3.1. Diagnosis
The classic symptoms of diabetes are thirst, polydipsia (increased drinking), polyuria (increased urine output), recurrent infections and weight loss. The diagnostic criteria for diabetes are the same in children, young people and adults.11 [evidence level IV]
Children and young people with diabetes nearly always present with symptoms such as those described above, as well as metabolic changes such as hyperglycaemia (excessive glucose in the blood), marked glycosuria (glucose in the urine) and ketonuria (excessive ketone bodies in the urine).11 [evidence level IV] Studies have shown that at diagnosis around 25% of children and young people present with diabetic ketoacidosis and in children under the age of 4 years the proportion is higher.12,13 [evidence level III] In children and young people with severe symptoms, the diagnosis can be confirmed by a random plasma glucose concentration ≥ 11.1 mmol/l.11 [evidence level IV] An oral glucose tolerance test (OGTT) is not usually necessary or appropriate for children and young people who present with symptoms.
In the unusual situation where a child presents without definitive symptoms but with a plasma glucose concentration ≥ 11.1 mmol/l, the World Health Organization recommends that a fasting plasma glucose test and/or an OGTT may be required to confirm the diagnosis.11 [evidence level IV] Fasting plasma glucose measurements should be obtained after more than 8 hours without caloric intake,14 [evidence level IV] and a fasting plasma glucose concentration ≥ 7.0mmol/l can be used to confirm the diagnosis.11 [evidence level IV] A suitable OGTT for children and young people involves oral administration of 1.75 g of glucose/kg body weight up to a maximum of 75 g of glucose, followed by measurement of glucose and insulin levels at 0, 1 and 2 hours. Confirmation of diagnosis by this method requires a plasma glucose concentration ≥ 11.1 mmol/l from a blood sample collected 2 hours after administering the glucose load.11 [evidence level IV]
Impaired glucose regulation (a metabolic state intermediate between normal glucose homeostasis and diabetes) occurs in two forms:11 [evidence level IV]
impaired glucose tolerance (fasting plasma glucose concentration < 7.0 mmol/l, and plasma glucose concentration ≥ 7.8 mmol/l but < 11.1 mmol/l 2 hours after OGGT)
impaired fasting glycaemia (fasting plasma glucose concentration ≥ 6.1 mmol/l but <7.0 mmol/l, and plasma glucose concentration < 7.8 mmol/l 2 hours after OGGT).
Impaired glucose tolerance and impaired fasting glycaemia are risk categories for future diabetes and/or adult cardiovascular disease, rather than clinical entities in their own right.11 [evidence level IV] Children and young people with impaired glucose regulation and/or asymptomatic presentation of mild hyperglycaemia may have non-type 1 diabetes (such as early-onset type 2 diabetes, other insulin resistance syndromes, maturity-onset diabetes in the young and molecular/enzymatic abnormalities). Non-type 1 diabetes should be considered if the child is obese, or of Black or Asian origin, or if there is a strong family history of early-onset type 2 diabetes or other syndromes.
Where uncertainty exists, additional support for the type of diagnosis can be made by measuring specific immunological markers of beta-cell damage: abnormal levels of islet cell antibodies, insulin auto-antibodies and glutamic acid decarboxylase antibodies usually signify type 1 diabetes.15 [evidence level IV]
An international expert committee considered the World Health Organization’s criteria for diagnosis and classification of type 1 diabetes.16 [evidence level IV] The expert committee agreed with the criteria used by the World Health Organization except for concluding that OGTTs should be discouraged in clinical practice due to their inconvenience, greater cost and lower reproducibility compared with fasting plasma glucose or 2 hours post-glucose plasma glucose tests.
