PANCE Blueprint Endocrinology (7%)

Diabetes Mellitus Type 2 (Lecture + ReelDx)


53 y/o with weakness, polydipsia, and polyuria

Patient will present as → a 35-year-old Mexican American male complaining of increased thirst, frequent urination, hunger, fatigue, and blurred vision random finger stick blood glucose is 225.

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Name four diagnostic criteria for diabetes?

  • Random glucose >200
  • Fasting glucose >126
  • 2-hour postprandial glucose >200
  • HgA1c >6.5%

How does metformin work?
Decreases the hepatic glucose production and increases peripheral glucose uptake.

Know your medication - side effects and functions

  • Metformin (Glumetza, Glucophage, Fortamet):
    • Mechanism: Decreases hepatic glucose production and peripheral glucose utilization, decreases intestinal glucose absorption (these are reasons it leads to weight loss)
    • Side effects: Can cause lactic acidosis and needs to be discontinued 24 hours before contrast and resumed 48 hours after with monitoring for creatinine, stop if creatine is > 1.5
  • Sulfonylureas - Glyburide (Glynase), Glipizide (Glucotrol, Glucotrol XL), Glimepiride (Amaryl):
    • Mechanism: Stimulates pancreatic beta-cell insulin release (insulin secretagogue)
    • Side effects: Causes hypoglycemia and weight gain
  • Thiazolidinediones - Pioglitazone (Actos) and Rosiglitazone (Avandia): 
    • Mechanism: Increases insulin sensitivity in peripheral receptor site adipose and muscle has no effect on pancreatic beta cells
    • Side effects: Can cause fluid retention, and edema. Cardiovascular toxicity with Avandia.
  • α-Glucosidase inhibitors - Acarbose (Precose) and Glyset (Miglitol):
    • Mechanism: Delays intestinal glucose absorption
    • Side effects: May cause increased LFTs and hepatitis, diarrhea, flatulence
  • Meglitinides - Repaglinide (Prandin)  and Nateglinide (Starlix):
    • Mechanism: Stimulates pancreatic beta-cell insulin release
    • Side effects: May cause hypoglycemia
  • GLP-1 Agonists - Exenatide (Bydureon, Byetta):
    • Mechanism: Lowers blood sugar by mimicking incretin - causes insulin secretion and decreased glucagon and delays gastric emptying
    • Side effects: May cause hypoglycemia, caution if gastroparesis
  • DDP-4 Inhibitors - Sitagliptin (Januvia):
    • Mechanism: Dipetpidylpetase inhibition - inhibits degradation of GLP-1 so more circulating GLP-1
    • Side effects: May cause pancreatitis and renal failure
  • SGLT2 Inhibitor - Canagliflozin (Invokana or Sulisent):
    • Mechanism: SGLT2 inhibition lowers renal glucose threshold which results in increased urinary glucose excretion
    • Side effects: hypoglycemia and urinary tract infections

Normal fasting glucose is between 70 and 100

Diagnostic criteria for DM Type II

  1. Fasting blood glucose > 126 mg/dl fasting at least 8 hours on two occasions GOLD STANDARD!
  2. Hemoglobin A1C > 6.5 indicates average blood sugar 10-12 weeks prior to measurement
  3. 2 hour plasma glucose of > 200 on an oral glucose tolerance test (3 hour GTT is gold standard in GDM)
  4. Random plasma glucose > 220 in patients with classical symptoms of hyperglycemia

Diagnostic criteria for prediabetes

  1. A1C 5.7-6.4, Fasting glucose 100-125, 2-hour oral glucose tolerance test 140-199

Diet and exercise with lifestyle changes are first line - carbs 50-60%, protein 15-20%,

Glucose goals and management

  • A1C < 7.0 % check every 3 months if not controlled and 2x per year if controlled
  • Preprandial glucose 80-110 (60-90 if pregnant)
  • Postprandial glucose goal is < 140
  • Annual dilated eye exams, ACEI if microalbuminuria, annual foot examination
  • Blood pressure**
    • ACC/AHA blood pressure targets - target for patients with comorbidities: < 130/80
    • JNC 8 treatment targets: Reduce BP to < 140/90 mm Hg for everyone < 60 including those with a kidney disorder or diabetes
  • New statin guidelines: recommend statins in persons with diabetes mellitus who are 40 to 75 years of age with LDL-C levels of 70 to 189 mg per dL but without clinical ASCVD (see guidelines)

osmosis Osmosis
Metformin (Glucophage)


