Table of contents
.
Physiology
- Insulin increases energy stores
- Liver
- Promotes anabolic synthesis of glycogen, TG, cholesterol, VLDL, and protein in liver.
- Inhibits breakdown of hepatic glycogen and gluconeogenesis - controling overnight hepatic glucose production.
- Muscles:
- Enhances ribosomal protein synthesis, increases amino acid transport.
- Increases glucose transport into muscle, Enhances activity of glycogen synthase, inhibits glycogen phosphorylase. -> muscle glycogen synthesis.
- Adipose:
- Promotes TG storage in adipocytes.
- Increases glucose transport into fat cells.
- Enahances lipoprotein lipase activity, inhibits lipolysis.
- Liver
- Terminology:
- Insulin-To-Carb Ratio
- Used by Type I DM patients to determine insulin requirements for each meal
- ICR = 500 / TotalDailyInsulin
- Example: 70kg male, requires 70*0.7=49 u/day. ITC = 500 / 49 = 10 (1 unit of Insulin will cover 10g of carbs)
- Insulin Sensitivity Factor
- 100 / TotalDailyInsulin = ISF
- Can be used to calculate insulin corrections
- (CurrentGlucose - Target Glucose) / ISF = Units of Insulin Required
- Example:
- (i.e. 70kg male requires 70*0.7 = 49 u/day. ISF =100/49 =2.0)
- If current BG is 12, targets 7. Then: (12 - 7)/2.0 =2.5 units to correct to 7 mmol/L glucose
- Insulin-To-Carb Ratio
Benefits of Insulin
Type I - Diabetes control and complications trial (DCCT):
- Multi-center, randomized controlled trial
- MDI or continuous SC insulin infusion (Intensive Therapy) vs. 1-2 daily injections (conventional)
- Intensive therapy: LOWER Microvascular complications
- Lower HbA1c, RRR 76% for retinopathy, 39% RRR for microalbuminuria, 64% RRR of neuropathy, and 40% RRR of developing high LDL (also decreases progression).
- Benefit of macrovascular complications there, but not statistically significant.
- Intensive therapy: LOWER Microvascular complications
- Meta analysis: Other studies: decreases macrovascular complications
Type II - United Kingdom Prospective Diabetes Trial (UKPDS)
- Multicenter randomized controlled study
- Whether intensive BG control affects microvascular and macrovascular end-points.
- 12% reduction of DMII endpoints, 25% reduction in microvascular end-points
- No difference WITHIN intensive therapy group (i.e. sulfonylureas vs. insulin).
- Macrovascular complications: Non-statistically significant drop in 16%
Diabetes Insulin-Glucose in Acute Myocardial Infarction (DIGAMI) Trial
- Insulin therapy after MI decreases all-cause mortality by 58%
Risks of Insulin
- MAIN RISKS:
- Weight Gain
- Hypoglycemia
- Insulin risks in Type I Diabetes: (DCCT trial)
- Hypoglycemia (inversely related to HbA1c)
- Weight Gain
- Rarely: Allergy and Infection
- Insulin Risks in Type II Diabetes (UKPDS)
- Same as DMI -
- hypoglycemia (less than in DMI)
- weight gain (significant - 4kg wt increase UKPDS P<0.001)
- allergy
- infection.
- Long-standing debate about causing atherosclerosis (but it's association rather than causation - insulin resistance causing hyperinsulinemia).
- Same as DMI -
Types of Insulin
- For 50 years - only available as bovine or porcine preparations.
- 1980's: human insulins and analogues, and animal insulins became obsolete.
-
Insulin forms hexamers in solution, once injected, they dissociate. Rapid acting insulins, dissociate faster, causing more rapid
absorption.
- Combinations;
- Humulin 70/30 - Insulin Regular and NPH Insulin
- Humalog Mix 75/25 or 50/50 - Insulin lispro protamine and insulin lispro
- Novolog Mix 70/30 - Insulin aspart protamine and insulin aspart
Insulin Dosing
- First figure out how much insulin needed (TDI = total daily insulin):
- If person is on insulin: Use home insulin requirement, add up all the insulins during the day.
OR - Newly diagnosed type 1 diabetes,start with 0.3 units/kg/day. Over time,most patients with type 1 diabetes require 0.7 unit/kg/day. Some patients with type 1 diabetes and obesity develop insulin resistance and may require > 0.7 units/kg/day.
- If person is on insulin: Use home insulin requirement, add up all the insulins during the day.
- Determine Regimen
- Multiple Daily Insulin (MDI) Dosing (aka Basal-Bolus Regimen)
- Advantage: Excellent glycemic control.
