Diabetes Mellitus and Disorders of Glucose Homeostasis - PowerPoint PPT Presentation


PPT – Diabetes Mellitus and Disorders of Glucose Homeostasis PowerPoint presentation | free to download - id: 3d84b2-MWJlO


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation

Diabetes Mellitus and Disorders of Glucose Homeostasis


Rosen s Chapter 124 December 21, 2006 Presented by: Dr. D Isa-Smith Prepared by: Michael Savino, DO (PGY-2) Normal Physiology Normal glucose range: 60-150 mg/dL ... – PowerPoint PPT presentation

Number of Views:172
Avg rating:3.0/5.0
Slides: 60
Provided by: cchseastO
Learn more at: http://www.cchseast.org


Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Diabetes Mellitus and Disorders of Glucose Homeostasis

Diabetes Mellitus and Disorders of Glucose
  • Rosens Chapter 124
  • December 21, 2006
  • Presented by Dr. DIsa-Smith
  • Prepared by Michael Savino, DO (PGY-2)

Normal Physiology
  • Normal glucose range 60-150 mg/dL
  • Normal plasma glucose levels are critical to
    survival, because glucose is main fuel for CNS
  • CNS does not synthesize glucose and only stores a
    few minutes supply of glucose.
  • Brief hypoglycemia can cause profound brain
  • Prolonged severe hypoglycemia can cause cellular

  • Derived from 3 sources
  • 1. intestinal absorption
  • 2. glycogenolysis glycogen breakdown
  • 3. gluconeogenesis glucose formed from
    precursors such as lactate, pyruvate, amino
    acids, glycerol
  • After glucose ingestion, plasma levels rise and
    endogenous production is suppressed.

  • b cells of the pancreas detect elevated glucose
    levels triggering release of insulin into the
    hepatic portal circulation
  • Major anabolic hormone in diabetic disorder
  • Stimulates glucose uptake, storage, and use by
    other insulin-sensitive tissues (fat, muscle)
  • Half-life of insulin is about 3-10 minutes
  • Metabolized through the liver and kidney

Liver and Kidney
  • Liver and kidney contain glucose-6-phosphatase
    enzyme necessary for the release of glucose into
    the circulation
  • The liver is the sole source of endogenous
    glucose production in normal conditions
  • The kidney undergoes gluconeogenesis under
    prolonged starvation

  • Hepatocytes do not require insulin for glucose
    transport across cell membrane
  • But, insulin augments hepatocyte glucose uptake
    and storage for energy
  • Insulin inhibits hepatic gluconeogenesis and

Muscle cells
  • Can store and use glucose via glycolysis
  • In muscle glucose ? pyruvate
  • Pyruvate ? lactate or alanine ? transported to
    liver ? precursor for gluconeogenesis
  • Fasting conditions
  • i glucose uptake use fatty acids as energy,
    mobilize amino acids to liver for energy.

Counterregulatory hormones
  • Glucagon
  • The major catabolic agent that increases blood
  • a cells of pancreas
  • Released in response to hypoglycemia, stress,
    trauma, infection, starvation.
  • Decreases glycoloysis, increases gluconeogenesis
  • Increases ketone production in liver
  • Epinephrine h hepatic glucose production and
    limits glucose use through a and b adrenergic
  • acts directly glycogenolysis, gluconeogenesis
  • Norepinephrine similar to epinephrine
  • Growth hormone and cortisol initially i
    glucose, but long-term h glucose

Types of Diabetes
  • Type 1 Diabetes Mellitus
  • Type 2 Diabetes Mellitus
  • Gestational Diabetes
  • Impaired Glucose Tolerance

Type 1 DM
  • Failure to produce insulin. Tendency to ketosis
  • Parenteral insulin required to sustain life
  • Autoimmune destruction of Beta cells of pancreas
  • Strong association with HLA

Type 1 DM
  • Typical patient is lean, younger than 40, prone
    to ketosis.
  • Plasma insulin levels are low or absent.
  • Glucagon levels are high, but suppressible with
  • Symptoms of polydipsia, polyuria, polyphagia, and
    wt. loss develop rapidly
  • Complications incl DKA, retinopathy,
    nephropathy, neuropathy, foot ulcers, severe

