Type 1 diabetes mellitus

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

It is important to note that different stages of life are heterogenous in their diabetes needs and challenges. For example, adolescence is associated with physiologic increases in insulin resistance and behavioral changes (including reduced impulse control), while very young children and older adults are more vulnerable to hypoglycemia.[1][48] These differences should be considered when developing individualized management plans.[1] Children and adolescents should be managed by an interprofessional pediatric diabetes team which understands the unique challenges for this population.[1]

Diabetes self-management education and support (DSMES) is an essential component of type 1 diabetes care.[72] The objective of DSMES is to provide those living with type 1 diabetes (and their caregivers, if applicable) with the knowledge, skills, and confidence to successfully self-manage their diabetes on a daily basis, thereby reducing the risk of acute and long-term complications while maintaining quality of life.[72] All patients should be advised to participate in developmentally and culturally appropriate DSMES to facilitate informed decision-making, self-care behaviors, problem-solving, and active collaboration with the healthcare team.[1] DSMES should be provided at diagnosis, annually and/or when treatment goals are not being met, when complicating factors develop (e.g., medical, functional, or psychosocial), and when transitions in life and care occur.[1] Both individual and group settings are recommended for the delivery of effective diabetes self-management education and support, as well as digital methods.[1][87][88]

Insulin replacement is the foundation of good glycemic control in type 1 diabetes. Attention should also be paid to lifestyle interventions such as diet and exercise. The limiting factor for tight glycemic control in type 1 diabetes is hypoglycemia. In the short term, insulin is life-saving because it prevents diabetic ketoacidosis (DKA), a potentially life-threatening condition. See Diabetic ketoacidosis.

Glycemic goals

The long-term goal of insulin treatment is the prevention of chronic complications by maintaining blood glucose levels as close to normal as possible. Generally, glycosylated hemoglobin (HbA1c) goals determine the aggressiveness of therapy, which is in turn individualized. The American Diabetes Association (ADA) recommends a target HbA1c goal of <7% (<53 mmol/mol) for most nonpregnant adults, adolescents, and children, provided they do not have significant or frequent hypoglycemia.[1] If using a continuous glucose monitoring (CGM) device, a parallel goal is >70% time in range (TIR; 70-180 mg/dL [3.9 to 10 mmol/L]) with time below range (<70 mg/dL [<3.9 mmol/L]) <4% and time <54 mg/dL (<3 mmol/L) <1%.[1][89] The International Society of Pediatric and Adolescent Diabetes (ISPAD) recommends that for preschoolers with type 1 diabetes, an alternative target of >50% of time in a tighter range (TITR; 70-140 mg/dL [3.9 to 7.8 mmol/L]) can be used.[90]

Less stringent goals (e.g., <7.5% to 8% [58-64 mmol/mol]) may be appropriate for very young children (who are often unable to recognize, articulate, and/or manage hypoglycemia), some older adults, people with a history of severe or frequent hypoglycemia or hypoglycemia unawareness, and those with advanced microvascular or macrovascular complications or comorbid conditions (or in other instances where the harms of stringent treatment outweigh the benefits).[1] For older adults with very poor or complex health, an approach focused on avoidance of hypoglycemia and symptomatic hyperglycemia may be more appropriate than relying on a glycemic goal approach.[1]

Conversely, some patients may have more stringent HbA1c goals (e.g., <6.5% [<48 mmol/mol]), where this can be achieved safely and without undue care burden, and if the clinician (in agreement with the patient) feels this is appropriate and could be beneficial.[1] Setting a glycemic goal during consultations has been shown to improve patient outcomes.[1]

Fructosamine and glycated albumin are alternative measures of chronic glycemia (both reflecting glycemia over the preceding 2-4 weeks) that may be useful for monitoring (but not diagnosing) glycemic control when HbA1c testing is unsuitable or unreliable due to coexisting conditions (e.g., homozygous hemoglobin variants such as sickle cell anemia).[1] Fructosamine reflects total glycated serum proteins (mostly albumin), whereas glycated albumin assays reflect the proportion of total albumin that is glycated.[1] Both show high correlation in people with diabetes, and have been linked to long-term diabetes complications.[1]

Initiating insulin

Intensive insulin replacement should be started as soon as possible after diagnosis.[91] Although intensive therapy at any time in type 1 diabetes is beneficial, earlier implementation is associated with greater reduction in kidney and cardiovascular complications.[92] Unlike older regimens that used nonphysiologic insulin dosing, intensive insulin therapy aims to mimic physiologic insulin release by combining basal insulin with bolus dosing at mealtimes (prandial insulin). Both continuous infusion with an insulin pump and a regimen of multiple daily injections (MDI) can provide this, with the choice based on patient interest and self-management skills, cost, and physician preference.[1][93] [ ]

In general, individuals with type 1 diabetes require approximately 30% to 50% of their daily insulin as basal and the remainder as prandial (mealtime) boluses. This proportion depends on several factors, including carbohydrate consumption, age, pregnancy status, and puberty stage.[1] Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1.0 units/kg/day.[1] A starting dose of 0.5 units/kg/day is usually appropriate for metabolically stable adults.[1] Higher doses are required during pregnancy, puberty, and illness.[1]

Blood glucose monitoring (BGM; previously known as self-monitoring of blood glucose) and/or continuous glucose monitoring (CGM) allow patients and physicians to evaluate response to therapy, and to assess whether glycemic targets are being safely achieved.[1] Insulin doses can be adjusted every 2-3 days to maintain target blood glucose. To achieve an HbA1c <7% (53 mmol/mol), the pre-meal blood glucose goal should be 80-130 mg/dL (4.4 to 7.2 mmol/L) and the post-meal blood glucose goal (1-2 hours after starting the meal) should be <180 mg/dL (<10.0 mmol/L).[1]

