Your patient is a 48-year-old Hispanic man with a 4-year history of type 2 diabetes mellitus. He is currently utilizing NPH insulin/regular insulin 40/20 units prior to breakfast and 20/10 units prior to supper. His supper time has become variable due to a new job and ranges from 5 to 8 PM. In reviewing his glucose diary you note some very low readings (40-60 mg/dL) during the past few weeks at 3 AM. When he awakens to urinate, he feels sweaty or jittery so has been checking a fingerstick blood glucose. Morning glucose levels following these episodes are always higher (200-250) than his average fasting glucose level (120-150). Which change in his insulin regimen is most likely to resolve this patient’s early AM hypoglycemic episodes?
To recognize the best insulin regimen, you must first understand the pharmacokinetics of different insulin preparation— namely the peak time of onset of action and effective duration. The following describes the insulin preparations from shortest to longest duration. Lispro (as well as the newer aspart and glulisine) has a peak onset of 0.5 to 1.5 hours and effective duration of 3 to 4 hours. Regular insulin has a peak onset of 2 to 3 hours and effective duration of 4 to 6 hours. NPH has a peak onset of 6 to 10 hours and effective duration of 10 to 16 hours. Glargine or detemir provides basal insulin with an effective duration of 24 hours and no peak effect. This patient is experiencing early morning hypoglycemia resulting from his erratic supper time; in addition his fasting blood glucose levels (120- 150 mg/dL) are not adequately controlled. The most appropriate insulin regimen for this patient is a long-acting insulin such as glargine at bedtime along with a short-acting insulin such as lispro before each meal. This will allow better regulation of basal glucose levels while providing coverage at mealtime and will address the issue of variable mealtimes. Twice-daily regimens with NPH and regular insulin have fallen out of favor as they rarely provide sufficient coverage for either basal or meal-associated glucose production. Although premeal regular insulin is cheaper, lispro more closely matches the meal-associated glucose surge and provides better overall control.
A 40-year-old alcoholic man is being treated for tuberculosis, but he has no compliant with his medications. He complains of increasing weakness, fatigue, weight loss, and nausea over the preceding 3 weeks. He appears thin, and his blood pressure is 80/50 mm Hg. There is increased pigmentation over the elbows and in the palmar creases. Cardiac examination is normal. Which of the following is the best next step in evaluation?
This patient’s symptoms of weakness, fatigue, and weight loss in combination with hypotension and extensor hyperpigmentation are all consistent with Addison disease (adrenal insufficiency). Tuberculosis can involve the adrenal glands and result in adrenal insufficiency. Measurement of serum cortisol baseline and then stimulation with cosyntropin (a synthetic ACTH analogue) will confirm the clinical suspicion. The ACTH stimulation test is used to determine the adrenal reserve capacity for steroid production. Cortisol response is measured 30 and 60 minutes after cosyntropin is given intramuscularly or intravenously; a value of 18 μg/dL or above effectively excludes adrenal insufficiency. Hemochromatosis can cause hyperpigmentation but not the weight loss and hypotension. Bacteremia would not cause the gradually increasing symptoms or the hyperpigmentation. In some patients with weight loss and nausea, an EGD may be warranted; however, the clinical features of adrenal insufficiency in conjunction with poorly treated tuberculosis would first direct attention toward adrenal status.
A 37-year-old woman presents with difficult-to-control diabetes. The diabetes developed 3 years prior to this visit, when the patient began to notice fatigue, nocturia, and visual blurriness. She has been placed on metformin, glyburide, and finally pioglitazone at maximal doses, and yet her hemoglobin A1C is still above target at 8.2. She has compliant with her medical regimen and is concerned about her health status. There is no family history of diabetes. On examination, her BP is 126/80, BMI is 23.7, and general physical examination is normal. She has no evidence or retinopathy or peripheral neuropathy. Anti-islet cell autoantibodies, including anti-glutamic acid decarboxylase (GAD) antibodies, are positive. What is the likely diagnosis?
