Endocrinology USMLE Step 3 > Section 1: Diabetes Mellitus > Flashcards
Section 1: Diabetes Mellitus Flashcards
How is DM dignosis made?
- Two fasting glucose ≥ 126
- One random glucose ≥ 200 with symptoms (polyuria, polydipsia, polyphagia)
- Abnormal glucose tolerance test > 200mg/dL (2-hour glucose tolerance test with 75 g glucose load)
- Hemoglobin A1c > 6.5%
Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kindle Locations 2896-2902). . Kindle Edition.
Best initial therapy for type 2 DM
Diet, exercise and weight loss
Best initial medical therapy for adult onset DM
Metformin
Why is metformin beneficial in obese DM patients?
Because it does not lead to weight gain
How does metformin work?
By blocking gluconeogenesis
What are the advantages of metformin (Glucophage(TM))?
- No risk of hypoglycemia
- Does not increase obesity
What are the contraindications to use of metformin?
- Renal insufficiency
- Use of contrast agents
Name the common classes of DM medications
- Metformin (Biguanide)
- Sulfonylureas
- Dipeptidyl peptidase IV (DPP IV) inhibitors
- Thiazolidinidiones
- Alpha glucosidase inhibitors
- Insulin secretagogues (Meglitinides)
- Glucagon-like peptides (GLP) analogues (Incretins)
- Long-acting insulin
- Short-acting insulin
Use the mneumonic “GLAD MISTS”
Name three examples of sulfonylureas
- Glyburide
- Glimepiride
- Glipizide
What is the mechanism of actions of sulfonylureas?
By increasing the release of insulin from the pancreas
Side effects of sulfonylureas
- Hypoglycemia
- SIADH
- Weight gain
Side effect of metformin
Risk of lactic acidosis in patients with renal insufficiency
Name three examples of Dipeptidyl peptidase IV (DPP-IV) inhibitors
- Sitagliptin (JanuviaTM)
- Saxagliptin (OnglyzaTM)
- Vildagliptin
- Linagliptin (TradjentaTM)
Remember “-gliptin”
Name two examples of thiazolidinediones (“glitazones”)
- Rosiglitazone (AvandiaTM)
- Pioglitazone (ActosTM)
Remember “-glitazones”
Side effects of thiazolidiones
- Hepatocellular injury
- Anemia
- Pedal edema
- CHF
Mechanism of action of thiazolidinediones
Increasing peripheral insulin sensitivity
Name two examples of alpha-glucosidase inhibitors
- Acarbose (PrecoseTM)
- Miglitol (GlysetTM)
Mechanism of action of alpha-glucosidase inhibitors
These agents block the absorption of glucose at the intestinal lining
Side effects of alpha-glucosidase inhibitors
- Diarrhea
- Abdominal pain
- Bloating
- Flatulence
- Elevated LFTs
Name two examples of Insulin secretagogues (Meglitinides)
- Nateglinide
- Repaglinide
Remember “-glinide”
Mechanism of action of Insulin secretagogues (Meglitinides)
Increased release of insulin from the pancreas (similar to sulfonylureas)
Side effects of of Insulin secretagogues (Meglitinides)
Hypoglycemia
Name two examples of Glucagon-like peptide-1 (GLP-1) analogs
- Exenatide (ByettaTM, BydureonTM)
- Liraglutide (VictozaTM)
Remember with “LE” my initials
Mechanism of action of Glucagon-like peptide-1 (GLP-1) analogs
Increase insulin and decrease glucagon
Side effects of Glucagon-like peptide-1 (GLP-1) analogs
- Nausea
- Vomiting
- Weight loss
- Hypoglycemia
These agents slow-gastric emptying and so promote weight loss
When is insulin introduced in the Rx of type 2 DM
If other agents do not sufficiently control the level of glucose, then the patient is switched to insulin. A long-acting insulin, such as insulin glargine, which is a once-a-day injection with an extremely steady-state level of insulin, is used in combination with a very short-acting insulin at mealtime.
