Behandling af gamle med diabetes - DSGdan آ  Behandling af gamle med diabetes herunder Nye

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  • Behandling af gamle med diabetes

    herunder

    Nye diagnostiske kriterier, prævalens, prognose, behandlingsmål og behandlingsguidelines

    Jan Erik Henriksen Ledende overlæge, klinisk lektor, PhD

    Endokrinologisk afd. M

    Odense Universitet Hospital

  • Diagnosen Diabetes

  • 1997 diagnosen FPG = 7.8 mM2 timers PG

    = 11.1 mM

    FPG = 7.0 mM

    2 timers OGTT 11.1 mM

  • 2009 diagnosen ! Vurdering af HbA1c som diagnostisk værktøj

  • Hvilken værdi ?

    Ca 28.000 personer fra ni forskellige lande

    HbA1c < 6.5 % stort ser ingen med retinopati

  • Begrænsninger! • Omkostninger

    • Hæmoglobinopatier

    • Hæmolytisk anæmi

    • Kronisk malaria

    • Efter større blødninger – blodtransfusion

    • Hurtigt indsættende diabetes (fx DM1)

    • Alder – race ?

  • Prævalens og prognose

  • Anders Green

    Model for udvikling af diabetes i DK

    Ultimo år

    Antal patienter

    700,000

  • 270.98537.12461.15077.13547.65527.68812.0664.7362.830601I alt

    138.83413.90731.10844.13726.99013.7835.0942.1171.401297Mænd

    132.15123.21730.04232.99820.66513.9056.9722.6191.429304Kvinder

    I alt80+70-7960-6950-5940-4930-39

    20-

    29

    10-

    190-9

    Antal diabetikere 2009

  • 1,591,701,482009

    1,571,631,512008

    1,621,691,542007

    1,651,711,602006

    1,691,771,622005

    1,701,801,602004

    1,751,831,682003

    1,751,881,642002

    1,761,821,702001

    1,841,921,762000

    1,861,981,751999

    1,851,901,791998

    1,901,961,831997

    AlleMændKvinder

    Diabetikeres dødelighed set i forhold til den øvrige

    befolkning

    Relativ dødelighed

  • Hvor langt skal Hba1c ned?

  • UKPDS – HbA1c – Endpoints Epidemiology

  • 20 08

  • 0.9 % point in difference between the two groups

  • Difference in HbA1c was only 0.6 % point between the metformin group and the conventional group

  • UKPDS 10-year post-trial monitoring

    from 1997-2007

  • ”Metabolic memory” or ”glucose memory”

    underscoring the importance of optimal glycaemic control

    from time of diagnosis

  • Multifactorial intervention

  • Steno Type 2 Study-Design

    • An open, parallel trial comprising 160 Caucasian type 2 diabetic patients with microalbuminuria

    • With consealed randomisation patients were allocated either to conventional therapy at their GP or intensive treatment at Steno Diabetes Center

    Conventional

    Intensive

    Endpoint examinations

    Microvascular Macrovascular

    4 years 8 years

    n=80

    n=80

    n=160

    Microvascular Macrovascular

    4 years 8 years

  • Hba1c

    Syst BT

    Dia BT

    Total Kol

    LDL

    Triglycerid

  • Kardiovaskulær

    sygdom

    Død

  • Steno-2: Number Needed to Treat for 13 Years to Prevent One ---

    Death 5 patients

    Cardiovascular death 8 patients

    Major cardiovascular event 3 patients

    Progression of nephropathy 5 patients

    Dialysis 16 patients

    Laser treatment 7 patients

  • ACCORD ADVANCE VADT

    de korte ”akutte” studier

  • Standard vs. intensive BG treatment

    ACCORD

    Standard: Goal: HbA1c 7 -7.9%

    Intensive: Goal: HbA1c

  • Tight glycaemic control reduces primary endpoint but not mortality

    Accord Advance VADT

    Primary CVD endpoint 10 % 6 % 13 %

    CVD mortality 39 %* 12 % 32 %

    Total mortality 22 %* 7 % 6 %

    What if the trials had been longer than 5 years ?

  • ACCORD

  • ACCORD: Treatment effects on glucose control

    ACCORD Study Group. N Engl J Med. 2008;358:2545-59.

    A1C (%)

    Time (years)

    Standard therapy

    Intensive therapy

    6

    9.0

    8.5

    8.0

    7.5

    7.0

    6.5

    6.0

    0 0 1 2 3 4 5

  • Which patients will benefit of strict glycaemic control?

