Diabetes Case 1

Patient Background:

A 64 year-old Caucasian woman with an 11-year history of type 2 diabetes is referred to you for further management. She is currently taking metformin 1000 mg bid, rosuvastatin 10 mg daily, and irbesartan 150 mg daily. Menopause was at age 47, and she has never taken any estrogen replacement therapy. Her examination is significant for a body mass index (BMI) of 32 kg/m2 (normal, 18.5 to 24.9 kg/m2), a blood pressure (BP) of 142/86 mm Hg, and decreased vibratory sensation in her feet with absent Achilles reflexes and pedal pulses. The patient does not have lower extremity edema.

Laboratory Results:

Glycated hemoglobin (A1c): 8.2% (normal, <5.7%)

Serum creatinine: 1.8 mg/dl (normal, 0.5 to 1.1 mg/dL)

Estimated glomerular filtration rate (eGFR): 28 mL/min/1.73 m2 (normal, >90 mL/min/1.73 m2)

Urine microalbumin/creatinine ratio of 62 mg/g (normal, <30 mg/g)

Low density lipoprotein (LDL) cholesterol: 93 mg/dL (normal, <100 mg/dL)

Question 1

Because the eGFR is <30/mL/min/1.73 m2, metformin was discontinued.
Which medication should be avoided given the patient’s eGFR?

Glyburide
Insulin Glargine
Pioglitazone
Linagliptin
Incorrect!
Correct!
Correct Answer
Glyburide

The risk of hypoglycemia is greatly increased with use of glimepiride and glyburide with an eGFR <60 mL/min/1.73 m2 due to the presence of two active metabolites cleared in part by the kidney. Thus, use of glyburide should be avoided with an eGFR <60 mL/min/1.73 m2.

Insulin doses often need to be adjusted as renal function declines, but insulin can still be used in patients with chronic kidney disease (CKD). No dose adjustment is indicated with thiazolidinediones such as pioglitazone in patients with CKD. However, thiazolidinediones are associated with fluid retention, and they should be used with caution if edema is present. Only a small amount of linagliptin is cleared renally; thus, no dose adjustment is indicated in patients with a reduced eGFR.

Diabetes Case 2

Patient Background:

A 75 year-old man with type 2 diabetes (T2D) for 8 years presents to the endocrinology office with pain and weakness of his thighs. He initially noted pain and weakness in his right thigh two months ago, but now has pain and weakness in both legs. He denies any back pain. He has difficulty getting up from the chair and has been using a wheelchair recently. He also reports that he has been losing weight. He currently takes glipizide 5 mg twice daily, metformin 1 g twice daily, aspirin 81 mg daily, rosuvastatin 40 mg daily, and enalapril 10 mg daily. Apart from diabetes and hypertension, he has no other known medical problems. He does not smoke or drink and is married. He denies any fever, trauma, or low back pain.

On examination, his height is 5' 9”, and his weight is 125 lb. His blood pressure is 130/80 mm Hg; his pulse is 60 beats per minute and regular. He is afebrile. He has 2/5 strength in both quadriceps and absent patellar reflexes bilaterally. No swelling, masses, or tenderness of the thigh muscles is noted, and distal pulses are normal. Straight leg raising produces no symptoms. Electrodiagnostic studies show markedly reduced amplitudes of sensory nerve and compound muscle action potentials with only mild slowing of conduction velocity in the motor fibers of femoral nerves bilaterally. Electromyogram of the paraspinal muscles is normal. His glycated hemoglobin (HbA1c) is 7.2% (normal, <5.7%); his serum creatinine is 1.0 mg/dL (normal, 0.8-1.3 mg/dL), and his creatine kinase levels are normal.

Question 1

Which of the following disorders is the most likely diagnosis in this patient?

Diabetic polyneuropathy
Diabetic muscle infarction
Diabetic amyotrophy
Statin induced rhabdomyolysis
Incorrect!
Correct!
Correct Answer
Diabetic amyotrophy

The patient has the classic presentation of diabetic amyotrophy. Diabetic amyotrophy (lumbosacral plexopathy, diabetic lumbosacral radiculoplexus neuropathy) presents classically in older type 2 diabetes patients with acute onset, asymmetric, focal pain in one thigh followed by weakness, which then progresses to involve the other leg over the next several months.