Name 4 short-acting insulin
- Regular insulin
- Lispro
- Aspart
- Glulisine
Name 3 long-acting insulin
- NPH (Neutral Protamine Hagedorn): twice a day
- Detemir
- Glargine: once a day
List the symptoms and signs of DKA including common lab findings
- “Fruity breath”
- Kussmaul hyperpnea
- Dehydration
- Abdominal pain
- Increase annion gap
- Hyperkalemia
- Hyperglycemia
- Ketones in blood/urine
Best initial test for DKA
Serum bicarbonate is the best way to determine the severity of illness
Lab findings in DKA
- Hyperglycemia
- Hyperkalemia
- Decreased serum bicarbonate
- Low pH, with low pCO2 as respiratory compensation
- Acetone, acetoacetate, and beta hydroxybutyrate levels are elevated
- Elevated anion gap
How is patient improvement monitored in DKA?
By monitoring anion gap
Outline the management of DKA
- Admit ICU/ward
- Fluid resuscitation (NS + IV insulin)
- Monitor Na+ K+ phosphate and glucose
- Change NS to D5NS when glucose level < 250 mg/L
- Change IV insulin to an SQ insulin sliding scale once the anion gap normalizes
- Continue IV insulin for at least 30 minutes following the administration of the first dose of SQ insulin
Name the complications of DM
- HTN
- Retinopathy (proliferative)
- Nephropathy
- Neuropathy
- Erectile dysfunction
- Gastroparesis
Rx for gastroparesis in DM
- Metoclopromide
- Erythromycin
Rx of DM neuropathy
- Gabapentin
- Pregabalin
LDL goal in DM
< 100 mg/dL
LDL goal in CAD and DM
< 70 mg/dL
Rx of retinopathy in DM
Laser photocoagulation
Diagnostic criteria for hyperglycemic hyperosmolar nonketotic diabetic state/coma
- Serum glucose > 600 mg/dL (hyperglycemia)
- Serum pH > 7.3
- Serum bicarbonate > 15 mEq/L
- Anion gap 14 mEq/L (normal)
- Serum osmolality > 310 mOsm/kg.
True or False:
Metformin leads to malabsorption of vitamin B12 in the GI tract
Metformin interferes with cobalamin metabolism and absorption
True
True
Outline the 5 important steps in the management of diabetic foot ulcer
- Offload the foot
- Tight glycemic control
- Aggressive wound care including proper antibiotic coverage
- Improve macrovascular and microvascular circulation (check ABI)
- Good nutrition
Rx of poor circulation in diabetic foot ulcer
Hyperbaric oxygen
What is the predominant ketone in DKA?
ß-hydroxybutyrate
A healthy 54-year-old woman with a strong family history of type 2 diabetes mellitus requests an oral glucose tolerance test to evaluate her risk of developing diabetes. The results of a 2-hour glucose tolerance test after a 75-g oral glucose load are as follows:
Laboratory Studies
Fasting glucose
104 mg/dL
2-hour glucose
168 mg/dL
Which of the following characterizes the patient’s glycemic status?
A Impaired fasting glucose
B Impaired glucose tolerance
C Impaired fasting glucose and impaired glucose tolerance
D Normal glucose tolerance
E Type 2 diabetes mellitus
Answer and Critique (Correct Answer = C)
This patient has impaired fasting glucose and impaired glucose tolerance. The American Diabetes Association and World Health Organization have similar classifications of the various glycemic abnormalities that are becoming increasingly common. Diabetes mellitus is now defined by a fasting plasma glucose level of ≥126 mg/dL or by a 2-hour plasma glucose level of ≥200 mg/dL during an oral glucose tolerance test (the oral glucose tolerance test is not recommended for routine clinical use by the American Diabetes Association). Alternatively, a “casual” (without respect to meals) plasma glucose level of ≥200 mg/dL, if accompanied by classic symptoms of hyperglycemia, may also be used to make the diagnosis. Prediabetes glycemic states consist of impaired glucose tolerance, defined as a 2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test, and impaired fasting glucose, defined as a fasting glucose level of 100–125 mg/dL.
This patient therefore has both impaired glucose tolerance and impaired fasting glucose. Both of these prediabetes states predispose a patient to type 2 diabetes mellitus; impaired glucose tolerance appears to be a stronger factor than impaired fasting glucose. When both are present, as in this patient, the risk is incrementally higher.
