Hypoglycemia
mc : DM
other disorders : insulinoma, large mesenchymal tumors, end-stage organ failure,
alcoholism,
endocrine deficiencies, postprandial reactive hypoglycemia condition,
inherited metabolic disorder
Tab 334-1 ¿øÀÎ
* Whipple's triad
i) hypoglycemia sx
ii) low plasma glucose(<45-50 mg/dL)
iii) plasma glucose levelÀ» ¿Ã¸°ÈÄ Áõ»ó È£Àü
1. systemic glucose balance & conterregulation
glycogenÀúÀåÀÌ °í°¥µÇ¸é gluconeogenesis¿¡ ÀÇÇØ ´çÀ» »ý¼ºÇÑ´Ù.
´ç »ý¼ºÀÇ ÀÏÂ÷Àû Àå¼Ò´Â liverÀÌ¸ç ±×´ÙÀ½ÀÌ kidneyÀÌ´Ù.
gluconeogenesis°¡ ÀϾ±â À§Çؼ´Â liver, muscle & adipose tissue¿¡¼ precursor¸¦
°ø±Þ¹Þ¾Æ¾ß ÇÑ´Ù.
¿¹> muscle -> lactate, pyruvate, alanine, and other amino acids
adipose tissue : TG -> glycerol(gluconeogenesisÀÇ precursor)·Î broken down
FFA -> acetyl CoA(brain ÀÌ¿Ü Á¶Á÷ÀÇ alternative fuel source)»ý¼º
* counterregulatory hormone response sequence
i) Glucagon : 1st & most important
ii) epinephrine : glucagonÀÌ ºÒÃæºÐÇÒ ¶§ Áß¿äÇÑ ¿ªÇÒ
iii) hypoglycemiaÁö¼Ó½Ã GH & cortisol
2. Clinical manifestations
i) Neuroglycopenic symptom
CNS neuronal glucose deprivationÀÇ °á°ú·Î ¹ß»ý
behavioral changes, confusion, fatigue, seizure, LOC
ii) hypoglycemia-induced autonomic response
adrenergic symptom(NE, Epi) : palpitation, tremor, anxiety
cholinergic symptom : sweating, hunger, paresthesia
3. ¿øÀÎ
postprandial or fasting
´ç´¢ Ä¡·áÁß¿¡ °¡Àå ÈçÈ÷ ¹ß»ý
1) Hypoglycemia in diabetes
¨ç ºóµµ
type 1 DMȯÀÚ »ç¸ÁÀÇ 2-4%°¡ hypoglycemia¶§¹®À¸·Î ÃßÁ¤µÈ´Ù.
type 2 DM¿¡¼´Â ´ú ÈçÇÏÁö¸¸ insulin or sulfonylureaÄ¡·áÁß¿¡ ¹ß»ýÇÒ¼ö ÀÖ´Ù.
short-acting sulfonylurea & repaglinide¿¡ ÀÇÇØ ÀϽÃÀûÀÎ ÀúÇ÷´çÀÌ ¹ß»ýÇÒ¼ö ÀÖ´Ù.
long-acting sulfonylurea(chlorpropamide & glyburide)´Â 24-36½Ã°£ Áö¼ÓÇÏ´Â severe
hypoglycemia¸¦ ÀÏÀ¸Å³¼ö ÀÖ´Ù.
¨è hypoglycemia-associated autonomic failure
reduced counterregulatory hormone responses( -> impaired glucose generation),
hypoglycemia anawareness
i) defective glucose counterregulation
type 1 DM¿¡¼ ¿ÜºÎ Àν¶¸°À» Åõ¿©ÇÏ°Ô µÇ´Âµ¥ glucose levelÀÌ ¶³¾îÁü¿¡ µû¶ó Ç×»ó
Àν¶¸°ÀÌ °¨¼ÒÇÏ´Â °ÍÀº ¾Æ´Ï´Ù(1st defense¼Ò½Ç).
½Ã°£ÀÌ Áö³¯¼ö·Ï glucose°¨¼Ò¿¡ µû¸¥ glucagon¹ÝÀÀ(=2nd defense)ÀÌ ¼Ò½ÇµÈ´Ù.
defective glucagon productionÀÇ ¿øÀÎÀº ¾Ë·ÁÁ® ÀÖÁö ¾ÊÁö¸¸ ¥â cell¿¡¼ÀÇ insulin
production°ú ¹ÐÁ¢ÇÑ °ü·ÃÀÌ ÀÖ´Ù. glucagonÀÇ absolute deficiency°¡ ¾Æ´Ï¶ó functional
abnormalityÀÌ´Ù.
hypoglycemia¿¡ ´ëÇÑ epinephrine response(=3rd defense)°¡ °¨¼ÒÇÑ´Ù.
epinephrine deficiency´Â threshold abnormalityÀÌ´Ù. epinephrine response´Â ¿©ÀüÈ÷
³²¾Æ ÀÖÁö¸¸ ´õ¿í ³·Àº Ç÷´ç¿¡¼ ¹ÝÀÀÇÑ´Ù. critical pathologic event°¡ ¹Ù·Î reduced
epinephrine responseÀÌ´Ù.
