Guideline WHO/IADPSG kriterier for diagnosen af gestationel diabetes mellitus (GDM) anbefales. Vi beder om mandat til i samarbejde med Sundhedsstyrelsen at arbejde for implementering af WHO/IADPSG diagnostiske kriterier i Danmark, herunder en vurdering af hvilken screeningsmetode, der er den rigtige til danske forhold, og hvilken opfølgning, der skal anbefales efter fødslen. 1

GLOBALT Peter G. Kopelman Nature 404, 635-643 (6 April 2000) Obesity as a medical problem Derek Yach, David Stuckler & Kelly D Brownell Nature Medicine 12, 62 - 66 (2006)

Gestationel diabetes 1997-2009 i Danmark Meget interessante data – som jeg ikke har set før – jeg tror at man skal stille lidt spørgsmål ved validiteten – mit indtryk er at der ofte er en vis forvirring mellem de forskellige diabetestyper. Men dette er jo nok ens over årene. Jeg undrer mig over at prævalensen er 3,2 - når man tænker på hvormange pt. med GDM vi har hos os, på hvidovre osv – synes snarere at vi ligger på 1-1½%. Mit bud er at nogle der har været til OGTT registreres som GDM. Men summasumarum – fantastisk slide til dit formål Frekvens DK 2004-2010: 2,3 %. DK 2010: 3,2% Danish National Patient Registry 2010 4

Gestationel diabetes mellitus (GDM) – screening og diagnose? Hvorfor diskutere dette? Fordi der anvendes mange forskellige diagnostiske kriterier og screeningsmetoder nationalt/globalt Ingen af kriterierne er baseret på perinatalt outcome 2 timers værdi – DK – ringe korrelation til perinatalt outcome Her kunne du jo nævne at vi synes at vores title ikke helt dækkede hvad vi synes der skal svares på 5

DIABETES CARE, VOLUME 33, NUMBER 3, MARCH 2010 Peter Damm Per Ovesen 7 7

Gestationel diabetes mellitus (GDM) – screening og diagnose? I 2012 diskuteredes 3 spørgsmål Skal vi indføre de nye IADPSG-kriterier i Danmark? Diagnostisering af manifest diabetes Diagnostisering af GDM Skal alle gravide screenes for GDM? Her kunne du jo nævne at vi synes at vores title ikke helt dækkede hvad vi synes der skal svares på 8

Gestationel diabetes mellitus (GDM) – screening og diagnose? I 2012 diskuteredes 3 spørgsmål Skal vi indføre de nye IADPSG-kriterier i Danmark? Diagnostisering af manifest diabetes Ja – Sandbjerg 2012 Her kunne du jo nævne at vi synes at vores title ikke helt dækkede hvad vi synes der skal svares på 9

Gestationel diabetes mellitus (GDM) – screening og diagnose? I 2012 diskuteredes 3 spørgsmål Skal vi indføre de nye IADPSG-kriterier i Danmark? Diagnostisering af manifest diabetes Diagnostisering af GDM Skal alle gravide screenes for GDM? Nej – fortsat selektiv screening – Sandbjerg 2012 Her kunne du jo nævne at vi synes at vores title ikke helt dækkede hvad vi synes der skal svares på 10

Fortsat selektiv screening med lidt nyt - Sandbjerg 2012 To nye risikofaktorer PCOS flerfoldsgraviditet Tidspunkt for OGTT GA 14-20 og GA 24-28 uger

Fortsat selektiv screening med lidt nyt - Sandbjerg 2012 To nye risikofaktorer PCOS flerfoldsgraviditet Tidspunkt for OGTT GA 10-20 og GA 24-28 uger

Gestationel diabetes mellitus (GDM) – screening og diagnose? I 2012 diskuteredes 3 spørgsmål Skal vi indføre de nye IADPSG-kriterier i Danmark? Diagnostisering af manifest diabetes Diagnostisering af GDM Skal alle gravide screenes for GDM? Her kunne du jo nævne at vi synes at vores title ikke helt dækkede hvad vi synes der skal svares på 13

