1. Diabetes in the older person Terry Aspray Tuesday pm

2. Diabetes in the older person Diabetes: A future epidemic? New drugs and old people –Old drugs and old people… Can we prevent complications?

3. A Future Epidemic? Old Age Older population in UK growing Demographics: Projections year 2000-2051 –Aged 65+ to rise by 80% –Aged 85+ to rise by 255% Source: Joseph Rowntree foundation 2005 http://www.jrf.Org.uk/knowledge/findings Population millions 85+ 65+ Year

4. A Future Epidemic? Diabetes In the UK Of people with diabetes –50% aged 65+ –25% aged 75+ Source: Diabetes UK 2004

5. A Future Epidemic? Diabetes & Death –Community study Population aged 75+ –Diabetic subjects Mortality x4.5 Melton Mowbray Survival- Aged 75+ Yrs Croxson et al Diab Med. 1994 Survival (%)

6. A Future Epidemic? Frailty & Care Homes Frail population in UK growing Care homes –450,000 residents Cost £13 billion (2000) –1,130,000 residents Cost £55 billion (2051) Cost £ billions Residents thousands Source: Joseph Rowntree foundation 2005 Http://www.jrf.Org.uk/knowledge/findings

7. A Future Epidemic? Diabetes & Care Homes 1630 Residents –1275 had blood tests Diabetes in at least 19.9% –105 new cases –186 already diagnosed EMI Care –Undiagnosed Diabetes common % *(p<0.001) Aspray et al (2006) Diabetes Care Aspray et al (2006) Public Health

8. A Future Epidemic? ↑Diabetes-all ages Especially in the old ↑Co-morbidities –Age –Diabetes Frailty with diabetes –e.g. Nursing homes

9. A Future Epidemic? Watch out for Diabetes in 2050… ↑Diabetes-all ages Especially in the old ↑Co-morbidities –Age –Diabetes Frailty with diabetes –e.g. Nursing homes

10. Case Based Discussion 1. Age 89 F. in a NH –Gliclazide 120mg –Metformin 1.5g –Pioglitazone 30mg –BP 152/72 –HbA1c 5.3% –Urea 7.5; creat 156 –TC 5.5 –Hb10g/dl Questions –Any concerns? –Would you change the treatments?

11. Case Based Discussion 1. Age 89 F. In a NH Weight 49 kg –Gliclazide 120mg –Metformin 1.5g –Pioglitazone 30mg –Bp 152/72 –HbA1c 5.3% –Urea 7.5; creat 156 –TC 5.5 –Hb 9.8g/dl Concerns –Low HbA1c Any hypos? –Mild anaemia Interpreting HbA1c Glitazone –Renal impairment Metformin Changes –Stop metformin? –Stop Pioglitazone? –Cut gliclazide dose?

12. Can We Prevent Complications? UKQOF Glucose Points Record of HbA1c in last 15months 3 HbA1c is 7.4 or less in the past 15 months 16 HbA1c is 10 or less in the past 15 months 11 BP HbA1c is 10 or less in the past 15 months 3 BP 145/85 or less in the past 15 months 17 Lipids Record of Cholesterol in last 15months 3 Cholesterol <5mmol in the past 15 months 6

13. Can We Prevent Complications? QOF & Glucose Not just about bringing down glucose… –No lower limit in QOF for HbA1c Safety first? –Avoiding Osmotic symptoms and Hypos Ensure regular and consistent meals. Consider withdrawal of treatment! Target HbA1c: ? ↑ 1% at 7.5-8.5%

14. Hypoglycaemia & Elderly Unawareness in old –↓counter-regulatory response –Take longer to recover. Misdiagnosis: –CVA, TIA –Fit –Confusion ?cause. Therefore:-. –Careful prescribing. –Ensure regular and consistent meals. –Consider withdrawal of treatment!