Classically, you think of type 1 diabetes as immune-mediated destruction of beta cells leading to insulin-dependent disease in children or adolescents, and type 2 diabetes as a disease of insulin resistance in obese adults with positive family history of the disease—but reality is more complex. Lateonset autoimmune diabetes of adults (LADA) typically occurs in nonobese adults, often without a family history of diabetes. It is slower in onset and less ketosis prone than type 1 diabetes, but responds poorly to agents such as metformin that improve insulin sensitivity. Autoantibodies (anti-GAD antibodies being the most sensitive and specific) characterize LADA as well as type 1 DM. An important aspect of LADA is that early use of insulin is necessary to adequately control the blood glucose levels. Maturity-onset diabetes of young is the opposite of LADA, that is, that is, a condition resembling type 2 diabetes (ie, often associated with obesity and a positive family history) yet occurring before the age of 20. This patient’s autoantibodies, thin body habitus, and unresponsiveness to oral hypoglycemic would not go with MODY. Cushing syndrome is often associated with hyperglycemia due to the insulin counter-regulatory effect of cortisol, but this patient does not have the other clinical features that almost always accompany cortisol excess. Glucagonomas are rare islet cell tumors that produce weight loss, malabsorption, and a severe skin rash. The patient in question has none of the features of this rare syndrome.
A 45-year-old G2P2 woman presents for annual examination. She reports regular menstrual cycles lasting 3 to 5 days. She exercises five times per week and reports no difficulty sleeping. Her weight is stable at 140 lb and she is 5 ft 8 in tall. Physical examination is unremarkable. Lab studies are normal with the exception of a TSH value of 6.6 mU/L (normal 0.4-4.0 mU/L). Free T4 is normal. Which of the following represents the best option for management of this patient’s elevated TSH?
In this patient with a TSH below 10 mU/L and no symptoms of hypothyroidism, the diagnosis is subclinical hypothyroidism. Recommendations include checking a free thyroxine level (it should be normal in subclinical hypothyroidism) and repeating the TSH in 3 months to monitor for progression toward overt hypothyroidism. The patient should be informed about the symptoms of hypothyroidism. Thyroxine therapy is not currently recommended for asymptomatic patients in whom the TSH level is below 10 mU/L. Although an abnormal TPO Ab increases the risk of progression to overt hypothyroidism, it does not affect your present management. Thyroid uptake scan may be useful in the diagnosis of hyperthyroidism, but not in possible hypothyroidism. Iodide deficiency is not seen in the United States because of dietary iodide supplementation.
A family brings their 82-year-old grandmother to the emergency room stating that they cannot care for her anymore. They tell you, “She has just been getting sicker and sicker.” Now she stays in bed and won’t eat because of stomach pain. She is too weak to go to the bathroom on her own. Her symptoms have been worsening over the past year, but she has refused to see a doctor. The patient denies symptoms of depression. Blood pressure is 90/54 with the patient supine; it drops to 76/40 when she stands. Heart and lungs are normal. Skin examination reveals a bronze coloring to the elbows and palmar creases. What laboratory abnormality would you expect to find in this patient?
This patient’s presentation suggests adrenal insufficiency (Addison disease). Hyponatremia is caused by loss of sodium in the urine (aldosterone deficiency) and free-water retention. Sodium loss causes volume depletion and orthostatic hypotension. Hyperkalemia is caused by aldosterone deficiency, impaired glomerular filtration, and acidosis. Ten to twenty percent of patients with adrenal insufficiency will have mild hypercalcemia; hypocalcemia is not expected. Complete blood count can reveal a normocytic anemia, relative lymphocytosis, and a moderate eosinophilia. Microcytic anemia would suggest an iron disorder or thalassemia. The hyperpigmentation results from the release of pro-opiomelanocortin which has melanocyte-stimulating activity. Hyperpigmentation is not seen if pituitary dysfunction is causing the adrenal insufficiency (ie, in secondary hypoadrenalism).
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