The ADA recommends simplifying complex treatment plans (especially insulin) in older people to reduce the risk of hypoglycemia, polypharmacy, and treatment burden, if this can be achieved within the individualized HbA1c target.[1] In older adults, overtreatment of diabetes is common, and steps should be taken to avoid and recognize this.[1]

MDI insulin regimens

Using a combination of long-acting insulin analogs (insulin glargine or insulin degludec) or intermediate-acting insulin (insulin NPH [Neutral Protamine Hagedorn]; also known as isophane insulin) for basal dosing, and rapid- and ultra rapid-acting insulin analogs (insulin lispro, insulin aspart, or insulin glulisine), inhaled insulin, or short-acting insulin (regular/human insulin) for bolus dosing, MDI regimens can be designed based on physician and patient preference and modified based on BGM or CGM data.

Insulin analogs are considered the insulins of choice for both basal and prandial dosing.[72] They may provide the benefit of increased flexibility of lifestyle and less hypoglycemia and weight gain compared with human insulins.[1][94] The preferred regimen is to use a long-acting insulin analog for basal insulin plus a rapid- or ultra-rapid-acting insulin analog (or inhaled insulin) for prandial dosing. This mimics human physiology as closely as possible.[72] Two injectable ultra-rapid-acting analog insulin formulations (faster-acting insulin aspart and ultra-rapid insulin lispro) are also available that contain excipients which accelerate absorption and provide more activity in the first portion of their profile compared with the other rapid-acting analogs.[1] One systematic review and meta-analysis that assessed the efficacy and safety of the ultra-rapid-acting insulins in adults with type 1 diabetes found them to be as efficacious and safe as rapid-acting insulins, with a favorable effect solely on postprandial glucose control.[95] These newer formulations may cause less hypoglycemia while improving postprandial glucose excursions and administration flexibility (in relation to prandial intake) compared with rapid-acting analogs.[1]

The cost of insulin analogs is a barrier for some people, while others do not wish to inject multiple times per day.[96][97] [ ] In these cases, subcutaneous regimens of short-acting (regular/human) insulin and NPH insulin, or premixed insulin, with BGM as frequently as feasible, may be used at a cost of higher glucose variability with higher risk of hypoglycemia and less flexibility of lifestyle.[72] Biosimilars of analog insulin may be available in some countries at a lower cost, making them more affordable.

The timing of basal insulin in MDI regimens should be based on both physician and patient preference. It is important that the natural profile of insulin secretion in the body is replicated by the use of basal insulin. The following should be considered when deciding on dose:

Insulin NPH is typically given twice daily
Insulin glargine is usually given once daily. It is important to take it at the same time each day, preferably at night. A morning dose may be preferable if a patient is anxious about nighttime hypoglycemia or if patient preference means this will help improve adherence. However, clinical experience, supported by a small study, suggests that insulin glargine may not last for 24 hours in some patients with type 1 diabetes mellitus and may therefore need to be given twice daily for optimum basal coverage.[98] Some patients take insulin glargine once daily at night and cover the tail end of the 24-hour period with extra rapid-acting insulin in the evening. Insulin glargine is available in a standard concentration (U-100 strength) or a more concentrated formulation (U-300 strength); the latter prolongs its duration of action and further smooths its profile. The U-300 strength has little peak effect and may reduce hурοglyсеmiа in individuals with type 1 ԁiabetеѕ.[1]
Insulin degludec is longer acting than insulin glargine with a smaller peak effect.[70] It can be given once daily in the morning or evening or any other time of the day. For consistency, this should preferably be delivered at the same time every day.

Injectable inѕuliո is available in prefilled disposable pens, reusable pens with disposable cartridges, or in vials. Insulin pens offer greater convenience and better dosing accuracy compared with vials and syringes.[99] "Smart" or "connected" pens offer additional benefits like dose logging, insulin calculators, temperature monitoring, reminders, and sharing features via smartphone connectivity, but these come at a higher cost and robust data on their impact on clinical endpoints are lacking.[100] Regardless of whether using pens or vials, the shortest available needle (e.g., 4 or 5 mm for pens) is recommended to minimize discomfort, tissue damage, and the risk of intramuscular injection.[101]

Inhaled human insulin may be used as an alternative to subcutaneous rapid-acting insulin analogs or short-acting insulin (regular/human insulin) for prandial dosing; it has a more rapid peak and shorter duration of action (1.5 to 3 hours) compared with rapid-acting analogs and can be useful for people with an aversion to injections.[1][102] One study found that its use at mealtimes improved prandial glucose control compared with injectable rapid-acting insulin aspart, without additional hypoglycemia or weight gain.[103] However, data on its efficacy and safety remain fairly limited, and one 2-year follow-up study of patients previously treated with inhaled insulin could not exclude an increased risk of lung cancer-related mortality.[104] Inhaled insulin is contraindicated in individuals with chronic lung diseases (including asthma and COPD), and is not recommended in smokers or recent ex-smokers (within the past 6 months).[1] Measurement of forced expiratory volume is required prior to and after starting therapy.[1]

