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Type 2 Diabetes. What is type 2 diabetes?. Definition of diabetes? WHO/International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia; 2006. Diabetes Fasting plasma glucose ≥ 7.0mmol/l (126mg/dl) or 2h plasma glucose ≥ 11.1mmol/l (200mg/dl)

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Type 2 Diabetes


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    1. Type 2 Diabetes

    2. What is type 2 diabetes?

    3. Definition of diabetes?WHO/International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia; 2006 • Diabetes • Fasting plasma glucose ≥ 7.0mmol/l (126mg/dl) or • 2h plasma glucose ≥ 11.1mmol/l (200mg/dl) • Impaired glucose tolerance (IGT) • Fasting plasma glucose < 7.0mmol/l (126mg/dl) and • 2h plasma glucose ≥ 7.8 and < 11.1mmol/l (140mg/dl and 200mg/dl) • Impaired fasting glucose (IFG) • Fasting plasma glucose 6.1 to 6.9mmol/l (110mg/dl to 125mg/dl) and • 2h plasma glucose < 7.8mmol/l

    4. Change of units for HbA1cDTB 2010; 48: 23-4, MeReC Rapid Review No. 356

    5. Type 1 vs. Type 2 diabetesLambert P, et al. Medicine 2006; 34: 47-51Nolan JJ, Medicine 2006; 34: 52-6 Features of type 1 diabetes Features of type 2 diabetes Usually presents in over-30s Associated with overweight / obesity Onset is gradual and diagnosis often missed (up to 50% cases) Not associated with ketoacidosis though ketosis can occur Family history is often positive with almost 100% concordance in identical twins • Onset in childhood / adolescence • Lean body habitus • Acute onset of osmotic symptoms • Ketosis-prone • High levels of islet autoantibodies • High prevalence of genetic predisposition

    6. Burden of type 2 diabetesNICE Clinical Guideline 87, May 2009Royal College of Physicians; 2008 • Type 2 diabetes is a cardiovascular disease: commonly associated with raised BP, disturbance of lipid levels and tendency to develop thrombosis • Increased cardiovascular risk (macrovascular disease) • Coronary heart disease (MIs, angina) • Peripheral artery disease (leg claudication, gangrene) • Carotid artery disease (strokes, dementia) • Specific microvascular complications: • Eye damage (blindness) • Kidney damage (sometimes requiring dialysis or transplantation) • Nerve damage (amputation, painful symptoms, erectile dysfunction, other problems)

    7. Deaths by cause in the general population: Men aged 40-59 years, 1999, UKLaing SP, et al. Diabetic Medicine 1999; 16: 466-471Office of National Statistics 2000General Register Office 2000

    8. Deaths by cause in people with diabetes: Men aged 40-59 years, 1972/99, UK

    9. What are the management priorities?

    10. Management for type 2 diabetes: AimsNICE Clinical Guideline 87; May 2009 • Adopt a healthy lifestyle (stop smoking, exercise, weight management etc) • Manage symptoms associated with having high blood glucose levels if patients have them) • Reduce risk of major life-threatening or disabling complications (heart attacks and stroke) • Manage diabetic kidney damage, eye damage and nerve damage (foot disease, neuropathic pain, erectile dysfunction etc) • Targets for all the different aspects of this condition (BP, lipids, blood glucose etc) can be demanding to reach • Agree the priorities for care and targets for each aspect of management on an individualised patient basis as aggressive therapy of each aspect may not be appropriate for all

    11. Type 2 diabetes management is multifactorial • Education • Lifestyle • Dietary advice • Obesity • Weight management • Smoking • Control BP • Assessing cardiovascular risk • Blood lipids • Aspirin • Control blood glucose

    12. Education

    13. Education – what does NICE say?NICE Clinical Guideline 87; May 2009 • Offer structured education to every person &/or their carer at and around the time of diagnosis, with annual reinforcement and review. Inform patients and their carers that structured education is an integral part of diabetes care • The necessary lifestyle changes, the complexities of management and the side effects of therapy make self-monitoring and education for people with diabetes central parts of management • “Patient centred care” • People with diabetes should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. Good communication is essential

