PANCE Blueprint Endocrinology (7%)

Diabetes Mellitus (PEARLS)

NCCPA™ PANCE Endocrine System Blueprint diabetes mellitus type I and type II (PEARLS)

Diabetes mellitus type 1

Patient will present as → a young patient with weight loss, increased thirst, and urination. The patient has felt tired and nauseous. On examination, her weight is below the 5th percentile, she looks thin, and her skin is pale. Her blood pressure is 100/70, and her pulse is 104 bpm. Her respirations are deep at a rate of 28 breaths/minute. Her breath smells fruity

Etiology: Autoimmune - HLA-DR3/4/O antibodies. Islet cell antibodies

Presentation of Type I DM:

  • Children
  • Polyuriapolydipsiapolyphagia, fatigue, and weight loss
  • Often first recognized as diabetic ketoacidosis:
    • Symptoms: Fruity breath, nausea, vomiting, dehydration
    • Treatment: IV regular insulin

Treatment of Type I DM: Insulin

Dawn Phenomenon: Normal glucose until 2-8 am when it rises. Results from decreased insulin sensitivity and a nightly surge of counter-regulatory hormones during nighttime fasting

  • Treat with bedtime injection of long-acting insulin (NPH) to blunt morning hyperglycemia, avoiding carbohydrate snacks late at night

Somogyi effect: Nocturnal hypoglycemia followed by rebound hyperglycemia due to a surge in growth hormone

  • Treat with decreased nighttime long-acting insulin (NPH) dose or give bedtime snack

Check 3 am blood sugar!

  • If the blood sugar level is low at 2 a.m. to 3 a.m., suspect the Somogyi effect
  • If the blood sugar level is normal or high at 2 a.m. to 3 a.m., it's likely the dawn phenomenon

Insulin waning: a progressive rise in glucose from bedtime to morning

  • Treat with a change of insulin dose to bedtime

DKA: Fruity breath, weight loss, rapid respirations, hypotension

  • Diabetic ketoacidosis (DKA) should always be handled in a hospitalized setting, usually an intensive care unit, and often with an endocrinologist’s consultation, if appropriate.
  • TREAT WITH FLUIDS! Patients with DKA are always dehydrated and need large-volume IV fluid resuscitation, usually isotonic fluids such as normal saline. If the corrected serum sodium level is high, this can be reduced to half-normal saline. Insulin should always be administered by an IV pump to guard against accidental overdose.

Diagnosis of DM is made by one of the following:

  • Random blood glucose level of > 200 mg/dL + diabetic symptoms
  • 2 separate fasting (8 hours) glucose levels of > 126 mg/dL
  • 2-hour plasma glucose of > 200 on an oral glucose tolerance test (3-hour GTT is the gold standard in GDM)
  • Hemoglobin A1c of > 6.5%

Insulin and C-peptide levels – low or inappropriately normal fasting C-peptide and insulin levels with concomitant hyperglycemia

  • High fasting insulin and C-peptide levels suggest T2DM

Insulin, GAD65, and IA-2 antibodies ⇒ if one or more of the antibodies is present, and especially if two or more are positive, the patient should be presumed to have type 1 diabetes and should be treated with insulin replacement therapy

Monitoring/evaluation of glycemic control

  • Hemoglobin A1c
    • Represents mean glucose level from the previous 8-12 weeks (approximate lifespan of an RBC)
    • Useful to gauge the "big-picture" overall efficacy of glucose control in patients (either Type 1 or Type 2) to assess the need for changes in medication/insulin levels
    • Treatment goal of A1c < 7.0%
  • Finger-stick blood glucose monitoring
    • Useful for insulin-dependent (either type 1 or 2) diabetics to monitor their glucose control and adjust insulin doses according to variations in diet or activity
    • Treatment goals: < 130 mg/dL fasting and < 180 mg/dL peak postprandial

