Improving cardiometabolic health in Major Mental Illness

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1 Improving cardiometabolic health in Major Mental Illness Dr. Adrian Heald Consultant in Endocrinology and Diabetes Leighton Hospital, Crewe and Macclesfield Research Fellow, Manchester University

2 Metabolic syndrome

3 The Inter-Relationship of Risk Factors and Consequences Raised fasting plasma glucose Obesity Raised triglyceride levels Reduced HDL cholesterol Raised blood pressure Metabolic syndrome Cardiovascular disease Mortality/morbidity HDL = High-density Lipoprotein; NECP = National Cholesterol Education Program Wilson et al. Circulation. 1998;97: ; NCEP Expert Panel. Circulation. 2002;106:

4 Metabolic Syndrome IDF definition 2005 Metabolic syndrome defined as criterion one plus any two of next four criteria: Central obesity Blood pressure Triglycerides Men 94 cm (37inches) Women 80 cm (31.5 inches) 130/85 mmhg* 150 mg/dl (1.7 mmol/l)* HDL cholesterol Men <40 mg/dl (1.03 mmol/l)* Women <50 mg/dl (1.29mmol/L)* Fasting blood glucose 100mg/dL ( 5.6 mmol/l) (recommend OGTT) *Or on treatment; or known type 2 diabetes IDF = International Diabetes Federation; HDL = High-density Lipoprotein; OGTT = Oral Glucose Tolerance Test Available at

5 Antipsychotics and weight gain

6 Weight change (kg) Weight change (lb) Antipsychotics and associated weight gain Short-term mean weight change with some antipsychotics 6 Estimated weight change at 10 weeks on standard dose Aripiprazole Allison DB, et al. Am J Psychiatry 1999;156:1686

7 Prevalence of Metabolic Syndrome by Age: ATP III and IDF criteria Metabolic syndrome prevalence (%) years (ATP III) years (IDF) General population years (ATP III) Patients with schizophrenia years (IDF) ATP III = Adult Treatment Panel III; IDF = International Diabetes Federation De Hert et al. Clin Pract Epidemol Ment Health. 2006;2:14

8 Prevalence of Diabetes in Schizophrenia vs. General Population Prevalence (%) General population People with schizophrenia n=415 patients with schizophrenia De Hert et al. Clin Pract Epidemiol Mental Health. 2006;2:14 Age range (years)

9 Odds ratios CVD Risk Factors: More than Additive Effect of Multiple Risk Factors Multiple risk factors Single risk factors BMI >27 Smoking TC >220 DM HTN Smoking + BMI Smoking + BMI + TC >220 Smoking + BMI + TC >220 + DM Smoking + BMI + TC >220 + DM + HTN CVD = Cardiovascular Disease; BMI = Body Mass Index; TC = Total Cholesterol; DM = Diabetes Mellitus; HTN = Hypertension Based on data from Framingham Heart Survey Casey et al. J Clin Psychiatry. 2004;65(Suppl 7):4 18; Data from Wilson et al. Circulation. 1998;97:

10 Primary Care data

11 Cheshire SMI data (GP database) 453 patients (55.8% male 44.2% female) on the SMI Register in Cheshire, UK were screened for dysglycaemia (screening rate 57.3 %) and dyslipidaemia (screening rate 36.2%) Multivariate linear regression analysis revealed a direct relation between fasting glucose levels and BMI (Spearman s rho = 0.22, p<0.001) independent of age, sex, systolic blood pressure and fasting cholesterol and triglycerides.

12 Fasting glucose (mmol/l) Cheshire SMI data 2008 Relation between fasting glucose and BMI Body Mass Index (kg/m2)

13 Cheshire SMI 10 year follow-up data (GP database) 1511 diabetes patients BMI Phenotypic measurements taken yearly from 2002 to of 1511 patients had at least 1 weight measurement with calculation of BMI

14 P-value <0.001; r 2 = 0.82

15 Cheshire SMI 10 year follow-up data (GP database) 1511 diabetes patients Glucose 1111 patients had plasma glucose data on at least 1 time point Followed up

16 Over the follow-up period there was a significant increase in fasting blood glucose (r 2 = 0.48, p 0.026) from 5.72 mmol/l to 6.79 mmol/l P-value 0.10; r 2 = 0.29 for glucose vs BMI over all time points

17 McCreadie et al. Br J Psych 2005; 187: people with schizophrenia in two areas of Scotland were randomly allocated: to receive free fruit and vegetables for 6 months alone to receive free fruit and vegetables for 6 months alone with instruction in meal planning and food preparation or to continue as before

18 Effects of any lifestyle intervention are not sustained McCreadie et al. Br J Psych 2005; 187:

19

20 Malhotra et al, 2012 Malhotra et al (2012) reported an association between a variant (rs469893) in the region of the MC4R gene and weight gain in individuals treated with neuroleptics This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale genome-wide association studies of obesity in the general population Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight during the 12-week trial

21 Epigenetics DNA methylation as a baseline genetic marker can aid in predicting weight loss (Milagro FI et al., 2011) Leptin and TNF-alpha promotor regions are two such sites where methylation levels have helped identify susceptibility to weight loss programs (Cordero P et al., 2011, Campion J et al., 2009)

22 Proposition Epigenetics could help to explain individual differences in weight change in early onset psychosis We want to study the changes in POMC gene expression in real time and how they relate to weight change, glycaemia and lipid profile With knowledge of their dietary history, the influence of diet on DNA methylation might be elucidated

23

24 Conclusion Obesity, metabolic syndrome and diabetes are highly prevalent in patients with SMI These health issues impact on life expectancy, quality of life and compliance with treatment Longitudinally monitor and target all risk factors: even one change can have a significant impact on risk (Framingham) link with Primary Care Lifestyle analysis with regular advice on diet and exercise is integral to improving cardiometabolic outcome in this group include in mental health reviews

25 Herophilus (Greek Physician, BC) When health is absent, wisdom cannot reveal itself, art cannot become manifest, strength cannot be exerted, wealth is useless and reason is powerless

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