Diabetes Complication

Diabetic retinopathy

Stroke

Leading cause of blindness in working-age adults1

1.2- to 1.8-fold increase in stroke3

Cardiovascular disease 75% diabetic patients die from CV events4

Diabetic neuropathy
Leading cause of non-traumatic lower extremity amputations5

Diabetic nephropathy
Leading cause of end-stage renal disease2

1Fong

DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99S102. 2Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94S98. 3Kannel WB, et al. Am Heart J 1990;120:672676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78S79.

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

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 terms 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
70

Ten Year Mortality (per 1000)

60 50 40 30 20 10 0 110 120 130 140 150 160 Systolic Blood pressure (mmHg) Non-diabetic Diabetic

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
Serum cholesterol vs Mortality
Ten Year Mortality (per 1000)
70 60 50 40 30 20 10 0 4 5 6 7 s-Cholesterol (mmol/L)

Non-diabetic Diabetic

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
Albuminuri a Overt

30 - 299
300

20 - 199

30 - 299
300

200

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 supported 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

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Symptoms of DKA
Abdominal pain Anorexia Dehydration Fuity breath Kussmauls Change LOC Hypotension N&V

Polyuria Somnolence Tachycardia Thirst Visual disturbances Warm, dry skin Weakness Wt. loss
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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
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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
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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 joint syndrome- prayer sign and atlantooccipital joint 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

Dos 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