Update on Diabetes Treatment and Care Tahseen A Chowdhury Consultant Diabetologist Royal London and Mile End Hospitals Diabetes prevalence (thousands) Diabetes in the UK: 1995-21 3 25 2 15 1 5 Type 1 Type 2 1995 2 21 1 2 Why is diabetes increasing? A case study Obesity Increased waist circumference 3 4 Poor diet Excessive fat Excessive carbohydrate Sedentary lifestyle little physical activity 5 6 1
7 8 What goes wrong in diabetes? Why is diabetes so important? Muscle Complications Glucose resistance Effect on Quality of Life Liver Reduction in Life Expectancy (1 years less) Increased glucose production Impaired insulin secretion Pancreas Cost to NHS and society 1 Life expectancy (yrs) 85 8 75 7 65 6 55 5 45 Life Expectancy and Diabetes 15-19 2-29 3-39 -49 5-59 6-7 Non Diabetics Diabetics Diabetic retinopathy Commonest cause of blindness in people of working age Age at diagnosis (yrs) Adults with diabetes have an annual mortality of about 5.4%, double the rate for non-diabetic adults. Life expectancy is decreased by 5 1 years. 12 2
Diabetic neuropathy Diabetic nephropathy Commonest cause of nontraumatic amputation Commonest cause of End stage renal failure 13 14 Cardiovascular disease CVD in Tower Hamlets 1 There is 2 3 fold increased risk of coronary heart disease and stroke Directly Age Standardised Rate 9 8 7 6 5 3 2 Tower Hamlets has the highest death rate from heart disease in London 1 15 ENGLAND LONDON Bromley LB Barnet LB Bexley LB Redbridge LB Havering LB C of L LB Brent LB Camden LB Waltham Forest LB C & H PCT Hackney LB B & D LB Newham LB Tower Hamlets LB 16 The Health Gap Need to treat cardiovascular risk factors Directly Age Standardised Rate 2 18 16 1 12 1 8 6 2 1998 1999 2 21 22 23 24 25 26 27 28 29 21 Tower Hamlets England Death rates from heart disease are falling, Step change to close the gap between Tower Hamlets and the national average 17 Diabetic patients without previous MI have as high a risk of MI as non-diabetic patients with previous MI 7-year incidence of MI (%) 45 35 3 25 2 15 1 5 non-diabetic with diabetes Without previous MI With previous MI 18 3
The cost of complications Total cost of DM 5 billion (1% NHS) 93million p.w. 13million p.d. 155- per second! ~% on inpatient care More frequent admissions, 2x length of stay Major cost of diabetes is complications 1 year reduction in life expectancy 1 in 1 deaths in UK due to diabetes Aims of treatment of diabetes Maintenance of good health by: Education / Information to self manage Dietary and Lifestyle advice Psychosocial care Control of cardiovascular risk factors Screening and surveillance for comps. 19 2 Structured Education Structured Education Good evidence that education about the effects of diabetes and how to self manage the condition improves outcomes DESMOND, X-PERT (Tower Hamlets HAMLET) 21 22 Smoking Cessation How do we prevent complications? 1 cigarette in a diabetic person = 5 cigarettes in a non-diabetic person Strong correlation between smoking and diabetic complications NHS has excellent smoking cessation services How do we prevent complications? Blood pressure Extremely important to lower BP to prevent diabetic complications Advice on weight loss, smoking cessation, alcohol reduction and salt reduction will help Aim for 1/8mmHg in all (although 13/8 if renal or CVD) First line ACEI, Calcium channel blockers (often >2) 23 24 4
How do we prevent complications? Cholesterol Very strong link between cholesterol levels and diabetes complications Diet reduce cholesterol by ~1% Statins All diabetic >yrs, Diabetic <years + 1 RF Aim for total cholesterol <4.mmol/l How do we prevent complications? Aspirin Aspirin reduces the clottability of the blood Good evidence that it reduces heart attacks and stokes in diabetes Consider in all people with diabetes >5 years with well controlled BP (Care in proliferative retinopathy) 25 26 How do we prevent complications? Improve blood glucose UKPDS Little effect on heart disease and stroke Dramatic effect on microvascular disease including retinopathy HbA 1c (%) Glycaemic Control: UKPDS 9 Conventional 8 Intensive 7 27 6 6.2% upper limit of normal range 3 6 9 12 15 Years from randomisation 28 UKPDS effects of tight control of glucose Treatment for blood glucose % risk reduction 35 3 25 2 15 1 5 P=.29 P=.99 Any Combined Microvascular P=.54 P=.46 P=.15 P=.52 M I Cataract Retinopathy Albuminuria extraction Diet Low in fat, refined CHO High in fruit, vegetables, starchy CHO Low in salt Lifestyle 3 minutes of exercise 3 times per week Walk / cycle rather than car, get off one stop earlier, stairs rather than lift etc. 29 3 5
