Diabetes Complication Lecture.ppt 3h4q3h

Diabetes Complication

Diabetic retinopathy

Leading cause of blindness in working-age adults1

1Fong

Stroke

1.2- to 1.8-fold increase in stroke3

Cardiovascular disease 75% diabetic patients die from CV events4

Diabetic nephropathy

Diabetic neuropathy

Leading cause of end-stage renal disease2

Leading cause of non-traumatic lower extremity amputations5

DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94–S98. 3Kannel WB, et al. Am Heart J 1990;120:672–676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78–S79.

Complication of insulin deficiency • Hyperglycemic emergencies – Diabetic ketoacidosis (DKA) – Hyperglycemic hyperosmolar nonketotic state (HHS) • Chronic complications – Neuropathy – Microangiopathy • • •

Retinopathy Nephropathy Foot ischemia

Macroangiopathy – Atherosclerosis Risk of cardiovascular death in type 1 diabetics vs. Nondiabetics : >5X higher in males, 7X higher in females

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Complication of insulin excess • Hypoglycemia : Activation of the sympathetic nervous system (diaphoresis, tremulousness and tachycardia) and insufficient delivery of oxygen to the brain (confusion, seizures and unconsciousness

Diabetes Complications • • • •

Macro vascular Micro vascular Neuropathy Infections

Mechanisms Genetic susceptibility

*Repeated acute changes in cellular metabolism

Hyperglycemia

Tissue damage

**Cumulative long term changes in stable macromolecules

Independent accelerating factors

Macro vascular Complications

Macrovascular Complications(1) • Have a 2 to 6 times higher risk for development of these complications than the general population • The major cardiovascular risk factors in the non-diabetic population (smoking, hypertension and hyperlipidemia) also operate in diabetes, but the risks are enhanced in the presence of diabetes. • Overall life expectancy in diabetic patients is 7 to 10 years shorter than non-diabetic people.

Macrovascular Complications(2) • Once clinical macro-vascular disease develops  poorer prognosis for survival than normoglycemic patients with macrovascular disease • The protective effect females have for the development of vascular disease are lost in diabetic females • Clinical manifestation : – Ischemic heart disease – Cerebrovascular disease – Peripheral vascular disease

CAD Morbidity and Mortality in Type 2 DM • Framingham Data: 20 year follow-up:Age 45-74: – 2-3 fold increase in clinically evident atherosclerotic disease in diabetics – women diabetics=male diabetics in of CAD mortality

• Multiple Risk Factor Intervention Trial (MRFIT) – 5000 men with type 2 DM – Followed for 12 years – Men with type 2 DM had absolute risk of CAD-related death 3 times higher than non-diabetic cohort

Risk Factor Clustering in Diabetes • Type 2 Diabetes at Diagnosis: – 50% have hypertension – 30% have dyslipidemia

• UKPDS: – Prospective study – Newly detected type 2 DM: • 335 with CAD, 8 year follow-up

– Associated with elevated LDL-C, low levels of HDLC, systolic hypertension

Risk of MI in Diabetes

Haffner, SM et al NEJM: 339: 229-234

Glycemic Control to Reduce CAD DCCT trial: – 1441 patients, type 1 diabetes – Randomized to intensive glycemic control vs. conventional therapy – Monitored prospectively for 6.5 years – Results: • Less retinopathy by 50% • Macrovascular complications: 41% reduction (not statistically significant) • -small number of events in young patient cohort

UKPDS: – 3867 patients with newly diagnosed type 2 DM – Intensive vs. Conventional therapy – 10 year follow-up – Microvascular endpoints improved – Trend only towards reduced incidence of MI ( p=0.052)

Effect of Hypertension Mortality vs systolic blood pressure

Ten Year Mortality (per 1000)

70 60 50 40

Non-diabetic Diabetic

30 20 10 0 110 120 130 140 150 160 Systolic Blood pressure (mmHg)

Benefits of hypertension treatment in DM Treating hypertension can reduce the risk of: Death 32% Microvascular disease 37% Stroke 44% Heart failure 56%

Hypertension in Type 1 and 2 Diabetes • Type 1 – Develop after several years of DM, ultimately affects ~30% of patients – Secondary to nephropathy, activation of the RAAS

• Type 2 – Mostly present at diagnosis, affects at least 60% of patients – Hyperinsulinemia, secondary to insulin resistance – Activation of the sympathetic nervous system

• Lower target for diabetic patients than nondiabetic patients: 130/85 UKPDS 38. BMJ 1998;317:703-713 HOT. Lancet 1998;351:1755-1762

Effect of Cholesterol

Ten Year Mortality (per 1000)

Serum cholesterol vs Mortality 70 60 50 40 30 20 10 0

Non-diabetic Diabetic

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5

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s-Cholesterol (mmol/L)

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Dyslipidaemia in DM • Most common abnormality is  s HDL and  s Triglyserides • A low HDL is the most constant predictor of CV disease in DM • Target lipid values: LDL <2.6 mmol/l, HDL >1.15 mmol/l, TG < 2.5 mmol/l

