Type 1 diabetes mellitus is an autoimmune disease that involves destruction of the insulin-secreting pancreatic beta cells, leading to impaired insulin secretion, hyperglycemia, and eventually variable degrees of peripheral insulin resistance. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, polyuria, and blurred vision. Later complications include vascular disease, peripheral neuropathy, nephropathy, and predisposition to infection. Diagnosis is by measuring plasma glucose and autoantibodies. Treatment is with insulin and glucose monitoring, as well as dietary and exercise modifications. Complications can be delayed or prevented with adequate glycemic control; cardiovascular disease remains the leading cause of premature mortality in type 1 diabetes mellitus.
Etiology of Type 1 Diabetes Mellitus
The hallmark of type 1 diabetes is:
Autoimmune pancreatic beta-cell destruction leading to insufficient insulin production
Type 1 accounts for 5 to 10% of all cases of diabetes mellitus (1).
In type 1 diabetes mellitus, insulin production is absent or severely deficient because of autoimmune pancreatic beta-cell destruction, possibly triggered by an environmental exposure in people who are genetically susceptible. Destruction progresses subclinically over months or years until beta-cell mass decreases to the point that insulin concentrations are no longer adequate to control plasma glucose levels. Type 1 diabetes generally develops in childhood or adolescence and is most common form diagnosed before age 20 years; however, it can also develop in adults (2, 3).
Susceptibility genes include those within the major histocompatibility complex (MHC)—especially the DR3-DQ2.5 and DR4-DQ8 haplotypes, which are present in > 90% of patients younger than 30 years with type 1 diabetes mellitus—and those outside the MHC, which seem to regulate insulin production and processing and confer risk of diabetes mellitus in concert with MHC genes (4). Susceptibility genes are more common among some populations than among others and explain the higher prevalence of type 1 diabetes in people with ancestry from certain areas (eg, Scandinavians, Sardinians).
Autoantigens include glutamic acid decarboxylase, insulin, proinsulin, insulinoma-associated protein, zinc transporter ZnT8, and other proteins in beta cells (4). It is thought that these proteins are exposed or released during normal beta-cell turnover or beta-cell injury (eg, due to infection), activating primarily a T cell‒mediated immune response that results in beta-cell destruction (insulitis). Glucagon-secreting alpha cells remain unharmed. Antibodies to these autoantigens (generally called islet cell autoantibodies), which can be detected in serum, seem to be a response to (not a cause of) beta-cell destruction.
Several viruses (especially coxsackievirus and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2 causing COVID-19], as well as congenital cytomegalovirus and rubella, and potentially retroviruses) have been linked to the onset of type 1 diabetes (5, 6, 7, 8, 9). Viruses may directly infect and destroy beta cells, or they may cause beta-cell destruction indirectly by exposing autoantigens, activating autoreactive lymphocytes, mimicking molecular sequences of autoantigens that stimulate an immune response (molecular mimicry), or other mechanisms.
Diet may also be a factor. Intake of cow's milk, oats, gluten, and dietary fiber during infancy is associated with an increased risk of type 1 diabetes (10, 11). Weaker associations are seen with sugar and carbohydrate intake, vitamin D supplementation, nitrite, and protein and the development of type 1 diabetes. Mechanisms for these associations are unclear. Protective dietary factors include later introduction of cow's milk, gluten, and fruit (for cow's milk, after 2 to 3 months; for gluten, after 3 to 6 months; for fruit, after 4 to 6 months).
Autoimmune diabetes can develop in adulthood (called latent autoimmune diabetes of adulthood [LADA]) and is often more slowly progressive than childhood type 1 diabetes.
Some cases of type 1 diabetes do not appear to be autoimmune in nature and are considered idiopathic.
Screening and Prevention of Type 1 Diabetes
Screening
People at high risk of type 1 diabetes (eg, siblings and children of people with type 1 diabetes) can be tested for the presence of autoantibodies (insulin autoantibodies, glutamic acid decarboxylase autoantibodies, insulinoma-associated-2-autoantibodies, zinc transporter-8 autoantibodies, or islet cell autoantibodies), which precede onset of clinical disease (1).
Prevention
There are no therapies to completely prevent type 1 diabetes.
