Diabetes Mellitus: Type 1, Type 2, and Insulin Management

Diabetes mellitus is a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The condition affects over 422 million people worldwide and represents a major cause of morbidity and mortality.

Classification

Type 1 Diabetes Mellitus (T1DM) results from autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency. It typically manifests in childhood or young adulthood but can occur at any age. [KEY_CONCEPT] T1DM accounts for 5-10% of all diabetes cases and requires lifelong insulin therapy from diagnosis.

Type 2 Diabetes Mellitus (T2DM) is characterized by insulin resistance and progressive β-cell dysfunction. It represents 90-95% of diabetes cases and typically develops in adults over 45 years, though increasing rates are seen in younger populations due to rising obesity.

[HIGH_YIELD] The diagnostic criteria for diabetes mellitus include: HbA1c ≥6.5% (48 mmol/mol), fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT, or random plasma glucose ≥200 mg/dL with symptoms.

Type 1 Diabetes Pathophysiology

[KEY_CONCEPT] T1DM results from T-cell mediated autoimmune destruction of pancreatic β-cells in the islets of Langerhans. Genetic susceptibility (HLA-DR and HLA-DQ alleles) combined with environmental triggers leads to autoantibody production against glutamic acid decarboxylase (GAD), insulinoma-associated antigen-2 (IA-2), zinc transporter 8 (ZnT8), and insulin.

Type 2 Diabetes Pathophysiology

T2DM involves a complex interplay of:

• Insulin resistance in muscle, liver, and adipose tissue
• Progressive β-cell dysfunction and eventual failure
• Increased hepatic glucose production
• Incretin deficiency (GLP-1 and GIP)
• Amylin deficiency

Clinical Presentation

Type 1 Diabetes

[CLINICAL_PEARL] T1DM often presents acutely with the classic triad of polyuria, polydipsia, and polyphagia, accompanied by unintentional weight loss despite increased appetite.

Acute presentation may include:

• Diabetic ketoacidosis (DKA) in 25-30% of cases
• Dehydration and electrolyte imbalances
• Fatigue and weakness
• Blurred vision
• Nausea and vomiting

Type 2 Diabetes

T2DM typically has an insidious onset with:

• Asymptomatic hyperglycemia detected on routine screening
• Mild polyuria and polydipsia
• Fatigue and decreased energy
• Recurrent infections (especially genitourinary)
• Slow wound healing
• Acanthosis nigricans (insulin resistance marker)

[HIGH_YIELD] Unlike T1DM, T2DM rarely presents with ketoacidosis at diagnosis, though it can occur during severe stress or illness (hyperosmolar hyperglycemic state is more common).

Diagnostic Criteria for Diabetes Mellitus

[KEY_CONCEPT] Diagnosis requires ONE of the following criteria on two separate occasions (unless symptoms are present):

Glycemic Criteria Checklist:

• HbA1c ≥6.5% (48 mmol/mol)
• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
  • Fasting = no caloric intake for ≥8 hours
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT
  • Using 75g glucose load
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with symptoms
  • Classic symptoms: polyuria, polydipsia, unexplained weight loss

Distinguishing Type 1 from Type 2

Laboratory Assessment:

Initial Workup Algorithm:

1. Confirm diabetes diagnosis ↓
2. Assess clinical presentation
   • Age, BMI, family history
   • Presence of ketosis ↓
3. Laboratory tests:
   • C-peptide (fasting or stimulated)
   • Autoantibodies (GAD, IA-2, ZnT8)
   • Consider MODY gene testing if family history ↓
4. Classification:
   • Low C-peptide + positive antibodies → T1DM
   • Normal/high C-peptide + negative antibodies → T2DM
   • Intermediate → Consider LADA or atypical diabetes

[CLINICAL_PEARL] Latent Autoimmune Diabetes in Adults (LADA) presents with features of both T1DM (positive autoantibodies) and T2DM (older age, slower progression). It accounts for 5-10% of adult-onset diabetes.

Prediabetes Screening

Prediabetes criteria:

• HbA1c: 5.7-6.4% (39-47 mmol/mol)
• Fasting plasma glucose: 100-125 mg/dL (5.6-6.9 mmol/L)
• 2-hour OGTT: 140-199 mg/dL (7.8-11.0 mmol/L)

[HIGH_YIELD] Screen adults ≥35 years with BMI ≥25 kg/m² or additional risk factors. Screen earlier and more frequently in high-risk populations (family history, ethnicity, PCOS, previous GDM).

Type 1 Diabetes Management

[KEY_CONCEPT] T1DM requires intensive insulin therapy from diagnosis, combined with comprehensive diabetes education and self-management training.

