Mrs. T, aged 40 years, presented to the clinic with complaints of polyuria, polydipsia and blurred vision, progressively worsening over a period of weeks. An obese woman with a family history of diabetes, Mrs. T underwent laboratory studies confirming fasting hyperglycemia (353 mg/dL), glucosuria and elevated hemoglobin (Hb)A1c (10.2%).
She was newly diagnosed with type 2 diabetes and started on metformin (Fortamet, Glucophage, Glumetza, Riomet) 500 mg daily and sent for a dietary consultation and diabetic education. Mrs. T was given a glucometer and told to check her blood glucose at least once a day, and to report to the office in eight days with her readings; further adjustments would be made thereafter.
Unfortunately, Mrs. T failed to report with her blood glucose levels, nor did she appear for a scheduled two-month follow-up visit. Three months after initial presentation, she came into the office with several more complaints. She reported progressive malaise and fatigue, bilateral upper and lower extremity cramps, nausea, abdominal pain and headache.
She denied fever and chills, but a review of systems was positive for an unintentional 50-lb weight loss over the past five months. She reported no cough, chest pain, or palpitations, but admitted to shortness of breath at rest. She had significant nausea but no vomiting and complained of early satiety and slight constipation. No dark or bloody stools were reported.
Mrs. T’s abdominal pain was described as generalized achiness and cramp-like, worsening with food. She had urinary frequency, but no dysuria. She had a dull nonlocalized headache and felt off-balance and was having difficulty concentrating. Moreover, her blurry vision and polydipsia had not improved.
Mrs. T stated that she took the metformin as directed and was checking her blood glucose on occasion. Her numbers, including fasting numbers, ranged from 300 mg/dL to 400 mg/dL.
A physical examination revealed an ill-appearing obese woman. Mrs. T was afebrile with the following vitals: BP 152/84, pulse 72 beats per minute and regular, respiratory rate 20 breaths per minute, weight 250 lb, height 68 in (BMI 41.5). Notably, the woman’s weight was down from 308 lb, measured four months ago. Her head and neck exam was unremarkable. The ears, nose and throat were also normal with moist mucous membranes.
Mrs. T’s lungs were clear to auscultation and percussion, and no cough was apparent. A cardiovascular exam showed regular heart sounds with an intact S1 and S2 and no audible murmurs. Her abdomen was protuberant but revealed normoactive bowel sounds. She was tympanic and soft to percussion and palpation, respectively. Diffuse, nonlocalized tenderness was noted with no rebound or guarding and no fluid wave. No obvious organomegaly or mass was noted on presentation.
Mrs. T’s skin had good turgor and was dry to the touch with no rash. A 1-cm abscess actively draining pus-like fluid was noted beneath her right breast. The abscess was mildly tender with surrounding erythema extending approximately 1 cm in every direction. There was no lower-extremity edema, and pulses were 2+ and symmetric.
Neurologic exam revealed a lethargic woman who was oriented to person, place and time. Despite a flat affect, Mrs. T’s judgment appeared intact. However, she had mild difficulty expressing her thoughts and completing sentences. Her gait was sluggish and mildly off-balance. Deep tendon reflexes throughout were 2+ and symmetric, and her strength of upper and lower extremities was normal and symmetric. Motor power and sensory perception were intact.
2. Laboratory Data
A study of Mrs. T’s lab results requires a retrospective view of those from three months earlier, which included a basic metabolic profile (BMP), urinalysis, lipid panel, HbA1c and urine microalbumin/creatinine ratio. Her fasting blood glucose was 353 mg/dL; blood urea nitrogen and creatinine were 7.0 mg/dL and 0.76 mg/dL, respectively. Sodium, potassium, and calcium levels were all normal.
Mrs. T’s carbon dioxide reading was 19 mmol/L (reference range 20-32). Her urine showed a specific gravity of >1.030 and had 3+ glucosuria and 1+ ketonuria. A trace of protein was also found. Her fasting lipid panel expressed a total cholesterol level of 199 mg/dL, triglycerides modestly high at 154 mg/dL, HDL 37 mg/dL, and LDL above goal at 131 mg/dL. The microalbumin/creatinine ratio was normal. Her HbA1c, however, was very high at 10.2%.
