Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 9/17/2012
Definition 
Diabetes Mellitus Type 1 (T1DM) is a metabolic disorder characterized by hyperglycemia due an absolute deficiency of insulin, a pancreatic hormone produced by beta cells within the pancreas. This insulin deficiency results from beta cell destruction, most commonly due autoimmune processes.
Description
- T1DM develops as a result of autoimmune destruction of pancreatic beta cells
- Pancreatic beta cell destruction not due to autoimmune causes is termed idiopathic T1DM
- Deposition of iron in pancreatic beta cells, due to hemochromatosis, can cause a variant of T1DM called bronze diabetes
- Familial incidence is attributable to susceptible types of human leukocyte antigen (HLA)
- T1DM was formerly known as Insulin Dependent Diabetes Mellitus (IDDM) or juvenile diabetes
- T1DM typically develops in children and adolescents (although onset can occur at any age)
- T1DM requires lifelong exogenous insulin
- Patients frequently present with symptoms such as weight loss, dehydration, hyperventilation, coma, and/or ketoacidosis
- Patients with T1DM are often thin, in contrast to T2DM patients who are typically overweight
Epidemiology
Incidence/prevalence
United States:
- Youth 10 years: T1DM annual incidence is 19.7/100,000
- Youth
10 years: T1DM annual incidence is 18.6/100,000 - Non-Hispanic white youth have the highest incidence
- African Americans have the lowest incidence
- Annually 15,600 youth are newly diagnosed with T1DM (U.S.)
Age
- Mean age of onset is 8-12 years (peaking in adolescence)
- Age of presentation has a bimodal distribution: highest at ages 4-6 and 10-14 years
Gender
- More common in males than females
Genetics
- HLA on chromosome 6 is thought to contribute to ~50% of familial cases
- HLA DR3 and DR4 are present in 90% of children with T1DM and are considered susceptibility genes (relative risk increases if both susceptibility genes are present)
- HLA B8 and B15 are associated with an increased risk
- Concordance rate in monozygotic twins is 23% probandwise, and 13% pairwise
Risk factors
- Certain human leukocyte antigen (HLA) types increase risk of developing T1DM
- Infectious agents (strongest evidence for congenital rubella and human enteroviruses)
- Family history of T1DM in first-degree relatives
- Dietary factors: T1DM is less common among those who were breastfed, and among those who ate solid foods at later ages. Exposure to cow’s milk at an early age is associated with increased risk
- Maternal age at birth may play an important role in development of the disease. A meta-analysis conducted by Cardwell in 2010 demonstrated a significant linear increase in the risk of childhood T1DM with increases in maternal age
- If either parent developed T1DM before age 11, a child’s risk is doubled; if both parents have T1DM the risk is amplified
Etiology
- Associated environmental triggers
- Cytotoxins
- Environmental toxins
- Viruses (such as Enterovirus, Mumps, Coxsackie B, Cytomegalovirus, Rubella and Hepatitis viruses)
- Genetic factors (see genetics section)
[Outline]
History
- Altered school or work performance
- Blurry vision (often intermittent)
- Headaches
- Increased fatigue, lethargy, muscle cramps (dehydration)
- Infections, often recurrent or severe. May have candidiasis (oral, genital, cutaneous) or UTI’s
- Lability (emotional/irritable)
- Numbness or tingling in hands and feet
- Polydipsia
- Polyphagia
- Polyuria (may present as nocturia, bedwetting, or incontinence in a previously continent child)
- Symptoms of ketoacidosis: Nausea, vomiting, altered level of consciousness, tachypnea, and abdominal discomfort or pain
- Weight loss (often rapid and unexplained)
Physical findings on examination
- Altered level of consciousness
- Dehydration (delayed capillary refill, dry mucous membranes, etc)
- Kussmaul breathing, suggestive of diabetic ketoacidosis
- Lower-extremity sensory neuropathy
- Muscle wasting
- Tachycardia
- Tachypnea
- Unexplained weight loss
[Outline]
Blood test findings
Blood-glucose monitoring and measurement of glycosylated hemoglobin levels 6.5% or greater on 2 or more occasions is diagnostic, efficient and reliable for diagnosis of DM (irrespective of type).
