Depressie en cognitie bij type 2 diabetes. Miranda Schram afdeling Interne Geneeskunde MUMC+

Transcription

1 Depressie en cognitie bij type 2 diabetes Miranda Schram afdeling Interne Geneeskunde MUMC+

2 Disclosure potential conflicts of interest Geen (potentiële) belangenverstrengeling Voor bijeenkomst mogelijk relevante relaties: Bedrijfsnamen Sponsoring of onderzoeksgeld - Honorarium of andere (financiële) vergoeding - Aandeelhouder - Andere relatie, namelijk -

3 Eén derde van de volwassen Limburgers heeft (pre)diabetes 2 van 6 vakken met publiek

4 Type 2 diabetes and depression Risk of depression in type 2 diabetes is doubled QoL, societal costs Mortality risk : OR for mortality 1.46 * OR for cvd mortality 1.39 * * F. van Dooren et al, Plos One 2013; 8(3):e57058

5 Course of depression in type 2 diabetes

6 Course of depression in type 2 diabetes Paucity of data Probably a chronic course Under reported, under recognised, under treatment Treatment resistance, ineffective treatment? Different etiology than early life depression Biology largely unknown

7 Mechanisms Psychosocial variables Lifestyle factors Biological mechanisms

8 Mechanisms Psychosocial variables Lifestyle factors Biological mechanisms

9 Mechanisms Psychosocial variables Inflammation Lifestyle factors Biological mechanisms Endothelial dysfunction

10 Research questions We investigated the associations between markers of - Hyperglycemia (glucose, AGEs) - Inflammation, and - Endothelial dysfunction with depressive symptoms and depressive disorder in a population-based study

11 Mechanisms Psychosocial variables Inflammation Lifestyle factors Biological mechanisms Endothelial dysfunction

12 The Maastricht Study 10,000 participants, years From the Maastricht area Oversampling of type 2 diabetes Advanced deep phenotyping Survey I: Dataset n~3400 (Nov 10-Sept 13) Eur J Epidemiology (2014) 29:

13 Extremely detailed phenotyping

14 Depression PHQ-9, MINI diagnostic interview (gold standard) Diabetes Oral glucose tolerance test Methods Glycemic control (fasting gluc, HbA1c, AGEs: SAF, Pentosidine, CEL, CML) Inflammation (hscrp, SAA, sicam-1, IL-6, IL-8, TNF-α) Endothelial function (svcam-1, sicam-1, se-selectin, vwf) MRI (brain atrophy and cerebral small vessel disease) Lifestyle (physical activity, sedentary time, nutrition)

15 General characteristics No type 2 diabetes (n=2349) Type 2 diabetes (n=918) Age, years 58.7 ± ± 7.6 Female sex, n (%) 1291 (55%) 298 (33%) Partner, n (%) 1972 (85%) 731 (82%) Educational level, % low/middle/high 28/28/44 46/28/26 HbA1c, % 5.5 ± ± 1.0 Smoking, % never/former/current 37/50/12 28/56/16 Body mass index, kg/m ± ± 5.0 Blood pressure, mmhg 132 ± 17 / 76 ± ± 18 / 77 ± 10 Total cholesterol, mmol/l 5.5 ± ± 1.0 HDL cholesterol, mmol/l 1.61 ± ± 0.37 N= 3267

16 Prevalence of depression prevalence in % ,4 * 6,2 * 2,7 2,7 * 6,3 4,0 * 9,0 Non-DM DM ,4 PHQ-9 score > 10 Minor depression Major depression Major and minor depression

17 Association of depression with T2DM Depressive symptoms Odds ratio 95% CI p-value PHQ-9 score (continuous) 1.06 ( ) < PHQ ( ) Depressive disorder Minor depressive disorder (MINI) 1.81 ( ) Major depressive disorder (MINI) 1.99 ( ) Adjusted for age, sex, educational level, bmi, smoking, partner status, systolic blood pressure, prior CVD, total cholesterol and HDL cholesterol

18 Hyperglycemia and depression Independent variables Fasting glucose per SD HbA1c per SD Skin Autofluoresence per SD Hyperglycemia sum score per SD Major depression OR (95%CI) P-value 1.30 ( ) ( ) ( ) ( ) <0.001 adjusted for age, sex, smoking, alcohol consumption, hypertension, cholesterol ratio, physical activity, and BMI

19 Advanced Glycation Endproducts (AGEs) * Adjusted for age, sex, type 2 diabetes, bmi, smoking, egfr Van Dooren et al, Depression and Anxiety, 2016 Jun 6

20 Insuline resistance and depression Independent variables Major depression OR (95%CI) P-value Fasting insulin per SD HOMA per SD Insulin resistance markers sum score per SD 0.97 ( ) ( ) ( ) adjusted for age, sex, smoking, alcohol consumption, hypertension, cholesterol ratio, physical activity, and BMI

21 Hyperglycemia, IR and depression

22 Conclusie Type 2 diabetes is geassocieerd met meer depressie Verschillende maten van hyperglycemie zijn geassocieerd met depressie Insuline resistentie is niet geassocieerd met depressie

23 Mechanisms Psychosocial variables Inflammation Lifestyle factors Biological mechanisms Endothelial dysfunction

24 Depression PHQ-9, MINI diagnostic interview (gold standard) Diabetes Oral glucose tolerance test Methods Glycemic control (fasting gluc, HbA1c, AGEs: SAF, Pentosidine, CEL, CML) Inflammation (hscrp, SAA, sicam-1, IL-6, IL-8, TNF-α) Endothelial function (svcam-1, sicam-1, se-selectin, vwf) MRI (brain atrophy and cerebral small vessel disease) Lifestyle (physical activity, sedentary time, nutrition)

25 Low grade inflammation * * * * * OR was 1,54 (1,18-2,02) for LGI sumscore after adjustment for age, sex, DM2, egfr, prior CVD Van Dooren et al, Brain Behaviour and Immunity, 2016 Aug;56:390-6.

