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8/3/2019 Hypoglycemia a Practical Approach 1
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An evidence basedapproach
hypoglycemia
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definition The condition called hypoglycemia literally
means low blood sugar.
Hypoglycemia occurs when blood glucoseconcentrations fall below a level necessary toproperly support the body's need for energy and
stability throughout its cells.
Typically symptoms of hypoglycemia occur whenblood sugar fall below 54 mg/dl.
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Classification of Hypoglycemia
Fasting hypoglycemia occurs in the post absorptiveperiod (hours after a meal)
Reactive (postprandial ) hypoglycemia.
Criticized as it is not diagnostically useful
Service FJ. Hypoglycemic disorders. N Engl J Med
1995;332:1144 –52.
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Causes of hypoglycemia
Service FJ. Classification of hypoglycemic disorders. Endocrinol Metab Clin North Am
1999;28:501 –
17.
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Hypoglycemia: Symptoms
Sympathoadrenal: diaphoresis, warmth, anxiety, tremor, nausea, hunger,
palpitations/tachycardia
Neuroglycopenic: Fatigue, dizziness, H/A, visual disturbance, drowsiness,
difficulty speaking, inability to concentrate, amnesia,abnormal behaviour, mood changes, loss of consciousness,seizure, focal neurological deficit
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Response to HypoglycemiaBlood Glucose Symptoms
< 60 mg/dl Sweating, tremor, anxiety,
palpitations, hunger
50 – 55 mg/dl Early cognitive dysfn.
(confusion, mood changes)
45 – 50 mg/dl Lethargy, obtundation
< 30 mg/dl Coma
< 20 mg/dl Convulsions
…Death
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Response to HypoglycemiaBlood Glucose Hormonal response
< 79.2 mg/dl Insulin to low levels
64.8 – 70.2 mg/dl Glucagon & catecholamines
< 59.4 mg/dl Growth Hormone & cortisol
< 45 mg/dl Pancreas: no insulin release
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Diagnosis
Establishing the cause History (liver failure, sepsis, autoimmune disease, neoplasm,
alcohol, drugs)
Establishing fasting hypoglycemia Supervised 72 hour fast test
In hospital setting to lower risk to the patient
Usually hypoglycemia develops in first 48 hours of the fast in 95%of cases
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72-HOUR FAST
Protocol
Date the onset of the fast as the time of the last intake of calories
Discontinue all non essential medications
Allow the patient to drink calorie-free and caffeine-free beverages
Collect blood specimens for measurement of plasma glucose, insulin,C-peptide, and proinsulin every six hours until the plasma glucoseconcentration is below 60 mg/dL (3.3 mmol/L) at this point, the
frequency of sampling should be increased to every one to two hours.
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Test end points and duration
the plasma glucose concentration is ≤45 mg/dL (2.5mmol/L)
the patient has symptoms or signs of hypoglycemia,
72 hours have elapsed,
or when the plasma glucose concentration is less than 55mg/dL (3 mmol/L) if Whipple's triad is present
Plasma beta-hydroxybutyrate and sulfonylurea levels aremeasured
1 mg of glucagon is given intravenously and the plasma
glucose measured 10, 20, and 30 minutes later.
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In normal subjects, the following thresholds have been identifiedin graded glucose reductions
Insulin secretion decreases,(BG < 80), followed by increase inGlucagon and Epinephrine, growth hormone( BG <65) andCortisol (BG<60)respectively
Normal subjects do not have symptomatic hypoglycemia after aprolonged fast because
Gluconeogenesis accounts for approximately 50 percent of
glucose production after an overnight fast and for almost allglucose production after 42 hours or more of fasting
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Interpretation of values after 72 hour test
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Cryer PE. Glucose Homeostasis and hypoglycemia. In: Kronenberg H, Melmed S,Polonsky K, et al, editors. Williams textbook of endocrinology. 11th edn. Philadelphia:Saunders Elsevier, 2008;1503 –33.
].
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Hypoglycemia Pathway
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Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemicdisorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab2009;94:709 –28.
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Causes
Drugs ( most common cause of hypoglycemia ) Insulin- most common cause,
Timing, dose, type
clearance of insulin (eg, renal failure);
altered counter regulation Sulfonylureas
Metformin does not cause hypoglycemia
High dose salicylates, pentamidine, quinine, quinolones
Malouf R, Brust JCM. Hypoglycemia: causes, neurologicalmanifestations, and outcome. Ann Neurol1985;17:421 –30.
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Renal failure
Second gluconeogenic organ decreased clearance of renally excreted drugs or their metabolites
(eg, insulin, chlorpropamide, metabolite of glyburide)
Hepatic Failure
Decreased glycogenolysis
Decresed gluconeogenesis
Large functional reserve,( 20% func required to preventhypoglycemia)
Genetic defects in glycometabolic pathways
Finally, compromised drug metabolism (tolbutamide, glyburide,glipizide )
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Endocrinopathies
Adrenal (glucocorticoid) insufficiency
Growth hormone deficiency
Glucagon deficiency
Pituitary disease ( decreased combined corticotropin and GHdeficiecy)
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Neoplasm Non –islet-cell tumors
Mesenchymal tumors,
hepatocellular carcinoma,
adrenocortical tumors, carcinoid tumors,
leukemia, and lymphomas
Most of these tumors secrete IGF –II molecule
Some also secrete Glucagon- like peptide(GLP-1) and Somatostatin
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Insulinoma
Pancreatic β-cell tumors that secrete Insulin
Small,solitary, benign( < 10% malignant)Inability of insulinoma cells to suppressinsulin secretion during low levels ofcirculating glucose, leading to severe
hypoglycemia
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Diagnosis and Tumor Localization
Whipple triad on a prolong fasting + insulin/c – peptide < 1
Carry sensitivity of 89% & specificity of 100%
80% of insulinomas are < 2 cm in size
Successful pre operative localization possible inonly 60%
CT ( helical or multislice) sensitivity – 82 to 94 %
MRI with gadolinium scan – sensitivity 85% Best test for preoperative localization – selective
arteriography 82 %
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Trans abdominal USG high resolution detectsonly 50% of insulinomas
Intraoperative high res. USG is 90% sensitive.
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Treatment
Medical—
Drugs – 1st line – Diazoxide – a drug used primarily
for hypertensive crisis
Belongs to thiazide group Half life – 28 hrs.
Used in insulinoma as inhibits insulin release frompancreas & some extrapancreatic effect by
increasing catecholamine release.
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Medical—
Octreotide –
Mimicks natural hormone somatostatinsuppresses secretion of gastropancreaticpeptides i.e.( insulin, gastrin, glucagon, secretin,motilin ) also growth hormone
Half life – 100 min.
In elderly HL increases by 46%, drug clearancedecreases by 26%.
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Autoimmune causes
Anti-insulin receptor antibody
Rarely, hypoglycemia is caused by autoantibodies that bind theinsulin receptor and mimic the biologic action of insulin
Most patients have elevated ESR, +ve ANA
Anti-insulin antibody autoantibodies against insulin bind free circulating plasma insulin
when its concentration is high and release insulin when theconcentration of free plasma insulin drops.
Release of insulin at inappropriate times can cause hypoglycemia.
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Thankyou