Common Endocrinologic Disorders

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CHAPTER 12 Common Endocrinologic Disorders

I. Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disorder characterized by glucose intolerance. People in the United States who are at the highest risk for diabetes are Latino Americans, African Americans, Native Americans, and Asian Americans. It is the leading cause of blindness in adults as well as a major cause of end-stage renal disease and amputations.

A. Classification

1. Type 1 diabetes is a failure of the pancreas to make enough insulin for the body to function. It was previously called insulin-dependent diabetes or juvenile-onset diabetes. It occurs more often in younger patients than older patients. Type 1 diabetes requires insulin therapy.
2. Type 2 diabetes refers to decreased insulin production from the pancreas, decreased sensitivity of cells to insulin, and decreased ability to get glucose into cells. It was previously called non–insulin dependent diabetes and adult-onset diabetes. It occurs more often in older patients than younger patients, although the incidence of type 2 diabetes is increasing in children in the United States. Patients may start with diet and exercise therapy. Most patients start with oral medications but may progress to requiring insulin therapy.
3. Gestational diabetes is diabetes that occurs during pregnancy. It does not mean the patient will have diabetes for the rest of her life, but she will have increased risk of developing type 2 diabetes. Patients typically use insulin therapy due to risk to the fetus when using oral antidiabetic medications. Gestational diabetes is usually detected through administration of an oral glucose tolerance test (OGTT) during pregnancy.
4. Prediabetes is the increased risk of developing DM.

a) Impaired fasting glucose (IFG): fasting glucose 100–125 mg/dL
b) Impaired glucose tolerance (IGT): Two-hour glucose 140–199 mg/dL during oral glucose tolerance test (OGTT)

B. Signs and symptoms

1. The 3 Ps: polyuria, polydipsia, polyphagia
2. Blurred vision
3. Fatigue
4. Dry, itchy skin
5. Slow wound healing
6. Weight loss (type 1 diabetes)

C. Diagnosis

1. Random plasma glucose > 200 mg/dL plus signs and symptoms of diabetes OR
2. Fasting plasma glucose > 126 mg/dL OR
3. Two-hour postprandial glucose > 200 mg/dL during OGTT
4. Confirm the above.
5. Hemoglobin A1c testing (HbA1c): HbA1c is not used to diagnose DM, but is used for long-term monitoring.

D. Goals of therapy

Goals of Therapy

Target Area Treatment Goals (for the patient with diabetes)
Preprandial plasma glucose (fasting) 90–130 mg/dL
Postprandial plasma glucose (after meals) <180 mg/dL
Glycosylated hemoglobin (HbA1c) <7%
Blood pressure <130/80 mmHg
Lipid levels

LDL cholesterol
HDL cholesterol
Triglycerides

<100 mg/dL
>40 mg/dL (men); >50 mg/dL (women)
<150 mg/dL

Based on the American Diabetes Association guidelines. Individual treatment goals may vary slightly from these guidelines based on personal medical history.

E. Treatment

1. Diet
2. Exercise
3. Type 1: insulin therapy, pramlintide (Symlin)
4. Type 2: oral agents and/or insulin, pramlintide (Symlin), exenatide (Byetta)

F. Insulin

1. Background

a) Insulin is produced in the beta cells of the pancreas. It is released at a basal rate of 0.5 to 1 U/h. Insulin response is increased in response to food.
b) The mechanism of action is not completely understood.

(1) Muscle: increase glucose transport into cell, glycogenesis, protein and triglyceride synthesis
(2) Liver: increase glucose transport into cell, glycogenesis, glucose utilization in Krebs cycle, protein synthesis
(3) Adipose: increase glucose transport into cell, glycogenesis, triglyceride synthesis
(4) Take home point: Insulin is necessary for the body to use glucose.

2. Types of insulin

a) Short-acting

(1) Used for mealtime control
(2) Administered 15–30 minutes before meal
(3) May also be used for sliding scale
(4) Examples

(a) Insulin aspart (NovoLog)
(b) Insulin lispro (Humalog)
(c) Insulin glulisine (Apidra)
(d) Regular (Humulin R)

b) Intermediate-acting

(1) Used for basal control
(2) Dosed twice daily for optimal control; may also be dosed once daily at bedtime for patients with type 2 diabetes who also take oral medications to suppress overnight hepatic gluconeogenesis
(3) Example

(a) Isophane insulin, NPH (Humulin N)

c) Long-acting

(1) Like intermediate-acting are used for basal control
(2) Usually dosed once daily
(3) Should not be mixed with any other insulin
(4) Examples

(a) Insulin glargine (Lantus)
(b) Insulin detemir (Levemir)

d) Combination products

(1) Humulin 70/30 (70% NPH, 30% regular)
(2) Humulin 50/50 (50% NPH, 50% regular)
(3) Humalog mix 50/50 (50% insulin lispro protamine suspension, 50% lispro)
(4) Humalog mix 75/25 (75% insulin lispro protamine suspension, 25% lispro)
(5) NovoLog mix 70/30 (70% insulin aspart protamine suspension, 30% aspart)

