Type 2 Diabetes Mellitus

Aka: Type 2 Diabetes Mellitus, Type II Diabetes Mellitus, Non-Insulin Dependent Diabetes Mellitus, NIDDM, Type II Diabetes

1. See Also
   1. Diabetes Mellitus
   2. Type I Diabetes Mellitus
   3. Insulin Resistance Syndrome
   4. Glucose Metabolism
   5. Diabetes Mellitus Education
   6. Diabetes Mellitus Complications
   7. Diabetic Ketoacidosis
   8. Hyperosmolar Hyperglycemic State
   9. Diabetes Mellitus Control in Hospital
   10. Diabetes Mellitus Glucose Management
   11. Hypertension in Diabetes Mellitus
   12. Hyperlipidemia in Diabetes Mellitus
   13. Diabetic Retinopathy
   14. Diabetic Nephropathy
   15. Diabetic Neuropathy
2. Epidemiology
   1. Represents 90% of all Diabetes Mellitus
   2. Typically occurs over age 40 years in obese patients
3. Pathophysiology
   1. Triad of factors contributing to Diabetes Mellitus
      1. Impairment of pancreatic beta-cell function
         1. Decreased beta cell response to Glucose
            1. Abnormal Glucagon secretion
         2. Amyloidosis of islet cells (40% of patients)
         3. Pancreatic fibrosis (66% of patients)
            1. Associated fatty infiltration, vessel sclerosis
      2. Decreased Insulin sensitivity (60-80% of patients)
         1. See Insulin Resistance
         2. Obesity
      3. Incretin Deficiency
   2. Course
      1. 12 years before diagnosis: Impaired Glucose Tolerance
         1. Insulin Resistance starts
         2. Insulin levels start to rise
         3. Fasting and post-meal Glucose normal
      2. 8 years before diagnosis: Postprandial Hyperglycemia
         1. Beta cell function at 75%
         2. Insulin levels increase to 150% of normal
         3. Fasting and post-meal Glucose normal
      3. 2 years before diagnosis: Type 2 diabetes phase I
         1. Beta cell function at 50%
         2. Insulin levels increase to 200% of normal (peak)
         3. Post-prandial Glucose 150-200 mg/dl
         4. Normal fasting Glucose
      4. 2 years after diagnosis: Type 2 diabetes phase II
         1. Insulin levels fall to 150% of normal
         2. Post-prandial Glucose 200 mg/dl
         3. Fasting Glucose >140-150 mg/dl
      5. 8 years after diagnosis: Type 2 diabetes phase III
         1. Beta cell function at 25%
         2. Insulin levels fall to 100% of normal
      6. 14 years after diagnosis
         1. Beta cell function approaches 0%
         2. Insulin levels fall below 50% and approach 0
4. Etiology
   1. Autosomal Recessive
5. Risk Factors:
   1. Obesity (especially Apple Obesity)
   2. Previous Gestational Diabetes (GDM)
   3. Family History of Type II Diabetes Mellitus
   4. Age over 40 years (risk increases with age)
      1. Type II Diabetes Mellitus does occur in children
   5. Sedentary lifestyle (decreased Physical Activity)
   6. Previously Impaired Glucose Tolerance (IGT)
   7. Western diet
      1. Red meats and processed meats
      2. High fat foods (french fries, high fat dairy, eggs)
      3. High sugar foods, desserts and drinks
      4. Van Dam (2002) Ann Intern Med 136:201-9
   8. Ethnicity
      1. Native American
      2. African American or Black
      3. Asian Type II Diabetics may be thin
      4. Hispanic
   9. Cigarette smoking decreases Insulin sensitivity
      1. Targher (1997) Clin Endocrinol Metab 82:3619-23
6. Protective Factors (based on initial study findings)
   1. See Insulin Resistance
7. Symptoms and Signs
   1. See Diabetes Mellitus
8. Diagnostic Criteria
   1. See Diabetes Mellitus
9. Associated Conditions
   1. See Insulin Resistance
   2. Acanthosis Nigricans
10. Labs
    1. Urine Ketones: Usually negative
       1. Exception: Children with Type II Diabetes
    2. See Diabetes Mellitus
11. Precautions: Accord Trial
    1. Suggests higher risk of aggressively lowering Blood Glucose in Type II Diabetes
    2. Risk increased with Hemoglobin A1C of 6.4% compared with 7.5%
    3. Mortality was higher in the 6.4% A1C group by 3 per thousand patients
