diabetesjukdomens många ansikten- steg mot...

Leif GroopLunds Universitets DiabetescentrumFinnish Institute for Molecular Medicine

Diabetesjukdomens maringnga ansikten-steg mot individualiserad behandling

Sveriges Endokrinologfoumlrening Umearing 30 januari 2019

SDR (7512)Skaringne Diabetes Register

ANDISANDIUAll New Diabetics In SkaringneUppsala

19086 880

httpandisludcmedluse

DIREVA (6139)Diabetes Register Vasa

ANDIS- All New Diabetics in ScaniaA Traditional classificationB Cluster-based classification

Age at diagnosisBMIHbA1cGADAC-peptide (HOMA-B)HOMA-IS)

ANDIS Hierarchical clustering and silhouette analysis

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Men n=5334 Women n=3646

Replication Diabetes Registry VAasaDIREVA Finland

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Diabetes duration lt 2 years N=878 Diabetes duration 10plusmn10 years N=2607

Replikerad i Peking KinaDet garingr inte att visa bilden

Xou X et al Lancet DampE 2019

SAIDSevere autoimmune diabetes

bull 64 of patientsbull All GADA positive = T1D+LADAbull High HbA1cbull Low insulin secretionbull Relatively leanbull Relatively young

SAID Mean (SD)

HBA1C at diagnosis mmoll 80 (31)

BMI kgm2 27 (6)Age at diagnosis years 50 (18)

HOMA2B 57 (45)HOMA2IR 22 (16)

HBA1C BMI AGE

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SIDDSevere insulin-deficient diabetes

bull 175 of patientsbull High HbA1cbull Low insulin secretionbull Relatively leanbull Relatively young

SIDD Mean (SD)

HBA1C at diagnosis mmoll 102 (19)

BMI kgm2 29 (5)Age at diagnosis years 57 (11)HOMA2B 48 (29)

HBA1C BMI AGE

HOMA2-B HOMA2-IRDet garingr inte att visa bilden

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1SAID 2SIDD 3SIRD 4MOD 5MARD

Proliferative

Non proliferative

Severe

Moderate

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025

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1SAID 2SIDD 3SIRD 4MOD 5MARD

ANDIS ANDIU

SIDD vs MARD OR 16 p=97x10-7 OR 46 p=41x10-13

SIDDSevere insulin-deficient diabetes

Diabetic retinopathy

Neuropathy is also increased in this group

Hba1

c m

mol

LHbA1c over time

Ketoacidosis at diagnosis

SIDDSevere insulin-deficient diabetes

ZnT8A auto-antibodiesGene - SNP SAID (N=313) SIDD (N=676)

OR P OR P

HLA DQB1 - rs2854275 205 57x10-10 082 008

HLA DQB1 - rs9273363 033 20x10-32 108 037

TCF7L2 - rs7903146 117 008 15

1 28x10-10

Genetics ndash cluster vs non-diabetic controls (N=2754)

0

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1SAID 2SIDD 3SIRD 4MOD 5MARD

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1SAID 2SIDD 3SIRD 4MOD 5MARD

ANDIS eGFRlt45 mLmin173m2

SDR Macroalbuminuria

SDR ESRD

eGFRlt15 mLmin173m2

HR(CI95) p

1SAID 10 (06-19) 098

2SIDD 17(12-25) 0003

3SIRD 33(26-43) 8x10-21

4MOD 17(10-30) 0045

HR(CI95) p

04(01-10) 0056

13(07-22) 039

22(13-36) 0003

13(07-24) 0371 -

HR(CI95) p19(07-53) 02323(11-46) 0024

49(27-89) 24x10-7

17(07-44) 0251 -

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SIRDSevere insulin-resistant diabetes

bull 216 of patientsbull Low HbA1cbull Very obesebull Relatively youngbull Low risk of complicationsMOD Mean (SD)

HBA1C at diagnosis mmoll 58 (16)

BMI kgm2 36 (5)Age at diagnosis years 49 (10)

HOMA2B 95 (32)HOMA2IR 34 (12)

MODModerate obesity-related diabetes

HBA1C BMI AGE

HOMA2-B HOMA2-IRDet garingr inte att visa bilden

MODModerate obesity-related diabetes

Gene - SNP 3SIRD (N=603) 4MOD (N=727)

OR P OR P

TM6SF2 - rs10401969 062 31x10-6 089 026

TCF7L2 - rs7903146 100 086 138 57x10-7

JAZF1 ndash rs864745 093 014 081 18x10-4

KCNJ11 ndash rs5219 103 067 128 12x10-4

Genetics ndash cluster vs non-diabetic controls (N=2754)

MARDModerate age-related diabetes

bull 391 of patientsbull Low HbA1cbull Relatively oldbull Relatively leanbull Low risk of complicationsMARD Mean (SD)

HBA1C at diagnosis mmoll 50 (10)

BMI kgm2 28 (3)Age at diagnosis years 67 (9)

HOMA2B 87 (26)HOMA2IR 26 (08)

HBA1C BMI AGE

HOMA2-B HOMA2-IRDet garingr inte att visa bilden

Emma Ahlqvist

296 kommentarer i internationell press de foumlljande 5 dagarna

En app foumlr diabetesmottagningenbaserad paring maskinlaumlrning

Olof Asplund

Naumlsta steg

TACK foumlr uppmaumlrksamheten

Naumlr foumlraumlndringens vindar blaringser aumlr det baumlttre med vaumlderkvarnar aumln vindskydd