3. Cautions

a) Causes hypoglycemia at high doses
b) Lispro has more rapid onset than regular and should not be interchanged with it
c) Patients with type 1 DM should not use once-daily dosing of insulin initially
d) Changes in insulin should only be made under supervision of medical personnel
e) Caution is warranted when switching from animal (either pork or bovine) to purified porcine insulin or biosynthetic human insulin due to increased potentcy or bioavailability and increased risk of hypoglycemia.
f) Injection needles should not be reused
g) Insulin should not be used during hypoglycemia
h) Insulin should still be used when ill (may need more insulin when ill)
i) Use of lispro has not been studied in pregnancy, fetal abnormalities occurred in two infants
j) Contraindication: hypersensitivity to the medications
k) Insulin dosing and use requires constant patient education and monitoring

4. Interactions

a) Medications affecting glucose: may increase or decrease effect of insulin
b) Pork and human insulin should not be mixed or used together

5. Toxicity and side effects

a) Hypoglycemia
b) Lipodystrophy
c) Weight gain
d) Patients may develop resistance to insulin treatment
e) Patients may develop sensitivity to animal insulin

6. Remarks regarding insulin

a) Should always be dosed in “units” (e.g., 10 units subcutaneous [SC])
b) Regular insulin solution should be clear
c) Mixing*

(1) Semilente/lente/ultralente: can be mixed in any proportion
(2) Regular + lente: bind immediately, if mixed, must use immediately after mixing or inject separately
(3) Lente + phosphate-buffered insulin (NPH, NovoNordisk, Humulin BR): must never be mixed; lente will become immediate-acting instead of delayed
(4) NPH and regular insulin can be combined in the same syringe and refrigerated for a maximum of 21 days

7. Injection technique

a) Use abdomen, arm, leg, or buttocks
b) Clean the injection area first with alcohol
c) Examine bottle and roll gently in hands
d) Inject air into vial, draw up desired dose
e) Pinch the skin with one hand, and insert the needle at an angle of 45°–90°
f) Dispose of the syringe properly
g) Rotate the injection site

8. Adjusting insulin dose

a) Adjustments are made based on glucose monitoring and HbA1c as well as pattern of response
b) Adjust basic insulin dose 1–2 units at a time; 2–4 units or more for extreme cases
c) For every unit of rapid-acting insulin, glucose may be reduced by 25–50 mg/dL
d) Long-acting insulin should be adjusted based on fasting glucose

Insulin Calculations

Starting Insulin: Staged Diabetes Management Guideline (SDM)

From Staged Diabetes Management, ed 4 © 2005, International Diabetes Center at Park Nicollet, Minneapolis, MN. All rights reserved. Reprinted with permission (+1)800-637-2675; and Pearson J, Powers M: Systematically Initiating Insulin: The Staged Diabetes Management Approach, The Diabetes Educator 32(Suppl)(1):23s–25s, 2006.

Guideline for starting and titrating background insulin: Background insulin + oral agent(s) insulin glargine or insulin detemir

<70 mg/dL Decrease 1–2 U
140–250 mg/dL Increase 2–4 U
>250 mg/dL Increase 4–8 U

0.1 U/kg body weight if A1c levels are <9% (long acting insulin)

0.2 U/kg body weight if A1c levels are ≥9%

Adjustments are made weekly based on fasting blood glucose.

It is common to start insulin therapy by using only insulin glargine (Lantus) at bedtime in combination with oral agents. The use of background insulin with oral antidiabetic agents is a common approach to initiate insulin therapy. The average dose that was effective in the Treat-to-Target study was 0.4 to 0.5 U/kg at bedtime. Continue to escalate dose if goal is not reached. If the dose surpasses 0.7 U/kg, transition return to background insulin. Mealtime regimen is recommended for tighter control.

Guideline for starting and titrating premixed insulin: Premixed insulin Aspart 70/30 or Lispro premix 75/25

Blood Glucose Adjust Insulin*

Prebreakfast

<70 mg/dL Decrease pm 1–2 U
140–250 mg/dL Increase pm 1–2 U
>250 mg/dL Increase pm 2–4 U

Presupper

<70 mg/dL Decrease am 1–2 U
140–250 mg/dL Increase am 1–2 U
>250 mg/dL Increase am 2–4 U

Start

0.1 U/kg in morning and evening if A1c <9%

0.2 U/kg in morning and evening if A1c ≥9%

Total daily units

0.2–0.4 U/kg

Adjust weekly based on am or pm blood glucose

Guidelines for starting and titrating background/mealtime insulin: Long-acting insulin (insulin glargine or insulin detemir) + rapid-acting insulin with meals

Blood Glucose Adjust Insulin†
Prebreakfast Long-acting (detemir or glargine)
Prelunch am Rapid acting
Presupper lunch Rapid acting
Prebedtime supper Rapid acting
Start If A1c <9%:
• 0.1 U/kg long-acting insulin
• 0.1 U/kg rapid-acting insulin divided between meals

If A1c ≥9%:
• 0.2 U/kg long-acting insulin
• 0.2 U/kg rapid-acting insulin divided between meals

Total units 0.2–0.4 U/kg Adjust Minimum weekly

* Stop secretagogue; consider continuing insulin sensitizer(s).

