Complications of diabetes mellitus Ceri Jones Cwm Taf University LHB 2014

Complications of diabetes mellitus Chronic complications: Microvascular Neuropathies Nephropathies Retinopathies Macrovascular complications Myocardial infarctions Cerebrovascular accidents Peripheral vascular disease

Aim & Objectives Understand the micro & macrovascular complications of diabetes Understand the factors, interventions and therapies which can prevent or delay the onset of complications Be able to advise people with diabetes on self-care strategies to prevent and manage macrovascular complications

Facing Facts: The burden of diabetes complications Diabetes is a progressive disease; many present with complications on diagnosis Complications can have devastating effects on individuals lives: human costs shortened life expectancy Healthcare costs for diabetes, account for 9% of total healthcare expenditure

NSF for Diabetes Standard 10 Regular surveillance for the long term complications of diabetes Standard 11 Agreed protocols and systems of care Standard 12 All people with diabetes requiring multi agency support will receive integrated health and social care

Why do Problems Occur? Long term exposure to hyperglycaemia leads to: Vessel closure (full or partial) – supply of oxygen and nutrients are decreased Vessel permeability – damaged vessels dilate and leak unwanted substances Diabetes risk factors for complications: Hyperglycaemia Hypertension Dyslipidaemia Smoking

Macrovascular Complications - Risk Factors Type 2 diabetes is a strong risk factor for CV disease in both men and women Risk of atherosclerotic cardiovascular disease is 2-4 times higher for those with Type 2 diabetes compared to non diabetic population CHD is the principle cause of death in people with diabetes Normal protection afforded to pre-menopausal women is negated by diabetes People with diabetes have the same risk as those without diabetes but who have had an MI

Acute Myocardial Infarction People with type 2 diabetes have the same risk of an MI as people without diabetes who have already had an MI Immediate and later mortality rates following MI are high in people with Type 2 diabetes MIs may be silent in people with diabetes or symptoms may be atypical

Cerebrovascular Events No long term studies on stroke management to date General consensus is to treat all vascular risk factors aggressively ACEi Statins Aspirin

Evidence for Primary Prevention of Strokes

Peripheral Vascular Disease Approx 20% of people with PVD will die within 2 yrs of symptoms Generally PVD is asymptomatic until arterial stenosis occurs Symptoms include: Intermittent claudication Rest pain Buttock pain Management: Aspirin Vasodilating agents Reconstructive surgery Angioplasty Amputation & rehabilitation & foot care

Aspirin For Secondary Prevention People with cardiovascular disease 75 mg once daily For Primary Prevention British Hypertension Society recommends aspirin 75 mg once daily for those aged 50 and over, with Type 2 diabetes, with a blood pressure controlled to <150/90 mmHg (NICE suggest <145 systolic). All people with a 10 year risk >15% to be prescribed aspirin - according to precautions and contra- indications in British National Formulary.

Microvascular Complications Nephropathy Neuropathy Retinopathy

Diabetic retinopathy A silent complication with no initial symptoms When symptoms occur, treatment is more complicated and often impossible Screening for retinopathy is of the utmost importance

When to screen for retinopathy Type 1 diabetes: within 5 years of diagnosis Type 2 diabetes: at time of diagnosis Thereafter, every 1 to 2 years, depending on the status of the retina

Diabetic eye disease Blurred vision: common symptom of hyperglycaemia Epidemiology: any retinopathy: 21-36% vision-threatening retinopathy: 6-13%

Risk factors Poor glycaemic control Long duration Hypertension Dyslipidemia Nephropathy Pregnancy

Intensive therapy DCCT – type 1 diabetes: Primary prevention cohort: reduced risk of developing retinopathy by 76% Secondary intervention cohort: reduced risk of progression of retinopathy by 54% DCCT 1993

Treatment Blood pressure: reduces macular oedema Blood glucose control: slows progression Control lipids Use of aspirin

Treatment Laser therapy: Pan-retinal for proliferative retinopathy Focal or grid for macular oedema

Laser therapy Side effects Loss of peripheral vision, tunnel vision, night blindness Colour blindness Vision can get worse but “laser saves sight” in long term

Summary 100% of people with diabetes will develop some retinopathy The higher the blood glucose level the greater the risk Different grades of retinopathy Laser therapy saves sight Timely treatment is most effective Regular screening is a must

Diabetic nephropathy About 20% to 30% of people with diabetes In type 2 diabetes, a smaller fraction of these progress to CKD People with type 2 diabetes – over half of those with diabetes starting on dialysis

Risk factors Poor glycaemic control Hyperlipidaemia Hypertension Genetic predisposition Glomerular hyper-filtration during early period Ethnicity Long disease duration Smoking

Type 1 diabetes Decreasing incidence over past 35 years Overall incidence 2.2% at 20 years duration 7.8% at 30 years duration Finne 2005

Microalbuminuria (incipient diabetic nephropathy) Acute renal hypertrophy-hyperfunction Normoalbuminuria Proteinuria (clinical overt diabetic nephropathy) Chronic renal failure 10 to 15 years Natural history of diabetic nephropathy

Diabetic renal assessment Urinalysis for proteinuria Spot urine for microalbuminuria morning and resting or preferably with albumin/creatinine ratio (normal <2.5 mg/mmol in men and <3.5 mg/mmol in women) Serum creatinine; preferably with adjustment of body size Estimated glomerular filtration rate Repeat the tests at about yearly intervals if normal If GFR <60 ml/min test 3-6 monthly

