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INSULIN ANALOGUES IN SPECIAL SITUATIONS

7/30/2012. E-MAIL: bhartihospital@rediffmail.com. 2. AGENDA. Insulin analogues : the need. Insulin analogues : the advantage Insulin regimes : indications Analogues in pregnancy. Analogues in children. Analogues in renal/hepatic failure. Analogues in indoor patients Innovat

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INSULIN ANALOGUES IN SPECIAL SITUATIONS

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    1. INSULIN ANALOGUES IN SPECIAL SITUATIONS Dr. SANJAY KALRA, D.M. [AIIMS] BHARTI HOSPITAL, KARNAL INDIA

    2. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 2 AGENDA Insulin analogues : the need. Insulin analogues : the advantage Insulin regimes : indications Analogues in pregnancy. Analogues in children. Analogues in renal/hepatic failure. Analogues in indoor patients Innovations

    3. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 3 LACUNAE Mismatch between glycemic excursions PP and insulin levels Delay in insulin absorption: Poor PP control Lack of truly basal insulin: Poor F control Hypoglycemia Variability in action: inter-patient, intra-patient

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    7. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 7 WE WANT TO BE BETTER! Create physiological regimes with newer insulins which mimic the natural variation in insulin levels Provide adequate basal levels Achieve post-prandial peaks when needed Ensure certainty of results

    8. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 8 INSULIN ANALOGUES RAPID ACTING Lispro = Lys(B28), Pro(B29) Aspart = Pro?Asp(B28) Glulisine = Lys(B3), Glu(B29) Rapid dissociation of hexamers Thyroxyl insulin = B1-l-thyroxine BASAL Glargine = Gly(A21),Arg(B31,B32); higher isoelectric point; precipitates in neutral SC tissue Detemir = B29-fatty acid acylation, B30 removed; 98% albumin binding

    9. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 9 Short acting analogues Variability only 20 – 30 % [Heinemann, 2002] Approved for IV use as well Can be given pre- or post- meal Dose adjustment can be done after meal/ CHO counting; to cover for incidental hyper/hypo Can be mixed with NPH immediately prior to injection Must not be mixed with glargine

    10. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 10 Advantages of RAA With lispro/ aspart, hypo may occur 90 mins after a meal, esp. with high fat, low CHO meal [Burge MR et al, 1997] rather than 2-3 hrs after the meal as with regular insulin RAA safer with exercise [Bolli GB et al, 1999] RAA use less snacks [Ronnemaa T et al, 1998] May ameliorate immunologic insulin resistance [ Kumar D, 1997]

    11. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 11 INDICATIONS FOR ANALOGUES

    12. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 12 INDICATIONS OF ANALOGUES 1-Uncertainty in lifestyle/meals 2-High/unpredictable fasting bl glucose 3-High PP bl glucose 4-‘Critical’ patients 5-Risk of hypoglycemia

    13. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 13 Indications-1 Variable lifestyle Uncertain mealtimes Uncertain meal quantity Uncertain snacks Unexpected exercise Inability to maintain injection-meal gap Children Elderly Busy working people Sportsmen Policemen/army personnel/fire-fighters

    14. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 14 Help your patient rule diabetes, not vice-versa

    15. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 15 Indications-2,5 High FBG Somogyi phenomenon Dawn phenomenon Unpredictable FBG Nocturnal hypo Brittle diabetes HIGH RISK OF HYPO

    16. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 16 Ensure efficacy, predictability, safety

    17. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 17 Indications-3 High PPBG Low premeal BG Poor HbA1c inspite of ‘good’ glucose values Pregnancy ?Weight gain with conventional insulin ?Acanthosis nigricans Steroid induced diabetes mellitus OPD management of ketonuria/ketosis with IM RAA

    18. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 18 Indications-4 ICU/ICCU patients being shifted from IV to SC insulin Post transplant diabetes mellitus Peri-operative patients OPD management of ketonuria/ketosis with IM RAA

    19. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 19 ANALOGUES IN PREGNANCY Unique problems high PPBG. comparatively low FBG. very strict control required. risk of foetal hypoglycemia. risk of neonatal hypoglycemia.

