creation date: 2025-11-28 09:22
tags: Pathologies
Diabetes Mellitus, Type 1
Background
Definitions
Type 1 diabetes mellitus (T1DM) is characterized by immune-mediated destruction of pancreatic beta cells, leading to a lack of insulin production and insulin deficiency.
Type 1 DM is more commonly diagnosed in younger individuals than adults (contrasted to type 2 diabetes).
Etiology and Pathogenesis
T1DM results from autoimmune destruction of the beta-cells in Langerhans pancreatic islet.
Genetics
A genetic predisposition is strongly linked to the development of T1DM. In particular, the specific human leukocyte antigen (HLA) alleles DR and DQ increase the risk of developing the disease.
Environmental triggers
The autoimmune destruction is thought to be triggered by environmental factors in genetically susceptible people. Factors found to be associated with triggering include:
- Infection with Coxsackie virus, enteroviruses, CMV, rubella, influenza B, mumps, SARS-CoV-2
- Pregnancy and perinatal conditions
- Childhood vaccination
- Dietary factors such as cow’s milk and cereal exposure
Autoimmunity
Genetic and environmental factors lead to immune system dysfunction. Islet-directed autoantibodies result in the immune-mediated destruction of beta cells. Autoantibodies are anti-GAD and anti-ICA resulting in a type 4 sensitivity reaction.
Beta cell stress is reflected in the release of prohormones such as proinsulin rather than processed insulin.
Development of T1DM
The onset of autoimmune beta-cell destruction and insulitis characterizes stage 1 or the preclinical stage of T1DM. As the beta-cell dysfunction worsens, the disease progresses to stage 2, where dysglycemia occurs.
Stage is is characterized by the clinical onset of disease where individuals have symptomatic hyperglycemia.
Clinical Presentation
Signs & Symptoms
Initial presentation may be one of the following:
- Polydipsia, polyuria, weight loss with hyperglycemia and ketonemia (classic new onset)
- Diabetic ketoacidosis
- Silent/asymptomatic incidental discovery
In the classic presentation, vague symptoms may be present including:
- Lethargy
- Perineal candidiasis (common in young children and girls)
- Acute visual disturbances
- Cataracts
History & Physical Exam
History should be comprehensive including family history and pregnancy history. History of prior diabetes education may also be relevant as well as history of acute complications such as DKA.
Screening for other autoimmune disorders such as thyroid pathology or celiac disease should be done. Psychosocial screening should be completed including eating disorders.
Physical exam should be comprehensive, evaluating for complications such as peripheral neuropathy, foot deformities, lesions, and sensation including vibrations. An abnormal 10-g monofilament exam suggests increased risk of ulceration.
If insulin is used, the skin should be examined around injection sites.
Risk factors
Diagnosis
Criteria
Diagnosis of diabetes mellitus
If asymptomatic, two results is needed for diagnosis (eg. two A1C after 3 months or A1C and FPG together immediately).
If symptoms of hyperglycemia present, then one result in diabetic range needed.
For A1C:
- Prediabetes: 6.0-6.4%
- Diabetes: ≥6.5%
For FPG (≥8 hr fasting): - Impaired fasting glucose: 6.1-6.9 mmol/L
- Diabetes: ≥7.0 mmol/L
OGTT: - Impaired fasting glucose: 7.8-11.0 mmol/L
- Diabetes: ≥11.1 mmol/L
A CBC is obtained to validate the A1C. A1C is a function of Hb turnover (longer RBC age is associated with falsely elevated A1C).
Diagnosis of type 1
Laboratory tests are used to distinguish between type 1 and type 2 diabetes:
- Pancreatic autoantibodies (GAD65, IA2, insulin, ZnT8) present
- Insulin and C-peptide levels (inappropriately low in T1)
Work-up
For both the initial workup and further reassessment:
- Basic metabolic panel (incl. renal function and electrolytes)
- Urinalysis for glucosuria, ketones, microalbuminuria
- CBC with platelets
- Liver tests
- Lipid panel
Differential
- Iatrogenic causes such as medications
- Genetic aberrations in beta-cell function and insulin action
- Infection
- Endocrinopathies such as acromegaly. Cushing disease, pheochromocytoma, hypothyroidism, etc.
- Conditions affecting the exocrine part of the pancreas such as pancreatitis, tumours, etc.
Red Flags / Complications
Acute complications include:
- Hypoglycemia
- Diabetic ketoacidosis
Chronic complications include:
- Nephropathy
- Peripheral and autonomic neuropathy
- Retinopathy
- Heart disease
- Peripheral arterial disease
- Cerebrovascular disease
- Diabetic foot
Management
Non-pharmacological
Diet
Nutrition is essential to management. Basic skills that are taught as part of diabetes education include:
- Determining carbohydrate content of foods
- Having balanced diet which may include carbohydrate limitation
Exercise
Regular exercise should be encouraged. It should be noted that insulin adjustments may be necessary to prevent hypoglycemia.
Glycemic monitoring
A number of techniques can be used to monitor:
- Blood glucose monitoring (fingerstick) several times daily (eg. before each meal, at bedtime, before and after exercise, and overnight)
- Continuous glucose monitoring (CGM)
A time in range (3.9 - 10 mmol/L) target of at least 70% should be used.
Insulin Therapy
For patients with stage 3 T1DM (clinical dysglycemia), insulin is the primary mean of treatment.
An insulin therapy regimen is individualized for the needs, meals, exercise, and fasting patterns of the patient. Components of the regimen include considering:
- Choice of insulin
- Route of administration (most common is multiple daily injection but some pediatric settings may use insulin pump)
In most patients, a basal-bolus multiple daily injection (MDI) regimen is recommended. This consist of:
- Long-acting basal insulin analog (eg. insulin glargine, insulin degludec)
- Rapid acting or short-acting bolus insulin given before each meal/snack