Cohort study 123 5 sushil

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Cohort study 123 5 sushil

  1. 1. SUSHIL SRIVASTAVA
  2. 2. OBJECTIVE <ul><li>To identify risk factors in early life , upto 3 years of age for obesity in children in the UK </li></ul><ul><li>DESIGN </li></ul><ul><li>Prospective cohort study </li></ul><ul><li>Avon longitudinal study of parents and children, United Kingdom </li></ul>
  3. 3. METHODOLOGY <ul><li>ALSPAC is a longitudinal birth cohort study of the determinants of development, health , disease during childhood and beyond. </li></ul><ul><li>14,541 pregnant women with EDD April 1991-Dec.1992. enrolled </li></ul><ul><li>85%-90% took part in the study. </li></ul><ul><li>13,971 formed the original cohort. </li></ul><ul><li>In this study, random selection of a subsample was done. </li></ul>
  4. 4. METHODOLOGY <ul><li>Random sub selection was done from last 6 months of selection. </li></ul><ul><li>Children between age 4 months to 5 years , along with their parents were invited for regular physical examination till 7 years of age. </li></ul><ul><li>Data were collected from the questionnaire, medical records and biological samples. </li></ul>
  5. 5. METHODOLOGY <ul><li>Overall 31 potential risk factors are identified. </li></ul><ul><li>Measures for 21 risk factors were available in this cohort. </li></ul>
  6. 6. Potential Risk Factors <ul><li>Confounders </li></ul><ul><li>maternal social class, education , energy intake of child. </li></ul><ul><li>Intrauterine / perinatal risk factors </li></ul><ul><li>birth wt. ,sex, parity , smoking etc. </li></ul><ul><li>Family chs. </li></ul><ul><li>parents BMI , ethnicity , etc. </li></ul><ul><li>Childhood lifestyle </li></ul><ul><li>time spent watching T.V., duration night time sleep , dietary pattern etc. </li></ul><ul><li>Risk factors in focus </li></ul><ul><li>wt. standard deviation score , catch up growth , adiposity rebound etc. </li></ul>
  7. 7. RESULT <ul><li>Total of 8234 children attended the clinic at age 7. </li></ul><ul><li>7758 children’s wt. /ht. were available (3934 boys , 3824 girls ) </li></ul><ul><li>Eight of 25 putative risk factors were associated with a risk of obesity. </li></ul><ul><li>Parental obesity, </li></ul><ul><li>BMI as early as 43 months, </li></ul><ul><li>> 8 hrs. of T.V. watching / wk. ( 3 yrs ) </li></ul><ul><li>< 10.5 hrs of sleep duration </li></ul><ul><li>birth wt. </li></ul><ul><li>wt. gain in first year </li></ul><ul><li>S.D. score for wt. at 8 months/ 18 months </li></ul><ul><li>catch up growth. </li></ul>
  8. 8. CONCLUSION <ul><li>Eight factors in early life are associated with an increased risk of obesity. </li></ul>
  9. 9. MERITS/ DEMERITS <ul><li>This study has a large sample size , longitudinal design and the use of multivariable analysis. </li></ul><ul><li>This study identifies only associations rather than confirming causality. </li></ul><ul><li>This study is unable to analyse several other risk factors eg. Physical activity , parental control over feeding , energy expenditure etc. </li></ul><ul><li>The use of definitions of obesity based on BMI ? </li></ul><ul><li>Ethnic minority group under represented in original cohort. </li></ul>
  10. 10. <ul><li>Thank You </li></ul>
  11. 11. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease SUSHIL SRIVASTAVA
  12. 12. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>OBJECTIVE —To evaluate the association between type 2 diabetes and newly reported Parkinson's disease. </li></ul><ul><li>RESEARCH DESIGN AND METHODS —The study included 21,841 participants in the Physicians’ Health Study, a cohort of U.S. male physicians. </li></ul><ul><li>Diabetes and Parkinson's disease were self-reported via questionnaire. </li></ul><ul><li>Time-varying Cox regression to calculate adjusted relative risk (RR) for Parkinson's disease. </li></ul>