Key Point
Prediabetes glycemic states consist of impaired glucose tolerance, defined as a 2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test, and impaired fasting glucose, defined as a fasting glucose level of 100–125 mg/dL.
Bibliography
American Diabetes Association. Standards of medical care in diabetes--2007. Diabetes Care. 2007;30 Suppl 1:S4-S41. [PMID: 17192377] [PubMed]
List the values for:
- Impaired FBS
- Impaired OGTT
Prediabetes glycemic states consist of impaired glucose tolerance, defined as a 2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test, and impaired fasting glucose, defined as a fasting glucose level of 100–125 mg/dL.
A 29-year-old woman who has had type 1 diabetes mellitus for 15 years is evaluated during a regular follow-up office visit. Her current insulin regimen consists of insulin glargine, 28 units at bedtime, and insulin lispro, 4 units three times a day with meals. She has occasional nightmares that awaken her from sleep; her blood glucose levels on two of these occasions were 53 mg/dL and 48 mg/dL.
On physical examination, the blood pressure is 115/70 mm Hg, heart rate is 80/min, and BMI is 22 (she weighs 60 kg [132 lb]). She has no evidence of retinopathy or peripheral neuropathy. Her hemoglobin A1c is 7.1%.
Laboratory Studies
Glucose profiles:
Fasting: Mean 210 mg/dL; Range 51–243 mg/dL
Pre-lunch: Mean 141 mg/dL; Range 65–203 mg/dL
Pre-dinner: Mean 125 mg/dL; Range 68–165 mg/dL
Bedtime: Mean 130 mg/dL; Range 71–158 mg/dL
Which of the following insulin adjustments should be made first?
A. Increase glargine at bedtime
B. Decrease glargine at bedtime
C. Increase lispro at all three meals
D. Decrease lispro at all three meals
E. Decrease lispro at dinner
Answer and Critique (Correct Answer = B)
The correct management step is to decrease glargine at bedtime. This patient is having significantly low blood glucose levels during the night and early morning with less severe low glucose levels throughout the day. Her highest glucose values also occur on arising each morning, possibly as a result of having low glucose levels at night. She is on basal bolus insulin therapy. The average patient with type 1 diabetes mellitus who does not have coexisting insulin resistance requires a total daily dose of about 0.4 to 0.5 units of insulin per kg of body weight. Most patients take 40% to 50% of their total daily dose as basal insulin (glargine) and 50% to 60% as meal boluses (lispro or aspart). This patient weighs 60 kg (132 lb) and would therefore have an anticipated total daily insulin dose of 24 to 30 units. However, she is currently taking 28 units of basal insulin and another 12 units as boluses. Her insulin dose may therefore be excessive and imbalanced because of excessive glargine. Therefore, her frequent hypoglycemia, which is most prominent during the night and early morning but which also occurs during the daytime, is most likely due to excessive bedtime glargine. Excessive lispro at dinner most often causes hypoglycemia 2 to 5 hours after dinner, rather than at 3 AM, and would not be expected to cause hypoglycemia during the day. Reducing her bedtime glargine is the most prudent initial adjustment to make. Once the hypoglycemia is corrected by lowering the bedtime glargine dose, preprandial and postprandial glucose monitoring will help to determine if her mealtime lispro doses should be adjusted.
Key Point
The average patient with type 1 diabetes mellitus who does not have coexisting insulin resistance requires a total daily dose of about 0.4 to 0.5 units of insulin per kg of body weight with 40% to 50% delivered as long-acting basal insulin.
Bibliography
Hirsch IB. Insulin analogues. N Engl J Med. 2005;352:174-83. [PMID: 15647580] [PubMed]
A 57-year-old woman with type 2 diabetes mellitus is evaluated during a routine follow-up office visit. She has had diabetes for 3 years and has no known complications. Her current medications for diabetes are metformin, 1000 mg twice a day; pioglitazone, 45 mg/d; and insulin glargine, 30 units every morning.
On physical examination, the blood pressure is 140/80 mm Hg, heart rate is 80/min, and BMI is 30.5. The hemoglobin A1c is 9.8%. The remainder of the physical examination is normal.
