Common Errors in Insulin Therapy

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

Alternative therapy to insulin in T1DM!

Omission of insulin in T1DM is SUICIDAL

Never stop insulin even during sickness

Follow sick day guidelines

Delay in Initiation of Insulin Therapy

The 2 Defects of T2DM

Insulin resistanceInsulin deficiency

Insulin resistance alone cannot produce T2DM

AJM 2000

Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(Suppl.):S21–S25

Adapted from Mudaliar S et al. In: Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY:Appleton and Lange; 2003:531-557.

Add insulin

Oral agent 2 Oral agents

Inadequate non-pharmacologic therapy

3 Oral agents3 Oral agents

Previous Algorithm – Type 2

4 Oral* agents4 Oral* agents

*-Indian scenario

At insulin initiation, the average patient had: 5 years with A1C >8% 10 years with A1C >7%

Standard Approaches to Therapy Result inProlonged Exposure to Elevated Glucose

Brown JB, et al. Diabetes Care. 2004;27:1535-1540.

Sulfonylurea or Metformin Monotherap

y

ADA Goal <7%

CombinationTherapy

Diet/Exercise

Mean

A1

C a

t Last

Vis

it

YearsDiagnosis 2 3 4 5 6 7 8 9 10

9.6%

9.0%8.6%

6%

7%

8%

9%

10%

Insulin

Psychological Insulin Resistance(PIR)

ADA 2012 Algorithm for T2DM

DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus; TZD=thiazolidinedioneAACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007; 13 (Suppl 1): 16–34.

American Association of Clinical Endocrinologists: algorithm for patients with T2DM

Drug-naïve patientsHbA1c 6%–7%

Initiate monotherapyMetformin, TZD, secretagogues, DPP-4 inhibitors, α-glucosidase inhibitors

HbA1c 7%–8% Initiate combination therapySecretagogue + metformin, TZD, or α-glucosidase inhibitor TZD + metforminDPP-4 + metformin or TZDSecretagogue + metformin + TZD Fixed-dose combinationsInsulin

As aboveExenatide may be combined with oral therapies in patients not achieving goals

Patients currently pharmacologically treated

HbA1c 8%–10% Intensify combination therapyTo address fasting and postprandial glucose levels

HbA1c >10% Initiate / intensify insulin therapy

Lif

esty

le C

han

ges

When to Add insulin?

At the initial diagnosis Failure of maximal doses of monotherapyFailure 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 T2DMSeverely symptomaticFPG>250 mg/dlRPG >300mg/dlHbA1c >10%Presence of ketosisBMI < 23 Kg/m2

Cardiac / renal / hepatic dysfunctions

Critically ill patients

ORIGIN study

N Engl J Med 2012; 367:309-318

Add Insulin

Patient on two OHA’s FPG > 130 mg/dlPPG > 180 mg/dlHbA1c >8.5%Tighter control is desiredContraindication/intolerant to

other OHA’s

Pre-injection Assessment is Not Done!

Pre- injection Assessment

Injection-related concernsPsychological insulin resistance (personal failure, anticipated

pain, once on insulin always on insulin)

Pre-injection Assessment

-Dexterity problems -Cognitive capacity -Health literacy -Numeracy skills -Visual impairment -Local infections, ulcers and

scars

How insulin should be stored ?

Injection StorageStore 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 is not Properly Advised!

Injection TechniqueRe-suspension of cloudy insulin is

essential (Rolled 20 cycles)Needle length 4-6 mmSite 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 massagedInjection site should be rotated

Insulin Dose Prescription is not Properly Written!

Inadvertent use of abbreviationsInj Reg insulin 4URoute of administration is not

mentionedSite of administration is not

writtenTime of administration is missingPremixed insulin strengths are

not mentioned (25:75, 30:70, 50:50)

Insulin is administered through clothing !

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

Insulin is Administered just Prior to Meal!

Lag time between insulin administration and meal

-30-45 min for conventional insulin (Hexamer to monomer)

-5-10 min for short acting analoguesTime 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 or thrice a day without intermediate or long acting

insulin!

This strategy will never control fasting hyperglycemia as short acting insulin acts

only for 4-6 hrs.

Characteristics of Currently Available Insulin

Insulin Onset of action(h)

Peak action(h)

Duration(h)

NPH 1-3 4-10 10-20

Glargine 2-4 No peak 20-24

Detemir 2 No peak 16-24

Regular 0.5-1 2-3 5-8

Lispro/aspart 0.1-0.25 0.5-1.5 3-5

Lispro 25/75 0.25-0.5 5.8 12-24

Aspart 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

LunchOne regular or short acting analogues to

control post-prandial hyperglycemiaOne 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?

Post-prandial hyperglycaemia

Post-prandial hyperglycaemia contributes HbA1c ~1%

B=breakfast; L=lunch; D=dinner.Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.

Pla

sm

a g

lucose (

mg

/dL) 300

200

100

0

Time of day (h)6 12 18 24 6

Uncontrolled Diabetes HbA1c 8%

Fasting hyperglycaemia

Basal hyperglycaemia contributes ~2%

B

L

D

NormalHbA1c ~5%

Basal vs Post-Prandial Hyperglycemia – A1c

HbA1c: LimitationsDoes not detect glycemic

excursionsDoes not reveal hypoglycemiaCautions:

◦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 -GastroparesisLong acting analogues -Elderly subjects -Targeting HbA1c <6.5% -Inability to inject multiple injections

Somogyi phenomenon is not Recognized?

Somogyi PhenomenonPost-hypoglycaemic

hyperglycemiaWide swings in blood glucose

profileCommon cause of fasting

hyperglycemiaPerform 4am BG level (<80mg/dl)

Dawn Phenomenon is usually Missed!

Dawn PhenomenonEarly morning hyperglycemia (nocturnal GH surge, increased

insulin clearance)Perform BG at 4 am >80mg/dl

Use of Biosimilars!

These preparations are structurally similar but pharmacokinetics and therapeutic efficacy are variable

Biosimilars with suboptimal efficacy may induce DKA

Consequences of Insulin Therapy

ImmediateHypoglycemiaShort term -Weight gain -Worsening of retinopathy and neuropathyLong term -Malignancy

Insulin-Induced Hypoglycemia

Major barrierCommon with -Advanced duration of disease -Concurrent OHA’s -Older age, DKD

ConclusionsDiabetes 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

Thank you