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Historical perspective on the diagnosis of diabetes mellitus

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Historical perspective on the diagnosis of diabetes mellitus Historical perspective on the diagnosis of diabetes mellitus Presentation Transcript

  • A historical perspective on thediagnosis of diabetes mellitusAaron Neinstein, MD
  • • 1674: PhysicianThomas Willis ofOxford notes sweetflavor of urine inpatients with diabetes• Initial diagnosiscentered aroundpresence of sugar inthe urine
  • Early 1900s: Glucose tolerance tests• 1917: Oral glucose tolerance test introduced byJacobsenJacobsen, Aa. Th.B. (1917). The Blood Sugar in NormalPersons and Diabetic Patients (in Danish).Gyldenal, Copenhagen.• 1923: Failed attempt made to establish IV glucosetolerance test as standard by JorgensenJorgensen, S.(1930). The Intravenous Glucose ToleranceTest (in Danish). Levin and Munksgaard, Copenhagen. AndPim, T (1923). Acts med scand., 58, 161.
  • 2-hour OGTT value was generallydiagnostic test of choice before 1979• Studies in Pima Indian population• Demonstrated a bimodal distribution ofglucose levels following OGTT• The problem with this: Most populations havea unimodal distribution of glucose levels1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis ofdiabetes. Diabetes Care 2009.Bimodal distribution
  • The diagnosis of diabetes mellitusbefore 1979
  • 1979: National Diabetes Data Group• Pre-1979: At least six different criteria used• 1979: First-ever generally accepted classificationsystem in the US published by NDDG• Numerous etiologically and clinically distinct disorderssharing hyperglycemia in common– Insulin-dependent diabetes mellitus– Non-insulin dependent diabetes mellitus– Gestational diabetes mellitus– Malnutrition-related diabetes mellitus– “Other” diabetes mellitus• 1980: NDDG recommendations endorsed by WHO1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on thediagnosis and classification of diabetes mellitus. Diabetes Care 2003;26 Suppl 1:S5–20.
  • 1979: National Diabetes Data Group• Diabetes:– FPG ≥140 mg/dl or– OGTT 2-hr glucose ≥200 mg/dl or– Classic symptoms present• Impaired glucose tolerance:– FPG ≤ 140 mg/dl and– 2-hour OGTT glucose 140-200 mg/dl1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care2003;26Suppl 1:S5–20.2. Nathan DM, on behalf of the International Expert Committee. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes: Response toKilpatrick, Bloomgarden, and Zimmet. Diabetes Care 2009 Nov.;32(12):e160–e160.
  • NDDG’s Methods For CreatingCriteria• NDDG acknowledged that: “there is no cleardivision between diabetics and non-diabetics inthe FPG concentration or their response to anoral glucose load,” and consequently, “anarbitrary decision has been made as to what leveljustifies the diagnosis of diabetes.”• Criteria chosen based on glucose concentrationsthat allegedly predicted development ofretinopathy• Based on 3 prospective trials with total of 1,213patients, 77 of whom developed retinopathy1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetesmellitus. Diabetes Care 2003;26 Suppl 1:S5–20.2. Nathan DM, on behalf of the International Expert Committee. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes:
  • 1997: ADA expert committee convened• Goal 1: To make FPG concentration and 2-hour OGTT glucoseequivalent (and negate 2HPG as gold-standard test)• Goal 2: To focus on making relationship between glucose levelsand presence of long-term complications the basis for diagnosis• Only 25-50% of patients with 2-hour OGTT ≥200 mg/dl had FPG≥140 mg/dl so the FPG criteria was lowered to ≥126 mg/dl• Terms IDDM and NIDDM eliminated (now Type 1 and Type 2)• Impaired fasting glucose created as category• Assigning a name to someone’s type of diabetes not asimportant as understanding and treating their particularpathogenesis1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care2003;26Suppl 1:S5–20.2. Nathan DM, on behalf of the International Expert Committee. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes: Response toKilpatrick, Bloomgarden, and Zimmet. Diabetes Care 2009 Nov.;32(12):e160–e160.
  • Prevalence of retinopathy by deciles ofdistribution of FPG, 2HPG, and A1c inPima Indians1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. DiabetesCare 2009FPG 140
  • Prevalence of retinopathy by deciles ofdistribution of FPG, 2HPG, and A1c in40-74 year-old participants in NHANESIII1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. DiabetesCare 2009;FPG 140
  • 1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on thediagnosis and classification of diabetes mellitus. Diabetes Care 2003;26 Suppl 1:S5–20.
  • 1997 Report + 2003 revision: Criteriafor diagnosis of diabetes mellitus1) Symptoms of diabetes plus casual plasma glucoseconcentration ≥200 mg/dl (11.1 mmol/l). Casual is defined as anytime of day without regard to last meal. Classic symptoms ofdiabetes include polyuria, polydipsia, and unexplained weightloss.or2) FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloricintake for at least 8 hours.or3) 2-hr PG ≥200 mg/dl (11.1) mmol/l during an OGTT. The testshould be performed as described by WHO, using a glucose loadcontaining the equivalent of 75 gm anhydrous glucose dissolved inwater.1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on thediagnosis and classification of diabetes mellitus. Diabetes Care 2003;26 Suppl 1:S5–20.
  • 1997: Fasting plasma glucose• FPG now preferred test over 2HPG– More convenient– Less costly and time consuming– Better repeat-test reproducibility• Problem: Only 70.4% of people with FPG ≥126 mg/dl on first test in NHANES III had FPG≥ 126 mg/dl when test repeated 2 weeks later
  • Impaired fasting glucose• Established as category in 1997• 1997: cut-off of ≥ 110 mg/dl• 2003: cut-off lowered to ≥ 100 mg/dl
  • 2009: Expert committee recommendsHbA1c as new diagnostic criteria• Correlation had already been shown between A1c and long-term complications• A1c had been considered in 1997 but not used because of lackof standardization of assay• Advantages of A1c over FPG or OGTT– Better index of overall glycemic exposure– Less biologic variability– Stable samples– No need for fasting or timed samples– Relatively unaffected by acute stressors– Used to guide management and adjust therapy1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis ofdiabetes. Diabetes Care 2009;
  • Prevalence of retinopathy by 0.5% A1cintervals1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis ofdiabetes. Diabetes Care 2009;
  • 2009: Diagnose diabetes at A1c > 6.5%• Confirm diagnosis with repeat A1c testing• Risk for diabetes is on a continuum• Pre-diabetes, impaired fasting glucose, andimpaired glucose tolerance will start to bephased out of use• People with A1c between 6.0-6.5% should“receive demonstrably effective preventiveinterventions.”1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis ofdiabetes. Diabetes Care 2009;
  • Prevalence of retinopathy by 0.5% A1cintervals1. Nathan D. International Expert Committee report on the role of the A1C assay in the diagnosis ofdiabetes. Diabetes Care 2009;
  • The evolution of testing for diabetes• Early criteria were attempt to categorizepeople who were at risk of overt clinicalsymptoms or future progression to symptoms• Later criteria are attempt to classify peoplewho are at risk of long-term complications andwould benefit from treatment
  • The evolution of testing for diabetesUrinetestingOralGlucoseToleranceTestFastingglucoseHbA1c