Type 1 diabetes mellitus

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

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

nonpregnant

1st line – basal-bolus insulin

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1st line –

basal-bolus insulin

Intensive insulin replacement should be started as soon as possible after diagnosis to maintain blood glucose levels as close to normal as possible. This prevents diabetic ketoacidosis and reduces the likelihood of chronic complications.[91][92]

Setting a glycemic goal during consultations improves patient outcomes.[1] The American Diabetes Association (ADA) recommends a target hemoglobin A1c (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 [3.9-10.0 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 recommends that for preschoolers with type 1 diabetes, an alternative target of >50% of time in a tighter range (TITR; 70-140 mg/dL [3.9-7.8 mmol/L]) can be used.[90] Less stringent goals (e.g., <7.5% to 8.0% [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]

The choice between continuous infusion with an insulin pump and a regimen of multiple daily injections (MDI) is based on patient interest and self-management skills, cost, and physician preference.[1][93] [ ] 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 decrease as frequent user input is necessary.[70] Thus emerged the concept of glucose responsive automated insulin delivery (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 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] As a result, 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]

In general, individuals with type 1 diabetes require approximately 30% to 50% of their daily insulin as basal and the remainder as prandial (which is divided and given as boluses before meals). This proportion depends on several factors, including carbohydrate consumption, age, pregnancy status, and puberty stage.[1] Total daily dose 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]

The ADA recommends that for most adults with type 1 diabetes, insulin analogs (or inhaled insulin) are preferred over injectable human insulins for both basal and prandial dosing to minimize hypoglycemia risk.[1] They may also provide the benefit of increased flexibility of lifestyle and less weight gain compared with human insulins.[94] However, they are more expensive.[96][97] [ ] Biosimilars of analog insulin may be available in some countries at a lower cost, making them more affordable.

Blood glucose monitoring (BGM; previously known as self-monitoring of blood glucose) and/or 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]

Basal insulin: can be administered as a basal rate of rapid-acting insulin via an insulin pump, or as daily or twice daily injections of long-acting analogs (insulin glargine or insulin degludec) or intermediate-acting insulin (insulin NPH [Neutral Protamine Hagedorn]; also known as isophane insulin).[1] 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. Insulin NPH is typically given twice daily. Insulin glargine is usually given once daily and should be delivered at the same time each day, preferably at night (although 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 it 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.

Prandial (bolus) insulin: rapid-acting insulin analogs (insulin lispro, insulin aspart, or insulin glulisine), ultra-rapid insulin analogs (faster-acting insulin aspart and ultra-rapid insulin lispro), or short-acting insulin (regular/human insulin) are used for prandial dosing. The ultra rapid-acting analogs may cause less hypoglycemia while improving postprandial glucose excursions and administration flexibility (in relation to prandial intake) compared with rapid-acting analogs.[1] Inhaled insulin may also be an option. 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 inhaled insulin therapy.[1]

For those using an insulin pump, the prandial dose is delivered 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 starting approach is to use one 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]

Regular insulin is given about 30 minutes prior to the meal, while rapid-acting insulin can be injected 15 minutes before to shortly after a meal. In children with erratic eating habits, rapid-acting insulin can be given just after the meal. Inhaled insulin is taken at the beginning of a meal.

The regimen should be individualized to obtain the best possible glycemic control. 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]

The regimen should be individualized to obtain the best possible glycemic control.

Primary options

insulin glargine

insulin NPH

insulin degludec

-- AND --

insulin regular

insulin lispro

insulin aspart

insulin glulisine

insulin inhaled

Plus – diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

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Plus –

diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

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]

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 American Diabetes Association (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]

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] Adult patients should also incorporate 2-3 sessions of resistance training per week on nonconsecutive days, and older adults should undertake 2-3 sessions of flexibility and balance training each week.[1] Prolonged sitting should be interrupted every 30 minutes with short bouts of physical activity for blood glucose benefits.[1]

Children and adolescents with diabetes should aim for ≥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]

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]

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]

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]

Due to the significant risk of macrovascular complications, the management of patients with type 1 diabetes also involves optimizing cardiovascular risk factors. Well-controlled blood pressure and lipids and avoidance of smoking are essential components of this.[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., diabetic ketoacidosis), 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] The role of antiplatelet agents in primary prevention of CVD is unclear and guidelines differ in their recommendations. Consult your local protocols.

Consider – pre-meal insulin correction dose

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Consider –

pre-meal insulin correction dose

Treatment recommended for SOME patients in selected patient group

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 blood glucose monitoring or CGM based on glucose value.[105]

Consider – amylin analog

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Consider –

amylin analog

Treatment recommended for SOME patients in selected patient group

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.

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.

Should not be used in a patient with gastroparesis. The most common side effect is nausea, occurring in 28% to 48% of patients.[155]

Primary options

pramlintide: 15-60 micrograms subcutaneously before each meal

2nd line – fixed-dose insulin

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2nd line –

fixed-dose insulin

Fixed-dose insulin is used when patients are already doing well on a fixed-dose multiple daily injections regimen; or cannot manage 3 to 4 insulin injections daily; or have trouble mixing insulin.

