INSULIN MANAGEMENT OF TYPE 1 DIABETES

INSULIN MANAGEMENT OF TYPE 1 DIABETES AFTER TREATMENT OF DKA. TYPES OF INSULIN AND ITS FEATURES EXPLAINED , INSULIN REGIMEN EXPLAINED.

1. INSULIN MANAGEMENT OF TYPE I DIABETES MELLITUS DR.NEVA JAY PG - MD PAEDIATRICS , VMKVMC

2. DIABETIC KETOACIDOSIS - LIFE THREATENING COMPLICATION OF DIABETES DKA – MAY BE THE FIRST PRESENTING SYMPTOMS OF TYPE I DM CHILD ONCE DKA HAS RESOLVED IN A NEWLY DIAGNOSED CHILD THERAPY IS TRANSITIONED TO THAT OF NON-KETOTIC ONSET CHILDREN WITH PREVIOUSLY DIAGNOSED DIABETES WHO DEVELOP DKA ARE USUALLY TRANSITIONED TO THEIR PREVIOUS INSULIN REGIMEN

3. CRITERIA FOR DIAGNOSIS DIABETES MELLITUS Symptoms of Diabetes & Random blood glucose > 11.1 mmol /l ( 200 mg/dl ) OR Fasting blood sugar > 7 mmol /l ( 126 mg/dl ) OR Two hour plasma glucose > 11.1 mmol /l ( 200 mg/dl ) during an oral glucose tolerance test ORAL GLUCOSE TOLERANCE TEST IS CONTRAINDICATED

4. GOALS Eliminate symptoms related to hyperglycemia Reduce & Delay complications Achieve a normal lifestyle & normal emotional & social development Achieve normal physical growth & development Detect associated diseases early

5. PEDIATRICIAN PEDIATRIC ENDOCRINOLOGIST EXPERIENCED NURSING STAFF DIETITIAN AS DIABETES EDUCATOR & SOCIAL WORKER A COMPREHENSIVE APPROACH WITH A COMPLETE TEAM STAFFING

6. CURRENT THERAPEUTIC REGIMEN INTENSIVE INSULIN THERAPY FREQUENT BLOOD SUGAR MONITORING & MULTIPLE INSULIN INJECTIONS or CONTINUOUS SUBCUTANEOUS INJECTION INFUSION ALONG WITH DIETARY MODIFICATIONS INTENSIVE INSULIN THERAPY RESULTS IN BETTER BLOOD SUGARS & REDUCED LATE COMPLICATIONS OF DIABETES BY 39 – 60 %

7. GOALS OF BLOOD SUGAR & GLYCATED HEMOGLOBIN (HBA1c) TODDLERS & PRESCHOOLERS (0-6 YR) Pre –meal glucose : 100 – 180 mg/dl Bedtime & overnight glucose : 110 – 200 mg/dl HbA1c < 8.5 % SCHOOL AGE (6-12 YR) Pre –meal glucose : 90 – 180 mg/dl Bedtime & overnight glucose : 100 – 180 mg/dl HbA1c < 8.0% ADOLESCENTS & YOUNG ADULT Pre –meal glucose : 90 – 130 mg/dl Bedtime & overnight glucose : 90 – 150 mg/dl HbA1c < 7.5 %

8. FEATURES OF DIFFERENT INSULIN PREPARATION PREPARATION PROPERTIES ONSET PEAK EFFECTIVE DURATION RAPID – ACTING : LISPRO , ASPART GLULISINE FASTER ONSET; SHORTER DURATION 15 mins 0.5 – 1.5 hr 3 – 4 hr SHORT – ACTING : REGULAR 30 mins 2 hr 3 – 6 hr INTERMEDIATE : NPH INSULIN ( protamine ) SLOWER ONSET; LONGER DURATION 2-4 hr 6 – 10 hr 10 - 16 hr LENTE (no longer used) SLOWER ONSET; LONGER DURATION 3-4 hr 6 – 12 hr 12 - 18 hr LONG – ACTING : ULTRA LENTE (no longer used) SLOWER ONSET; LONGER DURATION 6 – 10 hr 10 – 16 hr 18– 20 hr GLARGINE (LANTUS) SLOWER ONSET; LONGER DURATION 4 hr NO PEAK 24 hr LEVEMIR 3-4 hr Relatively peakless 12 – 24 hr

