Type 1 diabetes - Approach | BMJ Best Practice

Approach

In the short term, insulin is life-saving because it prevents diabetic ketoacidosis, 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 haemoglobin (HbA1c) goals determine the aggressiveness of therapy, which is in turn individualised. Current guidelines recommend a target HbA1c of <53 mmol/mol (<7%) for adult patients and many children.[1][35][43] In the UK, national guidance recommends that patients with type 1 diabetes aim for a target HbA1c level of 48 mmol/mol (6.5%) or lower to minimise the risk of long‑term vascular complications.[44][45] Less stringent goals may be appropriate for very young children, older adults, people with a history of severe hypoglycaemia, and those with limited life expectancies, advanced microvascular or macrovascular complications, or comorbid conditions.[1]

Good glycaemic control in type 1 diabetes requires attention to diet, exercise, and insulin therapy. All three components should be co-ordinated for ideal control. Self-monitoring of blood glucose (SMBG) is a core component of good glycaemic control. Patients on multiple injections daily should consider SMBG before meals, occasionally after meals and at bedtime, and before exercising to assess presence and adequate treatment of hypoglycaemia, and before any task during which hypoglycaemia could have particularly dangerous consequences.[1] Some patients will need to check their blood glucose 6-10 times daily.[46]

As continuous glucose monitoring (CGM) technology continues to improve, the indications for its use are likely to expand.[47] Evidence supports use of CGM for improved glucose control in adults and children.[48][49][50] Appropriate use of CGM is when it is targeted at people with type 1 diabetes who have hypoglycaemic unawareness, frequent hypoglycaemia, or continued poor control during intensified insulin therapy, and at those who are willing to use CGM frequently.[1][51] The limiting factor for tight glycaemic control in type 1 diabetes is hypoglycaemia. Well-controlled blood pressure and lipids, and avoidance of smoking are essential components of cardiovascular risk reduction.

Including technology-based methods, along with individual and group settings are recommended for the delivery of effective diabetes self-management education and support.[1] This approach can be used for adults,[52] as well as children and adolescents.[53]

Diet and exercise

There is no standardised dietary advice that is suitable for all individuals with diabetes.[1] Individualised nutrition advice should be based on personal and cultural preferences, health literacy and numeracy, access to healthful food choices, and willingness and ability to make behavioural changes. It should also address barriers to change. All patients with diabetes should receive individualised medical nutrition therapy, preferably provided by a registered dietitian who is experienced in providing this type of therapy to diabetes patients.[54] Carbohydrate counting or consistent carbohydrate intake with respect to time and amount may improve glycaemic control. Rapid-acting insulins may make timing of meals less crucial than in the past, but regular meals are still important.

Adults with diabetes are recommended to engage in 150 minutes/week of moderate-intensity aerobic exercise (to 50% to 70% of max heart rate) spread over at least 3 days per week, with no more than 2 consecutive days without exercise.[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.[35] Patients with type 1 diabetes can safely exercise and manage their glucose levels.[35][55] Pre-exercise carbohydrate intake and insulin doses can be effectively modified to avoid hypoglycaemia during exercise and sport.[56][57] Hypoglycaemia can occur up to 24 hours after exercise and may require reducing insulin dosage on days of planned exercise. A carbohydrate snack should be given at the start of exercise if the blood sugar is <5.6 mmol/L (<100 mg/dL).

Clinical judgement should be used in determining whether to screen asymptomatic individuals for coronary artery disease prior to recommending an exercise programme.[1]

The following should be assessed prior to starting an exercise programme: age; physical condition; blood pressure; and presence or absence of autonomic neuropathy or peripheral neuropathy, preproliferative or proliferative retinopathy, or macular oedema. Vigorous exercise may be contraindicated with proliferative or severe preproliferative diabetic retinopathy. Non-weight-bearing exercise may be advisable in patients with severe peripheral neuropathy.

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

Initiating insulin

Intensive therapy with insulin should be started as soon as possible after diagnosis.[58] Unlike older regimens that used non-physiological insulin dosing, intensive therapy aims to mimic physiological insulin release by combining basal insulin with bolus dosing at mealtimes. Both continuous infusion with an insulin pump and a regimen of multiple daily injections (MDI) can provide intensive therapy.[59] [ ]

The choice between pump and MDI is based on patient interest and self-management skills, as well as physician preference, as outcomes are generally similar.[60] The insulin pump uses regular or rapid-acting insulin, and provides a basal rate of insulin and delivers mealtime bolus dosing. However, the patient or parent must still measure blood glucose frequently in order to adjust the pump to deliver the appropriate amount of insulin. Insulin pumps may reduce hypoglycaemia, especially when combined with continuous glucose monitoring systems (CGMS) and threshold suspend features,[61] and improve HbA1c, while providing greater flexibility.[62][63][64] Use of a pump requires a motivated patient with strong family support (for children) and access to practitioners trained in pump therapy.[65]

