slide1 n.
Skip this Video
Loading SlideShow in 5 Seconds..
Download Presentation


599 Views Download Presentation
Download Presentation


- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript


    2. 7/30/2012 E-MAIL: 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: 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

    4. 7/30/2012 E-MAIL: 4

    5. 7/30/2012 E-MAIL: 5

    6. 7/30/2012 E-MAIL: 6

    7. 7/30/2012 E-MAIL: 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: 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: 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: 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]


    12. 7/30/2012 E-MAIL: 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: 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: 14 Help your patient rule diabetes, not vice-versa

    15. 7/30/2012 E-MAIL: 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: 16 Ensure efficacy, predictability, safety

    17. 7/30/2012 E-MAIL: 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: 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: 19 ANALOGUES IN PREGNANCY Unique problems high PPBG. comparatively low FBG. very strict control required. risk of foetal hypoglycemia. risk of neonatal hypoglycemia.

    20. 7/30/2012 E-MAIL: 20

    21. 7/30/2012 E-MAIL: 21

    22. 7/30/2012 E-MAIL: 22

    23. 7/30/2012 E-MAIL: 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: 24 NEONATAL HYPO

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

    26. 7/30/2012 E-MAIL: 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.

    27. 7/30/2012 E-MAIL: 27

    28. 7/30/2012 E-MAIL: 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: 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: 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: 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.

    32. 7/30/2012 E-MAIL: 32

    33. 7/30/2012 E-MAIL: 33 RESULTS IN CHILDREN

    34. 7/30/2012 E-MAIL: 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: 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: 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: 37 TDS premixed aspart

    38. 7/30/2012 E-MAIL: 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: 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 ]

    40. 7/30/2012 E-MAIL: 40