Diabetes, Diet and SMI: How can we make a difference? Dr. Adrian Heald Consultant in Endocrinology and Diabetes Leighton Hospital, Crewe and Macclesfield Research Fellow, Manchester University
Relative risk Weight gain significantly increases diabetes risk Relative risk of type 2 diabetes according to BMI in women aged 30 55 years 100 90 80 70 60 50 40 30 20 10 0 <22.0 22.0 22.9 23.0 23.9 24.0 24.9 25.0 26.9 27.0 28.9 BMI (kg/m 2 ) 29.0 30.9 31.0 32.9 33.0 34.9 35.0 Colditz GA, et al. Ann Intern Med. 1995;122(7):481-486.
Metabolic syndrome
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;97:1837 1847; NCEP Expert Panel. Circulation. 2002;106:3143 3421
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 www.idf.org
Fasting blood sample Definitions Fasting venous glucose 6.0mM or less normal Fasting venous glucose 6.1 6.9 impaired fasting glycaemia Fasting venous glucose 7.0mM or more type 2 diabetes if symptomatic (2 blood levels of 7.0mM or more required if patient is asymptomatic) 75 gram oral glucose tolerance test 2hour venous glucose 11.1mM or more type 2 diabetes 2hour venous glucose 7.8-11mm impaired glucose tolerance
Metabolic Health is a Major Controversy in Mental Health Care Life expectancy for individuals with schizophrenia is 20% lower than that of the general population Schizophrenia carries a 1.5 to 3 times greater mortality risk than is found in the general population Increased risk of morbidity Medical illnesses, Psychiatric comorbidities Decreased access to care Poverty Limited insight Harris & Barraclough. Br J Psychiatry. 1998;173:11 53; Brown et al. Br J Psychiatry. 2000;177:212 217; Baxter. Br J Psychiatry. 1996;168:772 779
Osborn et al, Arch Gen Psychiatry Vol 64 Feb 2007 A total of 46 136 people with Severe Enduring Mental illness (SMI) and 300 426 without SMI were selected for the study Hazard ratios (HRs) in people with SMI compared with controls were: for CHD mortality 3.22 (95% [CI], 1.99-5.21) for people 18-49 years old 1.86 (95%CI, 1.63-2.12) for those 50 through 75 years old 1.05(95% CI, 0.92-1.19) for those older than 75 years
Osborn et al, Arch Gen Psychiatry Feb 2007 For stroke deaths, the HRs were: 2.53 (95% CI, 0.99-6.47) for those younger than 50 years 1.89 (95% CI, 1.50-2.38) for those 50 through 75 years old 1.34 (95% CI, 1.17-1.54) for those older than 75 years Lung tumour related death rate of 1.32 (95% CI, 1.04-1.68) for those 50 to 75 years old lost statistical significance after controlling for smoking and social deprivation
Increased HRs for CHD mortality occurred irrespective of sex, SMI diagnosis, or prescription of antipsychotic medication However, a higher prescribed dose of antipsychotics predicted greater risk of mortality from CHD and stroke
Antipsychotics and weight gain
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 13.2 5 4 3 11.0 8.8 6.6 2 1 0-1 -2-3 Aripiprazole 4.4 2.2 0-2.2-4.4-6.6 Allison DB, et al. Am J Psychiatry 1999;156:1686
Metabolic syndrome prevalence (%) Metabolic syndrome prevalence over the disease course of schizophrenia (n=415) 50 40 34.9 39.6 42.4 36.7 44.3 49.4 30 20 17 18 17 21.5 24.6 28.5 10 0 First episode <10 years 10-20 years >20 years ATP III ATP IIIA IDF De Hert M, et al. Clin Pract Epidemol Ment Health 2006;2:14
Prevalence of Metabolic Syndrome by Age: ATP III and IDF criteria Metabolic syndrome prevalence (%) 60 50 49.3 40 30 32.3 36.4 38.0 24.4 20 10 6.5 12.0 14.1 0 34 45 years (ATP III) 35 45 years (IDF) General population 45 55 years (ATP III) Patients with schizophrenia 45 55 years (IDF) ATP III = Adult Treatment Panel III; IDF = International Diabetes Federation De Hert et al. Clin Pract Epidemol Ment Health. 2006;2:14
Mortality (%) Metabolic Syndrome Increases Total and Cardiovascular Mortality 20 18 16 *** 18.0 Metabolic syndrome present Metabolic syndrome absent 14 12 10 8 *** 12.0 6 4 2 0 4.6 Total mortality CV mortality 2.2 ***p<0.001 vs. patients without metabolic syndrome CV = Cardiovascular Isomaa et al. Diabetes Care. 2001;24:683 689 Median follow-up: 6.9 years
Prevalence of Diabetes in Schizophrenia vs. General Population Prevalence (%) 30 25 20 General population People with schizophrenia 15 10 5 0 15 35 25 35 35 45 45 55 55 65 n=415 patients with schizophrenia De Hert et al. Clin Pract Epidemiol Mental Health. 2006;2:14 Age range (years)
Odds ratios CVD Risk Factors: More than Additive Effect of Multiple Risk Factors 14 5 12 Multiple risk factors 10 4 8 6 Single risk factors 3 4 2 2 0 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;97:1837 1847
Primary Care data
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.