- Criteria for diagnosis of DM
- Random plasma glucose: 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, or weight loss) OR
- Fasting plasma glucose: 126 mg/dL (6.9 mmol/L) on 2 occasions OR
- Glycosylated hemoglobin (HbA1c): 6.5% on 2 or more occasions OR
- Oral glucose tolerance test; plasma glucose 200 mg/dL (11.1 mmol/L) 2 hours after a glucose load of 1.75 g/kg (max. dose 75g)
- Note: Diagnosis of T1DM is usually obvious due to severe hyperglycemia, ketoacidosis and symptomatology. It is more common to see borderline and less obvious presentations with T2DM
- Other tests
- Low levels of C-peptide indicate absence of insulin secretion consistent with T1DM, and can be helpful to differentiate from T2DM
- Plasma acetone, especially beta-hydroxybutyrate level is a reliable indicator of diabetic ketoacidosis
- ADA minimal criteria for diabetic ketoacidosis (DKA):
- Plasma glucose concentration: >250mg/dL (13.9 mmol/L)
- pH: 7.30
- Serum bicarbonate:
18meq/L (18 mmol/L) - beta-hydroxybutyrate or ketones in urine or blood
- Anion gap > 10 mEq/L (10 mmol/L)
*All 5 items must be present to support a diagnosis of DKA
Other laboratory test findings
- Urinalysis for glucose and ketones can be performed. Note: Elevation of ketones and/or glucose in serum or urine may be due to conditions other than diabetes
- Pathological findings: Inflammatory changes, lymphocytic infiltration, in the pancreas, around the islets of Langerhans, or islet cell loss
- Presence of pancreatic autoantibodies such as glutamic acid decarboxylase antibodies (GADA) and islet cell antibodies (ICA) may indicate autoimmune destruction of pancreatic beta cells
[Outline]
General treatment items
- The goal of long-term treatment includes both symptom relief and prevention/delay of complications due to hyperglycemia
- Ketoacidosis treatment requires intensive therapy, generally including hospitalization. It is a potentially immediate life-threat
- Lifelong exogenous insulin (injection or infusion) is required
- Injections: It is typical to combine short-acting and long-acting insulins, along with injections prior to meals
- Infusion: An insulin pump administers a basal (steady state) amount of short acting insulin. Boluses of short acting insulin are given in addition to the basal rate (typically before or with meals)
- Early detection through screening (at intervals recommended by national and international guidelines) to treat complications
- Ongoing care includes dietician/diabetic educator referral, eye exams, microalbumin urine tests, foot care, blood pressure monitoring, and other specialist referrals
- Patients need to monitor themselves for signs or symptoms of hypoglycemia such as:
- Confusssion or drowsiness
- Diaphoresis
- Dizziness
- Hunger
- Palpitations
- Shakiness
- Patients also need to monitor for both hyperglycemia, and signs or symptoms of ketoacidosis such as:
- Abdominal pain
- Confusion
- Dehydration/rapid weight loss
- Ketotic-fruity breath
- Nausea
- Polyurea
- Polydipsea
- Tachypnea or shortness of breath
- Vomiting
- Weakness
- Patient education on diet, exercise, and foot care
- Common insulin regimens:
- Split or mixed, such as NPH given twice daily, with rapid-acting (eg, lispro, aspart, or glulisine), or regular insulin before each meal
- Multiple daily injections (MDI), a long-acting insulin (eg, glargine or detemir) once daily in the morning or evening (or twice daily in ~20% of patients), and rapid-acting insulin before meals or snacks (dose adjusted based on carbohydrate intake and blood glucose level)
- Continuous subcutaneous insulin infusion (CSII), rapid-acting insulin infused 24 hours per day through an insulin pump at one or more basal rates, with additional boluses administered before each meal. Correction doses should be administered if blood glucose levels exceed target levels
- Initiation of insulin therapy in adults:
- Initial daily dose should be calculated based upon weight. The actual distribution of which type of insulin and frequency of dosing relates to that which best suits the patient
- The total dose of insulin (both short and long acting) is typically 0.5-1 U/kg/day. The selection of initial dose, adjusted dose, types and timing depend upon plasma glucose levels and multifactorial patient dependent issues. These dose ranges are typical for long-term management. Note that dosing of insulin in DKA is substantially different; please see topic
- Doses are adjusted to maintain pre-prandial plasma glucose at 80-150 mg/dL (4.4-8.3 mmol/L)
- Doses are typically adjusted in 10% increments, with the effects assessed over several days following a change