Laboratory Studies
Glucose profiles:
Fasting
Mean 105 mg/dL
Range 82–123 mg/dL
Pre-lunch
Mean 136 mg/dL
Range 128–163 mg/dL
Pre-dinner
Mean 138 mg/dL
Range 122–171 mg/dL
Bedtime
Mean 143 mg/dL
Range 129–188 mg/dL
2-Hour postprandial (done 3 times)
232–295 mg/dL
Which of the following medication adjustments is most likely to improve this patient’s blood glucose profile?
A Add acarbose
B Add NPH insulin at bedtime
C Add NPH insulin in the morning
D Add short-acting insulin (lispro or aspart) with meals
E Increase glargine dose
Answer and Critique (Correct Answer = D)
The most appropriate change in this patient’s medical program is to add short-acting insulin (lispro or aspart) with meals. This patient is having significant postprandial hyperglycemia. Postprandial glucose excursions should ideally be limited to 30 to 50 mg/dL above premeal glucose values. This patient should do more postprandial glucose testing, but the values she has obtained so far show excursions much greater than 50 mg/dL above premeal values. This can be best corrected by using a bolus of short-acting insulin (lispro or aspart) just before or with each meal.
Acarbose is not effective enough to reduce postprandial glucose excursions sufficiently in this situation. Bedtime NPH insulin is used mainly to lower elevated fasting glucose levels, which are not a problem in this patient. Morning NPH insulin would provide a peak in mid-afternoon, but the NPH peak would not occur at a completely reliable time and would also not cover breakfast or dinner. Since glargine is a basal insulin, increasing the dose would still not provide the post-meal insulin peaks that are required to control postprandial hyperglycemia.
Key Point
Significant postprandial hyperglycemia can be managed by using a bolus of short-acting insulin (lispro or aspart) just before or with each meal.
Bibliography
Hirsch IB. Intensifying insulin therapy in patients with type 2 diabetes mellitus. Am J Med. 2005;118 Suppl 5A:21S-6S. [PMID: 15850550] [PubMed]
A 48-year-old man with a history of alcoholism is evaluated after discharge from the hospital where he was admitted with acute pancreatitis. The patient was found to have a pancreatic pseudocyst on abdominal CT scan. During the hospitalization, his fasting glucose level ranged from 150 to 200 mg/dL. The patient had normal glucose concentrations before this episode and has no personal or family history of diabetes mellitus.
On physical examination, the patient is lean, and blood pressure is normal. The abdomen is soft, and the liver is enlarged.
Laboratory Studies
Fasting glucose
172 mg/dL
Triglycerides
Normal
Aspartate aminotransferase
84 U/L
Alanine aminotransferase
69 U/L
Amylase
Normal
Lipase
Normal
Which of the following types of diabetes is this patient most likely to have?
A Latent autoimmune diabetes of adulthood
B Secondary diabetes
C Type 1 diabetes mellitus
D Type 2 diabetes mellitus
Answer and Critique (Correct Answer = B)
This patient has diabetes secondary to pancreatic disease. Diabetes may be the direct result of other underlying disease states, in which case it is referred to as “secondary diabetes.” Potentiating conditions include other endocrinopathies, such as Cushing’s syndrome, acromegaly, pheochromocytoma, and hyperthyroidism. Rarely, islet cell neoplasms, such as glucagonoma and somatostatinoma, lead to diabetes. Medications, such as glucocorticoids, may lead to diabetes as well. Disorders of the exocrine pancreas can also manifest as hyperglycemia as a result of, among other things, direct damage to the pancreatic islet cells. These conditions include acute or chronic pancreatitis, pancreatic malignancies, and cystic fibrosis. The patient’s recent hospitalization showed convincing evidence of pancreatitis. Therefore, his condition should be classified as secondary diabetes. Treatment may be challenging. Sulfonylureas may be effective, depending on the number of functioning islet cells remaining. Insulin sensitizers have no role in treating this patient’s secondary diabetes. He may eventually require insulin. Unfortunately, patients with pancreatic disease and diabetes may be quite labile regarding glycemic control, since they often lack adequate glucagon secretion for counterregulation.
