Hypoglycemia a Practical Approach 1

8/3/2019 Hypoglycemia a Practical Approach 1

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An evidence basedapproach

hypoglycemia



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.





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.



Causes of hypoglycemia

Service FJ. Classification of hypoglycemic disorders. Endocrinol Metab Clin North Am

1999;28:501 –

17.



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



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



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



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



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.



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.



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



Interpretation of values after 72 hour test



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.

].



Hypoglycemia Pathway



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.



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.



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 )



Endocrinopathies

Adrenal (glucocorticoid) insufficiency

Growth hormone deficiency

Glucagon deficiency

Pituitary disease ( decreased combined corticotropin and GHdeficiecy)





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



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





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 %



Trans abdominal USG high resolution detectsonly 50% of insulinomas

Intraoperative high res. USG is 90% sensitive.



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.



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%.



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.



Thankyou

Hypoglycemia a Practical Approach 1

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