6: Special topics

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Section 6 Special topics

Childhood and adolescence 

Diabetes in the elderly 

Management of diabetes in women of childbearing age 

Surgery and diabetes 

Intercurrent illnesses 

Bariatric surgery 

Male and female sexual dysfunction 

Psychosocial and legal aspects 

Appendix 6.1 Principles of dietary planning in children with diabetes 

Appendix 6.2 Checklist for provision of information to women with GDM 

Childhood and adolescence

Diabetes is one of the most common chronic diseases of childhood; 1 in 300 in Europe and North America develop diabetes by the age of 20 years. Over the past few decades the incidence has been increasing by 3–5% per year.

Type 1a (autoimmune) diabetes mellitus (T1aDM) accounts for the vast majority of children with diabetes. Newborn babies and infants rarely develop the disease (1 in 250 000 in those younger than 6 months) and the aetiology is usually monogenic, not autoimmune. T1aDM is believed to be caused by the interplay of genetic and environmental factors. The initial step is the development of islet autoimmunity, which is marked by the presence of islet autoantibodies. This is thought to be driven by one or more environmental triggers. After this initiation of islet autoimmunity, most patients have a long preclinical period that does offer the opportunity for secondary prevention of the progression to clinical diabetes. The presence of more than one of the autoantibodies combined with susceptibility human leukocyte antigen (HLA)-DR and HLA-DQ genotypes identifies those at high risk of developing diabetes.

Type 1b diabetes has the same clinical presentation as T1aDM, but islet autoantibodies are absent.

The diagnosis of diabetes in children is based on polyuria, polydipsia, weight loss, fatigue and random blood glucose level above 11.1 mmol/L (200 mg/dL). With the increased community recognition of diabetes, most children present with mild hyperglycaemia of short duration. However, 75% of children have the symptoms for more than 2 weeks, suggesting that the diagnosis could be made earlier in many cases. The diagnosis of diabetes should be considered in all sick children; urine or blood testing for glucose and ketones leads to an early diagnosis. Young children may have a non-specific presentation, possibly presenting with enuresis, vomiting or rapid breathing during the course of an infection. Nearly all patients admitted with severe diabetic ketoacidosis (DKA) have been seen hours or days earlier by health-care providers who missed the diagnosis. Most children do not require intravenous (IV) fluids or insulin infusion at the diagnosis of diabetes.

The availability of outpatient care centres has helped to decrease hospitalization at diagnosis. Admission with DKA is more often found among younger children and in children with lower socioeconomic status who encounter possible barriers in accessing medical care.

A family history of an autosomal dominant inheritance of diabetes appearing under the age of 25 years is highly suggestive of maturity-onset diabetes of the young (MODY). It is not uncommon for young people with MODY to be diagnosed when they present with an intercurrent illness.

The principal aims of treatment of diabetes in childhood are:

• achievement of good metabolic control

• attainment of normal growth and development

• avoidance of serious hypoglycaemia

• prevention of long-term complications of diabetes.

The difficulties posed by insulin treatment in children and adolescents mean that these ideals can be difficult to achieve. Emphasis should, however, be placed on the favourable prospects for the child with diabetes; diabetes should be a bar to few recreational activities or occupations.

Management of diabetes in childhood

Diabetic ketoacidosis

The principles of therapy are similar to those for adults. Soluble insulin is infused IV at a rate of 0.1 units per kg per h. Particular care should be exercised with IV fluid replacement in view of the risk to children of the uncommon but potentially fatal complication of cerebral oedema during treatment. Hydration status should be assessed, and fluid deficit and osmolality calculated to help guide fluid and electrolyte replacement. Serum electrolytes, glucose, blood urea nitrogen (BUN), creatinine, calcium, magnesium, phosphorus and blood gas testing should be repeated every 2–4 hours, or more frequently in severe cases.

Cerebral oedema

Subclinical cerebral oedema occurs in most children with DKA. Severe clinical oedema affects 0.5–1% and is fatal in over 20%. Neurological status should be monitored at frequent and regular intervals. Typically, cerebral oedema occurs at 4–12 hours and potential risk factors for symptomatic cerebral oedema in children include:

• more profound dehydration, hyperventilation and acidosis at presentation

• bicarbonate therapy

• excessive and rapid fluid administration, especially if initial serum osmolality is greater than 320 mOsm/L

• failure of serum sodium level to rise as hyperglycaemia resolves

• initial IV insulin bolus or too early initiation of insulin infusion.

