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HYPOGLYCEMIA

Dr SANJAY KALRA, D.M. [AIIMS]

DEFINITION
Hypoglycemia or low blood glucose is a clinical state associated with < 50mg/dl or low plasma glucose with typical symptoms.

Whipples triad =
venous plasma glucose <50mg/dl. Classical symptoms. Relief of symptoms with glucose.

DCCT Definition
Event resulting in seizure,coma ,confusion or symptoms like sweating,palpitation,hunger with finger stick glucose < 50 mg/dl and amelioration of symptom by elevation of blood glucose. Prodromal symptoms occuring before the event are well remembered. Severe hypoglycemic symptoms requiring hospital admission and treatment with IV glucose or glucagon.

Mechanisms for fasting hypoglycemia

Under production
hormone deficiencies enzyme defects substrate deficiency chronic infections. drugs

Over utilization
hyper insulinism insulinoma exogeneous insulin overdose. auto immunity Normal insulin level extra pancreatic tumour carnitine def, cachexia.

Fed state hypoglycemia

Early(alimentary)within 23 hours after meals Alimentary hyperinsulinism Postgastrectomy Functional(increased vagal tone) Hereditary fructose intolerance Galactosemia Leucine sensitivity Late(occult diabetic) 3-5 hours after meals Delayed insulin release due to beta cell dysfunction Counter regulatory deficiency of growth hormone,glucagon, cortisone,autonomic response,epinephrine.

Factors that precipitate hypoglycaemia Excessive insulin or SU administration- Error by patient or doctor. - Poor matching to patients lifestyle.

Increased insulin bioavailability-Exercise. -Injecting into abdomen. -Change to human insulin/analogs -Insulin antibodies. -Mismatch of syringes

Risk factors for severe hypo

Intensive insulin therapy & tight glycemic control. Hypoglycemia unawareness acute & chronic. Long duration of diabetes. Increasing age. Sleep. Excessive alcohol. Renal failure/ Hepatic failure Hypothyroidism/ Hypopituitarism/ Hypoadrenalism

Hypoglycemia in non diabetic scenario

ZE syndrome -Whipples triad, diarrhea ,muscle wasting,tiredness. May be associated with neurofibroma. 5 hour OGGT shows < 50mg/dl. Serum insulin level-20micro units /ml, increased proinsulin level. Hereditary fructose intolerance enlarged liver,jaundice,cirrhosis,albuminurIa, aminoaciduria,mental retardation. Ingestion of fruit leading to vomiting and hypoglycemia.

Common symptoms
Autonomic Adrenergic Sweating Palpitation Tremor Hunger Neuroglycopenic General

confusion nausea drowsiness headache speech problems incoordination atypical behaviour diplopia

Grading of Hypoglycaemia
Grade 1 or mild : patient can recognize hypo and able to self treat Grade 2 or moderate : severe hypo prevents patient from self treating but with assistance oral treatment is possible. Grade 3 or severe : severe degree of neuroglycopenia requiring parenteral glucagon/dextrose.

Sequence of responses to decrements in plasma glucose mg/dl

70 60 50 40 30 20 10 0 Counter regulation Adrenergic symptoms Neuroglycopenic symptoms Lethargy Coma Convulsions Permanent Damage Death

Hierarchy of Glucoregulation
Insulin (83 + 9 mg) Glucagon (68 + 2 mg) Epinephrine (68 + 2 mg) Growth hormone (66 + 2 mg) Cortisol (58 + 6 mg) Symptoms of hypoglycemia (53 + 2) Cognitive dysfunction (49 + 2)

Nocturnal Hypoglycemia
Is common (biochem hypos occur frequently). Asymptomatic/morning headache/hangover. Often identified by partner: sweating, fretting. May lead to sudden death. Unsatisfactory time action profile of certain insulins; physio defences against hypo reduced in flat position; sympathetic responses to hypo reduced in slow wave sleep Dawn phenomenon vs Somogyi effect.

Morbidity of Hypoglycemia
CNS Coma/convulsions/transient deficits/ataxia/brain damage/ intellectual impairment. Psycho Cognitive disorders/personality changes/ behavioural disorders/ automatism/ psychosis. CVS Arrhythmia/MI/TIA/stroke. Eye Vitreous haemorrhage Musculoskeletal Fracture/accidental injury.

