Patient weight, appetite, fluid intake/output; 3)
Blood, urine ketones (if warranted); 4) Glycosylated hemoglobin (if available and warranted)
Client Information - Keep insulin products away from temperature extremes. If stored in the refrigerator, allow to come to room temperature in syringe before injecting.
Clients must be instructed in proper techniques for withdrawing insulin into the syringe, includingrolling the vial, not shaking before withdrawing into syringe, and to use the proper syringe size withinsulin concentration (e.g., don't use U-40 insulin with U-100 syringes). Proper injectiontechniques should be taught and practiced with the client before the animal's discharge. Thesymptoms of hypoglycemia should be thoroughly reviewed with the owner. A written protocoloutlining monitoring procedures and treatment steps for hypoglycemia should be also be sent homewith the owner.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - All products except500 U/ml insulin are available without prescription.
Veterinary-Approved Products: None
Human-Approved Products (partial listing):
Insulin Injection, Regular
From pork sources; 100 Units/ml
Regular Insulin (Novo-Nordisk)
Regular Purified Pork insulin (Novo-Nordisk); Pork Regular Iletin II (Lilly)
Human (either rDNA or semi-synthetic) insulin:
Humulin® R (Lilly); Novolin® R (Novo-Nordisk), Velosulin® Human (Novo-Nordisk)
Insulin, Isophane Suspension (NPH)
From beef sources; 100 Units/ml
Insulin, NPH (Novo-Nordisk)
From pork sources (purified); 100 Units/ml
Iletin® II, NPH Purified Pork (Lilly), NPH-N® (Novo-Nordisk)
Human (either rDNA or semi-synthetic) insulin:
Humulin® N, (Lilly); Novolin® N (Novo-Nordisk),
Insulin, Zinc Suspension, Extended (Ultralente)
From rDNA Human sources; 100 Units/ml
Humulin® U Ultralente (Lilly)
Other insulins that are commercially available, but have not been used extensively in veterinarypatients, include: Insulin Zinc (Lente), and fixed dose combination products containing regularinsulin and isophane insulin (NPH).
Dogs: 
For adjunctive therapy (must also correct dehydration, electrolyte & acid/base imbalances, identify and treat precipitating factors (e.g., infection), and provide a carbohydrate substratewhen necessary) for diabetic ketoacidosis: a) Regular insulin: Loading dose of 0.2 U/kg IM, repeat IM doses of 0.1 U/kg hourlyuntil blood glucose drops below 250 mg/dl. Monitor blood glucoses every hour.
Attempt to reduce blood glucose by 50 - 100 mg/dl/hr. When blood glucose reaches250 mg/dl, begin concomitant IV dextrose 5% and maintain fluid therapy. Then regularinsulin 0.5 U/kg IM (or SQ if hydration is normal) q4-6h.
Insulin may be diluted with normal saline, sterile water or special diluent (not availablecommercially; obtained from Eli Lilly Co.) if necessary. Once animal is eating, alert, notreceiving IV fluids, and relatively stable, may switch to either PZI or NPH insulin usingthe protocol listed under "Insulin treatment for uncomplicated diabetes mellitus", below. (Nelson and Feldman 1988)
b) Low dose regular insulin infusion method: Add 1 Unit of regular insulin for each 100ml of IV fluid. Administer at a rate so that animal receives between 0.5 - 1 Unit per houror 0.025 - 0.05 Units/kg/hour. Use the lowest dose in small dogs.
Low dose IM method: Initially, 2 Units of regular insulin for dogs less than 10 kg and0.25 Units/kg for dogs over 10 kg of body weight. Thereafter, 1 Unit IM every hour fordogs <10 kg and 0.1 Unit/kg IM every hour for dogs >10 kg.
With either method blood glucose should be monitored hourly and the insulin dosagesoutlined above stopped when blood glucose is between 200-250 mg/dl. Then, eitherinfuse glucose and insulin to promote ketone utilization or convert to conventionaltherapy.