Signs and symptoms of cerebral oedema include headache, change in mental status or behaviour, incontinence, focal neurological findings, sudden normalization of heart rate in a previously tachycardic dehydrated patient, or a worsening clinical course in a patient with improved laboratory values. Bradycardia, hypertension and irregular respiration (Cushing triad) are signs of greatly increased intracranial pressure. Early intervention is essential and treatment includes:

• administration of mannitol (1 g/kg over 30 min)

• decreasing fluid rate to 75% or less of maintenance rate

• elevation of head of bed.

Mannitol therapy may need to be repeated. IV hypertonic saline has also been used as an alternative to mannitol. Radiographic imaging (such as computed tomography of the head) should be obtained after, rather than during, treatment of cerebral oedema.

Insulin therapy

Injection regimens should be individualized and include:

• Basal bolus regimen: 40–60% of the total daily dose as a basal insulin analogue (glargine, detemir) in 1–2 doses a day plus a rapid-acting insulin analogue with each meal (in some patients after the meal); soluble human insulin requires administration at least 20–30 min before each meal

• Intermediate-acting human (or neutral protamine Hagedorm; NPH) insulin twice daily and soluble human insulin 20–30 min before each meal

• Two injections daily of a (pre-mixed) mixture of short or rapid and intermediate-acting insulin before breakfast and before the evening meal

• Three injections using some variation of the following: a mixture of short- or rapid-acting and intermediate-acting insulin before breakfast, rapid-acting or soluble human insulin before the afternoon snack or evening meal, and intermediate or basal/long-acting insulin before bed.

Intermediate-acting insulins such as NPH are often mixed with soluble human (regular) or rapid-acting analogues (aspart, lispro or glulisine). Patients and families should be taught how to mix the insulin properly, in order to avoid contamination. It is generally taught to draw up clear (regular or short-acting) insulin before drawing up cloudy insulin (NPH).

Pre-mixed insulins contain a mixture of regular (or rapid-acting) insulin and NPH insulin in various fixed ratios. These preparations may be useful for children who do not want to draw insulin from separate vials before injecting. They may also be useful in reducing the number of injections when compliance is an issue, especially among teenagers. Pre-mixed insulins are also available for use in pen injector devices. The main disadvantage to using pre-mixed insulin preparations is the lack of flexibility in adjusting the separate insulin doses, which is often necessary with varied food intake or during illness or exercise.

Glargine or detemir insulins should not be mixed with any other insulin.

Insulin pump therapy

Insulin pump therapy is the best way to restore the body’s physiological insulin profile. Rapid-acting insulin analogues perform better in pumps than regular insulin, in terms of both mimicking the first-phase insulin release after meals and avoidance of postprandial hypoglycaemia. The user initiates bolus doses before meals and to correct hyperglycaemia. Even with the analogues, however, insulin has to be administered at least 10–15 min before a meal in order to reach effective levels in time. The pump delivers a variable programmed basal rate that corresponds to the diurnal variation in insulin needs.

Currently, the most frequent complications of insulin treatment include failures of insulin delivery because of a displaced or obstructed infusion set, local skin infections and DKA. Patients and their families must be instructed on troubleshooting and treatment of hyperglycaemia, particularly if ketones are present, as this may be an indication of pump malfunction. Syringes should always be available so that insulin may be administered via injection in the event of a pump failure.

Most clinical trials have demonstrated that, compared with multiple daily injections (MDI), pump therapy delivers better glycated haemoglobin (HbA1c), less severe hypoglycaemia, and can improve the quality of life in children.

Insulin pump treatment is significantly more expensive than regimens based on injections. For some patients, pumps may be too difficult to operate or comply with the multiple testing and carbohydrate counting requirements, or may be unacceptable because of body image issues or extreme physical activity (e.g. swimming, contact sports).

Paediatric diabetes outpatient care

Diabetes is managed primarily in the outpatient setting by a team including:

• a paediatrician specializing in diabetes

• a diabetes specialist nurse

• a diabetes dietitian

• a paediatric psychologist with knowledge of childhood diabetes and chronic illness

• possibly a paediatric social worker trained in childhood diabetes.

Health-care providers and the diabetes care team should be aware of and sensitive to the cultural needs and barriers to care that may arise with children from minority ethnic groups.

Tip box

Anxieties and feelings of guilt are common in parents and require considerate and informed handling.

Education

Initial education should provide a basic understanding of the pathophysiology of diabetes and its treatment to ensure that families feel confident in providing diabetes care at home. In most centres where appropriate outpatient resources are available, diabetes education and initiation of insulin therapy can occur as an outpatient, which has been shown to be cost-effective.

