Insulin Therapy

By Dr. Adithya Polavarapu

 Principles of insulin therapy
On average, the body requires 40 USP units of insulin daily.
Total daily requirement of
20 units for basic metabolism → basal insulin
insulin
20 units for calorie consumption → bolus insulin

1 unit of insulin lowers the blood glucose level by 30–40 mg/dL (1.7–2.2
Insulin correction factor
mmol/L)

10 g of carbohydrates increases the blood glucose level by 30–40 mg/dL (1.7–

Carbohydrate counting
2.2 mmol/L).

On average, 1 unit of insulin is required for 15 g carbs = 1 carb serving (carb

unit); however, this varies greatly from patient to patient.
Insulin-to-carbohydrate
Insulin sensitivity fluctuates over the course of a day → Insulin-to-
ratio
carbohydrate ratio changes over the course of a day.

Morning hours: 2 units insulin, lunchtime: 1 unit, evening hours: 1.5 units
Principles of insulin therapy

Insulin replacement therapy: The exogenous insulin requirement

depends on the residual insulin production of the pancreas.

Type 1 diabetes The initial total daily dose (TDD) of insulin should be 0.6–1.0 U/kg.

After beginning insulin treatment, there is often a temporary reduction

in exogenous insulin demand.

Residual endogenous insulin production is augmented with exogenous

insulin, depending on the extent of insulin resistance (which in turn
Type 2 diabetes depends on the level of obesity).

The TDD of insulin should be 0.1–0.2 U/kg.

Indications of insulin therapy
• Newly diagnosed patients with significantly elevated A1C levels (>
8.5%) or symptomatic diabetes: Initiate insulin therapy with or without
an antidiabetic drug.
• Patients with insufficient glycemic control (target A1C not reached) over
a 3-month treatment period with metformin or another antidiabetic drug:
• Initiate basal insulin supported oral therapy (BOT).
• Consider initiating insulin therapy.
• Pregestational and gestational diabetes
• Patients with end stage renal failure (oral antidiabetic drugs are
contraindicated in this case)
Insulin types

Types of insulin Examples

Lispro
Rapid acting Aspart
Glulisine

Short acting Insulin Regular Insulin

Intermediate acting insulin NPH insulin

Glargine
Long acting insulin Detemir
Degludec
Insulin injection sites
Insulin Regimens
Conventional insulin therapy

1. Fixed regimen of insulin injections:

• usually twice daily injection of insulin (mixture of 30% regular
insulin and 70% intermediate insulin) with self-monitoring of
blood glucose levels
• For example, ⅔ of the daily dosage before breakfast and ⅓
before dinner. The interval between injection and meal times
should be about 30 minutes.
2. Advantages: simple regimen, requiring minimal patient education,
not very time-consuming
3. Disadvantages: patients must adhere to a rigid diet and exercise
plan. Snacks may be required between meals to avoid
hypoglycemia.
Insulin Regimens
Intensive insulin therapy
1. The goal is to simulate physiological glucose metabolism by keeping fasting
blood glucose levels < 100 mg/dL (5.6 mmol/L) and postprandial blood glucose
levels < 140 mg/dL (< 7.8 mmol/L)
2. Intensified conventional therapy
• Basal-bolus regimen: basal insulin 1–2 times daily, + bolus insulin injection
30–45 minutes before meals adjusted to preprandial blood glucose
measurements
• The bolus insulin dose depends on the preprandial blood glucose level, meal
size and time of day
• Indication: type 1 diabetes; insulin-dependent type 2 diabetes with a high
degree of compliance
3. Insulin pump
• Continuous subcutaneous insulin infusion (regular or rapid-acting insulin
analogs)
• Basal and bolus insulin may be managed individually
• Indication: type 1 diabetes, children, pregnancy, dawn phenomenon
Insulin Regimens
Intensive insulin therapy
• Advantages
1. Optimal glycemic control and reduced risk of complications in patients with
good compliance
2. More flexibility in the daily diet and exercise plan
• Disadvantages
1. Complex and time-consuming therapy; requires frequent blood glucose
measurements
2. High risk of hypoglycemia
3. Patients require intensive education and must be motivated and committed.

Basal Supported Oral Therapy

Alternative to conventional or intensive insulin therapy
Indication: combination therapy for type 2 diabetic patients with persistently elevated
A1C levels despite oral antidiabetic regimen
Regimen: long-acting insulin injection (e.g., glargine) before bedtime combined with
an oral antidiabetic drug regimen
Sliding-scale insulin regimen
• If the patient is eating all or most of each meal: Administer as short-
acting insulin (or rapid-acting insulin) before each meal and at bedtime.