¿¹> glucagon + epinephrine deficiency µ¿½Ã¿¡ ÀÖÀ» ¶§ absent glucagon´Üµ¶À϶§º¸´Ù
severe hypoglycemiaÀ§ÇèÀÌ 25¹è ´õ ³ô´Ù.
ii) hypoglycemia anawareness
hypoglycemiaÀÇ 1st manifestation : neuroglycopenia
hypoglycemia anawareness & defective glucose counterregulation(reduced
epinephrine)Àº hypoglycemia¸¦ 2ÁÖ°£ ÇÇÇÏ¸é °¡¿ªÀûÀÌ´Ù.
¨é hypoglycemia risk factor reduction
pt education, frequent SMBG, flexible insulin(and other drug), rational glycemic goal,
ongoing professional guidance & support
nonselective ¥â blocker(propranolol)º¸´Ù´Â selective ¥â1 antagonist(metoprolol or
atenolol) 2-3ÁÖ°£ hypoglycemia¸¦ ÇÇÇÒ °ÍÀ» ±ÇÇÑ´Ù.
2) Reactive(postprandial) hypoglycemia
i) carbohydrate metabolismÀÇ enzymatic defect°¡ ÀÖ´Â ¾ÆÀÌ¿¡°Ô¼ ¹ß»ý(rare)
: hereditary fructose intolerance, galactosemia
ii) gastric surgery(late dumping)
iii) alimentary hypoglycemia
½ÄÈÄ ±Þ¼ÓÇÑ Ç÷´ç »ó½Â ¹× gut incretinºÐºñ¸¦ ÀÏÀ¸ÄÑ insulin response¿Í µÚÀÌÀº
hypoglycemia¸¦ ÀÏÀ¸Å²´Ù.
reactive hypoglycemiaÀÇ Ä¡·á·Î ¥á-glucosidase inhibitor¸¦ °í·ÁÇÒ¼ö ÀÖ´Ù.
3) Fasting hypoglycemia Tab 334-1
¨ç drugs
i) sulfonylurea³ª repaglinide¿Í´Â ´Þ¸® ´Ù¸¥ OHA(biguanides, ¥á-glucosidase inhibitor,
thiazolidinediones)Àº insulin secretionÀ» ÀÚ±ØÇÏÁö ¾Ê´Â´Ù. ±×·¯¹Ç·Î plasma glucose
levelÀÌ ¶³¾îÁö¸é¼ insulin levelµµ ÈçÈ÷ °¨¼ÒÇÑ´Ù. ±×·³¿¡µµ ºÒ±¸Çϰí ÀÌ·± ¾àÁ¦µéÀº
´Ù¸¥ ¹æ½ÄÀ¸·Î hypoglycemia¸¦ ÀÏÀ¸Å³¼ö ÀÖ´Ù.
(insulin or insulin secretagogue¿Í º´ÇÕÄ¡·á½Ã)
ii) ethanol : gluconeogenesis block(glycogenolysis¸¦ blockÇÏÁø ¾Ê´Â´Ù)
ethanol-induced hypoglycemia´Â ÀüÇüÀûÀ¸·Î À½½ÄÀ» °ÅÀÇ ¸ÔÁö ¾ÊÀº »óÅ¿¡¼ ¼öÀϰ£
ÆøÀ½ÇÒ ¶§ »ý±ä´Ù. mortality rate = 10%
iii) pentamidine(1 vial = 300mg)
pneumocystis pneumonia & other parasite infectionÄ¡·á¿¡ ÀÌ¿ë
-> pancreatic ¥â cell¿¡ toxic
óÀ½¿£ insulin release, hypoglycemia(10%)
³ªÁß¿£ DM¹ß»ý
iv) quinine : insulin secretionÀÚ±Ø
v) salicylate & sulfonamide(rare)
vi) nonselective ¥â antagonist(propranolol)
¨è critical illness
extensive hepatic destruction(severe toxic hepatitis), renal failure(insulin clearance¡é),
sepsis, prolonged starvation
¨é endocrine deficiency
i) untreated primary adrenocortical failure(Addison's disease) or hypopituitarism
ii) chronic cortisol deficiency: anorexia & wt loss
iii) GH deficiency
iv) hypopituitarism¿¡¼ exercise, pregnancy, alcohol ingestionÈÄ
¨ê Non-¥â-cell tumor
non-islet cell tumor hypoglycemia
large mesenchymal or other tumor(hepatoma, adrenocortical tumors, carcinoids)
: IGF IIÀÇ overproduction¶§¹®
-> insulin or IGF-I receptor¸¦ ÅëÇÏ¿© ÀÛ¿ë
GH secretionÀÇ negative-feedback suppression ¶§¹®¿¡ IGF-I levelÀº ³·´Ù.