9. LISPRO (L) AND ASPART (A) INSULIN ANALOGS : Absorbed much quicker because they do not form hexamers Has a Discrete pulses and short tail effect BETTER CONTROL OF POST-MEAL GLUCOSE & REDUCED BETWEEN-MEAL OR NIGHTTIME HYPOGLYCEMIA REGULAR INSULIN : Conversion of Hexamers to Monomers Thus onset of action is 30 min slower Has a wide peak and a long tail for bolus insulin Limits postprandial glucose control , Excessive hypoglycemic effects between meals & Increases the risk of nighttime hypoglycemia Feeding the insulin with snacks

10. PATHOGENESIS FOLLOWING MEAL: Energy released from ingested food for immediate use or stored as glycogen in Liver or Muscle & any excess is deposited as adipose tissue Anabolic steps are carried through insulin secretion & action FASTING : Sleeping at night Insulin level falls Catabolic state Mobilization of energy from the stores

11. TYPE 1 DM Absence of Insulin Peripheral utilisation of Glucose is halted & Post prandial hyperglycemia results Low plasma insulin Catabolic activity in liver by Glycogenolysis & Gluconeogenesis Endogenous glucose production Fasting hyperglycemia Counter-regulatory hormones induces glycogenolysis & gluconeogenesis , lipolysis & ketogenesis Epinephrin , cortisol & growth hormones oppose the action of insulin & Decrease the peripheral tissue utilization of glucose & glucose clearance Elevated blood glucose level

12. INTERMEDIATE OR LONG-ACTING INSULIN To provide background insulin to maintain glycemic control during the FASTING STATE SHORT-ACTING INSULIN To provide glycemic control in the POST-PRANDIAL STATE

13. INSULIN STORAGE Insulin has a “use by date” & a “expiry date” Stored inside the Fridge – 2 – 8 C Unopened Insulin – Stored until expiration date Open vials : stored in fridge at 2-8 C – used for 3months Controlled room temperature - 28 days PENS Pen should not be stored in fridge Controlled room temperature-used for 7–28 dys depending the pen you use NEVER TO BE FROZEN Hot places / Hot cars / Sunlight / light Never use insulin if expired INSPECT YOUR INSULIN : Clumps/solid white particles/crystals in bottle or pen Clear insulin should be clear & never cloudy In use insulin Discard after 28 days whether vial or cartridge DO DON’T

14. INSULIN INJECTION Preferred for Split mix regimen 40 units /ml vial = 40 U syringe 100 units/ml vial = 100 U syringe Insulin syringe: 30 G -31 G -Pain free Re – usable till bent Never clean with spirit

15. INSULIN PEN Preferred for Basal Bolus regimen Used Multiple times - Pain free

16. Continuous subcutaneous insulin (CSII) via battery-powered pump

17. INSULIN PUMP

18. SUB-CUTANEOUS INSULIN INJECTION SITE Insulin kept in fridge should be allowed to reach room temperature before injection Abdominal Injection sites – Best Followed by outer arm Followed by Thigh & then Buttocks

19. Preventing FATTY LUMP LIPOHYPERTROPHY Retards uniform distribution of Insulin Poor Glycemic control FATTY LUMP LIPOHYPERTROPHY LIPOATROPHY SUB CUTANEOUS INJECTION - Different sites Always rotated regularly Not given in the same site in the morning & evening

