800 mg/dL)Absence of or only slight ketosisNonketotic acidosisSevere dehydrationDepressed sensorium or frank comaNeurologic signs that may include grand mal seizures, hyperthermia, hemiparesis. and positive Babinski signs.Clinical FeaturesClassically, elderly individual with type 2 DM. with a several-week history of polyuria, weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma.The physical examination reflects profound dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status.Nausea, vomiting, abdominal pain and Kussmaul respirations (characteristic of DKA) are ABSENTPrecipitated by a serious, concurrent illness such as myocardial infarction, stroke or Sepsis.PathophysiologyRelative insulin deficiency and inadequate fluid intake are the underlying causes of HHS.Insulin deficiency increases hepatic glucose production (through glycogenolysis and gluconeogenesis) and impairs glucose utilization in skeletal muscle.Hyperglycemia induces an osmotic diuresis that leads to intravascular volume depletion, which is exacerbated by inadequate fluid replacement.The absence of ketosis in HHS is not well understood.Presumably, the insulin deficiency is only- relative and less severe than in DKA.Lower levels of counterregulatory hormones and free fatty acids have been found in HHS than in DKA.Liver is less capable of ketone body synthesis or that the insulin,''glucagon ratio does not favor ketogenesis.Laboratory Abnormalities and DiagnosisMost notable are the:Marked hyperglycemia ,Hyperosmolality (>350 mosmol/L), andPrerenal azotemia.The measured serum sodium may be normal or slightly low despite the marked hyperglycemia.The corrected serum sodium is usually increased ladd 1.6 meq to measured sodium for each 5.6- mmol/L (100 mg/dL) rise in the serum glucose].In contrast to DKA. acidosis and ketonemia are absent or mild.A small anion-gap metabolic acidosis may be present secondary to increased lactic acid.Moderate ketonuria. if present, is secondary to starvation.Treatment:Volume depletion and hyperglycemia are prominent features of both HHS and DKA.In both disorders, careful monitoring of the patient's fluid status, laboratory values, and insulin infusion rate is crucial.Underlying or precipitating problems should be aggressively sought and treated.In HHS, fluid losses and dehydration are usually more pronounced than in DKAThe patient with HHS is usually older, more likely to have mental status changes, and more likely to have a life-threatening precipitating event with accompanying comorbidities.Even with proper treatment, HHS has a substantially higher mortality rate than DKA (up to 15%).Fluid replacement should initially stabilize the hemodynamic status of the patient (1-3 L of 0.9% normal saline over the first 2-3 h).Because the fluid deficit in HHS is accumulated over a period of days to weeks, the rapidity of reversal of the hyperosmolar state must balance the need for free water repletion with the risk that too rapid a reversal may worsen neurologic function.If the serum sodium > 150 mmol/L (150 meq/ L), 0.45% saline should be used.After hemodynamic stability is achieved, the IV tluid administration is directed at reversing the free water deficit using hypotonic fluids (0.45% saline initially, then 5% dextrose in water, D5W). The calculated free water deficit (which averages 9-10 L) should be reversed over the next 1-2 days (infusion rates of 200-300 mL/h of hypotonic solution).Hypophosphatemia may occur during therapy and can be improved by using KPG4 and beginning nutrition.A reasonable regimen for HHS begins with an IV insulin bolus of 0.1 units/kg followed by IV insulin at a constant infusion rate of 0.1 units/ kg per hour.The insulin infusion should be continued until the patient has resumed eating and can be transferred to a SC insulin regimen.">