For those on MDI, the simplest approach to covering mealtime insulin requirements is to suggest a range of doses, such as 4 units for a small meal, 6 units for a medium-sized meal, and 8 units for a larger meal. However, for greater flexibility of carbohydrate content of meals, pre-meal insulin should be calculated based on the estimated amount of carbohydrate in the meal and the patient's individual insulin-to-carbohydrate ratio.[1] A simple starting approach is to use 1 unit of mealtime insulin for every 15 g of carbohydrate in the meal. Patients can use the carbohydrate content per serving listed on food packaging to assess the number of grams in their anticipated meal, but carbohydrate counting is best learned with the help of a nutritionist. Using a food diary and 2-hour postprandial blood glucose measurements, the insulin-to-carbohydrate ratio can be adjusted. Estimates of the fat and protein content of meals may be incorporated into prandial dosing for added benefit.[1]

A correction dose may be added to the bolus insulin based on the pre-meal blood glucose level. Correction dosing may be calculated as follows when the patient's total daily dose of insulin (TDD) and food intake is stable: 1800/TDD = the predicted point drop in blood glucose per unit of rapid-acting insulin. For example, if the TDD is 40 units of insulin, 1800/40 = 45 point drop per unit of insulin.

Example of correction dosing based on pre-meal glucose and above calculation:

45-90 mg/dL (2.2 to 4.9 mmol/L): subtract 1 unit from mealtime insulin
91-135 mg/dL (5.0 to 7.4 mmol/L): add 0 units of correction insulin
136-180 mg/dL (7.5 to 9.9 mmol/L): add 1 unit of correction insulin
181-225 mg/dL (9.9 to 12.4 mmol/L): add 2 units of correction insulin
226-270 mg/dL (12.4 to 14.5 mmol/L): add 3 units of correction insulin
271-315 mg/dL (14.5 to 17.3 mmol/L): add 4 units of correction insulin
316-360 mg/dL (17.4 to 19.8 mmol/L): add 5 units of correction insulin
361-405 mg/dL (19.8 to 22.3 mmol/L): add 6 units of correction insulin
>405 mg/dL (>22.3 mmol/L): add 7 units of correction insulin; call healthcare provider.

The number used to calculate the correction dose may be as low as 1500 or as high as 2200. There are no specific guidelines to determine this number. In general, a lower number should be used for insulin-resistant patients with obesity, and a higher number should be used for lean, insulin-sensitive patients.

This correction dose can be added to the patient's mealtime insulin requirement (whether based on general meal size or carbohydrate counting) and given as the total bolus dose. Most insulin pumps use a wizard to automatically calculate the bolus insulin dose, based on user-entered carbohydrate count, and BGM or CGM based on glucose value.[105]

Insulin pumps and automated insulin delivery (AID) systems

CGM systems and insulin pumps have shown improvement in glycemic control and a reduction in the risk of severe hypoglycemia compared with capillary BGM and MDI in patients with type 1 diabetes.[70] The insulin pump uses a subcutaneous insulin injection port which is changed every 2-3 days. Using rapid-acting insulin, it provides a basal rate of insulin and delivers mealtime bolus dosing. It can be used with a CGM system (referred to as sensor-augmented pump therapy), allowing users to see their blood glucose levels in real-time and make insulin adjustments accordingly. The sensor-augmented pump requires manual input from the user for insulin boluses and basal rates. Insulin pump therapy is associated with improved glycemic control and lower risk of hypoglycemia, including in children, adolescents, and young adults.[106][107][108][109] However, the management burden of diabetes does not necessarily decrease as frequent user input is necessary.[70] Thus emerged the concept of glucose responsive AID systems, in which data from CGM can inform and allow adjustment of insulin delivery, including adjusting insulin rates for both hypoglycemia and hyperglycemia.[70] AID systems (also called closed loop or artificial pancreas systems) include three components - an insulin pump that continuously delivers rapid-acting insulin, a continuous glucose sensor that measures interstitial fluid glucose at frequent intervals, and a control algorithm that continuously adjusts insulin delivery (this computerized algorithm resides in the insulin pump or a smartphone application or handheld device).[70] All AID systems that are available today are referred to as “hybrid” closed loop (HCL) systems, as users are required to manually enter prandial insulin boluses and signal exercise but insulin delivery is automated at nighttime and between meals.[70] User input is variable depending on the device. In both children and adults, AID systems have been found to be superior to insulin pump therapy, sensor-augmented pumps, and MDI in terms of time in target glucose range, hypoglycemia (including nocturnal hypoglycemia), and HbA1c levels.[110][111][112][113][114][115][116][117][118][119][120] Use of AID technology has also been shown to improve quality of life and psychological well-being in patients with type 1 diabetes and their caregivers.[121][122][123]

Both pediatric and adult guidelines recommend that AID systems should be offered to all patients with type 1 diabetes to improve glycemic control, providing they (or their caregivers) are able to use them safely.[1][48][124]

Some models come with smartphone apps that can be used to monitor glucose and insulin dosing. Patients who have the most success in using AID systems are those who are technically capable of using insulin pump therapy and those with realistic expectations of the systems, given their limitations.[125] Healthcare professionals should have knowledge of the various AID systems available and their differences, or be able to direct people toward further information or support.[125][Figure caption and citation for the preceding image starts]: The continuous glucose monitor senses interstitial glucose concentrations and sends the information via Bluetooth to a control algorithm hosted on an insulin pump (or smartphone). The algorithm calculates the amount of insulin required, and the insulin pump delivers rapid acting insulin subcutaneouslySubramanian S, et al. BMJ 2024; 384: e075681; used with permission [Citation ends]. com.bmj.content.model.Caption@1bdd4558

Adjusting treatment regimen in response to hypoglycemia

Hypoglycemia is the most common and potentially most serious side effect of insulin therapy, as it can lead to decreased quality of life, confusion, seizures, and coma.[1] Hypoglycemia history should be reviewed at each visit, and efforts made to determine contributing factors, and the ability of the patient to recognize and treat episodes appropriately.[1] All patients should be screened for hypoglycemia unawareness at least annually.[1] The ADA defines three levels of hypoglycemia, all of which are considered clinically important:[1]

Level 1: glucose ≥54 mg/dL but <70 mg/dL (≥3.0 mmol/L but <3.9 mmol/L)
Level 2: glucose <54 mg/dL (<3.0 mmol/L)
Level 3 (severe hypoglycemia): any low blood glucose level leading to cognitive and/or physical impairment requiring assistance from another person for recovery.