0 5 10 15 20 Fasting glucose (mmol/l) Cheshire SMI data 2008 Relation between fasting glucose and BMI 0 20 40 60 Body Mass Index (kg/m2)
Cheshire SMI 10 year follow-up data (GP database) 1511 diabetes patients BMI Phenotypic measurements taken yearly from 2002 to 2011 1347 of 1511 patients had at least 1 weight measurement with calculation of BMI
246 patients had measurements at 1 time point 240 patients had measurements at 2 time points 225 patients had measurements at 3 time points 172 patients had measurements at 4 time points 140 patients had measurements at 5 time points 114 patients had measurements at 6 time points 76 patients had measurements at 7 time points 44 patients had measurements at 8 time points 29 patients had measurements at 9 time points 23 patients had measurements at 10 time points
P-value <0.001; r 2 = 0.82
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 2002-2011
280 patients had measurements at 1 time point 259 patients had measurements at 2 time points 187 patients had measurements at 3 time points 159 patients had measurements at 4 time points 110 patients had measurements at 5 time points 71 patients had measurements at 6 time points 26 patients had measurements at 7 time points 14 patients had measurements at 8 time points 5 patients had measurements at 9 time points 0 patients had measurements at 10 time points
P-value 0.022; r 2 = 0.50 for glucose vs time P-value 0.10; r 2 = 0.29 for glucose vs BMI over all time points
Lifestyle Factors
Cromwell House Study 2007 (Salford UK) 25 men and 12 women with SMI Mean illness duration was 11.6 years Mean portions of fruit per day were 1.1 1.0 (standard deviation) and of vegetables was 1.7 1.2) Total fruit and vegetable portions were 2.8 1.8 Vegetables were eaten on 3 days or more each week by 59.4% of individuals but fruit was only eaten on 3 days or more each week by 34.4% of the group with 37.5% reporting not eating fruit on any day of the week
Exercise (moderate activities) 10% 6% 3-5hours >5hours None 29% 16.1 1-2hours <1hour 39%
Insight Diet: Patient ratings on a visual scale of 1-10 for the Q. Would you describe your diet as healthy (average over last 3 months)? gave a mean of 5.7/10 Activity: Q. Would you consider yourself fairly physically active (average over last 3 months)? gave a mean of 5.0/10 Medication compliance: Q. Are you compliant with medication prescribed for you to take (over last 3 months)? gave a mean of 9.8/10
Conclusion 1 Within this sample there was a high prevalence of poor diet, smoking and inadequate exercise Many did not follow national recommendations for dietary intake of fruit and vegetables and daily exercise But many had insight into their unhealthy lifestyles Thus there is potential for interventions to improve lifestyle factors and reduce the risk of cardiometabolic disease
McCreadie et al. Br J Psych 2005; 187: 346-51 102 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
Effects of any lifestyle intervention are not sustained McCreadie et al. Br J Psych 2005; 187: 346-51
Update on Lipids
Annual age-standardised CHD mortality (%) CHD mortality rises in line with total cholesterol 100 10 1 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 Total cholesterol (mmol/l) Stamler J, Wentworth D, Neaton JD. JAMA 1986; 256: 2823-2828
Benefits of lowering cholesterol Nine large randomised trials (n=60,078) show that lowering cholesterol improves cardiovascular outcomes Reducing total cholesterol by 20% reduces CHD event rates by 20-30% Patients at highest risk of an event show most benefit
Survival free of event SIMVASTATIN: VASCULAR EVENT by FOLLOW-UP DURATION 100% 95% 90% 85% 80% 75% 55 ± 5.8 LESS per 1000 allocated SIMVASTATIN (logrank 2P<0.00001) STATIN PLACEBO 0 1 2 3 4 5 6 Years of follow-up
Annual CHD mortality rate Reducing cholesterol reduces CHD mortality 1.8% 1.6% 1.4% 1.2% LIPID CARE HPS 4S High risk study groups 1.0% POSCH 0.8% Low risk study groups 0.6% 0.4% WOSCOPS LRC 0.2% Helsinki AFCAPS/TexCAPS 0.0% 4 4.5 5 5.5 6 6.5 7 7.5 Start of study End of study Total cholesterol (mmol/l)
Joint British Guidelines - Update 2006
Actions to make a difference Ensure that hyperlipidaemia and hypertension are identified and treated Screen for type 2 diabetes Weight reduction and healthy eating advice Encourage smoking cessation
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
Herophilus (Greek Physician, 335 280 BC) When health is absent, wisdom cannot reveal itself, art cannot become manifest, strength cannot be exerted, wealth is useless and reason is powerless