Hypoglycaemic mortality Causes

Severe brain damage Hypostatic pneumonia Acute vascular events Dead in Bed Cardiac arrhythmia

Hypoglycaemic Unawareness
Absence of classical adrenergic warning symptom,
More vulnerable to develop severe hypoglycaemia Counter-regulatory failure :

Glucagon failure - 5 yr.to20 yr. Adrenaline failure - follows then 25 times higher risk for severe hypoglycaemia

Hypoglycemia unawareness
Perception of early warning symptoms impaired. Is not an all-or-none phenomenon. Affects one quarter of Type 1 diabetic patients. Correlates with glycemic control ? Duration of diabetes ? May be Acute or Chronic (Central autonomic failure).

Hypoglycaemia in Diabetes Hypothyroidism

Insulin degradation is less Insulin sensitivity is more Decreased appetite Decreased GH Decreased glycogenolysis

Hypoglycaemia in Diabetes Hypocortisolism

Decreased gluconeogenesis
By decreasing substrate By decreasing PEPCK By decreasing Glu-6phosphatase.

Decreased permissive effect on glucagon and epinephrine Decreased appetite

Hypoglycaemia in Diabetes Diabetic Nephropathy

Decreased catabolism of insulin Proteinuria Decreased appetite Nausea and vomiting Impaired absorption Impaired gluconeogenesis

Alcohol and hypoglycemia

Reduced gluconeogenesis Reduced hypo awareness Reduced tremors

DD of hypoglycemic and hyperglycemic coma

Symptoms,signs and laboratory findings Physical findings pulse rate pulse volume temperature respiration blood pressure skin Tongue tissue turgor eyeball tension breath reflex reflexes hypoglycemic coma hyperglycemic coma

increased full may be decreased shallow or normal normal,may be increased clammy,sweating moist normal normal no acetone brisk reflexes

increased weak may be decreased rapid and deep decreased dry dry reduced reduced acetone may be present diminished

Symptoms,signs and coma laboratory findings Laboratory tests urine glucose plasma glucose 200mg/dl plasma acetone plasma bicarbonate plasma CO2 blood pH

hypoglycemic coma

hyperglycemic

-ve to +ve depending on time of last voiding -ve to +ve -ve normal normal normal

+ve +ve greater than usually present low less than 20mg/litre diminished less than 7.35

MANAGEMENT ALGORITHM
Patient conscious Oral glucose/sucrose Patient unconscious IV glucose (50%) IM/SC glucagon

Recovery

No recovery I.V glucose (5%)

Follow up

-Identify cause -Re-educate

CAUTION
Glucagon may lose effect with repeated use. Glucagon is contraindicated in SU induced hypos. SU induced hypoglycemia may be very prolonged.It can be more fatal than insulin induced hypoglycemia. Duration of treatment depends on cause of hypo

Measures to avoid hypoglycemia in patients on insulin and/or sulfonylureas

Do not delay,skip or reduce food intake. Take a snack before physical exercise. Avoid insulin injections in the limb which is actively involved in the exercise. Avoid exercise during the peak time period of insulin action. When on human insulins,the time gap between insulin and food should be 15 minutes. When on analogs, keep the time gap less than 5 minutes Do not use sulfonylureas in patients with hepatic/ renal insufficiency. Ask the patient to avoid alcohol. In older diabetics do not insist on very tight control of blood glucose;prefer short acting sulfonylureas Regularly monitor blood glucose.

Drugs causing hypo

Increase in SU effect
Salicylates, probenecid, sulfonamides, nicoumalone, fluconazole [inhibits CYP2C9 which metabolizes glimepiride], ketoconazole, ciprofloxacin [inhibits CYP3A4 which metabolizes glibenclamide], gatifloxacin

Direct hypoglycemic effect

ACE(I), disopyramide, SSRIs, quinine, sulfamethoxazole, mefloquine, pentamidine, doxycycline, ethanol

Neonatal hypoglycemia
Hypoglycemia in the immediate postpartum period needs recognition,as this phenomenon is transient. Every newborn of diabetic mothers must be given a 5% glucose infusion for the first six hours and subsequently blood glucose monitored to prevent potentially fatal hypoglycemic convulsions.

Take home message

Single most important limiting factor in maintaining strict glycemic control. Can be life threatening Delicate balance needs to be kept between tight control & hypoglycemia. BE ON THE LOOK OUT FOR HYPO ALL THE TIME

Dhanya vaad
Have a safe journey back home