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), and very young children and older adults are more vulnerable to hypoglycemia.[1][56] These differences should be considered when developing individualized management plans.[1] Children and adolescents should be managed by an interprofessional pediatric diabetes team who understand the unique challenges for this population.[1]

In the short term, insulin is life-saving because it prevents diabetic ketoacidosis (DKA), a potentially life-threatening condition. 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) without significant hypoglycemia for many nonpregnant adults, adolescents, and children.[1][46] Less stringent goals (e.g., 7.5% to 8% [58-64 mmol/mol]) may be appropriate for very young children, some older adults, people with a history of severe or frequent hypoglycemia, and those with limited life expectancies, 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] Equally, 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, if the clinician (in agreement with the patient) feels this is appropriate and could be beneficial.[1] Time in range is another glycemic variable that can be measured and targeted in patients using continuous glucose monitoring (CGM). In general, >70% time in range (70-180 mg/dL [3.9-10 mmol/L]) with <4% time in hypoglycemia (<70 mg/dL [<3.9 mmol/L]) will correlate with goal HbA1c and can be considered adequate glycemic control.[1][58] However, for those with frailty, or at a high risk of hypoglycemia, a target of >50% time in range with <1% time below range is recommended.[1] Setting a glycemic goal during consultations should improve patient outcomes.[1]

Fructosamine and glycated albumin are alternative measures of chronic glycemia (both reflecting glycemia over the preceding 2 to 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]

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.

Initiating insulin

Intensive insulin replacement should be started as soon as possible after diagnosis.[59] Although intensive therapy at any time in type 1 diabetes is beneficial, earlier implementation is associated with greater reduction in kidney and cardiovascular complications.[60] 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 intensive insulin replacement.[1][61] [ ] The choice between an insulin pump and MDI is based on patient interest and self-management skills, cost, and physician preference.[1][62]

MDI insulin regimens

Using a combination of long-acting insulin (insulin glargine, insulin detemir, or insulin degludec) or intermediate-acting insulin (insulin NPH [Neutral Protamine Hagedorn]/isophane) for basal dosing, and rapid-acting insulin (insulin lispro, insulin aspart, or insulin glulisine) 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 finger-stick data. Treatment with analog insulins may provide the benefit of increased flexibility of lifestyle and less hypoglycemia as compared with human insulins.[63] In fact, in patients who are at high risk of hypoglycemia, the Endocrine Society recommends using long-acting insulin analogs rather than insulin NPH for those on basal insulin therapy, and rapid-acting insulin analogs rather than short-acting human insulins for those on basal-bolus insulin.[64] Similarly, the ADA recommends that for most adults with type 1 diabetes, insulin analogs are preferred over injectable human insulins to minimize hypoglycemia risk.[1] However, insulin analogs are more expensive.[65][66] [ ] Biosimilars of analog insulin may be available in some countries at a lower cost, making them more affordable. Ultra-rapid acting insulin analogs are also available for a more favorable postprandial glycemic effect.

One systematic review and meta-analysis that assessed the efficacy and safety of the novel, ultra-rapid acting insulins (next-generation faster-acting insulin aspart and insulin lispro) 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.[67]

Many patients are managed with twice-daily injections of a mixture of rapid-acting and intermediate-acting insulin. This regimen may be used if patients are unable to comply with MDI, but it is not a first-line recommendation for management because of its lack of flexibility.

Subcutaneous injection animation demonstration

Demonstration of subcutaneous injection techniques, including how to identify an appropriate site for injection.

Insulin pumps

The insulin pump uses rapid-acting insulin, and provides a basal rate of insulin and delivers mealtime bolus dosing. When used with an integrated CGM system, the pump can adjust the insulin delivery rates to maintain glucose levels in a pre-set target range. There is increasing evidence that insulin pump therapy is associated with improved glycemic control and lower risk of hypoglycemia, including in children, adolescents, and young adults.[72][73][74][75] Patients selected for pump therapy must be skilled in diabetes self-management and able to manage and troubleshoot the various pump components.[76][77] The insulin pump uses a subcutaneous insulin injection port. The port is changed every 2 to 3 days and may reduce anxiety and help achieve better glycemic control in selected patients.[78][79]