In the first few months following diagnosis, close contact in the form of frequent outpatient visits, home visits, telephone communication and other methods of communication is essential to address the frequently changing requirements.

Diabetes education is a continuous process and must be repeated to be effective. It must be adapted and appropriate to the age of the child. Infants and toddlers often have unpredictable eating and activity patterns.

Needle phobia can present a significant issue with the perception of pain inflicted by the caregiver.

Hypoglycaemia is more common in this age group and the prevention, recognition and management of hypoglycaemia is a priority.

Education should also focus on age-appropriate stepwise handover of diabetes responsibilities. This becomes particularly important in adolescence, during which there is a critical balance between promoting independent responsible management of diabetes while maintaining parental involvement.

Once established, it is common practice for children to be seen in the diabetes clinic at least every 3 months; visits should be more often if the patient does not meet the treatment goals or treatment requires intensified, for example if insulin pump treatment is initiated. During these visits:

• overall health and well-being is assessed

• growth and vital signs are monitored

• routine screening for diabetes-associated complications and comorbidities is performed

• blood glucose records (including HbA1c) are assessed

• medications and school plans need to be reviewed.

The advent of new technology, including downloadable glucometers, insulin pumps and continuous glucose sensors, has made it increasingly possible for the diabetes care team to gain insight into the home management of diabetes.

The dietitian should review dietary habits and provide ongoing nutrition education as needed.

Diabetes management in school

Children with diabetes spend a significant portion of their day in school; therefore, diabetes management in school is a critical portion of their diabetes management plan. A school health plan should be in place and should include:

• contact information for the child’s family as well as their diabetes care providers

• information regarding routine management of diabetes (blood sugar monitoring, insulin administration and dosing, snack times)

• an emergency plan for management of hypoglycaemia and hyperglycaemia.

Extracurricular activities are an important component of a child’s school experience, and children with diabetes should be allowed to participate and their needs accommodated accordingly.

Nutrition

Nutritional management in children with diabetes remains a key component of diabetes care and education. The management does not require a restrictive diet, just a healthy dietary regimen that the children and their families can benefit from. A thorough dietary history should be obtained including the family’s dietary habits and traditions, the child’s typical meal times and patterns of food intake. Current guidelines target optimal glycaemic control, reduction of cardiovascular risk, psychosocial well-being and family dynamics. Insulin pump and MDI therapy utilize carbohydrate counting in which the grams of carbohydrate to be eaten are counted and a matching dose of insulin is administered. This plan allows for the greatest freedom and flexibility in food choices, but it requires expert education and commitment, and may not be suitable for many families or situations (e.g. school lunches, teenagers).

Principles of dietary planning in children with diabetes can be found in Appendix 6.1.

Exercise

Children with diabetes derive the same benefits from exercise as children without diabetes and therefore should be allowed to participate with equal opportunities and safety. When children without diabetes exercise, there is a decrease in pancreatic insulin secretion and an increase in counter-regulatory hormones resulting in an increase in liver glucose production. This matches skeletal muscle uptake of glucose during exercise, maintaining stable blood glucose concentrations. In children with T1DM, there is no pancreatic regulation of insulin in response to exercise and there may be impaired counter-regulation. These factors combine to increase the risk of hypoglycaemia. It can be helpful to keep a record of the insulin doses, timing and type of exercise, blood glucose levels before and after exercise, snacks eaten and the time of any episode of hypoglycaemia.

Hypoglycaemia

Hypoglycaemia is the most common acute complication in the treatment of T1DM and is responsible for a significant proportion of deaths in people with diabetes aged under 40 years.

Ideally, blood glucose levels should be checked before, during and after the exercise. Children should consume carbohydrates prior to exercise, with the amount depending on the blood sugar level before the exercise and the duration and intensity of exercise. The site of insulin injection should also be taken into account. Exercise increases blood flow in the part of the body being used, increasing insulin absorption if that area is where the insulin injection was administered. For example, before running, insulin should not be administered in the legs. Hypoglycaemia can occur several hours after exercise secondary to increased glucose transport into the skeletal muscle, the late effect of increased insulin sensitivity, and the delay in replenishing liver and muscle glycogen stores. Blood glucose levels must be monitored for several hours after exercise, at bedtime, and sometimes during the night on days with strenuous exercise.

For anticipated exercise, the dose of insulin can be reduced depending on the intensity of the exercise. The details are beyond the scope of this book. Reduction of insulin administered should mean less carbohydrate intake and may aid weight loss.