  13. 13. RESULTS <ul><li>Over 23 years, 556 individuals with Parkinson's disease were identified. </li></ul><ul><li>Subjects with diabetes had an increased Parkinson's disease risk (multivariable-adjusted RR 1.34 [95% CI 1.01–1.77]). </li></ul><ul><li>The association remained significant after exclusion of those with known vascular disease. </li></ul><ul><li>The diagnosis of diabetes was clustered around the diagnosis of Parkinson's disease </li></ul><ul><li>It was more apparent among men with short diabetes duration and those without complications from diabetes. </li></ul>
  14. 14. Physicians’ Health Study <ul><li>The Physicians’ Health Study is a completed randomized trial of aspirin and β-carotene in the prevention of cardiovascular disease and cancer among 22,071 U.S. male physicians </li></ul><ul><li>At baseline in 1982, participants were aged 40–84 years and free of major diseases. </li></ul><ul><li>Health information was self-reported through questionnaires at baseline and during yearly follow-ups. </li></ul><ul><li>A validation study of the self-report of Parkinson's disease in the Physicians’ Health Study found it to be 90% accurate. </li></ul>
  15. 15. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>Participants with Parkinson's disease were excluded before study entry, (Similarly dementia before or within the same year as Parkinson's disease, diabetes before age 25 years, or missing information on diabetes or smoking status) </li></ul><ul><li>21,841 individuals were analyzed. </li></ul><ul><li>They used Cox proportional hazards models to estimate the relative risk (RR) of Parkinson's disease. </li></ul><ul><li>Information on diabetes was updated to incorporate incident case subjects. </li></ul><ul><li>They adjusted for baseline age, smoking status, alcohol use, BMI, physical activity, and history of hypertension or hypercholesterolemia. </li></ul>
  16. 16. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>They stratified models by baseline smoking status, age, and BMI. </li></ul><ul><li>They performed sensitivity analyses to determine if diabetes characteristics or known vascular disease (coronary heart disease or stroke) affected the association. </li></ul><ul><li>They compared the pattern of diabetes diagnosis in Parkinson's disease patients with comorbidity-matched control subjects . </li></ul><ul><li>Diabetes was not included in the comorbidity score. </li></ul><ul><li>Statistical calculations were performed using SAS (version 9.1; SAS Institute). P < 0.05 was considered significant. </li></ul>
  17. 17. RR’ of Parkinson’s according to history of type 2 diabetes No DIAB DIAB RR RR in DIAB p value Participants 19431 2410 1 1.34 <55 yrs 11684 1247 1 1.12 0.81 55--64 5140 790 1 1.57 > 65 2607 373 1 1.25 BMI < 25 11720 858 1 1.88 0.04 25-- <30 7097 1247 1 1.14 >30 614 305 1 0.36
  18. 18. RR’ of Parkinson’s according to history of type 2 diabetes No DIAB DIAB RR RR in DIAB p value Diab. complication 19431 No 1475 1 1.63 .0002 Yes 935 1 1.10 Diab. duration 19432 <5 562 1 7.17 <.0001 5—9 631 1 2.03 10—14 482 1 0.82 >15 734 1 0.73
  19. 19. RR’ of Parkinson’s according to history of type 2 diabetes No DIAB. DIAB RR RR in DIAB P value Age at onset of diabetes < 63.7 1213 1 1.18 <o.ooo2 > 63.7 1197 1 1.49
  20. 20. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>Type 2 diabetes was reported by 423 participants at baseline and by 1,987 during the study. </li></ul><ul><li>Over a median follow-up of 23.1 years (453,954 person-years), 556 participants reported incident Parkinson's disease (median age of diagnosis 73.1 years). </li></ul>
  21. 21. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>Men with diabetes had an increased risk of Parkinson's disease (age- and smoking status–adjusted RR 1.34 [95% CI 1.02–1.77]) compared with nondiabetic men. </li></ul><ul><li>Further adjustment did not change this risk (1.34 [1.01–1.77]). </li></ul><ul><li>The association between diabetes and Parkinson's disease was significantly modified by BMI ,indicating increased risk for the low BMI group </li></ul>
  22. 22. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>Age and smoking status did not modify this association. Exclusion of patients who developed vascular disease ( n = 5,418) did not attenuate the risk (adjusted RR 1.46 [95% CI 1.00–2.13]). </li></ul><ul><li>The highest Parkinson's disease risk was seen in individuals with short-duration, older-onset diabetes without complications. </li></ul>
