Clinical Quiz: Diabetes Case Questions

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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.

Diabetes Case 4

Case Background:

A 21 year-old man with a 7-year history of type 2 diabetes mellitus (T2DM) presents for follow-up. He was diagnosed with T2DM at age 14 years. At that time, his body mass index (BMI) was in the 99th percentile for his age. His mother has a history of gestational diabetes mellitus during her pregnancy with him and was diagnosed with T2DM in her early forties, when he was ten years old. His current BMI is 41 kg/m2  (normal, 18.5 to 24.9 kg/m2). He has been treated with metformin and insulin analogues, but he has not been taking the insulin recently because he feels unwell after he exercises with symptoms of shakiness, sweatiness, and hunger. His glycated hemoglobin (HbA1c) is 9.2% (normal, <5.7%). He wants to know more about diabetes mellitus and asks if there are other medication options for him.

Question 1

Q1. The pathophysiology of the diabetes mellitus of this patient is characterized by which of the following?

A. Increased glucagon secretion
B. Insulin resistance and beta cell dysfunction
C. Increased peripheral glucose uptake
D. Decreased hepatic gluconeogenesis
E. A and B
Incorrect!
Correct!
Correct Answer
E. A and B

Rationale: Insulin, produced and secreted by beta cells located in clusters of pancreatic cells called the islets of Langerhans, is the most potent anabolic hormone, promoting the uptake, utilization, and storage of both glucose and lipids. T2DM is characterized by resistance to the actions of insulin in target tissues. Pancreatic beta cells compensate by increasing insulin secretion, and patients with insulin resistance initially have high circulating levels of insulin and maintain normal serum levels of glucose. Eventually, however, pancreatic beta cells start to fail. When they can no longer supply enough insulin to meet these increased requirements, T2DM develops. It is believed that the chronic demand for elevated insulin secretion in insulin resistant subjects unmasks a secondary defect in the beta cells, resulting in progressive loss of beta cell function. Thus, both insulin resistance and insufficiency of beta cell function are important features in T2DM pathogenesis. In addition, glucagon secretion by pancreatic alpha cells appears to be inappropriately elevated in many patients with T2DM, and thus, a decreased insulin:glucagon ratio may also contribute to hyperglycemia in these patients.

Rationale is missing for incorrect answer

Question 2

Q2. Which of the following statements is correct regarding insulin and its actions?

A. Insulin increases the total number of glucose transporters in the skeletal muscle cell membrane
B. Insulin enhances lipolysis in adipocytes resulting in increased levels of circulating free fatty acid levels
C. In the liver, insulin stimulates glycogenolysis and gluconeogenesis
D. In the pancreas, insulin is co-secreted from alpha cells with glucagon.
Incorrect!
Correct!
Correct Answer
A. Insulin increases the total number of glucose transporters in the skeletal muscle cell membrane

Rationale: Insulin acts by acutely modulating rate-controlling enzymes of metabolism and by inducing longer-term changes through its effects upon gene expression. The three main targets of insulin in the body are skeletal muscle and liver, which help maintain plasma glucose homeostasis, and adipose tissue, which is regulated hormonally to ensure delivery of plasma free fatty acids (FFAs) to and removal of triglycerides from the circulation, as appropriate to condition. Insulin binding to a single receptor is able to differentially control energy metabolism in these three tissues in part through the unique, tissue-specific expression of protein isoforms.

In response to an elevation of circulating glucose levels after a meal and other stimuli associated with eating, pancreatic beta cells increase insulin secretion until plasma glucose levels return to the pre-meal physiological set point. Insulin binds to a cell surface receptor on target cells, which causes a conformation change that is transduced across the cell membrane and disinhibits an intrinsic tyrosine kinase activity present in the intracellular portion of the receptor. The activation of the insulin receptor tyrosine kinase results in the autophosphorylation of the receptor on tyrosine residues and the recruitment of several signaling molecules, which are then phosphorylated by the insulin receptor. The most important of these substrates is a family of insulin receptor substrate (IRS) proteins. The tyrosine phosphorylation of IRS proteins activates numerous signaling cascades that mediate the plethora of responses in target cells. Insulin's effects can be broadly divided into two categories: mitogenic, those promoting cell growth and division, and metabolic, those promoting glucose and triglyceride uptake, utilization, and storage.

The principal physiological effect of insulin secretion is to reduce plasma glucose levels. Enhanced glucose uptake in skeletal muscle accounts for up to 90% of insulin-mediated glucose disposal in peripheral tissues, making it a critical step in the maintenance of blood glucose levels. Skeletal muscle is also a key site for the development of insulin resistance preceding diabetes. Insulin promotes glucose uptake in muscle by stimulating the translocation of specialized vesicles containing the facilitative glucose transporter isoform GLUT4 from the perinuclear region to the cell surface.

The liver is the principal organ responsible for maintaining plasma glucose levels during times of fasting or increased demand, such as during exercise. When blood glucose levels start to fall, counter-regulatory hormones such as glucagon elevate cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity, which stimulate glycogen breakdown and gluconeogenesis (de novo production of glucose), increasing hepatic glucose output. In contrast, insulin suppresses hepatic glucose production and promotes glucose storage as glycogen in hepatocytes. The ratio of insulin to glucagon levels dictates whether the liver will store glucose (high insulin) or produce glucose for use by the rest of the body (low insulin). Hepatocytes express an insulin-insensitive glucose transporter isoform termed GLUT2 that is always present at the cell surface, enabling glucose uptake during hyperglycemia and glucose release into the bloodstream during episodes of hypoglycemia. Thus, insulin does not directly stimulate glucose uptake by liver cells. However, insulin does increase rate-limiting enzymes controlling glycogen metabolism and promotes glucose storage as glycogen. Additionally, if hepatic glycogen stores are full, excess glucose can be converted to fatty acids and shipped within triglycerides on very low density lipoproteins (VLDLs) via the circulation to adipose tissue for long-term storage. Thus, the liver is the second most important peripheral tissue after skeletal muscle for clearance of plasma glucose following a meal.

The adipocyte is the third major site of insulin action. 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, which is the backbone for triglycerides.

Rationale is missing for incorrect answer