Monitoring and goals of diabetes management

Self-monitoring of blood glucose (SMBG) provides an immediate measure of hyperglycaemia and hypoglycaemia, helps to determine immediate and daily insulin requirements, detects hypoglycaemia and assists in its management.

Increased HbA1c levels predict an increased risk of long-term microvascular and macrovascular complications. HbA1c levels, in terms of the optimal glycaemic control, should be considered along with quality of life and documented hypoglycaemia.

The safest recommendation for glycaemic control in children is to achieve the lowest HbA1c that can be sustained without severe hypoglycaemia or frequent moderate hypoglycaemia. Each child should have targets individually determined.

Sick-day management

Children with diabetes with good metabolic control should not experience more illness than non-diabetic children. Health-care providers should equip patients and their carers with the tools necessary to avoid dehydration, uncontrolled hyperglycaemia/ketoacidosis, and hypoglycaemia in the face of intercurrent illnesses.

• Face to face education

• Written instructions are important

• Most parents require telephone advice when first facing sickness in their child and some may need repeated support.

Over time, most parents should be able to manage sick days independently as well as identify when it is appropriate to seek help from their diabetes provider or emergency services.

Insulin therapy must never be stopped during a sick day, although the dose may need to be decreased if the child is vomiting or eating less than usual.

However, infections and other illnesses may be associated with an increase in insulin requirements.

Psychological care

The diagnosis of T1DM changes the lives of affected families and can pose significant problems. It is impossible to take a ’holiday’ from diabetes. Persisting problems with adjusting to T1DM may trigger underlying dysfunction or psychopathology of the child or the family/caregiver. Young people with T1DM are diagnosed with and treated for psychiatric disorders, eating disorders, neurocognitive problems, learning problems, family dysfunction and poor coping skills more frequently than the general population.

Coeliac disease

Many children with diabetes are asymptomatic but are positive for specific serological markers of coeliac disease, such as autoantibodies to tissue transglutaminase. The prevalence of biopsy-confirmed coeliac disease in patients with T1DM is around 5%, compared with less than 1% in the general population.

Thyroid disease

Hypothyroidism is present in approximately 15% of children with T1DM. Long-term follow-up suggests that as many as 30% of people with T1DM develop autoimmune thyroiditis. The presence of hypothyroidism is associated with thyroid autoantibodies, female sex, increasing age and diabetes duration.

Addison’s disease

Addison’s disease affects approximately 1 in 10 000 of the general population, but 1% of subjects with T1DM. The autoimmune process resulting in Addison’s disease can be identified by the detection of autoantibodies reacting to 21-hydroxylase (21-OH).

Transition to the adult diabetes clinic

The terms ’transition’ and ’transfer’ have been used interchangeably in the literature when referring to adolescents moving between diabetes services. Transition may be interpreted as simply a process of physical transfer of a patient to a different service with a failure to acknowledge the psychosocial needs of the adolescent and family members/carers.

Adolescence is a period characterized by transition and change regardless of health status. Diabetes in adolescence is a life-changing condition requiring very careful and consistent management by a multidisciplinary team of clinicians, in addition to the support provided by the family unit/carers. Many young people with diabetes establish a long-term relationship with their paediatric health-care team and the transition to an adult diabetes service provider is an enormous event. The seamless transfer of adolescents with diabetes from paediatric to adult services is a challenge for diabetes teams.

Adolescence is a transitional stage of human development that:

• occurs between childhood and adulthood

• is characterized by significant and complex biological, social and psychological changes.

During this time the adolescent is developing a sense of self and identity, establishing autonomy and understanding sexuality. It is usually accompanied by an increase in independence and generally less overall supervision. This is true too of adolescents transferring to an adult care service. The intention is to provide the adolescent with the practical and cognitive skills required for diabetes self-care and the capability to interact with others such as health-care providers. Age itself may not be a reliable indicator, as adolescents may have different needs and mature at different rates. The parents of the adolescent must also be prepared to relinquish some of the responsibility for diabetes care that they may have undertaken for many years. For some parents, this shift in responsibility can be a time of high anxiety. Fundamental to a successful transition programme is to work with parents to help them find a balance between shifting the responsibility to the adolescent and continuing to maintain an appropriate level of interest.

Transition should be planned, coordinated, and viewed holistically as opposed to focusing solely on the referral from one medical doctor to another. Transition should promote better management for adolescents with T1DM by developing their capacity to self-care through healthy choices.

A powerful predictor of good self-care is self-efficacy. Adolescents should be encouraged to have confidence in their capability to make decisions and take actions that demonstrate good diabetes self-care (see Appendix 6.1: Principles of dietary planning in children with diabetes).