Type 2 DM
  • Typical patient is middle aged or older,
    overweight, normal to high insulin levels.
  • Impaired insulin function related to poor insulin
    production, failure of insulin to reach the site
    of action, or failure of end organ response to
  • Symptoms begin more gradually than in Type 1

Type 2 DM - Subgroups
  • Most are obese, but 20 are not
  • Nonobese Type 2 patients present more like Type 1
  • Young persons with mature-onset diabetes

Type 2 DM
  • Symptoms come on gradually
  • Diagnosis usually made by elevated blood glucose
    on routine lab work
  • Blood glucose levels controlled by diet, oral
    hypoglycemics, or insulin.
  • Decompensation usually leads to hyperosmolar
    nonketotic coma rather than ketosis.

Gestational Diabetes
  • Characterized by abnormal oral glucose tolerance
    test (OGTT).
  • During pregnancy
  • Reverts to normal in postpartum period or remains
  • Clinical pathogenesis similar to Type 2
  • Clinical presentation usually nonketotic
    hyperglycemia during pregnancy

Impaired glucose toleranceImpaired Fasting
  • Plasma glucose levels between normal and diabetic
    and who are at increased risk for development of
  • Pathogenesis related to insulin resistance
  • Presentations nonketotic hyperglycemia, insulin
    resistance, hyperinsulinism, often obesity
  • Less complications than diabetes

Diagnostic Strategies
  • Diagnosis made by
  • Random plasma glucose gt 200 mg/dL
  • or Fasting glucose gt 140 mg/dL
  • or 2 hr postload OGTT
  • HbA1c high glucose binds to Hb b chain.
    Half-life of RBCs allows index of glucose for
    prior 6-8 weeks (normal 4-6)
  • Glucose dipstick tests use glucose oxidase
  • Ketone dipstick tests use nitroprusside rxn.

Dipstick Blood Glucose (Accucheck)
  • Generally more accurate than urine dip
  • Hematocrits lt30 or gt55 cause unduly high or low
    readings, respectively

  • Common problem in Type 1 diabetics
  • 9 120 episodes per 100 patient-years
  • Severe hypoglycemia associated with blood sugar
    below 40-50 mg/dL and impaired cognitive function
  • Hypoglycemia unawareness a dangerous
    complication of Type 1. Pts become unarousable
    without warning
  • Somogyi phenomenon

Hypoglycemia - symptoms
  • Blood glucose level below 40-50 mg/dL
  • Rate at which glucose decreases, age, gender,
    overall health, and previous hypoglycemic
    reactions all contribute to symptom severity
  • S/Sx caused by excessive epinephrine secretion
    and CNS dysfunction
  • Sweating
  • Nervousness, tremor
  • Tachycardia
  • Bizarre behavior, confusion
  • Seizures
  • Coma

Hypoglycemia - treatment
  • 1. Suspect hypoglycemia
  • Check serum glucose if strong suspicion treat
    before results available
  • 2. Correct serum glucose
  • If awake, cooperative PO intake
  • If unable to take PO 25-75 g glucose as D50W
    (1-3 amps) IV
  • Children 0.5-1 g/kg glucose as D25W IV
  • Neonates 0.5-1 g/kg glucose as D10W IV
  • If unable to get IV access 1-2 mg glucagon IM
    or SC may repeat q20 min
  • Glucagon onset of action 10-20 min, peaks at
    30-60 min
  • Ineffective in alcohol-induced hypoglycemia b/c
    lack of glycogen

Hypoglycemia - Management
  • ABCs
  • Aspiration, seizure precautions
  • If ETOH suspected, give thiamine
  • D50W should not be used in infants or young
    children because venous sclerosis causes rebound
  • Oral hypoglycemics (chlorpropamide) can cause
    prolonged hypoglycemia. Should be admitted for
  • May require constant infusion of D10W

  • Non-diabetic patients
  • Most common cause of postprandial hypoglycemia is
    alimentary hyperinsulinism (s/p gastrectomy,
    gastrojejunostomy, vagotomy, pyloroplasty)
  • Fasting hypoglycemia inadequate glucose
    production (hormone deficiencies, enzyme and
    substrate defects, severe liver disease)