Beslutning 2012 Afvente udmelding fra WHO samt andre nationale organisationer (NIH) Nu foreligger en del af dette inkl. en klar udmelding fra WHO

Resume af 2 store RCT – Det hjælper at behandle GDM Opsporing og behandling af GDM reducerer: Risikoen for alvorlige perinatale komplikationer med 67% Risikoen for makrosomi med 50% Risikoen for skulderdystoci med mere end 50% Risikoen for sectio med 0-20% Risikoen for præeklampsi med 30-50% NJEM 2005;352:2477-2486 og 2009; 361:1339-48

Resume af baggrund for IADPSG kriterier for GDM Baseret på data fra HAPO-studiet

HAPO – 23.316 gravide Ved stigende maternelt blodsukker øges hyppighed af: Præeklampsi Præterm fødsel Sectio Makrosomi Skulderdystoci Neonatal hypoglykæmi Indlæggelse på neo Gulsot Lineær sammenhæng uden tærskelværdi HAPO Study N Engl J Med 2008;358:1991-2002

Resume af baggrund for IADPSG kriterier for GDM Baseret på data fra HAPO-studiet Baseret på perinatale outcomes Consensus

Main neonatal adverse outcome Characteristics of an offspring of a diabetic mother Birthweight >90th percentile (LGA) Cord C-peptide >90th percentile (hyperinsulinemia) % Body fat >90th percentile Jeg skulle have holdt min diæt! 19

Fasting Plasma Glucose and Outcomes mean Slide 16 This figure shows the association between categories of fasting plasma glucose and birthweight > 90th percentile in blue, % body fat > 90th percentile in pink, and cord C-peptide > 90th percentile in orange. Each of the outcomes rose across levels of fasting plasma glucose.

De nye IADPSG-kriterier - tærskelværdier Diagnosis of GDM & Proportion of HAPO Cohort with values > Threshold* Glucose Measure mmol/l >threshold (%) FPG 5.1 8.3 1-hr OGTT-PG 10.0 14.0 2-hr OGTT-PG 8.5 16.1 *GDM = 1 or more values > threshold Slide 26 In the entire HAPO cohort, 8.3% had an FPG => threshold (with or without 1-hr or 2-hr values => threshold). Another 5.7% not captured in the FPG group had a 1-hr value =>10.0 mmol/L (180 mg/dl). Finally 2.1% not captured by either FPG or 1-hr thresholds had a 2-hr value => 8.5 mmol/L (153 mg/dl). In all, a total of 16.1% of the blinded HAPO cohort have values => threshold. In addition to the cumulative incidence of 16.1% in the HAPO blinded cohort, 1.7% of those undergoing the diagnostic OGTT were unblinded with 1 or more glucose values above predefined cutoffs. This brings the total to 17.8%. 3 venøse prøver 21

De nye IADPSG-kriterier - tærskelværdier Diagnosis of GDM & Proportion of HAPO Cohort with values > Threshold* Glucose Measure mmol/l >threshold (%) FPG 5.1 8.3 1-hr OGTT-PG 10.0 14.0 2-hr OGTT-PG 8.5 16.1 *GDM = 1 or more values > threshold Slide 26 In the entire HAPO cohort, 8.3% had an FPG => threshold (with or without 1-hr or 2-hr values => threshold). Another 5.7% not captured in the FPG group had a 1-hr value =>10.0 mmol/L (180 mg/dl). Finally 2.1% not captured by either FPG or 1-hr thresholds had a 2-hr value => 8.5 mmol/L (153 mg/dl). In all, a total of 16.1% of the blinded HAPO cohort have values => threshold. In addition to the cumulative incidence of 16.1% in the HAPO blinded cohort, 1.7% of those undergoing the diagnostic OGTT were unblinded with 1 or more glucose values above predefined cutoffs. This brings the total to 17.8%. 3 venøse prøver Add 1.7% unblinded cases 22

Fordeling af forhøjede værdier under OGTT % GDM diagnosticeret ved % GDM med forhøjet værdi FPG 1h-PG 2h-PG HAPO total 55 33 12 38 Belfast 63 30 7 46 25