† Adjust insulin by 1–2 U based on blood glucose pattern. Review insulin-to-carbohydrate ratios and activity. Stop secretagogue; consider continuing insulin sensitizer(s).

9. Alternative methods of insulin administration

a) Pen

(1) Portable and convenient; an alternative to vial and syringe
(2) NovoPen 3, Flex Pen (NovoLog, NovoLog 70/30, Levemir)
(3) Humalog, Humalog mix 75/25, Humulin N, Humulin 70/30

b) Pump

(1) Continuous subcutaneous infusion

c) Inhaled insulin (Exubera)

(1) Withdrawn from the market due to lack of demand
(2) High cost
(3) Long-term pulmonary safety profile of concern

10. Somogyi effect and dawn phenomenon

a) Somogyi effect

(1) Rebound hyperglycemia due to insulin-induced hypoglycemia
(2) Treatment

(a) Adjust evening snack
(b) Decrease evening NPH or give at a later time
(c) Switch to a basal insulin

b) Dawn phenomenon

(1) Rise in blood glucose level upon waking during the early morning hours (usually between 4 am and 9 am)
(2) Treatment

(a) Limit or regulate evening snacks
(b) Possibly increase NPH dose or basal insulin

G. Synthetic amylin analog, pramlintide acetate (Symlin)

1. Mechanism of action: synthetic analog of human amylin

a) Amylin, like insulin, is located in pancreatic beta cells. It is secreted with insulin in response to food intake.
b) Reduces postprandial glucose
c) Slows gastric emptying
d) Decreases food intake
e) Increases satiety

2. Indications

a) Type 1 and type 2 diabetes as an adjunct to mealtime insulin

3. Usual adult dosage

a) Type 1 diabetes: initially, 15 mcg SC before meals; may titrate up at 15 mcg increments (without nausea for 3 days); maintenance: 30–60 mcg SC before meals
b) Type 2 diabetes: initially, 60 mcg SC before meals; may increase dose to 120 mcg SC before meals (without nausea for three days)

4. Adverse effects

a) Nausea
b) Hypoglycemia

5. Contraindications and considerations

a) Avoid in gastroparesis and hypoglycemia unawareness
b) Potential for drug interactions due to delayed gastric emptying
c) Reduce premeal insulin by 50% when initiating pramlintide

H. Incretin mimetic agent, exenatide (Byetta)

1. Mechanism of action

a) Stimulates the body’s ability to produce insulin in response to elevated concentrations of blood glucose
b) Inhibits the release of glucagon after meals
c) Slows the rate of gastric emptying
d) Reduces food intake

2. Indications

a) Treatment of type 2 diabetes (adjunct to metformin, sulfonylurea, or thiazolidinedione)

3. Usual adult dosage

a) Initially, 5 mcg SC bid given within 60 minutes before morning and evening meal
b) May increase dose to 10 mcg SC bid after one month
c) Available in prefilled pens (must refrigerate)

4. Adverse effects

a) Hypoglycemia (more likely when combined with a sulfonylurea)
b) Nausea

5. Contraindications and considerations

a) Hypersensitivity to exenatide
b) Potential for drug interactions due to delayed gastric emptying
c) Has not been studied for use with insulin
d) Pancreatitis

I. Oral agents for diabetes

1. Sulfonylureas

a) Mechanism of action

(1) Stimulates insulin release from pancreatic beta cells; increases peripheral sensitivity
(2) Inhibits hepatic glucose production; enhances glucose uptake in muscle
(3) Insulin secretagogues

b) First generation versus second generation-

(1) Fewer adverse effects with second generation agents (e.g., glyburide, glipizide), although patient is still at risk for hypoglycemia
(2) Second generation (e.g., glyburide, glipizide, glimepiride) more potent
(3) Comparable efficacy

c) Indications: management of type 2 diabetes as monotherapy; also combined with other antidiabetic medications if needed (e.g., metformin, insulin)
d) Usual adult dosage

Comparable Efficacy

  Generic (Brand) Adult Daily Dose Range
First generation Acetohexamide (Dymelor) 250–1500 mg
Tolbutamide (Orinase) 500–3000 mg
Tolazamide (Tolinase) 100–1000 mg
Chlorpropamide (Diabinese) 100–500 mg
Second generation Glipizide:

Glucotrol
Glucotrol XL

2.5–40 mg
2.5–20 mg

Glyburide:

Micronase, DiaBeta
Glynase

2.5–20 mg
1.5–12 mg
  Glimepiride (Amaryl) 1–4 mg
e) Adverse effects

(1) Hypoglycemia
(2) Nausea/vomiting
(3) Weight gain
(4) Rash
(5) Dyspepsia
(6) Hematologic reactions

f) Contraindications and considerations

(1) Hypersensitivity
(2) Type 1 diabetes
(3) Avoid alcohol

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