When Mrs. T presented to the clinic three months later, a finger-stick glucose was 386 mg/dL, which led to a BMP and complete blood count. WBC was 16.3 × 103/µL with a left shift: neutrophils 13.2 (reference range 1.63-6.96). Hemoglobin and hematocrit were 16.1 g/dL and 50.9%, respectively, and platelets were normal at 327 × 103/µL.
Most remarkable was a nonfasting glucose of 403 mg/dL and bicarbonate of 6.5 mmol/L (reference range 24.4-33.0). Mrs. T’s potassium was 5.7 mmol/L, sodium 131 mmol/L, chloride 102 mmol/L (reference range 98-107), and calcium 9.0 mg/dL.
Diabetic ketoacidosis (DKA) and its counterpart hyperosmolar hyperglycemic state (HHS) are both severe complications of diabetes mellitus. The conditions differ in the amount of ketosis and severity of hyperglycemia but can also have some overlapping features.
In general, DKA is seen more frequently in type 1 insulin-dependent diabetes and is a common presentation in the new onset of that condition. Typically, patients who develop DKA have higher arterial pH and lower bicarbonate levels than those who have HHS.
Individuals with HHS frequently have type 2 diabetes with uncontrolled hyperglycemia, in which serum glucose measurements may reach >1,000 mg/dL. Urine and serum ketones are seen infrequently in HHS, since those patients may still have a small amount of endogenous insulin production. Urine and serum ketones are both associated with significant water deficit.
DKA and HHS may be precipitated by such events as infection or inadequate insulin therapy. Compromised fluid intake is often a contributing factor, particularly in the elderly.1 HHS often develops more insidiously than does DKA, possibly over weeks rather than days.
In both conditions, hyperglycemia is accompanied by polyuria, polydipsia and weight loss. As severity increases, such neurologic symptoms as lethargy and obtundation, which can lead to coma in severe cases, can be seen. Neurologic deficits are more commonly seen in HHS due to the greater degree of hyperosmolality. Hyperventilation and abdominal pain are more commonly seen in DKA and correlate in severity with the degree of acidosis.2
Fluid depletion tends to be greater in HHS than DKA, yet fluid replacement is paramount in the treatment of both. Providers must take care not to replete fluids too rapidly so as to avoid cerebral edema associated with rapid reduction in the plasma osmolality. Typically, isotonic saline is used.3
Once fluid replacement is initiated, continuous insulin infusion is the treatment of choice, with careful monitoring of potassium levels.4 In fact, potassium chloride is typically added to the replacement fluid once the serum levels fall, reflecting potassium entering the cells once again with infusion of insulin.5
Mrs. T was admitted to the hospital intensive care unit with a diagnosis of diabetic ketoacidosis, possibly precipitated by cellulitis. She was fluid-resuscitated with normal saline and then given an insulin drip. The infection on her right breast resolved with a short course of antibiotics, and her obtundation and malaise were completely abated on discharge.
Mrs. T received diabetes education, was started on long-acting insulin, and on discharge was using rapid-acting insulin while counting carbohydrates. She now checks her blood glucose approximately four times a day. Mrs. T continues to be followed by an endocrinologist and hopes to begin using an insulin pump in the near future.
This patient’s initial presentation as an obese woman aged 40 years with impaired fasting glucose yielded a natural tendency to diagnose her with type 2 non-insulin-dependent diabetes. However, Mrs. T’s progressive weight loss and hyperglycemia despite metformin therapy, coupled with lab data supporting an acidotic state, illustrates why the astute clinician must keep an open differential diagnosis to include type 1 diabetes.
Michele D. Tinge, MPAS, PA-C, is a physician assistant at Alton Internal Medicine in Alton, Ill.
- Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the diabetic hyperosmolar state. J Am Geriatr Soc. 1987; 35:737-741.
- Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001; 24:131-153. Available at care.diabetesjournals.org/content/24/1/131.long.
- Waldhäusl W, Kleinberger G, Korn A, et al. Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentration. Diabetes. 1979; 28:577-584.
- Barrett EJ, DeFronzo RA. Diabetic ketoacidosis: diagnosis and treatment. Hosp Pract (Off Ed). 1984;19:89-95.
- Umpierrez GE, Cuervo R, Karabell A, et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004; 27:1873-1878. Available at care.diabetesjournals.org/content/27/8/1873.long.