    4. Endocrinologists still recommend goal of <7.0% and await larger trial (Advance)
    5. References: NHLBI Questions and Answers regarding Accord Study
       1. http://www.nhlbi.nih.gov/health/prof/heart/other/accord/q_a.htm
12. Management: Summary
    1. Medical nutrition therapy
       1. Indications to start at presentation
          1. Hemoglobin A1C <8%, Fasting BG <200, Random BG <250
       2. Efficacy: A1C decrease 1%
       3. Protocol
          1. Obese patients (Fasting Glucose high)
             1. Insulin Resistance primary problem in early phase
             2. Focus on weight loss and activity
          2. Lean patients (Postprandial Glucose high)
             1. Insulin deficiency is primary problem
             2. Focus on Carbohydrate Counting
    2. Oral agents
       1. Indications to start at presentation
          1. Hemoglobin A1C 8-8.9%
          2. Fasting BG 200-250 mg/dl
          3. Random or casual BG 250-300 mg/dl
       2. Efficacy: A1C decrease 1-2% (combined with above)
       3. Protocol
          1. Obese patients (Fasting Glucose high)
             1. Metformin (Glucophage)
             2. Glitazone (e.g. Pioglitazone, Rosiglitazone)
          2. Lean patients (Postprandial Glucose high)
             1. Oral secretagogue (e.g. Sulfonylurea)
    3. Combination therapy
       1. Indications to start at presentation
          1. Hemoglobin A1C 9-11%
          2. Fasting BG 251-300 mg/dl
          3. Random or casual BG 301-350 mg/dl
       2. Efficacy: A1C decrease 2-4% (combined with above)
       3. Protocol: Options
          1. Glucophage with Glitazone (esp. obese patients)
          2. Insulin Secretagogue with Glitazone
          3. Insulin Secretagogue with Glucophage
          4. Incretin with Sulfnylurea (use caution)
          5. Incretin with Glucophage
    4. Insulin Therapy
       1. Indications to start at presentation
          1. Hemoglobin A1C >11%
          2. Fasting BG >300 mg/dl
          3. Random or casual BG >350 mg/dl
       2. Protocol: Options
          1. Basal Insulin
          2. Basal with bolus Insulin
          3. Mixed Insulin
13. Management: General
    1. Intensive Diabetic Education
       1. Goal Hemoglobin A1C <7.0 to 8.0
          1. Goal relaxed to 8% in 2009 based on ACCORD and ADVANCE results
       2. Fasting plasma Glucose: 70 to 140 mg/dl (ideal <105)
          1. New guidelines may suggest 70 to 120 mg/dl
       3. 2 hour postprandial Glucose: <160 mg/dl (ideal <135)
          1. Ideally, only 20-40 mg/dl rise over pre-meal
       4. Bedtime Glucose: 100-140 mg/dl
    2. Weight loss if Overweight
       1. Recommend 10-20 pound weight loss
       2. Lower caloric intake by 250-500 calories per day
    3. Cardiovascular Disease Prevention
       1. Lower LDL Cholesterol <80-100 (Statin)
       2. Lower Blood Pressure <130/80 (ACE Inhibitor or ARB as first line medication)
          1. Keep systolic Blood Pressure between 120 and 130 mmHg
       3. Aspirin 81-160 mg PO qd
       4. ACE Inhibitor (Indicated in Proteinuria)
14. Management: Medications in children with Type II Diabetes
    1. First-line agents
       1. Metformin
       2. Insulin
          1. Start with basal Insulin
          2. Consider pre-mixed Insulin (e.g. 70/30) for postprandial Hyperglycemia
    2. Second-line agents
       1. Sulfonylureas (risk of Hypoglycemia)
       2. Acarbose or Colesevelam
    3. Agents with unknown safety in children
       1. Actos
       2. Januvia
       3. Byetta
    4. References
       1. (2012) Presc Lett 19(7): 40
15. Management: Medications
    1. First-line Oral Hypoglycemics
       1. See Oral Hypoglycemic agents
       2. Glucophage (Metformin) or
       3. Thiazolidinedione (if Glucophage contraindicated)
    2. Insulin
       1. Indications
          1. Glucose toxicity
             1. Fasting Blood Glucose >250 mg/dl and
             2. Ketosis or weight loss