15. Benefits of Glucose Control: 2008 trials Intensive glucose control x3 –Target HbA1c 6.0-6.4% Little CVS benefit? –Already diagnosed DM –Over age 60 –Up to 6 years’ f.u. ↑Risk severe hypos ↑Risk Death (ACCORD) – Thanks to Gillian Hawthorne – BGS Spring Meeting 2009 intervention

16. Benefits of Glucose Control: 2008 trials Legacy Studies x2 Long Term benefit –New cases T2DM –Urine micro albumin Despite moderate control in long term –HbA1c: 8+% at 10+yrs Intensive glucose control x3 –Target HbA1c 6.0-6.4% Little CVS benefit? –Already diagnosed DM –Over age 60 –Up to 6 years’ f.u. ↑Risk severe hypos ↑Risk Death (ACCORD) intervention

17. ADOPT (4351 subjects) *Also Pioglitazone (Takeda) Rosiglitazone █ –Metformin █ –Sulphonylurea █ Hand, humerus, foot –NOT hip or spine Other risks –Cardiovascular (Rosi) –Fluid retention/heart failure –Anaemia Thiazolidinediones & Old People women

18. Case based discussion 2. 79yrs T2DM 15 yrs –Retinopathy –Neuropathy –BP 188/90 –Glargine/metformin –Bendrofluazide –Lisinoprol –Amlodipine –Atenolol –Why is her BP poorly controlled? –What side effects do you think she suffers from? –What is the target BP?

19. Case based discussion 2. 79yrs T2DM 15 yrs –Retinopathy –Neuropathy –BP 188/90 –Glargine/metformin –Bendrofluazide –Lisinoprol –Amlodipine –Atenolol –BP Drug adherence –Side effects Diuretic Ca antagonist Combinations… –Target BP Evidence supports Rx at all ages but…

20. Can We Prevent Complications? BP BHS for Diabetes –start at >140/90 target <130/80… Achievable? HOT 140/81 UKPDS. 144/82 PROGRESS: Post stroke- 138/82- half normotensive HYVET: target <150/80- achieved in 48% Side effects of treatment. –e.g. Orthostatic Hypotension…falls!

21. Case Based Discussion 3. 88 year old with T2DM for 30 yrs Living with daughter Needs help feeding Incontinent No longer takes tablets as was getting hypos Cholesterol 5.6mmol How should you manage her? Any risks to treatment?

22. Case Based Discussion 3. 88 year old with T2DM for 30 yrs Living with daughter Requires help with feeding Incontinent No longer takes tablets as was getting hypos Cholesterol 5.6mmol Statin? Risks & benefits of treatment?

23. Can We Prevent Complications? Lipids Should we give statin? –CVS events ↓by 7-10% at 7 years in the old Dementia: no benefit –(Cochrane 2009) HPS –5% reduction in 5yrs (2P<0.00001) Rate ratio & 95% CI STATIN betterPLACEBO better 24% SE 3 reduction 0.40.60.81.01.21.4 <65 >65 DM No DM DM No DM

24. Can We Prevent Complications? Lipids Statin safety –1.5x MSK symptoms Mosshammer D 2009 –Only 10% monitor LFTs correctly Leaver 2009 –High dose Atorva is safe up to age 78 Koren MJ 2009 Dementia: no benefit –(Cochrane 2009)

25. Case Based Discussion 4. Age 72 F. Diabetes for 7 years Gaining weight… –Gliclazide 320mg –Metformin 1.5g –Pioglitazone 45mg –BP 152/72 –HbA1c 9.5% –Urea 4.5; creat 111 Questions –How about insulin? –What if she refuses?

26. Case Based Discussion 4. Age 71 F. Diabetes for 7 years –Gliclazide 320mg –Metformin 1.5g –Pioglitazone 45mg –BP 152/72 –HbA1c 9.5% –Urea 4.5; creat 111 Insulin –Once daily –Twice daily –Four times daily –With or without OHA Newer Drugs…?