However, progression of type 1 diabetes from preclinical to diagnosable disease can be delayed with pharmacologic therapy. Teplizumab is a monoclonal antibody that binds to CD3 cell surface antigens on T cells, which leads to an increase in the proportion of regulatory T cells and exhausted CD8+ T cells and attenuates the autoimmune response that leads to beta-cell destruction. Trials have shown that However, progression of type 1 diabetes from preclinical to diagnosable disease can be delayed with pharmacologic therapy. Teplizumab is a monoclonal antibody that binds to CD3 cell surface antigens on T cells, which leads to an increase in the proportion of regulatory T cells and exhausted CD8+ T cells and attenuates the autoimmune response that leads to beta-cell destruction. Trials have shown thatteplizumab can delay onset of clinical type 1 diabetes and preserve beta-cell function but mixed results on glycemic control and insulin dosing requirements (2, 3).
Antithymocyte globulin (ATG), tumor necrosis factor- alpha (TNF-alpha) inhibitors, and abatacept (CTLA-4-Ig) have shown some promise in preserving beta-cell function in recent-onset type 1 diabetes (Antithymocyte globulin (ATG), tumor necrosis factor- alpha (TNF-alpha) inhibitors, and abatacept (CTLA-4-Ig) have shown some promise in preserving beta-cell function in recent-onset type 1 diabetes (4). Verapamil may also preserve beta-cell function in patients with newly diagnosed diabetes (). Verapamil may also preserve beta-cell function in patients with newly diagnosed diabetes (5).
Screening and prevention references
1. Sims EK, Besser REJ, Dayan C, et al. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes 2022;71(4):610-623. doi:10.2337/dbi20-0054
2. Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes [published correction appears in N Engl J Med 2020 Feb 6;382(6):586]. N Engl J Med 2019;381(7):603-613. doi:10.1056/NEJMoa1902226
3. Ramos EL, Dayan CM, Chatenoud L, et al. Teplizumab and Beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389(23):2151-2161. doi:10.1056/NEJMoa2308743
4. Nagy G, Szekely TE, Somogyi A, Herold M, Herold Z. New therapeutic approaches for type 1 diabetes: Disease-modifying therapies. World J Diabetes. 2022;13(10):835-850. doi:10.4239/wjd.v13.i10.835
5. Forlenza GP, McVean J, Beck RW, et al. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023;329(12):990-999. doi:10.1001/jama.2023.2064
Symptoms and Signs of Type 1 Diabetes Mellitus
Islet cell destruction generally precedes the initial presentation of type 1 diabetes, causing hyperglycemia and eventually symptoms when insulin production falls below a physiologic threshold.
Type 1 diabetes mellitus progresses in stages:
Stage 1: Presence of ≥ 2 islet autoantibodies with normal plasma glucose and no symptoms
Stage 2: Glucose intolerance or dysglycemia but no symptoms
Stage 3: Clinical symptoms
More significant hyperglycemia (above 160 to 180 mg/dL [8.9 to 10.0 mmol/L]) causes glycosuria and thus an osmotic diuresis, leading to urinary frequency, polyuria, and polydipsia that may progress to orthostatic hypotension and dehydration. Severe dehydration causes weakness, fatigue, and mental status changes. Symptoms may come and go as plasma glucose levels fluctuate.
Polyphagia may accompany symptoms of hyperglycemia but is not typically a primary patient concern. Hyperglycemia can also cause weight loss, nausea and vomiting, and blurred vision, and it may predispose to bacterial or fungal infections.
Patients with type 1 diabetes may also present with diabetic ketoacidosis (DKA).
Some patients in stage 3 experience a long but transient phase of near-normal glucose levels after acute onset of the disease (honeymoon phase) due to partial recovery of insulin secretion.
Diagnosis of Type 1 Diabetes Mellitus
Fasting plasma glucose, glycosylated hemoglobin (HbA1C), or oral glucose tolerance test
Sometimes autoantibodies, C-peptide, or genetic markers
The diagnosis of type 1 diabetes may be suspected based upon typical symptoms or a family history of elevated fasting plasma glucose or HbA1C level, oral glucose tolerance test findings, or random glucose in the presence of certain symptoms. (See Diagnosis of Diabetes Mellitus and table Diagnostic Criteria for Diabetes Mellitus and Prediabetes for more details.)