Levels 2 and 3 require immediate correction of low blood glucose. Prompt treatment of level 1 is also recommended to avoid progression to more severe hypoglycemia.[1]

For those at high risk of hypoglycemia, or when one or more episodes of level 2 or 3 hypoglycemia occur, the treatment plan and HbA1c goal should be reevaluated.[1] Use of CGM is recommended by the ADA for those at high risk of hypoglycemia, and also for older adults with type 1 diabetes to reduce hypoglycemia.[1] It further advises consideration of AID systems (and other advanced insulin delivery devices) for reduction of hypoglycemia risk in older adults.[1]

See Diabetic hypoglycemia for further information.

Blood glucose monitoring

Most patients on intensive insulin should be encouraged to use BGM and/or CGM to obtain blood glucose values before meals and snacks, at bedtime, occasionally after meals, before, during, and after exercising, when they suspect hypo- or hyperglycemia and after treating hypoglycemia (to ensure adequate treatment), and before (and during) any task during which hypoglycemia could have particularly dangerous consequences (e.g., driving).[1] Many patients using BGM will need to check their blood glucose 6 to 10 times daily to ensure good glycemic control.[1]

CGM has an increasingly important role in the management of type 1 diabetes.[1] CGM devices measure interstitial glucose, which generally correlates well with plasma glucose unless levels are rapidly fluctuating.[1] CGM devices may provide real-time data or need intermittent scanning to obtain glucose data.[1] Patients using personal CGM devices need to change the sensor after every 6-14 days.[48] An implantable CGM device that requires sensor change by a medical provider every 3-6 months is also available, but is used less often.[126]

Professional CGM devices (owned by the clinician, and applied in the clinic) may help physicians adjust insulin doses by identifying patterns of hypo- and hyperglycemia.[1] CGM devices may provide real-time (i.e., continuous) data or need intermittent scanning to obtain glucose data.[1][127] Evidence supports use of CGM in both adults and children.[1][128][129][130][131][132][133][134][135] Systematic review and meta-analysis data from studies in type 1 diabetes show that compared with BGM, CGM can improve glycemic control, and can lead to longer TIR, reducing HbA1c and reducing severe hypoglycemia.[127][136][137][138][139][140][141][142] One large retrospective study on hospitalizations for acute diabetes complications demonstrated that use of CGM was associated with a significantly lower incidence of admissions for DKA and diabetes-related coma, although there is some discrepancy in the literature regarding the impact of CGM on DKA incidence.[139][140][143] Use of CGM has also been associated with improved quality of life in people with type 1 diabetes and their caregivers.[144][145] Furthermore, studies have shown that CGM use is cost-effective as it lowers the indirect costs of diabetes.[146] However, various factors can affect the accuracy of CGM, such as sensor interference caused by the use of drugs and substances including acetaminophen, ascorbic acid (vitamin C), hydroxyurea, mannitol, and sorbitol.[1] It is therefore important to educate CGM users on potential interfering factors, and to routinely review their drug history to identify such substances.[1] Patients using CGM need to have access to BGM testing for safety reasons, including if there is suspicion that the CGM is inaccurate.[1][124]

Although CGM is generally considered less burdensome for patients, choice of device should be based on individual circumstances, desires, costs, and needs.[1] People with diabetes should have uninterrupted access to their supplies to minimize gaps in CGM.[1]

Specific recommendations for the use of CGM vary slightly between guidelines. The ADA notes that the initiation of CGM early in the treatment of type 1 diabetes can be beneficial, and should therefore be offered early, even at diagnosis.[1] It recommends that CGM should be offered to all adults and young people with diabetes on intensive insulin therapy, and to adults on basal insulin.[1] It also recommends CGM for older adults with type 1 diabetes to reduce hypoglycemia.[1] The Endocrine Society recommends CGM, rather than BGM by fingerstick, for patients with type 1 diabetes receiving MDI.[124] The American Association of Clinical Endocrinology (AACE) recommends CGM for all individuals with diabetes who are treated with intensive insulin therapy, those who have problematic hypoglycemia, and for children/adolescents with type 1 diabetes, caveating that structured BGM should be used in people who have limited success with, or are unable or unwilling to use, CGM.[147]

The ADA recommends continuing CGM use during hospital admissions (if clinically appropriate, and if this can be done in line with institutional protocol and the resources and training are available), with confirmatory blood glucose measurements taken for insulin dosing and hypoglycemia assessment.[1]

Diet and exercise

Individualized nutrition advice should be based on personal, cultural, and religious preferences (including providing education and support to accommodate religious fasting), health literacy and numeracy, access to healthy food choices, food security, and willingness and ability to make behavioral changes.[1] It should also address barriers to change. All patients with diabetes should receive individualized medical nutrition therapy, preferably provided by a registered dietitian who is experienced in providing this type of therapy to diabetes patients.[148]