Micro vascular Complications

Eye Complications • Retinopathy (stages) – – – – –

Background Pre-proliferative Proliferative Advanced diabetic eye disease Maculopathy

• Glaucoma • Cataracts

Diabetic Retinopathy (DR) • DR is the leading cause of blindness in the working population of the Western world • The prevalence increase with the duration of the disease (few within 5 years, 80 – 100% will have some form of DR after 20 years) • Maculopathy is most common in type 2 patients and can cause severe visual loss

Pre-Proliferative Retinopathy • Rapid increase in amount of micro aneurisms • Multiple hemorrhages • Cotton wool spots (>5) • Venous beading, looping and duplication

Proliferative retinopathy

Proliferative Retinopathy • New vessels (on disc, elsewhere) • Fibrous proliferation (on disc, elsewhere) • Hemorrhages (preretinal, vitreous) Panretinal photo-coagulation

Diabetic Nephropathy (DN) • Diabetes has become the most common cause of end stage renal failure in the US and Europe • About 20 – 30% of patients with diabetes develop evidence of nephropathy • The prevalence of DN is higher in Black Americans than in Whites (Figures for South Africa is not available)

Stages of Diabetic Nephropathy

Stages of DN Stage I :  glomerular filtration and kidney hypertrophy Stage II : u-albumin excretion < 30mg/24h Stage III : Microalbuminuria (30 – 300 mg/24h) Stage IV : Overt nephropathy (> 300mg/24h, positive u dipstick) Stage V : ESRD characterized by  blood urea and creatinine levels, hyperkalaemia and fluid overload

Screening for Nephropathy • Type 1 Diabetes : begin with puberty, after 5 years duration of disease • Type 2 Diabetes : start screening at the diagnosis of diabetes • Annually, do one of the following: – – – –

u Albumin:Creatinine ratio (spot sample) 24h u Albumin excretion rate Early morning Albumin concentration (spot sample) Dipstick for Microalbuminuria

• Microalbuminuria with incipient nephropathy is diagnosed if 2 or more of the tests are within the microalbumin range

Microalbuminuria • Increased risk for overt nephropathy • Increased cardiovascular mortality • Increased risk of Retinopathy • Increased all-cause mortality

Microalbuminuria is an indication for screening for possible vascular disease and aggressive intervention to reduce all cardiovascular risk factors

Screening Tests for Microalbuminuria Category

24h u collection (mg/24h)

Timed collection (mg/min)

Spot collection (mg/mg creat)

Normal

 30

 20

 30

Microalbum inuria

30 - 299

20 - 199

30 - 299

Albuminuri a Overt

 300

 200

 300

Management of Nephropathy • Improvement of glycemic control • Treatment of hypertension • Treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonis (AIIRA) • Restriction of dietary intake of protein • Once persistent elevation in u-Albumin is found refer to a Internist or Nephrologist

Diabetic Neuropathy • Sensorimotor neuropathy (acute/chronic) • Autonomic neuropathy • Mononeuropathy – Spontaneous – Entrapment – External pressure palsies

• Proximal motor neuropathy

Sensorimotor Neuropathy • Patients may be asymptomatic / complain of numbness, paresthesias, allodynia or pain • Feet are mostly affected, hands are seldom affected • In Diabetic patients sensory neuropathy usually predominates

Complications of Sensorimotor neuropathy • • • •

Ulceration (painless) Neuropathic edema Charcot arthropathy Callosities

Autonomic Neuropathy • • • • • • • • •

Symptomatic Postural hypotension Gastroparesis Diabetic diarrhea Neuropathic bladder Erectile dysfunction Neuropathic edema Charcot arthropathy Gustatatory sweating

• • • •

Subclinical abnormalities Abnormal pupillary reflexes Esophageal dysfunction Abnormal cardiovascular reflexes • Blunted counter-regulatory responses to hypoglycemia • Increased peripheral blood flow

Entrapment Neuropathies • Carpal tunnel syndrome (median nerve) • Ulnar compression syndrome • Meralgia paresthetica (lat cut nerve to the thigh) • Lat Popliteal nerve compression (drop foot) • All the above are more common in diabetic patients

Mononeuropathies • Cranial nerve palsies (most common are n. IV,VI,VII)

Proximal Motor Neuropathy • Amyotrophy – most common proximal neuropathy, affects the Quadriceps muscles with weakness and atrophy (synonym: Diabetic Femoral radiculoneuropathy)

Screening for Neuropathy • 128 Hz tuning fork for testing of vibration perception • 10g Semmers monofilament The main reason is to identify patients at risk for development of diabetic foot

Using of the Monofilament

Management of Neuropathy • Burning pain – TADs / Capsaicin • Lancinating pain – Anticonvulsants / TAD / Capsaicin • Painful cramps – Quinidine sulphate • Restless legs - Clonazepam

Infections • The association between diabetes and increased susceptibility to infection in general is not ed by strong evidence • However, many specific infections are more common in diabetic patients and some occur almost exclusively in them • Other infections occur with increased severity and are associated with an increased risk of complications

Infections (cont) • Several aspects of immunity are altered in patients with diabetes • There is evidence that improving glycemic control patients improves immune function