Insulin pumps can be used without CGM, but the patient or caregiver must test blood glucose frequently and adjust pump rates or take boluses as needed. Patients may use stand-alone CGM along with an insulin pump, and use the CGM data to adjust insulin rates via the pump. However, insulin pumps with integrated CGM are a major advance in technology. Sensor-augmented insulin pumps temporarily suspend insulin delivery to prevent hypoglycemia. Automated insulin delivery (AID) systems or hybrid closed-loop systems adjust insulin rates for both hypoglycemia and hyperglycemia.[1] These devices use a computerized control algorithm to create the closed-loop insulin delivery system, which functions as an artificial pancreas.[46][80] Insulin delivery is determined automatically based on sensed glucose levels.[1] In clinical trials, such systems have been shown to reduce the risk of nocturnal hypoglycemia and to improve glucose control, including in children.[81][82][83] Early evidence suggests that closed-loop systems improve glucose control more significantly than sensor-augmented pumps.[84] The ADA advises that AID systems should be offered to young people and adults (including older adults) with type 1 diabetes to improve glycemic control, providing they are able to use them safely (either themselves or their caregivers).[1] Further, the Endocrine Society recommends algorithm-driven insulin pumps with CGM, rather than MDI with self-monitoring of blood glucose, for adults and children with type 1 diabetes.[64] 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.[85] 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.[85] The ADA recommends that for those using an AID system alongside CGM, these should be continued 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]

Inhaled insulin

Inhaled insulin is available as a rapid-acting insulin and can be useful for people with an aversion to injection.[1] In one study in type 1 diabetes, use of inhaled insulin at mealtimes improved prandial glucose control, compared with injectable rapid-acting insulin aspart, without additional hypoglycemia or weight gain.[86] Further, another study in type 1 diabetes showed that inhaled insulin can have a faster onset and shorter duration of action than the injectable rapid-acting insulin lispro.[1][87] However, data on the efficacy and safety of inhaled insulin 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.[88] 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 inhaled insulin therapy.[1]

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] Episodes of hypoglycemia should be sought at each visit, and efforts made to determine contributing factors, and the ability of the patient to recognize and treat it appropriately.[1] All patients should be screened for hypoglycemia unawareness.[1] The ADA defines three levels of hypoglycemia, all of which are considered clinically important: level 1 is a glucose level ≥54 mg/dL but <70 mg/dL (≥3.0 mmol/L but <3.9 mmol/L); level 2 is a glucose level <54 mg/dL (<3.0 mmol/L); and level 3 (severe hypoglycemia) is defined as any low blood glucose level leading to cognitive and/or physical impairment requiring assistance from another person for recovery.[1] Both levels 2 and 3 require immediate correction of low blood glucose, and prompt treatment of level 1 is also recommended, to avoid progression to more severe hypoglycemia.[1] Fast-acting carbohydrates should be used to treat hypoglycemia, and oral glucose is preferred if the person is conscious (but any form of carbohydrate containing glucose may be used).[1] Treatment should be repeated if hypoglycemia persists 15 minutes after initial treatment.[1] Glucagon should be used if the person is unable or unwilling to consume carbohydrates by mouth, and should be prescribed and available to all patients taking insulin.[1] Ready-to-use preparations of glucagon that do not need to be reconstituted are preferred but are associated with increased cost.[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] They further advise consideration of AID systems (and other advanced insulin delivery devices) for reduction of hypoglycemia risk in older adults.[1]

Blood glucose monitoring

Most patients on intensive insulin should be encouraged to use blood glucose monitoring (BGM; previously known as self-monitoring of blood glucose) 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 to 14 days.[56] An implantable CGM device that requires sensor change by a medical provider every 3 to 6 months is also available, but is used less often.[89]

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] Real-time CGM, worn by a patient on a regular basis, may help improve glycemic control, and evidence supports use of CGM in both adults and children.[1][90][91][92][93][94][95][96] One systematic review and meta-analysis found CGM to be superior to BGM in improving glycemic control among individuals with type 1 diabetes in the community, especially in those with uncontrolled glycemia.[84] A 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.[97] Intermittently scanned CGM devices are also available, and have been associated with reductions in HbA1c and acute diabetes complications.[1][98] This remains true when intermittently scanned CGM devices are used alongside patient-driven lifestyle modification.[99] In addition, in patients with high glycated hemoglobin levels, the use of intermittently scanned CGM resulted in significantly lower glycated hemoglobin levels than those using fingerstick testing.[98] Studies have shown that CGM use is cost-effective as it lowers the indirect costs of diabetes.[100] However, various factors can affect the accuracy of CGM, for example, sensor interference caused by the use of medications and substances such as 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 medication list 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][64]