To promote ketone utilization infuse glucose (2 - 3 mg/kg/min) and regular insulin(about 0.035 U/kg/hr) until animal is eating without vomiting. Alternatively, beginconventional therapy by following the guidelines outlined below: "Insulin treatment ofuncomplicated diabetes mellitus". (Schall 1985)
Insulin treatment of uncomplicated diabetes mellitus:
a) Begin NPH at 1 Unit/kg for smaller dogs (<15 kg) and 0.5 Units/kg for larger dogs(>25 kg). Determine blood glucose once or twice an afternoon for the first 2-3 days oftreatment to determine if dose is too high. Animal should preferably be hospitalizedduring the this period. Begin dietary therapy at this time; multiple (3-4) small mealsthroughout the day, beginning with the insulin dose is best. After this initial equilibration period, serial blood glucose measurements (every 1-2 hours) should be taken over the course of the day. Adjust feeding times, frequency of insulin administration, insulin dosage, insulin type (PZI, if once daily NPH doesn't adequately cover and twicea day NPH is not feasible) so that the lowest blood glucose level occurs about 10-12hours after injection with a range of 80-120 mg/dl. At no time should the blood glucoseget below 80 mg/dl. The highest acceptable blood glucose is 180 - 200 mg/dl 24 hourspost-injection. (Nelson and Feldman 1986)
b) Begin PZI at 1 Unit/kg body weight once daily, usually in the morning. Initially, monitor urine glucose (at home) every AM. If there is deviation from the desired 100 - 250 mg/dl urine glucose, increase/decrease insulin by 5-10% accordingly. Feed 1/2 of daily ration in the morning and the remainder in the late afternoon or evening. If theanimal refuses food in the AM, give only 1/2 the scheduled dose.
Alternatively, use NPH at same dosage as PZI, but most animals will require twice dailyinjections to obtain adequate 24 hour control. (Schall 1985)
For adjunctive treatment of hyperkalemia:
a) Regular insulin 5 Units/kg/hr IV combined with glucose at 2 grams per Unit of insulingiven. Onset of action approximately 30 minutes and effects may last for several hours.(Senior 1989)
b) For hyperkalemia associated with hypoadrenocorticism: Regular insulin IV bolus at 0.5
Units/kg. Follow with 1.0 - 1.5 grams of dextrose per unit of insulin administered.
Dextrose should be added to IV fluids and administered over 4-6 hours. (Feldman,
Schrader, and Twedt 1988)
Cats: Because at the present time PZI insulin is unavailable, most veterinarians are substitutingultralente insulin initially on a unit for unit basis, although some recommend reducing insulin doseby 25%, particularly when switching to r-DNA human ultralente. Animals should be carefullymonitored during this intial phase ideally with glucose-response curves, but at a minimum for signsof hyper- or hypoglycemia.
For adjunctive therapy (must also correct dehydration, electrolyte & acid/base imbalances, identify and treat precipitating factors (e.g., infection), and provide a carbohydrate substratewhen necessary) for diabetic ketoacidosis:
a) Regular insulin: Loading dose of 0.2 U/kg IM, repeat IM doses of 0.1 U/kg hourlyuntil blood glucose drops below 250 mg/dl. When blood glucose reaches 250 mg/dl, begin concomitant IV dextrose 2.5 - 5% and maintain fluid therapy until cat can begineating. Then regular insulin 0.5 U/kg SQ q6h; adjust in increments of 0.5 - 1 units tomaintain blood glucose between 100-250 mg/dl.
Insulin may be diluted 1:10 with normal saline or special diluent (not available commercially; obtained from Eli Lilly Co.) if necessary. Monitor blood glucose frequently(every 1-2 hours until patient stabilizes). Once cat is eating and relatively stable, mayswitch to either PZI or NPH insulin using the protocol listed under "Insulin treatmentfor uncomplicated diabetes mellitus". (Peterson and Randolph 1989)
Insulin treatment of uncomplicated diabetes mellitus:
a) Patients on NPH insulin should receive doses every 12 hours. PZI insulin may be usedonce daily. Begin at 0.25 - 0.5 U/kg/day and slowly increase dose as needed. Feed one-half of daily caloric allotment at the time the morning injection is given (both NPH &
PZI) and the other half 12 hours later (with 2nd NPH injection, if used). If diluted withsterile water or isotonic saline when using very low dosages, discard unused insulinafter 2 months.
During first 1-2 weeks of therapy the owner should monitor urine glucose and ketonelevels 1-2 times per day, if possible. Dosage should be adjusted by 0.5 - 1 Unit increments every 3-4 days if necessary (based on serial urine glucose, clinical symptomatology). Dosage should not be adjusted based on a single urine glucose value. Frequentblood glucose measurements (over the course of day, preferable at 1-2 week intervalsuntil stable) are a better method of monitoring therapy and adjusting dosage. (Petersonand Randolph 1989)
b) Begin PZI at 0.5 Unit/kg body weight once daily, usually in the morning. Initially, monitor urine glucose (at home) every AM. If there is deviation from the desired 100 - 250 mg/dl urine glucose, increase/decrease insulin by 5-10% accordingly. Feed 1/2 of daily ration in the morning and the remainder in the late afternoon or evening. If the animal refuses food in the AM, give only 1/2 the scheduled dose.
