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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.