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INTRODUCTION

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Hypoglycemia is a common cause of altered mental status. Although classically associated with tachycardia, tremor, and diaphoresis, the predictive value of these manifestations is too low to be relied on.25 As a result, all patients with altered consciousness require either rapid point-of-care testing of their glucose concentrations or empiric treatment for presumed hypoglycemia. When rapidly diagnosed and treated, hypoglycemic patients typically recover without sequelae. Delayed or incomplete therapy may lead to permanent neurologic dysfunction.

HISTORY

In 1891, Fisher performed the unbelievable feat of identifying the 16 possible different spatial configurations of aldohexose (C6H12O6), the most prominent member being dextrose or D-glucose.44 This discovery won him the 1902 Nobel Prize in chemistry. This chapter will use dextrose as the term for the antidote and glucose as the general term for aldohexose.10 The diverse manifestations of hypoglycemia, and the treatment of severe cases with intravenous dextrose, have been appreciated for decades.80

Chemistry and Physiology

Sugar is the general term used for sweet carbohydrates that are used as food. Simple sugars are called monosaccharides and include glucose (also known as dextrose, as the L-isomer is hardly found in nature), fructose (also known as fruit sugar, the sweetest of them all) and galactose. The disaccharides include maltose, lactose, and sucrose (also known as table or granulated sugar).

Sugars (sucrose) are found in the tissues of most plants but are only present in sufficient concentrations for efficient extraction in sugarcane and sugar beet. Commercially, glucose is produced from the hydrolysis of starch. Several crops are the source of starch, with corn being the most common in the United States.

In humans, carbohydrates are absorbed and transported via 2 main systems. Sodium-dependent glucose transporters (SGLT1 through SGLT6) are responsible for the intestinal and renal glucose absorption.20 Their discovery was the first description of the mechanism of “flux coupling” or co-transporting, in which transporting one substrate down its concentration gradient (sodium in this case) creates energy that is used to transport a second substrate against a concentration gradient (glucose). The SGLT2 inhibitors (commonly termed “gliflozins”) are a family of drugs used to manage type 2 diabetes mellitus that inhibit SGLT2 in the proximal tubule of the nephron, resulting in glycosuria.41,99,105,147 Glucose uptake transporters include GLUT1-GLUT14 and HMIT (H+/myoinositol transporter). Facilitative transporters move molecules down their concentration gradient. This facilitative diffusion process does not require energy. Binding of glucose to one of the GLUT receptors causes a conformational change that results in its translocation across the membrane.64 GLUT4 is expressed in insulin-sensitive tissues and regulates whole-body glucose homeostasis.96 Even in low substrate conditions such as in neurons and the placenta, the high affinity for glucose by GLUT3 facilitates transport.12 The absorption of fructose in ...

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