Microalbuminuria Type 1 diabetes indicates incipient nephropathy Type 2 diabetes marker of increased cardiovascular morbidity and mortality Presence of microalbuminuria is an indication for screening of vascular disease and intensive intervention

Interventions: glycaemic control Diabetes Control and Complications Trial (DCCT)  occurrence of microalbuminuria by 40%  occurrence of macroalbuminuria by 50% United Kingdom Prospective Diabetes Study (UKPDS)  overall microvascular complication rate by 25%

Diabetic nephropathy Treatment intensive treatment of blood pressure target <130/80 mmHg reduce salt in diet reduce alcohol Sacks, 2001

Management of people with elevated creatinine Caution should be taken when using the following: metformin non-steroidal anti-inflammatory drugs glibenclamide radiographic contrast

Management of people with elevated creatinine Insulin dosage may need adjustment due to change in insulin half life and dialysis Anaemia is common and may need treatment – measure haemoglobin every 6 months if eGFR is <60 ml/min/1.73 m 2 Refer to nephrologist when eGFR <30 ml/min/1.73m 2

Estimated Glomerular Filtration Rate (eGFR) May underestimate actual renal function especially in women, the young and the obese More accurate in lower ranges <60 ml/min If eGFR is <60 ml/min, 30% risk of CVD Most common cause of death in CKD is cardiac arrest (22%)

Summary Diabetes is a common cause of CKD Various grades of nephropathy The higher the A 1c the higher the risk Control matters Blood pressure

Diabetic foot disease – the high-risk foot Peripheral vascular disease Peripheral neuropathy Peripheral neuropathy and peripheral vascular disease

Some statistics Half of all limb amputations are caused by diabetes Risk is 40 times increased in diabetes 70% of people die five years following an amputation Foot problems account for 40% of healthcare resources in developing countries; 15% in developed countries

Some statistics 85% of all amputations begin with an ulcer 49-85% of amputations can be prevented

Peripheral neuropathy – sensory motor Most common form of neuropathy Affects approximately 50% after 15 years Affects long nerves (feet and legs) first glove and stocking distribution Bilateral Equal symptoms in both limbs

Diabetic peripheral neuropathy – risk factors Poor glycaemic control Long duration Age Height Excessive alcohol

Nerve damage – neuropathy Symptoms: burning pins and needles pain No symptoms

Painless nature of diabetic foot disease

Sensory nerve damage

Motor nerve damage

Autonomic nerve damage

Take off the shoes!

Diabetic peripheral neuropathy screening tests Test sensation Biothesiometer Tuning fork 10 gm monofilament Ankle reflexes

Assessment of high risk characteristics

Peripheral vascular disease Symptoms Intermittent claudication Rest pain No symptoms Inactivity Neuropathy

Signs of vascular disease Diminished or absent pedal pulses Coolness of the feet and toes Poor skin and nails Absence of hair on feet and legs

Vascular assessment Palpation of foot pulses Dorsalis pedis (10% absent due to anatomical reasons) Tibialis posterior

Peripheral vascular disease non-invasive evaluation Methods Doppler pressure studies (ABI) Duplex arterial imaging Rationale Identify and confirm presence of disease Predict healing of ulcers or determine need for early surgical intervention

Peripheral vascular disease Treatment Quit smoking Walk through pain Surgical intervention

Cause of diabetic amputation Pecararo Trauma Ulcer Failure to heal Infection Amputation Neuropathy or vascular disease

An amputation every 30 seconds due to diabetes

Modifiable Risk Factors Hyperglycaemia Hypertension Dyslipidaemia Smoking Excess visceral adiposity Lifestyle

Why Treat to Target? Many people with Type 2 diabetes have both microvascular and macrovascular complications (1) UKPDS showed that treating to target levels helped reduce the complications of Type 2 diabetes (2,3) HbA1c and blood pressure are modifiable cardiovascular risk factors in Type 2 diabetes (2,3) Treating to target levels reduces complications and reduces the burden of Type 2 diabetes (2,3) Each 1% reduction in HbA1c for 10 years was associated with 37% reduction in microvascular problems. 1.UKPDS 6. Diabetes Research 1990;13:1–11 2. UKPDS 33. Lancet1998;352:837–835. 3, UKPDS 38. BMJ 1998;317:703–713

UKPDS The risk of each of the macrovascular and microvascular complications in type 2 diabetes was strongly associated with hyperglycaemia, as measured by HbA1c. Good glycaemic control reduces the risk of complications.

DCCT This landmark diabetes study established that good control prevents and delays the progression of chronic complications in people with type 1 diabetes. Retinopathy and nephropathy (urine albumin excretion) were reduced by 35-75% in the group with tight control. In those with initial early retinopathy, risk of progression reduced by about 50%. The tight control group experienced 3x more severe hypos than the control group.

Conclusion Macrovascular complications of diabetes can have a profound and devastating affect on the quality of life and life expectancy of people with diabetes. Many factors, interventions and therapies which can prevent or delay the onset of complications are available. Ongoing and new research strive to reach more positive outcomes for people with diabetes. As healthcare professionals our roles are to advise people with diabetes on self-care strategies to prevent and manage macrovascular complications.