Metformin is part of the Biguanide class of diabetic drugs. It is the first-line medical treatment for diabetes mellitus type 2 and can also be used for PCOS. Its exact mechanism of action is unknown, but this medication leads to decreased gluconeogenesis and increased insulin sensitivity, subsequently equating to lower blood sugar levels. Side effects of this drug include lactic acidosis and GI distress, and Metformin should not be used in patients with renal failure.

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Insulins for medical use are synthetically created analogs of the human hormone. Some are chemically altered in structure to change the rate of absorption and duration of action within the human body. When classified according to time course, insulin preparations fall into three major groups: short duration, intermediate duration, and long duration.

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Glyburide and Glipizide (2nd Generation Sulfonylureas)


Glyburide and glipizide are second-generation sulfonylureas that stimulate the release of insulin from pancreatic islet cells. This action increases the amount of circulating insulin to maintain normal blood glucose levels in the body. These drugs are indicated for patients with type 2 diabetes who have the ability to produce insulin (refer to Picmonic “Insulin”). Second-generation sulfonylureas have replaced first-generation agents due to their increased potency and fewer drug-drug interactions. Hypoglycemia is a major side effect. These drugs should not be used while consuming alcohol and 2nd generation sulfonylureas (except glyburide) should not be used in pregnancy or breastfeeding.

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Glucagon (GlucaGen)


Glucagon (GlucaGen) is a polypeptide hormone that causes the hepatic conversion of stored glycogen into readily-available glucose. This medication is indicated for hypoglycemia caused by insulin overdose and not related to starvation. It is given when IV glucose is not available. Side effects may include nausea and vomiting. This drug must be reconstituted with a powder supplied by the manufacturer. Once conscious, the patient should be given oral carbohydrates within an hour to avoid rebound hypoglycemia. If the patient shows no improvement, IV 50% glucose may be given for immediate results.

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Exenatide (Byetta)


Exenatide (Byetta) is an injectable hypoglycemic drug indicated for patients with Type 2 diabetes. The medication functions as an incretin mimetic and GLP-1 synthetic analog. Side effects include hypoglycemia, nausea, vomiting, diarrhea, pancreatitis, and renal failure. Since exenatide delays gastric emptying, it should be administered at least 1 hour after giving other medications. Exenatide is considered adjunct therapy and administered with other antidiabetic drugs.

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Chlorpropamide and Tolbutamide (Orinase) (1st Generation Sulfonylureas)


Chlorpropamide and tolbutamide are first-generation sulfonylureas that promote insulin release. This action increases the amount of circulating insulin to maintain normal blood glucose levels in the body. These drugs are indicated for patients with type 2 diabetes who have the ability to produce insulin (refer to Picmonic “Insulin”). However, first-generation sulfonylureas are rarely used due to their lower potency and significant drug-drug interactions. Side effects of these medications include hypoglycemia and cardiovascular toxicity. These drugs should not be used while pregnant, breastfeeding, consuming alcohol, or taking beta-blockers.

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Acarbose (Precose) and miglitol (Glyset)


Acarbose (Precose) and miglitol (Glyset) are alpha-glucosidase inhibitors used to help control blood glucose levels in diabetic patients. By inhibiting an intestinal enzyme that converts complex carbohydrates into digestible forms, these medications decrease the rate of carbohydrate digestion and absorption. This action decreases the rise of glucose levels caused by eating. These medications are indicated for patients with type 2 diabetes. Side effects include flatulence, cramps, diarrhea, and anemia. Since these drugs may cause liver damage, liver function tests should be monitored frequently. In the event of hypoglycemia, glucose (not sucrose) should be administered.