Both BGM and CGM allow patients and physicians to evaluate response to therapy, and to assess whether glycemic targets are being safely achieved.[1] 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] They recommend that CGM is offered to all adults and young people with diabetes on intensive insulin therapy, and to adults on basal insulin.[1] They also recommend 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.[64] 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.[101] However, AACE recommends structured self-monitoring of blood glucose in people with type 1 diabetes who have limited success with, or are unable or unwilling to use, CGM.[101]

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]

Both individual and group settings are recommended for the delivery of effective diabetes self-management education and support, as well as technology-based methods.[1] This approach can be used for adults as well as children and adolescents.[102][103]

Designing a regimen

Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1 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] In general, one half of the total dose is given as basal insulin to control glucose levels overnight and between meals, and one half as bolus dosing to control glucose levels after meals.[1] The bolus dosing, known as prandial insulin, is divided and given before meals. Patients need to use BGM or CGM.[1] The insulin doses can be adjusted every 2 to 3 days to maintain target blood glucose. To achieve an HbA1c <7% (53 mmol/mol), the pre-meal blood glucose goal is 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) is <180 mg/dL (<10.0 mmol/L).[1]

Basal insulin can be administered as a basal rate of rapid-acting insulin via an insulin pump, or as daily injections of a long-acting insulin.[1] Patients on an insulin pump will take prandial insulin as a bolus before each meal. 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 beginning 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.[104]

The timing of 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 detemir is typically given twice daily
Insulin degludec is long-acting and 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
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 night-time 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.[105] 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.

One Cochrane review found that, when comparing intermediate- and long-acting insulins (i.e., insulin NPH, insulin detemir, insulin glargine) there were no clear differences for the following main outcomes: death, health‐related quality of life, severe (night‐time) hypoglycemia, serious unwanted events, nonfatal complications of diabetes (e.g., heart attacks, strokes) and HbA1c levels.[106] However, the Endocrine Society recommends using long-acting insulin analogs rather than insulin NPH for patients on basal insulin therapy who are at a high risk of hypoglycemia based on moderate-certainty evidence for severe hypoglycemia reduction in those using long-acting insulin analogs vs human insulin NPH.[64] Similarly, the ADA recommends that, for most adults with type 1 diabetes, insulin analogs are preferred over injectable human insulins to minimize hypoglycemia risk.[1]

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

Diet and exercise

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 non-starchy vegetables, whole fruits, legumes, whole grains, nuts, seeds, and low-fat dairy products; and minimizing consumption of meat, sugar-sweetened beverages, candy, refined grains, and ultra-processed foods.[1][107] 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]

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.[108] 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.[109] 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.[107] Dietary patterns (like the Mediterranean-style or dietary approaches to stop hypertension [DASH]) with a focus on plant-based foods, lean protein, mono- and poly-unsaturated fats, and low-fat dairy products (while limiting processed foods and sugary drinks) are linked to improved long-term health outcomes.[107] 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).[107] 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][107] If a low- or very-low carbohydrate approach is used, this should only be done with close specialist supervision and monitoring.[107]

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][110] 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 participate in 2 to 3 sessions of resistance training per week on nonconsecutive days.[1] The ADA also advises 2 to 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][46]

Patients with type 1 diabetes can safely exercise and manage their glucose levels.[46][111] Pre-exercise carbohydrate intake and insulin doses can be effectively modified to avoid hypoglycemia during exercise and sports.[112] Hypoglycemia can occur up to 24 hours after exercise and may require reducing insulin dosage on days of planned exercise.[1][56] 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 (<5.0 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 of nocturnal hypoglycemia.[113] Alcohol may cause acute hypoglycemia, but both alcohol and exercise can cause delayed hypoglycemia as well (by up to 24 hours).[1][56]

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][56] Thyroid disease and psychologic disorders should be screened for at diagnosis (thyroid screening should be done once clinically stable) and then on a regular basis.[1][56] In children and adolescents, celiac disease should also be screened for shortly after diagnosis.[1][56] Increased clinical suspicion should prompt screening for celiac disease in adults, and for other associated conditions (that may lead to unstable diabetes) such as primary adrenal insufficiency and pernicious anemia in all patients.[1][56] 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.[56] Pubertal physiologic changes culminate in increased insulin resistance (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.[56]

