Insulin Treatment. J A O Hare. www.3bv.org. Bones, Brains & Blood Vessels

Insulin Treatment J A O Hare www.3bv.org Bones, Brains & Blood Vessels

Insulin

Indications for Insulin Treatment Diabetic Ketoacidosis Diabetics with unstable acute illness Gestational Diabetes: diet failure Type 2 diabetes: after oral agent Failure Optimise Hyperalimentation? Myocardial infarction and stroke

Insulin: Main Metabolic Actions Suppress Hepatic Glucose Output Enhance glucose uptake in muscle Suppress ketone production Inhibit glycolysis Iinhibit Gluconeogenesis Inhibit Lipolysis Enhance Amin-acid muscle uptake

Insulin stimulates. Appetite Growth Sodium retention Appetite Sympathetic Nervous Activity (BMR) Vasodilatation Androgens in women

Insulin: Mode of action Binds to surface receptor Tyrosine kinase activation Glucose Transporter activation Complex intracellular cascade

Insulin Action

Modes of administration Intravenous Intramuscular Subcutaenous Intraperitoneal Inhaled Transcutaneous jet Buccal

Pharmacokinetics I.V. insulin Half life 20mns Onset of action 20 mns Cleared by liver 50% and kidney 50%

Subcutaneous Insulin Absorption inverly related to volume Increased with exercise Varies with site Slower absorption in Shock Less with Lipohypertrophy

Insulin Origin Animal Porcine, Beef Human -recominant Analogues Quick Lispro, aspart Long acting Glargine, Detemir

Insulin Time-Action profiles Hrs.

Insulin Fixed Mixtures Short acting + Intermediate Acting Mixtard 10-50% usual 30/70 (Novonordisk) Novo Mix 30/70 (Novonordisc) Insuman- Combi (Aventis) Humulin M1-5 (Lilly)

Adjusting Dose with b.d. soluble and NPH (fixed or separate) Pre Meal AM Fasting Evening NPH Pre Lunch Morning soluble Pre Dinner morning NPH Pre Bed.Evening Soluble

Pens Advantages One piece More acceptable Convenience for 3 +injections Disadvantages Higher failure rate More expensive Warning! Pens do not result in better control! But some patients prefer them!

Setting up a sliding scale units of insulin sliding scales of insulin 4-6 hourly for subcutaneous 30 23 15 8 0 0 4 6 8 10 12 14 16 18 20 24 Glocose mmol/l Resistant Normal Sensitive

Insulin Resistance

Insulin Resistance (>1 unit /Kg body weight) Acute Illness Obesity Recent Persisting Hyperglycaemia Steroid Treatment Adolescence Pseudo = non-compliance Rare Syndromes

I.V. Sliding scale for Unstable DM in acute illnes Soluble human Insulin (Actrapid) only If glucose Insulin/hour 0-4 0.5 >4-6 1 >6-8 2 >8.-12 3 >12-16 4 >16-20 5 >20 6 >25 Review Scale

Managing Acute Hyperglycaemia in Illness

Minor operations (<1 hour) Fast Over night 5 % Dextrose infusion + 10 KCl Half of usual Intermediate acting Insulin Sub-cutaneous Sliding scale on 2 hourly values Usual p. m. insulin if eating

Major operations Stop Oral Agents at least 2 days before hand Do Early in day 5% Dextrose infusion Separate I.V. Infusion as 50U in 50 mls saline Hourly monitoring with sliding scale Anticipate: 0.5 to 1 unit per Kg over 24 hours

Starting Insulin Type 1 Diabetes (Non-Ketotic) Requirements 0.5-0.8 units per kg Foundation insulin -suppress hepatic glucose output: NPH insulin + Post Prandial peaks soluble insulin or analogue

Starting insulin type 1 diabetes Choises according to evolving patterns Injection /Day 2-4

Insulin Regimens for Type 1 DM Basic: Mixed fixed b.d (am and pm) Mixed Flexible: SolubleAnologue and NPH b.d Mixed Flexible 3 injections am: sol/nph(br) sol(din) NPH(bed) 4 injections: pre meal: soluble/analogue + Glargine, Detemer 5 injections

Injection problems Problem Fear Cant see Allergy Lipohypertrophy Solution Demonstration Click devises Alternate insulin Rotate sites

Multiple daily injections Basic Plan Suppress hepatic output +meal glucose disposal 50% long acting + 50 % for meals+snacks NPH(1 or 2 ) or Glargine + Soluble or analogue

Sample calculation for pre-meal soluble anologue 1. Calculate insulin sensitivity 100 and 500 rules 2. Decide Pre- meal target 3. Dose for carbohydrate load

Multiple daily Injection Options for meals Fixed pre- meal Insulin Example. Breakfast 8 units Lunch 6 units Dinner 10 Units Timing Flexibility Less monitoring? Inferior Variable Pre-meal Alter dose < to pre meal glucose + fixed dose for meal Alter Dose according to premeal glucose + Dose adjust for meal Carbohydrate Theoretical superiority Greater meal dietary freedom

Calculating Pre-meal Dose Dose to normalise glucose pre meal Insulin sensitivity 100/Total daily dose = Glucose (mmol) fall per unit soluble E.G. 100/50 2 mmol fall for 1 unit Dose calculation for carbohydrate content 500 rule 500/total daily dose = Grams of CHO dispossed for I unit of soluble/anologue

