1. INSULININJECTIONINSULININJECTION Multiple Insulin Injection Therapy

2. The presentation Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Introduction: Goals of multiple insulin injection. High light of treatment method. Glycemic control effect. Diet treatment. Type of insulin: Insulin preparation. What to mix and what not to mix. Type of regimen: Western regimen. Our regimen. Future regimen. Important phenomena: Somogyi phenomena. Dawn and predawn phenomena.

3. Goals Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Clinical Goals: Elimination of ketosis. Elimination of hyperglycemia and it’s symptoms. Prevention of chronic complications. Additional Goals: Maintaining desirable weight. Maintaining normal growth and sexual maturation. Maintaining psychosocial well-being. Achieving normal fertility and pregnancy. Sustaining normal family and sexual life. Control Goals: HbA1c <7%. Pre-meal SMBG 80-120 mg/dl (4.4-6.7 mmol/l). Bed time SMBG 100-140 mg/dl (5.6-7.8 mmol/l). No ketonuria. Mean blood glucose level 120-160 mg/dl (6.7-8.9 mmol/l).

4. Highlights Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Insulin: Type 1 diabetes is dependent on insulin for survival. Insulin is classified by source or duration of action. Human insulin has less allergy or lipoatrophy. More than one injection is needed and different types. Proper action During honeymoon phase. The commonest side effect is hypoglycemia. Nutrition: Enable near normal blood glucose level. Maintain a reasonable body weight. Protein 10-20%, Fat 15-25%, Carbohydrate 65%. Fibers, vitamins, and minerals. Food exchanges or carbohydrate counting. Total daily calorie intake adjustment. Exercise: Should be integrated. Weight control and improve well being. Pre-exercise medical evaluation. Monitoring: Glucometer use SMBG to monitor blood glucose level. Adjustment of insulin, diet, and exercise. Urine testing for both glucose and ketones. HbA1c the best index for control.

5. Glycemic control Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Years from randomization Conventional Intensive 6.2% upper limit of normal range 03691215 9876098760 HbA 1c (%) UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837–853.

6. Diet Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION 30 25 20 35 30 25 40 35 30 Physical activity Body weight 25 years male IBW 60 kgm Carbohydrate (65%)390 Protein (10%) 60 Fat (25%)150 Carbohydrate 100 gm Protein (10%) 15 gm Fat (25%) 17 gm Diet Carbohy. Protein Fat _ Arabian bread 30 gm --- --- Cheese 5 gm 10 gm 10 gm Honey 50 gm 2 gm 3 gm Glass of milk 10 gm 5 gm 5 gm_ Total 95 gm 17 gm 18 gm Carbohydrate (65%)520 Protein (10%) 80 Fat (25%)200 Carbohydrate 130 gm Protein (10%) 20 gm Fat (25%) 22 gm Diet Carbohy. Protein Fat _ Rice 80 gm --- 6 gm chicken 5 gm 15 gm 12 gm Salad 30 gm 4 gm 4 gm Orange 10 gm --- ---___ Total 125 gm 19 gm 22 gm Carbohydrate (65%)260 Protein (10%) 40 Fat (25%)100 Carbohydrate 65 gm Protein (10%) 10 gm Fat (25%) 11 gm Diet Carbohy. Protein Fat _ Tuna sandwich 45 gm 12 gm 10 gm Apple 15 gm --- --- Tea --- --- --- _ Total 95 gm 17 gm 18 gm 60 Kg X 30 kcal = 1800 kcal Breakfast 600 kcalLunch 800 kcalDinner 400 kcal The total calories intake depends on patients age and activity but have to related to the desirable body weight. Total daily calories = IBW X Estimated daily energy Total daily calories = IBW X Estimated daily energy Add 300 kcal/day during pregnancy. Add 500 kcal/day during lactation. Fibers, sweeteners, vitamins, and minerals.

7. Glucose sensor Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION The plan of insulin type and dose will depend on: - The shape of glucose curve. - The diet and exercise.

