History

Fact Explanation
Tremors, Palpitations, anxiety [1] Due to catecholamine mediated (adrenergic) autonomic effects [2] Neurogenic (autonomic) symptoms are triggered by a falling glucose level.These symptoms are activated by the autonomic nervous system and are mediated in part by sympathoadrenal release of catecholamines (norepinephrine and epinephrine) from the adrenal medullae and acetylcholine from postsynaptic sympathetic nerve endings [3]
Sweating,hunger, tingling [1] Due to acetylcholine mediated (cholinergic) autonomic effects [1]
Neuroglycopenic symptoms-Irritability, Drowsiness,Blurred vision,Difficulty with speech,Confusion, Feeling faint, Seizure,Changes in behavior [4] Neuroglycopenic symptoms occur as a result of brain neuronal glucose deprivation [3]
History of renal failure (risk factor) [7] Renal insufficiency increase the risk of drug-induced hypoglycemia due to decreased insulin clearance [4]
History of liver failure (risk factor) [7] Hepatic insufficiency increase the risk of drug-induced hypoglycemia due to decreased gluconeogenesis [4]
Other risk factors - excessive alcohol intake,decreased food intake (skipping meals) , advancing age, polypharmacy [4] Excessive alcohol intake - Decreased gluconeogenesis Advanced age - Decreased awareness, decreased counter regulatory response to low blood glucose Decreased food intake - Insufficient glucose intake Polypharmacy - Increased risk of drug interactions resulting in hypoglycemia [4]
Improper use of anti diabetic drugs [8] treatment-limiting adverse effect in patients with diabetes [11] Leads to reduction of blood glucose levels to a level which is more than the required level [2] insulin and sulphonylureas are the most common drugs which causes hypoglycemia [6] Insulin treated patients have a higher mortality due to hypoglycemia than the patients who are not treated with insulin [9]
Usage of drugs which can lead to hypoglycemia (eg : ACE inhibitors, Fluoroquinolones,Indomethacin,Quinine,Beta blockers ) [2] ACE inhibitors- Increase insulin sensitivity Fluoroquinolones- May increase insulin secretion from pancreas Indomethacin- Increase insulin secretion from pancreas, decrease in insulin clearance, decrease in gluconeogenesis Quinine- Increased insulin secretion from pancreas Beta blockers- Mask signs/symptoms of hypoglycemia, increase in glucose uptake in the periphery [2]
History of depression [2] Should be assessed as drug induced hypoglycemia may be a suicidal attempt (self-harm with hypoglycemic agents) [5] Recurrent hypoglycemia can also cause depression [10]
References
  1. MUKHERJEE E, CARROLL R, MATFIN G. Endocrine and metabolic emergencies: hypoglycaemia. Ther Adv Endocrinol Metab [online] 2011 Apr, 2(2):81-93 [viewed 13 September 2014] Available from: doi:10.1177/2042018811401644
  2. VUE M. H., SETTER S. M.. Drug-Induced Glucose Alterations Part 1: Drug-Induced Hypoglycemia. Diabetes Spectrum [online] December, 24(3):171-177 [viewed 13 June 2014] Available from: doi:10.2337/diaspect.24.3.171
  3. BRISCOE V. J.. Hypoglycemia in Type 1 and Type 2 Diabetes: Physiology, Pathophysiology, and Management. Clinical Diabetes [online] 2006 July, 24(3):115-121 [viewed 13 June 2014] Available from: doi:10.2337/diaclin.24.3.115
  4. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf
  5. NIRANTHARAKUMAR KRISHNARAJAH, MARSHALL TOM, HODSON JAMES, NARENDRAN PARTH, DEEKS JON, COLEMAN JAMIE J., FERNER ROBIN E., SESTI GIORGIO. Hypoglycemia in Non-Diabetic In-Patients: Clinical or Criminal?. PLoS ONE [online] 2012 July [viewed 13 September 2014] Available from: doi:10.1371/journal.pone.0040384
  6. NG CL. Hypoglycaemia in nondiabetic patients - an evidence. Aust Fam Physician [online] 2010 Jun, 39(6):399-404 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20628679
  7. GHATAK TANMOY, SINGH RATENDERKUMAR, BARONIA ARVINDKUMAR. Enteral voriconazole induced hypoglycemia: A potentially life threatening complication. Indian J Pharmacol [online] 2012 December [viewed 13 September 2014] Available from: doi:10.4103/0253-7613.91890
  8. AHREN BO. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. VHRM [online] 2013 April [viewed 13 September 2014] Available from: doi:10.2147/VHRM.S33934
  9. GARG R., HURWITZ S., TURCHIN A., TRIVEDI A.. Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients. Diabetes Care [online] December, 36(5):1107-1110 [viewed 13 September 2014] Available from: doi:10.2337/dc12-1296
  10. PERLMUTER L. C., FLANAGAN B. P., SHAH P. H., SINGH S. P.. Glycemic Control and Hypoglycemia: Is the loser the winner?. Diabetes Care [online] 2008 June, 31(10):2072-2076 [viewed 13 September 2014] Available from: doi:10.2337/dc08-1441
  11. MCCOY R. G., VAN HOUTEN H. K., ZIEGENFUSS J. Y., SHAH N. D., WERMERS R. A., SMITH S. A.. Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia. Diabetes Care [online] December, 35(9):1897-1901 [viewed 13 September 2014] Available from: doi:10.2337/dc11-2054

