Acute Complication of DM by Dr Shahjada Selim

Dr Shahjada Selim Assistant Professor

Department of EndocrinologyBangabandhu Sheikh Mujib Medical University, Dhaka

Email: [email protected], [email protected]

COMPLICATIONS OFCOMPLICATIONS OFDIABETES MELLITUSDIABETES MELLITUS

mailto:[email protected]

mailto:[email protected]

According to on set:I.Acute Complications

A. HypoglycemiaB. Hyperglycemic emergencies

Complications of DiabetesComplications of Diabetes

TitleTitle

II. Chronic Complications of DiabetesA. Microvascular complications:

• Neuropathy, Nephropathy, Retinopathy B. Macrovascular complications:

• Coronary artery disease, peripheral vascular disease, stroke

According to on glycemiaI. Hypoglycemia II. Hyperglycemic Crisis

Complications of DiabetesComplications of Diabetes

DIABETES MELLITUSDIABETES MELLITUS

Hyperglycemic complications

Diabetic Ketoacidosis

(DKA)

Hyperosmolar Hyperglycemic State

(HHS)

DIABETIC KETOACIDOSIS (DKA)DIABETIC KETOACIDOSIS (DKA)

Too Much Insulin

Too Little Insulin, Illness or Stress

Definition: A life-threatening state that results from a relative or absolute deficiency of insulin

Hypoglycemia DKA


Definition: A life-threatening state that results from a relative or absolute deficiency of insulin.

INSULINSTRESS

HORMONES

Hypoglycemia Hyperglycemia & DKA

• Usually occurs in individuals with Type 1 diabetes.

• Insulin levels are very low.

• High levels of “stress hormones”: epinephrine, norepinephrine, growth hormone and cortisol.


PRECIPITATING FACTORS (VERY IMPORTANT):

INSULINSTRESS

HORMONES

Hypoglycemia Hyperglycemia & DKA

• Insufficient or no insulin.• Physical stress: dehydration, trauma.• Surgery, infections, heart attacks, etc.

BLOOD GLUCOSE

80-120 mg/dL

Diabetic Ketoacidosis:Diabetic Ketoacidosis:PathophysiologyPathophysiology

PANCREAS

Liver

FAT

MUSCLE

INSULIN

INSULIN

INSULIN-STIMULATED GLUCOSE TRANSPORT

HEPATIC GLUCOSE OUTPUT

INSULIN-MEDIATED INHIBITION OF

LIPOLYSIS


PANCREAS

Liver

FAT

MUSCLE

INSULIN

INSULIN

BLOOD GLUCOSE


INSULIN-STIMULATED GLUCOSE TRANSPORT


LIPOLYSIS

GLUCAGON


PANCREAS

Liver

FAT

MUSCLE

INSULINGLUCAGON

INSULIN

FREE FATTY ACIDS

(FFA)FREE AMINO ACIDS

BLOOD GLUCOSE


LIPOLYSIS


KETONESKETONES

EPINEPHRINE, NOREPINEPHRINE EPINEPHRINE-

STIMULATED MYOLYSIS

Diabetic Ketoacidosis:Diabetic Ketoacidosis:KetoacidsKetoacids

O=CCH3

CH2COO- O-C-H

CH3

CH2COO-

O=CCH3

CH3

HCO3-

NADH + H+ NAD

ACETOACETATE -HYDROXYBUTYRATE

Acetone Bicarbonate

Diabetic Ketoacidosis:Diabetic Ketoacidosis:Signs & SymptomsSigns & Symptoms

HYPERGLYCEMIA

KETONES

• Polyuria and polydipsia• Severe volume depletion• Electrolyte depletion • Eventual: renal hypoperfusion,

prerenal azotemia, hypotension and shock

• Acidosis• Compensatory resp. alkalosis• Hypotension• Shock

Diabetic Ketoacidosis:Diabetic Ketoacidosis:Clinical Course (Worst Case Scenario)Clinical Course (Worst Case Scenario)

“Doing Well” •Precipitating Event

•Polyuria, polydipsia, dehydration

•Anorexia, nausea, vomiting, abd. pain

• Kussmal respirations, “Juicy Fruit” Breath

•Altered consciousness

•Cardiovascular collapse

CLINICAL DETERIORATIONComa & Death

Diabetic Ketoacidosis:Diabetic Ketoacidosis:Effects on Mental StatusEffects on Mental Status

HYPEROSMOLALITYHYPOTENSION

ACIDOSIS

Factors leading to impairment of CNS function:

OUCH

ConsequencesConsequences

• The latter observation is annoying because it implies the following:

The late diagnosis of type 1 diabetes in many developing countries particularly in Africa.

