Type 1

Type 1

Usually <30 yr of age

Usually >40 yr of age

More common in Caucasians

Less common in Asians, Hispanics, Aboriginals, and Blacks

Accounts for 5-10% of all DM

Increasing incidence in pediatric population 2o to obesity

More common in Blacks, Hispanics, Aboriginals, and Asians

Accounts for >90% of all DM

Autoimmune

Complex and multifactorial

Monozygotic twin concordance is 30-40%

Associated with HLA class II DR3 and DR4, with either allele present in up to 95% of type 1 DM

Certain DQ alleles also confer a risk

Greater heritability than type 1 DM

Monozygotic twin concordance is 70-90%

Polygenic

Non-HLA associated

Synergistic effects of genetic, immune, and environmental factors that cause β cell destruction resulting in impaired insulin secretion

Autoimmune process is believed to be triggered by environmental factors (e.g. viruses, bovine milk protein, urea compounds)

Pancreatic cells are infiltrated with lymphocytes resulting in islet cell destruction

80% of β cell mass is destroyed before features of DM present

Impaired insulin secretion, peripheral insulin resistance (likely due to receptor and postreceptor abnormality), and excess hepatic glucose production

After initial presentation, honeymoon period often occurs where glycemic control can be achieved with little or no insulin treatment as residual cells are still able to produce insulin

Once these cells are destroyed, there is complete insulin deficiency

Early on, glucose tolerance remains normal despite insulin resistance as β cells compensate with increased insulin production

As insulin resistance and compensatory hyperinsulinemia continue, the β cells are unable to maintain the hyperinsulinemic state which results in glucose intolerance and DM

Islet cell Ab present in up to 60-85%

Most common islet cell Ab is against glutamic acid decarboxylase (GAD)

Up to 60% have Ab against insulin

<10%

Personal history of other autoimmune diseases including Graves’, myasthenia gravis, autoimmune thyroid disease, celiac disease, and pernicious anemia

Family history of autoimmune diseases

• Age >40 yr

• Schizophrenia

• Abdominal obesity/overweight

• Fatty liver

• First-degree relative with DM

• Hyperuricemia

• Race/ethnicity (Black, Aboriginal, Hispanic, Asian-American, Pacific Islander)

• Hx of IGT or IFG

• HTN

• Dyslipidemia

• Medications e.g. 2nd generation antipsychotics

• PCOS

• Hx of gestational DM or macrosomic baby (>9 lb or 4 kg)

Normal to thin

Typically overweight with increased central obesity

Insulin

Lifestyle modification

Oral antihyperglycemic agents

Incretin therapy

Insulin therapy

Diabetic ketoacidosis (DKA) in severe cases

Hyperosmolar hyperglycemic state (HHS)

DKA in severe cases

Subclinical prodrome can be detected in first and second-degree relatives of those with type 1 DM by the presence of pancreatic islet autoantibodies

Screen individuals with risk factors