20. INSULIN REQUIREMENT CURRENT INSULIN - generated using recombinant DNA technology DOSAGE : During DKA : 0.1U/kg/hr of Short acting insulin During Recovery : 2-3 U/kg/day Honey moon phase : 0.5U/kg/day or Less or Virtually no insulin Intensification phase : Infection – 0.7 to 1 U /kg/day Puberty - 1 – 1.5 U/kg/day INSULIN RQUIREMENT IS HIGHER IN PUBERTAL CHILDREN Insulin sensitivity reduces during puberty – Insulin dose is increased upto 1.5 units/kg/day Insulin sensitivity normalises at the End of puberty - Insulin dose reverted to 1unit/kg/day

21. Honey moon Period New – onset diabetes have some residual  - cell function Reduces exogenous insulin need Insulin may needed to be stopped temporarily Thus avoiding Hypoglycemia Residual  - cell function usually fades within a few months and is reflected as a steady increase in insulin requirement & wider glucose excursions Newly Diagnosed children in Honey moon require 60 – 70 % of full replacement

22. Diabetes in Toddlers (1-3 yrs) Present with more acute & severe symptoms of Insulinopenia compared to older children Goals of therapy is relaxed as they eat unpredictability Hence Hypoglycemia Goals in TODDLERS (0-3 yr): High Target of Blood glucose levels : 110 – 220 mg/dl HbA1c : 8 - 8.5 % MANIFESTATION : Pale , cranky, sweating, let out a particular cry, become clumsy, develop bluish tinge of lips & fingers, Temper tantrum may be the chief symptoms REPEATED HYPOGLYCEMIC EPISODES: Affects the developing brain by resulting in PERMANENT COGNITIVE , INTELLECTUAL & LEARNING DEFECTS MRI : MESIAL TEMPORAL SCLEROSIS a defect that is never observed in normal children

23. INSULIN REGIMEN 2 DOSE SPLIT - MIX Regime (NPH) Intermediate acting + Short Acting (Regular) BASAL - BOLUS INSULIN Regime Long-acting insulin typically insulin Glargine (Lantus) + Rapid Acting

24. 2 DOSE SPLIT - MIX Regime COMMOMLY USED CONVENTIONAL INSULIN PLAN (NPH) Intermediate acting + Short Acting (Regular) 2 Injections are given daily DAILY CALCULATED DOSE OF INSULIN IS DIVIDED 2/3 rd 1/3 rd MORNING PRIOR TO BREAKFAST & EVENING PRIOR TO DINNER 2/3 NPH + 1/3 Short acting 1/2 - 2/3 NPH + 1/3 - 1/2 Short acting (At Dinner or Bedtime)

25. Insulin injection is given 20 – 30 mins before meal as the onset of action of Regular Insulin is 30 minutes after Injection as the hexamers must dissociate into monomers subcutaneously before being absorbed into the circulation Delaying the meal 30-60 min after the injection for optimal effect a delay rarely attained in a busy child’s life REGULAR + NPH OR LENTE POORLY MIMICS NORMAL ENDOGENOUS INSULIN SECRETION

26. 2 DOSE SPLIT - MIX Regime

27. DRAWING UP A MIXED DOSE OF INSULIN SHORT - ACTING INSULIN IS DRAWN BEFORE INTERMEDIATE ACTING INSULIN CLEAR THEN CLOUDY accidental introduction of longer-acting insulin in short-acting insulin can result in increasing the duration of effect of short-acting insulin

28. Disadvantages of 2 DOSE SPLIT - MIX Regime Peaking in blood sugar following lunch is not covered adequately by morning short-acting insulin as it is nearly over by then Adolescents & Children without optimal blood sugar control Extra dose of Short-acting insulin at Lunch time is added to the regimen Peak action of the morning NPH falls between lunch & dinner Late Evening snacks NPH insulin peaks around the middle of the night leading to increasing risk of night time hypoglycemia & NPH insulin is not sufficient to prevent the rise of hyperglycemia before breakfast

29. MEAL PLAN 3 MEALS and 2 or 3 SNACKS [Mid-morning , in the afternoon & late evening] IN REGULAR INTERVAL & EQUAL IN CARBOHYDRATE & CALORIE CONTENT Big meal = Hyperglycemia Delayed or Reduced intake = Hypoglycemia