The late presentation of DKA, which is associated with risk of morbidity & mortality

Death of young children with DKA undiagnosed or wrongly diagnosed as malaria or meningitis.

Diabetic Ketoacidosis:Diabetic Ketoacidosis:DiagnosisDiagnosis

DKADKA

Blood Glucose

“Gap”Metabolic Acidosis

Serum Ketones

The Diagnostic Triad of DKA:

Diabetic Ketoacidosis:Diabetic Ketoacidosis:DiagnosisDiagnosis

The “Anion Gap” represents the presence of unmeasured anions.

Na+

K+

Cl-

HCO3-

Anion Gap = Na+ - (Cl- + HCO3-)

(Normal = 12)

Organic acids, such as acetoacetate and -hydroxybutyrate, decrease the HCO3

- (which is a biologic buffer) and aren’t measured in the gap. Therefore, the gap increases.

Diagnosis of Diabetic KetoacidosisDiagnosis of Diabetic Ketoacidosis

Signs and symptoms of DKA may be accompanied by those of the underlying precipitating disorder;

HOWEVER,

DKA per se DOES NOT CAUSE FEVER.

Therefore, if a fever is present, assume there is an infection until

proven otherwise!!

DIAGNOSISDIAGNOSIS• You should suspect DKA if a diabetic

patient presents with: Dehydration. Acidotic (Kussmaul’s) breathing, with a

fruity smell (acetone). Abdominal pain &\or distension. Vomiting. An altered mental status ranging from

disorientation to coma.

The three major metabolic derangements in DKA are:

• Hyperglycemia• Ketosis• Metabolic acidosis

•The definitive diagnosis consists of hyperglycemia (blood glucose levels >16.6 mmo/L)•low bicarbonate (<15 mEq/L)•and low pH (<7.3)•with ketonemia (positive at 1:2 dilution) and moderate ketonuria.

Diagnosis

Hyperglycemia leads to osmotic diuresis, dehydration, and a critical loss of electrolytes.

Hyperosmolality of extracellular fluids from hyperglycemia leads to a shift of water and potassium from the intracellular to the extracellular compartment.

Extracellular sodium concentration frequently is low or normal despite enteric water losses because of the intracellular-extracellular fluid shift. This dilutional effect is referred to as pseudohyponatremia.

Serum potassium levels may be normal or elevated, despite total potassium depletion resulting from protracted polyuria and vomiting.

Metabolic acidosis is caused by the excess ketoacids that require buffering by bicarbonate ions; this leads to a marked decrease in serum bicarbonate levels.

ManagementManagement

The management steps of DKA includes:

Assessment of causes & sequele of DKA by taking

a short history & performing a scan examination.

Quick diagnosis of DKA at the ER.

Baseline investigations.

Treatment, Monitoring & avoiding complications.

Transition to outpatient management.

AssessmentAssessment History: Symptoms of hyperglycemia, precipitating factors,

diet and insulin dose. Examination: Look for signs of dehydration, acidosis,

electrolytes imbalance, including shock, hypotension, acidotic breathing, CNS status…etc. Look for signs of hidden infections (Fever strongly suggests infection) and If possible,

obtain accurate weight before starting treatment.

Quick DiagnosisQuick Diagnosis Known diabetic children confirm D hyperglycemia, K

ketonuria & A acidosis.Newly diagnosed diabetic children be careful not to

miss because it may mimic serious infections like meningitis.

Both Hyperglycemia (using glucometer) glycosuria, & ketonuria (with strips) must be done in the ER and treatment started, without waiting for Lab results which may be delayed.