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    23. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 23 NEONATAL HYPOGLYCEMIA IN OFFSPRING OF TREATED MOTHERS 75 pregnancies ; 77 child births analyzed 22 conventional premixed 11 conventional 3 or 4 dose 27 aspart premixed 17 aspart 3 dose Gestation, mode of delivery, birth weight, insulin dose similar.

    24. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 24 NEONATAL HYPO

    25. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 25 OPD Mx of KETOSIS IN PREGNANCY

    26. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 26 RENAL FAILURE Due to insulin resistance, renal patients need higher dosage of regular insulin With increasing doses, duration of action of regular insulin increases. This increases the risk for late-postprandial hypoglycemia Nosek et al (2003): Aspart unlike regular human insulin does not show a significant prolongation in its duration of action with higher doses.

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    28. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 28 RENAL FAILURE Aspart: rapid, shorter and predictable duration of action, leading to reduced frequency of hypoglycemic episodes. Lyness et al (2001): Kinetics of Insulin Aspart were unaffected by renal impairment safety profile was comparable among persons with diabetes with various degrees of renal dysfunction.

    29. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 29 ANALOGUES IN SCHOOL CHILDREN Unique problems. uncertain moods /meal quantity. long breakfast- lunch gap. midday meal at school, without insulin. risk of hypoglycemia in school. unplanned exercise/ physical activity. unplanned snacks.

    30. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 30 3- DOSE ASPART REGIME IN SCHOOL CHILDREN 12 week long single – centre, prospective, randomized, open-label study. Premixed aspart B/BF & B/dinner ; regular aspart B/lunch vs. conventional bolus- basal regime. 29 in aspart group, 23 in conventional group (3 drop outs). Baseline age, duration of diabetes, HbA1c similar.

    31. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 31 3 –DOSE ASPART REGIME IN SCHOOL CHILDREN Self reported concordance higher with aspart regime (3/29 missed = 1 injection in preceding 1 week) than conventional regime(6/20). Mild hypoglycemia lower in aspart regime (0.66 episodes/pt./week) than conventional regime (2.59). 3 drop outs in conventional regime.

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    33. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 33 RESULTS IN CHILDREN

    34. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 34 ANALOGUES IN INDOOR PATIENTS Sliding scale :difficult to control BG. ‘Reactive’ approach. Basal – bolus traditional insulin :comparatively delayed onset risk of hypoglycemia. Intra-patient variability. Analogue insulin : quick onset of action. Less risk of hypoglycemia. ‘Pro –active’ approach.

    35. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 35 ASPART IN INDOOR Aspart preferred for s.c. use in hospitalized patients: benefits Superior prandial control Maintains long-term glucose control Low risk of hypoglycemia Freedom from meal time constraints Aspart IV: no switch in insulin formulation & therefore no loss of insulin Patients with DKA : when antibodies are suspected to HI Different receptor-binding characteristics : glucose-lowering response (pharmacodynamics) could be different

    36. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 36 TROUBLE SHOOTIN’ TECHNIQUE-RELATED Blocked needle Air bubble Wrong storage Use of spirit on needle Inter-site rotation Intra-site rotation Hypertrophy PRESCRIPTION-RELATED Meal-injection gap RAA for PP glucose Basal for pre-meal glucose Delay night dose for fasting control Increase no. of doses instead of total dose Add sensitizer

    37. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 37 TDS premixed aspart

    38. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 38 Innovation: daytime insulin, bedtime sulfonylurea Long acting insulin [non-physio hyperinsulism] leads to weight gain, by chronically stimulating lipogenesis and blocking lipolysis. Aspart tds [average 24.1 U/d] + glimepiride [average 4.4 mg] at 8 pm achieved glycemic control in 56% patients without hypo or weight gain Glimepiride increases endogenous insulin portal circulation and suppresses HGO [de Boer et al, 2004]

    39. 7/30/2012 E-MAIL: bhartihospital@rediffmail.com 39 TAKE HOME from DHAKA Utilize available physiological insulins Achieve smoother control Tackle special situations: Pregnancy School children Renal failure Hepatic failure Indoor patients [ surgical, medical ]

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