Using a combination of long- (insulins glargine, detemir, or degludec) or intermediate-acting (NPH) insulin for basal dosing, and rapid- (insulins lispro, aspart, or glulisine) or short- (regular-) acting insulin for bolus dosing, MDI regimens can be designed based on physician and patient preference and modified based on finger-prick data. There is no consensus as to whether insulin analogues are superior to conventional insulins for glycaemic control or reductions in complications.[66][67] [ ]

In the past, many patients were 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 no longer a first-line recommendation for management because of its lack of flexibility.

Designing a regimen

An initial total daily dose of insulin in adults can be 0.2 to 0.4 units/kg/day. In children, an initial daily dose will be 0.5 to 1.0 units/kg/day, and during puberty the requirements may increase to as much as 1.5 units/kg/day. Often, when first started on insulin, patients with type 1 diabetes will experience a honeymoon period, during which they may require only 10 or 15 units/day. One half of the total dose is given as basal insulin and one half as bolus dosing.[1] The bolus dosing is divided and given before meals. Patients need to self-monitor their blood glucose levels. The insulin doses can be adjusted every 2-3 days to maintain target blood glucose. To achieve an HbA1c <53 mmol/mol (<7%), the pre-meal blood glucose goal is 4.4 to 7.2 mmol/L (80-130 mg/dL) and the post-meal blood glucose goal (1-2 hours after starting the meal) is <10.0 mmol/L (180 mg/dL).

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. For greater flexibility of carbohydrate content of meals, pre-meal insulin can be calculated based on the estimated amount of carbohydrate in the meal and the patient's individual insulin-to-carbohydrate ratio. 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.

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:

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

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 obese, insulin-resistant patients, 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.

Pump therapy utilises a similar concept as basal and bolus dosing and does not require multiple injections of insulin. However, patients still need to monitor their blood glucose from 4-7 times daily. There is some evidence that insulin pump therapy may be associated with improved glycaemic control and lower risk of hypoglycaemia,[68] including in children, adolescents, and young adults.[69] Because of the monitoring and dose adjustment required, patients selected for pump therapy must be skilled in diabetes self-management and able to manage and troubleshoot the various pump components.[70]

The insulin pump uses a subcutaneous insulin injection port. The port is changed every 3 days and may reduce anxiety and help achieve better glycaemic control in selected patients.[71][72]

CGMS measure subcutaneous interstitial fluid glucose every 5 minutes. CGMS may be indicated in selected patients with widely fluctuating glucose levels or hypoglycaemia unawareness. A 3-day glucose monitoring system using a CGMS may help the physician adjust insulin doses. Real-time CGMS, worn by a patient on a regular basis, may help improve glycaemic control.[73][74][75][76] The glucose sensors used in CGMS are not reliable at lower ranges of glucose, and thus do not eliminate the need for fingersticks. Development of these systems is ongoing.[47]

CGMS are also less accurate than traditional capillary blood glucose-monitoring methods. However, they provide information on glucose trends, provide alarms to alert patients to impending hypo- or hyperglycaemia, and reduce episodes of hypoglycaemia.[61][77] Insulin pumps with glucose sensors integrated into the same unit are called sensor-augmented insulin pumps. Functionality between sensor and pump has been integrated in one available device: a 'closed loop' system. The insulin delivery can be determined automatically based on sensed glucose levels. These integrated devices use a computerised control algorithm to create the closed loop insulin delivery system, which functions as an artificial pancreas.[35][78] In clinical trials, such systems have been shown to reduce the risk of nocturnal hypoglycaemia and to improve glucose control, including in children.[48][79][80] Some models come with smartphone apps that can be used to monitor glucose and insulin dosing. Use of sensors and sensor-augmented pumps is increasing and is increasingly reimbursed by insurance providers in the US.

Hypoglycaemia 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. Episodes of hypoglycaemia should be sought at each visit, and efforts made to determine contributing factors, and the ability of the patient to recognise and treat it appropriately.

Goal not met

If glycaemic control is not adequate as measured by the HbA1c or by episodes of hypoglycaemia, the patient's nutrition, exercise, and insulin regimen must be re-examined. Children and adolescents may have erratic eating patterns or snack frequently. Consultation with a nutritionist is an invaluable part of the treatment approach, as patients can learn how to count carbohydrates and adjust their pre-meal insulin to allow for flexibility in meal content and activity. Consistent hyperglycaemia may require an increase in basal insulin. Pre-prandial and postprandial hyperglycaemia 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.

