What are the different types of diabetes and their respective treatments?

Diabetes Classification and Treatment

Diabetes is classified into four main categories: Type 1 diabetes (autoimmune β-cell destruction leading to absolute insulin deficiency), Type 2 diabetes (progressive non-autoimmune loss of β-cell function with insulin resistance), specific types due to other causes (monogenic syndromes, pancreatic disease, drug-induced), and gestational diabetes mellitus. 1

Type 1 Diabetes

Type 1 diabetes represents 5-10% of all diabetes cases and results from autoimmune destruction of pancreatic β-cells, requiring insulin therapy for survival. 2

Clinical Presentation

• Children typically present with polyuria/polydipsia, and approximately 50% present with diabetic ketoacidosis (DKA) at diagnosis 2, 3
• Adults may have more variable presentation without classic symptoms and may progress more slowly toward insulin requirement 3
• Autoantibodies against islets (GAD, IA-2, ZnT8, anti-insulin) are present in 85-90% of individuals at diagnosis 2

Staging System

Type 1 diabetes progresses through three distinct stages 1:

• Stage 1: Multiple islet autoantibodies + normoglycemia + presymptomatic
• Stage 2: Islet autoantibodies + dysglycemia (FPG 100-125 mg/dL, 2-h PG 140-199 mg/dL, or A1C 5.7-6.4%) + presymptomatic
• Stage 3: Overt hyperglycemia + symptomatic diabetes

Treatment

Insulin therapy is the cornerstone of Type 1 diabetes management and must be initiated immediately upon diagnosis. 4

• Basal-bolus insulin regimens combining long-acting basal insulin (e.g., insulin detemir, insulin glargine) with rapid-acting bolus insulin (e.g., insulin aspart) before meals achieve optimal glycemic control 4
• Typical dosing starts at 0.4-0.5 U/kg/day for basal insulin and 0.4-0.5 U/kg/day for bolus insulin 4

Type 2 Diabetes

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. 2

Epidemiology and Risk Factors

• Prevalence is highest in 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 ages 18-44,17% in ages 45-64, and 25% in those over 65 2

Clinical Features

• Higher BMI (typically >25 kg/m²), older age at onset, gradual onset without acute symptoms 3
• Presence of metabolic syndrome features including hypertension, dyslipidemia, and central obesity 3
• Insulin resistance with relative (not absolute) insulin deficiency 3

Treatment

Metformin is first-line pharmacotherapy for Type 2 diabetes unless contraindicated, combined with lifestyle modification including diet and exercise. 5

• Metformin lowers blood sugar by improving insulin sensitivity and reducing hepatic glucose production 5
• If glycemic targets are not achieved with metformin alone, add additional agents or insulin based on individual metabolic characteristics 4, 5

Latent Autoimmune Diabetes in Adults (LADA)

LADA is a form of autoimmune diabetes that presents phenotypically like Type 2 diabetes but progresses to insulin dependence over months to years, accounting for 2-12% of all diabetes cases. 2, 6, 7

Distinguishing Features from Type 2 Diabetes

• Adult onset typically after age 30-35 years with initial non-insulin-requiring presentation 3, 7
• Lower BMI, fewer metabolic risk factors, and better lipid profiles compared to Type 2 diabetes 3
• Presence of islet autoantibodies (particularly GAD antibodies) distinguishes LADA from Type 2 diabetes 3, 8
• C-peptide levels in the 200-600 pmol/L range or low-normal range (versus >600 pmol/L in Type 2 diabetes) 3
• Slower progression to insulin dependence (typically over a few years) compared to Type 1 diabetes (weeks to months) 3

Diagnostic Approach

When suspecting autoimmune diabetes in adults, test for islet autoantibodies starting with GAD, followed by IA-2 and/or ZnT8 if negative. 2

• Measure C-peptide to assess β-cell function: <200 pmol/L suggests Type 1 diabetes, 200-600 pmol/L suggests LADA, >600 pmol/L suggests Type 2 diabetes 3
• Clinical features suggestive of LADA include younger age, unintentional weight loss, lean body habitus, or rapid progression to insulin requirement despite initial response to oral agents 3

Treatment Considerations

LADA patients initially respond to oral antidiabetic agents but eventually require insulin therapy more rapidly than Type 2 diabetes patients. 7

• Sulfonylureas may accelerate β-cell destruction due to increased metabolic stress on already compromised β-cells 7
• Earlier initiation of insulin therapy may preserve residual β-cell function 9
• Metformin and other insulin-sensitizing agents may be beneficial given the role of insulin resistance in LADA pathogenesis 6, 9

Specific Types of Diabetes Due to Other Causes

These represent approximately 3-5% of all diagnosed diabetes cases and include monogenic diabetes syndromes, exocrine pancreatic diseases, and drug-induced diabetes. 2

Monogenic Diabetes Syndromes

• Maturity-Onset Diabetes of the Young (MODY): Consider in patients with mild 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
• Neonatal diabetes: All children diagnosed with diabetes in the first 6 months of life should have genetic testing 2

Other Causes

• Exocrine pancreatic diseases including cystic fibrosis and pancreatitis 1, 2
• Drug or chemical-induced diabetes from glucocorticoids, HIV/AIDS treatment, or post-organ transplantation 1, 2

Gestational Diabetes Mellitus

Gestational diabetes is diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. 1

• Screen all pregnant women at 24-28 weeks of gestation using either a one-step strategy with 75-g oral glucose tolerance test 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

Misdiagnosis occurs in 40% of adults with new Type 1 diabetes, with adults with Type 1 diabetes commonly misdiagnosed as having Type 2 diabetes and individuals with MODY misdiagnosed as having Type 1 diabetes. 1

AABBCC Approach for Distinguishing Diabetes Type

Use this clinical tool when diabetes type is unclear 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 diabetes
• Background: Family history of Type 1 diabetes
• Control: Level of glucose control on non-insulin therapies
• Comorbidities: Treatment with immune checkpoint inhibitors for cancer can cause acute autoimmune Type 1 diabetes

Key Diagnostic Algorithm

• Multiple autoantibodies + acute presentation + age <35 years + low C-peptide (<200 pmol/L) = Type 1 Diabetes 3
• Single or multiple autoantibodies + gradual onset + age >30-35 years + intermediate C-peptide (200-600 pmol/L) + initial response to oral agents = LADA 3
• Age >35 years + BMI >25 kg/m² + metabolic syndrome features + elevated C-peptide (>600 pmol/L) = Type 2 Diabetes 3