Type 1 Diabetes Mellitus

Aka: Type 1 Diabetes Mellitus, Type I Diabetes Mellitus, Insulin Dependent Diabetes Mellitus, IDDM, Type I Diabetes, Juvenile Diabetes Mellitus

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II. Epidemiology

  1. Typical onset before age 30 years
  2. Non-obese patients
    1. However, teens with Type I Diabetes are more Overweight than teens without diabetes
  3. Prevalence (2015, U.S.): 1.25 Million (4% of the 30.3 Million Diabetes Mellitus cases in U.S.)
    1. http://www.diabetes.org/diabetes-basics/statistics/
  4. Ethnic disparity in management (based on T1D registry data)
    1. White patients have a higher utilization of Insulin Pumps than black or hispanic patients
    2. Black patients have higher Hemoglobin A1C levels than white or hispanic patients

III. Pathophysiology

  1. Type 1A
    1. Environmental and genetic factors
    2. HLA-DR4 association
    3. Cell mediated pancreatic beta cell destruction
  2. Type 1B (uncommon)
    1. Primary Autoimmune Condition
    2. Associated with other Autoimmune Conditions
      1. Hashimoto's Thyroiditis
      2. Grave's Disease
      3. Myasthenia Gravis
    3. HLA-DR3 association
    4. Incidence highest in 30-50 year olds
  3. Neonatal Diabetes Mellitus
    1. Congenital malfunction or malformation of pancreatic beta cells leading to severe Hyperglycemia in neonates
    2. Rare, inherited condition (case reports of families with Autosomal Dominant inheritance)
    3. Beltrand (2020) Front Pediatr 8:540718 [PubMed]
  4. Secondary Diabetes Mellitus
    1. Cystic Fibrosis
  5. Environmental Factors
    1. Medications
      1. Streptozocin
      2. Pentamidine
    2. Viruses
      1. Mumps
      2. Cytomegalovirus (CMV)
      3. Coxsackie
        1. Enterovirus IgM linked to IDDM in adolescents
          1. Studied 128 children with new onset IDDM
          2. Non-specific to subtype (coxsackie, echovirus)
          3. Helfand (1995) J Infect Dis 172:1206-11 [PubMed]
      4. Congenital Rubella
        1. Late Type I Diabetes Mellitus develops in 40%

IV. Findings: Symptoms and Signs

  1. See Diabetes Mellitus

V. Findings: Common Presentations

  1. Diabetic Ketoacidosis
    1. Major presenting syndrome in 25% of cases
    2. More common in under 3 years and adolescence
  2. Incidental glucosuria or Hyperglycemia
  3. Acute Abdominal Pain
  4. Influenza-like illness

VI. Diagnosis

  1. See Diabetes Mellitus
  2. Oral Glucose Tolerance Test
  3. Fasting Blood Glucose or Random Blood Glucose
  4. Two hour post-prandial Glucose
  5. Intravenous Glucose Tolerance Test

VII. Labs

  1. Initial studies
    1. Urinalysis
    2. Blood Glucose
    3. Electrolytes
    4. Glycosylated Hemoglobin (Hemoglobin A1C)
    5. Thyroid Stimulating Hormone (TSH)
    6. Consider Celiac Sprue testing (if suggestive symptoms)
  2. Diagnostics in Atypical Presentation
    1. Approach
      1. Antibodies are often ordered as panel (Anti-GAD65 Antibody, ICA, IA-2a/b)
    2. Anti-Glutamic Acid Decarboxylase Antibody (Anti-GAD65 Antibody) - most useful of markers
      1. Test Sensitivity in Type I Diabetes: 60% in adults (60-73% in children)
      2. Not specific, also found in 7-34% in adults and children with Type II Diabetes
        1. Absence of Antibody makes requring inulin withn 6 years in adults unlikely (NPV 94%)
    3. Anti-islet cell surface Antibody (ICA)
      1. Test Sensitivity in Type I Diabetes: 75-85% in adults and children
      2. Not specific for Type I Diabetes (seen in up to 21% of Type II Diabetes adults)
    4. Anti-insulin Antibody (IA-2a and IA-2b)
      1. Test Sensitivity in Type I Diabetes: 40% in adults and 40-86% in children
      2. More specific for Type I Diabetes (only present in ~2% of Type II Diabetes)
    5. C-peptide low or absent (<1.51 ng)
      1. Consider after Sustacal challenge
      2. Not specific for Type I Diabetes Mellitus (also seen in Type II)
        1. Fasting C-Peptide <0.6 ng/ml (0.2 nmol/L) is consistent with Insulin deficiency
      3. C-Peptide is best interpreted during significant Hyperglycemia (Serum Glucose >300 or 400 mg/dl)
        1. Low C-Peptide suggests Insulin deficiency
        2. High C-Peptide suggests Insulin Resistance
      4. Normal C-Peptide levels in non-diabetics
        1. Fasting: 0.9 to 1.8 ng/ml (0.3 to 0.6 mmol/L)
        2. Postprandial: 3 to 9 ng/ml (1 to 3 mmol/L)
    6. Zinc transporter 8 autoantibody
      1. May confirm autoimmune-mediated Diabetes Mellitus when other autoantibody tests are negative
  3. References
    1. Patel (2010) Am Fam Physician 81(7): 863-70 [PubMed]