Diabetes in the elderly

Diabetes, mainly type 2 diabetes, is particularly common in the elderly; more than 50% of patients in the UK are over 60 years of age (the majority having type 2 diabetes). In many countries diabetes affects 10–25% of elderly people (> 65 years), with particularly high rates in populations such as Pima Indians, Mexican Americans and South Asians. Glucose tolerance worsens with age, the main factor being impairment of insulin-stimulated glucose uptake and glycogen synthesis in skeletal muscle; progressive insulin resistance also contributes (Table 6.1). Symptoms of diabetes may be non-specific, vague or absent.

Table 6.1 Factors contributing to glucose intolerance in old age

Impaired glucose disposal and utilization

• Insulin-mediated uptake into skeletal muscle

• Insulin-mediated vasodilatation in muscle

• Non-insulin-mediated glucose uptake (NIMGU)

NIMGU accounts for 70% of glucose uptake under fasting conditions (primarily into the CNS) and for 50% of post-prandial glucose uptake (especially into skeletal muscle)

Impaired glucose-induced insulin secretion

• Obesity

• Physical inactivity

• Reduced dietary carbohydrate

• Diabetogenic drugs (thiazides, glucocorticoids)

Aims of treatment

The management of T2DM and its common comorbidity of cardiovascular disease is complicated because of the added effects of ageing on metabolism and renal function, the use of potentially diabetogenic drugs, and low levels of physical activity. Cardiovascular risk is particularly high because many risk factors of the metabolic syndrome can be present for up to a decade before T2DM is diagnosed. Management strategies for many elderly people with diabetes are the same as those for the younger population, with similar lipid-lowering and antihypertensive treatment schedules, and aspirin or clopidogrel for patients with increased cardiovascular risk. Effective delivery of diabetes care depends on close cooperation between hospital and community, the involvement of diabetes teams and practice nurses, and attention to all causes of disability and ill-health (Table 6.2).

Table 6.2 Special characteristics of older subjects with diabetes

• High level of associated medical comorbidities

• Increased risk of cognitive dysfunction

• Mood disorder

• Varying evidence for impaired activities of daily living and lower limb function

• Increased vulnerability to hypoglycaemia

• Increased risk of inpatient mortality

• Increased need to involve spouses/family and carers in management

Comorbidity

Coexisting cardiovascular and cerebrovascular disease are especially common; polypharmacy is often necessary and carries risks of adverse effects and drug interactions. Degrees of renal impairment, arising for a multiplicity of reasons (e.g. diuretic therapy, prostatic obstruction), are relatively common in the elderly population; care must be exercised with renally excreted drugs. In addition, impaired hepatic function (e.g. hepatic congestion secondary to cardiac failure) may render certain antidiabetic medications inappropriate.

The prevalence of hypertension rises with age together with the risk of cardiovascular events. Attention should be directed towards modifiable cardiovascular risk factors, notably hypertension and dyslipidaemia. Cardiovascular events may present with atypical symptoms in the elderly (e.g. acute confusion).

Oral antidiabetic agents

Care should be exercised with sulphonylureas because severe hypoglycaemia, although uncommon, carries a relatively high mortality rate. Agents with a short duration of action are preferred.

Insulin treatment

Although the majority of elderly patients have type 2 diabetes, insulin therapy becomes necessary in a significant proportion as oral agents lose their capacity to provide adequate glycaemic control. Other patients will require insulin because of contraindications to oral agents arising from comorbidity (see above). Avoidance of insulin-induced hypoglycaemia is often paramount for the very elderly and those living alone. Insulin may be appropriately commenced during an intercurrent illness and continued thereafter when oral agents may suffice.

Institutional care of the elderly diabetic

Elderly people with diabetes in care homes are particularly vulnerable and require greater diabetes specialist input. High levels of disability are common in older people with diabetes and lead to heavy usage of health-care resources and premature death. The burden of hospital care is increased 2–3-fold in those with diabetes compared with the general aged population, with more frequent clinic visits and a 5-fold higher admission rate.

About 16% of elderly people with diabetes in the UK are registered blind or partially sighted (8-fold high than in the non-diabetic population); this justifies regular screening for undetected eye disease.

Risk factors for foot ulceration affect 25% of elderly people with type 2 diabetes.

Older people with diabetes use primary care services two to three times more often than their counterparts without diabetes.

Hospital admissions last twice as long for older patients with diabetes compared with age-matched control groups without diabetes.