Specific Infections • Community acquired pneumonia • Acute bacterial cystitis • Acute pyelonephritis • Emphysematous pyelonephritis • Perinephric abscess • Fungal cystitis

• Necrotizing fasciitis • Invasive otitis externa • Rhinocerebral mucormycosis • Emphysematous cholecystitis

Acute Complications of Diabetes DKA HHNK Hypoglycemia

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Diabetic Keto-Acidosis • Diabetic Ketoacidosis • Most serious complication in Type 1 diabetes • Precipitating Causes – – – –

Not enough insulin Skipping insulin Stress, trauma Insulin resistance

• Ketosis • Dehydration • Electrolyte imbalance 45

Symptoms of DKA • • • • • • • •

Abdominal pain Anorexia Dehydration Fuity breath Kussmaul’s Change LOC Hypotension N&V

• • • • •

Polyuria Somnolence Tachycardia Thirst Visual disturbances • Warm, dry skin • Weakness • Wt. loss 46

Assessment DKA • • • •

Hyperglycemia Hyperosmolality Dehydration Electrolyte imbalances • Metabolic acidosis • Hypoglycemia • Fluid overload

• • • • •

Rehydrate Reverse shock Give Potassium Corret pH Give insulin

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Treatment principle

• • • •

IV Fluids Potassium Replacement Correct pH Give Regular Insulin only – Initial bolus IV (0.15u/kg) – Then Regular Insulin IV drip

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HHNK Hyperglycemic Hyperosmolar Noketotic Syndrome

• Most commonly occurs in older adults with Type II diabetes • Always look for precipitating factors • Factors Associated with HHNK : Drugs, procedures, chronic illness, acute illness

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• Four Major Clinical Features – Severe hyperglycemia – No or slight ketosis – Profound dehydration – Hyperosmolality

• Treatment – Similar to DKA – More agresive fluid replacement – Find underlying cause 50

Hypoglycemia • Also known as insulin reaction or hypoglycemic reaction • Risk Factors – – – – –

Overdose of insulin Omitting a meal Overexertion Nausea and vomiting Alcohol intake

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Symptoms of Hypoglycemia • Adrenergic – – – – – – – – –

Shakiness Irritability Nervousness Tachycardia Tremor Hunger Diaphoresis Pallor Paresthesias

• Neuroglycopenic – – – – – – – – –

Headache Mental illness Inability to concentrate Slurred speech Blurred vision Confusion Irrational behavior Lethargy LOC, coma, seizure 52

Interventions • Mild – carbohydrate 10-15 gram

• Moderate – 20-30 gram of carbs – Glucagon, 1 mg SC or IM

• Severe – 50% dextrose 25 g IV – Glucagon 1 mg IM or IV

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• Retinopathy • microaneurysms cluster at macula->terminal vessels obstructed->ischemia->new vessel proliferation • Nephropathy-leads to hypertension. Assoc with the highest mortality. • Cardiovascular disease- “silent ischemia” • Peripheral neuropathy- numbness and tingling progressing to total insensitivity • Stiff t syndrome- “prayer sign” and atlantooccipital t involvement

• Autonomic nervous system dysfunction -orthostatic hypotension, resting tachycardia, absent beat-to-beat variation -hypogylcemic unawareness -gastroparesis occurs in 20-30%

DKA • Insulin transfers glucose and amino acids into the cells. • Hyperglycemia->osmotic diuresis>dehydration->acidosis. Also, a build up of amino acids in the blood->lipolysis->free fatty acids->converted to ketone bodies in the liver • Results in a intravascular fluid volume deficit of 5-8 liters, potassium deficit of 200-400 mEq, and NaCl deficit of 350-600 mEq

Treatment of DKA • Intubate for CNS depression • Regular insulin 10 units IVP followed by 5-10 units/hr IV • Normal saline 5-10 ml/kg/hr IV • Add 5% glucose when serum blood sugar<250 mg/dl • Potassium 0.3-0.5 mEq/kg/hr IV • Monitor blood sugar, potassium, arterial pH and urine ketones hourly • Identify cause (sepsis, MI, compliance)

HYPEROSMOLAR, HYPERGLYCEMIC NONKETOTIC COMA -elderly, insulin deficiency, renal insufficiency, thirst deficiency -sepsis, hyperalimentation or drugs (corticosteriods) -glucose >600 mg/dl -osmotic diuresis->hypokalemia and dehydration -serum osmolarity >350 mOsm/L -pH >7.3 -hypovolemia (severe, up to 25% total body water) -patients are insulin deficient but liver insulin levels sufficient for metabolism of free fatty acids->no ketosis -coma due to shrinkage of brain cells

Do’s and Don'ts of foot care Patient should – – – – – –

check feet daily Wash feet daily Keep toenails short Protect feet Always wear shoes Look inside shoes before putting them on – Always wear socks – Break in new shoes gradually

Conclusion • This is just an outline of the major diabetic complications, and doesn't aim to be comprehensive • All complications are preventable with good glycaemic control • The progression of most complications can be halted if detected early and appropriate therapy instituted