There is no standardized dietary advice that is suitable for all individuals with diabetes.[1] A variety of eating patterns are acceptable, and healthcare professionals should emphasize the core principles common among these: inclusion of nonstarchy vegetables, whole fruits, legumes, lean proteins, whole grains, nuts, seeds, and low-fat dairy products or nondairy alternatives; and minimizing consumption of red meat, sugar-sweetened beverages, candy, refined grains, and processed and ultra-processed foods.[1] The ADA also recommends emphasizing minimally processed, nutrient-dense, high-fiber sources of carbohydrate (with a minimum of 14 g of fiber/1000 kcal).[1] Regular adequate fiber intake has been associated with lower all-cause mortality in diabetes.[1]

Carbohydrate counting or consistent carbohydrate intake with respect to time and amount may improve glycemic control. One systematic review and meta-analysis found that in adults with moderately controlled type 1 diabetes, a low-glycemic index dietary pattern resulted in small but important improvements in established targets of glycemic control, blood lipids, adiposity, blood pressure, and inflammation, beyond concurrent treatment with insulin.[149] Rapid-acting insulins and insulin pumps may make timing of meals less crucial than in the past, but regular meals are still important.

Evidence for dietary patterns in children and adolescents with type 1 diabetes is limited but what is available suggests that a balanced dietary pattern with increased fiber and reduced ultra-processed carbohydrates is acceptable.[150] Dietary patterns (like the Mediterranean-style or dietary approaches to stop hypertension [DASH]) with a focus on plant-based foods, lean protein, mono- and polyunsaturated fats, and low-fat dairy products (while limiting processed foods and sugary drinks) are linked to improved long-term health outcomes.[150] There is some limited evidence for restricting carbohydrates to improve glycemic and metabolic profiles in youth with type 1 diabetes, but there are also safety concerns with this approach: adverse effects on growth, bone health, and nutrition, and importantly, increased risk of disordered eating (which is already increased in type 1 diabetes).[150] Low- and very low-carbohydrate diets in children and adolescents with type 1 diabetes are not recommended by the International Society for Pediatric and Adolescent Diabetes or the ADA for generalized use, and the same conclusion was drawn from a 2023 review by the American Academy of Paediatrics.[1][150] If a low- or very-low carbohydrate approach is used, this should only be done with close specialist supervision and monitoring.[150]

One meta-analysis found an overall small beneficial effect of physical activity on glycemic control in people with type 1 diabetes.[151] However, the relationship between type 1 diabetes and physical activity remains poorly understood. The ADA recommends that adults with diabetes should engage in ≥150 minutes/week of moderate- to vigorous-intensity aerobic exercise spread over at least 3 days per week, with no more than 2 consecutive days without exercise.[1] For those who are younger and more physically fit, shorter durations (at least 75 minutes/week) of vigorous-intensity exercise or interval training may be sufficient.[1] Adults should also participate in 2-3 sessions of resistance training per week on nonconsecutive days.[1] The ADA also advises 2-3 sessions of flexibility and balance training each week for older adults.[1] Children and adolescents with diabetes should aim for at least 60 minutes of moderate- to vigorous-intensity aerobic activity daily and vigorous muscle-strengthening and bone-strengthening activities at least 3 days per week.[1]

Patients with type 1 diabetes can safely exercise and manage their glucose levels.[152] Preexercise carbohydrate intake and insulin doses can be effectively modified to avoid hypoglycemia during exercise and sports.[153] Hypoglycemia can occur up to 24 hours after exercise and may require reducing insulin dosage on days of planned exercise.[1][48] Blood glucose should be checked before, during, and after exercise to monitor for exercise-related hypo- and hyperglycemia, so that these can be appropriately managed (with treatment easily accessible).[1] A carbohydrate snack may need to be given at the start of exercise if the blood sugar is <90 mg/dL (<5 mmol/L).[1]

Clinical judgment should be used in determining whether to screen asymptomatic individuals for coronary artery disease prior to recommending an exercise program.[1] It may be suitable to encourage high-risk patients to start with short periods of low-intensity exercise and slowly increase the intensity and duration as tolerated.[1]

The following should be assessed prior to starting an exercise program: age; physical condition; blood pressure; and presence or absence of autonomic neuropathy or peripheral neuropathy, preproliferative or proliferative retinopathy, or macular edema.[1] Vigorous exercise may be contraindicated with proliferative or severe preproliferative diabetic retinopathy.[1] Nonweight-bearing exercise may be advisable in some patients with severe peripheral neuropathy (e.g., those with an open sore or foot injury).[1] Older adults may require a tailored approach to exercise depending on their functional status and the presence of frailty.[1]

Prolonged sitting should be interrupted every 30 minutes with short bouts of physical activity for blood glucose benefits.[1]

Goal not met

If glycemic control is not adequate, the patient's nutrition, exercise, and insulin regimen must be re-examined. Children and adolescents may have erratic eating patterns or snack frequently without insulin bolus. Consultation with a nutritionist is an invaluable part of the treatment approach, as patients can learn how to count carbohydrates, fats, and proteins, and adjust their pre-meal insulin to allow for flexibility in meal content and activity.[1] Consistent hyperglycemia may require an increase in basal insulin. Preprandial and postprandial hyperglycemia may be due to inadequate insulin coverage for the most recent meal, and may be addressed by considering carbohydrate content of meals, the patient's assessment of their carbohydrate intake, and subsequent pre-meal insulin dosing. If a patient is getting regular insulin, replacing it with rapid-acting insulin may reduce postprandial glucose excursions.