30. BASAL - BOLUS INSULIN Regime Long-acting insulin typically Glargine ( Lantus ) + Short / Rapid Acting insulin Long-acting analog glargine (G) with rapid bolus (L or A) on top of the basal insulin More physiologic pattern of insulin effect Insulin Glargine is steadily absorbed & acts over 24 hours provides a constant background level of insulin without definite peak of action - FLATTER 24-HR PROFILE Given once daily before bedtime ADVANTAGES : Postprandial glucose elevations are better controlled Between-meal hypoglycemia and nighttime hypoglycemia are reduced

31. BASAL - BOLUS INSULIN Regime Long-acting insulin typically Glargine ( Lantus ) + Short Acting insulin

32. SUBCUTANEOUS INSULIN DOSING AGE (yr) TARGET GLUCOSE (mg/dl) TOTAL DAILY INSULIN (U/kg/Day) BASAL INSULIN % OF TOTAL DAILY DOSE BOLUS INSULIN UNITS ADDED PER 100 mg/dl above Target UNITS ADDED PER 15 g AT MEAL 0-5 100 - 200 0.6 – 0.7 25 - 30 0.50 0.50 5-12 80 - 150 0.7 – 1.0 40 - 50 0.75 0.75 12-18 80 – 130 1.0 – 1.2 40 – 50 1.0 - 2.0 1.0 - 2.0 Example 6 yr old child x 20 kg : 0.7 U/kg/24hr x 20 kg = 14 U / day = 7 U (50 %) as Basal + 7 U as Total daily bolus Subtract 1 U if below target Add 0.75 U for each 100 mg/dl above target (round the dose to the nearest 0.5 U)

33. Dose of the short-acting insulin = amount of carbohydrate intake & level of blood sugar UNITS OF INSULIN PER G OF CARBOHYDRATE INGESTED Most infants and young children : 1 unit of insulin per 20-30 g of carbohydrates Older children : 1 unit per 10-15 g of carbohydrate Adolescents : 1 unit of insulin per 5 g of carbohydrate Insulin to carbohydrate ratio = 500 Total daily dose of insulin g/unit Example 6 yr old child x 20 kg : 1 U/kg/24hr x 20 kg = 20 U / day = 500 20 = 25 g of carbohydrates 1 U = 25 g of carbohydrate = 1 U is added

34. UNABLE TO ADMINISTER 4 DAILY INJECTIONS COMPROMISE 3-INJECTION REGIMEN NPH + RAPID ANALOG BOLUS AT BREAKFAST RAPID-ACTING ANALOG BOLUS AT SUPPER & NPH AT BEDTIME FURTHER COMPROMISE 2-INJECTION REGIMEN NPH + RAPID ANALOG AT BREAKFAST AND SUPPER POOR COVERAGE FOR LUNCH AND EARLY MORNING & INCREASE RISK OF HYPOGLYCEMIA AT MID-MORNING & EARLY NIGHT

35. GOAL TO ACHIEVE A NEAR NORMAL BLOOD SUGAR AT ALL TIMES WITH MINIMAL HYPOGLYCEMIA THUS DELAYING LONG TERM COMPLICATIONS OF DM

36. HOME BLOOD GLUCOSE MONITORING provides a basic idea of Correctness of insulin doses used & fine tuning to control blood sugar DONE 3 or AT LEAST 2 CONSECUTIVE DAYS 4 TIMES A DAY : PRE- BREAKFAST 2 HOURS AFTER BREAKFAST PRE-DINNER 2 HOURS AFTER DINNER Frequent blood glucose monitoring & insulin adjustment are necessary in the 1 st weeks as the child returns to routine activities & adapts to a new nutritional schedule & as the total daily insulin requirements are determined

37. MODEL DIABETES DIARY or LOG BOOK NAME : AGE (DOB): ADDRESS : PHONE / MOBILE NO (PATIENT) : PHONE / MOBILE NO (PARENTS) : CLINIC NUMBER : WEIGHT: HEIGHT: INSULIN REGIMEN & INSULIN DOSE DATE FASTING PRE-LUNCH PRE-DINNER BED TIME 2-3 AM OTHER TIME INSULIN ADJUSTED REMARKS

