胰岛素注射后脂肪增生与脂肪萎缩

1、LIPOHYPERTROPHY: the State of the ArtKen Strauss, MDGlobal Medical Director, BDDirector Safety in Medicine, European Medical AssociationLypohypertrophyPicture courtesy of Nurse Ruth Gaspar, Madrid, SpainSeven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Ins

2、ulin reductions7. Cost savingsLH is common15.9% (Kashi et al 2008)27.1% (Raile et al. 2001)34.5% (Partanen, Rissanen 2000) 48.0% (Kordonuri et al 2002)57.0% (Teft 2002)Have you ever noticed swelling of fatty tissue or small bumps at your injection sites? 48%said yes*2009 ITQ Survey44,6USA44,6RUSSIA4

3、5,6NETHERLANDS54,2BELGIUM50,4FRANCE51,7SPAIN44,6ITALIA73,3SWITZERLAND54,2UK & IRELAND56,6DENMARK60,0SWEDEN52,2GERMANY31,1CHINA33,1TURKEY30,0PORTUGAL88,0FINLANDDe Coninck C, et al. Results and analysis of the 2008-2009 Insulin Injection Technique Questionnaire survey. J Diabetes. 2010 Sep;2(3):168-79

4、.What is your experience?Seven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Insulin reductions7. Cost savingsResults: Frequency lipohypertrophy : 48.8%Three independent risk factors :1. Using insulin for long time (p=0.001), 2. Giving injection in same plac

5、e (p=0.004), 3. Reusing the same needle (p=0.004).Could there be other causes?Seven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Insulin reductions7. Cost savingsHow is insulin absorbed in lipohypertrophy?Seven landmark studies1. Frequency2. Causes3. Histop

6、athology4. Absorption5. Glucose control6. Insulin reductions7. Cost savingsDiabetes Care 2005; 28:2025-2027Continuous glucose monitoring systemShows the patient not only concrete moments, but provides a global vision of the situationMedtronic Injection in lipohypertropy Average= 220 mg/dl; SD = 66 I

7、nsulin = 33 U/dayInjection in healthy area Average= 155 mg/dl; SD = 47 Insulin = 28 U/dayDo you think of lipohypertrophy in patients with unstable glucose?Seven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Insulin reductions7. Cost savings2;2011: 80-83.Pati

8、ent case1.19 year old woman, DM for 6 years2.4 injections a day (1 needle/day)3.High glucose variability (3 mmol/l to 24 mmol/l)4.No palpable or visible lipohypertrophy at injection sitesCase Patient Outcome DataInjection into Lipohypertrophy Daily total insulin = 82U HbA1C was 11.8% Injection into

9、Normal Tissue Daily dose fell to 42U Target glucose levels were reachedCase Patient Outcome DataInjection into Lipohypertrophy Daily total insulin = 82U HbA1C was 11.8% Injection into Normal Tissue Daily dose fell to only 42U Target glucose levels were reachedCase Patient Outcome DataInjection into

10、Lipohypertrophy Daily total insulin = 82U HbA1C level was11.8% Injection into Normal Tissue Daily dose fell to 42U Target glucose levels were reachedWhat are clues lipohypertrophy might be present?Seven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Insulin r

11、eductions7. Cost savingsFranzen I, J. Ludvigsson, Linkping 1997 Specific Instructions Gave Reduction of Lipomas and Improved Metabolic Control in Diabetic Children, Diabetologia Vol 40, Supplement 1: A615 (1997) 20 Children with clinically detectable lipos Received instructions: Rotate! Dont reuse!

12、In 3 months 90% of lipos had resolved HbA1c was improved significantly Insulin requirements had decreased How much does lipohypertrophy cost?Dr. Treichel, MagdeburgGERMANY 102 Adults with clinically detectable lipos Received instructions:Rotate!Dont reuse! 7 point glucose panel done Patients evaluat

13、ed at Entry and 14 days laterResultsCost of TherapyPatient A (per year)BasalHumalogPen NeedlesSumCo-Paymentprior to IT training2.005 1.499 45 3.550 275 after IT training573 551 498 1.622 128 difference(savings)1.432 948 (453 )1.928 147 Daily Insulin Dose and Cost of TherapyPatient B HumalogLantusCos

14、tDay of entry48 IU/d82 IU/d2198 /yearDay of release (after IT-Training)20 IU/d14 IU/d564 /yearDifference (savings)- 58 %- 83 %- 74 %Daily Insulin Dose and Cost of TherapyPatient C (per year)BasalPrandialInsulinCo-paymentprior to IT training105 IU33 IU2.112 168 after IT training34 IU24 IU888 71 diffe

