Diabetic & Complications. Dr. A K Viswanath Consultant Diabetologist

Transcription

1 Diabetic & Complications Dr. A K Viswanath Consultant Diabetologist

2 Outline Challenges in diabetes How do we fare? Diabetes complications Improving outcomes in diabetes

3

4 Types of Diabetes

5 Type-1 DM Genetic predisposition Younger age of onset Usually underweight Ketosis prone Insulin dependent Type-2 diabetes Polygenic older age of onset Obesity Ketosis is rare Responsive to oral agents

6 Diabetes prevalence in the UK The prevalence of diabetes is expected to increase significantly It is estimated that 5 million people will have been diagnosed with diabetes by 2025 Diabetes prevalence in England by primary care trust % and over 9% to 10% 8% to 9% 7% to 8% Under 7% Adapted from: Diabetes UK (2012) State of the Nation 2012: England. Available at: (accessed )

7 The problem is obvious

8 Type 2 diabetes is closely linked to obesity 60 OVERWEIGHT OBESE Age-adjusted relative risk of Type 2 diabetes < > 35 BMI Chan JM et al. Diabetes Care 1994; 17: ,983 men followed for 5 years

9 Prevalence of Diabetes by Age Distribution

10 Advancing age & Multi-morbidity

11 Cost of Diabetes care Primary care 11% 10% of budget at present ( 10 Billion) All other drugs 16% Insulin 16% Outpatient care 14% In-patient care 41% 4/5 th of diabetes budget spent on treating complications Diabetes can bankrupt the National Health Service

12 How do we fare: National audits

13 Annual Care Processes: National Diabetes Audit All people with diabetes aged 12 years and over should receive all of the nine, NICE recommended care processes 1,2 and attend a structured education program when diagnosed. Nine Annual Care Processes for all people with diabetes age 12 and over Responsibility of Diabetes Care Providers (included in the NDA 8 Care Processes) 1 - HbA1c (blood test for glucose control) 5 - Urine Albumin/Creatinine Ratio (urine test for kidney function) 2 - Blood Pressure (measurement for cardiovascular risk) 3 - Serum Cholesterol (blood test for cardiovascular risk) 4 - Serum Creatinine (blood test for kidney function) 6 - Foot Risk Surveillance (foot examination for foot ulcer risk) 7 - Body Mass Index (measurement for cardiovascular risk) 8 - Smoking History (question for cardiovascular risk) Responsibility of NHS Diabetes Eye Screening (screening register drawn from practices) 9 - Digital Retinal Screening Photographic eye test for eye risk 1,2. Please see full list of footnotes in the definitions and footnote section (page 36) 13

14 Recording Care Processes: NDA 2014/15 Key Finding Blood tests (Hba1c, serum creatinine, cholesterol) and blood pressure are more reliably performed than other care processes. Table 3: Percentage of people with diabetes in England and Wales receiving NICE recommended care processes by care process, diabetes type and audit year Type 1 Type 2 and other HbA1c Blood pressure Cholesterol Serum creatinine Urine albumin * Foot surveillance BMI Smoking Eight care processes * There is a health warning regarding the screening test for early kidney disease (Urine Albumin Creatinine Ratio, UACR) prior to ; please see the NDA Data Quality statement 3,4. Please see full list of footnotes in the definitions and footnote section (page 36) 14

15 Locality variation: Care Processes, Type 2 diabetes Key Finding For people with Type 2 diabetes blood tests (Hba1c, cholesterol and serum creatinine) and blood pressure checks are performed much more reliably than other care processes. Figure 6: The range of CCG/LHB care process completion for people with Type 2 diabetes in England and Wales, HbA1c Blood pressure Cholesterol Care process Serum creatinine Urine albumin Foot surveillance BMI Smoking All eight care processes 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Percentage of patients 3. Please see full list of footnotes in the definitions and footnote section (page 36) 15