Episodes of hypoglycemia occur with different frequency among patients. Patients should check a 3 a.m. blood glucose if there is concern about risk of nocturnal hypoglycemia. Nocturnal hypoglycemia may result in rebound hyperglycemia in the morning. The dose of basal insulin or basal insulin rate at night may be decreased to prevent nocturnal hypoglycemia. A bedtime snack is not an effective way of decreasing the risk.[154] Alcohol may cause acute hypoglycemia, and both alcohol and exercise can cause delayed hypoglycemia (by up to 24 hours).[1][48]

Conditions contributing to unstable diabetes and that coexist commonly with type 1 diabetes include celiac disease, thyroid disease, and psychologic disorders such as diabetes distress and depression.[1][48] Thyroid disease should be screened for soon after diagnosis (once clinically stable) and thereafter at repeated intervals if clinically indicated.[1][48] In children and adolescents, celiac disease should also be screened for shortly after diagnosis.[1][48] Adults with type 1 diabetes should be screened for celiac disease in the presence of gastrointestinal symptoms (e.g., diarrhoea, malabsorption, and abdominal pain), signs (e.g., osteoporosis, vitamin deficiencies, and iron deficiency anemia), laboratory manifestations, or clinical suspicion.[1] Increased clinical suspicion should also prompt screening for other autoimmune conditions associated with type 1 diabetes, such as pernicious anemia, autoimmune liver disease, primary adrenal insufficiency (Addison disease), vitiligo, collagen vascular diseases, and myasthenia gravis. Measurement of vitamin B12 levels should be considered for people with type 1 diabetes and peripheral neuropathy or unexplained anemia.[1] See Monitoring.

Adolescence

Adolescence is a common time for deterioration in glycemic control: data from the US Type 1 Diabetes Exchange shows a clear decline in glycemic control between ages 10 and 20 years, findings which are not unique to the US.[48] Pubertal physiologic changes culminate in increased insulin resistance (and thus increased insulin requirements), and behavioral changes during adolescence (e.g., reduced impulse control, increased risk-taking, desire for increased independence) can impact on treatment adherence and diabetes self-management.[48]

There also appears to be an increased burden of coexisting mental health problems in adolescents, and body habitus changes during puberty may be associated with reduced self-esteem, insulin-avoidance for weight loss, and increased risk of disordered eating.[48] Regular screening for, and prompt management of, psychosocial problems is important, and ISPAD advises that in some adolescents, mental health needs may supersede other clinical needs for a short time.[48]

A focus on family cohesion and support is advised, and there is substantial evidence showing that outcomes in adolescents with type 1 diabetes are linked to ongoing parental engagement.[48] Parenting styles that are compassionate and supportive with clear expectations are linked to improved diabetes-outcomes, including improved adherence and better glycemic control.[48] Allowing for developmentally appropriate levels of autonomy is beneficial, but premature transfer of sole care to the adolescent is associated with worse outcomes.[1][48]

ISPAD recommends directing youth toward local and online peer support at diagnosis, and it advises the use of psychologist-facilitated motivational interviewing to help optimize outcomes in this age-group.[48] School performance and peer issues (and their impacts on diabetes self-management) should be considered: peer support in school is linked to better outcomes, and telemedicine in school can be considered for additional support where needed.[1][48]

The transition period from pediatric to adult care is associated with worsening glycemic control.[1] The ADA and ISPAD both emphasize that preparation for this transition is best started early in adolescence, with the timing of transition preferably individualized in agreement with the patient and their family.[1][48] Interprofessional support during transition is recommended, including the use of transition care coordinators and transition tools.[1][48]

Noninsulin treatments

Pramlintide is a synthetic analog of human amylin, a protein that is co-secreted with insulin by pancreatic beta cells. It reduces postprandial glucose increases by prolonging gastric emptying time, reducing postprandial glucagon secretion, and reducing food intake through centrally mediated appetite suppression.[155] It is approved for use as an adjunctive treatment (alongside insulin) in adults with type 1 diabetes and postprandial hyperglycemia that cannot be controlled with pre-meal insulin alone.[1][155] For example, it may be useful in a patient with high postprandial glucose, but who develops late hypoglycemia when pre-meal insulin is increased. It may be given as an injection before each meal to get more stable glycemic control. At initiation, the current pre-meal insulin dose should be reduced by about 50% to avoid hypoglycemia, and then titrated up. Pramlintide should not be used in a patient with gastroparesis. The most common side effect is nausea, occurring in 28% to 48% of patients.[155]

Pregnancy

Individuals with diabetes are at a higher risk of miscarriage and having infants with major congenital malformations than the general population.[156] Preconception diabetes care reduces this risk.[157] Preconception counseling should, therefore, be incorporated in every routine diabetes clinic visit for all individuals of childbearing potential, starting at onset of puberty.[1][48][158][159][160] For pregnancy intent screening to be effective, individuals with diabetes should be counseled about the benefits of preconception care.[160]

The use of an appropriate preconception program for young adolescents (e.g., READY-girls) has been demonstrated to have lasting benefits.[48] Counseling should include discussion of family planning, and the use of an effective method of contraception is recommended until the individual’s treatment regimen and HbA1c are optimized for pregnancy.[1]