  23. 23. Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease <ul><li>Differences in diabetes incidence between Parkinson's disease patients and matched control subjects was greatest during the year of Parkinson's disease diagnosis and the few years prior </li></ul><ul><li>A similar clustering was not seen for the diagnosis of hypercholesterolemia </li></ul>
  24. 24. Discussion <ul><li>In this large prospective study of men, a history of type 2 diabetes was associated with an increased risk of Parkinson's disease. </li></ul><ul><li>The association remained significant after adjustment for confounders and the exclusion of participants with known vascular disease. </li></ul><ul><li>If diabetes causes Parkinson's disease, one would expect increased duration and severity to increase Parkinson's disease risk. </li></ul>
  25. 25. Discussion <ul><li>The highest risk for Parkinson's disease among individuals with uncomplicated or short-duration diabetes, regardless of baseline age. </li></ul><ul><li>This was not explained by selective mortality among those with longer diabetes duration </li></ul><ul><li>Diabetic individuals who developed Parkinson's disease had a longer median time to first complication (17.0 vs. 15.4 years), consistent with decreased severity. </li></ul>
  26. 26. Discussion <ul><li>Those with a normal BMI at baseline had the highest risk of Parkinson's disease, </li></ul><ul><li>suggesting a biological pathway other then obesity. </li></ul><ul><li>Thus, the findings do not suggest that diabetes is a preceding risk factor for Parkinson's disease. </li></ul>
  27. 27. Discussion <ul><li>Comparison of Parkinson's disease risk between case and matched control subjects showed that the difference in risk was primarily due to a clustering of diabetes cases around the time of Parkinson's disease identification </li></ul><ul><li>Thus, the explanation for the association may be detection bias from increased medical surveillance. </li></ul><ul><li>However, the diagnosis of hypercholesterolemia, another condition diagnosed by a blood test, no similar pattern was observed. </li></ul>
  28. 28. Discussion <ul><li>Another possible explanation is that the development of Parkinson's disease may influence diabetes risk. </li></ul><ul><li>By the time Parkinson's disease becomes clinically apparent, dopaminergic cell loss has reached 70–80% </li></ul><ul><li>Dopaminergic neurons help motivate feeding behavior when glucose levels are low. </li></ul><ul><li>This feedback loop is mediated by insulin receptors in the substantia nigra , and postmortem studies of Parkinson's disease show a loss of these receptors. </li></ul>
  29. 29. Discussion <ul><li>Drugs that modulate central dopamine, such as bromocriptine, are known to affect peripheral glucose control. </li></ul><ul><li>Changes in glucose control associated with loss of dopaminergic function might occur early in the course of Parkinson's disease, perhaps even before neurological symptoms develop. </li></ul><ul><li>If Parkinson's disease were a cause of diabetes, one would expect an increased incidence after the diagnosis of Parkinson's disease. </li></ul><ul><li>However, the incidence dropped dramatically the year after Parkinson's disease diagnosis </li></ul>
  30. 30. Discussion <ul><li>As over 25% of the Parkinson's disease patients in this study were aged ≥80 years at diagnosis, this might reflect decreased reporting from increased comorbidity and mortality. </li></ul><ul><li>Parkinson's disease treatment might also modulate diabetes risk. </li></ul>
  31. 31. CONCLUSION <ul><li>Results of this large prospective study in men do not suggest that diabetes is a preceding risk factor for Parkinson's disease. </li></ul><ul><li>The observed clustering of diabetes cases around the time of Parkinson's disease diagnosis suggests ascertainment bias or an underlying common biological mechanism. </li></ul><ul><li>Future studies are warranted to further unveil this association. </li></ul>
  32. 32. <ul><li>THANK YOU </li></ul>

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