HyperglycemiaDiabetic Ketoacidosis
  • Syndrome in which insulin deficiency and glucagon
    excess produce
  • Hyperglycemia
  • Dehydration
  • Acidosis
  • Electrolyte imbalance
  • DKA is typically characterized by
  • Hyperglycemia over 300 mg/dL,
  • Low bicarbonate (lt15 mEq/L), and
  • Acidosis (pH lt7.30) with ketonemia and ketonuria

Etiology of DKA
  • Almost always in Type 1 Diabetics
  • Non-compliance with insulin
  • Stress (Physical or emotional) despite insulin
  • Myocardial infarction
  • Infection/ Sepsis
  • Gastrointestinal bleeding
  • 25 of all episodes of DKA occur in undiagnosed

DKA History and Physical
  • Polydipsia, polyuria, polyphagia, visual
    blurring, weakness, wt loss, N/V, abd pain
  • May have altered mental status
  • Kussmaul respirations
  • Odor of acetone (sweet) on breath
  • Signs of dehydration
  • Tachycardia
  • Orthostatic changes

Pathophysiology DKA
  • Markedly elevated glucose levels spill over into
    the urine, drawing water, sodium, potassium,
    magnesium, calcium, phosphorus into the urine.
  • This combined with vomiting contribute to
    dehydration experienced in DKA
  • Exocrine pancreas dysfunction produces
    malabsorption, further limiting bodys intake of
    fluid and electrolytes.

Falsely elevated Elyte levels
  • 95 of DKA patients
  • Na normal or low
  • K very low (5-7 mEq/L)
  • Mg very low
  • Phos very low (3 mEq/L)
  • Because of dehydration and acidosis, however,
    these lab values are reported as high!

  • Adipose tissue fails to clear the circulation of
    lipids. Insulin deficiency results in activation
    of hormone-sensitive lipase increasing free fatty
    acid FFA levels. Overload of FFAs on the
    liver oxidizes them to acetoacetate and
  • Result is oxidation of FFAs to ketones instead
    of reesterification to triglycerides
  • The body while increasing ketone production,
    utilizes less ketones in peripheral tissues
    leading to ketoacidosis.

  • Glucagon levels are 4-5x higher in DKA and is the
    most influential ketogenic hormone.
  • Glucagon inhibits malonyl coenzyme A and inhibits

  • The counterregulatory hormones Epinephrine,
    norepinephrine, cortisol, growth hormone,
    dopamine, and thyroxin enhance ketogenesis
    indirectly by stimulating lipolysis.
  • Propranolol and metyrapone can block the effect
    of counterregulatory hormones. They have been
    used to prevent recurrent episodes in known DKA

Acidosis in clinical presentation
  • Acidotic patient attempts to increase lung
    ventilation and rid the body of excess acid with
    Kussmauls respiration. Bicarbonate is used up
    in the process.
  • Current evidence suggests that acidosis compounds
    the effects of ketosis and hyperosmolality to
    depress mental status directly.

Pathophysiology of DKA
Adapted from figure 124-1, p. 1963
Laboratory Tests
  • Allow confirmation of diagnosis
  • serum and urine glucose (usually greater than
    350, but up to 18 of patients may have
    euglycemic DKA)
  • Electrolytes
  • ABG/venous pH (w/ K if available)
  • Obtain EKG immediately

Metabolic acidosis
  • Metabolic acidosis with elevated anion gap is
    secondary to elevated plasma levels of
    acetoacetate and b-hydroxybutyrate. Also
    contributed by lactate, FFAs, phosphates, volume

Other tests
  • CBC w/ differential
  • BMP elevated BUN/Cr suggest dehydration.
  • Mag, calcium, amylase, ketone, and lactate levels
  • U/A rule out infection/renal dz

  • Serum sodium value often misleading!
  • Sodium is often low in presence of dehydration
    because affected by
  • Hyperglycemia
  • Hypertriglyceridemia
  • Salt-poor fluid intake
  • Insensible losses
  • Marked hyperglycemia water flows from cells
    into vessels to decrease osmolar gradient,
    causing dilutional hyponatremia
  • Correction Na (Gluc 100) 1.6 / 100
  • For every increase of 100 mg/dL glucose, the
    serum sodium decreases by 1.6

  • Common in DKA
  • Impaired lipoprotein lipase activity and hepatic
    overproduction of VLDL