38. INSULIN ADJUSTMENTS IN SPLIT- MIX REGIMEN SMBG INSULIN TO BE ALTERED Fasting Night NPH (SOMOGYI PHENOMENON) Pre- Lunch Morning regular Pre-Dinner Morning NPH Bed Time Night regular SMBG INSULIN TO BE ALTERED Fasting & Pre-meals Long acting analog Post meal Rapid or Regular before that meal INSULIN ADJUSTMENTS IN BASAL BOLUS REGIMEN

39. SOMOGYI PHENOMENON Rebound hyperglycemia - rare DAWN PHENOMENON Nocturnal secretion of growth hormones Early morning hyperglycemia (usually recurrent) shifting the timing of evening dose of intermediate acting insulin from pre-dinner to 2 hours after dinner or at bedtime evening short- acting insulin dose is given at pre-dinner Excess Exogenous insulin [evening dose of intermediate – acting ] SILENT HYPOGLYCEMIA DURING THE NIGHT Release of counter-regulatory hormones in the night [Glucagon , cortisol , growth hormone & adrenaline] Early morning hyperglycemia Appropriate reduction in the evening dose of intermediate – acting insulin

40. Diagnosis of Dawn & Somogyi phenomenon Check for hypoglycemic event during middle of night periodically at the same time Hypoglycemia Blood sugar normal Somogyi phenomenon Dawn phenomenon

41. EXERCISE & PHYSICAL ACTIVITY Important aspect in the management of Type 1 DM Improves glycemic control , Physical fitness , muscle strength , Psycological well-being Children participating in Sports or programmed exercises should be supervised & have access to sweetened drinks & snacks Blood glucose should be monitored before , during & after physical activity Do not inject insulin into muscle – heavily involved in muscular activity Extra carbohydrate intake and /or reduced insulin dose is necessary Every 30 mins of of moderate exercise to intensive sports or physical activity = 15 g or extra serving of Carbohydrate is added If Blood glucose < 100 mg/dl at bedtime = extra Carbohydrate is taken Check blodd glucose at 3 am Avoid Streneous physical activity = If Blod glucose > 250 mg/dl ,especially if ketones are present = Insulin

42. INFORMING SCHOOL AUTHORITIES Staff members & some close schoolmates of the child should be familiar with the special needs of the child : Type 1 DM is not contagious disease They need to take 2 – 4 injections of insulin each day , Check blood glucose , Eat healthy food at fixed timings and take precautions prior to physical activities Should not be treated differenly from other children Diabetes doe not affect academic performance , provided it is well controlled Teachers & close friends should be familiar with symptoms of high blood sugar - Parents should be altered and Needs to consume extra snacks before , during & after exercise School nurse should supervise /administer Insulin Staff needs to have the Telephone number of the Child’s parent & the medical team in case of Emergency

43. HYPOGLYCEMIA Need to know the early symptoms & first aid management of Hypoglycemia If child complaints of Hypoglycemia or found drowsy , confused or behaving in an erratic manner Rx: 3 teaspoon of glucose powder or powered sugar is given , followed by snacks in the form of fruits, sandwich or biscuits Administer glucagon (0.3-0.5 – young children & 1 mg for older children SC) shot if severe hypoglycemia occurs (Blood Glucose < 70 mg/dl)

44. COMPLETELY AUTOMATED CLOSED LOOP INSULIN PUMP Currently being evaluated INHALED INSULIN Under clinical trials

45. O.P.Ghai 8 th Edition Nelson Textbook of Pediatrics -19 th Edition IAP Textbook of Pediatrics 5 th Edition Achar’s Txtbk of Pediatrics ISPAE Guidelines ADA Guidelines REFERENCE

46. THANK YOU HAPPY LEARNING DR.NEVA.JAY