HYPOGLYCEMIC AGENTS Rama B. Rao, M.D. Bellevue Hospital Center/NYUMC New York, N.Y.

Glycemic Control Agents Insulin Sulfonylureas Meglitinides: Repaglinide Biguanides: Metformin Thiazolidinediones: Pioglitazone  Glucosidase inhibitors

Glycogen Glucose MUSCLE CELL Storage P Pyruvate Kreb’s Oxidative ATP Phosphorylation Cycle I I

Glucose MUSCLE CELLS P Pyruvate I Kreb’s ATP Glycogen EPINEPHRINE GLUCAGON Oxidative Phosphorylation

Glucose MUSCLE CELLS P Pyruvate I Kreb’s ATP KETONES FFA Phosphorylation Oxidative

P Glycogen Glucose BRAIN Pyruvate Krebs Oxidative Phosphorylation ATP KETONES

HYPOGLYCEMIA Hunger/Anxiety Focal neurological deficits Confusion Seizures Coma Hypothermia

P Glucos e BRAIN: Anterior Pituitary ATP GH EXCITATORY NT Adrenal medulla Catecholamines

Other Manifestations Tachycardia Tremor Diaphoresis

ALPHA CELL OF PANCREAS GLUCAGON Decreased Glucose Catecholamines, Amino acids

Glucose MUSCLE CELLS P Pyruvate I Kreb’s ATP Glycogen EPINEPHRINE GLUCAGON Oxidative Phosphorylation

Glycogen Glucose LIVER CELL Storage I P Pyruvate Kreb’s ATP EPINEPHRINE GLUCAGON Oxidative Cycle Phosphorylation

Ca 2+ PANCREAS: BETA ISLET CELL Insulin MEMBRANE DEPOLARIZATION

K+K+ ATP Ca 2+ PANCREAS: BETA ISLET CELL Insulin Sulfonylurea, Meglitinides* *Repaglinide

SULFONYLUREAS Risk of hypoglycemia –Fasting –Elderly: variable data –Chronic renal failure

SULFONYLUREA INDUCED HYPOGLYEMIA Administration of glucose for acute correction Decontamination Nutrition, IV access Admission

SULFONYLUREAS Monitor potassium, phosphate Urinary alkalinization for chlorpropamide Octreotide for refractory hypoglycemia Observation for at least 12 hours after last dose octreotide

Octreotide Dosing Adults: 50  g subcutaneously every 6 hours Children: 4-5  g/kg/day subcutaneously divided every 6 hours, with maximum not exceeding the adult dose

K+K+ ATP Ca 2+ PANCREAS: BETA ISLET CELL Insulin DIAZOXIDE

Ca 2+ PANCREAS: BETA ISLET CELL Insulin OCTREOTIDE G

SUFONYLUREAS: Other Effects Inhibition of aldehyde dehydrogenase SIADH

INSULIN Oral exposure is benign Parenteral Exposures –Unpredictable in overdose –May be dependent upon quantity injection –Formulation Treatment: nutrition, supplemental glucose infusion

HYPOGLYCEMICS: MANAGEMENT Identify and treat hypoglycemia Admission especially if brought to coma or seizure Nutrition –Consider enteral infusion of feeds via NG Tube Monitor electrolytes

GLUCOSE ADMINISTRATION Adults –D 50 W 1 gram/kg Children –D 25 W gram/kg –D 10 W gram/kg in neonates Infusion of D 10 W at a total of 1 gram/kg/hr Monitor potassium

METFORMIN Rarely causes true hypoglycemia Adverse reaction –Lactic acidosis only in patients with renal insufficiency or shock states. –Treatment of lactic acidosis: hemodialysis Caveat: Co-ingested substances

Glycogen Glucose MUSCLE CELL P Pyruvate I Kreb’s ATP METFORMIN Oxidative Phosphorylation

Glycogen LIVER CELL P Pyruvate ATP METFORMIN Phosphorylation Oxidative

OTHER AGENTS AFFECTING CARBOHYDRATE METABOLISM Ethanol Beta adrenergic antagonists Unripened ackee fruit Valproic acid Salicylates Pentamidine Quinidine Disopyramide

Glycogen Glucose LIVER CELL Pyruvate Oxidative ATP Lactate Phosphorylation NAD+ NADH+H + ETHANOL Acetate

ALPHA CELL OF PANCREAS GLUCAGON Decreased Glucose Catecholamines, Amino acids BETA ADRENERGIC ANTAGONISTS

Glycogen LIVER CELL P Pyruvate ATP Phosphorylation Oxidative ACKEE

Glucose LIVER P Pyruvate I Kreb’s ATP KETONES FFA Phosphorylation Oxidative ACKEE VALPROIC ACID

Glucose LIVER P Pyruvate I Kreb’s ATP Phosphorylation Oxidative Alanine SALICYLATES

Ca 2+ PANCREAS: BETA ISLET CELL Insulin Membrane depolarization PENTAMIDINE ALLOXAN STREPTOZOCIN

P BRAIN Pyruvate Kreb’s Oxidative Phosphorylation ATP Acetyl Co A THIAMINE GLUCOSE

Glycogen Glucose MUSCLE CELL Storage P Pyruvate Kreb’s Oxidative ATP Phosphorylation Cycle I I

Glucose MUSCLE CELLS P Pyruvate I Kreb’s ATP Glycogen EPINEPHRINE GLUCAGON Oxidative Phosphorylation

Glucose MUSCLE CELLS P Pyruvate I Kreb’s ATP KETONES FFA Phosphorylation Oxidative

P Glycogen Glucose BRAIN Pyruvate Krebs Oxidative Phosphorylation ATP KETONES

Glycogen Glucose LIVER CELL Storage I P Pyruvate Kreb’s ATP EPINEPHRINE GLUCAGON Oxidative Cycle Phosphorylation