15、rence(savings)- 67 %- 27 %1.224 97 ( All EURO data were calculated according the reimbursment prices Dt. Apothekentaxe, Ausgabe Oktober 2009 )Do any studies answer the cost question?Seven landmark studies1. Frequency2. Causes3. Histopathology4. Absorption5. Glucose control6. Insulin reductions7. Cos

16、t savingsPatients 430 outpatients177 with DM1 253 with DM2 Then each subject was examined by a study nurse for the presence of lipohypertrophy and for correct site rotation technique. Correct Rotation = at least 1 cm between successive injectionsPrevalence of LH 2/3 of patients (64.4%) had LHMore co

17、mmonly in DM 1 (72.3%)Than DM2 (53.4%)Lipohypertrophy and Observed Correct Rotation: Actual Results LipoNo LipoTotalCorrect6100106Not26218280Total268118386p= 0.0001 Lipohypertrophy and Observed Correct Rotation : hypothetical results if there were a perfect causative relationship LipoNo LipoTotalCor

18、rect0106106Not2800280Total280106386p= 0.00000000001 Hypoglycemia Of those with LH 39.1% had unexplained hypoglycemia For those without it was 5.9% (p=0.03)Hypoglycemia Of those with LH 39.1% had unexplained hypoglycemia For those without it was 5.9% (p=0.03)Glucose Variability Of those with LH 49.1%

19、 had glycemic variability For those without it was 6.5% (p=0.02)Glucose Variability Of those with LH 49.1% had glycemic variability For those without it was 6.5% (p=0.02)LH and Total Insulin Dose LipohypertrophyDose categoryYesNoTotal Dose (mean IU/day)5641Total Dose DM 15042Total Dose DM 26241Healt

20、h Economic Costs This 15 IU difference multiplied over the number of daily injections into LH Assuming a cost of 0.0243 euros/IU Total annual cost to the Spanish health care system of over 122 million euros.Learnings about LH1. LH is very frequent2. Main causes: insulin, non- rotation, reuse3. LH di

21、storts insulin absorption4. LH worsens glucose control5. LH leads to excessive and avoidable medical costsSite RotationANDRotation within SitesBut wont this increase the risk of IM injections?7 mm10 mm4-5 mmBut wont this increase the risk of IM injections?YES, unless we use shorter needlesAll needle

22、s are at least twice as long as the skin is thickNeedle length and IM injectionsNeedle Length (mm)% IM Injections12.745815665240.4Gibney M, et al. Curr Med Res Opin 2010;26:1519-30If a Patient is giving 3 injections a day, how often would he inject IM using the different needles?Days of IM injection

23、 with 12.7 mm needle=EVERY DAY!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 12.7 mm = EVERY DAY !Days of IM injection with 8 mm needle=EVERY 2 DAYS!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 8 mm = EVERY 2 DAYS !Days of IM injection with 6 mm needle=EVERY 5 DAYS!MondayTuesdayWednesdayT

24、hursdayFridaySaturdaySunday 6 mm = EVERY 5 DAYS !Days of IM injection with 5 mm needle=EVERY 17 DAYS!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 5 mm = EVERY 17 DAYS !Days of IM injection with 4 mm needle=EVERY 83 DAYS!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 4 mm = MONTH 1Days of I

25、M injection with 4 mm needle=EVERY 83 DAYS!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 4 mm = MONTH 2Days of IM injection with 4 mm needle=EVERY 83 DAYS!MondayTuesdayWednesdayThursdayFridaySaturdaySunday 4 mm = MONTH 34 mm = EVERY 83 DAYS !Studies Link IM injection to Hypos1.Karges B, Boehm B

26、O, Karges W. Early hypoglycaemia after accidental intramuscular injection of insulin glargine. Diabet Med 2005;22:14441445.2.Vaag A, Handberg A, Lauritzen M, et al. Variation in absorption of NPH insulin due to intramuscular injection. Diabetes Care 1990;13:74-76.3.Vaag A, Damgaard Pedersen K, Lauri

27、tzen M, et al. Intramuscular versus subcutaneous injection of unmodified insulin; consequences for blood glucose control in patients with type 1 diabetes mellitus. Diabet Med 1990;7:335-342.4.Frid A, Ostman J, Linde B. Hypoglycemia risk during exercise after intramuscular injection of insulin in thi

28、gh in IDDM. Diabetes Care 1990;13:473-477.1 hypo out of 5 is possibly linked to IM injectionHow many Hypos for our Patient on 3 injections / day ?Needle Length (mm)Hypos due to IM injections12.7Every 5 days8Every 10 days6Every 25 days5Every 85 days4Every 415 daysInjection Technique Training Improves Glucose Control in Only 3 MonthsStudy Design Patients (N=346) with diabetes from 18 ambulatory centers i