16 Achievement of Treatment Target Key Findings: For people with Type 2 diabetes, HbA1c and cholesterol target achievement rates are stable but blood pressure target achievement rates have improved steadily. For those with Type 1 diabetes, cholesterol target achievement rates have been stable, HbA1c may show a slight improvement but blood pressure target achievement has improved steadily. Table 4: Percentage of people with diabetes in England and Wales achieving their treatment targets by diabetes type and audit year Type 1 Type 2 and other HbA1 c < 58 mmol/mol Blood Pressure < 140/80* Cholesterol < 5mmol/L Meeting all three treatment targets * The blood pressure target does not exactly match NICE (<140/80) but was changed to align with the relevant QOF indicator (<140/80). More information can be found here 16

17 Complications NDA England & Wales (2012/13) Figure 1: Additional risk of complication among people with diabetes, comparing people with diabetes to those without diabates i with a one year follow up period, to audits Addtional risk % Included 2.46 million people with diabetes from 2011/12 NDA were still alive on 31 March year prevalence Additional RISK Attributed Angina Myocardial Infarction (heart attack) Heart Failure Stroke Major Amputation (above the ankle) (audit) (audit) (audit) Minor Amputation (below the ankle) Renal Replacement Therapy (ESKD) to diabetes i People classed as not having diabetes are those people not identified as having diabetes as part of the National Diabetes Audit and therefore this may contain people diagnosed w ith diabetes that are not participants in the audit

18 Age specific mortality ratio by gender and type of DM DM is associated with additional risk of death Risk high at all ages and both sexes compared to the general population Risk greatest in younger ages, in females and in Type-1 diabetes

19 Diabetes complications Microvascular Macrovascular

20 Metabolic Pathways Leading to Microvascular Complications Brownlee M. Diabetes 54:1615, 2005

21 Metabolic Pathways Leading to Microvascular Complications Brownlee M. Diabetes 54:1615, 2005

22 HbA1c & Microvascular Complications Relative Risk HbA 1c (%) Skyler JS. Endocrinol Metab Clin. 1996;25: Retinopathy Nephropathy Neuropathy Microalbuminu

23 Risk of MI in Diabetes Haffner, SM et al NEJM: 339:

24 Diabetic Retinopathy Normal Retinal Vasculature CAPILLARY DAMAGE Loss of Percicytes & BM Thickening Capillary leakage Capillary closure

25 Diabetic Retinopathy Retinal capillaries Macula Optic nerve Macular edema Exudates New Vessel Formation NORMAL RETINA NON-PROLIFERATIVE OR BACKGROUND RETINOPATHY PROLIFERATIVE RETINOPATHY Disease Progression

26 WESDR 2008 Diabetic Retinopathy: Incidence & Progression

27 DR: Commonest cause of Blindness Medical management: Improve glucose control BP reduction Treat hyperlipidemia Anti-VEGF treatment for macular edema Laser New Vessels: very effective before bleeding Macular edema: Less effective and the main aim of treatment is to prevent further visual loss Surgery Indication: Bleeding or Retinal Detachment Vitrectomy: This removes the jelly which contains the blood or is causing traction

28 Diabetes Nehropathy: Leading cause of ESRD Adjusted ESRD incident rates, by primary diagnosis, & diabetes in the general population USRDS, accessed July 13, 2007

29 Stages of Diabetic Nephropathy Stage I: glomerular filtration and hypertrophy Stage II: u-albumin excretion < 30mg/24h Stage III: Microalbuminuria ( mg/24h) Stage IV: Overt proteinuria Stage V: ESRD Diabetic nephropathy may be diagnosed in its earliest and potentially, reversible stages by detection of extremely small amounts of albumin in the urine, so-called microalbumin

30 Management of Nephropathy Improve glucose control SBP <130 Treat with ACEi Monitor renal functions Referral to specialist service (declining GFR, worsening proteinuria)

31 Diabetic Neuropathy Sensorimotor neuropathy Autonomic neuropathy Mononeuropathy Spontaneous Entrapment External pressure palsies Proximal motor neuropathy

32 Sensorimotor Neuropathy Small fibres: Pins and needles, tingling or burning sensation Loss of temperature Pain usually worse at night Cold extremities Swelling of feet or ankle Large fibres: Abnormal sensations Loss of balance Lack of position sense Motor nerve damage: Weakness and atrophy of intrinsic foot muscles Deformed toes & foot