The ADA recommends that HbA1c should be <6.5% (<48 mmol/mol) before conception if this can be achieved without hypoglycemia, as this has been shown to reduce fetal and maternal risks.[1] An interprofessional approach to preconception care (including specialists in endocrinology, maternal-fetal medicine and diabetes care and education, and a registered dietitian) should ideally be implemented for those planning a pregnancy.[1] Nutrition counseling, endorsing a balance of macronutrients, and extra focus on physical activity and diabetes self-care education is also recommended.[1]

Individuals should also be evaluated before pregnancy for diabetes complications and comorbidities, including retinopathy, nephropathy, neuropathy, and possible cardiovascular disease, which may worsen during or complicate pregnancy.[1]

Retinopathy is of particular concern, as for some patients, particularly those with proliferative rеtiոоpаthy, it may worsen during рrеgոаncy. This is related to the often rapid intensification of antihyperglycemic therapy, as well as рrеgոanϲy-related vascular, volume, and hormonal changes.[1] Individuals with type 1 diabetes should be counseled appropriately and have an eye exam before pregnancy and in the first trimester, and then be monitored every trimester and for 1 year postpartum as indicated by the degree of retinopathy and as recommended by the eye care healthcare professional.[1]

Most studies have failed to demonstrate permanent deterioration in renal function associated with pregnancy in women with mild-to-moderate diabetic nephropathy.[161][162] However, progression to end-stage renal disease has been reported in women with serum creatinine levels exceeding 1.5 mg/dL or severe proteinuria (more than 3 g per 24 hours) at baseline.[159] Women with preexisting diabetic nephropathy are at significantly higher risk for several adverse obstetric complications, including hypertensive disorders, uteroplacental insufficiency, and iatrogenic preterm birth because of worsening renal function.[159] Before becoming pregnant, a baseline evaluation of renal function by serum creatinine and assessment of urinary protein excretion (urine protein-to-creatinine ratio or 24-hour protein excretion) are recommended, with follow-up measurements at regular intervals throughout pregnancy.[159] If a 24-hour collection for creatinine clearance has not been done in the year before pregnancy, it is common for this assessment to be done early in pregnancy to establish a baseline.[159]

Drugs should be reviewed and potentially teratogenic drugs discontinued. In particular, ACE inhibitors and angiotensin-II receptor antagonists should be discontinued preconception (and avoided in individuals of childbearing potential not using reliable contraception) or as soon as possible in the first trimester.[1] Hypertension should be treated with agents considered safe in pregnancy.[1] These include methyldopa, nifedipine, labetalol, and clonidine.[1] Atenolol is not recommended, but other beta-blockers may be used if necessary.[1] Diuretic use during pregnancy is generally not recommended, although it may be used safely when prescribed at lower doses for individuals in certain circumstances (e.g., chronic kidney disease and reduced glomerular filtration rate.[1]

In pregnant women with diabetes and chronic hypertension, a blood pressure threshold of 140/90 mmHg for initiation or titration of therapy is associated with better pregnancy outcomes than reserving treatment for severe hypertension.[1] There are limited data on the optimal lower limit, but the ADA recommends a blood pressure goal of 110-135/85 mmHg and advises that therapy should be deintensified if blood pressure is <90/60 mmHg.[1]

In individuals with type 2 diabetes on a glucagon-like peptide-1 (GLP-1) receptor agonist, the Endocrine Society suggests ideally discontinuing this treatment and actively managing glycemia before conception, rather than discontinuation of the GLP-1 receptor agonist between the start of pregnancy and the end of the first trimester.[160] Sudden discontinuation of a GLP-1 receptor agonist may cause hyperglycemia and weight gain, which increases the risk for congenital malformations and spontaneous abortion.

The ADA recommends that in most circumstances, nonstatin lipid-lowering drugs (e.g., bempedoic acid, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, fibrates) should be stopped prior to conception or at the first pregnancy visit, and avoided in sexually active individuals of childbearing potential who are not using reliable contraception.[1] However, continuation of statins can be considered in women at high-risk, such as those with a history of atherosclerotic cardiovascular disease or familial hypercholesterolemia, as part of a shared decision-making process between patients and their healthcare team.[1] Hydrophilic statins, such as pravastatin, may be associated with less fetal harm than lipophilic statins.[1] The Food and Drug Administration (FDA) takes a similar stance, recommending that individuals should be considered on an individual basis, particularly those at very high risk for cardiovascular events during pregnancy.[163]

In addition to the increased risk of miscarriage and congenital malformations, specific risks of pregnancy in patients with diabetes include macrosomia, neonatal respiratory distress syndrome, and preeclampsia.[1][159] Euglycemia or near-euglycemia reduces the risk of complications.[1][159] Antepartum fetal surveillance is routinely used to monitor for complications and assess the risk of fetal death in pregnant individuals with diabetes.[164] Surveillance techniques in clinical use include maternal perception of fetal movement, contraction stress test (CST), nonstress test (NST), biophysical profile (BPP), modified BPP, and umbilical artery Doppler velocimetry. The American College of Obstetricians and Gynecologists (ACOG) advises that surveillance can be appropriately initiated at 32 weeks gestation (or later) in most at-risk patients (but may be used earlier if indicated and if delivery would be considered for perinatal benefit).[164]

Daily low-dose aspirin is recommended in pregnant individuals with type 1 diabetes to reduce the risk of preeclampsia: the ADA recommends starting this treatment at 12-16 weeks’ gestation; similarly, ACOG recommends starting treatment between 12 and 28 weeks’ gestation, but ideally before 16 weeks.[1][159] Once started, it should be taken until delivery.[159] See Preeclampsia.

