Insulins And Insulin Delivery

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  • Insulins And Insulin Delivery

    1. 1. Insulins and Insulin Delivery Rob Dyer 6 February 2009
    2. 2. Case 1 <ul><li>37 year old man referred by GP. </li></ul><ul><li>Type 1 diabetes for 18 years. HbA1c consistently 9.0 – 10.5% </li></ul><ul><li>Was on bd H Mixtard until 2002. Transferred to Actrapid 20, 20, 20 and H Insulatard 20 when in hospital in 2002. </li></ul><ul><li>‘ Would he be a good candidate for Glargine?’ </li></ul>
    3. 3. Miss RL – HbA1c Normal range Target Age 10 Age 17
    4. 4. Glycaemic excursion and Premixed insulin
    5. 5. DCCT Effect of intensive therapy on complications and hypoglycaemia
    6. 6. Intensive education, the German experience. <ul><li>1983 Muhlhauser et al (Michael Berger). 5 day intensive educational programme for patients with Type 1 diabetes </li></ul><ul><li>636 patients </li></ul><ul><li>6 years of follow up </li></ul><ul><li>Sustained improvement in HbA1c to 7.6% </li></ul><ul><li>Reduced risk of hypoglycaemia </li></ul><ul><li>Refs Mulhauser I et al, Diabetologia 25;470-6, 1983 </li></ul><ul><li>Bott S et al, Diabetologia 40:926-32, 1997 </li></ul>
    7. 7. Food Comparisons How much carbohydrate?
    8. 9. SALAD MEAL 15g Lettuce minimal Cucumber &quot; Tomatoes &quot; Radish &quot; Red Pepper &quot; Cold chicken &quot; Mayonnaise &quot; Crisps 15g
    9. 10. Italian Meal Garlic Bread Whole Pizza Ice Cream ???g
    10. 11. Italian Meal Garlic Bread 70g Whole Pizza 100g Ice Cream 30g 200g
    11. 12. Mrs BS (3 months after course) <ul><li>Running marathons </li></ul><ul><li>1 unit insulin: 12g CHO when inactive </li></ul><ul><li>1 unit insulin: 20g CHO when active </li></ul><ul><li>No nocturnal hypos </li></ul><ul><li>HbA1c 7.9% (9.5% before course) </li></ul>
    12. 13. Mrs BS (4) <ul><li>Insulin dose before course </li></ul><ul><li>Lispro 8, 8, 8 </li></ul><ul><li>Humulin I 8 32 </li></ul><ul><li>Insulin dose after course </li></ul><ul><li>Lispro 9 approx </li></ul><ul><li>Humulin I 5 14 </li></ul>
    13. 14. Case 1 (contin) <ul><li>Has completed CHO counting course. </li></ul><ul><li>HbA1c 8.9% </li></ul><ul><li>On Novorapid variable doses with meals </li></ul><ul><li>H Insulatard at bedtime 22 units </li></ul><ul><li>Prone to hypos if increases H Insulatard. </li></ul><ul><li>What are the options? </li></ul>
    14. 15. Short acting analogues <ul><li>Are more convenient to take than standard soluble insulin </li></ul><ul><li>Give better post-prandial glycaemic control </li></ul><ul><li>Probably do not result in better HbA1c </li></ul><ul><li>May reduce hypoglycaemia </li></ul>
    15. 16. 1530 Levemir® vs. NPH in treat-to-target trial: Hypoglycaemia Hypoglycaemia Hermansen K, et al., Diabetologia 2004;47(Supplement 1):A273
    16. 18. Within-patient variability with NPH insulin Selected clamp profiles on 4 identical study days for 8 out of 17 subjects on NPH who completed the study The CV for all 17 patients on NPH who completed the study was 68% Heise, T. et al., Diabetes, 2004; Vol. 53: 1614-1620 Data on file: InsDet 09 2004
    17. 19. Within-patient variability with Levemir ® Selected clamp profiles on 4 identical study days for 8 out of 18 subjects on Levemir ® who completed the study The CV for all 18 patients on Levemir ® who completed the study was 27% Heise, T. et al., Diabetes, 2004; Vol. 53: 1614-1620 Data on file: InsDet 09 2004
    18. 20. HbA1c (%) Post- Baseline Post-CSII Post-TIFA Changes in HbA1c during transfer to Pump therapy (CSII) Individual patients
    19. 21. Torbay CSII First 11 patients
    20. 22. Other benefits of CSII <ul><li>Reduction in hypoglycaemia </li></ul><ul><li>Reduction of post-prandial glucose excursion </li></ul><ul><li>Reduction in Hba1c (in the majority) </li></ul><ul><li>Easier to manage illness </li></ul><ul><li>Management of ‘dawn phenomenon’ </li></ul><ul><li>Less swings in blood glucose levels </li></ul><ul><li>Improved QOL. </li></ul><ul><li>Feeling in control </li></ul><ul><li>‘ Patient power’ </li></ul>
    21. 23. Primary Care Insulin Initiation <ul><li>A practice is just starting out on insulin initiation in Type 2 diabetes. </li></ul><ul><li>The staff find it confusing that there are so many insulins. </li></ul><ul><li>They ask you to advise them on a limited range to make life simpler as they are starting out. </li></ul><ul><li>What would you advise? </li></ul>