Baseline InvestigationsBaseline Investigations The initial Lab evaluation includes: Plasma & urine levels of glucose & ketones. ABG, U&E (including Na, K, Ca, Mg, Cl, PO4,

HCO3), & arterial pH (with calculated anion gap).

Venous pH is as accurate as arterial (an error of 0.025 less than arterial pH)

Complete Blood Count with differential. Further tests e.g., cultures, X-rays…etc , are

done when needed.

Pitfalls in DKAPitfalls in DKA High WCC: may be seen in the absence of

infections. BUN: may be elevated with prerenal

azotemia secondary to dehydration. Creatinine: some assays may cross-react

with ketone bodies, so it may not reflect true renal function.

Serum Amylase: is often raised, & when there is abdominal pain, a diagnosis of pancreatitis may mistakenly be made.

TreatmentTreatment Principles of Treatment: Careful replacement of fluid deficits. Correction of acidosis & hyperglycemia via

Insulin administration. Correction of electrolytes imbalance. Treatment of underlying cause. Monitoring for complications of treatment. Manage DKA in the PICU. If not available it

can be managed in the special care room of the pediatric inpatient ward.

Fluids replacementFluids replacement Determine hydration status: A. Hypovolemic shock: administer 0.9% saline,

Ringer’s lactate or a plasma expander as a bolus dose of 20-30 ml/kg. This can be repeated if the state of shock persists. Once the patient is out of shock, you go to the 2nd step of management.

Fluids replacement/2Fluids replacement/2

B- Dehydration without shock:1. Administer 0.9% Saline 10 ml/kg/hour for an

initial hour, to restore blood volume and renal perfusion.

2. The remaining deficit should be added to the maintenance, & the total being replaced over 36-48 hours. To avoid rapid shifts in serum osmolality 0.9% Saline can be used for the initial 4-6 hours, followed by 0.45% saline.

Fluids replacement/3Fluids replacement/3• When serum glucose reaches 250mg/dl

change fluid to 5% dextrose with 0.45 saline, at a rate that allow complete restoration in 48 hours, & to maintain glucose at 150-250mg/dl.

• Pediatric saline 0.18% Na Cl should not be used even in young children.

Insulin TherapyInsulin Therapy start infusing regular insulin at a rate of

0.1U/kg/hour using a syringe pump. Optimally, serum glucose should decrease in a rate no faster than 100mg/dl/hour. If serum glucose falls < 200 prior to correction of acidosis, change IV fluid from D5 to D10, butdon’t decrease the rate of insulin infusion. The use of initial bolus of insulin (IV/IM) is

controversial.

Insulin Therapy/2Insulin Therapy/2

Continue the Insulin infusion until acidosis is cleared: pH > 7.3.

Bicarbonate > 15 mmol/l

Normal anion gap 10-12.

Correction of AcidosisCorrection of Acidosis• Insulin therapy stops lipolysis and

promotes the metabolism of ketone bodies. This together with correction of dehydration normalize the blood PH.

Bicarbonate therapy should not be used unless severe acidosis (pH<7.0) results in hemodynamic instability. If it must be given, it must infused slowly over several hours.

As acidosis is corrected, urine KB appear to rise. Urine KB are not of prognostic value in DKA.

Insulin Therapy/3Insulin Therapy/3 If no adequate settings (i.e. no infusion or

syringe pumps & no ICU care which is the usual situation in many developing countries) Give regular Insulin 0.1 U/kg/hour IM till acidosis disappears and blood glucose drops to <250 mg/dl, then us SC insulin in a dose of 0.25 U/kg every 4 hours.

When patient is out of DKA return to the previous insulin dose.

Correction of Electrolyte Correction of Electrolyte ImbalanceImbalance Regardless of K conc. at presentation, total

body K is low. So, as soon as the urine output is restored, potassium supplementation must be added to IV fluid at a conc. of 20-40 mmol/l, where 50% of it given as KCl, & the rest as potassium phosphate, this will provide phosphate for replacement, & avoids excess phosphate (may precipitate hypocalcaemia) & excess Cl (may precipitate cerebral edema or adds to acidosis).