Pre-Meal soluble calculation Sensitivity = 2: glucose falls 2 mmol for 1 unit Glucose Measure = 10, target = 6 Restoration to target dose = + 4/sensitivity 4/2 = 2 units Meal carbohydrate say 60 grams breakfast, 6 units for glucose post prandial Total dose = Restoration dose + CHO Disposal dose 2 units + 6 units = 8 units Validate with 2 hour post prandial measurements over one week and re-adjust

Variables effecting calculation (unmeasurable at time) Insulin phrmacokinetics for this injection Counterregulatory hormone activity Hypo, illness, stress, menstrual, streroids Exercise Recent illness Actual v/splanned CHO intake Glycaemic index Gastric activity

Simple pre meal sliding scale If Glucose mmol/l Soluble/anologue 2-4 treat hypo >4-6 6 >6-8 8 >8-10 10 >10-12 12 >12 14 Check 2 hours post prandial and observe pattern then readjust

Monitoring and Adjusting Do they monitor? Did they bring results? results authentic? do they understand?

How to monitor and adjust For soluble, NPH, Glargine. Pre meal Anologues (aspart) 2 hours post meal

Hypoglycaemia The short term problem!

Hypoglycaemia Symptoms Sweating Trembling Weakness anxiety Hunger Signs Diaphoresis Tremor Strong pulse Slowed mentation

Highly motivated Demonstrate stamina and understanding for frequent monitoring and adjustment No Hypoglyceamic unawareness Hypoglycaemia

Physiology of Hypoglcaemic Counterregulation Glucosensors: central and mesenteric Hypothalamic coordination Glucagon insulin turned off adrenaline cortisol/ growth hormone

Causes of Hypoglycaemia Meals missed Exercise Alcohol Dose errors Inappropriate insulin administration Recovery from temporary insulin resistance Increasing insulin sensitivity Combined therapy delayed Effects Deliberate

Increasing Insulin Sensitivity Honeymoon Weight loss/dieting Cancer Adrenal Insuffiency Steroid withdrawal Coeliac Renal Failure Poor to good control! Compliance!

Hyoglycamemic Unawareness Diminished adrenergic response Glucorecptor failure Commoner in long duration Worseded by repeated hypoglycaemia Reversible Stop Beta blockers if possible

Oral glucose drinks Glucagon I.V. Glucose Treating hypos

Avoiding hypoglycaemia Appropriate insulin regimen Adapting to circumstances Monitoring Patient education

Intensive Therapy Treatment with the goal of near normoglycaemia with a view to reducing the onset or progress of diabetic complications

Selecting Patients for Intensive Therapy Highly motivated Good Understanding Proven Reliable Monitoring, Adjustment, Attendance Intact Hypoglyceamic Awareness

Pumps Continuous subcutaneous soluble insulin infusion (CSSI) Adjustment of basal according to pattern of fasting glucose Bolus infusion pre meal and snack

Pump Problems Higher Risk of DKA.. line failure Higher hypoglycaemic risk Infection Cost Educator Time

Difficult Situations Aadolescent in conflict Shift Work Steroid therapy (asthma/ Rheumatoid) Elderly female Addicted Long Haul Travel

Adolescence Rapid Growth Increased and varying Food intake Growth Hormone --Insulin antagonist Insulin resistance Rebellion/manipulation/conflict

Recognising Non-compliance Glucose Hbaic high and home tests perfect Many tests results few scars Immaculate results book, no comments Hba1c. 10% despite adequate insulin Falling weight and increasing insulin dose!

Children May be brittle Hypo seizures Handling parental anxiety Avoid excessive protection

Goals of therapy in the elderly Avoidance of coma symptom control simplicity Security avoid excess fuss

Pregnancy High risk /Reward situation Highly motivated Intensive management Care with vomiting of pregnancy Changing situation

Renal failure Creatinine > 400 Half usual requirements Some Type 2 patients stop insulin!

Decreasing insulin sensitivity Hypocaloric Diets Cancer Advanced Heart Failure Withdrawl of Steroid treatment Addison disease Advanced renal failure

Case1 16 year old male new onset glucose 18 ketone + manage? Oral rehydration Mixtard b.d. 0.4 units/kg

Case 2 58 year old female thin 70 Kg loosing weight, thirsty 10 years of type 2 on tablets Glucose 18 no infection or meds Insulin insultard bd 0.6-1 unit/kg

Case 3 Male type 1 male 30 years age 48 Acute cholylithiasis septic Glucose 35, ketones +2, ph 7.2 I.V, Insulin infusion by sliding scale with saline and Potassium through surgery

Case 4 35 year female Praeder Willi syndrome 140KG on 200 Mixtard b.d poor veins glucose 15 no ketones Acute cellulitis 250 mixtard b.d + top up sc actrapid with sliding scale 60-120 units 6 hourly Feeding restraint

Case 5 78 year old coma type 2 for 5 years on sulphonyluria Glucose 102 no ketones ph 7.31 Na 118 K 3.8 urea 20 Nnormal saline alternating with dextrose saline up to 10 litres over 3 days avoid too rapid correction of sodium Insulin at 2-5 units hour I.V.

Case 6 35 year old type 1 x17 years new proliferative retinopathy No test results, usual HBa1c 9% Demands to go on the insulin pump as seen in promotional video? Hypo awareness? Willingness to test adjust and follow diet on conventional therapy

The Most Difficult Problem