¡Å IGF-II/IGF-I ratio¡è
4) endogenous hyperinsulinism
i) primary pancreatic islet cell disorder, typically cell tumor(insulinoma)
ii) cell secretagogue, often a sulfonylurea and theoretically a cell stimulating
autoantibody
iii) autoantibody to insulin
iv) ectopic insulin secretion
insulin, proinsulin & C-peptide¸¦ ÃøÁ¤
* endogenous hyperinsulinismÀÇ critical diagnostic findings
fasting state with symptom of hypoglycemia »óÅ¿¡¼
plasma insulin > 6 uU/mL
plasma C-peptide > 0.6 ng/mL
plasma glucose < 45 mg/dL
5) insulinoma and other primary ¥â cell disorders
insulinoma´Â µå¹°Áö¸¸ 90%°¡ ¾ç¼ºÀ̹ǷΠfatal hypoglycemiaÀÇ Ä¡·á°¡´ÉÇÑ ¿øÀÎÀÌ´Ù.
¸Å³â 250,000¸í´ç 1¸í¿¡¼ ¹ß»ýÇϰí, 60%°¡ ¿©¼ºÀÌ´Ù
Ư¹ß¼ºÀ¸·Î ¹ß»ýÇÒ¶§´Â Æò±Õ 50¼¼¿¡¼ ¹ß»ýÇÏÁö¸¸ MEN 1°ú µ¿¹ÝµÉ¶§´Â 20´ë¿¡ ¹ß»ýÇÒ
¼öµµ ÀÖ´Ù.
99%À̻󿡼 ÃéÀå³»¿¡ À§Ä¡Çϰí Å©±â´Â º¸Åë 1-2cmÁ¤µµ·Î ÀÛ´Ù. 5-10%°¡ ¾Ç¼ºÀ̸ç
metastasis·Î ³ªÅ¸³´Ù. Mass effectº¸´Ù´Â hypoglycemia¶§¹®¿¡ ÀÓ»óÁõ»óÀÌ ³ªÅ¸³´Ù.
Symptomatic hypoglycemia°¡ overnight fastÈÄ¿¡ ³ªÅ¸³ªÁö¸¸ exerciseÈÄ¿¡ ³ªÅ¸³¯ ¼öµµ
ÀÖ´Ù.
<¿µ»óÁø´Ü>
i) octreotide scans : ¹Ý¼ö¿¡¼ localizeÇÒ¼ö ÀÖ´Ù.
ii) Arteriography: °ú°Å¿¡´Â ³Î¸® »ç¿ëÇßÀ¸³ª false-negative & false-positive result¶§¹®¿¡
ÇöÀç´Â ´ú ħ½ÀÀûÀÎ CT or MRI scanÀ» ÀϹÝÀûÀ¸·Î ³Î¸® »ç¿ëÇϸç tumorÀÇ 45-75%¸¦
detectÇÒ¼ö ÀÖ´Ù.
iii) preop ultrasound : ÀϺΠȯÀÚ¿¡¼ À¯¿ëÇÏ´Ù.
iv) Intraoperative ultrasonography : high sensitivity, ¸¸Á®ÁöÁö ¾Ê´Â tumor¸¦ localizeÇÒ ¼ö
ÀÖ´Ù.
<Ä¡·á>
i) surgical resection: solitary insulinomaÀÇ surgical resectionÀº ÀϹÝÀûÀ¸·Î curativeÇÏ´Ù.
ii) Diazoxide´Â insulin secretionÀ» ¾ïÁ¦Çϰí, somatostatin analogueÀÎ octreotide´Â
unresectable insulinomaȯÀÚ¿¡°Ô¼ hypoglycemia¸¦ Ä¡·áÇϱâ À§ÇØ »ç¿ëÇÒ¼ö ÀÖ´Ù.
6) factitious hypoglycemia
¿ÜºÎ Àν¶¸°À» Åõ¿©¹Þ´Â ȯÀÚ¿¡°Ô¼ insulinoma¿Í ±¸º°ÇÏ´Â ¹æ¹ýÀº
insulin levelÀº ³ôÀ¸³ª C-peptide levelÀº ³·´Ù.
sulfonylureaµµ endogenous insulinÀ» ÀÚ±ØÇϹǷΠfactitious hypoglycemia¸¦ ÀÏÀ¸Å³ ¼ö
Àִµ¥ À̶§´Â Ç÷Áß ¹× ¼Òº¯¿¡¼ ¾à¹°À» °ËÃâÇÔÀ¸·Î½á ¾Ë¼ö ÀÖ´Ù.