Hyperglycemic Hyperosmolar Nonketotic Coma (HHNKC) - Case Discussion

A 63-year-old man is brought to the emergency room in an unconscious state. He was apparently in good health until 1 week before admission, when he experienced an insatiable thirst that he attempted to satisfy by drinking large quantities of beer and soda drinks. He had complained of having nocturia for several days, and had several bouts of diarrhea yesterday. He took to his bed yesterday and was found unconscious this morning.
He takes no drugs, has not seen a physician for several years, and works regularly as a house painter. His health has been good previously. His mother had diabetes in her eighties and died of a stroke.

Physical examination reveals a deeply unconscious, acutely ill man who has several focal right-sided seizures during examination. His skin and mucous membranes are dry and his ocular globes are quite soft. His BP is 98/60 mm Hg, pulse is 120 per minute, and rectal temperature is 38°C (100.9°F), and he exhibits unlabored respirations at a rate of 13 per minute. Except for the findings of minimal hepatomegaly, absent knee jerks, and bilateral Babinski's reflexes, the examination findings are otherwise normal.

Laboratory data consist of the following:

• Hgb, 16.2 g/dL; Hct, 51%; and WBC, 1,340/ mm3 (92% polymorphonuclear leukocytes). 
• Urinalysis reveals a specific gravity of 1.030; pH, 6.0; glucose, 4+; acetone, moderate amounts; and protein, trace amounts. 
• Arterial blood gas analysis reveals a pH of 7.41, PCO2 of 35 mm Hg, and PO2 of 68 mm Hg. 
• Both chest radiographic and head CT scan findings are normal. 
• His ECG show s sinus tachycardia with nonspecific ST-T–w ave changes. 
• Serum findings are BUN, 68 mg/dL; creatinine, 2.3 mg/dL; glucose, 1,420 mg/dL; ketones, trace amounts; sodium, 153 mEq/L; potassium, 4.6 mEq/L; chloride, 110 mEq/L; and bicarbonate, 26 mEq/L.

1. What is the diagnosis in this patient and how would you relate it to the major physical and laboratory findings?
2. What is the nature of this patient's endogenous insulin secretion, and is this type of diabetes hereditary?
3. Why did ketoacidosis not develop in this patient?
4. How is his liver involved in the pathogenesis of his hyperglycemia?
5. What are the major hormones that are counterregulatory to insulin action? Are they playing any role in this man's illness?
6. What would you predict about the state of his intravascular volume?
7. What are the major therapeutic goals in this patient?

Answers And Case Discussion


1. What is the diagnosis in this patient and how would you relate it to the major physical and laboratory findings?
This elderly patient presents in a comatose state preceded by several days of progressive symptoms of polyuria, polydipsia, and nocturia. His laboratory data show the presence of marked hyperglycemia but no acidosis. In this setting, his moderate ketonemia and ketonuria are most likely secondary to starvation. Therefore, the diagnosis in this patient is  Hyperglycemic Hyperosmolar Nonketotic Coma (HHNKC)
.
His serum osmolality can be calculated using the formula:

• estimated osmolality = 2([Na] + [K]) + [glucose]/18 + [BUN]/2.8. 

For this patient, the estimated osmolality is calculated to be 418, which is consistent with a severe hyperosmolar state.

2. What is the nature of this patient's endogenous insulin secretion, and is this type of diabetes hereditary?
This patient has type 2 Diabetes mellitus. When type 2 Diabetes mellitus is of short duration, such as in this patient, and when patients are obese, the endogenous insulin levels are typically normal or elevated. Such patients are still able to maintain sufficient endogenous insulin secretion to prevent ketoacidosis from developing under basal conditions. Only severe stress with elevated catecholamines plus glucagon and decreased insulin secretion will precipitate DKA in people with
type 2 Diabetes mellitus
Heredity plays an important role in type 2 Diabetes mellitus, although the mode of inheritance is largely unknown. type 2 Diabetes mellitus is also a heterogeneous disorder, and different forms of genetic influences or defects may exist. Evidence for a genetic influence in the acquisition of type 2 Diabetes mellitus include
(a) a strong family history of the disease,
(b) a very high prevalence of the disease in certain population groups
(c) a concordance rate of 90% to 100% in monozygotic twins, and
(d) an apparent autosomal dominant mode of transmission of maturity-onset diabetes of the young (an uncommon monogenic form of type 2 Diabetes mellitus).

3. Why did ketoacidosis not develop in this patient?
This patient has sufficient endogenous insulin to prevent
(a) lipolysis (FFA levels are lower in the setting of HHNKC than of DKA), and
(b) full activation of the hepatic ketogenic system.
In the presence of a reasonable level of endogenous insulin, the glucagon-to-insulin ratio is not high enough to lead to significant ketogenesis and ketoacidosis.

4. How is his liver involved in the pathogenesis of his hyperglycemia?
The hyperglycemia in this patient results from the increased hepatic production of glucose due to increased glycogenolysis and gluconeogenesis, and from the decreased uptake and utilization of glucose by the liver, muscle, and adipose tissue. All of these changes are due to the underlying
insulin resistance of type 2 Diabetes mellitus and the relative, but not absolute, insulin deficiency in the presence of acute stressful conditions. In addition, people with type 2 Diabetes mellitus and underlying renal disease may present with HHNKC due to decreased clearance of insulin.

5. What are the major hormones that are counterregulatory to insulin action? Are they playing any role in this man's illness?
Glucagon, cortisol, catecholamines, and growth hormone (GH) are the chief insulin counterregulatory hormones that are elevated in major stressful conditions like HHNKC. Through the operation of several specific mechanisms, they counteract the effects of insulin, and this worsens the hyperglycemic state.

6. What would you predict about the state of his intravascular volume?
The intravascular volume is severely depleted in this patient (note the related findings revealed by the physical examination). The following sequence of events
may take place in patients with type 2 Diabetes mellitus if they are not adequately treated:

hyperglycemia → osmotic diuresis → loss of fluid and electrolytes → dehydration → worsening hyperosmolarity and osmotic diuresis → elevated counterregulatory hormones → hemoconcentration and hypovolemia → prerenal azotemia → circulatory insufficiency/shock/lactic acidosis → irreversible coma → death.

Therefore, if this patient's condition is not rapidly treated, irreversible coma and death may ensue.

7. What are the major therapeutic goals in this patient?
The major immediate therapeutic goals are
(a) replacement of fluid and electrolytes,
(b) correction of the hyperglycemia (relatively small doses of insulin are sufficient for patients in HHNKC compared with DKA), and
(c) identification and management of the precipitating factors.
HHNKC is a very serious medical emergency with a high risk of mortality unless an immediate, aggressive, and comprehensive management regimen is instituted. Once the acute situation is resolved, the diabetes may be managed in the long term either with diet and oral agents or with insulin.