8. INSULIN TYPES DURATION OF ACTION 03691215182124 Insulin Preparations Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION ActionNameOnsetDuration Very rapidLispro / Novo rapid10-15 min2-3 hrs RapidCrystalline zinc (CZI)30-45 min4-6 hrs IntermediateNeutral Protamine Hagedorn (NPH)1-2 hrs6-12 hrs Lente zinc Long actingUltralente zinc6-8 hrs18 hrs Lantus (glargine)4-8 hrs24 hrs Premixed 80% NPH+20%CZI30-45 min6-12 hrs 70% NPH+30%CZI30-45 min6-12 hrs 50% NPH+50%CZI30-45 min6-12 hrs

9. Insulin Mixing Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION ActionNameMix (1) Very rapidLispro / Novo rapidYes (2) RapidCrystalline zinc (CZI)Yes (2) IntermediateNeutral ProtamineYes (2) Hagedorn (NPH)Yes (2) Lente zinc Yes (2) Long actingUltralente zincNo Lantus (glargine)No_ Premixed 80% NPH+20%CZINo 70% NPH+30%CZINo 50% NPH+50%CZINo_ (1) Mixing different type of insulin has to be fron the same source (ie same company) (2) Mixing different type of insulin has to be fron the same source (ie same company)

10. Pre-mixed insulin Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION 10/90 20/80 30/70 40/60 50/50 Post- prandial hyperglycemia Pre-prandial hyperglycemia

11. Western regimen Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Time of day 0 10 20 30 40 50 60 70 0600 09001200150018002100240003000600 Insulin (mU/l) Normal free insulin levels (Mean) Simulated s.c. injected soluble human insulin + NPH Adapted from Polonsky et al. 1988 DinnerNPHBreakfastLunch Simulated s.c. injected insulin aspart + NPH Meal   

12. Western regimen Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION   Two doses: The usual dosing commonly used. Initial insulin therapy     Four doses: Brittle diabetic patient. Pregnant mothers specially type 1.     Four doses: Brittle diabetic patient. Pregnant mothers specially type 1. Motivated patients.    Three doses: Used for active patients. Patients taking two main meals.

13. Western regimen Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION   Two doses: The usual dosing commonly used. Initial insulin therapy    Three doses: Used for active patients. Patients taking two main meals.     Four doses: Brittle diabetic patient. Pregnant mothers specially type 1.     Four doses: Brittle diabetic patient. Pregnant mothers specially type 1. Motivated patients.

14. Blood Glucose Curve Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Glucose variations in our culture:

15. Insulin Use Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Regular and NPH use twice daily the commonest regimen used. Premixed with different concentration (30/70, 40/60, 50/50). Lunch is the biggest meal usually but no insulin dosing.

16. Hyper-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Hyperglycemia Window Cause: Lack of insulin Lunch effect afternoon snacks Effect: Pre-meal hyperglycemia  HbA1c by 1.7%

17. Hyper-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Treat by adding regular dose pre-lunch

18. Hyper-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Treat by adding regular dose pre-meals and small one before sleep

19. Hypo-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Hypoglycemia Window Cause: NPH evening dose ? Late sleep Effect: Somogyi effect Week end Problem

20. Hypo-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Treat by moving am dose late and regular dose pre-supper and NPH at night

21. Hypo-glycemia window Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Treat by moving am dose late and regular dose pre-supper and another dose pre bed

22. Somogyi Phenomenon Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Cause: Counter regulatory hormones response to hypoglycemia at med-night. Increase in hepatic glucose production. Insulin resistance because of the Counter regulatory hormones. Treatment: Decrease pre-supper intermediate insulin. Defer the dose to 9 PM. Change or start pre-bed snack.

23. Dawn Phenomenon Multiple Insulin Injection Therapy INSULININJECTIONINSULININJECTION Cause: Less insulin at bed time. More food at bed time. Not using NPH at night. Treatment: Use enough dose. Reduce bed time snack. Add NPH pre-supper.