33 Complications of Sensorimotor neuropathy Callosities Ulceration (painless) Neuropathic edema Charcot arthropathy

34 Autonomic Neuropathy Symptomatic Postural hypotension Gastroparesis Diabetic diarrhoea Neuropathic bladder Erectile dysfunction Neuropathic edema Gustatatory sweating Subclinical abnormalities Abnormal cardiovascular reflexes Blunted counter-regulatory responses to hypoglycemia Abnormal pupillary reflexes Esophageal dysfunction Increased peripheral blood flow

35 Mononeuropathies Entrapment Neuropathies Cranial nerve palsies (most common are IV,VI,VII) Carpal tunnel syndrome (median nerve) Ulnar compression syndrome Lat Popliteal nerve compression (drop foot) Meralgia paresthetica (lat cut nerve to the thigh)

36 Macro-vascular Complications Ischemic heart disease Cerebrovascular disease Peripheral vascular disease

37 Atherosclerosis

38 Causes of Death in People With Diabetes of Diabetic Patients Deaths 65% are from CV Causes

39 Cardiovascular Risk Factor Modifiable factors Hypertension Diabetes dyslipidemia Obesity Sedentary habits Glucose control Non-modifiable Age Family history Familial dyslipidemia Ethnicity

40 Diabetes & Hypertension Mortality vs systolic blood pressure 70 Ten Year Mortality (per 1000) Non-diabetic Diabetic Systolic Blood pressure (mmhg)

41 NICE: BP management Check BP annually Repeat blood pressure measurements within: 1 month if blood pressure is higher than 150/90 mmhg 2 months if blood pressure is higher than 140/80 mmhg (or >13/80 with evidence of microvascular or CVD) Treat: BP consistently above 140/80 mmhg or above 130/ 80mmHg if there is kidney, eye or cerebrovascular damage First-line antihypertensive drug treatment should be a once-daily, generic angiotensin-converting enzyme (ACE) inhibitor. African or Caribbean family origin: ACE inhibitor plus either a diuretic or a generic calcium-channel blocker Woman planning pregnancy: Calcium-channel blocker ACEi intolerance: (other than renal deterioration or hyperkalaemia), substitute for an ARB Do not combine an ACE inhibitor with an ARB Second Line: add a calcium-channel blocker or a diuretic Third line: add the other drug (that is, the calcium-channel blocker or diuretic) if the target is not reached with dual therapy. Quadruple therapy: add an alpha-blocker, a beta-blocker or a potassium-sparing diuretic

42 Diabetes Dyslipidemia Most common abnormality is reduced HDL and elevated Triglycerides A low HDL is the most constant predictor of CV disease in DM Check fasting & include HDL Target lipid values: LDL <2.6 mmol/l, HDL >1.15 mmol/l, TG < 2.5 mmol/l

43 Nice CG181 (July 2014) replaces NICE CG 67 Changes Lipid measurement Assessing CV risk Risk calculation Lipid therapy Targets Measure non-hdl cholesterol rather than LDL- cholesterol. Non-HDL Chol: T-Chol-HDL. T2 DM: Use QRISK2 risk assessment tool to assess CVD risk for the primary prevention in people up to and including age 84 Type-1 DM, Renal failure: QRISK2 score unhelpful Offer treatment for primary prevention if 10-year risk of CVD 10% 40% reduction of non-hdl Cholesterol from baseline Atorvastatin-first choice

44 Improving glucose control: Evidence base Does it reduce the risk of microvasclar disease? What is the impact on macrovascular outcomes? Landmark Diabetes Studies: T1 DM: DCCT T2DM: UKPDS

45 DCCT/EDIC: Lower Glycemia in DM-1 Diabetes Control & Complications Trial (Randomized Intervention) / Epidemiology of Diabetes Interventions & Complications (Observational F/U) 11 Conventional Intensive Conventional Intensive % 10 mean 8.2% A1c (%) 9 8 Between group A1c difference 1.8% 8 7.8% 7.9% 7 6 Normal 6.05 Normal 7.1% 6 mean 8.0% DCCT Study yr EDIC yr Adapted from DCCT Research Group. N Engl J Med 1993;329: DCCT/EDIC Study Research Group, N Engl J Med 2005; 353:

46 Risk Reduction in DCCT Effects of reduction of A1c by 1.9% in intensively treated group 80 Onset Risk Reduction % Progression 54% 60% 54% 39% 0 P=0.002 P=0.002 P=0.002 P=0.04 P=0.04 Retinopathy Neuropathy Albuminuria albuminuria DCCT Research Group. N Engl J Med. 1993;329:

47 Lower Glycemia in DM-1 Decreases CVD But Benefits are Delayed (DCCT-EDIC) MACE (NF MI, 0.04 CVA, or CVD death) 0.02 Intervention Follow-up Conventional treatment 57% RRR p=0.02) Intensive treatment No. at Risk Years since entry Intensive Conventional DCCT/EDIC Study Research Group, N Engl J Med 2005; 353:

48 UKPDS: Lower Glycemia in DM-2 with Intensive Intervention Over 10 years HbA1c was 7 0% ( ) in the intensive group compared with 7 9% ( ) in the conventional group Median A 1c (%) Conventional Intensive (Sulfonylurea or Insulin) Average between group A1c difference = 0.9% Years from randomization UKPDS Group. Lancet. 1998;352:

49 UKPDS Outcome after 10 years FU

50 Diabetes therapeutics

51 Diabetes medications: mechanism of action Glucose absorption Pancreatic insulin secretion Acarbose SU, Gliptin, GLP-1A REDUCE Appetite GLP-1 agonist GLUCOSE Uptake by muscle & fat Glitazones INCREASE Hepatic glucose output Renal glucose excretion Metformin SGLT-2 inhibitors

52 Appraising Therapeutic options HbA1c % reduction Hypo risk Weight Side effects/ tolerability Caution CV benefit Metformin 1-1.5% N Neutral GI related Renal/hepatic /cardiac impairment Yes in obese patients SoU 1% Yes Gain Well tolerated elderly unclear Gliptin 0.8-1% N Neutral Well tolerated... No harm Pioglitazone 0.7-1% Yes Gain Fluid retention/ hepatic HF/bladder Ca/ bone loss Possible benefit SGLT-2 inhibitor 0.7-1% N Loss Genital infection UTI Renal impairment Elderly/ HF GLP % N Loss GI side effects Renal impairment Empa-? benefit No harm Insulin 1-2% Yes Gain No benefit

53 NICE: Glucose control Intensification steps

54 Barriers to improving diabetes control

55 Traditional: Treat-to-Fail Approach Published Conceptual Approach Diet and exercise OAD monotherapy OAD up-titration OAD combination OAD + basal insulin OAD + multiple daily insulin injections HbA 1c Goal 6 OAD=oral antihyperglycemic agent. Duration of Diabetes Conventional stepwise treatment approach Adapted from Campbell IW. Need for intensive, early glycaemic control in patients with type 2 diabetes. Br J Cardiol. 2000;7(10): Del Prato S et al. Int J Clin Pract. 2005;59:

56 COMPLIANCE in people with T2 DM Drug class n % Adherent 95% CI Oral antidiabetic drugs Antihypertensive drugs Lipid-lowering drugs Antiplatelet drugs All drugs Mateo JF et al. Int J Clin Pract. 2006;60:

57 Clinical Inertia: Failure to Advance Therapy Percentage of Subjects advancing when HbA 1C >8% % Age of Subjects % At Insulin Initiation, the average patient had: 5 years with HbA 1C >8% 10 years with HbA1C >7% 35.3% 44.6% 18.6% 0 Diet Sulfonylurea Metformin Combination 1 Brown et al. The Burden of Treatment Failure in Type 2 Diabetes. Diabetes Care , 2004

58 Summary SELF-CARE is integral component of diabetes management. Sustained improvement in glucose control is HARD. Key drivers are OBESITY & HYPOGLYCAEMIA. Intervention should be MULTI-FACTORIAL. Aim for good control of BP & LIPIDS. Complications are PREVENTABLE.