Blood pressure management

  • Current ADA guidelines recommend a treatment goal of SBP <140 mmHg and DBP <90 mmHg for most patients with diabetes. Those at higher cardiovascular risk may require more intensive blood pressure control to <130/80 mmHg.
    • ACE inhibitors or ARBs are indicated for patients with evidence of early nephropathy (microalbuminuria or proteinuria), even in the absence of hypertension, and are a good choice for treating hypertension in patients who have DM and who have not yet shown renal impairment
    • Thiazide-like diuretic - long-acting agents were shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred
    • Dihydropyridine CCB (amlodipine)

From ADA Standards - Section 10, CV Disease  **Thiazide-like diuretic; long-acting agents shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine calcium channel blocker (CCB).

Insulins

Image by A. Peters, M. Komorniczak. License: CC BY 3.0

Insulin effect Type of Insulin Onset of action Peak of action Duration of action
Fast acting Lispro 15–30 minutes 1–3 hours 4–6 hours
Aspart
Glulisine
Short-acting Regular 30 minutes 1.5–3.5 hours 8 hours
Intermediate-acting NPH 1–2 hours 4–6 hours > 12 hours
Long-acting Detemir 1–2 hours 3–9 hours 14–24 hours
Glargine 3–4 hours No peak Approximately 24 hours
Degludec Approximately 1 hour No peak > 40 hours
Example of insulin regimen: 

  • Breakfast: Rapid-acting → Lunch: Rapid-acting → Dinner: Rapid-acting → Bedtime: Long-acting

Oral therapies
Intervention Expected decrease in A1C with monotherapy (%) Advantages Disadvantages
Lifestyle changes to decrease weight and increase activity 1.0 to 2.0 Broad benefits Insufficient for most within the first year owing to inadequate weight loss and weight regain
Metformin 1.0 to 2.0 Weight neutral GI side effects, contraindicated with renal insufficiency (eGFR <30 mL/min)
Additional therapies
Insulin (usually with a single daily injection of intermediate- or long-acting insulin initially) 1.5 to 3.5 No dose limit, rapidly effective, improved lipid profile One to four injections daily, monitoring, weight gain, hypoglycemia, analogues are expensive
Sulfonylurea (shorter-acting agents preferred) 1.0 to 2.0 Rapidly effective Weight gain, hypoglycemia
GLP-1 agonist (daily to weekly injections) 0.5 to 1.0 Weight loss and reduced cardiovascular mortality (liraglutide, semaglutide) in patients with established CVD Requires injection, frequent GI side effects, long-term safety not established, expensive
Thiazolidinedione 0.5 to 1.4 Improved lipid profile (pioglitazone), potential decrease in MI (pioglitazone) Fluid retention, HF, weight gain, bone fractures, potential increase in MI (rosiglitazone) and bladder cancer (pioglitazone)
Meglitinides 0.5 to 1.5 Rapidly effective Weight gain, three times/day dosing, hypoglycemia
SGLT2 inhibitor 0.5 to 0.7 Weight loss, reduction in systolic blood pressure, reduced cardiovascular mortality in patients with established Vulvovaginal candidiasis, urinary tract infections, bone fractures, lower limb amputations, acute kidney injury, DKA, long-term safety not established
DPP-4 inhibitor 0.5 to 0.8 Weight neutral Long-term safety not established, expensive, possible increased risk of HF with saxagliptin
Alpha-glucosidase inhibitor 0.5 to 0.8 Weight neutral Frequent GI side effects, three times/day dosing
Pramlintide 0.5 to 1.0 Weight loss Three injections daily, frequent GI side effects, long-term safety not established, expensive
Table source: UpToDate

Monitoring in patients with diabetes mellitus (summary table) 