    14. What is the evidence? The DESMOND programmeDavies MJ, et al. BMJ 2008; 336: 491-495.Gillett M, et al. BMJ 2010; 341: c4093 • Diabetes Education and Self-Management for Ongoing and Newly Diagnosed programme • Patients taking part were significantly more likely to lose a little weight and stop smoking than those in the control group • Primary outcomes of the DESMOND programme trial found no statistical differences in HbA1c and no benefits for cholesterol levels and BP

    15. Lifestyle

    16. Dietary adviceNICE Clinical Guideline 87; May 2009 • Provide individualised and ongoing nutritional advice from a healthcare professional with specific expertise and competencies in nutrition • Healthy balanced eating applicable to general population • Integrate dietary advice with advice to increase physical activity and lose weight • Target initial weight loss is 5-10% of body weight is overweight • Individualised recommendations for carbohydrate and alcohol intake • Limited substitution for sucrose containing foods and other carbohydrates is allowable but take care to avoid excess energy intake • Discourage use of foods specifically marketed for people with diabetes

    17. Obesity: exercise and dietNational Audit Office. Tackling obesity in England. 15 February 2001Avenell A, et al. Health Technol Assess 2004; 8(21): 1-465 • Virtually all obese people develop some associated physical symptoms by the age of 40 years • The majority require medical intervention for diseases that develop as a result of obesity by the age of 60 years • National Audit Office suggests that 47% of type 2 diabetes can be attributed to obesity • As obesity rates increase, so will the prevalence of type 2 diabetes • Even modest losses in weight can confer significant metabolic and vascular benefits. Losing weight is associated with a reduction in: • Mortality (all-cause, cancer, CVD and diabetes-related) • The risk of developing type 2 diabetes • Hypertension • Cholesterol

    18. Weight managementSIGN 116, Management of diabetes. March 2010 • Obese adults with type 2 diabetes should be offered individualised interventions to encourage weight loss (including lifestyle, pharmacological or surgical interventions) in order to improve metabolic control • A single approach is not recommended due to an absence of head-to-head comparisons • Consider drug treatment only after dietary, exercise and behavioural approaches have been started and evaluated • Consider drug treatment for patients who have not reached their target weight loss or have reached a plateau on dietary, activity and behavioural changes alone

    19. Smoking

    20. Smoking cessation • Advising and effectively assisting a person to stop smoking is the single most important thing that can be done for health • All healthcare professionals should take the opportunity to advise smokers to stop smoking, and consider referral to the NHS Stop Smoking Service

    21. Control BP

    22. Blood pressure – what does NICE say?NICE Clinical Guideline 87; May 2009 • Target BP • <140/80mmHg • <130/80mmHg if kidney, eye or cerebrovascular damage • Drug choices • ACE inhibitor (first-line) • Add CCB or diuretic • Add other drug (CCB or diuretic) • Add alpha-blocker, beta-blocker or potassium sparing diuretic

    23. ACE inhibitors first lineNICE Clinical Guideline 87; May 2009NICE Full Diabetes Guideline 66, 2008 • ACE inhibitors have no significant differences in CV outcomes compared with other antihypertensives but have greater benefits in terms of renal outcomes in those with type 2 diabetes • Exceptions: • Afro-Caribbeans who should receive an ACE inhibitor plus either a diuretic or CCB • Women who may become pregnant should receive a CCB • Those with a continuing intolerance to an ACE inhibitor eg cough should substitute an A2RB

    24. Blood pressure managementNICE Clinical Guideline 87; May 2009 • Targets • If kidney, eye or cerebrovascular damage, set a target <130/80mmHg • Others, set a target , 140/80mmHg • If on antihypertensive therapy at diagnosis of diabetes • Review BP control and medication use • Make changes only if BP is poorly controlled or current medications are inappropriate because of microvascular complications or metabolic problems • If the person’s BP reaches and consistently remains at the target • Monitor every 4-6 months and check for possible adverse effects of antihypertensive therapy (including those from unnecessarily low BP) • Measure BP annually if not hypertensive or with renal disease • If BP > target, repeat measurements within: • 1 month if > 150/90mmHg • 2 months if > 140/80mmHg • 2 months if > 130/80mmHg and kidney, eye or cerebrovascular damage