Once diabetes is diagnosed, it may be classified as Type 1 diabetes based on evidence of autoimmune destruction of beta cells, in particular by autoantibodies including antibodies to islet cells, glutamic acid decarboxylase, islet antigen 2, zinc transporter 8, and insulin (1). Low levels of C-peptide may indicate a lack of endogenous insulin production. Genetic markers may also help distinguish type 1 from type 2 diabetes (2). The age and manner of presentation may also suggest the classification of the patient's diabetes, with younger age at presentation more common in type 1 diabetes, and polydipsia and polyuria and diabetic ketoacidosis being more common presenting signs and symptoms (1, 3). Note, however, that adults as well as children can and do develop type 1 diabetes, so age alone is not a reliable differentiator. (See table General Characteristics of Types 1 and 2 Diabetes Mellitus for more details.)
Diagnosis references
1. American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(Supplement_1):S27-S49. doi:10.2337/dc25-S002
2. Sacks DB, Arnold M, Bakris GL, et al. Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Diabetes Care. 2023;46(10):e151-e199. doi:10.2337/dci23-0036
3. Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 64(12):2609–2652, 2021. doi: 10.1007/s00125-021-05568-3
Treatment of Type 1 Diabetes Mellitus
Insulin and glucose monitoring
Diabetes education
Dietary management
To prevent complications, often renin-angiotensin-aldosterone system blockers (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers) and statins
Patients with type 1 diabetes require insulin. Other key elements of treatment for all patients are patient education, dietary management, and monitoring of glucose control.
Pharmacotherapy
(See also Medication Treatment of Diabetes.)
Insulin
All patients with type 1 diabetes require insulin therapy (1). The goal is to try to replicate the pattern of insulin secretion of a person who does not have diabetes by using basal-bolus insulin therapy. In basal-bolus therapy, a longer-acting insulin (or a continuous subcutaneous infusion of rapid-acting insulin delivered by a pump) is used to simulate basal insulin production that suppresses hepatic glucose production, especially in the fasting state, and a shorter-acting insulin is used before meals to control postprandial glucose excursions.
Patients with type 1 diabetes should use carbohydrate counting or the carbohydrate exchange system to match insulin dose to carbohydrate intake and facilitate physiologic insulin replacement. “Counting” the amount of carbohydrate in the meal is done to calculate the preprandial insulin dose. For example, if a carbohydrate-to-insulin ratio (CIR) of 15 gram:1 unit is used, a patient will require 1 unit of rapid-acting insulin for each 15 g of carbohydrate in a meal. These ratios can vary significantly between patients, depending on their degree of insulin sensitivity and must be tailored to the patient and adjusted over time. Patients should also be educated that meals with higher protein or fat content can increase insulin requirements and dose adjustments may be necessary. This approach requires detailed patient education and is most successful when guided by a dietitian experienced in working with patients with diabetes. Some experts have advised use of the glycemic index (a measure of the impact of an ingested carbohydrate-containing food on the blood glucose level) to delineate between rapid and slowly metabolized carbohydrates, but there is no recommendation to support the use of glycemic index specifically for insulin dosing (1, 2).
Insulin pumps can be integrated with continuous glucose monitoring (CGM) systems to provide real-time adjustment of insulin doses based on blood glucose levels. Such systems, known as automated insulin delivery (AID) systems or hybrid closed-loop systems, are recommended for all patients who take multiple daily injections of insulin and have been shown to lower HbA1C levels and decrease hypoglycemia (3, 4, 5). They are commonly used, and some versions do not require daily fingerstick glucose testing to calibrate the glucose monitor. They are especially useful in patients with type 1 diabetes, particularly for patients with hypoglycemia unawareness or nocturnal hypoglycemia. Hybrid closed-loop systems require patients to input carbohydrate intake prior to meals, whereas fully closed-loop systems (not yet available) will not.
Sliding-scale insulin is a strategy in which varying doses of rapid-acting insulin are given depending on the patient's plasma glucose level. However, a sliding scale insulin regimen on its own is not an effective strategy for maintaining euglycemia in patients with type 1 diabetes (6, 7).
Other medications for patients with comorbidities
Pramlintide, an amylin analogue produced by beta-cells, can be used as an Pramlintide, an amylin analogue produced by beta-cells, can be used as aninsulin adjunct (1).
An angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) is recommended for patients who have type 1 diabetes with hypertension or chronic kidney disease (albuminuria and/or reduced glomerular filtration rate) (8, 9).
A statin is recommended for all patients who are 40 to 75 years old with type 1 diabetes, for those who are 20 to 39 years old with additional risk factors for atherosclerotic cardiovascular disease (ASCVD), and those of any age with chronic kidney disease (8, 9). The intensity of statin therapy depends upon specific risk factors. The risk of teratogenicity should be considered in all individuals of childbearing potential.