Other conditions contributing to unstable diabetes and that co-exist most commonly with diabetes include coeliac disease, thyroid disease, Addison's disease, and psychosocial distress. Coeliac disease, thyroid disease, and psychosocial distress should be screened for at diagnosis and on a regular basis, while increased clinical suspicion should prompt screening for Addison's disease and pernicious anaemia.

Episodes of hypoglycaemia occur with different frequency among patients. Patients should check a 3 a.m. blood glucose if there is concern about risk of nocturnal hypoglycaemia. Nocturnal hypoglycaemia may result in rebound hyperglycaemia in the morning. The dose of basal insulin should be decreased to prevent nocturnal hypoglycaemia. A bedtime snack is not an effective way of decreasing the risk of nocturnal hypoglycaemia.[81] Alcohol may cause acute hypoglycaemia, but both alcohol and exercise can cause delayed hypoglycaemia (by up to 24 hours).

Non-insulin treatments

Pramlintide is indicated as adjunctive treatment in patients with postprandial hyperglycaemia that cannot be controlled with pre-meal insulin alone. For example, it may be useful in a patient with high postprandial glucose, but who develops late hypoglycaemia when pre-meal insulin is increased.

The therapy of people with type 1 diabetes also involves regular eye examinations, foot care, treatment of dyslipidaemia, and blood pressure control.

Adults with type 1 diabetes are at three times the risk of clinical depression compared with those without type 1 diabetes.[82] The prevalence of depression in diabetes is higher in women (28%) compared with men (18%).[83] The risk may also be higher in adolescents, at diagnosis, or when there is a change in disease status.[84] Psychosocial screening and support can help to ameliorate distress and improve the individual’s and family's capacity for self-care.

Pregnancy

Infants of women with diabetes are at high risk of major congenital malformations and miscarriage.[85] Pre-conception diabetes care reduces this risk.[86] Pre-conception counselling should, therefore, be incorporated in the routine diabetes clinic visit for all women of childbearing potential. Women with type 1 diabetes should use an effective method of contraception until they plan pregnancy. The American Diabetes Association (ADA) recommends that HbA1c should be <48 mmol/mol (<6.5%) before conception if this can be achieved without hypoglycaemia.[1] Women should also be evaluated before pregnancy for retinopathy, nephropathy, neuropathy, and possible cardiovascular disease, which may worsen during or complicate pregnancy.

In addition to the complications noted above, infants of mothers with hyperglycaemic diabetes are at risk of macrosomia and neonatal distress. Pre-eclampsia is also more common in diabetic pregnancies. Euglycaemia or near-euglycaemia reduces the risk of complications. During pregnancy women should be cared for by a multidisciplinary team including a nutritionist, a nurse educator, an endocrinologist, and an obstetrician. All pregnant women require a dilated eye examination soon before or early in pregnancy. Women with diabetes have an increased risk of having infants with neural tube defects compared with the general population,[87] and should take a folic acid supplement prior to and during pregnancy. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers should be discontinued pre-conception. Intensive insulin treatment with MDI or insulin pump should be started. Commonly used insulins during pregnancy include NPH, detemir, regular, lispro, and aspart.[88] Use of CGM during pregnancy may help in improving glycaemic control and neonatal outcomes.[89]

There are no large randomised trials supporting the safety of insulin glargine in pregnant patients with diabetes. However, insulin glargine has been safely used in many patients during pregnancy. It can be considered second-line to NPH or insulin detemir for basal insulin dosing during pregnancy because there are fewer long-term safety monitoring data. There are few data comparing outcomes for continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.[90] [ ] However, one randomised controlled trial reports better glycaemic outcomes with use of multiple daily injection therapy versus insulin pump therapy.[91] ADA guidelines recommend the following blood glucose targets in pregnant women with pre-existing type 1 diabetes (the same as for gestational diabetes): <5.3 mmol/L (<95 mg/dL) fasting, and either <7.8 mmol/L (<140 mg/dL) 1 hour postprandially or <6.7 mmol/L (<120 mg/dL) 2 hours postprandially, with HbA1c goal individualised <42 mmol/mol (<6%) or up to <53 mmol/mol (<7%) as necessary to prevent hypoglycaemia.[1]

The ADA recommends that all pregnant women with pre-existing type 1 diabetes should consider daily low-dose aspirin starting at the end of the first trimester in order to reduce the risk of pre-eclampsia.[1]

Ongoing comprehensive medical evaluation

Includes assessment of diabetic complications, a psychosocial assessment, and management of comorbid conditions (e.g., autoimmune diseases).[1]

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