PotassiumPotassium If K conc. < 2.5, administer 1mmol/kg of KCl in IV saline over 1 hour. Withhold Insulin until K conc. becomes> 2.5 and monitor K conc. hourly.If serum potassium is 6 or more, do not give

potassium till you check renal function and patients passes adequate urine.

MonitoringMonitoring

A flow chart must be used to monitor fluid balance & Lab measures. serum glucose must be measured hourly. electrolytes also 2-3 hourly. Ca, Mg, & phosphate must be measured

initially & at least once during therapy. Neurological & mental state must examined

frequently, & any complaints of headache or deterioration of mental status should prompt rapid evaluation for possible cerebral edema.

ComplicationsComplications Cerebral Edema Intracranial thrombosis or infarction. Acute tubular necrosis. peripheral edema.

Cerebral EdemaCerebral Edema

Clinically apparent Cerebral edema occurs in 1-2% of children with DKA. It is a serious complication with a mortality of > 70%. Only 15% recover without permanent damage.

Typically it takes place 6-10 hours after initiation of treatment, often following a period of clinical improvement.

Causes of Cerebral Edema Causes of Cerebral Edema

The mechanism of CE is not fully understood, but many factors have been implicated:

rapid and/or sharp decline in serum osmolality with treatment.

high initial corrected serum Na concentration. high initial serum glucose concentration. longer duration of symptoms prior to

initiation of treatment. younger age. failure of serum Na to raise as serum glucose

falls during treatment.

Presentations of C. EdemaPresentations of C. Edema

Cerebral Edema Presentations include:

deterioration of level of consciousness. lethargy & decrease in arousal. headache & pupillary changes. seizures & incontinence. bradycardia. & respiratory arrest when

brain stem herniation takes place.

Treatment of C. EdemaTreatment of C. Edema• Reduce IV fluids• Raise foot of Bed• IV Mannitol • Elective Ventilation• Dialysis if associated with fluid overload or

renal failure.• Use of IV dexamethasone is not

recommended.

Hyperosmolar Hyperglycemic State

• Less common than DKA• Seen in Type 2 DM• Age group is often older (>65 years)• Mortality 5-20%! • Often present with altered level of

consciousness due to hyperosmolar state (when sOsm > 300mosm/kg)

HHSHHS

• Hyperglycemia, hyper osmolality and dehydration without ketosis

• Most frequent precipitants: • Acute Stressors (5 I’s)• Renal Failure• Hyperglycemic inducing medications

Precipitating FactorsPrecipitating Factors

• Acute stressors or illness increase the secretion of glucagon, cortisol and epinephrine precipitating hyperglycemia

• 5 I’s: • Infection• Infarction• Insulin (compliance/omission)• Ischemia• Intoxication (alcohol, drug abuse)

Regulatory HormonesRegulatory Hormones

• 2 main hormones responsible to hyperglycemia and ketoacidosis• Insulin - deficiency or resistance• Glucagon - excess

Normal ResponseNormal Response

• Glucose is ingested during a meal, stimulates the release of Insulin from b-cells of the pancreas

• Insulin action is to restore normoglycemia:

• Decreasing hepatic glucose production• Inhibiting glycogenolysis and gluconeogensis• Increases the skeletal muscle and adipose tissue

uptake• Inhibits glucagon secretion and production

Treatment of Diabetic Ketoacidosis:Treatment of Diabetic Ketoacidosis:Don’t Let an Elevated KDon’t Let an Elevated K++ Fool You! Fool You!

MUSCLE

ACIDOSIS

H+

K+ K+

During acidosis, H+ shifts into cells to be buffered by intracellular buffers.

K+ shifts out of cells in exchange.

INSULIN Rx

Treatment with insulin causes K+ to shift back into cells, and serum K+

may drop like a rock during therapy.

K+

INSULIN

SERUM K+

Consequently, serum K+ may be elevated DESPITE total body K+ depletion .

SERUM K+

Bottom Line: “As soon as you see pee, give K+!

