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• 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.

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

Mechanisms for fasting hypoglycemia Under production hormone deficiencies enzyme defects substrate deficiency chronic infections. cachexia. auto immunity Normal insulin level extra pancreatic tumour carnitine def. . drugs Over utilization hyper insulinism insulinoma exogeneous insulin overdose.

.glucagon.autonomic response. cortisone.epinephrine.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.

.Error by patient or doctor.Factors that precipitate hypoglycaemia Excessive insulin or SU administration. -Injecting into abdomen.Poor matching to patient’s lifestyle. Increased insulin bioavailability-Exercise. -Mismatch of syringes . -Change to human insulin/analogs -Insulin antibodies.

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

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

Common symptoms Autonomic Adrenergic Sweating Palpitation Tremor Hunger Neuroglycopenic General confusion nausea drowsiness headache speech problems incoordination atypical behaviour diplopia .

• Grade 3 or severe : severe degree of neuroglycopenia requiring parenteral glucagon/dextrose. .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.

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) .

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

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

Hypoglycaemic mortality Causes • • • • Severe brain damage Hypostatic pneumonia Acute vascular events ―Dead in Bed‖ Cardiac arrhythmia .

follows then • 25 times higher risk for severe hypoglycaemia . Adrenaline failure .Hypoglycaemic Unawareness • Absence of classical adrenergic warning symptom.to20 yr.5 yr. More vulnerable to develop severe hypoglycaemia Counter-regulatory failure : Glucagon failure .

.  Affects one quarter of Type 1 diabetic patients.Hypoglycemia unawareness  Perception of early warning symptoms impaired.  Is not an all-or-none phenomenon.  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 .

Decreased permissive effect on glucagon and epinephrine Decreased appetite .Hypoglycaemia in Diabetes Hypocortisolism Decreased gluconeogenesis By decreasing substrate By decreasing PEPCK By decreasing Glu-6phosphatase.

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 .

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.DD of hypoglycemic and hyperglycemic coma Symptoms.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 .

35 .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.Symptoms.

V glucose (5%) Follow up -Identify cause -Re-educate .MANAGEMENT ALGORITHM Patient conscious Oral glucose/sucrose Patient unconscious IV glucose (50%) IM/SC glucagon Recovery No recovery I.

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

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

probenecid. fluconazole [inhibits CYP2C9 which metabolizes glimepiride]. sulfonamides. doxycycline. ketoconazole. ciprofloxacin [inhibits CYP3A4 which metabolizes glibenclamide]. ethanol . gatifloxacin • • Direct hypoglycemic effect ACE(I). sulfamethoxazole. pentamidine.Drugs causing hypo • • Increase in SU effect Salicylates. mefloquine. disopyramide. quinine. nicoumalone. SSRIs.

.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.

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

Dhanya vaad Have a safe journey back home .

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