Diabetes mellitus (DM) is a group of metabolic diseases resulting from defects in insulin secretion, insulin action or both.

Classification of diabetes mellitus

• Type 1
• Type 2
• Other specific types of diabetes mellitus due to other causes (eg, cystic fibrosis, drug-induced)
• Gestational diabetes mellitus

Type 1 diabetes

• Epidemiology
  • Incidence
    • Varies by nationality
    • >150,000 under the age of 18 in the U.S. have DM
  • Age
    • Majority diagnosed at or before adolescence
    • Up to 1/3 diagnosed during adolescence  
  • Sex - males and females equally affected
  • Inheritance
    • Interplay between genetic susceptibility and environmental factors
    • Presence of tyrosine phosphatase (IA-2) antibodies is the best predictor of eventual DM type 1 in siblings of diabetic patients   
• Pathophysiology
  • Insulin produced in B-cells of the islet of Langerhans of the pancreas
  • Insulin regulates how body stores glucose and how the body uses the stored glucose
  • In DM type 1, chronic inflammatory response against the islet cells, along with antibody production that destroys islet cells, leads to absolute insulin deficiency
    • Three types of antibodies are present but not routinely used to diagnose or monitor DM
    • Chronic inflammation and antibodies lead to destruction of B-cells with eventual insulin deficiency
      • May be assistive in testing family members of probands
        • Islet cell antibodies (ICA)
          • May be detected years prior to clinical symptoms
          • Almost exclusively in Type 1 DM
        • Tyrosine phosphatase antibodies (IA-2)
          • Best predictor of eventual Type 1 DM in siblings of diabetic patients
        • Glutamic acid decarboxylase antibodies (GAD65)
          • Found in around 70% of patients with Type 1 DM at diagnosis
          • May be found prior to clinical disease and therefore may predict who develops Type 1 DM
• Clinical Presentation
  • Polydipsia, polyuria, polyphagia
  • Nonspecific symptoms
    • Fatigue
    • Nausea, emesis
    • Weight loss
  • Length of time from clinical presentation to diagnosis is typically a few weeks

Type 2 diabetes

• Epidemiology
  • Prevalence - affects >20 million in U.S.
    • 6.5% of population
  • Age - usually diagnosed after 30 years
  • Sex - affects males and females equally
  • Increase in obesity in teenagers is associated with increased occurrence of DM type 2
• Risk Factors
  • Obesity
  • Impaired glucose tolerance
  • Older age
  • Previous gestational DM
  • Disproportionate risk in minority groups such as African Americans, Native Americans, Latinos and Pacific Islanders
• Inheritance
  • 75% concordance rate between identical twins
  • Several susceptibility genes have been identified
• Pathophysiology
  • Combination of progressive B-cell dysfunction with insulin secretory defect on the background of insulin resistance
  • No known autoimmune destruction of the pancreas
• Clinical Presentation
  • May have polyuria, polydipsia, polyphagia
  • Headache, fatigue, blurred vision, recurring Candida infections
  • More often presents with microvascular, macrovascular and neuropathic complications
    • Tingling, numbness in extremities
    • Lipid abnormalities
    • Renal insufficiency

Gestational Diabetes (GDM)

• Epidemiology
  • Prevalence - 7% of all pregnancies
• Risk Factors
  • History of previous GDM
  • Previous birth of baby >4.5 kg
  • Severe obesity
  • Strong family history of DM type 2
  • Diagnosis of PCOS
• Clinical Presentation
  • Large for gestational age fetus
  • Post term delivery
  • Neonatal hypoglycemia
  • Premature labor
  • Preeclampsia

Diagnosis of DM

• Indications for testing
  • Testing to detect prediabetes and diabetes type 2 in asymptomatic people should be considered in adults whose BMI >25 kg/m^2 and have risk factors (see disease screening section below)
• Laboratory testing
  • Fasting plasma glucose is the preferred test to diagnose diabetes in children and nonpregnant adults
  • C-peptide testing can be used to confirm lack of insulin production
  • C-peptide levels, hemoglobin AIC or insulin levels to diagnose diabetes is not recommended

Disease Screening

• Adults
  • greater than or equal to 45 years, repeat at 3 year intervals
  • Or less than or equasl to45 years and BMI greater than or equal to 25 kg/m^2 and one or more risk factors
    • First degree relative with DM
    • Have polycystic ovarian syndrome or acanthosis nigricans
    • High-risk ethnic group
    • History of gestational DM
    • Hypertension (greater than or equal to 140/90 mmHg)
    • Physically inactive
    • Triglycerides >250 mg/dL or HDL cholesterol <35 mg/dL
• Pregnant women
  • Assess risk for gestational diabetes in all pregnant women at first prenatal visit
  • Plasma glucose testing is an adequate initial screening during the first prenatal visit
    • If initial screen is positive, follow up with an OGTT
    • If initial screen is negative, but patient is high risk, should have OGTT at 24-28 weeks gestation

Refer to Diabetes Mellitus Diagnosis topic at www.arupconsult.com for additional information about the chart of Comparison of Diagnostic Testing Recommendations

• • Repeat screening 6-12 weeks postpartum
• Children (>10 years of age), repeat every 2 years if:
  • BMI >85% and any 2 of the following
    • First or second degree relative with DM
    • Maternal history of DM or gestational DM
    • Member of at-risk minority group
    • Signs and symptoms of insulin resistance - polycystic ovarian syndrome, hypertension, acanthosis nigricans