  • Acidosis and hyperosmolarity by high glucose
    levels shift potassium, magnesium, and
    phosphorous from intracellular to extracellular
  • Dehydration produces hemoconcentration, which
    contributes to normal-high initial serum
    potassium, mag, and phos

Calculate Correction for potassium
  • Correction for the effects of acidosis on serum
  • Subtract 0.6 mEq/L from lab K for every 0.1
    decrease in pH on ABGs
  • Ex if K is reported as 5 mEq/L and the pH is
    6.94, the corrected K 2 mEq/L

Management of DKA
  • Consider intubation in vomiting decompensated
    patient for airway protection
  • Once intubated, hyperventilation should be
    maintained to prevent worsening acidosis
  • Hypovolemic shock requires aggressive fluid
    resuscitation with 0.9 NSS, rather than pressors
  • Consider other causes of shock MI, sepsis
  • Diagnosis Hyperglycemia, ketosis, acidosis
  • Fluids, electrolytes, insulin therapy begins.

Summary of treatment for DKA
  • Identify DKA glucose, electrolytes, ketones,
    ABG. CBC, U/A, CXR, EKG. Support ABC.
  • 1. Rehydrate 1-2 L NSS over 1-3 hours
  • Children 20 mL/kg NSS over first hr, then
    follow w/ 0.45 NSS
  • 2. Insulin bolus 0.1 U/kg regular IV
  • Maintenance 0.1 U/kg/hr regular IV
  • Change to D5W/0.45NS when glucose lt300 mg/dL
  • 3. Correct electrolytes.
  • Na 0.9 NSS and 0.45
  • K add 20-40 mEq KCl to each liter. Ensure good
    renal fxn
  • Phos usually not necessary to replenish
  • Mg 1-2 g MgSO4

  • 4. Correct acidosis add 44-88 mEq/L bicarb to
    1st liter of IV fluids if pH lt 7.0. Correct to a
    pH of 7.1
  • Correct underlying precipitant
  • Monitor VS, I Os, serum glucose, and
  • Admit to ICU

  • Historically, high dosages of insulin were used,
    but resulted in hypoglycemia and hypokalemia
  • Now, low-dose insulin therapy with aggressive
    fluid therapy is used, more gradual decrease in
    blood glucose levels, while decreasing risk of

  • May start with bolus of 10 units regular insulin
  • Or infuse regular insulin at a rate of 0.1
    U/kg/hr up to 5-10 U/hr, mixed with IV fluids.
  • In children, dosing is 0.1 U/kg. Reduction of
    plasma glucose should be more gradual because of
    greater risk of developing cerebral edema.

  • Half-life of regular insulin is 3 10 minutes.
  • Therefore, it should be infused, rather than
    given as repeated boluses.
  • When blood glucose has dropped to 250-300 mg/dL,
    then start D5W/0.45 NS to prevent iatrogenic
    hypoglycemia and cerebral edema

  • DKA
  • Glucose gt350
  • Sodium low 130s
  • Potassium 4.5-6.0
  • Bicarbonate lt 10
  • BUN 25-50
  • Serum ketones present
  • HHNC
  • Glucose gt700
  • Sodium 140s
  • Potassium 5
  • Bicarbonate gt 15
  • BUN gt 50
  • Serum ketones absent

Hyperglycemic Hyperosmolar Nonketotic Coma
  • Acute diabetic decomposition
  • Results from severe dehydration that results from
    sustained hyperglycemic diuresis, in which
    patient is unable to drink enough fluids to
    sustain hydration
  • Characterized by Hyperglycemia, hyperosmolarity,
  • Absence of ketoacidosis is unknown, but FFA
    levels are lower than in DKA, thus less
    substrates to form ketones. Most likely because
    still producing tiny amount of insulin required
    to block ketogenesis

  • More common in elderly with Type 2, but has been
    reported in children with Type 1
  • May occur in pts who are not diabetic after
    burns, parenteral hyperalimentation, peritoneal
    dialysis, or hemodialysis
  • Clinically signs of dehydration and CNS
    findings predominate
  • Most common associated diseases CRI, gm
    pneumonia/sepsis, GI bleeding
  • On average, the HHNC patient has 24 or 9L fluid
    fluid deficit