Management of diabetes in women of childbearing age

An optimal outcome may be obtained from pregnancy in women with diabetes if excellent glycaemic control is achieved before and during pregnancy. However, type 1 and 2 diabetes are high-risk states for both the woman and her fetus. There is an increased risk of complications of diabetes, including severe hypoglycaemia and progression of microvascular complications.

Ketoacidosis must be avoided.

There are also increased risks of obstetric complications, such as miscarriage, maternal infection, pre-eclampsia, premature labour, polyhydramnios and failure to progress in first or second stage. Fetal and neonatal complications include congenital malformation, later intrauterine death, fetal distress, hypoglycaemia, respiratory distress syndrome and jaundice. Rates of fetal and neonatal loss and congenital malformation are increased by at least 2–3-fold. The prevalence of type 2 diabetes is increasing in women of reproductive age, and outcomes may be equivalent or worse than in those with type 1 diabetes. Management before and during pregnancy should follow the same intensive programme of metabolic, obstetric and neonatal supervision.

An experienced multidisciplinary team, led by a named obstetrician and physician with an interest in diabetes, and including a diabetes specialist nurse, diabetes specialist midwife and dietitian, should provide comprehensive care from pre-pregnancy to postnatal review.

Pre-pregnancy and pregnancy care

Contraception

Contraception should be discussed on an individual basis with all women of childbearing age with diabetes. There is little evidence on choice of contraceptive method specifically for a woman with diabetes. The contraceptive advice should follow that in the general population. The combined oral contraceptive (COC) may be contraindicated in women with diabetes according to the presence and severity of diabetic complications and/or other risk factors for vascular disease. Progestogen-only preparations, oral or intramuscular, are suitable in these women. World Health Organization (WHO) evidence-based guidance for medical eligibility criteria for contraceptive use makes recommendations for women with diabetes.

Long-acting methods such as implants, intrauterine systems (IUS) and copper intrauterine devices (IUD) are safe methods of contraception that may be particularly suitable for use in women with diabetes as they are as effective as sterilization and produce low circulating hormone levels.

Pregnancy should be planned; good contraceptive advice and pre-pregnancy counselling are essential.

Health-care professionals should refer to the WHO medical eligibility criteria for contraceptive use prior to offering contraceptive advice to women with diabetes.

Pre-pregnancy clinic

Attendance at a pre-pregnancy clinic is associated with a reduction in the rate of miscarriage and complications of pregnancy; babies have fewer problems and are kept in special care units for shorter periods than infants of non-attending mothers.

Tip box

Pre-pregnancy care for women with diabetes should be provided by a multidisciplinary team.

The essential components of a pre-pregnancy care programme include review and consideration of the medical (including pharmacological treatment) obstetric and gynaecological history; advice on glycaemic control to optimize HbA1c levels; screening for complications of diabetes; and counselling for maternal and fetal complications.

Tip box

Women contemplating pregnancy should have access to structured education in line with the recommendations for adults for diabetes.

All health-care professionals in contact with women of childbearing age with diabetes should be aware of the importance of pre-pregnancy care and local arrangements for its delivery, and should share this information with the woman.

Pre-pregnancy targets for blood sugar

Observational evidence has found an association between maternal glycaemia (before and during pregnancy) and the increased risk of congenital malformation and miscarriage. The risk of congenital anomaly in the offspring of women with pre-pregnancy diabetes is increased with an increasing level of HbA1c. No HbA1c threshold for such effects has been identified (Table 6.3).

Table 6.3 Derived absolute risk of major or minor congenital anomaly in association with the number of standard deviations (SD) of glycosylated haemoglobin above normal, and the approximate corresponding HbA1c concentration, measured periconceptually

image

Pre-pregnancy glycaemic control should be maintained as close to the non-diabetic range as possible, taking into account risk of maternal hypoglycaemia.

The target for pre-pregnancy glycaemic control for most women should, as a minimum, be an HbA1c of less than 7% (53 mmol/mol), although lower targets of HbA1c may be appropriate if maternal hypoglycaemia can be minimized.

Oral medication before and during pregnancy

Folic acid

Neural tube defects in high-risk pregnancies are associated with lower levels of folate. All women with diabetes should be prescribed high-dose pre-pregnancy folate supplementation, continuing up to 12 weeks’ gestation.

Folic acid 5-mg tablets are readily available, suitable, and should be provided wherever pre-pregnancy care is delivered.

Metformin and sulphonylureas

Metformin and sulphonylureas are not shown to be associated with an increase in congenital malformation or early pregnancy loss. Sulphonylureas other than glibenclamide are unsafe due to placental passage. Recent evidence suggests that metformin may be used in pregnancy (after discussion with patient)-NICE & IDF guidelines.