Treatment of Diabetic Ketoacidosis:Treatment of Diabetic Ketoacidosis:“Watch the Gap”“Watch the Gap”

O=C

CH3

CH2COO-O-C-H

CH3

CH2COO-

O=CCH3

CH3

HCO3-

NADH + H+ NAD


Acetone Bicarbonate

Acetone is produced during the normal regeneration of bicarbonate and is detected by most serum ketone assays. Therefore, the serum

ketones normally increase during recovery from DKA.

Treatment of Diabetic Ketoacidosis:Treatment of Diabetic Ketoacidosis:“Watch the Gap”“Watch the Gap”

O=C

CH3

CH2COO-O-C-H

CH3

CH2COO-

O=CCH3

CH3

HCO3-

NADH + H+ NAD


Acetone Bicarbonate

Acetone is produced during the normal regeneration of bicarbonate and is detected by most serum ketone assays. Therefore, the serum

ketones normally increase during recovery from DKA.

Therefore, during management of DKA, don’t watch the ketones; WATCH THE GAP!

IMPORTANT!

Treatment of Diabetic KetoacidosisTreatment of Diabetic Ketoacidosis

Finally,

Diagnose and treat the underlying precipitating

event!

DIABETES MELLITUSDIABETES MELLITUS

Acute Metabolic Complications

Diabetic Ketoacidosis(DKA)

Hyperosmolar Nonketotic Coma

(HONK)

Hyperosmolar Hyperglycemic State (HHS)Hyperosmolar Hyperglycemic State (HHS)

• Life-threatening metabolic disorder of extreme hyperglycemia without ketosis.

• Typically seen in elderly with type 2 diabetes, some of whom are previously not diagnosed with diabetes.

• Common precipitating events: myocardial infarction, stroke, sepsis.

• Potentially deadly: mortality may exceed 30-50%.

Hyperosmolar Hyperglycemic Hyperosmolar Hyperglycemic State (HHS)State (HHS)

Hyperosmolar Hyperglycemic State (HHS)Hyperosmolar Hyperglycemic State (HHS)

Relative Insulin Deficiency HYPERGLYCEMIA

THE VICIOUS

CYCLE OF HONK

POLYURIA

VOLUME DEPLETION

HEMO-CONCENTRATION

HHSHHSClinical AspectsClinical Aspects

Increasing volume depletion and hemoconcentration may result in:

• Hyperviscosity and increased risk of thrombosis. • Disturbed mentation. • Neurologic Signs:

i. Focal signs, e.g., sensory or motor deficits or focal seizures.

ii. Motor abnormalities, e.g., flaccidity, depressed reflexes, tremor or fasciculations.

• Ultimately, without Rx, coma and death.

HHSHHSTreatmentTreatment

• Volume correction with normal saline.• Replacement of electrolytes.• IV insulin.• Diagnosis and treatment of underlying cause.

Similar to the treatment of DKA:

• 50 year male diabetic using metformin 1000 mg since 8 year became drowsy. On examination his pulse 90 beats per minute BP 120/80, respiratory rate 50 per minute, chest clear. On investigation random blood sugar 300, blood urea 20 meg, ketone body in urine nil.

• What is your diagonosis?• Name 3 investigation with reasons • What is the treatment?

Diabetes MellitusDiabetes Mellitus

CHRONIC COMPLICATIONS:Microvascular and Macrovascular

Complications

Diabetes: Chronic ComplicationsDiabetes: Chronic Complications

Microvascular Complications

Diabetic Retinopathy

Diabetic NeuropathyDiabetic

Nephropathy

Diabetic RetinopathyDiabetic Retinopathy

Retinal Fundus Photographs

NORMAL RETINA

Retinal capillaries Macula

Optic nerveMacular edema

Exudates

Disease Progression

New Vessel Formation

PROLIFERATIVE RETINOPATHYNON-PROLIFERATIVE OR

“BACKGROUND”RETINOPATHY


EM Photograph of Plastic Cast of Retinal Capillaries from Diabetic Retina

Microaneurysms

Exudates • leakage of plasma proteins into neuroretina.

