Diabetes Mellitus, Type 1

Basics

Chronic disease caused by autoimmune destruction of pancreatic β-cells.
Leads to absolute insulin deficiency and hyperglycemia.
Rapid onset; symptoms include polyphagia, polydipsia, polyuria, nocturia, and ketoacidosis.
Typical body habitus: normal or thin at diagnosis.
Affects endocrine, metabolic, cardiovascular, neurologic, renal, ocular systems.

Pregnancy Considerations

Increased maternal and fetal risks: spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia/hyperbilirubinemia.
Preconception counseling crucial for tight glycemic control.
Glycemic targets during pregnancy: fasting <95 mg/dL, 1-hour postprandial <140 mg/dL, 2-hour postprandial <120 mg/dL.
HbA1c target: ideally <6% if no hypoglycemia, otherwise <7%.
Eye exams before pregnancy, each trimester, and 1 year postpartum.
Low-dose aspirin (81 mg/day) by end of 1st trimester for preeclampsia prevention if no contraindications.

Epidemiology

Bimodal age of onset: 4-6 years and 10-14 years (early puberty).
US incidence: 23.6/100,000 in non-Hispanic white youth; lower in other ethnic groups.
Pediatric symptoms may be subtle in infants and toddlers.

Etiology and Pathophysiology

Two categories:
Immune-mediated: autoimmune β-cell destruction; autoantibodies include insulin, GAD65, IA-2, ZnT8.
Idiopathic: no autoimmunity but insulin deficiency.
85-90% have at least one autoantibody.
Genetic factors: HLA class II (DQA1, DQB1, DRB1) major susceptibility locus on chromosome 6p21; >40 loci implicated.

Risk Factors

Viral infections, vitamin D deficiency.
Perinatal factors: maternal age, preeclampsia, neonatal jaundice.
High birth weight, lower gestational age.
Inheritable susceptibility:
50% concordance in monozygotic twins.
Siblings risk 5-10% by age 20.
Offspring of diabetic fathers (~12%) higher risk than mothers (~6%).

General Prevention

No accepted screening programs currently.
Referral of relatives to research risk assessment programs (e.g., TrialNet).

Commonly Associated Conditions

Autoimmune diseases: Addison disease, celiac disease, autoimmune hepatitis, pernicious anemia, myasthenia gravis, vitiligo, Graves, Hashimoto thyroiditis.

Diagnosis

History

New onset polyuria, polydipsia.
Polyuria may present as nocturia, bedwetting, or incontinence.
Polyuria occurs once glucose >180 mg/dL.

Physical Exam

Weight loss, fatigue, lethargy, muscle cramps.
Abdominal pain, nausea with ketosis/DKA.
Blurry vision.

Differential Diagnosis

Type 2 diabetes.
Monogenic diabetes (MODY) when diagnosis before 6 months or nonobese without autoantibodies.
Secondary diabetes: pancreatitis, endocrine tumors, drug-induced.
Poisonings mimicking DKA.

Diagnostic Tests

Diagnostic criteria:
Fasting glucose ≥126 mg/dL on 2 occasions.
Random glucose ≥200 mg/dL with symptoms.
OGTT 2-hour glucose ≥200 mg/dL.
HbA1c ≥6.5%.
Additional tests:
Urinalysis (glucose, ketones, albuminuria).
Pancreatic autoantibodies (islet cell, IAA, GAD, IA2A, ZnT8).
Serum β-hydroxybutyrate, urine ketones.
Fructosamine.
Continuous glucose monitoring.
C-peptide to differentiate from T2DM (low in T1DM).
Screen for thyroid disease at diagnosis and periodically.

Treatment

General Measures

Insulin replacement is essential.
Educate on insulin dosing relative to carbohydrate intake, premeal glucose, and activity.
Blood glucose goals:
Premeal: 90–130 mg/dL.
Bedtime: 90–150 mg/dL.
HbA1c goals:
Pediatric: <7.5% (ideal <7% without hypoglycemia).
Adult: <7% (less strict in elderly).
CGM targets: ≥70% readings between 70-180 mg/dL.

Medication

Most use multiple daily injections (MDI) of basal and prandial insulin or continuous subcutaneous insulin infusion (CSII).
Prefer rapid-acting insulin analogs to reduce hypoglycemia.
Types:
Long-acting: glargine, detemir, degludec.
Intermediate-acting: NPH.
Short-acting: Regular insulin.
Rapid-acting analogs: lispro, aspart, glulisine.

First Line

Flexible intensive insulin therapy.
Initial dose: 0.2–0.4 units/kg/day (up to 1.0 in puberty).
About 50% basal insulin, 50% prandial insulin.
MDI regimens with correction doses.

Second Line

Twice-daily NPH + regular or rapid insulin (lower cost, less physiologic).
Pramlintide as adjunct.

Issues for Referral

Endocrinology referral recommended for diagnosis and management.

Additional Therapies

Inhaled rapid-acting insulin.
Pancreatic/islet transplantation (for select severe cases).
Investigational therapies: ultra-long-acting insulin, metformin, GLP-1 agonists, DPP-4 inhibitors, SGLT inhibitors, DIY automated insulin delivery.

Surgery/Procedures

Continue basal insulin perioperatively.
Hold prandial insulin if NPO before surgery.

Admission/Inpatient

Hospitalization common at diagnosis for insulin initiation.

Ongoing Care

Follow-up

Regular aerobic exercise; adjust insulin or eat carbs to prevent hypoglycemia.
Monitor BP (<130/80).
Home glucose monitoring 4–6 times/day.
Annual foot exam.
Quarterly HbA1c.
Statins for ASCVD prevention based on age and risk.
Annual screening: albuminuria, eye exams, neuropathy.

Diet

ADA diet guidelines.
Carbohydrate counting with insulin ratio.

Patient Education

Diagnosis education, carb counting, nutrition.

Prognosis

Honeymoon phase may last 3–6 months.
Improved outcomes with good glucose control and insulin management.

Complications

Microvascular: retinopathy, nephropathy, neuropathy.
Macrovascular: coronary, cerebrovascular disease.
Foot ulcers, amputations.
Hypoglycemia.
DKA.
Weight gain.
Infection risk.
Pregnancy risks: preeclampsia, preterm delivery.

ICD10 Codes:
- E10.319 Type 1 diabetes mellitus with unspecified diabetic retinopathy without macular edema
- E10.321 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema
- E10.351 Type 1 diabetes mellitus with proliferative diabetic retinopathy with macular edema

Clinical Pearls:
- Bimodal age of presentation: 4-6 years and 10-14 years.
- MDI or CSII with multidisciplinary team improves outcomes.
- Individualize HbA1c goals; <7% for adults, <7.5% for pediatrics.