Statins

The British National Formulary recommends that statins (atorvastatin, fluvastatin, pravastatin and simvastatin) should be avoided during pregnancy and lactation. Congenital malformations have been reported and decreased synthesis of cholesterol may further affect fetal development. The malformations include major defects of the central nervous system.

Angiotensin converting enzyme inhibitors

Angiotensin converting enzyme (ACE) inhibitors have been associated with an increased risk of congenital malformation. and both ACE inhibitors and angiotensin receptor blocking medications should be avoided throughout pregnancy.

Tip box

The use of statins, ACE inhibitors and angiotensin receptor blocking medications should be reviewed in women pre-pregnancy, and avoided during pregnancy.

Nutritional management

It is good clinical practice to provide dietary advice to women before, during and after pregnancy.

Advice on diet and exercise should be offered in line with recommendations for adults with diabetes.

Tip box

Dietetic advice should be available in all diabetic antenatal clinics.

Optimization of glycaemic control

Glucose monitoring

Optimal glucose control before pregnancy reduces congenital malformations and miscarriage, while during pregnancy it reduces macrosomia, stillbirth, neonatal hypoglycaemia and respiratory distress syndrome.

All women with pre-gestational diabetes should be encouraged to achieve excellent glycaemic control.

During pregnancy, preprandial testing and where appropriate postprandial testing may be advised. A reduced incidence of pre-eclampsia is associated with postprandial monitoring and targeting.

In women with gestational diabetes, measurement and targeting of postprandial glucose is associated with improved outcomes (including birth weight, reduced perinatal morbidity and macrosomia).

Postprandial glucose monitoring should be carried out in pregnant women with gestational diabetes and may be considered in pregnant women with type 1 or type 2 diabetes.

Tip box

Postprandial glucose monitoring should be carried out in pregnant women with gestational diabetes and should be considered in pregnant women with either type 1 or type 2 diabetes.

In women with type 1 or type 2 diabetes, as long as hypoglycaemia can be minimized, aim to achieve blood glucose:

• between 4 and 6 mmol/L preprandially

• < 8 mmol/L 1 hour postprandially, or

• < 7 mmol/L 2 hours postprandially

• < 6 mmol/L before bed.

There is limited evidence that continuous glucose monitoring may be of benefit to women during pregnancy.

Diabetes specialist nurses and midwives have an important role in educating women on the need for home blood glucose monitoring and intensive insulin regimens. Intensive basal bolus regimens are commonly used and insulin analogues are increasingly used, although research on their role and safety in pregnancy is limited.

Insulin therapy

Intensive insulin therapy is beneficial in terms of maternal and neonatal outcomes. Use of insulin analogues is associated with limited evidence in terms of reduction in hypoglycaemia. The choice of insulin therapy should be discussed as part of pre-pregnancy counselling.

Lispro and aspart are associated with an improved glycaemic profile with a trend towards reduced major hypoglycaemia and nocturnal hypoglycaemia. There is a lack of high-quality evidence regarding outcomes of pregnancy using basal insulin analogue therapy or continuous subcutaneous insulin infusion (CSII) in women who are pregnant. Current evidence also suggests neither benefit nor harm with CSII.

NPH insulin should remain the basal insulin of choice in pregnancy unless the clinical benefit of a basal insulin analogue has been demonstrated on an individual basis. Rapid-acting insulin analogues (lispro and aspart) appear safe in pregnancy and may be considered in individual patients where hypoglycaemia is problematic.

Women should be advised that, although most commonly used regular human insulins are licensed for use during pregnancy, other insulins and oral glucose-lowering agents (e.g. metformin, glibenclamide, other sulphonylureas, detemir) are not.

Complications during pregnancy

Obstetric complications

There is no specific evidence on management of obstetric complications, including pregnancy-induced hypertension and increased risk of thromboembolism, in women with diabetes. These risks should be managed as for other pregnant women.

Metabolic complications

During pregnancy, hypoglycaemic unawareness and severe hypoglycaemia are common. Diabetic ketoacidosis can develop more rapidly, at lower levels of blood glucose and in response to therapeutic glucocorticoids. Women and their partners need education on the management of hypoglycaemia, including the use of glucagon; avoiding hypoglycaemia while driving; and on the recognition and prevention of ketoacidosis. Ketoacidosis may result in fetal death. Local emergency contact arrangements must also be explicit.