Individuals with diabetes have an increased risk of having infants with neural tube defects compared with the general population and, as for those without diabetes, should take a folic acid supplement prior to and during pregnancy.[165]

Insulin therapy

Intensive insulin should be administered for the management of type 1 diabetes in pregnancy, either via continuous infusion with an insulin pump or in a regimen of MDI.[1][159] There are few data comparing outcomes for insulin pump versus MDI regimens for pregnant individuals; however, one randomized controlled trial reported better glycemic outcomes with use of MDI.[166][167] [ ] Owing to the complexity of insulin management during pregnancy, referral to a specialist center that can offer multidisciplinary care is desirable.[1]

Commonly used insulins during pregnancy include insulin NPH, regular/human insulin, and the rapid-acting analogs insulin lispro and insulin aspart.[168] Limited evidence suggests that insulin aspart and insulin lispro may be associated with a reduced risk of hypoglycemia and improved glycemic control compared with regular/human insulin.[169] There are no large randomized trials supporting the safety of insulin glargine in pregnancy.[170] However, it has been safely used in many patients.[159] It should be considered second-line to insulin NPH for basal insulin dosing during pregnancy because there are fewer long-term safety monitoring data. There are limited data regarding the use of insulin degludec during pregnancy; however, one randomized controlled trial of pregnant women with type 1 diabetes (EXPECT) compared its efficacy and safety with insulin detemir (a long-acting insulin analog, production of which has now been discontinued) and found it to be noninferior.[171]

Use of CGM during pregnancy can help to improve glycemic control and neonatal outcomes.[1][172][173] The use of HCL systems has shown promise for the management of type 1 diabetes in pregnant women, but currently no HCL pump in the US has FDA approval for use in pregnancy.[174][175] There are few data comparing outcomes for insulin pump versus MDI regimens for pregnant individuals; however, one randomized controlled trial reported better glycemic outcomes with use of MDI.[166][167] [ ] A patient on an insulin pump and CGM should continue using these devices but switch to manual mode during pregnancy because HCL systems are not designed for the very tight glycemic control that is required. Patients well controlled on MDI are usually not switched to an insulin pump due to fear of worsening of glycemic control during the transition period. However, those with poor diabetes control on MDI may be candidates for insulin pump initiation during pregnancy.[159]

There may be increased sensitivity to insulin in early pregnancy, resulting in increased risk of hypoglycemia.[1] By about 16 weeks of gestation, insulin resistance starts increasing, rising until around week 36, often resulting in a doubling of the daily insulin requirements compared with prepregnancy.[1] Insulin resistance then significantly reduces immediately postpartum, requiring further dosage adjustments (initial postpartum requirements are often ~50% that of prepregnancy).[1]

Fasting, preprandial and postprandial blood glucose monitoring during pregnancy is recommended to help optimize glucose levels.[1] ADA guidelines recommend the following blood glucose targets in pregnant individuals with preexisting type 1 diabetes (the same as for gestational diabetes):[1]

70-95 mg/dL (3.9 to 5.3 mmol/L) fasting, and either
110-140 mg/dL (6.1 to 7.8 mmol/L) 1 hour postprandially, or
100-120 mg/dL (5.6 to 6.7 mmol/L) 2 hours postprandially.

Due to increased red blood cell turnover, HbA1c is slightly lower during pregnancy in women both with and without diabetes. Ideally, the HbA1c goal in pregnancy should be <6% (<42 mmol/mol) if this can be achieved without significant hypoglycemia, but the target may be relaxed to <7% (<53 mmol/mol) if necessary to prevent hypoglycemia.[1] For those using CGM, suggested goals are time in range (TIR) >70% (range 63 to 140 mg/dL [3.5 to 7.8 mmol/L]), with time below range (TBR) <4% (<63 mg/dL [3.5 mmol/L]); however, this should be used in addition to, not in place of, other recommended glycemic monitoring.[1]

A postpartum contraceptive plan should be in place for those with ongoing childbearing potential, and breastfeeding is recommended for all patients.[1]

Ongoing comprehensive medical evaluation for all patients

Due to the significant risk of diabetes-related complications, the management of patients with type 1 diabetes involves regular monitoring for conditions including diabetic retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease.[1]

Well-controlled blood pressure and lipids and avoidance of smoking are essential components of cardiovascular risk reduction.[1] Smoking has also been linked to an increased risk of microvascular complications, poorer glycemic outcomes, and premature death.[1] As a routine part of management, enquire about use of cigarettes (and e-cigarettes/vapes) and other tobacco products, and refer for smoking cessation counseling and pharmacologic therapy.[1] Given its increased prevalence and possible links to diabetes-related health implications (e.g., DKA), cannabis-use should also be explored and patients should be counseled not to use recreational cannabis in any form due to the risk of cannabis hyperemesis syndrome.[1]

Psychosocial screening and support can help to prevent diabetes distress, anxiety, depression, disordered eating, and improve the individual’s and family's capacity for self-care.[1][176][177][178] Cognitive capacity should be monitored throughout life, with particular attention to those who experience severe hypoglycemia, and very young children and older adults.[1] Screening for sleep health, including sleep disorders and sleep disruption (e.g., due to diabetes symptoms, management needs, and worry), should be considered, and referral to specialist sleep services made as appropriate.[1] Sleep disturbance is associated with reduced engagement in diabetes self-management and may affect glycemic control.[1] People with diabetes should be counseled on sleep hygiene practices (e.g., consistent sleep schedule, limiting caffeine).[1] See Monitoring.

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