Diabetes education
Formal diabetes education for patients and families (diabetes self-management education and support, or DSMES), generally conducted by diabetes nurses and nutrition specialists, is often very effective and has been shown to improve diabetes outcomes (6). Education is considered as important as pharmacologic therapy in managing type 1 diabetes. Education should include information about the following:
Causes of diabetes
Diet
Exercise
Insulin and other medication useInsulin and other medication use
Adjusting insulin doses based carbohydrate intake and glucose level
Self-monitoring with fingerstick testing or continuous glucose monitoring
Monitoring HbA1C
Symptoms and signs of hypoglycemia, hyperglycemia, and diabetic complications
Education should be reinforced at every physician visit and hospitalization.
Diet
Individualized medical nutrition therapy with a dietitian should complement physician counseling and diabetes education; the patient and any person who prepares the patient’s meals should be present (6, 10).
There are no specific recommendations on the percentages of calories that should come from carbohydrate, protein, or fat. Adjusting diet to individual circumstances can help patients control fluctuations in their glucose level. Dietary management should be individualized based on patient age, size, activity level, tastes, preferences, culture, and goals and should be formulated to accommodate requirements posed by comorbid conditions. Patients should be educated on consuming a diet rich in whole foods rather than processed foods. Carbohydrates should be high quality and should contain adequate amounts of fiber, vitamins, and minerals and be low in added sugar, fat, and sodium.
Patients should be educated about using carbohydrate consumption ("counting" carbohydrates) to guide bolus insulin dosing. The concept of the glycemic index (a measure of the impact of an ingested carbohydrate-containing food on the blood glucose level) may be useful in general dietary management as well (6).
Exercise
Exercise has been shown to decrease mortality although the effect on HbA1C lowering is less clear (11, 12, 13). Regular physical activity can have a direct positive impact on overall glycemic control, physical function, and quality of life, as well as cardiometabolic risk factors, including blood pressure, lipid profile, and depression (6). Adults with diabetes and without physical limitations should exercise for a minimum of 150 minutes/week (divided over at least 3 days); for those with physical limitations, physical activity should increase incrementally to whatever level a patient can tolerate. Physical activity should include moderate or vigorous aerobic activity, strength training, and, for older adults, flexibility and balance training.
Exercise has a variable short-term effect on blood glucose, depending on the timing of exercise in relation to meals and the duration, intensity, and type of exercise. In patients with type 1 diabetes in particular, exercise can lead to hypoglycemia. Therefore, blood glucose should be monitored immediately before and after exercise. The target range for blood glucose prior to exercise should be between 90 mg/dL and 250 mg/dL (5 mmol/L to 14 mmol/L) (14).
Patients who experience hypoglycemic symptoms during exercise should be advised to test their blood glucose and ingest carbohydrates or lower their insulin dose as needed so that their glucose is slightly above normal just before exercise. Hypoglycemia during vigorous exercise may require carbohydrate ingestion during the workout period, typically 5 to 15 g of sucrose or another simple sugar.
Patients with known or suspected cardiovascular disease may benefit from a pre-exercise evaluation, possibly including exercise stress testing before beginning an exercise program (6). Activity goals may need to be modified for patients with complications of diabetes such as neuropathy and retinopathy.
Foot care
All adults with diabetes, including type 1 diabetes, should undergo a comprehensive foot examination at least annually (15, 16). Individuals with peripheral neuropathy, history of ulcers or amputations, or poorly controlled glucose, should have an examination at every visit and certain guidelines, recommend this approach for all patients with diabetes. Assessment of neuropathy includes 10 g monofilament test as well as pinprick, temperature, vibration testing.