Primary options

insulin NPH/insulin regular

insulin aspart protamine/insulin aspart

insulin lispro protamine/insulin lispro

insulin degludec/insulin aspart

Plus – diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

Back

Plus –

diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

Treatment recommended for ALL patients in selected patient group

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 poly-unsaturated 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]

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. Adult patients should also incorporate 2-3 sessions of resistance training per week on nonconsecutive days, and older adults should undertake 2-3 sessions of flexibility and balance training each week.[1] Prolonged sitting should be interrupted every 30 minutes with short bouts of physical activity for blood glucose benefits.[1]

pregnant

1st line – basal-bolus insulin

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1st line –

basal-bolus insulin

Individuals with diabetes are at a higher risk of miscarriage and having infants with major congenital malformations than the general population.[156] Other complications include macrosomia, neonatal respiratory distress syndrome, and preeclampsia.[1][159] Euglycemia or near-euglycemia reduces the risk of complications.[1][159]

Prior to conception, the American Diabetes Association (ADA) recommends a target HbA1c goal of <6.5% (<48 mmol/mol) if this can be achieved without hypoglycemia, as this has been shown to reduce fetal and maternal risks.[1] A goal of <6% (<42 mmol/mol) is recommended during pregnancy; however, the ADA advises that this may be relaxed to <7% (<53 mmol/mol) if necessary to prevent hypoglycemia.[1] For those using continuous glucose monitoring (CGM), suggested goals are time in range (TIR) >70% (range 63-140 mg/dL [3.5 to 7.8 mmol/L]), with time below range (TBR) <4% (<63 mg/dL [3.5 mmol/L]). Use of CGM during pregnancy may help to improve 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][172][173]

Patients should monitor their blood glucose from 4 to 7 times per day (or use CGM) and the pattern should be examined every few weeks early in pregnancy so that nutrition content and timing, exercise patterns, and the insulin doses can be modified to achieve optimal control.

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 multiple daily injections (MDI).[1][159] The use of hybrid closed-loop (HCL) systems has shown promise for the management of type 1 diabetes during pregnancy but no HCL pump in the US has FDA approval for use in pregnancy.[174][175] A patient who was using an insulin pump and CGM prepregnancy should continue using these devices but switch to manual mode during pregnancy. This is because HCL systems are not designed for the very tight glycemic control needed during pregnancy. 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.

Total daily dose 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, but higher doses are required during pregnancy.[1]

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 leading to a doubling of the daily insulin requirements compared with prepregnancy.[1] Insulin resistance significantly reduces immediately postpartum, requiring further dosage adjustments (initial postpartum requirements are often ~50% that of prepregnancy).[1]

Commonly used insulins during pregnancy include insulin NPH (Neutral Protamine Hagedorn; also known as isophane insulin), regular/human insulin, and the rapid-acting analogs insulin lispro and insulin aspart.[168] Limited evidence suggests that these rapid-acting analogs 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]

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

Owing to the complexity of insulin management during pregnancy, referral to a specialist center that can offer multidisciplinary care is desirable.[1]

Primary options

insulin NPH

-- AND --

insulin regular

insulin lispro

insulin aspart

Secondary options

insulin glargine

-- AND --

insulin regular

insulin lispro

insulin aspart

Plus – low-dose aspirin

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Plus –

low-dose aspirin

Treatment recommended for ALL patients in selected patient group

Daily low-dose aspirin is recommended to reduce the risk of preeclampsia in all pregnant individuals with preexisting type 1 diabetes. The American Diabetes Association recommends starting this treatment at 12-16 weeks’ gestation, while the American College of Obstetricians and Gynecologists recommends starting it between 12 and 28 weeks’ gestation, but ideally before 16 weeks.[1][159] Once started, it should be taken until delivery. See Preeclampsia.

Plus – lifestyle measures and evaluation for complications/comorbidities and drug history review

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Plus –

lifestyle measures and evaluation for complications/comorbidities and drug history review

Treatment recommended for ALL patients in selected patient group

Nutrition counseling, endorsing a balance of macronutrients, and extra focus on physical activity and diabetes self-care education, is recommended.[1]

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]

Ideally, 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 as the pregnancy progresses. This is related to the often rapid intensification of antihyperglycemic therapy, as well as рrеgոanϲy-related vascular, volume, and hormonal changes.[1] Pregnant women should be appropriately counseled and have an eye exam in the first trimester. They should 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).[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] 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 American Diabetes Association 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.

In most circumstances, nonstatin lipid-lowering drugs (e.g., bempedoic acid, proprotein convertase subtilisin/kexin type 9 inhibitors, fibrates) should be stopped at the first pregnancy visit (or ideally prior to conception).[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]

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.[164] Antepartum fetal surveillance techniques in clinical use include maternal perception of fetal movement, contraction stress test, nonstress test, 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).[164]

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Type 1 diabetes mellitus

Treatment algorithm

nonpregnant

basal-bolus insulin

Primary options

diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

pre-meal insulin correction dose

amylin analog

Primary options

fixed-dose insulin

Primary options

diabetes self-management education and support (DSMES) and lifestyle modifications and cardiovascular risk reduction

pregnant

basal-bolus insulin

Primary options

Secondary options

low-dose aspirin

lifestyle measures and evaluation for complications/comorbidities and drug history review