Diabetes Mellitus Definition and Symptoms

Diabetes Mellitus

Definition and Symptoms

• Defined as a group of metabolic diseases characterized by inappropriate hyperglycemia
• Symptoms include:
  • Polyuria
  • Polydipsia
  • Polyphagia
  • Weight loss
  • Blurred vision
  • Fatigue
  • Headache
  • Poor wound healing

Classification

• Four clinical classes of diabetes:
  1. Type 1 Diabetes Mellitus (T1DM):
     • Characterized by an absolute insulin deficiency
     • Autoimmune destruction of the β-cells of the islets of Langerhans
     • Can be diagnosed at any age, but most likely to be diagnosed prior to the age of 30 years
  2. Type 2 Diabetes Mellitus (T2DM):
     • Most common form of DM
     • Typically identified in individuals over the age of 30 years
     • Associated with overweight or obesity, positive family history, and signs of insulin resistance
  3. Gestational Diabetes Mellitus (GDM):
     • Condition in which women first exhibit levels of elevated plasma glucose during pregnancy
     • Diagnostic classification of GDM may be changed based on postpartum testing
  4. Other Specific Types:
     • Secondary diabetes occurs when the diagnosis of diabetes is a result of other disorders or treatments
     • Monogenic DM (formerly maturity-onset diabetes of the young) should be considered in children with an atypical presentation or response to therapy

Diabetes Demographics and Statistics

• In the United States, an estimated 8.3% of the population has DM and 35% of adults have prediabetes
• Disparities exist in the diagnosis of diabetes across ethnic groups and minority populations
• T2DM accounts for more than 90% of the cases of diabetes

Insulin

• Types of insulin:
  • Rapid-acting insulin
  • Short-acting insulin
  • Intermediate-acting insulin
  • Long-acting insulin
• Premixed insulin products:
  • 50/50 insulin
  • 70/30 insulin
  • 75/25 insulin
• Extemporaneous mixtures:
  • Two insulins mixed in one syringe, before administration

Insulin Concentration and Sources

• Concentration of insulin products available in the United States:
  • U-100: a concentration of 100 units/mL
  • U-500: a concentration of 500 units/mL
• Chemical sources of commercial insulin available in the United States:
  • Biosynthetic human insulin
  • Insulin analog

Pathophysiology of the Diabetic State

• Normal glucose regulation involves:
  • Insulin
  • Counterregulatory hormones
  • Incretin hormones
  • Amylin
• Insulin regulates the metabolism of:
  • Carbohydrate
  • Protein
  • Fat

Development of Diabetes

• Type 1 Diabetes:
  • Genetic predisposition, environmental factors, and autoimmunity are proposed as causes of T1DM
  • T1DM is the result of immune-mediated destruction of the B-cells
• Type 2 Diabetes:
  • Genetic factors, B-cell dysfunction, and peripheral site defect contribute to T2DM
  • May arise from other disorders or treatments

Clinical Evaluation

• Physical findings:
  • Polyuria
  • Polydipsia
  • Polyphagia
  • Weight loss
  • Blurred vision
  • Fatigue
  • Headache
  • Poor wound healing
• Diagnostic testing:
  • Venipuncture testing
  • A1c tests
  • Fasting blood glucose
  • Random (casual) blood glucose
  • Oral glucose tolerance test (OGTT)

Glycemic Treatment Goals

• Two available techniques for monitoring glycemic control:
  • Patient self-monitoring blood glucose (SMBG)
  • A1c
• Guideline recommendations for the use of these two techniques:
  • American Diabetes Association (ADA)
  • American Association of Clinical Endocrinologists (AACE)

Meglitinides and Phenylalanine Derivatives

• Indications:
  • Used for the management of type 2 diabetes
  • Target postprandial control
• Contraindications:
  • Should be avoided in patients with severe renal or hepatic dysfunction
  • Caution should be used in elderly patients due to the increased risk of falls with hypoglycemic events

Biguanides

• Agents:
  • Metformin
• Indications:
  • Used for the glycemic management of type 1 and type 2 diabetes
  • Recommended for initiation at diagnosis of T2DM unless contraindicated
• Contraindications:
  • Renal disease
  • Hepatic impairment
  • Heart failure
  • Intravascular iodinated contrast media