Regular professional podiatric care, including trimming of toenails and calluses, is important for patients with sensory loss or circulatory impairment. Such patients should be advised to inspect their feet daily for cracks, fissures, calluses, corns, and ulcers. Feet should be washed daily in lukewarm water, using mild soap, and dried gently and thoroughly. A lubricant (eg, lanolin) should be applied to dry, scaly skin. Nonmedicated foot powders should be applied to moist feet. Toenails should be cut, preferably by a podiatrist, straight across and not too close to the skin. Adhesive plasters and tape, harsh chemicals, corn cures, water bottles, and electric pads should not be used on skin. Patients should change socks or stockings daily and not wear constricting clothing (eg, garters, socks, or stockings with tight elastic tops). Regular professional podiatric care, including trimming of toenails and calluses, is important for patients with sensory loss or circulatory impairment. Such patients should be advised to inspect their feet daily for cracks, fissures, calluses, corns, and ulcers. Feet should be washed daily in lukewarm water, using mild soap, and dried gently and thoroughly. A lubricant (eg, lanolin) should be applied to dry, scaly skin. Nonmedicated foot powders should be applied to moist feet. Toenails should be cut, preferably by a podiatrist, straight across and not too close to the skin. Adhesive plasters and tape, harsh chemicals, corn cures, water bottles, and electric pads should not be used on skin. Patients should change socks or stockings daily and not wear constricting clothing (eg, garters, socks, or stockings with tight elastic tops).
Shoes should fit well, be wide-toed without open heels or toes, and be changed frequently. Special shoes should be prescribed to reduce trauma if the foot is deformed (eg, previous toe amputation, hammer toe, bunion). Walking barefoot should be avoided.
Patients with neuropathic foot ulcers should avoid weight bearing until ulcers heal. If they cannot, they should wear appropriate orthotic protection. Because most patients with these ulcers have little or no macrovascular occlusive disease, debridement and antibiotics frequently result in good healing and may prevent major surgery. After the ulcer has healed, appropriate inserts or special shoes should be prescribed. In refractory cases, especially if osteomyelitis is present, surgical removal of the metatarsal head (the source of pressure), amputation of the involved toe, or transmetatarsal amputation may be required. A neuropathic joint can often be satisfactorily managed with orthopedic devices (eg, short leg braces, molded shoes, sponge-rubber arch supports, crutches, prostheses).
Vaccination
All patients with diabetes, including type 1 diabetes, should be vaccinated against Streptococcus pneumoniae, influenza virus, hepatitis B, varicella, respiratory syncytial virus, and SARS-CoV-2 as per standard recommendations (17).
Pancreas and islet cell transplantation
Pancreas transplantation and transplantation of pancreatic islet cells are alternative means of insulin delivery (18, 19); both techniques effectively transplant insulin-producing beta-cells into patients who are insulin deficient (have type 1 diabetes mellitus).
Stem-cell derived islet cell preparations (eg, zimislecel, donislecel) are administered directly into the portal vein and have been successful in controlling hyperglycemia in patients with previously treatment-limiting hypoglycemic episodes (20, 21).
Monitoring Type 1 Diabetes Treatment
The goals of diabetes treatment are to control hyperglycemia while minimizing hypoglycemic episodes, to relieve symptoms, and to prevent complications. Diabetes mellitus control can be monitored by measuring levels of:
Plasma glucose
HbA1C
Plasma fructosamine
Urine ketones (when symptomatic)
Goals for glycemic control for most people are (1):
HbA1C levels < 7% (< 53 mmol/mol)
Preprandial blood glucose between 80 and 130 mg/dL (4.4 and 7.2 mmol/L)
Peak postprandial (1 to 2 hours after beginning of the meal) blood glucose < 180 mg/dL (< 10 mmol/L)
With continuous glucose monitoring (CGM), 14-day time in range (TIR) > 70% (target blood glucose range 70 to 180 mg/mL [3.9 to 9.9 mmol/L])
These goals may be adjusted to be less strict for patients in whom strict glucose control may be inadvisable, such as (1):
Frail older patients
Patients with a short life expectancy
Patients who experience repeated episodes of hypoglycemia, especially those who do not develop symptoms of hypoglycemia (hypoglycemia unawareness)
Patients who cannot communicate the presence of hypoglycemia symptoms (eg, young children, patients with dementia)
Clinicians may also recommend stricter glycemic goals (eg HbA1C < 6.5%) in select patients if these goals can be achieved without hypoglycemia (1). Potential candidates for tighter glycemic control include:
Patients not being treated with medications that induce hypoglycemia
Patients who have had a shorter duration (< 10 years) of diabetes mellitus
Patients who have a long life expectancy
Patients who have no cardiovascular disease
Glucose levels are typically determined by home monitoring of capillary blood glucose (eg, from a fingerstick) or continuous glucose monitoring. Both of these monitoring modalities help patients adjust dietary intake and insulin dosing and help physicians recommend adjustments in the timing and doses of medications Most patients with type 1 diabetes benefit from testing at least 4 times a day (2). The frequency depends on blood glucose levels, the patient’s needs and abilities, and the complexity of the treatment regimen. More frequent self-monitoring is recommended when blood glucose levels are suboptimal or when there are changes in the medication regimen.
