Common Errors in InsulinTherapy Anil Bhansali Department of Endocrinology PGIMER, Chandigarh
Insulin Therapy1. Alternative therapy to insulin in T1DM2. Delay in initiating insulin therapy3. Pre-injection assessment4. Insulin injection techniques5. Regimens of insulin treatment6. Insulin analogues7. Consequences of Insulin Therapy -Short term -Long term
The 2 Defects of T2DM Insulin resistance Insulin deficiencyInsulin resistance alone cannot produce T2DM AJM 2000
Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(Suppl.):S21–S25
Previous Algorithm – Type 2 Inadequate non- pharmacologic therapy 2 Oral 3 Oral 4 Oral* Oral agent agents agents agents Add insulinAdapted from Mudaliar S et al. In: Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY:Appleton and Lange; 2003:531-557. *-Indian scenario
Standard Approaches to Therapy Result in Prolonged Exposure to Elevated Glucose 10% Diet/Exercise Sulfonylurea or Combination Insulin Metformin Therapy Monotherapy 9.6%Mean A1C at Last 9% 9.0% 8.6% Visit 8% 7% ADA Goal <7% 6% Diagnosis 2 3 4 5 6 7 8 9 10 Years At insulin initiation, the average patient had: 5 years with A1C >8% 10 years with A1C >7% Psychological Insulin Resistance(PIR) Brown JB, et al. Diabetes Care. 2004;27:1535-1540.
American Association of Clinical Endocrinologists: algorithm for patients with T2DM Drug-naïve patients Initiate monotherapy HbA1c 6%–7% Metformin, TZD, secretagogues, DPP-4 inhibitors, α-glucosidase inhibitors HbA1c 7%–8% Initiate combination therapy Secretagogue + metformin, TZD, or α-glucosidase inhibitorLifestyle Changes TZD + metformin DPP-4 + metformin or TZD Secretagogue + metformin + TZD Fixed-dose combinations Insulin HbA1c 8%–10% Intensify combination therapy To address fasting and postprandial glucose levels HbA1c >10% Initiate / intensify insulin therapy Patients currently As above pharmacologically Exenatide may be combined with oral therapies in patients treated not achieving goals DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus; TZD=thiazolidinedione AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007; 13 (Suppl 1): 16–34.
When to Add insulin? At the initial diagnosis Failure of maximal doses of monotherapy Failure of submaximal doses of 2 OHA’s Failure of maximal doses of 2 OHA’s Failure of submaximal doses of triple therapy
At the Diagnosis of T2DM Severely symptomatic FPG>250 mg/dl RPG >300mg/dl HbA1c >10% Presence of ketosis BMI < 23 Kg/m2 Cardiac / renal / hepatic dysfunctions Critically ill patients
Injection Storage Store insulin in use at room temperature (15-25oC) and discard 30 days after initial use Short acting analogue,Lispro, in use should be stored at 40 C after use Currently unused vials/refill cartridges should be refrigerated Never freeze the insulin
Injection Technique Re-suspension of cloudy insulin is essential (Rolled 20 cycles) Needle length 4-6 mm Site of injection should be looked for lipohypertrophy or any bruise/blisters Recommend use of alcohol swabs or cotton ball dipped in water for cleaning Injection site : Abdomen < thigh <arm
Ensure the correct insulin syringe with correct strength of insulin (40U vial with 40U syringe) Insulin pen should be primed with two units of insulin as the first step Insert the needle at 90o to the skin fold and count till 10 before pulling the needle out Needle site should not be massaged Injection site should be rotated
Insulin Dose Prescription is not Properly Written!
Inadvertent use of abbreviations Inj Reg insulin 4U Route of administration is not mentioned Site of administration is not written Time of administration is missing Premixed insulin strengths are not mentioned (25:75, 30:70, 50:50)
Pre- and post-injection site assessment is not possible The needle becomes unsterile and can cause infection Skin pinch-up may not be correct through clothing Fiber from the cloth could enter the skin and cause irritation
Lag time between insulin administration and meal -30-45 min for conventional insulin (Hexamer to monomer) -5-10 min for short acting analogues Time of administration of long acting analogues -Preferably at bed time, usually at fixed time -If early morning hypoglycemia, then administer in morning
Short acting insulin is used twice orthrice a day without intermediate or long acting insulin!
This strategy will never control fastinghyperglycemia as short acting insulin acts only for 4-6 hrs.
Characteristics of Currently Available InsulinInsulin Onset of Peak action(h) Duration(h) action(h)NPH 1-3 4-10 10-20Glargine 2-4 No peak 20-24Detemir 2 No peak 16-24Regular 0.5-1 2-3 5-8Lispro/aspart 0.1-0.25 0.5-1.5 3-5Lispro 25/75 0.25-0.5 5.8 12-24Aspart 30/70 0.17-0.33 2.4 ± 0.8 12-24
Insulin Regimens Basal-bolus (3 prandial and one/two NPH or Glargine) Only Basal (NPH or Glargine or Detemir) Premixed twice a day (30:70 either conventional or analogues) Premixed twice a day + one regular insulin at Lunch One regular or short acting analogues to control post-prandial hyperglycemia One dose of premixed insulin before major meals
Insulin Regimens Fasting hyperglycemia -NPH -Glargine at bed time -Detemir Post-prandial hyperglycemia -Regular insulin -Short acting analogues -Premixed Predinner hyperglycemia -NPH, Glargine, Detemir at morning -Premixed before lunch, if it is a major meal ‘Global hyperglycemia’ -Basal and bolus
What should be targeted?-FPG, PPG, HbA1c or all three-Which should be the first?
Basal vs Post-Prandial Hyperglycemia – A1c Uncontrolled Diabetes HbA1c 8% Basal hyperglycaemia 300 contributes ~2% Post-prandial Plasma glucose (mg/dL) hyperglycaemia contributes HbA1c ~1% 200 Post-prandial hyperglycaemia Fasting hyperglycaemia 100 Normal HbA1c ~5% 0 6 B 12 L 18 D 24 6 Time of day (h)B=breakfast; L=lunch; D=dinner.Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.
HbA1c: Limitations Does not detect glycemic excursions Does not reveal hypoglycemia Cautions: ◦ Anemia ◦ Uremia ◦ EPO therapy
Short acting and Long acting Analogues are Indiscriminately Used!
Short acting analogues used as i.v infusion for the treatment of hyperglycemic emergencies Use of short acting analogues with premixed conventional insulin Mixing of glargine with short acting insulin Premixed insulin twice a day and glargine at bedtime
Distinctive Uses of Analogues Short acting analogues -School going children -Pregnancy with diabetes -Busy executives -Gastroparesis Long acting analogues -Elderly subjects -Targeting HbA1c <6.5% -Inability to inject multiple injections
Immediate HypoglycemiaShort term -Weight gain -Worsening of retinopathy and neuropathyLong term -Malignancy
Insulin-Induced Hypoglycemia Major barrier Common with -Advanced duration of disease -Concurrent OHA’s -Older age, DKD
Conclusions Diabetes is an insulin deficient disorder, hence it should be repleted Insulin administration is a state-of-art The time of initiation may be variable but delay should be avoided Close monitoring should be done for hypoglycemia and weight gain