Sveriges Endokrinologförening, Umeå 30 januari 2019 Diabetesjukdomens många ansiktensteg mot individualiserad behandling Leif Groop Lunds Universitets Diabetescentrum Finnish Institute for Molecular Medicine
http://andis.ludc.med.lu.se/ 19086 880 ANDIS/ANDIU All New Diabetics In Skåne/Uppsala SDR (7512) Skåne Diabetes Register DIREVA (6139) Diabetes Register Vasa
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)
ANDIS Hierarchical clustering and silhouette analysis Men n=5,334 Women n=3,646
Replication: Diabetes Registry VAasa DIREVA, Finland Diabetes duration < 2 years; N=878 Diabetes duration 10±10 years; N=2,607
Replikerad i Peking, Kina Xou X et al. Lancet D&E 2019
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)
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)
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
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 - rs2854275 2.05 5.7x10-10 0.82 0.08 0,1 0,05 0 1/SAID 2/SIDD 3/SIRD 4/MOD 5/MARD HLA DQB1 - rs9273363 0.33 2.0x10-32 1.08 0.37 TCF7L2 - rs7903146 1.1 7 0.08 1.5 1 2.8x10-10
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 (0.6-1.9) p 0.98 2/SIDD 1.7(1.2-2.5) 0.003 3/SIRD 3.3(2.6-4.3) 8x10-21 4/MOD 1.7(1.0-3.0) 0.045 HR(CI95%)* p 0.4(0.1-1.0) 0.056 1.3(0.7-2.2) 0.39 2.2(1.3-3.6) 0.003 1.3(0.7-2.4) 0.37 1 - HR(CI95%)* p 1.9(0.7-5.3) 0.23 2.3(1.1-4.6) 0.024 4.9(2.7-8.9) 2.4x10-7 1.7(0.7-4.4) 0.25 1 -
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)
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 - rs10401969 0.62 3.1x10-6 0.8 9 0.26 TCF7L2 - rs7903146 1.00 0.86 1.3 8 5.7x10-7 JAZF1 rs864745 0.93 0.14 0.8 1 1.8x10-4 KCNJ11 rs5219 1.03 0.67 1.2 8 1.2x10-4
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)
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