HbA1C levels measured in venous plasma are monitored every 3 months or, for patients with consistently good control, every 6 months.
Fingerstick glucose monitoring
Fingerstick glucose monitors measure capillary blood glucose. Many different glucose meters are available. Nearly all require test strips and a means for pricking the skin and obtaining a blood sample. Choice among devices is usually based on patient preferences for features such as time to results (usually 5 to 30 seconds), size of display panel (large screens may benefit patients with poor eyesight), voice readout (for those with visual impairment), smartphone app connectivity (3), and availability, affordability, and insurance coverage of test strips.
Continuous glucose monitoring
Continuous glucose monitoring (CGM) systems estimate capillary blood glucose from interstitial glucose detected by a subcutaneous sensor. They can either provide glucose measurements continuously (real-time CGM) or intermittently when scanned with a device (intermittently scanned CGM). CGMs provide real-time glucose data including an alarm to warn of hypoglycemia, hyperglycemia, or rapidly changing glucose levels.
Although CGMs have less stringent accuracy requirements than capillary blood glucose monitors, they allow users and clinicians to assess for patterns of hyperglycemia and hypoglycemia that are not identified with fingerstick glucose monitoring. Use of CGMs has been shown to increase patients' time in target range (TIR) and decrease HbA1C (4, 5, 6). Use of CGMs is recommended for all patients who are treated with intensive insulin therapy and can use the devices safely (7).
For patients with diabetes who use CGMs, TIR is defined as the percentage of time blood glucose measurement on CGM is within the target blood glucose range (70 to 180 mg/mL [3.9 to 9.9 mmol/L]) over 14 days. A 14-day TIR > 70% is associated with decreased risk of diabetes complications and is inversely correlated with HbA1C level.
To decrease risk of severe hypoglycemia (1, 8):
Time below glucose range < 70 mg/dL (< 3.9 mmol/L) should be < 4%
Time below glucose range < 54 mg/L (< 3.0 mmol/L) should be < 1%
As with all glycemic targets, the CGM target range should be individualized depending on age, comorbidities, and risk of hypoglycemia.
External CGM sensors can be used for up to 2 weeks or before they need to be replaced, while implantable systems may last for 1 year. Clinicians can review the recorded data to determine whether the patient is experiencing undetected hyperglycemia or hypoglycemia.
(Closed-loop systems that include a CGM and an insulin pump are discussed elsewhere.)
Hemoglobin A1C
HbA1C levels reflect glucose control over the preceding 3 months and hence assess control between physician visits (1). HbA1C should be assessed quarterly in patients with type 1 diabetes. For most patients, the goal HbA1C is < 7%; however, this goal should be individualized. Home testing kits are available but are used infrequently.
Control suggested by HbA1C values sometimes appears to differ from that suggested by daily glucose readings because of falsely elevated or normal HbA1C values (9). False elevations of HbA1C may occur with low red blood cell turnover (as occurs with iron, folate, or vitamin B12 deficiency anemia), high doses of aspirin, and high blood alcohol concentrations. Falsely normal HbA1C values (ie, values that are normal despite underlying hyperglycemia) occur with increased red blood cell turnover, as occurs with hemolytic anemias and hemoglobinopathies (eg, HbS disease, HbC disease), or during treatment of deficiency anemias. In patients with cirrhosis or chronic kidney disease stages 4 and 5, correlation between HbA1C and glycemic levels is poor, and HbA1C can be falsely decreased in these patients. Pregnancy also falsely decreases HbA1C values.
Fructosamine
Fructosamine, which is mostly glycosylated albumin but also comprises other glycosylated proteins, reflects glucose control in the previous 1 to 2 weeks. Fructosamine monitoring may be used during intensive treatment of diabetes and for patients with hemoglobin variants or high red blood cell turnover (which cause false HbA1C results) (1, 9).
Urine monitoring
Self-measurement of urine ketones is recommended for patients with type 1 diabetes if they experience symptoms, signs, or triggers of ketoacidosis, such as nausea or vomiting, abdominal pain, fever, cold or flu-like symptoms, especially in the setting of hyperglycemia (> 200 mg/dL [> 11.1 mmol/L]), or if they experience sustained hyperglycemia (> 250 to 300 mg/dL [> 13.9-16.7 mmol/L]) during glucose self-monitoring (1).
