What are the different types of diabetes and their typical treatment approaches?

Types of Diabetes and Treatment Approaches

Diabetes is classified into four main categories: Type 1 diabetes (autoimmune β-cell destruction requiring insulin), Type 2 diabetes (progressive insulin secretory defect with insulin resistance), specific types due to other causes (monogenic, drug-induced, or pancreatic disease), and gestational diabetes mellitus (diagnosed during pregnancy). 1

Type 1 Diabetes

Pathophysiology and Presentation

• Type 1 diabetes accounts for 5-10% of all diabetes cases and results from autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency. 1, 2
• Autoantibodies (GAD, IA-2, ZnT8, anti-insulin) are present in 85-90% of individuals at diagnosis and can be detected months to years before symptom onset. 2, 3
• Children typically present with polyuria, polydipsia, and approximately one-third to one-half present with diabetic ketoacidosis (DKA) at diagnosis. 1, 2
• Adults may have more variable presentation without classic symptoms and may experience temporary remission from insulin need (latent autoimmune diabetes in adults). 1

Treatment Approach

• All patients with Type 1 diabetes require immediate insulin therapy using either multiple daily injections (basal-bolus regimen) or continuous subcutaneous insulin infusion via pump. 4
• Insulin analogs are strongly preferred over human insulins to reduce hypoglycemia risk. 1, 4
• Initial dosing starts at 0.5 units/kg/day total daily insulin (50% basal, 50% prandial) in metabolically stable patients, with higher doses (up to 1.0 units/kg/day) required during puberty, pregnancy, or acute illness. 4
• Rapid-acting insulin analogs (aspart, lispro, glulisine) should be used for prandial coverage rather than regular human insulin. 4
• Long-acting basal analogs (glargine, degludec) are preferred over NPH insulin due to reduced hypoglycemia risk and more stable pharmacokinetics. 1, 4
• Automated insulin delivery systems (hybrid closed-loop) should be considered for all adults to improve glycemic control and reduce hypoglycemia. 1, 4
• Continuous glucose monitoring is standard of care for most patients with Type 1 diabetes. 1, 4

Type 2 Diabetes

Pathophysiology and Presentation

• Type 2 diabetes represents 90-95% of all diabetes cases and results from progressive non-autoimmune loss of adequate β-cell insulin secretion, frequently on a background of insulin resistance. 1, 2
• Prevalence is higher in certain ethnic groups: Native Americans/Alaska Natives (15.1%), non-Hispanic African Americans (12.7%), and Hispanics (12.1%) compared to Asians (8.0%) and non-Hispanic whites (7.4%). 2
• Prevalence increases with age: 4% in individuals 18-44 years, 17% in those 45-64 years, and 25% in those over 65 years. 2
• Patients may occasionally present with DKA, particularly in ethnic and racial minorities. 1

Treatment Approach

• Metformin is the preferred initial pharmacological agent combined with lifestyle modifications (weight loss education, exercise counseling), unless contraindicated or not tolerated. 4
• Lifestyle changes should be started at diagnosis, with addition of metformin monotherapy at or soon after diagnosis. 4
• Insulin therapy should be considered immediately in patients with markedly symptomatic presentation and/or elevated blood glucose levels or A1C, and when A1C ≥7.5% and glycemic goals are not met. 4
• Target A1C <7% (53 mmol/mol) for most nonpregnant adults, accounting for hypoglycemia risk and individual patient factors. 4

Specific Types of Diabetes Due to Other Causes

Categories and Recognition

• These represent approximately 3-5% of all diagnosed diabetes cases and include monogenic diabetes syndromes, exocrine pancreatic diseases, and drug/chemical-induced diabetes. 2
• Monogenic diabetes syndromes include neonatal diabetes and maturity-onset diabetes of the young (MODY). 1, 2
• Exocrine pancreatic diseases include cystic fibrosis and pancreatitis. 1, 2
• Drug or chemical-induced diabetes occurs with glucocorticoid use, HIV/AIDS treatment, or after organ transplantation. 1, 2

Diagnostic Considerations

• Consider MODY in patients with mild and stable fasting hyperglycemia, stable A1C between 5.6-7.6%, multiple family members with non-typical Type 1 or Type 2 diabetes, and absence of obesity. 2
• All children diagnosed with diabetes in the first 6 months of life should have genetic testing. 2

Gestational Diabetes Mellitus

Definition and Screening

• Gestational diabetes mellitus is diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. 1, 2
• Screen all pregnant women at 24-28 weeks of gestation using either a one-step strategy with 75-g oral glucose tolerance test (OGTT) or a two-step approach with 50-g non-fasting screen followed by 100-g OGTT for those who test positive. 2

Critical Diagnostic Pitfalls

Misclassification Issues

• Classification of diabetes type is not always straightforward at presentation, and misdiagnosis is common, occurring in 40% of adults with new Type 1 diabetes (often misdiagnosed as Type 2). 1
• The traditional paradigm that Type 2 diabetes occurs only in adults and Type 1 only in children is no longer accurate, as both diseases occur in both age groups. 1
• The diagnosis becomes more obvious over time in people with β-cell deficiency as the degree of deficiency becomes clear. 1

AABBCC Approach for Distinguishing Diabetes Type

Use this clinical tool when classification is uncertain: 1

• Age: For individuals <35 years old, consider Type 1 diabetes
• Autoimmunity: Personal or family history of autoimmune disease or polyglandular autoimmune syndromes
• Body habitus: BMI <25 kg/m² suggests Type 1
• Background: Family history of Type 1 diabetes
• Control (goal): Inability to achieve glycemic goals on non-insulin therapies
• Comorbidities: Treatment with immune checkpoint inhibitors for cancer can cause acute autoimmune Type 1 diabetes

Laboratory Testing for Classification

• When suspecting Type 1 diabetes in adults, test for islet autoantibodies (GAD as primary, followed by IA-2 and/or ZnT8 if negative). 2
• Measuring C-peptide serves as a stable surrogate marker: C-peptide >200 pmol/L suggests residual β-cell function, while <200 pmol/L suggests Type 1 diabetes. 2
• Standardized islet autoantibody tests are recommended for classification in adults with phenotypic risk factors overlapping with Type 1 diabetes (younger age at diagnosis, unintentional weight loss, ketoacidosis, or short time to insulin treatment). 1