VIII. Management: Initial

  1. Treat acute problems (includes non-diabetic issues)
  2. Set initial goals and targets
    1. See Diabetes Mellitus Glucose Management
  3. Initiate Insulin therapy
    1. See Insulin Dosing
    2. If atypical presentation, then base on Ketones (unclear if Type I or Type II)
      1. Ketones positive: Start Insulin
      2. Ketones negative: Consider treating as Type II
  4. Education
    1. See Diabetes Mellitus Education
    2. Teach survival skills
    3. Establish plan for ongoing care and education
    4. Review importance of intensive therapy (compared with conventional care)
      1. See Diabetes Mellitus Glucose Management
  5. Precautions: Honeymoon Period
    1. Honeymoon period (partial remission of diabetes) occurs in 50% of children with Type 1 Diabetes Mellitus
    2. Associated with Hypoglycemia risk
      1. Partial return of B-Cell Insulin secretion with lower exogenous Insulin requirements
      2. Increased Insulin sensitivity
    3. Timing
      1. Onset 2-3 months after Insulin initiated
      2. Last for weeks to months, and in some cases years (mean 9 months)
    4. Requires adjustment in Insulin Dosing and monitoring
      1. Decrease Insulin (often to very low levels or stopping completely)
      2. Close Glucose monitoring
      3. Respond to Hypoglycemia by reducing or eliminating Insulin

IX. Management: Follow-up

  1. Initial
    1. Daily phone contact for first 3 days
    2. Office visit within 2 weeks
    3. Emergency 24 hour phone number given
  2. Adjustment phase
    1. Consider weekly phone call
    2. Monthly office visit
  3. Maintenance Phase
    1. Office visit every 3-4 months
    2. Review Blood Sugar Log
      1. Hypoglycemic Episodes
      2. Hyperglycemia
      3. Ketones
    3. Review food plan
    4. Review Exercise program
    5. Review Medications
    6. Exam
      1. Height, Weight and Body Mass Index (BMI)
      2. Growth rate (pediatric Diabetes Mellitus)
      3. Blood Pressure
    7. Labs
      1. Check Glucose Meter against Serum Glucose
      2. Hemoglobin A1C
    8. Education
      1. Nutrition in Diabetes Mellitus
      2. Exercise in Diabetes Mellitus
      3. Tobacco Cessation
      4. Contraception or Preconception Counseling
        1. See Diabetes Mellitus Preconception Counseling
    9. Manage Comorbidities
      1. Hypertension in Diabetes Mellitus
      2. Hyperlipidemia in Diabetes Mellitus
      3. Diabetic Retinopathy
      4. Diabetic Nephropathy
      5. Diabetic Neuropathy
  4. Yearly Exam
    1. Health Maintenance Exam
    2. Fasting lipid profile within 6 months of diagnosis (and then every 5 years if otherwise low risk)
      1. Triglycerides commonly elevated
    3. Neurologic Exam
    4. Dental exam
    5. Skin exam
      1. Evaluate injection sites (or pump insertion sites) for lipodistrophy
    6. Foot exam
      1. See Diabetic Neuropathy Testing (5.07-Gauge Monofilament)
      2. See Diabetic Foot Care
      3. Inspect feet for lesions
      4. Obtain dorsalis pedis and posterior tibial pulses
      5. Perform monofilament testing
    7. Optometry or Ophthalmology Exam
      1. See Diabetic Retinopathy
      2. Age over 12 years or Diabetes Mellitus for 5 years
    8. Urine Microalbumin yearly
      1. See Diabetic Nephropathy
      2. Age over 12 years or Diabetes Mellitus for 5 years
  5. Vaccination
    1. Pneumovax-23
    2. Influenza Vaccine yearly
    3. Hepatitis B Vaccine (if age <60 years old)

X. Management: New Strategies

  1. Monitoring
    1. Continuous Glucose Monitoring
      1. Reduces average Hemoglobin A1C 7.6% to 7.1% over 6 months
      2. Tamborlane (2008) N Engl J Med 359(14): 1464-76 [PubMed]
    2. Transcutaneous Serum Glucose monitoring (watch)
  2. Treatment options
    1. Islet Cell Transplants (high efficacy in trials)
    2. Insulin Pump
    3. Other medications
      1. Pramlintide (Symlin) has been FDA approved in Type I Diabetes
        1. Lee (2010) Ann Fam Med 8(6): 542-9 [PubMed]
      2. Metformin is not effective in Type I Diabetes
        1. Petrie (2017) Lancet Diabetes Endocrinol 5(8): 597-609 [PubMed]

XI. Resources

  1. T1D Registry
    1. https://t1dexchange.org/pages/resources/clinic-registry/
  2. American Diabetes Association Type I (patients)
    1. http://www.diabetes.org/diabetes-basics/type-1/

XII. References

  1. Smith (2018) Am Fam Physician 98(3): 154-62 [PubMed]

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