Insulin Regimens:

Multiple Daily Injections (MDI):

• Basal insulin: Long-acting (glargine, detemir, degludec) once or twice daily
• Prandial insulin: Rapid-acting (lispro, aspart, glulisine) with meals
• Correction doses: Additional rapid-acting for hyperglycemia

Continuous Subcutaneous Insulin Infusion (CSII/Pump):

• Programmable basal rates
• Bolus doses for meals and corrections
• Better glycemic control and flexibility

Glycemic Targets:

• HbA1c: <7% for most adults (<6.5% if achievable without hypoglycemia)
• Preprandial glucose: 80-130 mg/dL (4.4-7.2 mmol/L)
• Postprandial glucose: <180 mg/dL (<10.0 mmol/L)

Type 2 Diabetes Management

Treatment Algorithm:

T2DM Management Approach:

1. Lifestyle modifications (diet, exercise, weight loss) ↓
2. Metformin (first-line unless contraindicated) ↓
3. Add second agent based on:
   • Cardiovascular disease → SGLT2i or GLP-1 RA
   • Heart failure → SGLT2i
   • Hypoglycemia concern → DPP-4i, GLP-1 RA, SGLT2i
   • Weight loss desired → GLP-1 RA, SGLT2i
   • Cost consideration → Sulfonylureas, TZDs ↓
4. Triple therapy or insulin if HbA1c remains elevated ↓
5. Insulin intensification (basal → basal-bolus)

Medication Classes:

[HIGH_YIELD] For patients with established cardiovascular disease, heart failure, or chronic kidney disease, prioritize SGLT2 inhibitors or GLP-1 receptor agonists with proven cardiovascular benefits.

Insulin Pharmacokinetics

[KEY_CONCEPT] Understanding insulin action profiles is essential for optimal diabetes management:

Insulin Dosing Calculations

Initial Dosing:

• Total daily dose: 0.4-0.5 units/kg/day for T1DM; 0.5-1.0 units/kg/day for T2DM
• Basal:Bolus ratio: 50:50 for T1DM; may vary in T2DM
• Carbohydrate ratio: 1 unit per 10-15g carbs (individualize)
• Correction factor: 1700 ÷ total daily dose = glucose drop per unit

Insulin Adjustment Protocol:

Glycemic Pattern Analysis:

1. Review glucose logs (2-week minimum) ↓
2. Identify patterns:
   • Fasting highs → ↑ basal or bedtime insulin
   • Post-meal highs → ↑ prandial insulin or adjust I:C ratio
   • Bedtime highs → ↑ dinner insulin
   • Dawn phenomenon → Switch basal timing or add AM dose ↓
3. Adjust one insulin at a time (10-20% changes) ↓
4. Wait 3-5 days before next adjustment ↓
5. Address hypoglycemia first, then hyperglycemia

Hypoglycemia Management

[CLINICAL_PEARL] The "Rule of 15" for conscious patients:

1. Consume 15g fast-acting carbs (glucose tablets, juice)
2. Wait 15 minutes
3. Recheck blood glucose
4. Repeat if <70 mg/dL
5. Follow with complex carbs if next meal >1 hour away

Severe hypoglycemia:

• Glucagon 1mg IM/SC (or nasal glucagon)
• IV dextrose if IV access available
• Never give oral carbs to unconscious patients

Special Situations

Sick Day Management:

• Never stop insulin (even if not eating)
• Check glucose and ketones every 2-4 hours
• Maintain hydration
• Contact provider if unable to maintain glucose <250 mg/dL

[HIGH_YIELD] During illness, insulin needs typically increase due to stress hormones (cortisol, epinephrine), even with decreased oral intake. Ketone monitoring becomes crucial in T1DM.

Acute Complications

Diabetic Ketoacidosis (DKA)

Diagnostic criteria:

• Glucose >250 mg/dL (13.9 mmol/L)
• pH <7.3 or bicarbonate <18 mEq/L
• Positive serum or urine ketones

[CLINICAL_PEARL] DKA can occur at any glucose level in T1DM, especially with SGLT2 inhibitor use ("euglycemic DKA"). Always check ketones during illness or stress.

Hyperosmolar Hyperglycemic State (HHS)

• More common in T2DM
• Glucose >600 mg/dL (33.3 mmol/L)
• Serum osmolality >320 mOsm/kg
• Minimal ketosis

Chronic Complications

Microvascular Complications:

Diabetic Nephropathy:

• Leading cause of end-stage renal disease
• Screen annually with urine albumin and eGFR
• ACE inhibitors/ARBs for albuminuria
• SGLT2 inhibitors for renal protection

Diabetic Retinopathy:

• Leading cause of blindness in working-age adults
• Annual dilated eye exams starting 5 years after T1DM diagnosis or at T2DM diagnosis
• [HIGH_YIELD] Rapid improvement in glycemic control can temporarily worsen retinopathy

Diabetic Neuropathy:

• Most common: distal symmetric sensorimotor neuropathy
• Screen annually with monofilament testing
• Pain management: gabapentin, pregabalin, duloxetine

Macrovascular Complications:

Cardiovascular Disease:

• 2-4 fold increased risk of MI, stroke
• Aggressive management of BP, lipids, antiplatelet therapy
• Statin therapy for most patients >40 years

Monitoring & Follow-up

Glycemic Monitoring:

• HbA1c: Every 3-6 months (quarterly if not at goal)
• Self-monitoring blood glucose: Multiple times daily for insulin users
• Continuous glucose monitoring: Increasingly recommended for T1DM and insulin-treated T2DM

Comprehensive Care Checklist:

• Annual dilated eye exam
• Annual foot exam with monofilament
• Annual urine microalbumin and eGFR
• Lipid profile (annually or more frequently)
• Blood pressure monitoring
• Dental care evaluation
• Immunizations (influenza, pneumococcal, COVID-19)
• Diabetes self-management education

[KEY_CONCEPT] The legacy effect demonstrates that early intensive glycemic control provides lasting benefits for microvascular complications, even if control later deteriorates. This emphasizes the importance of achieving target HbA1c early in the disease course.