INSULIN THERAY دکتر رحیم وکیلی استاد غدد ومتابولیسم کودکان دانشگاه علوم پزشکی مشهد

Transcription

1 INSULIN THERAY DIABETES1 IN TYPE دکتر رحیم وکیلی استاد غدد ومتابولیسم کودکان دانشگاه علوم پزشکی مشهد

2 Goals of management Manage symptoms Prevent acute and late complications Improve quality of life Avoid premature diabetes-associated death An individualised approach Glycaemic control Lifestyle (e.g. diet & exercise) BP Management Lipids Patient education Microalbuminuria & kidneys Foot care Eye care

3 Diabetes Management Principles An effective insulin regimen Monitoring of glucose As flexible with food and activity as possible Must remember Young children need routine and rules Young children need to develop autonomy Young children need to explore and experience Young children need to begin to make decisions

4 Question What are the glycemic targets for young children?

5 Glycemic Targets Glucose values are plasma (mg/ml) Age Pre-Meal BG HS/Night BG HbA1c Toddler (0-5 yrs) School-age (6-11 yrs) Adolescent (12-19 yrs) & 8.5% <8% <7.5% Diabetes Care 28: , 2005

6 ISPAD guidelines: Target indicators of glycaemic control for children & adolescents Parameter Ideal (non-diabetic) Optimal Suboptimal High risk (action required) HbA 1c (%) (DCCT stand.) <6.0 <7.5 [<7.0]* SMBG values, mmol/l [ ]* >9.0 >8.0 >9.0 BG, mmol/l PPBG >14 [<10.0]* Bedtime BG <6.7 or <4.4 or >11.0 Nocturnal BG <4.2 or >9.0 <4.0 or >11.0 *Levels recommended for adults shown in square brackets; AM fasting or pre-prandial; DCCT=Diabetes Control and Complications Trial SMBG=self-monitored blood glucose; BG=blood glucose; PPBG=post-prandial blood glucose Rewers M, et al. Pediatr Diabetes 2007;8:

7 Question Can Intensive Management Be Done Safely in Young Children?

8 The ideal insulin therapy should mimic endogenous insulin secretion Plasma glucose profiles Endogenous insulin secretion 0.08 Glucose homeostasis Insulin (U/l) Plasma glucose (mmol/l) Time (hours) Owens DR, et al. Lancet 2001;358:

9 Insulin management Fixed dose regimens: requires scheduled meals and snacks and is not flexible enough for most young children Basal: bolus regimens: MDI useful only if child is willing to take frequent injections Insulin pumps child must be willing to wear the pump

10 Basal insulin Insulin Terminology Long-acting, all Type 1 and most Type 2 DM patients should have basal insulin whether they are eating or not (insulin glargine, insulin detemir, or NPH) Nutritional or pre-meal / prandial insulin Short-acting insulin given with meals in anticipation of carbohydrate load glycemic spike (scheduled insulin aspart, insulin lispro, insulin glulisine, regular insulin) Correction or supplemental insulin Short-acting insulin given to cover high glucose; if substantial use, it should drive adjustment of basal and nutritional insulins

11 Approximate pharmacokinetic profiles of human insulin and insulin analogues Hirsch IB. N Engl J Med 2005; 352: N.B. Duration of action will vary widely between and within people NPH = neutal protamine hagedorn/isophane insulin

12 Rationale for basal-bolus therapy Basal-bolus should be the regimen of choice for maintaining overall glycaemic control 1 An ideal basal insulin Peakless profile, prolonged duration of action Flexible dosing Suppresses hepatic glucose production between meals and overnight 1 An ideal bolus insulin (a bolus with every meal) Rapid onset and short duration of action Limits postmeal hyperglycaemia 1 Prevents post-prandial hypoglycaemia 2 1. Rosenstock J. Clin Cornerstone 2001;4: Dave JA, Delport SV. S Afr Family Practice 2006;48:30 6.

13 Commonly used insulin regimens Basal-bolus insulin regimens 1 long-acting basal + mealtime insulin injections or 2 intermediate-acting basal + mealtime insulin injections 1,2 Pre-mixed insulin regimens 2 or more pre-mixed insulin injections 2 Continuous subcutaneous insulin infusion (CSII) Continuous (rapid-acting) insulin infusion to meet basal insulin needs + 3 or more mealtime doses 2 1. DeWitt DE, Hirsch IB. JAMA 2003;289: Rosenstock J. Clin Cornerstone 2001;4:50 64.