Microvascular complications

Diabetic retinal and renal disease can deteriorate during pregnancy. The presence of retinopathy alone is not associated with a poorer pregnancy outcome for the fetus, unless concurrent nephropathy is evident.

Retinopathy

Poor glycaemic control in the first trimester and pregnancy-induced or chronic hypertension are independently associated with the progression of retinopathy.

Nearly 40% of women with baseline retinopathy will progress during pregnancy, although sight-threatening retinopathy is rare (around 2% of pregnancies).

Examination of the retina prior to conception and during each trimester is advised in women with type 1 or type 2 diabetes. More frequent assessment may be required in those with poor glycaemic control, hypertension or pre-existing retinopathy.

Multidisciplinary teams should have locally agreed protocols for the grade of retinopathy required for referral. Owing to the potential for rapid development of neovascularization, early referral of pregnant women with referable retinopathy to an ophthalmologist is recommended.

Parous women with type 1 diabetes have significantly lower levels of retinopathy compared with nulliparous women. Women should be reassured that tight glycaemic control during and immediately after pregnancy can effectively reduce the long-term risk of retinopathy.

Nephropathy

There is an association between pre-existing nephropathy (microalbuminuria or albuminuria) and a poorer pregnancy outcome, although this is not due to any increase in congenital malformations. Proteinuria increases transiently during pregnancy, returning to a pre-pregnancy level within 3 months of delivery. The incidence of worsening chronic hypertension or pregnancy-induced hypertension/pre-eclampsia is high in women with both incipient and overt nephropathy, occurring in over 50% of women where overt nephropathy is present. Nephropathy and superimposed pre-eclampsia are the most common causes of pre-term delivery in women with diabetes.

Women with diabetic nephropathy require careful monitoring and management of blood pressure.

ACE inhibitors and angiotensin receptor blocking medications should be avoided as they may adversely affect the fetus.

Appropriate antihypertensive agents that may be used during pregnancy include methyldopa, labetalol and nifedipine.

Fetal assessment

An early pregnancy scan is considered good practice to confirm viability in women with pre-existing diabetes, particularly when changes in medication are required or diabetic control is suboptimal.

There is evidence of an increased incidence of congenital malformations in women with pre-existing diabetes (type 1 and type 2). In general, the sensitivity of ultrasound scanning for detecting structural abnormalities increase with gestational age. It is not possible to determine when during the second trimester scanning should take place to maximize detection rates. A detailed anomaly scan, including evaluation of the four-chamber heart and outflow tracts, undertaken at around 20 weeks (18–22 weeks) enables detection of many major structural abnormalities.

All women should be offered scanning to include:

• an early viability scan

• a gestational age scan between 11 and 13 weeks (+ 6 days) in association with biochemical screening and nuchal translucency measurement to risk assess for trisomies

• a detailed anomaly scan including four-chamber cardiac view and outflow tracts between 20 and 22 weeks.

In pregnancies complicated by maternal diabetes, the fetus is at risk of both macrosomia and intrauterine growth restriction (IUGR). The risk of macrosomia is greater when there has been poor glycaemic control. The risk of IUGR is greater in women with vascular complications of diabetes (retinopathy, nephropathy) or when pre-eclampsia develops.

Fetal monitoring includes cardiotocography (CTG), Doppler ultrasonography and ultrasound measurement of fetal growth and liquor volume. Although regular fetal monitoring is common practice, no evidence has been identified on the effectiveness of any single or multiple techniques, and therefore the clinical judgement of an obstetrician experienced in diabetic pregnancy is essential.

When IUGR is suspected, additional monitoring with serial ultrasonography and umbilical arterial Doppler velocimetry is associated with improved outcomes (fewer inductions of labour and hospital admissions, with a trend to improved perinatal mortality rates).

The evidence for the accuracy of ultrasonography in predicting macrosomia (birth weight above 4000 g) is mixed. The accuracy of fetal weight estimation in women with diabetes is at least comparable to that in women who are not diabetic. The negative predictive value of ultrasonography is high (80–96%), and therefore it is feasible that the true value of ultrasonography in the management of these women is its ability to rule out the diagnosis of macrosomia.

There is evidence to suggest that the incorrect diagnosis of a large-for-gestational-age fetus increases the induction and caesarean section rate without improving clinical outcome. Numerous studies have concluded that the reliability of ultrasound estimation of fetal weight is suboptimal. The ability to predict shoulder dystocia in the non-diabetic population is poor and evidence in the diabetic population limited. However, the determination of polyhydramnios is clinically useful as it may be associated with an adverse clinical outcome.

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