26 Endothelial dysfunction Odds ratio 1,8 1,7 1,6 1,5 1,4 1,3 1,2 1,1 1 Endothelial function is associated with depressive disorder * 1,25 * * 1,35 1,36 1,19 1,64 svcam-1 sicam-1 E-selectine vwf ED sumscore * OR was 1,40 (1,10-1,77) for ED sumscore after adjustment for age, sex, DM2, egfr, prior CVD Van Dooren et al, Brain Behaviour and Immunity, 2016 Aug;56:390-6.

27 Inflammation and incident depression Longitudinal associations of low-grade inflammation sum score with incident depression Odds ratio 95% CI p value Model 1: crude + demographics <0.001 Model 2: model 1 + cardiovascular risk factors Model 3: model 2 + lifestyle risk factors Model 1 included age, sex, education status and partner status; model 2 additionally incorporated cardiovascular risk factors as type 2 diabetes status, history of cardiovascular disorder, kidney function and HbA1c; model 3 added modifiable lifestyle risk factors as body mass index (BMI), blood pressure, smoking and physical activity.

28 Endothelial dysfunction and incident depression Longitudinal associations of endothelial dysfunction sum score with incident depression Odds ratio 95% CI p value Model 1: crude + demographics <0.001 Model 2: model 1 + cardiovascular risk factors Model 3: model 2 + lifestyle risk factors Model 1 included age, sex, education status and partner status; model 2 additionally incorporated cardiovascular risk factors as type 2 diabetes status, history of cardiovascular disorder, kidney function and HbA1c; model 3 added modifiable lifestyle risk factors as body mass index (BMI), blood pressure, smoking and physical activity.

29 LGI, ED and incident depression 55% 45%

30 Inflammation, endothelial dysfunction and chronic depression Remission Resistant or recurrent LGI Odds ratio 95% CI p value Odds ratio 95% CI p value Model 1: demographics ; ; Model 2: model 1 + cardiovascular risk factors Model 3: model 2 + lifestyle risk factors ; ; ; ; ED Model 1: demographics ; ; Model 2: model 1 + cardiovascular risk factors Model 3: model 2 + lifestyle risk factors ; ; ; ; Model 1 included age, sex, education status and partner status; model 2 additionally incorporated cardiovascular risk factors as type 2 diabetes status, history of cardiovascular disorder, kidney function and HbA1c; model 3 added modifiable lifestyle risk factors as body mass index (BMI), blood pressure, smoking and physical activity.

31 Depressie als gevolg van vaatschade ORs = Agtmaal et al JAMA Psychiatry 2017 Jul 1;74(7):

32 Conclusie Inflammatie en endotheel dysfunctie zijn geassocieerd met incidente depressie, mogelijk causaal verband Inflammatie en endotheel dysfunctie samen kunnen chronische depressie voorspellen

33 Mechanisms Psychosocial variables Inflammation Lifestyle factors Biological mechanisms Endothelial dysfunction

34 Type 2 diabetes and dementia 2x greater risk of dementia in type 2 diabetes Via hyperglycaemia? Via vascular brain damage?

35 Type 2 diabetes and cognitieve functie

36 White matter hyperintensities

37 Brain tissue volumes

38 Vaatschade in het brein Vaatschade op MRI Geen diabetes Pre-diabetes Diabetes Van Agtmaal et al, submitted

39 White matter volume Geen diabetes Pre-diabetes Diabetes Van Agtmaal et al, submitted

40 Grey matter volume Geen diabetes Pre-diabetes Diabetes Van Agtmaal et al, submitted

41 Cerebrospinal fluid Geen diabetes Pre-diabetes Diabetes Van Agtmaal et al, submitted

42 Conclusion Prediabetes is associated with White matter hyperintensities Lower white matter volume 4 years of aging T2DM is associated with White matter hyperintensities Lower white matter volume Higher CSF volume 8.5 years of aging

43 Take home message Depressie en dementie komen 2x zo veel voor bij type 2 diabetes Verklarende mechanismen hiervoor zijn: Hyperglycemie Inflammatie Endotheel dysfunctie Vasculaire brein schade Zowel prediabetes als type 2 diabetes zijn geassocieerd met versnelde veroudering van het brein weefsel vergelijkbaar met 4 vs 8 jaar veroudering

44 Eén derde van de volwassen Limburgers heeft (pre)diabetes 2 van 6 vakken met publiek

45 17 PhD theses on The Maastricht Study A further 20 PhD theses in preparation