  • Hazard Ratios for the Primary outcome Post-hoc analyses ACCORD

  • Mortality in relation to treatment and HbA1c

  • Risk of death over a range of HbA1c

    Steady increase of risk from 6 to 9% HbA1c with intensive strategy

    Excess risk with intensive strategy vs standard occured above HbA1c 7%

    Riddle MC et al. Diabetes Care 2010; 33: 983-90.

  • Excess risk with intensive strategy vs standard occured when intensive participants failed to reduce HbA1c in yr 1

    Riddle MC et al. Diabetes Care 2010; 33: 983-90.

  • Number of participants with severe hypoglycemia

    Intensive Standard P

    N (%) N (%)

    Requiring any assistance 830 (16.2) 261 (5.1)

  • Severe hypoglycaemia in ACCORD study

    • 5 death of the excess of 57 death in the intensive arm could be explain by hypoglycaemia

    • Thus the increase risk of death in the intensive arm can not be explained by hypoglycaemia

    Miller ME et al. BMJ 2010

  • Compared with Standard Therapy the Intensive Strategy had:

    • Lower HbA1c • Greater use of medications:

    - more multiple OAD: 70 % vs 45 % on 3-5 oral classes - more insulin: 77 % vs. 55 % on insulin

    - more combination OAD and insulin: 62 % vs. 18 % on 3-5 OAD + insulin

    • More severe hypoglycemia 10.5 % vs. 3.5 % • More weight gain 28 % vs. 14 % > 10 kg

  • Possible Reasons for increased Mortality

    with Intensive Treatment in ACCORD

    • Hypoglycemia • Rapid glucose lowering • Weight gain

    • Medication interactions, ”treatment resistance”

  • ADVANCE

  • ADVANCE: Treatment effect on glucose control

    ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-72.

    Follow-up (months)

    Mean A1C (%)

    Standard control

    Intensive control

    10.0

    9.0

    8.0

    7.0

    6.0

    5.0

    0.0 0 6 12 18 24 30 36 42 48 54 60 66

    P < 0.001

  • VADT

  • HbA1c-VADT

  • Intensive Glucose-Lowering Therapy Reduces Cardiovascular Disease Events in Veterans Affairs Diabetes Trial Participants

    With Lower Calcified Coronary Atherosclerosis

    Reaven PD et al. Diabetes 2009; 58: 2642-48

  • Intensive Glucose-Lowering Therapy Reduces Cardiovascular Disease Events in Veterans Affairs Diabetes Trial Participants With Lower Calcified

    Coronary Atherosclerosis

    Reaven PD et al. Diabetes 2009; 58: 2642-48

  • VADT-Predictors of CV death

    HR • Prior CV events 3.1 p=0.0001

    • Age/10 yr 2.1 p

  • VADT conclusions • Intensive - CV events slightly reduced (231 vs. 263, ns) - CV mortality slightly increased (19 vs 15, ns)

    • Main predictor of MI was recent severe hypoglycemic episode

    • Early glycaemic control is beneficial • Late intensive control (eg. > 12-15 years after diagnosis) produces little extra benefit

    • No CV risk attributed to any particular therapy

  • What is the optimal level of HbA1c in relation to outcomes and deaths in type 2 diabetes?

    An epidemiological study from UK

    Currie CJ et al. Lancet 2010

  • Hazard ratios for all-cause mortality by HbA1c in people given oral combination and insulin-based therapies.

    Mean follow-up was 4.5 years and 5.2 years.

    Currie CJ et al. Lancet 2010;

    Age: 59.7-67.9 yr.

    Duration: 5.2-5.6 yr.

    Age: 60.3-66.3 yr.

    Duration: 6.8-8.2 yr.

    N = 27965. N = 20005.

    OHA Insulin

  • Interpretation

    • Low and high mean HbA1c values were associated with increased all cause mortality and cardiac events

  • Final HbA1c conclusion Glycaemic control and CVD outcomes

    • Early intervention and intensive control is worthwhile if it can be obtained without high risk of severe hypoglycaemia and major increase in weight

    • After long diabetes duration the effect of intensive glycaemic control seems to be minimal and in some groups of patients may even increase mortality

    • However there are still many unanswered questions, including questions about the choice of agents

  • Behandling af hyperglykæmi

  • Treatments for Type 2 Diabetes

    Gluc ose

    (G)

    Carbohydrate

    Glucose

    DIGESTIVE ENZYMES

    Insulin (I)

    I

    Acarbose Reduces absorption --

    Sulphonylurea Repaglinide

    Stimulates insulin secretion

    ++

    Metformin Reduces hepatic glucose output +

    Limited effect on insulin resistance

    -- Thiazolidinediones

    Reduce Insulin Resistance

    -- ++ --

    I

    I

    I I

    I

    I