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Pioglitazone (Thiazolidinediones)


Pioglitazone stimulates receptors in the body to increase cellular response to insulin, thus decreasing insulin resistance. This medication is only effective in the presence of insulin and can only be used in patients with type II diabetes. Side effects of pioglitazone include upper respiratory infection, muscle pain, sinusitis, headache, and heart failure. Patients taking pioglitazone are at increased risk for bladder cancer, and women taking this medication are more prone to bone fractures. Liver enzymes should be routinely monitored while taking pioglitazone due to the risk of liver toxicity.

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Pramlintide (Symlin)


Pramlintide (Symlin) is an injectable hypoglycemic drug indicated for type 1 and 2 diabetes. As a synthetic amylin analog, pramlintide is used to supplement mealtime insulin in diabetic patients unable to maintain glucose control despite insulin therapy. Side effects of pramlintide include nausea and reactions at the injection site. While administering the medication, monitor the patient for symptoms of hypoglycemia. Since it delays the absorption of other medications, avoid giving pramlintide concurrently with other drugs.

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Repaglinide (Prandin) and nateglinide (Starlix)


Repaglinide (Prandin) and nateglinide (Starlix) are oral hypoglycemic medications classified as meglitinides or “glinides.” By stimulating the pancreatic cells to release more insulin, these medications decrease blood glucose levels. A major side effect of meglitinides is hypoglycemia. Since these drugs have a short half-life, instruct the patient to eat within 30 minutes of administration. Gemfibrozil (Lopid) decreases the metabolism rate of meglitinides and should not be administered to prevent drug accumulation leading to hypoglycemia.

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Sitagliptin (Januvia) and Saxagliptin (Onglyza) (DPP-4 Inhibitors)


Sitagliptin (Januvia) and Saxagliptin (Onglyza) are antidiabetic medications that work by blocking the DPP-4 enzyme, allowing for increased action of incretin hormones and increased release of insulin. These medications are only effective in the presence of insulin and can only be used in patients with type II diabetes. Keep in mind, however, DPP-4 inhibitors are considered third-line medications for the treatment of diabetes and should only be used if first and second-line medications have failed to provide adequate blood glucose control. Side effects include upper respiratory infection, pancreatitis, and hypersensitivity reactions.

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Question 1
Which of the following glucose-lowering agents acts by decreasing peripheral tissue resistance to insulin resistance?
α-Glucosidase inhibitors, such as acarbose (Precose), reduce glucose by delaying carbohydrate absorption
Glipizide (Glucotrol) and other sulfonylureas work by increased insulin secretion from pancreatic β cells.
Metformin (Glucophage), a biguanide, lowers glucose by decreasing hepatic glucose production and increasing glucose utilization.
Question 1 Explanation: 
Pioglitazone (Actos) is a thiazolidinedione (TZD) and decreases insulin resistance and increases glucose utilization by sensitizing peripheral tissues to insulin.
Question 2
A 66-year-old male was found wandering in the streets by the police. There are no signs of trauma. BP is 90/54 mm Hg, pulse rate is 115 bpm, and respiratory rate is 12 breaths/min. Physical exam reveals mild dehydration as well as decreased mental state without focal neurological findings. Initial laboratory findings include glucose of 750 mg/dL, Na of 124 mEq/L, K of 3.0 mEq/L, Cl of 102 mEq/dL, CO2 of 37 mEq/L, BUN of 101 mg/dL, creatinine of 1.0 mg/dL, blood pH of 7.3. Which of the following is the most appropriate first step in managing this patient?
Glucagon would further increase the blood glucose
Insulin is typically not needed unless the glucose is resistant to fluids
Bicarbonate should not be administered because the blood pH is above 7.0
Question 2 Explanation: 
Hyperglycemia in the absence of ketosis is common in elderly type 2 diabetics. With mild dehydration, sodium is low but rises as the dehydration worsens. Elevated BUN is key to diagnosis. This patient is presenting with hyperglycemic hyperosmolar state and is dehydrated. Correction of the hypovolemia will reduce the hyperglycemia and thereby allow the kidneys to excrete the glucose
There are 2 questions to complete.
Shaded items are complete.

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