II. History: Diabetes Mellitus Pharmacology

  1. 1922: Crude Insulin Extracts by Banting and Best
  2. 1940: NPH Insulin developed
  3. 1950: Sulfonylureas developed
  4. 1960: Biguanides off market
  5. 1970: Second Generation Sulfonylureas

III. Protocol: Blood Glucose Monitoring Goals

  1. Target Blood Glucose (>50% of readings in range)
    1. Children under age 6
      1. Before meals: 100-180 mg/dl
      2. Bedtime and overnight: 110-200 mg/dl
    2. Children age 6 to 12
      1. Before meals: 90-180 mg/dl
      2. Bedtime and overnight: 100-180 mg/dl
    3. Children age 13 to 19
      1. Before meals: 90-130 mg/dl
      2. Bedtime and overnight: 90-150 mg/dl
    4. Adult
      1. Fasting (before breakfast): <105 mg/dl
      2. Before Meals: 70-120 mg/dl
      3. Two hour post-prandial <160 mg/dl
      4. Before bedtime: 100-160 mg/dl
    5. Adjust target to Blood Glucose 100-160 mg/dl before meals IF
      1. Recurrent Hypoglycemia
      2. Decreased Life Expectancy
        1. Frail elderly
        2. Cognitive disorder
      3. Serious comorbid medical condition
        1. Coronary Artery Disease
        2. Cerebrovascular Accident
        3. End Stage Renal Disease
        4. Hypoglycemia unaware
  2. Target Hemoglobin A1C (check 3-4 times per year)
    1. Under age 6 years: 7.5 to 8.5%
    2. Age 6 to 12: <8.0%
    3. Age 13-19: <7.5%
    4. Age 20 and older: <7.0%
    5. Frail, elderly or severe Hypoglycemia risk or history: <8.0%
  3. Additional Monitoring
    1. Urine Ketone Indication (Type I Diabetes Mellitus)
      1. Blood Glucose exceeds 240 for 2 values
      2. Concurrent illness or infection

IV. Protocol: Scheduled Blood Glucose Monitoring

  1. Individualized and negotiated
  2. Minimum monitoring routine
    1. Type I Diabetes Mellitus: At least three times daily
    2. Type II Diabetes Mellitus
      1. At least once daily for those on Insulin, uncontrolled Diabetes Mellitus, or those at risk for Hypoglycemia
        1. Karter (2001) Am J Med 111:1-9 [PubMed]
      2. Periodic monitoring is reasonable for well controlled Type II Diabetes Mellitus on Oral Hypoglycemics
        1. As needed Blood Sugar Monitoring should be reviewed with patient (see special circumstances below)
  3. Ideal monitoring routine
    1. Before meals (qAC)
    2. After meals (2 hours post-prandial)
    3. Bedtime (qHS)
  4. Monitoring in Special Circumstances
    1. See Diabetes Sick Day Management
    2. See Hypoglycemia Management
    3. Blood Sugar at 3 am
      1. Obtain prior to adjusting overnight Insulin
      2. Obtain if morning Hyperglycemia
        1. Hyperglycemia (Dawn Phenomena)
        2. Nocturnal Hypoglycemia (Somogyi Phenomena)
    4. Exercise in Diabetes Mellitus
      1. Check Glucose before and after Exercise
  5. Consider 2 hour post-prandial Glucose (PPG) weekly
    1. PPG is earliest detectable glycemic abnormality
    2. PPG correlates best with Hemoglobin A1C
    3. PPG correlates with vascular complications

V. Protocol: Blood Glucose data utilization

  1. Imperative to review Blood Sugar logs frequently
  2. Certain monitors can download stored values to PC
    1. Calculates Glucose ranges, median, and means
    2. Plots Glucose trends overall and by time of day
    3. Shows pie chart of high, low, and ideal Glucose
  3. Correlate Blood Sugar readings with Hemoglobin A1C
  4. Review Blood Sugar trends between clinic visits
  5. If Hemoglobin A1C does not correlate with Glucose
    1. Check meter accuracy
    2. Assess patient finger stick Blood Sugar skills
    3. Monitor Blood Glucose more frequently
    4. Refer for diabetes education
  6. Adjust Management if
    1. Hypoglycemic Episodes (treat these first)
    2. Blood Glucose or Hemoglobin A1C target goals per age not met
    3. Example of adult indications for adjusted medications
      1. Fasting or pre-meal Serum Glucose exceeds 140 (>50% of readings)
      2. Bedtime Glucose exceeds 160 (>50% of readings)
      3. Hemoglobin A1C exceeds 7.0%

VI. Efficacy: Intensive Glucose lowering effects (on average goal of Hgb A1c <7.0%)

  1. Type I Diabetes Mellitus: Significant benefit of intensive glycemic control
    1. DCCT results
      1. Retinopathy reduced by 63%
      2. Neuropathy reduced by 60%
      3. Nephropathy reduced by 54%
      4. Complication-free living increased by >15 years
      5. Life Expectancy extended by >5 years
      6. (1993) N Engl J Med 329:977-86 [PubMed]
      7. (1996) JAMA 276:1409-15 [PubMed]
      8. (2005) N Engl J Med 353: 2643-53 [PubMed]
    2. Significant reduction in cardiovascular events and mortality
      1. Lind (2014) N Engl J Med 371(21):1972-82 [PubMed]
  2. Type II Diabetes Mellitus: NO significant benefit of intensive glycemic control (although mixed early results)
    1. Increased mortality with intensive control (ACCORD)
      1. (2008) N Engl J Med 358: 2545-59 [PubMed]
    2. No significant benefit in cardiovascular disease or events (ACCORD)
      1. Gerstein (2014) Lancet 384(9958): 1936-41 [PubMed]
    3. Minimal longterm cardiovascular benefit and no mortality benefit to intensive control
      1. Hayward (2015) 372(23): 2197-206 [PubMed]
    4. Reduced nephropathy with intensive glycemic control (ADVANCE)
      1. (2008) N Engl J Med 358: 2560-72 [PubMed]
    5. Reduced microvascular complications (retinopathy, nephropathy, Neuropathy) with intensive control (UKPDS)
      1. (1998) Lancet 352: 837-53 [PubMed]
  3. References
    1. Kendall (2008) Park Nicollet Primary Care Update Lecture, St Louis Park, MN [PubMed]

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