    25. Summary of BP management • BP control is very important in patients with type 2 diabetes • Before starting drug therapy • Use immaculate technique and do at least two readings on each of three different occasions • Drug treatment • In general ACE inhibitors are 1st line, with CCBs or thiazides 2nd line • Think about switching drug classes if no response • No robust evidence that A2RB are superior to ACE inhibitors • No evidence to suggest increased effectiveness with ACE plus A2RB • Treat the patient, not the BP • Compliance is critical – a drug not taken will not work • Weigh potential benefits to be gained from decreasing BP further against the acceptability to the patient of aggressive therapy with multiple drugs

    26. Assessing cardiovascular risk

    27. What about assessing CV risk?NICE Clinical Guideline 87; May 2009 • NICE recommends annual review of CV risk: • Assess risk factors • Note changes in personal or family history • Perform a full lipid profile • Consider to be at high CV risk unless all of the following apply: • Not overweight • Normotensive • No microalbuminuria • Non-smoker • No high-risk lipid profile • No history of CV disease • No family history of CV disease

    28. Blood lipids

    29. Management of blood lipids (1)NICE Clinical Guideline 87; May 2009 • Offer simvastatin 40mg or a statin of similar efficacy or cost • Give to those: • Aged 40+ and normal to high CV risk with type 2 diabetes • Aged 40+ and low CV risk with type 2 diabetes but CV risk >20% risk when assessed using UKPDS risk engine • Aged <40 and poor CV risk factor profile • Assess lipid profile and modifiable risk factors 1-3 months after starting therapy. Continue to monitor annually • Do not use in women who may become pregnant unless issues discussed and agreement reached

    30. Management of blood lipids (2)NICE Clinical Guideline 87; May 2009 • Increase to simvastatin 80mg unless TC <4.0mmol/l or LDL <2.0mmol/l • If there is existing or newly diagnosed CV disease or increased albumin excretion rate consider intensifying therapy with or more effective statin or ezetimibe to achieve a TC <4.0mmol/l or LDL <2.0mmol/l

    31. NICE guidance comparedNICE Diabetes CG 87, May 2009NICE Lipids CG 67, May 2008

    32. Lipid modification in T2DMSummary • Lipid modification is very important • Baseline risk is the key to the size of absolute benefits • Most patients should be on a statin • Simvastatin 40mg is first line • Increase to 80mg if TC >4mmol/l and also LDL >2mmol/l • If existing or newly diagnosed CV disease or increased albumin excretion rate consider intensifying therapy (with more effective statin or ezetimibe (if primary hypercholesterolaemia) to achieve TC <4mmol/l or LDL <2mmol/l • NICE recommends fibrates only in particular circumstances

    33. Aspirin

    34. Anti-thrombotic therapyNICE Clinical Guideline 87; May 2009 • NICE says offer aspirin 75mg daily: • To a person who is ≥ 50 years if BP is <145/90mmHg • To a person <50 years and has significant other risk factors (features of metabolic syndrome, strong early FH of CV disease, smoking, hypertension, microalbuminuria) • MRHA advice: • Aspirin is not licensed for the primary prevention of vascular events. If used the balance of benefits and risks should be considered for each individual, particularly the presence of risk factors for vascular disease (including conditions such as diabetes) and the risk of GI bleeding

    35. AspirinSummary • Aspirin should still be offered to patients with diabetes and evidence of CV disease ie for secondary prevention of CV events • In primary prevention a more individualised approach should be adopted as the presence of personal risk factors may change the risk : benefit profile • Aspirin is not licensed for primary prevention

    36. Control blood glucose

    37. What does NICE say?NICE Clinical Guideline 87; May 2009 • Setting a target HbA1c • Involve the patient in decision making • Encourage the patient to maintain their individual target unless the resulting side effects or efforts to achieve this impair their quality of life • Offer therapy (lifestyle and medication) to help achieve and maintain the target level • Inform the patient with a higher HbA1c that any reduction is advantageous to future health • Avoid pursuing highly intensive management plans to level of < 6.5%

