What is the evaluation and treatment approach for type 1 diabetes mellitus?

Evaluation of Type 1 Diabetes Mellitus

The evaluation of type 1 diabetes mellitus centers on confirming the diagnosis through detection of islet-targeting autoantibodies (insulin, GAD65, IA-2, and ZnT8 antibodies) and assessing metabolic status, followed by immediate initiation of intensive insulin therapy with multiple daily injections or continuous subcutaneous insulin infusion to prevent microvascular and macrovascular complications. 1

Diagnostic Evaluation

Autoantibody Testing

• Measure all four islet autoantibodies (insulin autoantibodies, GAD65, IA-2, and ZnT8) as these are detectable months to years before symptom onset and serve as biomarkers of T1DM-associated autoimmunity 1
• The specific autoantibody that appears first depends on environmental triggers and genetic factors 1
• Autoantibody testing allows identification of individuals at risk and enables staging of disease progression 1

Metabolic Assessment

• Obtain fasting plasma glucose and HbA1c to establish baseline glycemic control and confirm hyperglycemia 2
• Perform oral glucose tolerance testing when diagnosis is uncertain 2
• Assess for diabetic ketoacidosis at presentation, particularly in children and adolescents, as this represents a hyperglycemic emergency requiring immediate intervention 3

Disease Staging

Type 1 diabetes is now recognized in three stages 1, 4:

• Stage 1: Normoglycemic with positive autoantibodies
• Stage 2: Asymptomatic with dysglycemia
• Stage 3: Overt hyperglycemia meeting diabetes diagnostic criteria

Initial Treatment Approach

Insulin Therapy Initiation

Most patients with type 1 diabetes should be treated with multiple daily injections (MDI) of both prandial and basal insulin or continuous subcutaneous insulin infusion (CSII). 5

• Starting total daily insulin dose: 0.5 units/kg body weight in metabolically stable patients, with 50% as basal and 50% as prandial insulin 5
• Higher doses (0.4-1.0 units/kg) may be needed for patients presenting with diabetic ketoacidosis or during puberty 5
• Use rapid-acting insulin analogs (lispro, aspart) rather than regular insulin to reduce hypoglycemia risk 5, 6

Insulin Regimen Selection

For intensive management, choose between:

Multiple Daily Injections (MDI):

• Long-acting basal insulin (glargine, detemir, degludec) once or twice daily 5
• Rapid-acting analog before each meal 5
• Adjust prandial doses based on carbohydrate intake, premeal glucose, and anticipated activity 5

Continuous Subcutaneous Insulin Infusion (CSII):

• Provides slightly better HbA1c reduction (0.30 percentage point lower) compared to MDI 5
• Associated with reduced severe hypoglycemia rates in children and adults 5
• Consider automated insulin delivery (AID) systems to improve time in range and reduce hypoglycemia 5

Glycemic Monitoring Strategy

Self-Monitoring Blood Glucose

Patients on intensive insulin regimens should test:

• Before all meals and snacks 5
• At bedtime 5
• When suspecting hypoglycemia and after treating until normoglycemic 5
• Before exercise and critical tasks like driving 5
• Occasionally after meals 5

Most patients require 6-10 or more tests daily, though individual needs vary 5

Continuous Glucose Monitoring

When used properly with intensive insulin regimens, CGM is a useful tool to lower HbA1c in adults aged ≥25 years with type 1 diabetes. 5

• Particularly beneficial for those with hypoglycemia unawareness or frequent hypoglycemic episodes 5
• Frequency of sensor use is the greatest predictor of HbA1c lowering 5
• Requires robust diabetes education, training, and ongoing support 5
• CGM use is associated with improved time in range and reduced hypoglycemia when incorporated into AID systems 5

HbA1c Monitoring

• Test at least twice yearly in patients meeting treatment goals with stable glycemic control 5
• Test quarterly in those whose therapy has changed or who are not meeting goals 5
• Point-of-care testing allows more timely treatment adjustments 5

Glycemic Targets

Target HbA1c <7% for most adults to reduce microvascular and macrovascular complications, as demonstrated by the DCCT and EDIC studies showing 57% reduction in cardiovascular events with intensive therapy 5

More stringent goals (<6.5%) may be appropriate for selected individuals with:

• Short diabetes duration 5
• Long life expectancy 5
• No significant cardiovascular disease 5
• Ability to achieve without significant hypoglycemia 5

Less stringent goals (<8%) are appropriate for patients with:

• History of severe hypoglycemia 5
• Limited life expectancy 5
• Advanced complications 5
• Extensive comorbidities 5
• Long-standing diabetes where goal is difficult to achieve 5

Patient Education Requirements

Provide comprehensive education on:

• Matching prandial insulin to carbohydrate intake using insulin-to-carbohydrate ratios 5
• Adjusting doses for premeal glucose levels using insulin sensitivity factors 5
• Modifying insulin for anticipated physical activity 5
• For those mastering carbohydrate counting, incorporate fat and protein estimation 5
• Proper injection technique including site rotation to avoid lipohypertrophy 5
• Recognition and treatment of hypoglycemia 5

Injection Technique Assessment

Evaluate and educate on proper technique to optimize outcomes:

• Use 4-mm pen needles to avoid intramuscular injection, which causes unpredictable absorption and hypoglycemia 5
• Inject into appropriate sites: abdomen, thigh, buttock, upper arm 5
• Rotate injection sites systematically to prevent lipohypertrophy 5
• Examine injection sites at each visit for lipohypertrophy 5

Advanced Therapies for Selected Patients

Pancreas/Islet Transplantation

Reserve for patients with:

• Simultaneous or post-kidney transplantation 5
• Recurrent ketoacidosis despite optimized management 5
• Severe hypoglycemia despite intensive glycemic management 5
• Hypoglycemia unawareness 5

These therapies normalize glucose levels and mitigate microvascular complications but require lifelong immunosuppression 5

Adjunctive Pharmacotherapy

Pramlintide is the only adjunctive agent FDA-approved for type 1 diabetes, showing modest HbA1c reduction (0.3-0.4%) and weight loss (1 kg) 5

GLP-1 receptor agonists (liraglutide) and SGLT2 inhibitors have shown benefits in clinical trials but carry risks (particularly diabetic ketoacidosis with SGLT2 inhibitors) and are not FDA-approved for type 1 diabetes 5

Critical Pitfalls to Avoid

• Do not delay insulin initiation in newly diagnosed patients, as this is essential to prevent diabetic ketoacidosis and long-term complications 3
• Avoid intramuscular insulin delivery by using short needles and proper technique, as IM injection causes unpredictable absorption and frequent unexplained hypoglycemia 5
• Do not inject into areas of lipohypertrophy, which causes erratic absorption and glycemic variability 5
• Ensure adequate SMBG frequency is maintained, as this is integral to intensive insulin management and associated with lower HbA1c 5
• Provide ongoing education and technique assessment, not just at diagnosis, as accuracy depends on proper user technique 5