- After calculating total daily dose of insulin
- Give 1/2 as basal insulin (i.e., glargine at bedtime)
- Give remaining 1/2 divided by 3 before each meal
- teach patient how to adjust insulin based on blood glucose readings before each meal
- Ideally teach patient how to perform carbohydrate counting for the meal time insulin
- To calculate 500 divided by TDD = 1 unit for ____ grams of carbohydrate
- Also teach them how to calculate a correction bolus
- To calculate insulin sensitivyt factor: 100 divided by TDD
-
- Patient takes current blood glucose - minus target glucose (typically 7 mmol/L) divide by your insulin sensitivity factor
- Also calculat
- 1 (prandial breakfast) : 1 (prandial lunch) : 1 (prandial supper) : 2 (basal bedtime)
- 8 : 8 : 8 : 16
- Can add supplemental insulin: (measure insulin TID before meals for hyperglycemia)
-
Before Meal
(glucose)
LOW DOSE
(< 50u daily)
HIGH DOSE
(> 50u daily)
8.1-10 0 units 2 units 10.1-12 1 units 4 units 12.1-14 2 units 6 units 14.1-16 3 units 8 units >16 4 units 10 units
-
- Example regimen #2:
- 50% Basal (i.e. 20U)
- 50% Bolus (i.e. 20U)
- Example regimen #3:
- 60% daytime bolus ( 1/3 for each of the 3 meals) (lantus = better due to pharmacokinetics)
- 40% bedtime basal long acting (glargine, detemir)
- Basal Insulin Only
- Advanage: Once/day injection, easy to administer, cheap.
- Disadvantage: No mealtime adjustments. Only useful for early insulin-dependent TIIDM
- All TDI given as evening Lantus or Detemir insulin
- Fixed Split/Premixed
- Advantages: less injections.
- Disadvantages: not recommended for Type I DM due to poor control.
- Continuous Subcutaneous Insulin Infusion (CSII)
- Advantages: Recommended for TIDM, Excellent glycemic control.
- Disadvantages: Requires a device, risk of hyperglycemia due to catheter blockage.
- Sliding Scale
- A scale that allows pre-defined insulin doses given based on the measured glucose levels.
- OBSOLETE, DO NOT USE
- Advantages: NONE (Less pages overnight)
- Disadvantages:
- Triples rate of hyperglycemia (Queale et al 1997)
- Increases incidence of sepsis, admission to ICU(McMaster Study in pts with pneumonia)
- Increases incidence of infection (RABBIT 2 trial)
- No difference in hypoglycemia rates compared to basal-bolus insulin regimen (RABBIT 2 trial)
- Regimen "Three-Times-a-Day Dosing"
- No longer used due to newer "Lantus" release which can be given once at bedtime.
Total Daily Insulin (TDI) -
Before Breakfast Before Dinner Bedtime Total Daily Insulin (TDI) Breakfast Dose
= 2/3 of TDI
Evening Dose:
1/3 of TDI
NPH Insulin 2/3 of Breakfast Dose NONE 2/3 of Evening Dose Mealtime Insulin 1/3 of Breakfast Dose 1/3 of Evening Dose None - Adjust basal NPH before breakfast --> based on afternoon glucose (before dinner)
- Adjust basal NPH at nightime --> based on morning fasting dose
- No longer used due to newer "Lantus" release which can be given once at bedtime.
- Regimen "Once Daily" or "Twice Daily"
- No longer recommended.
- Level 1A evidence in Type I DM -> MDI and CSII achieves lower HbA1c levels and significan reduces microvascular complications compared to once-daily and twice-daily regimens. (DCCT trial)
- Also calculat
- Multiple Daily Insulin (MDI) Dosing (aka Basal-Bolus Regimen)
NOTES:
- Long-acting given before dinner increases risk of hypoglycemia at night
- Twice-daily dosing not recommended for Type 1 diabetics.
- Insulin-Only regimens are EQUIVALENT to Insulin + Oral agent regimens. (3 references in "Insulin for treating Type 1 and Type 2 Diabetes; Cheng et al"
- HOWEVER: Adding metformin to insulin in poorly controled TIIDM lowers glucose+lipids better than insulin alone (same reference above)
- Best Regimen: Bedtime NPH + metformin (better glycemic control, less hypoglycemia, and prevention of wt gain"
- Some evidence of weight loss of evening NPH + oral agents group compared to other regimens.
- Insulin Infusion Pump (IIP)
- Same HbA1C as MDI, but less glycemic variation, less wt gain, less hypoglycemia episodes, better quality of life.
- Biggest risk is blocked catheter.
Chart that may or may not be helpful:
Comments