    38. What does NICE say?NICE Clinical Guideline 87; May 2009 • Levels of HbA1c for addition of extra glucose lowering drugs • 6.5% (or other higher level) for people on one oral glucose lowering drug • 7.5% (or other higher level) for people on two or more oral glucose lowering drugs or insulin

    39. Intensive blood glucose control has benefits but also harms • Reduction in CHD and CVD risk, but no reduction in mortality • Recent studies show mixed results on microvascular endpoints • Increased risk of severe hypoglycaemia • ACCORD: intensive therapy associated with increased risk of death • Other interventions to reduce CV risk (smoking cessation, exercise, losing weight, controlling BP, lowering cholesterol, taking metformin) may have more benefit overall • The Goldilocks effect • Observational study identified that HbA1c of about 7.5% is associated with lowest risk of all-cause mortality (increase above or decrease below) is associated with greater risk

    40. Drug treatment for blood glucose control

    41. Hypoglycaemic drugs used in type 2 diabetesBNF 60, September 2010

    42. Drug treatment for blood glucose controlBased on NICE Clinical Guideline 87; May 2009

    43. What does the NICE guideline say (1)NICE Clinical Guideline 87; May 2009MeReC Rapid review No. 355 • Same levels of HbA1c for addition of extra glucose lowering drugs • 6.5% (or other higher level) for people on one oral glucose lowering drug • 7.5% (or other higher level) for people on two or more oral glucose lowering drugs or insulin • Metformin still first line hypoglycaemic drug • Sulphonylurea is an option if: • Patient is not overweight • A rapid therapeutic response is required • Metformin is contraindicated / not tolerated • If blood glucose control is inadequate on monotherapy dual therapy with metformin and a sulphonylurea remains the usual second line therapy • Rapid acting insulin secretagogues (rapaglinide and nateglinide) still only recommended as a consideration for people with erratic lifestyles • Other alternatives may be considered in particular patient circumstances

    44. What does the NICE guideline say (2)NICE Clinical Guideline 87; May 2009MeReC Rapid review No. 355 • Glitazones (and gliptins) can be considered for dual therapy with either metformin or sulphonylurea • Pioglitazone, sitagliptin or vildagliptin should be continued only if the person has a beneficial metabolic response (reduction of at least 0.5% in HbA1c in 6 months) • Which to choose? • Gliptin may be preferred if further weight gain would be a significant problem • Glitazone may be preferred if a person has marked insulin insensitivity

    45. What does the NICE guideline say (3)NICE Clinical Guideline 87; May 2009MeReC Rapid review No. 355 • Normal third line option is insulin in addition to metformin and a sulphonylurea • Intermediate acting human isophane insulin (human NPH insulin) remains preferred basal insulin taken at bedtime or twice daily according to need • Combining pioglitazone with insulin can be considered in a person with previous marked glucose lowering response to glitazone, or person on high-dose insulin whose blood glucose is inadequately controlled

    46. What does the NICE guideline say (4)NICE Clinical Guideline 87; May 2009MeReC Rapid review No. 355 • What are the alternatives to insulin? • Sitagliptin or glitazones can be considered for triple therapy with metformin and SU instead of insulin if insulin is unacceptable / inappropriate because of: • Employment • Social issues related to hypoglycaemia • Injection anxieties • Other personal issues • obesity • Exenatide can be used for triple therapy in addition to metformin and SU if • BMI ≥ 35kg/m² in people of European descent and specific psychological / medical problems associated with high body weight • BMI < 35kg/m² and insulin would have significant occupational implications or weight loss would benefit other significant obesity related comorbidities • Exenatide should be continued only if the person has a beneficial metabolic response (reduction of at least 1% in HbA1c and a body weight loss of at least 3% of initial body weight at 6 months)

    47. Established oral hypoglycaemics Metformin Sulphonylureas

    48. Step up dose of metformin to minimise GI side effects; consider trial of MR metformin if tolerability prevents continuation • Review metformin if serum creatinine > 130 or eGFR <45 • Stop metformin if serum creatinine >150 or eGFR <30

    49. Newer agents Glitazones Gliptins GLP-1 mimetics

    50. How do the newer drugs compare?NICE Clinical Guideline 66; May 2008NICE Clinical Guideline 87; May 2009