Insulin therapy in various type 1 diabetes patients workshop

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1 Insulin therapy in various type 1 diabetes patients workshop Bruce H.R. Wolffenbuttel, MD PhD Dept of Endocrinology, UMC Groningen website: & Case no. 1 Male of 35 years of age T1DM for over 20 years Relatively limited microvascular complications Uses multiple insulin regimen consisting of insulin glargine and insulin aspart before the main meals For his glycaemic control: see the recording made with an ipro (blinded continuous glucose sensor) What would be your strategy, and what would be your advice to the patient? 1

2 Insulin treatment in type 1 diabetes Mimic normal physiology Normal physiology = 3 main meals Fast acting or ultra fast acting insulin Basal = longacting insulin at bedtime (NPH or analogue) Treatment needs to be adjusted the local or country nutritional habits, exercise, etc. 2

3 Goals of treatment Blood glucose Good Acceptable Poor Fasting (mmol/l) > 8 Before the main meals (mmol/l) > 8 Postprandial (mmol/l) < > 10 At bedtime > 10 Action profile of current day insulin preparations 3

4 Fast acting (normal/regular) insulin Actrapid Humulin regular Isuhuman Rapid hours uren Ultrafast acting insulin Insulin aspart Insulin lispro Insulin glulisine uren hours 4

5 Ultrafast acting insulin Reconstructed / modified insulin: Insulin lispro, insulin aspart, insulin glulisin Faster resorption from the subcutaneous tissue But also shorter acting, around 4 5 hours May be too short when long period between lunch and dinner Patients may need additional injection with basal insulin, eventually taking 2 x daily a basal insulin, 3 x fast acting insulin before meals 5

6 Insulin profiles Insulin (mu/l) Endogenous insulin Fast acting insulin Ultrafast acting insulin Meal Minutes 6

7 Hypoglycaemic events during treatment with insulin aspart and human insulin Insulin aspart Human insulin RR (95% CI) P value N /pt year N /pt year Minor ( ) Major all ( ) 0.12 night ( ) daytime ( ) 0.27 Heller et al. Diab Med 2004;21: Self monitored blood glucose profiles obtained during the last week of treatment periods human insulin (, solid line), insulin aspart (, dashed line) HbA1c Heller et al. Diab Med 2004;21:

8 Longacting insulin (NPH, Neutral Protamine Hagedorn) Humulin NPH Insulatard Isuhuman Basal hours 14 Twice daily insulin mix Breakfast Lunch Dinner Bedtime 8

9 Multiple insulin injection regimen Breakfast Lunch Dinner Bedtime Long acting insulin analogues Modified insulin: Insulin glargine, insulin detemir Slow and gradual resorption from the subcutaneous tissue More comparable action from day to day, less variation, hence less variation of the fasting blood glucose 9

10 Insulin glargine (Lantus R ) 21 A Gly 30 B a L Arg 30 B b L Arg humaan insuline (di arginyl insuline) Gly Replacement Gly Ile Val Glu Gln Ile Gl u Cys Asn Phe Val Asn Gln His His Leu Gly Phe Pro Lys Arg Arg Acid insulin (ph 4.5), will after injection.. Subsequently gradual uptake into the blood stream Added Insulin glargine (Lantus R ) 10

11 Insulin detemir Lys B29 (N tetradecanoyl)des(b30) human insulin S S A-chain S S Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys B-chain Mode of action of insulin detemir Insulin pen device resorption distribution binding to cells in the body 11

12 Where to inject insulin? (U)shortacting NPH/ Long acting Long insuline the upper leg (slower resorption of insulin) Mix insulines: Morning: in the abdomen Evening: in the leg Rotate injection sites Resorption of insulin is influenced by temperature, sports/exercise, massage 12

13 Modern insulin treatment with pumps 13

14 Continuous subcutaneous insulin infusion (CSII) Advantages More natural mode of administration of insulin (but still by subcutaneous route!) More predictable resorption of insulin into the blood Better glycaemic control with less hypoglycaemia (especially with ultrafast acting analogue in pump) Smaller chance of severe hypoglycaemia (coma) More normal living Disadvantages Slightly faster glycaemic derangements / keto acidosis Skin infections Reasons to start insulin pump treatment Achieve better glycaemic control Repeated and /or severe hypoglycaemia Pregnancy or desire to become pregnant Improve insulin sensitivity The Dawn phenomena Diabetic complications despite reasonable glycaemic control Variable work / daily activities 14

15 CSII in the DCCT study 34% of the patients was using an insulin pump HbA 1c was % lower in the pump patients Comparable number / severity of hypoglycaemia (remember: this was still in the period before ultrafast acting analogues) Severe hypo s: 1 episode per 5.6 patient years Infections: 1 episode per 8.3 patient years Somogyi effect Reactive hyperglycaemia as a reaction on a nocturnal hypoglycaemia Its relevance is still under debate Dawn phenomena Early morning hyperglycaemia caused by rise of cortisol and other BG increasing hormones Difficult to correct with long acting insulin, pump is perfect as a treatment for this 15

16 Causes of fasting hyperglycaemia Innovations: the artificial pancreas De Vries H

17 Innovations: developments in insulin therapy Innovations: faster acting insulin analogues 17

18 To pump or not to pump.. Learn to critically review the literature. To pump or not to pump.. Learn to critically review the literature. Insulin pen users: were older were less well educated had longer duration of diabetes had higher bloodpressure had more cardiovascular disease but similar HbA1c levels 18

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