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.[56] Regular screening for, and prompt management of, psychosocial problems is important, and the International Society for Pediatric and Adolescent Diabetes (ISPAD) advises that in some adolescents, their mental health needs may supersede their other clinical needs for a short time.[56]

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.[56] Parenting styles that are compassionate and supportive with clear expectations are linked to improved diabetes-outcomes, including improved adherence and better glycemic control.[56] Allowing for developmentally appropriate levels of autonomy is beneficial, but premature transfer of sole care to the adolescent is associated with worse outcomes.[1][56]

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.[56] 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][56]

Additionally, the transition period from pediatric to adult care is associated with worse 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][56] Interprofessional support during transition is recommended, including the use of transition care coordinators and transition tools.[1][56]

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.[114] It may be given as an injection before each meal to get more stable glycemic control. However, insulin treatment must continue in addition to pramlintide. At initiation the current pre-meal insulin dose should be reduced by about 50% to avoid hypoglycemia, and then titrated up.

Pramlintide is indicated as adjunctive treatment in patients with postprandial hyperglycemia that cannot be controlled with pre-meal insulin alone.[114] 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 should not be used in a patient with gastroparesis. The most common side effect is nausea, occurring in 28% to 48% of patients.[114]

Pregnancy

Individuals with diabetes are at high a higher risk of miscarriage and having infants with major congenital malformations than the general population.[115] Preconception diabetes care reduces this risk.[116] Preconception counseling should, therefore, be incorporated in the routine diabetes clinic visit for all individuals of childbearing potential, starting at onset of puberty.[1][56][117][118] The use of an appropriate preconception program for young adolescents (e.g., READY-girls) has been demonstrated to have lasting benefits.[56] 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, to reduce fetal and maternal risks.[1] The ADA also recommends that 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 during pregnancy; 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.[1]

In addition to the complications noted above, specific risks of diabetic pregnancy include macrosomia, neonatal respiratory distress syndrome, and preeclampsia.[1][118] Euglycemia or near-euglycemia reduces the risk of complications.[1][118] Antepartum fetal surveillance is routinely used during pregnancy to monitor for complications and assess the risk of fetal death in pregnant individuals with a preexisting condition such as diabetes.[119] Antepartum fetal 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 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).[119]

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.[120] Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists should be discontinued preconception (and avoided in individuals of childbearing potential not using reliable contraception).[1] Hypertension should be treated with agents considered safe in pregnancy.[1] The ADA recommends discontinuation of statins, but the Food and Drug Administration indicates that individuals should be considered on an individual basis, particularly those at very high risk for cardiovascular events during pregnancy.[1][121] 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 to 16 weeks’ gestation; similarly the American College of Obstetricians and Gynecologists recommends starting the treatment between 12 and 28 weeks’ gestation, but ideally before 16 weeks.[1][118]

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][118] The Endocrine Society indicates that insulin is the only recommended pharmacologic treatment for type 1 diabetes during pregnancy.[117] There are few data comparing outcomes for continuous infusion versus MDI for pregnant individuals with diabetes; however, one randomized controlled trial reports better glycemic outcomes with use of MDI versus insulin pump therapy.[122][123] [ ] 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/isophane, insulin detemir, regular/human insulin, insulin lispro, and insulin aspart.[124] Use of CGM during pregnancy may help in improving glycemic control and neonatal outcomes, and the ADA recommends its use in pregnancy in addition to (but not as a substitute for) blood glucose monitoring for those with type 1 diabetes.[1][125][126] There are no large randomized trials supporting the safety of insulin glargine in pregnant patients with diabetes.[127] However, insulin glargine has been safely used in many patients during pregnancy.[118] It can be considered second-line to insulin NPH/isophane or insulin detemir for basal insulin dosing during pregnancy because there are fewer long-term safety monitoring data. It should be noted that there may be increased sensitivity to insulin in early pregnancy, resulting in increased risk of hypoglycemia.[1] By about 16 weeks gestation, insulin resistance starts increasing, rising until around week 36, often resulting in a doubling of the daily insulin requirements compared to 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 by the ADA 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.

HbA1c goal during pregnancy is individualized to <6% (<42 mmol/mol) or up to <7% (<53 mmol/mol) as 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 breast-feeding efforts are recommended for all patients.[1]

Ongoing comprehensive medical evaluation

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 in people with diabetes.[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.[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][128][129][130] 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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