Frequencies of Outcomes: Glucose Values < or > Threshold ie -/+ GDM Birthweight >90th percentile 8.3 16.2 Cord C-pept. >90th percentile 6.7 17.5 % Body fat >90th percentile 8.5 16.6 Preeclampsia 4.5 9.1 Preterm birth (<37 weeks) 6.4 9.4 Shoulder dystocia/birth injury 1.3 1.8 Primary Cesarean section 16.8 24.4 Slide 23 As shown in the upper part of the table in yellow, the frequencies of large babies, hyperinsulinemic, or “fat” babies are about twofold higher with 1 or more values =>threshold compared to frequencies in those with all values <threshold. Note below that preeclampsia frequency is twice as great and risks of preterm delivery or shoulder dystocia are ~40% higher with 1 or more glucose values => threshold and Primary Cesarean section is 45% more frequent. Thus, these threshold values clearly identify participants at substantial risk for adverse perinatal outcomes. 24

August 2013

Executive summary - WHO The WHO 1999 diagnostic criteria for hyperglycaemia in pregnancy were not evidence-based and need to be updated Systematic review of cohort studies showed that women with hyperglycaemia detected during pregnancy are at greater risk for adverse pregnancy outcomes, even after excluding the more severe cases of hyperglycaemia that required treatment.

Executive summary - WHO Treatment of gestational diabetes (GDM) is effective The risk reduction for important outcomes is in general large, the number need to treat is low, and the quality of evidence is adequate to justify treatment of GDM Diagnostic criteria for GDM are based on the risk of adverse pregnancy outcomes

Executive summary - WHO In the interest of moving towards a universal standard recommendation for the diagnosis of GDM, the WHO decided to accept the IADPSG rather than introduce another set of arbitrary cut-off values.

IADPSG - Adoption of Criteria Accepted Rejected In progress / Pending Polen Spain UK (NICE) Austria New Zealand (EBCOG) Germany Israel Australia Japan India Brazil Canada USA (ADA) USA (ACOG/NIH) WHO The Endocrine Society

Hvad sker der, hvis vi skifter til IADPSG-kriterier i DK? Nuværende kriterier 3,2 % GDM IADPSG-kriterier 8-10% GDM

Fælledparken 2020 LOKAL GDM Klinik

Hvad taler for indførelse af de nye WHO/IADPSG GDM-diagnostiske kriterier? Det er perinatalt outcome-baserede værdier God overensstemmende med de 2 RCT Venøs plasma = ”the golden standard” I dag anvendes 2 timers glukose Kapillær blod 9,0 mmol/l Venøs plasma 9,0 mmol/l Kapillær plasma 10,0 mmol/l WHO har netop accepteret IADPSG kriterierne Det er muligt at sammenligne os med resten af verden GDM behandling god til overvægtige generelt

Hvad taler imod indførelse af de nye IADPSG-GDM-diagnostiske kriterier? Flere sygeliggøres Dyrt (Flere diætister, sygepl,osv) Øget stigmatisering af gravide som syge Øget ressourceforbrug Logistiske problemer med stort antal med GDM Anvender kun venøse prøver Går fra 1 til 3 blodprøver 33

Guideline WHO/IADPSG kriterier for GDM anbefales Vi beder om mandat til i samarbejde med Sundhedsstyrelsen at arbejde for implementering af WHO/IADPSG diagnostiske kriterier i DK herunder vurdering af hvilken screenings-metode, der er den rigtige til danske forhold, og hvilken opfølgning, der skal anbefales efter fødslen. Indtil videre anvendes de gældende diagnostiske kriterier for GDM 34