    22. 24. 4T Baseline Characteristics <ul><li>Biphasic Prandial Basal N=235 N=239 N=234 </li></ul><ul><li>Age (years) 61.7 ±8.9 61.6 ±10.5 61.9±10.0 </li></ul><ul><li>Diabetes duration (years)* 9 (6-2) 9 (6-4) 9 (6-12) </li></ul><ul><li>Body weight (kg) 86.9 ±16.8 84.9 ±14.4 85.5 ±16.3 </li></ul><ul><li>Body mass index (kg/m 2 ) 30.2 ±4.8 29.6 ±4.5 29.7 ±4.6 </li></ul><ul><li>HbA 1c (%) 8.6 ±0.8 8.6 ±0.8 8.4 ±0.8 </li></ul><ul><li>Fasting plasma glucose (mmol/l) 9.7 ±2.8 9.6 ±2.7 9.5 ±2.6 </li></ul><ul><li>LDL cholesterol (mmol/l) 2.5 ±0.7 2.4 ±0.7 2.3 ±0.7 </li></ul><ul><li>HDL cholesterol (mmol/l) 1.0 ±0.3 1.0 ±0.2 1.0 ±0.3 </li></ul><ul><li>Triglycerides (mmol/l) * 1.6 (1.2-2.1) 1.5 (1.2-2.3) 1.5 (1.1-2.2) </li></ul><ul><li>No significant differences between groups *interquartile range </li></ul>N Engl J Med 2007; 357: 1716-30
    23. 25. Randomisation N Engl J Med 2007; 357: 1716-30 * Intensify to a combination insulin regimen in year one if unacceptable hyperglycaemia 708 T2DM on dual OAD Add biphasic insulin twice a day Add prandial insulin three times a day R Year 1 Comparison of three single insulin regimens, added to OADs* Add basal insulin once (or twice) daily Add prandial insulin at midday Add basal insulin before bed Years 2 and 3 If HbA 1c >6.5%, stop sulfonylurea and add a second insulin formulation Add prandial insulin three times a day
    24. 26. Insulin Dose Adjustments <ul><li>Morning injection of basal insulin </li></ul><ul><ul><li>34% (n=79) of patients randomised to pre-bedtime basal insulin required, per protocol, an additional morning injection by one year </li></ul></ul><ul><li>Adherence to dose adjustment suggestions (±10%) </li></ul><ul><ul><li>Biphasic 89.7% </li></ul></ul><ul><ul><li>Prandial 80.4% </li></ul></ul><ul><ul><li>Basal 90.2% </li></ul></ul>N Engl J Med 2007; 357: 1716-30
    25. 27. Primary Outcome: HbA 1c at One Year N Engl J Med 2007; 357: 1716-30 — Biphasic — Prandial — Basal Mean ±SD at 1 year (%) 7.3±0.9 Baseline to 1 year (%) -1.3±1.1 7.2±0.9, p=0.08 vs. biphasic 7.6±1.0, p<0.001 vs. biphasic or prandial -0.8±1.0 -1.4±1.0 Months since randomisation Glycated haemoglobin (%) P<0.001
    26. 28. Glucose Profiles Before & After Starting Insulin — Biphasic — Prandial — Basal Change in FPG (mmol/l)) -2.5±3.1 Change in PPG (mmol/l) -3.8±3.5 - 1.3±2.7 -3.3±2.9 -2.6 ±3.0 -4.6±3.0 p<0.001 vs. biphasic p<0.001 vs. biphasic or prandial 0 — At baseline
    27. 29. Hypoglycaemia (≥ Grade 2) at One Year N Engl J Med 2007; 357: 1716-30 Months since randomisation Proportion with events (%) P=0.001 — Biphasic — Prandial — Basal Mean at 1 year (events/patient/year) 5.7 12.0, p<0.002 vs. biphasic 2.3, p=0.01 vs. biphasic, p<0.001 vs.prandial
    28. 30. Biphasic analogue insulins vs standard biphasic insulin <ul><li>Are more convenient to take </li></ul><ul><li>May give better post-prandial control </li></ul><ul><li>Probably don’t result in better HbA1c </li></ul><ul><li>Probably cause less hypoglycaemia than standard biphasic insulins </li></ul><ul><li>‘ Convenience insulins’ </li></ul><ul><li>Good devices </li></ul>
    29. 31. <ul><li>Conclusions – </li></ul><ul><li>In 518 patients with type 2 diabetes, once daily bedtime insulin glargine is as effective as once or twice daily NPH in improving and maintaining glycemic control. </li></ul>
    30. 32. <ul><li>Conclusions – </li></ul><ul><li>In 518 patients with type 2 diabetes, once daily bedtime insulin glargine is as effective as once or twice daily NPH in improving and maintaining glycemic control. </li></ul><ul><li>But </li></ul><ul><li>All patients were taking multiple injection therapy </li></ul>
    31. 33. Raskin P, Rojas P, Hu P et al. Comparison of twice-daily biphasic insulin aspart 70/30 (NovoLog Mix® 70/30) with once-daily insulin glargine in patients with type 2 DM on oral antidiabetic agents. Diabetes Care 2005; 28; 260-5.
    32. 34. 1530 Levemir® vs. NPH insulin Treat-to-target trial: Weight p<0.001 Hermansen K, et al., Diabetologia 2004;47(Supplement 1):A273
    33. 35. Baseline BMI 35 36 34 39 55 37 42 50 69 76 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 -0.5 Mean weight change (kg)  25 >25-27 >27-29 >29-31 >31 Insulin detemir NPH insulin 1530 Hermansen: Change in weight by baseline BMI K. Hermansen et al. EASD 2005
    34. 36. Type 1 effect of improved HbA1c
    35. 37. HbA 1c cross-sectional, median values
    36. 38. Any diabetes related endpoint M v I p=0.0034 overweight patients M v C p=0.0023

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