<prompt> A 50-year-old obese woman has long-standing type 2 diabetes mellitus inadequately controlled on metformin and pioglitazone. Insulin glargine 15 units subcutaneously at bedtime has recently been started because of a hemoglobin A1C level of 8.4. Over the weekend, she develops nausea, vomiting, and diarrhea after exposure to family members with a similar illness. Afraid of hypoglycemia, the patient omits the insulin for 3 nights. Over the next 24 hours, she develops lethargy and is brought to the emergency room. On examination, she is afebrile and unresponsive to verbal command. Blood pressure is 8452. Skin turgor is poor and mucous membranes dry. Neurological examination is nonfocal; she does not have neck rigidity.Laboratory results are as follows:Na: 126 mEqLK: 4.0 mEqLCl: 95 mEqLHCO3: 22 mEqLGlucose: 1100 mgdLBUN: 84 mgdLCreatinine: 3.0 mgdLWhich of the following is the most likely cause of this patients coma?Diabetic ketoacidosisHyperosmolar nonketotic stateSyndrome of inappropriate antidiuretic hormone ADH secretionDrug-induced hyponatremia  <response>: This woman with poorly controlled diabetes has developed hyperglycemia and lethargy during an episode suggestive of viral gastroenteritis. Her presentation is most consistent with hyperosmolar nonketotic state. This condition typically occurs in type 2 diabetics who become volume depleted and develop renal insufficiency. Glucose is no longer able to spill out into the urine, the blood glucose skyrockets, and severe hypertonicity leads to brain dysfunction and coma. Serum osmolarity is calculated by the formula:18Plasmaglucose 2NaK2.8bloodureanitrogen This patients serum osmolarity is as follows:181100 12642.884 6126030351Thus, the serum osmolarity is greater than 350 mOsmL. Although the serum sodium is usually the main determinant of osmolarity, extreme hyperglycemia contributes significantly to this patients hypertonicity. Osmotically active particles in the extracellular fluid space pull water out of the intracellular space. This causes cellular dehydration in the brain and consequently the patients CNS changes.Diabetic ketoacidosis would be associated with a much lower serum bicarbonate level and with an elevated anion gap. This patients anion gap is 9 mEqL 126-, which is well within the normal range. This patients hyponatremia is minimal and is related to the osmotic effects of hyperglycemia. Patients with SIADH have an inappropriate production of ADH, leading to water retention and consequent hypotonicity not hypertonicity, as in this case. The diagnosis of SIADH or drug-induced hyponatremia cannot be made in the setting of severe hypovolemia. Although the oral hypoglycemic chlorpropamide can cause drug-induced hyponatremia, this patient was not taking a sulfonylurea. Although meningitis can be associated with hyponatremia, this patients hypertonicity and lack of meningeal signs point toward hyperosmolar nonketotic state as the cause of her illness. 