14 Action profile of different basal insulins Glucose infusion rate (mg/kg/min) s.c. injection 0.3 IU/kg 3 or CSII Ultralente 0.3 IU/kg/24h Peak 4 6 hours NPH Insulin glargine CSII Insulin lispro Flat action profile lasting for 24 hours Time (hours) Rates of glucose infusion needed to maintain plasma glucose at 130 mg/dl (7.2 mmol/l) after s.c. injection in patients with T1DM (n=20) Lepore M, et al. Diabetes 2000;49:

15 Activity profiles of glargine and detemir diverge after 12 hours in T1DM patients Detemir Glargine 12 BG (steady state) 2.0 GIR (steady state) BG (mmol/l) GIR (mg/kg/min) Time (h) Time (h) Activity profile of insulin glargine allows once-daily dosing, whereas most patients require twice-daily dosing with detemir particularly T1DM patients GIR = glucose infusion rate Bock G, et al. Diabetologia 2008;51(Suppl. 1):S390.

16 Type 1 Diabetes: Serum Insulin Concentrations Following Subcutaneous Injection of Insulin Lispro or Human Regular 3.0 Serum Insulin Conc. (ng/ml) Injection Insulin Lispro (n=10) Human Regular (n=10) Mean + SE Meal 0.2 mu/min/kg insulin infusion Time (minutes) Heinemann et al. Diabetic Medicine,13: , 1996

17 Rapid-acting insulin analogues reduce risk of PP hyperglycaemia and late hypoglycaemia 80 Meal Normal post-prandial values Plasma-free insulin (µu/ml) Subcutaneous insulin Better PPBG control Regular human insulin (RHI) Insulin lispro, insulin aspart, or insulin glulisine Lower risk of late post-prandial hypoglycaemia Time after insulin injection or meal ingestion (hours) 0 PPBG=post-prandial blood glucose Bolli GB. Av Diabetol 2007;23:

18 Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs Breakfast Lunch Dinner Plasma insulin Aspart Aspart Aspart Lispro Lispro Lispro Glulysene Glulysine Glulysine Glargine or Detemir 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00

19 The ideal insulin therapy should mimic endogenous insulin secretion Plasma glucose profiles Endogenous insulin secretion 0.08 Glucose homeostasis Insulin (U/l) Plasma glucose (mmol/l) Time (hours) Owens DR, et al. Lancet 2001;358:

20 Effectiveness of Postprandial Humalog in Toddlers Rutledge, Chase, Klingensmith et al Pediatrics 100:968,97 Determine if postprandial rapid-acting insulin effective Subjects < 5 years old Results: 2-hour glucose excursions lower with postprandial Humalog compared to preprandial regular Similar to preprandial Humalog

21 Outcomes of Pump Therapy Kaufman, et al, Diabetes Metabolism and Reviews, month data 130 subjects PRE POST P value HbA1c % BMI NS Hypoglycemia events/pt/y DKA events/pt/y

22 Results of Insulin Pump Therapy In Young Children Kaufman, et al, Diabetes Spectrum, 2001 Pre Post P Value HbA1c Mean BG Hypo-glycemia ND Quality of Life Family Cohesion

23 Question Why About the Risk of Hypoglycemia From Intensive Regimens?

24 Adverse Events in Intensively Treated Children and Adolescents with Type 1 Nordfeldt, Ludvigsson Acta Pediatr 88:1184, Subjects, ages 1-18 yrs on MDI Mean HbA1c 6.9% Severe Hypoglycemia events/pt/yr Decreased from 1-2 injections Correlated with previous severe hypoglycemia r=.38,p< DKA rate events/pt/yr MDI effective and safe

25 Conclusion Ultimate Goals Of Diabetes Sustained Normal Blood Glucose Control Treatment = No Long-Term Diabetes Complications Lowest Possible Incidence of Hypoglycemia = No Acute Diabetes Complications Best Quality of Life with Diabetes For the child and your family

26 Summary Basal-bolus therapy is the treatment of choice Separate FBG and PPBG control Flexible dosing and timing of injections Insulin glargine and insulin glulisine are an effective combination for basal-bolus therapy Glargine: peakless 24 hour coverage Glulisine: fast onset of action and effective PPBG control As effective in children and adolescents as adults Adding glulisine to basal insulin provided more effective glycaemic control than adding lispro in children and adolescents T1DM patients Particularly in adolescents aged years The particularities of adolescents need to be considered when treating T1DM

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