Diabetic Ketoacidosis and Hyperglycaemic Hyperosmolar Syndrome by Dr. B. C. Kamanga - University of Zambia School of Medicine - Endocrinology-unza

Diabetic Ketoacidosis and Hyperglycaemic Hyperosmolar Syndrome B. C. Kamanga. MD Endocrinologist Department of Internal Medicine University of Zambia School of Medicine Lusaka Introduction DKA and HHS are acute life threatening hyperglycemic complications of DM If not efficiently and effectively treated, mortality rates for DKA and HHS in developed countries are 2–5% and 15%, respectively [1,2] Mortality rates in developing countries are higher for both conditions Mortality is usually a consequence of the underlying trigger(s) Graves EJ, Gillium BS. Vital Health Stat 13 (no. 133), 1997 Kitabchi AE et al. Diabetes Care 24:31–53, 2001 DKA is more common in T1DM than T2DM DKA occurs in both T1DM and T2DM Patients with T1DM have severe insulinopaenia DKA in T2DM ocurs during stressful situations, as a result of insulin resistance DKA Characteristics Hyperglycemia Wide anion gap metabolic acidosis Increased ketone production. Bicarbonate < 15.0 mmo/L pH <7.35 Pathogenesis Insulin deficiency and increased counterregulatory hormones leads to hyperglycaemia, lipolysis and ketone production. Hyperglycemia results from gluconeogenesis, glycogenolysis and impaired glucose utilization in peripheral tissues [1] Non-carbohydrate substrates for gluconeogenesis in the liver are alanine, lactate, and glycerol [2] Glutamine (9) is the non-carbohydrate substrate for gluconeogenesis in the kidneys Gerich JE et al., J Clin Invest 57:875–884, 1976 Felig P et al., J Clin Invest 50:1702–1711, 1971 Pathogenesis Hyperglycemia and elevated ketone levels cause osmotic diuresis that leads to hypovolemia and later decreased glomerular filtration rate. Decreased glomerular filtration rate aggravates the hyperglycemia Insulin deficiency and increased counterregulatory hormone levels activate hormone-sensitive lipase in adipose tissue, which breaks down triglyceride into glycerol and free fatty acids (FFA). Glycerol becomes a substrate for gluconeogenesis in the liver, while FFAs become hepatic precursors of the ketoacids. Oxidation of FFAs to ketone bodies is predominantly stimulated by glucagon. Precipitating Factors DKA and HH may be the initial manifestation of diabetes Precipitating factors for both DKA and HHS include infections, intercurrent illnesses, psychological stress, and poor treatment compliance Infection is the most common precipitating factor for DKA Urinary tract infection and pneumonia are the common infections Pathogenesis Lower amaounts of insulin are needed for antilipolysis, explaining why DKA is not common in T2DM [1,2] Yu SS, Kitabchi AE. J Biol Chem 248:3753–3761, 1973 Shade DS, Eaton RP. J Clin Endocrinol Metab 44:1038–1053, 1977 Precipitating Factors Other precipitating factors are CVA, alcohol/drug abuse, pancreatitis, pulmonary embolism, MI, and trauma. Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, beta-blockers may also precipitate the development of DKA and HHS Psychological problems complicated by eating disorders were a contributing factor in 20% of recurrent ketoacidosis in young women with T1DM [1] Polonsky WH et al., Diabetes Care 17:1178–1185, 1994 Symptoms DKA Symptoms Develop with hours to days Abdominal pain may mimic an acute abdomen HHS Symptoms Develop over days to weeks The most common clinical presentation for HHS is altered sensorium Signs of DKA and HHS Dehydration is more pronounced in HHS than DKA Lethargy Loss of consciousness in a few patients Acetone on breath (DKA) Kussmaul respiration due to severe metabolic acidosis (DKA). Focal neurological signs (e.g., hemiparesis) and seizures (HHS) Laboratory Findings Triad of hyglycaemia, hyperketonemia, and a wide anion gap metabolic acidosis(DKA) Diagnostic criteria for HHS include: Plasma glucose concentration >600 mg/dl Serum osmolality >320 mOsm/kg of water pH >7.3 Bicarbonate >18 mEq/l Insignificant ketonaemia Anion gap may increase, due to an increase in serum lactate levels [Kitabchi AE et al. Diabetes Care 24:31–53, 2001] Laboratory Findings Leukocytosis in the absence of infection Reduced serum sodium, due to hyperglycaemia-induced osmotic flux of water from the intracellular space into the blood Hypernatraemia in the presence of hyperglycemia results from profound water loss Hypertriglyceridemia results from impaired lipoprotein lipase activity Hypertriglyceridemia may spuriously lower serum sodium (pseudohyponatremia) in the specimen bottle Laboratory Findings Serum potassium concentration may be elevated in patients with DKA, because potassium shifts from the intracellular to the extracellular space due to acidemia, insulin deficiency, and hypertonicity Serum phosphate level may be normal or elevated because of metabolic acidosis. Dehydration can lead to increases in total serum protein, albumin, amylase, and creatine phosphokinase concentration Differentials for Ketosis Alcoholic ketoacidosis (hyperglycaemia is absent) [Umpierrez GE et al. J Crit Care 15:52–59, 2000] Decreased food intake (<500 …