Treatment for blood glucose Oral Hypoglycaemic Agents Metformin Sulphonylureas / Meglitinides Glitazones Acarbose 4. Liver: hepatic glucose output Metformin 1. Intestine: glucose absorption 2. Muscle and adipose tissue: glucose uptake Blood glucose resistance resistance 3. Pancreas: insulin secretion 31 32 Metformin UKPDS effects of metformin Very important to use metformin in all people with type 2 diabetes Start slowly and build up Take after meals (can cause nausea and diarrhoea) Contraindicated in significant renal failure 33 % risk reduction 5 45 35 3 25 2 15 1 5 P=.23 P=.2 Any Macrovascular diabetes related P=.1 Myocardial infarction P=.17 Diabetes related death P=.11 All cause mortality 34 secretagogues Gliclazide / Repaglinide 4. Liver: hepatic glucose output 1. Intestine: glucose absorption resistance Blood glucose resistance 2. Muscle and adipose tissue: glucose uptake 3. Pancreas: insulin secretion 35 Liver insulin resistance hepatic glucose production Blood glucose Balfour, et al. Drugs 1999;57:921-93. Whitcomb, et al. From Diabetes Mellitus, Ch. 74, p. 661-668. Glitazones Muscle and adipose tissue insulin resistance glucose uptake Pancreas demand for insulin secretion beta-cell insulin content 36 6
Advantages Good glycaemic control Generally well tolerated HbA1c reduction 1% - 3% Disadvantages Injection (needs considerable nursing input) Blood glucose monitoring Hypoglycaemia Weight gain 3-5kg 37 38 Commonly given once daily with tablets Glargine (lantus) or Levemir Twice daily fixed mixture Novomix 3 pre-breakfast and pre-evening meal Basal bolus Rapid acting with meals (eg novorapid) Long acting at night (insulin glargine) Better results when started early (HbA1c ~7.5%) Continue metformin less weight gain and less insulin requirement Hypoglycaemia Common complication of therapy Hypoglycaemic symptoms typically occur at glu < 3.6 Sweating Palpitations Tremor Hunger Confusion 39 Hypoglycaemia Hypoglycaemia Treatment 2 sweet biscuits or 4 plain biscuits Or Lucozade 1 glass (2ml) CHECK BG IN 5 MINUTES AND REPEAT ABOVE IF STILL LESS THAN 4.mmol/L On recovery give a good carbohydrate snack or meal If unconscious or unable to swallow Give glucogel (one-third of a bottle initially) Consider need for 25ml of 5% glucose IV as bolus over 5 minutes Or Glucagon IM On recovery give a good carbohydrate snack or meal. 41 42 7
Treatment of hypoglycaemia Commonly given once daily with tablets Glargine (lantus) or Levemir Twice daily fixed mixture Novomix 3 pre-breakfast and pre-evening meal Basal bolus Rapid acting with meals (eg novorapid) Long acting at night (insulin glargine) Better results when started early (HbA1c ~7.5%) Continue metformin less weight gain and less insulin requirement New treatments for glucose control GLP-1 analogues - BYETTA DPP-IV inhibitors - JANUVIA 43 44 What is GLP-1? GLP-1 analogues IR-insulin (mu/l) Increased insulin response 8 6 2 Incretin effect * * * * * * * 1 5 6 12 18 Time (min) Key observations A hormone (like insulin) produced from the intestine Produced when you eat Stimulates insulin release from the pancreas Helps increase size and number of beta cells Reduces appetite Is reduced in diabetes 45 46 Gila Monster (Heloderma suspectum) Exendin-4 (Exenatide) GLP-1 analogue Twice daily injection 47 48 8
Does it work? Adverse Effects 3 week trials: In addition to tablets HbA1c reduction of ~1% 2.5kg weight loss Around 1 people treated for 4 years: Sustained reduction in HbA1c of 1.1% Continued weight loss of ~4.5kg Nausea % Reduces with continued use Minimised by slow dose titration Led to discontinuation in 1% Hypoglycaemia common with SU 49 5 Where does it fit in? Another option in Obese type 2 Problem is tolerability, cost and injection Might be an option in obese type 2 who accepts injections, but you are worried about weight gain Exenatide LAR likely to be more widely used DPP-IV Inhibitors - Gliptins Gliptins Sitagliptin (Januvia) Additional class of OHGA few side effects no weight gain Oral Once daily Larger studies required for these drugs to be widely used 51 52 Oral Buccal Oral-Lyn (Generex) Aerosolised insulin, with enhancers to help absorb insulin across buccal membrane Prandial insulin (similar profile for short acting insulin) Recently published study: Type 1 diabetes Equivalent post prandial glucose lowering to short acting insulin over 9 days Future therapies? Pancreatic beta cell transplants Artificial pancreas Stem cells Very little published, but: Available for sale in Ecuador Approved for sale in India 53 54 9
Summary Diabetes is on the increase Major cost to NHS and society With good care, many complications can be prevented Many exciting new therapies available to treat the condition 55 1