Diabetesjukdomens många ansiktensteg mot individualiserad behandling

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1 Sveriges Endokrinologförening, Umeå 30 januari 2019 Diabetesjukdomens många ansiktensteg mot individualiserad behandling Leif Groop Lunds Universitets Diabetescentrum Finnish Institute for Molecular Medicine

2 ANDIS/ANDIU All New Diabetics In Skåne/Uppsala SDR (7512) Skåne Diabetes Register DIREVA (6139) Diabetes Register Vasa

3 ANDIS- All New Diabetics in Scania A: Traditional classification B: Cluster-based classification Age at diagnosis BMI HbA1c GADA C-peptide (HOMA-B) HOMA-IS)

4 ANDIS Hierarchical clustering and silhouette analysis Men n=5,334 Women n=3,646

5 Replication: Diabetes Registry VAasa DIREVA, Finland Diabetes duration < 2 years; N=878 Diabetes duration 10±10 years; N=2,607

6 Replikerad i Peking, Kina Xou X et al. Lancet D&E 2019

7 SAID Severe autoimmune diabetes 6.4% of patients All GADA positive = T1D+LADA High HbA1c Low insulin secretion Relatively lean Relatively young SAID Mean (SD) HBA1C BMI AGE HBA1C at diagnosis, mmol/l 80 (31) HOMA2-B HOMA2-IR BMI, kg/m2 27 (6) Age at diagnosis, years 50 (18) HOMA2B 57 (45) HOMA2IR 2.2 (1.6)

8 SIDD Severe insulin-deficient diabetes 17.5% of patients High HbA1c Low insulin secretion Relatively lean Relatively young HBA1C BMI AGE SIDD Mean (SD) HOMA2-B HOMA2-IR HBA1C at diagnosis, mmol/l 102 (19) BMI, kg/m2 29 (5) Age at diagnosis, years 57 (11) HOMA2B 48 (29)

9 SIDD Severe insulin-deficient diabetes Diabetic retinopathy 0,16 0,14 0,12 0,1 0,08 ANDIS Proliferative Non proliferative 0,3 0,25 0,2 0,15 ANDIU 0,06 0,04 0,02 0 1/SAID 2/SIDD 3/SIRD 4/MOD 5/MARD Severe Moderate 0,1 0,05 0 1/SAID 2/SIDD 3/SIRD 4/MOD 5/MARD SIDD vs MARD : OR 1.6, p=9.7x10-7 OR 4.6, p=4.1x10-13 Neuropathy is also increased in this group

10 SIDD Severe insulin-deficient diabetes HbA1c over time 0,35 0,3 Ketoacidosis at diagnosis Hba1c mmol/l 0,25 0,2 0,15 0,1 0,05 0,3 0,25 0,2 ZnT8A auto-antibodies 0 1/SAID 2/SIDD 3/SIRD 4/MOD 5/MARD Genetics cluster vs non-diabetic controls (N=2,754) Gene - SNP SAID (N=313) SIDD (N=676) OR P OR P 0,15 HLA DQB1 - rs x ,1 0,05 0 1/SAID 2/SIDD 3/SIRD 4/MOD 5/MARD HLA DQB1 - rs x TCF7L2 - rs x10-10

11 SIRD ANDIS egfr<45 ml/min/1 73m 2 Severe insulin-resistant diabetes SDR Macroalbuminuria SDR ESRD egfr<15 ml/min/1 73m 2 1-cumulative survival 1-cumulative survival 1-cumulative survival 1/SAID HR(CI95%)* 1.0 ( ) p /SIDD 1.7( ) /SIRD 3.3( ) 8x /MOD 1.7( ) HR(CI95%)* p 0.4( ) ( ) ( ) ( ) HR(CI95%)* p 1.9( ) ( ) ( ) 2.4x ( )

12 MOD Moderate obesity-related diabetes 21.6% of patients Low HbA1c Very obese Relatively young Low risk of complications MOD Mean (SD) HBA1C BMI AGE HBA1C at diagnosis, mmol/l 58 (16) HOMA2-B HOMA2-IR BMI, kg/m2 36 (5) Age at diagnosis, years 49 (10) HOMA2B 95 (32) HOMA2IR 3.4 (1.2)

13 MOD Moderate obesity-related diabetes Genetics cluster vs non-diabetic controls (N=2,754) Gene - SNP 3/SIRD (N=603) 4/MOD (N=727) OR P OR P TM6SF2 - rs x TCF7L2 - rs x10-7 JAZF1 rs x10-4 KCNJ11 rs x10-4

14 MARD Moderate age-related diabetes 39.1% of patients Low HbA1c Relatively old Relatively lean Low risk of complications MARD Mean (SD) HBA1C BMI AGE HBA1C at diagnosis, mmol/l 50 (10) HOMA2-B HOMA2-IR BMI, kg/m2 28 (3) Age at diagnosis, years 67 (9) HOMA2B 87 (26) HOMA2IR 2.6 (0.8)

15 Emma Ahlqvist 296 kommentarer i internationell press de följande 5 dagarna

16 Nästa steg En app för diabetesmottagningen baserad på maskinlärning Olof Asplund

17 TACK för uppmärksamheten När förändringens vindar blåser är det bättre med väderkvarnar än vindskydd