Examination

Fact Explanation
Assessment of level of consciousness [2] Assessed according to Glasgow coma scale. Motor Response 6 Obeying command 5 Localizing response to pain. 4 Withdrawal to pain 3 Flexor response to pain 2 Extensor posturing to pain 1 No response to pain. Verbal Response 5 Oriented 4 Confused conversation 3 Inappropriate speech 2 Incomprehensible speech 1 No verbal response. Eye Opening 4 Spontaneous eye opening. 3 Eye opening in response to speech 2 Eye opening in response to pain. 1 No eye opening [2]
Pallor [2] Drop of blood glucose level triggers adrenalin release and constriction of skin arteries [2]
Increased heart rate [1] Autonomic symptoms are triggered by a falling glucose level [2]
Elevated systolic blood pressure [1] Autonomic symptoms are triggered by a falling glucose level [2]
Diaphoresis [3] Due to sympathoadrenal activation triggered by a falling glucose level [3]
References
  1. VUE M. H., SETTER S. M.. Drug-Induced Glucose Alterations Part 1: Drug-Induced Hypoglycemia. Diabetes Spectrum [online] December, 24(3):171-177 [viewed 13 June 2014] Available from: doi:10.2337/diaspect.24.3.171
  2. BRISCOE V. J.. Hypoglycemia in Type 1 and Type 2 Diabetes: Physiology, Pathophysiology, and Management. Clinical Diabetes [online] 2006 July, 24(3):115-121 [viewed 13 June 2014] Available from: doi:10.2337/diaclin.24.3.115
  3. MUKHERJEE E, CARROLL R, MATFIN G. Endocrine and metabolic emergencies: hypoglycaemia. Ther Adv Endocrinol Metab [online] 2011 Apr, 2(2):81-93 [viewed 13 September 2014] Available from: doi:10.1177/2042018811401644