          2. Hemoglobin A1C > 10% or random Blood Glucose consistently >300 mg/dl
          3. Inadequate Blood Sugar control on oral agents and Hemoglobin A1C >9%
          4. Late stage Type II Diabetes (>5-10 years)
          5. Perioperative Diabetes Management
          6. Chronic Renal Failure
          7. Pregnancy
          8. Acute illness
       2. Protocol
          1. See Insulin Dosing
          2. See Insulin Dosing in Type II Diabetes
          3. Option 1: Insulin augmentation
             1. Start Dose: 0.15 to 0.20 units/kg daily (10-14 units/day)
             2. Titrate Dose: Increase by 2 units every 3 days
             3. Preparations
                1. Insulin Glargine (Lantus) daily or
                2. NPH (Novolin N, Humulin N) at bedtime or twice daily
          4. Option 2: Insulin replacement
             1. Titrate dose up to 0.5 units/kg daily
             2. Long-acting basal Insulin (NPH or Lantus) and
             3. Short-acting bolus Insulin (Lispro, Aspart, Reg)
       3. Efficacy
          1. Insulin therapy does not reduce quality of life
          2. No increase in hypoglycemic episodes
          3. Significant improvement in glycemic control
          4. De Grauw (2001) Br J Gen Pract 51:527-32
16. Management: Initial
    1. See Diabetes Mellitus Glucose Management
    2. Sample Initial Protocol
       1. Fasting Blood Sugar <200 or random Glucose <250
          1. Consider trial of diet and Exercise for 1-2 months
          2. Strongly consider concurrent Oral Hypoglycemic
       2. Fasting Blood Sugar <300 or random Glucose <350
          1. Start Oral Hypoglycemic agent (see above)
       3. Fasting Blood Glucose >250 mg/dl and Glucose toxicity
          1. Start Insulin replacement protocol (see above)
          2. Concurrently start Oral Hypoglycemic (Metformin)
       4. Fasting Blood Sugar >300 or random Glucose >350
          1. Start Insulin replacement protocol (see above)
          2. Concurrently start Oral Hypoglycemic (Metformin)
17. Management: Follow-up Adjustment Phase
    1. Weekly phone call to review Blood Glucose log
    2. Monthly clinic visits
    3. Dietician or nutritionist every 2-4 weeks
    4. Goal Blood Glucose not met (Hemoglobin A1C >7.0)
       1. Oral Hypoglycemic agents not maximized
          1. Maximize dosing of current agents
          2. Add Sulfonylurea to Glucophage
          3. Add Thiazolidinedione if not already added
          4. Add Incretin (GLP-1 Analog or DPP-4 Inhibitor)
             1. Avoid using 2 Incretins in combination (raises cost, risk of Pancreatitis without significant benefit)
             2. (2012) Presc Lett 19(8): 45
       2. Oral Hypoglycemics maximized or contraindicated
          1. Start Insulin augmentation (see above)
       3. Insulin augmentation has already been started
          1. Start Insulin replacement (see above)
18. Management: Follow-up Maintenance Phase
    1. Clinic visits every 3-4 months
       1. Review Blood Sugar log and Hypoglycemic episodes
       2. Review medication dosages
       3. Evaluate comorbid conditions
          1. Evaluate weight or BMI
          2. Check Blood Pressure
       4. Clean and check Glucometer
    2. Education
       1. Nutrition in Diabetes Mellitus
       2. Exercise in Diabetes Mellitus
       3. Foot Care (examine feet at every visit)
    3. Examination
       1. Annual Health Maintenance Exam
       2. Annual Eye examination with Pupil Dilation
       3. Annual Dental Exam
    4. Labs
       1. Daily
          1. Home Glucose monitoring before meals and bedtime
          2. Postprandial Glucose (2 hours after meal)
             1. May be better marker for control
       2. Every 3 months
          1. Hemoglobin A1C
       3. Annual
          1. Fasting Lipid Profile
          2. Renal Function tests (BUN and Creatinine)
          3. Urinalysis
          4. Urine Microalbumin
19. References
    1. Mayfield (2004) Am Fam Physician 70:489-512
    2. Yki-Jarvinen (2001) 24:758-67