Patients with diabetic amyotrophy often have unintentional weight loss and may have autonomic symptoms, with or without associated peripheral neuropathy. This often presents in patients with relatively recent onset diabetes, which is usually in fair control. The exact pathogenesis is unclear, but likely involves ischemia, metabolic, and inflammatory factors. An ischemic nonsystemic vasculitis has been hypothesized as the cause. Electrodiagnostic studies (EDS) reveal markedly reduced amplitudes of sensory nerve and compound muscle action potentials with only mild slowing of nerve conduction velocities.

The proximal distribution of the pain in this case contrasts with the distribution that characterizes diabetic polyneuropathy, in which distal symptoms are typically greater than proximal symptoms. Sensory symptoms are not prominent with chronic inflammatory demyelinating polyradiculoneuropathy.

Incorrect: The clinical picture is not characteristic of statin-induced rhabdomyolosis, and the creatine kinase (CK) levels are normal. Diagnosis is based on classic clinical presentation in a diabetes patient with supporting EDS.

Incorrect: Diabetic muscle infarction usually presents with unilateral, acute onset pain and tenderness of thigh (or calf); swelling and tenderness of the affected muscle usually occurs. CK levels are often elevated; magnetic resonance imaging (MRI) reveals increased signal on T2- weighted images.

Incorrect: Spinal disc herniation is unlikely with absence of low back pain and normal straight leg raising test, and diabetic radiculopathy can be discounted based on the normal electromyogram of the paraspinal muscles.

Diabetes Case 3

Patient Background:

A 52 year-old woman presents to the emergency department reporting severe abdominal pain. She describes the pain as a 10, with 10 being the worst pain, and points to the epigastric area, stating that the pain sometimes feels as though it is moving towards her back. Her pain is associated with nausea, but no vomiting. She reports no known medical history other than being told that she might have “borderline” or “prediabetes” eight to ten years ago, but she has not followed up regularly with her doctor. She does not smoke or drink alcohol. In the emergency department, she is found to have a blood glucose level of 718 mg/dL (normal random, <140 mg/dL) and a glycated hemoglobin (HbA1c) of 15.8% (normal, <5.7%). Biochemical evaluation is significant for slight lactic acidosis and a markedly elevated serum lipase, but no evidence of ketosis. Because her blood sample appeared lipemic, her triglycerides are measured and found to be over 2000 mg/dL (desirable, <150 mg/dL).

The patient receives fluid resuscitation and is started on intravenous insulin in normal saline. Her blood glucose and triglyceride levels improve while her pain resolves and her appetite returns. After recovery, she understands that she is being discharged on insulin therapy and asks how diabetes mellitus may have contributed to her high triglyceride levels.

Question 1

Which of the following best explains the relationship between type 2 diabetes mellitus and hypertriglyceridemia-induced pancreatitis?

Insulin resistance is associated with suppression of low-density lipoprotein (LDL)
Insulin excess causes an increase in lipolysis and circulating levels of free fatty acids (FTAs)
Glucotoxicity results in insulin release
Insufficient insulin can lead to diminished lipoprotein lipase expression.
Incorrect!
Correct!
Correct Answer
Insufficient insulin can lead to diminished lipoprotein lipase expression.

Insulin promotes glucose uptake in the fat cell through the translocation of GLUT4 storage vesicles similar to that found in muscle cells. However, the glucose that adipocytes take up is not stored as glycogen, but rather partially metabolized down the glycolytic pathway to form glycerol-3-phosphate. This key metabolic intermediary serves as a backbone to which three FFAs are esterified to form triglyceride, which is then stored in the lipid droplet occupying most of the fat cell. Lipids are delivered to the fat cell through the circulation. Lipoprotein lipase located on the outside of the fat cell cleaves triglycerides to FFAs; these free fatty acids are taken up by adipocytes where they are re-esterified. Insulin enhances adipose tissue lipoprotein lipase expression. Insufficient insulin can contribute to excess levels of circulating FFAs and triglycerides.

Insulin promotes glucose uptake in the fat cell through the translocation of GLUT4 storage vesicles similar to that found in muscle cells. However, the glucose that adipocytes take up is not stored as glycogen, but rather partially metabolized down the glycolytic pathway to form glycerol-3-phosphate. This key metabolic intermediary serves as a backbone to which three FFAs are esterified to form triglyceride, which is then stored in the lipid droplet occupying most of the fat cell. Lipids are delivered to the fat cell through the circulation. Lipoprotein lipase located on the outside of the fat cell cleaves triglycerides to FFAs; these free fatty acids are taken up by adipocytes where they are re-esterified. Insulin enhances adipose tissue lipoprotein lipase expression. Insufficient insulin can contribute to excess levels of circulating FFAs and triglycerides.