Differential Diagnoses

Fact Explanation
Critical illnesses ( renal failure, liver failure,heart failure ) [1] Renal insufficiency-decrease insulin clearance,thus giving rise to hypoglycemia. Hepatic insufficiency-decrease gluconeogenesis and leads to hypoglycemia. Heart failure-Increased glucose utilisation from the ischemic tissues [1]
Addison's disease [2] Hypoglycemia occurs due to decreased gluconeogenesis and increased insulin-mediated glucose uptake by skeletal muscle [2]
Hormone deficiency Cortisol Glucagon and epinephrine [2] Decreased gluconeogenesis [2]
Endogenous hyperinsulinism ( eg: insulinoma autoimmune diseases-Antibody to insulin receptor )[3] High insulin levels give rise to hypoglycemia.In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and circulating oral hypoglycemic agents during an episode of hypoglycemia and measure insulin antibodies [3]
Sepsis [2] Hypoglycemia occurs due to liver dysfunction, impairment of insulin degradation and enhanced glucose utilization [2]
Non islet cell tumours [4] overproduction of incompletely processed forms of proinsulin-like growth factor-II (pro-IGF-II), which may lead to an excessive stimulation of the insulin receptors at various target tissues [4]
References
  1. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf
  2. PHILIP E.,ASHLEY B., Evaluation and Management of Adult Hypoglycemic Disorders,The journal of clinical endocrinology and metabolism [online] March 2009 [viewed on 13 June 2014] Available from: https://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/FINAL-Standalone-Hypo-Guideline.pdf
  3. CRYER PE, AXELROD L, GROSSMAN AB, HELLER SR, MONTORI VM, SEAQUIST ER, SERVICE FJ, ENDOCRINE SOCIETY. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab [online] 2009 Mar, 94(3):709-28 [viewed 13 June 2014] Available from: doi:10.1210/jc.2008-1410
  4. HAMBERG P.. Non-Islet-Cell Tumor Induced Hypoglycemia in Patients With Advanced Gastrointestinal Stromal Tumor Possibly Worsened By Imatinib. Journal of Clinical Oncology [online] 2006 June, 24(18):e30-e31 [viewed 13 June 2014] Available from: doi:10.1200/JCO.2006.06.5318

Investigations - for Diagnosis

Fact Explanation
Plasma glucose levels [1] Classification of drug induced hypoglycemia 1) Severe hypoglycemia. An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions. 2) Documented symptomatic hypoglycemia. An event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration ≤70 mg/dl (3.9 mmol/l). 3) Asymptomatic hypoglycemia. An event not accompanied by typical hypoglycemic symptoms but with a measured concentration of plasma glucose ≤70 mg/dl (3.9 mmol/l). 4) Probable symptomatic hypoglycemia. An event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination (but that was presumably caused by a plasma glucose concentration ≤70 mg/dl [3.9 mmol/l]). 5) Relative hypoglycemia. An event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets those as indicative of hypoglycemia, but with a measured plasma glucose concentration >70 mg/dl (3.9 mmol/l). [2]
Usage of drugs which can lead to hypoglycemia (eg : ACE inhibitors, Fluoroquinolones,Indomethacin,Quinine,Beta blockers ) [3] ACE inhibitors- Increase insulin sensitivity Fluoroquinolones- May increase insulin secretion from pancreas Indomethacin- Increase insulin secretion from pancreas, decrease in insulin clearance, decrease in gluconeogenesis Quinine- Increased insulin secretion from pancreas Beta blockers- Mask signs/symptoms of hypoglycemia, increase in glucose uptake in the periphery [3]
References
  1. Defining and Reporting Hypoglycemia in Diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care [online] 2005 May, 28(5):1245-1249 [viewed 13 June 2014] Available from: doi:10.2337/diacare.28.5.1245
  2. AHREN BO. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. VHRM [online] 2013 April [viewed 13 September 2014] Available from: doi:10.2147/VHRM.S33934
  3. VUE M. H., SETTER S. M.. Drug-Induced Glucose Alterations Part 1: Drug-Induced Hypoglycemia. Diabetes Spectrum [online] December, 24(3):171-177 [viewed 13 June 2014] Available from: doi:10.2337/diaspect.24.3.171

Investigations - Fitness for Management

Fact Explanation
HbA1c [1] To see the diabetic control [1]
Full blood count [1] Check the hemoglobin levels in patients with pallor [1]
Fasting blood sugar, oral glucose tolerance test [1] Done to diagnose diabetic [1]
References
  1. Defining and Reporting Hypoglycemia in Diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care [online] 2005 May, 28(5):1245-1249 [viewed 13 June 2014] Available from: doi:10.2337/diacare.28.5.1245

Investigations - Followup

Fact Explanation
Serum creatinin, blood urea [1] To check for the renal functions as renal insufficiency increase the risk of drug-induced hypoglycemia [2]
Liver enzyme levels [1] To check liver functions as hepatic insufficiency increase the risk of drug-induced hypoglycemia [2]
References
  1. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf
  2. GHATAK TANMOY, SINGH RATENDERKUMAR, BARONIA ARVINDKUMAR. Enteral voriconazole induced hypoglycemia: A potentially life threatening complication. Indian J Pharmacol [online] 2012 December [viewed 13 September 2014] Available from: doi:10.4103/0253-7613.91890