Frequencies of Outcomes: Comparison of RCT & HAPO “Landon” RCT FPG <5.3 (1-hr ≥10; 2hr ≥8.6) FPG <5.3 (1-hr <10; 2-hr < 8.6) Not treated Treated BW >90th percentile 14.5 7.1 14.0 9.0 C-peptide >95th percentile 22.8 17.7 18.2 (>90th %) 7.5 (>90th %) NICU admission 11.6 11.4 7.9 Shoulder Dystocia 4.0 1.5 1.9 1.3 Preeclampsia 5.5 2.5 8.3 4.9 Slide 31 The percentages in the two columns on the right are data from the HAPO Study. Those in yellow are the percent of subjects with all glucose values less than 5.3, 10 and 8.6 mmol/l that have each outcome. The rust colored figures in the column next to it indicate frequencies of the same outcomes in HAPO subjects with OGTT glucose values similar to those in the NICHD RCT (FPG <5.3 mmol/l, 1-hr >10.0 and 2-hr >8.6). Note the similar trends for birth weight >90th percentile, NICU admission, and preeclampsia between the HAPO subjects and the treated and untreated mild GDM in the RCT. 37

Confusion : Adjusted Odds Ratios (aORs) and Risk Ratios Outcome Risk ratio aOR 1.5 aOR 1.75 aOR 2.0 Birthweight >90th percentile 1.79 1.95 2.01 Cord C-peptide >90th percentile 2.56 2.62 2.68 % Body fat >90th percentile 1.86 1.96 2.12 Slide 23 As shown in the upper part of the table in yellow, the frequencies of large babies, hyperinsulinemic, or “fat” babies are about twofold higher with 1 or more values =>threshold compared to frequencies in those with all values <threshold. Note below that preeclampsia frequency is twice as great and risks of preterm delivery or shoulder dystocia are ~40% higher with 1 or more glucose values => threshold and Primary Cesarean section is 45% more frequent. Thus, these threshold values clearly identify participants at substantial risk for adverse perinatal outcomes. 38

Confusion: AORs and Risk Ratios Outcome Risk ratio aOR 1.5 aOR 1.75 aOR 2.0 Preeclampsia 2.07 2.02 2.10 Preterm birth (<37 weeks) 1.39 1.47 1.49 Shoulder dystocia/birth injury 1.41 1.44 Primary Cesarean section 1.43 1.45 Slide 23 As shown in the upper part of the table in yellow, the frequencies of large babies, hyperinsulinemic, or “fat” babies are about twofold higher with 1 or more values =>threshold compared to frequencies in those with all values <threshold. Note below that preeclampsia frequency is twice as great and risks of preterm delivery or shoulder dystocia are ~40% higher with 1 or more glucose values => threshold and Primary Cesarean section is 45% more frequent. Thus, these threshold values clearly identify participants at substantial risk for adverse perinatal outcomes. 39

What is the “right” prevalence of GDM? Measure USA (%)* Australia (%)** IADPSG GDM 17.3 – 25.5 13.0 Non pregnant ♀ Age 18 - 44 ♀ Age 35 - 44 Known T2DM 2.8 2.3 (total) Undiagnosed T2DM 1.7 - IFG or IGT 26.4 10.7 Total 30.9 Sacks D Care 2012; Metzger JMFNM 2012; Dunstan AusDiab 2000; Moses MJA 2011

Comparative GDM Criteria and RCTs ACHOIS Criteria MFMNU Criteria IADPSG aOR 1.75 Fasting mg / dL < 7.8 < 140 < 5.3 < 95 5.1 92 1 hour mg/dL NA 10 180 2 hour 7.8 140 8.6 155 3 hour * Controls; MFMNU trial – 100g glucose load and 2 or more > Criterion

Evidens bag guideline Vi anbefaler indførelse af IADPGS-kriterier da: stigende maternelle glukoseværdier giver flere obstetriske og perinatale komplikationer (A) IADPSG-kriterierne er baseret på neonatalt outcome (B) opsporing er vigtig idet behandling nedsætter risikoen for obstetriske og perinatale komplikationer (A) forekomsten af GDM med IADPSG-kriterierne matcher forekomsten af abnorm glukosemetabolisme i baggrundsbefolkningen (B) internationale kriterier er en væsentlig forudsætning for fremtidig forskning og muligheden for at applicere dem på en dansk population 42