History and physical examination
Height, weight, and BMI Every visit
Smoking cessation counseling Every visit For smokers only.
Blood pressure Every visit Goal systolic pressure 125 to 130 mmHg.
Dilated eye examination Annually Begin at onset of type 2 diabetes, 3 to 5 years after onset of type 1 diabetes. Examine yearly (or more frequently) if retinopathy is present, every 2 to 3 years if there is no evidence of retinopathy.
Comprehensive foot examination Annually Every visit if peripheral vascular disease or neuropathy.
Dental examination Annually Periodontal disease is more severe but not necessarily more prevalent in patients with diabetes.
Laboratory studies
Lipid profile Initially, as indicated In people without dyslipidemia and not on cholesterol-lowering therapy, testing may be infrequent.
A1C Every 3 to 6 months Goal ≤ 7% (may be lower or higher in selected patients).
Urinary albumin-to-creatinine ratio Annually Begin 3 to 5 years after onset of type 1 diabetes and at diagnosis in patients with type 2 diabetes; protein excretion should also be monitored if persistent albuminuria is present.
Serum creatinine Initially, as indicated Typically annually; more often in the presence of chronic kidney disease.
Vaccinations
Pneumococcus
  • PPSV23
1 dose, ages 19 to 64 years Once the patient is ≥ 65 years (and ≥1 year after PCV13 and > 5 years after previous dose of PPSV23), give a second dose of PPSV23. Revaccinate every 10 years.
  • PCV13
1 dose at age ≥ 65 years Once the patient is ≥65 years (and ≥1 year after PPSV23), give PCV13.
  • PCV20
1 dose, ages 19 to 64 years or ≥ 65 years if no prior dose. No additional pneumococcal vaccine is needed!
Influenza Annually
Hepatitis B 3-dose series Administer to unvaccinated adults who are ages 19 to 59 years. For older patients, administer based upon risk of acquiring hepatitis B, including the need for assisted blood glucose monitoring and the likelihood of an adequate immune response to vaccination.
Provide other routine vaccinations for adults with diabetes according to age-related recommendations.
Education, self-management review
Annually More often at onset of diabetes and when there is a change in regimen.
Diabetes Mellitus Type 2
ReelDx Virtual Rounds (Diabetes Mellitus Type 2)
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.

Diagnosis: random glucose > 200 x two or fasting glucose > 126 x two, A1c of > 6.5%

Diabetes Medications:

Metformin - decreases hepatic glucose production and peripheral glucose utilization, decreases intestinal glucose absorption (these are reasons it leads to weight loss)

  • Side effects: Lactic acidosis, GI side effects, initiation is contraindicated with eGFR <30 mL/min and not recommended with eGFR 30 to 45 mL/min, discontinue 24 hours before contrast and resume 48 hours after with monitoring for creatinine, stop if creatinine is > 1.5
  • Benefits: Weight loss, inexpensive

Sulfonylureas - stimulates pancreatic beta-cell insulin release (insulin secretagogue)

  • Glyburide (Diabeta), glipizide (Glucotrol), glimepiride (Amaryl)
  • Side effects: Hypoglycemia
  • Benefits: cheap, rapidly effective

Thiazolidinediones - increases insulin sensitivity in peripheral receptor site adipose and muscle has no effect on pancreatic beta cells

  • Pioglitazone (Actos), Rosiglitazone (Avandia)
  • Contraindications: CHF, liver disease, fluid retention, weight gain, bladder cancer (pioglitazone), potential increase in MI (rosiglitazone)

Alpha-glucosidase inhibitors - Delays intestinal glucose absorption

  • Acarbose (Precose), miglitol (Glyset)
  • GI side effects, three times a day dosing

Meglitinides - stimulates pancreatic beta-cell insulin release

  • Repaglinide (Prandin) and Nateglinide (Starlix)
  • Side effects: May cause hypoglycemia

GLP-1 Agonists - lowers blood sugar by mimicking incretin - causes insulin secretion and decreased glucagon and delays gastric emptying

  • Exenatide (Bydureon, Byetta), dulaglutide (Trulicity), semaglutide (Ozempic), liraglutide (Victoza, Saxenda)
  • Side effects: Requires injection, frequent GI side effects, caution if gastroparesis
  • Benefits: Weight loss, reduced CV mortality (semaglutide, liraglutide) in patients with CVD