Investigations - Screening/Staging

Fact Explanation
Renal function tests (Serum creatinine ,blood urea levels, glomerular filtration rate ) [1] Renal insufficiency increase the risk of drug-induced hypoglycemia due to decreased insulin clearance [1]
Liver function tests ( Liver enzyme levels, bilirubin levels ) [1] Hepatic insufficiency increase the risk of drug-induced hypoglycemia due to decreased gluconeogenesis [1]
Other risk factors - excessive alcohol intake,decreased food intake (skipping meals) , advancing age, polypharmacy [1] Excessive alcohol intake - Decreased gluconeogenesis Advanced age - Decreased awareness, decreased counter regulatory response to low blood glucose Decreased food intake - Insufficient glucose intake Polypharmacy - Increased risk of drug interactions resulting in hypoglycemia [1]
References
  1. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf

Management - General Measures

Fact Explanation
Recognition of signs and symptoms of hypoglycemia [1] Hypoglycemia should be clinically diagnosed prior to treatment.Should differentiate between mild – moderate versus severe signs and symptoms [1]
Initial treatment of hypoglycemia [1] 1)Consume 15-20 grams of glucose or simple carbohydrates 2)Recheck your blood glucose after 15 minutes 3)If hypoglycemia continues, repeat 4)Once blood glucose returns to normal, eat a small snack if your next planned meal or snack is more than an hour or two away [1]
Appropriate treatment of hypoglycemia [1] Patient-treated with a quick acting glucose source versus caregiver assisted with glucagon or healthcare provider treatment with dextrose [1]
Treatment in chronic alcohol abused patients [2] If the patient has a history of malnutrition or chronic alcohol abuse, intravenous (IV) thiamine at a bolus dose of 1–2 mg/kg should be given before initiation of glucose treatment, to avoid precipitating Wernicke's encephalopathy [2]
References
  1. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf
  2. MUKHERJEE E, CARROLL R, MATFIN G. Endocrine and metabolic emergencies: hypoglycaemia. Ther Adv Endocrinol Metab [online] 2011 Apr, 2(2):81-93 [viewed 13 September 2014] Available from: doi:10.1177/2042018811401644

Management - Specific Treatments

Fact Explanation
Plan for prevention of future episodes of drug induced hypoglycemia [1] Evaluation of offending medication for adjustment in dosage and length of therapy Consider of timing of administration of medication with meals Consistent intake of meals/snacks Institute blood glucose monitoring [1]
Patient Education [1] Demonstration of self-monitoring of blood glucose Discussion of timing of blood glucose monitoring and target levels Monitor for signs/symptoms of hypoglycemia Review appropriate treatment of hypoglycemia [1]
glucagon IM injections [2] Glucagon 1mg IM- May take up to 15 minutes to take effect, mobilises glycogen from the liver and will be less effective in those who are chronically malnourished (e.g. alcoholics), or in patients who have had a prolonged period of starvation and have depleted glycogen stores or in those with severe liver disease [1]
In ward management of hypoglycemia with IV dextrose [1] If IV access available, give 75-80ml of 20% glucose or 50ml of 50% dextrose (over 10-15 minutes). If an infusion pump is available use this, but if not readily available the infusion should not be delayed.Repeat capillary blood glucose measurement 10 minutes later.If it is still less than 4.0mmol/L, repeat [1]
In ward management when the patient is recovered [1] Once the blood glucose is greater than 4.0mmol/L and the patient has recovered give a long acting carbohydrate of the patient’s choice where possible, taking into consideration any specific dietary requirements [1]
References
  1. HELMS K., KELLEY K., Drug-Induced Hypoglycemia, Hypoglycemia - Causes and Occurrences [online] October 2011, page 113-130 [viewed 13 June 2014] Available from: http://cdn.intechopen.com/pdfs-wm/21469.pdf
  2. MUKHERJEE E, CARROLL R, MATFIN G. Endocrine and metabolic emergencies: hypoglycaemia. Ther Adv Endocrinol Metab [online] 2011 Apr, 2(2):81-93 [viewed 13 September 2014] Available from: doi:10.1177/2042018811401644