Type 1 diabetes mellitus is the result of islet cell destruction due to autoimmunity. Type 2 diabetes mellitus culminates from the combination of both insulin resistance and relative insulin deficiency and comprises more than 90% of all cases of diabetes worldwide. Gestational diabetes is diagnosed during pregnancy and has a similar pathogenesis to that of type 2 diabetes. The form of diabetes recently called latent autoimmune diabetes of adulthood (LADA) occurs in patients with type 2 diabetes who develop insulin requirements later in life and exhibit labile glycemic tendencies and many of the autoimmune markers that occur in those with type 1 diabetes. LADA involves slowly progressive loss of β-cell function and usually occurs in lean, older patients.
Key Point
Secondary diabetes mellitus is the direct result of other underlying disease states.
Bibliography
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007;30 Suppl 1:S42-7. [PMID: 17192378] [PubMed]
A 62-year-old woman is evaluated in the office during follow-up for type 2 diabetes mellitus. The diagnosis of diabetes was confirmed 8 months ago, when she had a fasting plasma glucose level of 141 mg/dL during routine screening. Attempts at nonpharmacologic control are started with a diet and exercise program. The patient has lost 5 kg (11 lb) and walks briskly 3 days a week for 45 minutes. She monitors her blood glucose with occasional finger-stick testing at home, and reports fasting values of 135 to 145 mg/dL. The patient’s medical history is notable for hypertension, hypercholesterolemia, renal insufficiency (creatinine, 1.9 mg/dL), and heart failure. She takes furosemide, lisinopril, metoprolol, simvastatin, and aspirin daily. She does not smoke.
On physical examination, the blood pressure is 130/70 mm Hg, heart rate is 60/min, and BMI is 32. Jugular venous pressure is not elevated. Lungs are clear. Cardiac examination is normal without murmur or extra sounds. There is 1+ pitting edema of the ankles.
Fasting plasma glucose level today is 142 mg/dL and hemoglobin A1c is 7.3%.
Which of the following is the most appropriate treatment option for this patient at this time?
A Glyburide
B Insulin
C Metformin
D Pioglitazone
E No additional intervention
Answer and Critique (Correct Answer = A)
Therapy with a sulfonylurea such as glyburide is indicated for this patient. Drug treatment for type 2 diabetes mellitus is initiated when diet and exercise have failed or are likely to fail because of the degree of hyperglycemia, or when there are symptoms secondary to hyperglycemia. The goal of therapy is a hemoglobin A1c value less than 7%. This patient has a value of 7.3% despite 8 months of diet and exercise. Although these lifestyle interventions should be continued, they are unlikely to lead to further reduction in blood glucose levels, and pharmacologic therapy is therefore indicated.
In the past decade, more than 12 new medications for type 2 diabetes have become available. Initial pharmacologic therapy for type 2 diabetes is generally an oral agent. There are few differences in outcomes with different drug classes, and patient characteristics and preferences help guide the initial choice of agent. For example, in obese patients the use of metformin as a first-line agent may reduce cardiovascular events and all-cause mortality, although these findings remain controversial. Stepped therapy with bedtime insulin is effective in achieving glycemic targets in patients for whom oral agents alone are ineffective; insulin also effectively controls the disease in a substantial proportion of patients for whom oral therapy is unsuccessful. In patients in whom insulin therapy is started, current oral therapy (metformin or the thiazolidinedione pioglitazone) should be continued.
For the choice of oral therapy, it is also important to understand the relative and absolute contraindications for each medication. Metformin is contraindicated in patients with renal insufficiency, defined as a serum creatinine concentration >1.6 mg/dL in men and >1.5 mg/dL in women. Metformin may increase the risk of lactic acidosis in such patients. This patient has a serum creatinine concentration of 1.9 mg/dL, precluding use of metformin. A thiazolidinedione pioglitazone is also contraindicated because of the patient’s heart failure. Thiazolidinediones increase fluid retention and can lead to decompensated heart failure. Metformin is also commonly avoided in patients with advanced heart failure because of the increased risk of tissue ischemia and lactic acidosis related to decreased cardiac output.
Key Points
Metformin is contraindicated in patients with type 2 diabetes mellitus and renal insufficiency. Thiazolidinediones are contraindicated in patients with type 2 diabetes mellitus and heart failure.
Bibliography
Nathan DM. Clinical practice. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med. 2002;347:1342-9. [PMID: 12397193] [PubMed]