Later stages of retinopathy involve death of endothelial cells and capillary “drop out,” progressive ischemia and

proliferative neovascular changes.


Diabetic retinopathy is the leading cause of new adult

blindness in the United States.

Remember:

Diabetic NephropathyDiabetic Nephropathy

Diabetic glomerulosclerosis

Diabetic glomerulosclerosis is characterized by basement membrane thickening and mesangial cell proliferation.

Diabetic nephropathy may be diagnosed in its earliest--and potentially, reversible--stages by detection of extremely small

amounts of albumin in the urine, so-called “microalbumin.”

This is EXTREMELY

important!

Diabetic NephropathyDiabetic Nephropathy

Diabetic nephropathy is the leading cause of renal

failure requiring dialysis in the United States.

Remember:

DIABETIC NEUROPATHY:DIABETIC NEUROPATHY:Peripheral Sensory NeuropathyPeripheral Sensory Neuropathy

Diabetic Foot Ulcer

Diabetic “Charcot Feet”

Symmetrical neuropathy is the most common:• Primarily involving the distal extremities with

“stocking-glove” distribution.• Sensory: decreased vibration, temperature,

proprioception.• Initially may present with painful

paresthesias: “burning” or “pins-and-needles” sensation. Eventually leads to complete loss of sensation.

• Predisposed to skin breakdown and ulcer formation and unrecognized trauma.

DIABETIC NEUROPATHY:DIABETIC NEUROPATHY:Autonomic NeuropathyAutonomic Neuropathy

• Gastroparesis• Constipation or

Diarrhea

•Cardiac arrhythmias•Sudden Death

• Chronic edema• Postural

hypotension

•IMPOTENCE•Urinary retention

Diabetic NeuropathyDiabetic Neuropathy

Diabetes is the leading cause of non-traumatic

lower extremity amputations in the

United States.

Remember:

DIABETIC COMPLICATIONSDIABETIC COMPLICATIONS

MACROVASCULAR COMPLICATIONSGangrene is 14 times more common in people with diabetes

than those without.

Coronary Heart Disease:• Twice as common in people with diabetes.• Occurs at an earlier age and places women at equal risk

with men.• For MI’s: individuals with diabetes have a high initial

mortality rate and lower 5-year survival rate.• MI’s often occur WITHOUT CHEST PAIN.

Risk of death from stroke is approximately 3 times greater for people with diabetes than for those without.

This is EXTREMELY

important!

DIABETIC COMPLICATIONS:DIABETIC COMPLICATIONS:Diabetes and PregnancyDiabetes and Pregnancy

I. Problems for the Mother:• Insulin requirements increase, and metabolic control

often worsens during pregnancy . • Diabetic retinopathy, and perhaps nephropathy , may

worsen.

II. Problems for the Baby:• Infant mortality is higher in babies of diabetic mothers. • Congenital malformations occur more frequently . • “Big babies” (macrosomia) • Respiratory distress syndrome (RDS) more frequent.

DIABETIC COMPLICATIONSDIABETIC COMPLICATIONS

INFECTIONS & HEALING

• Hyperglycemia impairs immune system function and defense against infection.

• Tuberculosis and pneumococcal pneunomia are more common.

• Monilial (yeast) infections are extremely common and hard to treat.

• Wound healing is delayed in individuals with diabetes.

DIABETIC COMPLICATIONS:DIABETIC COMPLICATIONS:Screening ExamsScreening Exams

• Retinopathy: Retina exam - annually

• Nephropathy: Urine microalbumin-to-creatinine ratio on random urine specimen - annually. More often if abnormal.

• Neuropathy: -- Test vibratory sensation with 128 Hz

tuning fork - annually. -- Foot exam (for cracks, fissures, foreign

bodies, etc.) Every visit.

Diabetic ComplicationsDiabetic Complications

“Diabetes is a dreadful affliction, the melting down of flesh and limbs into urine…Life is short, unpleasant and painful...

-- Areteus of Capadocia, 2nd C. A.D.

What can we do???

Acute Complication of DM by Dr Shahjada Selim

Health & Medicine

Transcript of Acute Complication of DM by Dr Shahjada Selim