Treatment of HHNC
  • Identify HHNC
  • Rehydrate 2-3 L NSS over first few hours.
    Correct ½ fluid deficit in first 8 hours,
    remainder over remaining 24 hrs
  • Insulin bolus 0.05-0.1 U/kg regular IV
  • Maintenance 0.05-0.1 U/kg/hr regular IV
  • Change to D5W/0.45NS when glucose lt300 mg/dL
  • . Correct electrolytes.
  • Na 0.9 NSS and 0.45
  • K add 20-40 mEq KCl to each liter. Ensure good
    renal fxn
  • Phos usually not necessary to replenish
  • Mg 1-2 g MgSO4

  • 4. Correct acidosis add 44-88 mEq/L bicarbonate
    to 1st liter of IV fluids if pH lt 7.0. Correct
    to a pH of 7.1
  • Correct underlying precipitant
  • Monitor VS, I Os, serum glucose, and
  • Admit to ICU

Late complications of DM
  • Develop 15-20 yrs after overt hyperglycemia
  • Vascular atheroslerosis, thromboembolic
    complications. Probably related to oxidated
    low-density lipoprotein and increased platelet
    activity. CAD, stroke, silent MI, claudication,
    non-healing ulcers, and impotence
  • Diabetic nephropathy renal disease is leading
    cause of death and disability in diabetic
  • Two pathological patterns diffuse and nodular

  • Retinopathy diabetes leading cause of adult
    blindness in US. (11-18 of diabetics)
  • Background (simple) retinopathy
  • Proliferative retinopathy
  • Complaints range from acute blurring of vision to
    sudden unilateral /bilateral blindness. Also may
    have snowflake cataract (vision improves with
    decreasing blood glucose levels)

  • Neuropathy peripheral neuropathy in 15-60.
    Poorly understood
  • Diabetic vascular dz effects on vasa nervorum,
    myoinositol, polyol pathway, and protein
    glycosylation may have roles
  • Types
  • 1. peripheral symmetrical slow, worse at night
  • 2. mononeuropathy rapid onset, muscle wasting
  • 3. autonomic neuropathy GI, bladder,
    orthostatic hypotension

The diabetic foot
  • Sensory neuropathy, ischemia, infection principle
    contributors to diabetic foot disease. Loss of
    sensation ? pressure necrosis
  • Must be Xrayed, no weight bearing, assessed for
  • Mild vs Deep infections managed differently
  • Mild gram , oral abiotics, no wt bearing, home
  • Deep full-thickness, cellulitis gt 2cm,
    lymphangitis, bone involvement. Polymicrobial
    aerobic gm cocci, gm bacilli, and anaerobes
  • Require hospitalization, cultures, IV tx with
    amp-sulbactam, ticarcillin-sulbactam, cefoxitin,
    imipenem, or fluoroquinolone clindamycin.
    Debridement, no wt. bearing

  • Diabetics at increased risk of extremity
    infections and pyelonephritis
  • Tuberculosis, mucocutaneous candidiasis,
    intertrigo, mucormycosis, soft tissue infections,
    nonclostridial gas gangrene, osteomyelitis, and
    malignant otitis externa.

Cutaneous manifestations
  • Dermal hypersensitivity pruritic, red,
    induration at insulin injection sites
  • Insulin lipoatrophy
  • Insulin lipohypertrophy
  • Insulin pumps sensitivity to catheters

Oral Hypoglycemic Agents
  • Sulfonylureas (developed 1940s) mainstay of
    treatment. Increase insulin secretion by binding
    to specific beta cell receptors. Risk of
  • Repaglinide similar to sulfonylureas. More
    rapid onset, but less risk of hypoglycemia. OK
    with sulfa allergies.
  • Metformin decreases hepatic glucose output.
    Contraindicated in renal insufficiency and
    metabolic acidosis. Withold for 48 hours of
    iodinated contrast media b/c risk of acidosis
  • Thiazolidinediones reduce insulin resistance.
    Monitor liver enzymes
  • Alpha glucosidase inhibitors delay intestinal
    absorption and prevent complex carb breakdown.
    GI side effects, monitor liver enzymes

New med on the block
  • Byetta (Exetinide) first in a class of encretin
  • mimics the enhancement of glucose-dependent
    insulin secretion
  • For Type 2 DM
  • Used with metformin and/or sulfonylurea
  • Pre-filled injection pen (SQ)
  • Dose 5 mcg BID for first 30 days
About PowerShow.com