• If the patient is not eating: Administer as short-acting insulin every 6

hours.
Basal-bolus insulin regimen
1. Calculate the total daily dose of insulin (TDD) needed.
If the patient is already on a correction scale: Increase or decrease TDD
by 10–20% as needed.
If the patient is lean, has T1DM, is aged ≥ 70 years, and/or has GFR <
60 mL/min: 0.2–0.3 units/kg
If none of the above criteria apply, use the blood glucose level:
BG 140–200 mg/dL: 0.4 units/kg
BG > 200 mg/dL: 0.5 units/kg

2. Divide the TDD of insulin into basal insulin (50%) and nutritional
insulin (50%).
Basal insulin: administer as long-acting insulin (e.g., glargine) at
bedtime
Nutritional insulin: administer as rapid-acting insulin (e.g., lispro) in
equally divided doses before meals
Basal-bolus insulin regimen
3. Add sliding scale insulin as supplemental insulin.
• Take 5% of the TDD (e.g., if the TDD is 50 units, 5% is 2.5).
• Round down to the nearest whole number (e.g., round down 2.5 units
to 2 units).
• For every 40 mg/dL above the goal serum glucose of 140 mg/dL,
increase the nutritional insulin scale by the appropriate increments

4. Adjust as needed.
• In cases of hypoglycemia < 70 mg/dL: Reduce basal insulin by 20%
and/or sliding scale insulin by 2 units.
• If glucose is persistently > 140 mg/dL and no episodes of
hypoglycemia occur: Increase basal insulin by 20% and/or increase
sliding scale insulin by 2 units.
Weight-based NPH insulin regimen for
glucocorticoid-induced hyperglycemia

1. Convert glucocorticoid to equivalent prednisone dose

2. Calculate daily NPH dose based on prednisone dose equivalent and
patient weight.
3. Administer glucocorticoid with NPH as a single dose in the morning.

Prednisone dose equivalent (mg/day) NPH (units/kg/day)

10 0.1

20 0.2

30 0.3

≥ 40 0.4
Insulin Regimens References
1. Sliding-scale insulin regimen [1]
2. Basal-bolus insulin regimen [2][3]
3. Weight-based NPH insulin regimen for glucocorticoid-induced
hyperglycemia [4]

[1]Umpierrez GE, Smiley D, Zisman A, et al. Randomized Study of Basal-Bolus Insulin Therapy in
the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial). Diabetes Care. 2007;
30(9): pp. 2181–2186. doi: 10.2337/dc07-0295.
[2] Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of Hyperglycemia in
Hospitalized Patients in Non-Critical Care Setting: An Endocrine Society Clinical Practice Guideline.
The Journal of Clinical Endocrinology & Metabolism. 2012; 97(1): pp. 16–38. doi: 10.1210/jc.2011-
2098.
[3] Umpierrez GE, Smiley D, Zisman A, et al. Randomized Study of Basal-Bolus Insulin Therapy in
the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial). Diabetes Care. 2007;
30(9): pp. 2181–2186. doi: 10.2337/dc07-0295.
[4]Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-Induced Hyperglycemia. Am J Med Sci.
2013; 345(4): pp. 274–277. doi: 10.1097/maj.0b013e31828a6a01.
Adverse effects
• Hypoglycemia
• Weight gain
• Lipodystrophy at the injection site
• Hypokalemia
• Allergic or hypersensitivity reactions
• Edema
• Pain and erythema at the injection site
Early-morning hyperglycemia
Dawn phenomenon
• A common problem (especially in young type 1 diabetic patients)
• Definition: early-morning hyperglycemia occurs because of the
physiological increase of growth hormone levels in the early morning
hours, which stimulates hepatic gluconeogenesis. The subsequent
increase in insulin demand cannot be met in insulin-dependent patients,
resulting in elevated blood glucose levels in the morning.
• Treatment: measurement of nocturnal blood glucose levels before
initiating insulin therapy. The long-acting insulin dose may be given
later (around 11 p.m.) or increased under careful glycemic control.
Treatment with an insulin pump may be considered in children.
Somogyi effect (rare)
• Definition: early-morning hyperglycemia because of a counterregulatory
secretion of hormones that is triggered by nocturnal hypoglycemia
secondary to an evening insulin injection
• Treatment: reduction of the evening dose of the long-acting insulin
 Conditions that require insulin adjustments

• Physical activity: decreases insulin by 1–2 units per 20–30 minutes

activity
• Illness, stress, and changes in diet
Increase in insulin demand: many illnesses are associated with
elevated blood glucose levels due to an acute stress reaction. The
subsequent increase in insulin demand cannot be met by patients
with insulin deficiency. A higher insulin dose is required.
Decrease in insulin demand: vomiting and diarrhea lead to
decreased glucose uptake, increasing the risk of hypoglycemia.
• Surgery: ⅓–½ of the usual daily requirement with frequent monitoring
Thank You