PANCE Blueprint Endocrinology (7%)

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

Presentation of Type I DM:

• Children
• Polyuria, polydipsia, polyphagia, 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 

ReelDx Virtual Rounds (Diabetes Mellitus Type 2)

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)