27. New Drugs: Incretins Insulin release –Response to glucose Orally > I.V. Incretins –Secreted from small bowel –Stimulate beta cells to produce more insulin. Incretin effect

28. New Drugs: Incretins Incretins: new class of drugs: –GLP-1: exenatide Metabolised by DPP4 –DPP4- inhibitors Oral Gliptins Range of effects –↑Glucose dependent insulin secretion –↓glucagon secretion –Slow gastric emptying –↓ Food intake –↑ Β-cell mass in rats –↑ Insulin sensitivity –↑ Glucose disposal

29. Incretins in older people Exenatide NICE 3 rd line –Injection –HbA1c ↓1% –Weight ↓ 1.5- 5.5kg Insulin ↑weight! Gliptins NICE 2 nd line –Tablet –HbA1c ↓1% –Weight ↓ 1.5- 5.5kg Incretins for older patients –Theoretically: ↓ β cell mass= less effect –Not licensed monotherapy Exenatide –Benefit into 7 th decade Gliptins –Safe and well tolerated –Efficacy maintained: Glycaemia and Weight

30. Case Based Discussion 4. Age 66 M. Diabetes for 21 years Poor control for 5 years –BD mix insulin 40/30 –Metformin 1.5g –Very irritable –Poor concentration –Nostalgic for the old days –Diabetes advice going nowhere… Could there be an underlying cause? What do you do?

31. Case Based Discussion 4. Age 66 M. Diabetes for 21 years Poor control for 5 years –BD mix insulin 40/30 –Metformin 1.5g –Very irritable –Poor concentration –Nostalgic for the old days –Diabetes advice going nowhere… Could there be an underlying cause? Hypoglycaemia??? BM 9.2; then what?

32. Complications: Dementia Epidemiological Evidence Risk with diabetes… –Alzheimer’s Dementia x2-4 –Vascular Dementia x3 –Diabetes for >15 yrs= x3 Gregg (2000) Arch Int Med 160: 174-180 Katzmann (1989) Ann Neurol 25: 317-24 Leibson (1997) Am J Epidemiology 145: 301-8 Yoshitake (1995) Neurology 45:1161-68

33. Can We Prevent Complications? Dementia Evaluation –Index of suspicion –Is it hypoglycaemia? –MTS (10 item) –MMSE (30 item) –Clock drawing test Draw a clock Put in the numbers Set hands at 10-to-3

34. Can We Prevent Complications? Dementia HypOglycaemia associate with dementia Kaiser Permanente –1980-2002 –16,667 patients –Mean Age 65yrs Hypo 8.8% Dementia 11% Hypo & Dementia 17% –Link has dose response Age Adjusted Incidence of dementia /10,000 person yrs Whitmer et al. JAMA. 2009;301(15):1565-1572

35. Can We Prevent Complications? Dementia HypERglycaemia ↑ HbA1c & ↓ cognition –Digital skills substitution test (DSST) Visuo-motor speed & learning –MMSE Global screening test –Memory score (Rey) Memorise/retrieve words –Stroop Executive skill: response time ACCORD-MIND Diabetes Care 2009… baseline data *P<0.0001 **P<0.0001 ** * *

36. Case Based Discussion 4. Age 66 M. Diabetes for 21 years Poor control for 5 years –BD mix insulin 40/30 –Metformin 1.5g –Very irritable –Poor concentration –Nostalgic for the old days –Diabetes advice going nowhere… Could there be an underlying cause? Needs Dementia work up Consider depression Consider psychological impairment…

37. Conclusion: Diabetes in older people We have an epidemic –Old People & Diabetes Drugs –Old drugs Benefits- Legacy Risks of tight control –New drugs Glita-bones: Concerns Incretins… Just as effective in the old? Complications –Risks of treatment Orthostatic Hypotension Hypoglycaemia awareness –Dementia Lack of clinician awareness Dysglycaemia causal? Benefits from statins

38. Conclusion: Diabetes in Older People Complications –Risks of treatment Orthostatic Hypotension Hypoglycaemia awareness –Dementia Lack of clinician awareness Dysglycaemia causal? No benefits from statins