- Specialized protocols exist when insulin pump is selected, as a highly individualized approach is often required
- 2011 American College of Physicians guidelines recommend a goal glucose level of 140-200 mg/dL when insulin is used to manage patients with diabetes in nonsurgical (medical) ICUs. It is important to note that this guideline is aimed at patients with T2DM. It is also important to note data indicating that either overly aggressive glycemic control or significant hyperglycemia were both potentially harmful
- Initiation of insulin therapy in children:
- Patients with moderate hyperglycemia without ketonuria or acidosis may be started with a single subcutaneous injection of 0.3-0.5 U/kg/day of intermediate/long-acting insulin
- Patients with hyperglycemia and ketonuria who are not acidotic or dehydrated, may be started on 0.5-0.7 U/kg/day of intermediate/long-acting insulin and subcutaneous injections of 0.1 U/kg/day of regular insulin at 4–6 hour intervals
- Specialized protocols exist when insulin pump is selected, as a highly individualized approach is often required
- Please see topic on DKA if this condition is present
Medications indicated with specific doses
- Rapid-acting insulins
- Insulin aspart [IV/SC]
- Insulin glulisine [IV/SC]
- Insulin lispro [SC]
- Short-acting insulins
- Intermediate-acting insulins
- Long-acting insulins
- Insulin detemir (rDNA origin) [SC]
- Insulin glargine [SC]
Dietary or Activity restrictions
- Diet should be directed toward healthy distribution and matching of carbohydrate intake with insulin action. Carbohydrates should comprise 55% of caloric intake, fats should be 30%, and protein should be 15%
- Fiber 50 grams/day is recommended (adult recommendation)
- Low glycemic index (GI) foods should comprise the majority of carbohydrate intake
- Calorie counting is helpful in flexible insulin regimens while evenly spaced meals or snacks are essential for fixed insulin regimens
- Reduction of saturated and trans fats may be beneficial
- Regular aerobic exercise recommended. Frequent exercise reduces blood glucose and insulin requirements
- In the event of excessive caloric intake (large consumption of high carbohydrate meal), additional short-acting insulin will be required
- Patients are advised to adjust their insulin dose according to their daily food intake and activity level. Regular eating on a fixed regimen is important
- To avoid hypoglycemia, patients may need to decrease medications in the event of illness affecting ability to eat, voluntary fasting for procedures or personal reasons, excessive physical activity or exercise
- Exercise may require additional caloric intake, or a reduced insulin dose, to prevent hypoglycemia
[Outline]
Prognosis
- Untreated T1DM would be expected to be fatal due to diabetic ketoacidosis
- The mortality and morbidity associated with T1DM depends upon short and long-term complications
- Patients with T1DM have a greater mortality rate than the general population. This is attributable to an increased rate of renal, vascular, neurological, and cardiovascular disease
- Early onset T1DM has a lower mortality than later onset T1DM
- Poorly controlled cases are a risk factor for chronic complications (eg, blindness, renal failure, foot amputation, stroke, and heart attack)
- Intensive glycemic control decreases the incidence of microvascular and macrovascular complications
- Cardiovascular disease is a major cause of death and morbidity in diabetic patients
- Women with T1DM are generally successful with pregnancy; however, careful planning and treatment are necessary
Associated conditions
- Autoimmune diseases (hypothyroidism and Addison’s disease)
- Multiple endocrine adenomatosis
Pregnancy/Pediatric effects on condition
- T1DM is associated with adverse perinatal outcomes such as stillbirth, perinatal mortality, fetal macrosomia, and congenital malformations
- Due to the increased incidence of congenital malformations during embryogenesis, strict blood glucose control is important prior to conception
- Women with microalbuminuria during the first trimester are at increased risk for preeclampsia and preterm delivery
- A safe pregnancy is possible with vaginal delivery of a term baby. It is important to monitor blood glucose during labor and in the infant post-delivery
- Insulin is considered safe for use in pregnancy
Synonyms/Abbreviations
Synonyms
- Insulin-Dependent Diabetes Mellitus (IDDM)
- Juvenile diabetes
- T1DM
ICD-9-CM
- 250.01 Diabetes mellitus without mention of complication, type I (juvenile type), not stated as uncontrolled
- 250.03 Diabetes mellitus without mention of complication, type I (juvenile type), uncontrolled
ICD-10-CM
- E10 Diabetes Mellitus Type 1
[Outline]