Urine glucose monitoring is inaccurate and not recommended.
Complications of Type 1 Diabetes
Most long-term complications that occur in patients with type 1 diabetes are the vascular neurologic, and immunologic complications of diabetes in general, but some are related to autoimmune comorbidities specific to type 1 diabetes. Screening recommendations exist for both general and specific complications.
Acute complications of type 1 diabetes and its treatment, including diabetic ketoacidosis and hypoglycemia and are discussed elsewhere.
For a more detailed discussion of specific complications, see Long-Term Complications of Diabetes Mellitus.
Long-term complications
Chronic hyperglycemia leads to complications that affect small vessels (microvascular), large vessels (macrovascular), or both.
Microvascular complications include retinopathy, nephropathy, and neuropathy. Neuropathy is a heterogeneous long-term complication, with multifactorial pathogenesis that includes toxic effects of hyperglycemia and advanced glycation end-products on nerves, and ischemia to nerves from microvascular disease.
Macrovascular complications include atherosclerosis of large vessels leading to angina pectoris and myocardial infarction, transient ischemic attacks and strokes, and peripheral artery disease.
Immune dysfunction is another major long-term complication.
Risk of complications can be decreased by strict control glycemic control and by management of hypertension and lipid levels. Specific measures for prevention of progression of complications once detected are described separately under Long-Term Complications.
Comorbidities specific to type 1 diabetes
Patients with type 1 diabetes are at risk for other autoimmune diseases. The most common of these are thyroid disease, celiac disease, and pernicious anemia (vitamin B12 deficiency); less commonly associated diseases include Addison disease, autoimmune liver disease, and myasthenia gravis (1).
Screening for complications of type 1 diabetes
Adults with type 1 diabetes should undergo the following screening for complications (2, 3, 4):
Retinopathy: Dilated and comprehensive eye examination within 5 years of diagnosis, and then every 1 to 2 years
Neuropathy and foot ulcers: Foot examination with pulses, reflexes, temperature or pinprick sensation, vibration, and monofilament testing) within 5 years of diagnosis, and then at least annually
Nephropathy: Spot urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) within 5 years of diagnosis, and then annually
Hypertension: Blood pressure measurement at every visit
Atherosclerotic cardiovascular disease: Lipid profile soon after diagnosis, then annually; additional screening depending on signs, symptoms, and additional risk factors
Heart failure: Consider measuring a natriuretic peptide
Peripheral artery disease: Consider ankle-brachial index if ≥ 65 years and any other microvascular disease, foot complications, or end-organ damage is present
Autoimmune thyroid disease: Thyroid function tests soon after diagnosis
Celiac disease: In the presence of diarrhea, malabsorption, or abdominal pain
Pernicious anemia: In the presence of peripheral neuropathy or unexplained anemia
Additional cardiovascular screening may include risk stratification, electrocardiography, or other testing. Screening for microvascular complications in children begins once the child has reached puberty or age 10 years (whichever is earlier) and 5 years after diagnosis.
Specific screening recommendations for children and adolescents with type 1 diabetes are similar.
Complications references
1. American Diabetes Association Professional Practice Committee. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S59-S85. doi:10.2337/dc25-S004
2. American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S207-S238. doi:10.2337/dc25-S010
3. American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S239-S251. doi:10.2337/dc25-S011
4. American Diabetes Association Professional Practice Committee. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S252-S265. doi:10.2337/dc25-S012
Key Points
Type 1 diabetes is caused by inadequate insulin production due to autoimmune-mediated destruction of pancreatic beta cells.
Diagnose by elevated fasting plasma glucose level and/or elevated hemoglobin A1C and/or elevated 2-hour value on oral glucose tolerance test.
Treat with insulin, glucose monitoring, and dietary management.
Perform regular screening for complications and comorbidities.
Microvascular complications include nephropathy, neuropathy, and retinopathy.
Macrovascular complications involve atherosclerosis resulting in coronary artery disease, transient ischemic attack or stroke, and peripheral arterial insufficiency.
Often, give renin-angiotensin-aldosterone system blockers (for proteinuria or hypertension), and statins (over age 40, or earlier if indicated).
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.
American Diabetes Association Professional Practice Committee. 1. Improving Care and Promoting Health in Populations: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(Supplement_1):S14-S26. doi:10.2337/dc25-S001
Drugs Mentioned In This Article
