Diabetes Complication

Diabeticretinopathy

Leading causeof blindnessin working-ageadults1

Diabeticnephropathy

Leading cause of end-stage renal disease2

Cardiovasculardisease

Stroke

1.2- to 1.8-fold increase in stroke3

Diabeticneuropathy

Leading cause of non-traumatic lower extremity amputations5

75% diabetic patients die from CV events4

1Fong 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)Diabetic ketoacidosis (DKA)– Hyperglycemic hyperosmolar nonketotic stateHyperglycemic hyperosmolar nonketotic state (HHS) (HHS)

• Chronic complications– NeuropathyNeuropathy– MicroangiopathyMicroangiopathy

• RetinopathyRetinopathy • NephropathyNephropathy • Foot ischemiaFoot ischemia

– Macroangiopathy – AtherosclerosisMacroangiopathy – Atherosclerosis

Risk of cardiovascular death in type 1 diabetics vs. Risk of cardiovascular death in type 1 diabetics vs. NondiabeticsNondiabetics : : >5X higher in males, 7X higher in >5X higher in males, 7X higher in femalesfemales

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

Hyperglycemia Tissue damage

*Repeated acute changes in cellular metabolism

**Cumulative long term changes in stable macromolecules

Genetic susceptibility

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.

• 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 diseaseIschemic heart disease– Cerebrovascular diseaseCerebrovascular disease– Peripheral vascular diseasePeripheral vascular disease

Macrovascular Complications(2)

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 HDL-C, 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 diabetes1441 patients, type 1 diabetes– Randomized to intensive Randomized to intensive

glycemic control vs. glycemic control vs. conventional therapyconventional therapy

– Monitored prospectively for 6.5 Monitored prospectively for 6.5 yearsyears

– Results:Results:• Less retinopathy by 50%Less retinopathy by 50%

• Macrovascular complications: Macrovascular complications: 41% reduction (not statistically 41% reduction (not statistically significant)significant)

• -small number of events in -small number of events in young patient cohortyoung patient cohort

UKPDS:– 3867 patients with newly 3867 patients with newly

diagnosed type 2 DMdiagnosed type 2 DM– Intensive vs. Intensive vs.

Conventional therapyConventional therapy– 10 year follow-up10 year follow-up– Microvascular endpoints Microvascular endpoints

improvedimproved– Trend only towards Trend only towards

reduced incidence of MI ( reduced incidence of MI ( p=0.052)p=0.052)

Effect of Hypertension

Mortality vs systolic blood pressure

0

10

20

30

40

50

60

70

110 120 130 140 150 160

Systolic Blood pressure (mmHg)

Te

n Y

ea

r M

orta

lity

(p

er 1

000)

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%

UKPDS BMJ 1998;317:703 - 713

Hypertension in Type 1 and 2 Diabetes

• Type 1– Develop after several years of DMDevelop after several years of DM, u, ultimately affects ltimately affects ~30% of ~30% of

patientspatients– Secondary toSecondary to nephropathynephropathy, a, activation of the RAASctivation of the RAAS

• Type 2– Mostly present at diagnosisMostly present at diagnosis, a, affects at least 60% of patientsffects at least 60% of patients– HyperinsulinemiaHyperinsulinemia, s, secondary to insulin resistanceecondary to insulin resistance– Activation of the sympathetic nervous systemActivation of the sympathetic nervous system

• Lower target for diabetic patients than non-diabetic patients: 130/85

UKPDS 38. BMJ 1998;317:703-713

HOT. Lancet 1998;351:1755-1762

Effect of Cholesterol

Serum cholesterol vs Mortality

010203040506070

4 5 6 7

s-Cholesterol (mmol/L)

Te

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r M

ort

alit

y (

pe

r 1

00

0)

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 collectio

n(mg/24h)

Timed collectio

n(mg/min)

Spot collectio

n(mg/mg creat)

Normal 30 20 30

Microalbuminuria

30 - 299 20 - 199 30 - 299

Albuminuria 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 radiculo-neuropathy)

Screening for Neuropathy

• 128 Hz tuning fork for testing of vibration perception

• 10g Semmers monofilament

The main reason is toidentify patients at riskfor development ofdiabetic 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

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Acute Complications of Diabetes

DKADKA

HHNKHHNK

HypoglycemiaHypoglycemia

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• Diabetic Ketoacidosis• Most serious complication in Type 1 diabetes• Precipitating Causes

– Not enough insulinNot enough insulin– Skipping insulinSkipping insulin– Stress, traumaStress, trauma– Insulin resistanceInsulin resistance

• Ketosis• Dehydration• Electrolyte imbalance

Diabetic Keto-Acidosis

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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

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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HHNKHyperglycemic 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 hyperglycemiaSevere hyperglycemia– No or slight ketosisNo or slight ketosis– Profound dehydrationProfound dehydration– HyperosmolalityHyperosmolality

• Treatment– Similar to DKASimilar to DKA– More agresive fluid replacementMore agresive fluid replacement– Find underlying causeFind underlying cause

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Hypoglycemia

• Also known as insulin reaction or hypoglycemic reaction

• Risk Factors– Overdose of insulinOverdose of insulin– Omitting a mealOmitting a meal– OverexertionOverexertion– Nausea and vomitingNausea and vomiting– Alcohol intakeAlcohol intake

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Symptoms of Hypoglycemia

• Adrenergic– ShakinessShakiness– IrritabilityIrritability– NervousnessNervousness– TachycardiaTachycardia– TremorTremor– HungerHunger– DiaphoresisDiaphoresis– PallorPallor– ParesthesiasParesthesias

• Neuroglycopenic– HeadacheHeadache– Mental illnessMental illness– Inability to concentrateInability to concentrate– Slurred speechSlurred speech– Blurred visionBlurred vision– ConfusionConfusion– Irrational behaviorIrrational behavior– LethargyLethargy– LOC, coma, seizureLOC, coma, seizure

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Interventions

• Mild– carbohydrate 10-15 gramcarbohydrate 10-15 gram

• Moderate– 20-30 gram of carbs20-30 gram of carbs– Glucagon, 1 mg SC or IMGlucagon, 1 mg SC or IM

• Severe– 50% dextrose 25 g IV50% dextrose 25 g IV– Glucagon 1 mg IM or IVGlucagon 1 mg IM or IV

• 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 atlanto-

occipital 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

Do’s and Don'ts of foot care

Patient should – check feet dailycheck feet daily– Wash feet dailyWash feet daily– Keep toenails shortKeep toenails short– Protect feetProtect feet– Always wear shoesAlways wear shoes– Look inside shoes before Look inside shoes before

putting them onputting them on– Always wear socksAlways wear socks– Break in new shoes graduallyBreak 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