DPP-IV Inhibitors, Bile Acid Sequestrants, Dopamine Agonists, and GLP-1 Agonists

• Agents:
  • Sitagliptin
  • Saxagliptin
  • Linagliptin
  • Colesevelam
  • Bromocriptine
  • Exenatide
  • Liraglutide
• Indications:
  • Used for the management of type 2 diabetes
  • Target postprandial control
• Contraindications:
  • Sitagliptin and saxagliptin require dosage adjustments for CrCI < 50 mL/min
  • Linagliptin may be used in mild-to-moderate hepatic impairment
  • Colesevelam avoid in persons with obstructive bowel disease or triglyceride levels > 500 mg/dL
  • Bromocriptine use with caution in persons with cardiovascular disease, peptic ulcer disease, psychosis, or dementia
  • Exenatide and liraglutide contraindicated in persons with pancreatitis or a history of pancreatitis, T1DM, and gastroparesis### Insulin Management
• Point-of-care calculation: (Current blood glucose - target blood glucose)/CF
• Example: If blood glucose level is 230 mg/dL and target is 120 mg/dL, individual needs to inject 2 units of rapid-acting insulin to bring blood glucose back into target range
• Note: CF should be rechecked at least once per year or when there is a significant change in weight, as this is a weight-based calculation

Insulin Adjustments

• Repeated Hypoglycemia or Hyperglycemia: Consider insulin dose, eating habits, exercise routine, and insulin onset, peak, and duration of action
• Example: If patient is taking 16 units of NPH and 6 units of regular insulin twice daily and has in-target pre-lunch blood glucose levels but experiences hypoglycemia at supper, lower the morning NPH dose
• Dawn Phenomenon: Increase evening basal insulin or move dosage to bedtime to correct for fasting hyperglycemia
• Somogyi Effect: Decrease evening basal insulin to prevent fasting hyperglycemia caused by rebound hyperglycemia

Routes of Insulin Administration

• Subcutaneous Injection:
  • Site selection: Abdomen, buttocks, upper arm, or outer thigh
  • Abdomen is the fastest absorption site
  • Site rotation: Rotate injection sites within an anatomical region to prevent lipohypertrophy and fibrosis
• Continuous Intravenous:
  • Use U-100 regular insulin
  • For acute hyperglycemia, hyperglycemic emergency (DKKA or HHS), or during surgical procedures
  • Transitioning from IV to SQ: Short or rapid-acting insulin 1-2 hours prior to IV discontinuation; Intermediate or long-acting insulin 2-3 hours prior to IV discontinuation
• Continuous Subcutaneous Infusion (Insulin Pump Therapy):
  • Provides tighter glycemic control by continuously infusing rapid-acting insulin
  • Requires understanding of pump complexity, blood glucose monitoring, and bolus insulin dosing for dietary intake

Insulin Secretagogues (Oral Hypoglycemic Agents)

• Sulfonylureas:
  • First-generation: Not commonly prescribed due to adverse events (thrombocytopenia, agranulocytosis, hemolytic anemia, hyponatremia, SIADH, disulfiram-like reactions)
  • Second-generation: Glyburide (DiaBeta, Glynase), Glipizide (Glucotrol), Glimepiride (Amaryl)

Oral and Noninsulin Injectable Agents

• a-Glucosidase Inhibitors:
  • Acarbose (Precose): 25 mg t.i.d. with the first bite of each main meal (60 kg: 100 mg t.i.d.); Adverse effects include diarrhea and abdominal stress, which is dose dependent and subsides with continued use
  • Miglitol (Glyset): 25 mg t.i.d. with the first bite of each main meal (100 mg t.i.d.); Dose should be increased slowly as tolerated
• Biguanide:
  • Metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet): 500 mg once or twice daily with meals (Short-acting: 2550 mg/day; long-acting: 2000 mg/day); Adverse effects: transient nausea and abdominal cramping (typically lasts up to 2 weeks); lactic acidosis (rare, but fatal)
• Thiazolidinediones (TZDs):
  • Pioglitazone (Actos): 15-30 mg once daily without regard to meals (45 mg/day); Adverse effects include weight gain and peripheral edema
  • Rosiglitazone (Avandia): 4 mg once daily without regard to meals (8 mg/day); Contraindicated in hepatic disease and heart failure (class III or IV)
• Sulfonylureas:
  • Glipizide (Glucotrol, Glucotrol XL): 5 mg once daily (Immediate release: 40 mg/day; extended release: 20 mg/day); Adverse effects: hypoglycemia, weight gain
  • Glyburide (DiaBeta, Glynase PresTab): DiaBeta: 2.5-5.0 mg/day with a meal (20 mg/day); Contraindications: Glyburide is not recommended if CrCI < 50 mL/min; however, glimepiride and glipizide may be used to a lower CrCl
  • Glimepiride (Amaryl): 1-2 mg once daily with a meal (8 mg/day)
• Meglitinides:
  • Repaglinide (Prandin): Not previously treated for DM or A1c < 8%: 0.5 mg before each meal; Previously treated for DM or A1c > 8%: 1-2 mg before each meal (16 mg/day); Primary adverse effect: hypoglycemia
• Phenylalanine Derivatives:
  • Nateglinide (Starlix): 120 mg t.i.d. with meals