DPP-4 Inhibitors - dipetpidylpetase inhibition - inhibits degradation of GLP-1 so more circulating GLP-1

  • Sitagliptin (Januvia), Saxagliptin (Onglyza)
  • Side effects: expensive, possible increased risk of heart failure with saxagliptin

SGLT2 Inhibitor - SGLT2 inhibition lowers renal glucose threshold which results in increased urinary glucose excretion

  • Canagliflozin (Invokana or Sulisent)
  • Side effects: Vulvovaginal candidiasis, urinary tract infections, bone fractures, lower limb amputations, acute kidney injury, DKA, long-term safety not established
  • Benefits: Weight loss, reduction in systolic blood pressure, reduced cardiovascular mortality in patients with established CVD

Insulin – add if HbA1C > 9

Follow Up: Annual- ophthalmologist visit, urine microalbumin

Complications – neuropathy (most common), retinopathy (the leading cause of blindness), nephropathy

Normal fasting glucose is between 70 and 100

Diagnosis of DM is made by one of the following:

  • A random blood glucose level of > 200 mg/dL AND diabetic symptoms
  • Two separate fasting (8 hours) glucose levels of > 126 mg/dL
  • 2-hour plasma glucose of > 200 on an oral glucose tolerance test (3-hour GTT is the gold standard in GDM)
  • Hemoglobin A1c of > 6.5%

Diagnostic criteria for prediabetes

  • A1C 5.7 - 6.4
  • Fasting glucose 100 - 125
  • 2-hour oral glucose tolerance test 140-199

Glucose goals and basic management

  • A1C < 7.0 % check every 3 months if not controlled and 2x per year if controlled
  • Preprandial glucose 80-130 mg/dL (60-90 if pregnant)
  • Peak postprandial (1 to 2 hours after the beginning of the meal) blood glucose < 180 mg/dL
  • Annual dilated eye exams, ACEI if microalbuminuria, annual foot examination
  • Blood pressure
    • ACC/AHA blood pressure targets - the target for patients with comorbidities is < 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)
Picmonic
Dawn Phenomenon

IM_DawnPhenomenon_V1.5_

The dawn phenomenon is the presence of hyperglycemia upon awakening. The increase in blood glucose is caused by increased hormone production in the early morning hours. Between the hours 2AM-6AM, the body naturally increases production of growth hormone and cortisol. Treatment involves changing the patient’s current insulin regimen. The patient may have their current administration times changed, be given a long-acting insulin in the evening, or be given an insulin pump. Since insulin affects blood glucose levels, the patient’s glucose levels should be closely monitored particularly between 2AM-6AM. Instruct the patient to limit carbohydrates before bedtime to avoid spikes in blood sugar during the night.

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Diabetic ketoacidosis (DKA)

IM_MED_DKAS&S_v1.3_

Diabetic ketoacidosis (DKA) is a medical emergency and complication of diabetes. Patients have increased insulin requirements, which leads to a shortage. As a response, the body begins burning excess fat (and fatty acids), causing ketone body buildup. Lab values seen in DKA include blood sugars above 250 mg/dL, and anion gap metabolic acidosis with pH below 7.3 and bicarbonate below 18. Patients will also show present plasma ketones. Due to an extracellular shift, patients may be hyperkalemic.

Diabetic Ketoacidosis (DKA) Treatment
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Diabetic Ketoacidosis (DKA) Signs and Symptoms
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Diabetic Ketoacidosis (DKA) Diagnosis and Labs
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Diabetic glomerulonephropathy

_DM_Diabetic_Glomerulonephropathy_v1.6_

Diabetic glomerulonephropathy is the kidney disease seen in patients with significantly progressed diabetes. There is damage to the kidney due to nonenzymatic glycosylation of the basement membrane which alters the permeability of arterioles and glomeruli and results in nephrotic syndrome. Patients will have increased GFR due to preferential efferent sclerosis, mesangial expansion due to hyperfiltration pressure, and will ultimately enter kidney failure if glucose levels are not controlled.

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