Alternatively, use NPH at same dosage as PZI, but most animals will require twice dailyinjections of NPH to obtain adequate 24 hour control. (Schall 1985)
For adjunctive treatment of hyperkalemia:
a) Regular insulin 0.5 Units/kg IV combined with glucose at 2 grams per Unit of insulingiven. Onset of action is approximately 30 minutes and effects may last for severalhours. (Senior 1989)
b) For hyperkalemia associated with hypoadrenocorticism: Regular insulin IV bolus at 0.5
Units/kg. Follow with 1.0 - 1.5 grams of dextrose per unit of insulin administered.
Dextrose should be added to IV fluids and administered over 4-6 hours. (Feldman,
Schrader, and Twedt 1988)
Cattle: 
For hyperglycemia: a) Adult cow:150 - 200 Units SQ every 36 hours (type of insulin not specified; PZI?).(Howard 1986)
Horses: 
For diabetes mellitus: a) True diabetes mellitus rarely occurs in horses. Most cases are a result of pituitary tumors that cause hyperglycemia secondary to excessive ACTH or Growth Hormone. A case is cited where an animal received 0.5 - 1.0 Unit/kg of PZI insulin and the hyperglycemia was controlled. Patients with hyperglycemia secondary to a pituitary tumor are apparently insulin-resistant. (Merritt 1987)
b) PZI insulin 0.15 U/kg IM or SQ bid (Robinson 1987)
Birds: 
For diabetes mellitus: a) NPH (U-40) insulin: 0.002 - 0.1 Units IM. Insulin should be diluted 1:1000 yielding aconcentration of 0.04 Units/ml. At this concentration, initially give 0.05 ml/30 gramsbody weight IM. Adjust dosage by monitoring urine glucose. When urine glucosereaches 1+, recheck blood glucose. Generally takes 1-2 weeks to regulate the dosage.(Stunkard 1984)
b) If urine glucose exceeds 0.5 per cent, check serum glucose. If it is > 1000 mg/dl, beginempiric insulin therapy. If serum glucose levels are between 600 - 1000 mg/dl; repeattest in 24 hours and start insulin if repeat test is the same or elevated.
Dilute 0.3 ml of insulin (U-40) with 2.7 ml of lactated Ringer's for larger birds, yielding a solution containing 4 Units/ml. For smaller birds, further dilute 0.1 ml (0.4
Units) of this solution with an additional 0.9 ml of lactated Ringer's to yield a 0.04
Units/0.1 ml solution. Diluted insulin may be stored in the refrigerator for 3-4 months.
Dosages of insulin are extremely variable. Smaller birds generally require more insulinper gram of body weight than larger birds. Reported dosages for budgerigars rangefrom 0.000067 - 0.00333 Units per gram of body weight. Bird should have free accessto food. Twice a day therapy is recommended with monitoring of droppings to maintaina slightly positive glucose level in the urine. (Lothrop et al. 1986)
Monitoring Parameters - 1) Blood glucose; 2) Patient weight, appetite, fluid intake/output; 3)
Blood, urine ketones (if warranted); 4) Glycosylated hemoglobin (if available and warranted)
Client Information - Keep insulin products away from temperature extremes. If stored in the refrigerator, allow to come to room temperature in syringe before injecting.
Clients must be instructed in proper techniques for withdrawing insulin into the syringe, includingrolling the vial, not shaking before withdrawing into syringe, and to use the proper syringe size withinsulin concentration (e.g., don't use U-40 insulin with U-100 syringes). Proper injectiontechniques should be taught and practiced with the client before the animal's discharge. Thesymptoms of hypoglycemia should be thoroughly reviewed with the owner. A written protocoloutlining monitoring procedures and treatment steps for hypoglycemia should be also be sent homewith the owner.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - All products except500 U/ml insulin are available without prescription.
Veterinary-Approved Products: None
Human-Approved Products (partial listing):
Insulin Injection, Regular
From pork sources; 100 Units/ml
Regular Insulin (Novo-Nordisk)
Regular Purified Pork insulin (Novo-Nordisk); Pork Regular Iletin II (Lilly)
Human (either rDNA or semi-synthetic) insulin:
Humulin® R (Lilly); Novolin® R (Novo-Nordisk), Velosulin® Human (Novo-Nordisk)
Insulin, Isophane Suspension (NPH)
From beef sources; 100 Units/ml
Insulin, NPH (Novo-Nordisk)
From pork sources (purified); 100 Units/ml
Iletin® II, NPH Purified Pork (Lilly), NPH-N® (Novo-Nordisk)
Human (either rDNA or semi-synthetic) insulin:
Humulin® N, (Lilly); Novolin® N (Novo-Nordisk),
Insulin, Zinc Suspension, Extended (Ultralente)
From rDNA Human sources; 100 Units/ml
Humulin® U Ultralente (Lilly)
Other insulins that are commercially available, but have not been used extensively in veterinarypatients, include: Insulin Zinc (Lente), and fixed dose combination products containing regularinsulin and isophane insulin (NPH).