Record keeping and registers
At present there is no complete national register of children and young people with type 1 diabetes in the UK. The National Paediatric Diabetes Audit, which started in 1999 and was funded through the Diabetes Foundation, is a joint initiative between Diabetes UK, the Royal College of Paediatrics and Child Health and the British Society for Paediatric Endocrinology and Diabetes. This audit project has now moved to the National Clinical Audit Support Programme. The aim of the audit is to establish a national paediatric diabetes recording system to facilitate a national audit mechanism and develop a cycle of continuous quality improvement in paediatric diabetes care throughout the UK.17
A 1998 survey of consultant paediatricians who provide care for children and young people with diabetes aged under 16 years in the UK found that 34% of consultants reported using a computer database. ‘Twinkle’ was used in 19 centres, ‘Novonet’ was used in five centres and ‘Diamond’ was used in four centres. The majority of services used locally developed databases.18 [evidence level III]
We identified no studies that investigated the clinical effectiveness of registers for children and young people with type 1 diabetes.
An RCT of different implementation strategies for using a diabetes register found that use of registers to produce letters to remind patients of clinic appointments showed no overall improvement in glycated haemoglobin level or attendance for testing of glycated haemoglobin compared with patients who did not receive letters.19 [evidence level Ib]
A retrospective cohort study of adult patients with all types of diabetes investigated the effects of an electronic management system compared with traditional paper medical records (n = 82).20 [evidence level IIb] The study found the electronic management system was associated with an increased number of foot examinations/year (2.9 ± 1.1 versus 1.8 ± 1.4, p < 0.001), an increased number of blood pressure readings/year (3.6 ± 1.6 versus 2.7 ± 1.6, p < 0.0035) and an increase in the number of patients having four glycated haemoglobin tests in the last year (76.9 versus 51.2, p = 0.016). However, there was no difference between the most recent glycated haemoglobin levels (9.7 ± 1.7% versus 10.2 ± 1.9%).
RECOMMENDATIONS
The diagnosis of type 1 diabetes in children and young people should be based on the criteria specified in the 1999 World Health Organization report on the diagnosis and classification of diabetes mellitus.
[D]
Children and young people with suspected type 1 diabetes should be offered immediate (same day) referral to a multidisciplinary paediatric diabetes care team that has the competencies needed to confirm diagnosis and to provide immediate care.
[GPP]
Consideration should be given to the possibility of other types of diabetes (such as early-onset type 2 diabetes, other insulin resistance syndromes, maturity-onset diabetes in the young and molecular/enzymatic abnormalities) in children and young people with suspected type 1 diabetes who:
[GPP]
have a strong family history of diabetes
are obese at presentation
are of Black or Asian origin
have an insulin requirement of less than 0.5 units/kg body weight/day outside a partial remission phase
have no insulin requirement
rarely or never produce ketone bodies in the urine (ketonuria) during episodes of
hyperglycaemiashow evidence of insulin resistance (for example, acanthosis nigricans)
have associated features, such as eye disease, deafness, or another systemic illness or syndrome.
Children and young people with type 1 diabetes should be entered on a population-based, practice-based and/or clinic-based diabetes register.
[GPP]
3.2. Management from diagnosis
Type 1 diabetes can have a potentially devastating acute and long-term effect on a child or young person and their family. The management of type 1 diabetes, education, empowerment and support of the child or young person and their family in the first few weeks can have a long-term effect on their acceptance of the condition, and their skills and enthusiasm in its management.21 [evidence level IV]
The National Service Framework for Children states that:22
‘Children and young people [with type 1 diabetes] should receive care that is integrated and coordinated around their particular needs, and the needs of their family. They, and their parents, should be treated with respect, and should be given support and information to enable them to understand and cope with the [diagnosis of diabetes] and the treatment needed. They should be encouraged to be active partners in decisions about their health and care, and, where possible, be able to exercise choice.’
The National Service Framework for Diabetes Delivery Strategy states that:23
‘A care plan is at the heart of a partnership approach to care and a central part of effective care management. The process of agreeing a care plan offers people active involvement in deciding, agreeing and owning how their diabetes will be managed. Whilst the overall goal is a genuine partnership, the person with diabetes must feel that they are comfortable with what is proposed and that they do not have to bear more responsibility than they wish.’
What is the optimum location (home versus hospital) for the management of children and young people with newly diagnosed type 1 diabetes?
In the past there has been some controversy as to whether or not children and young people with type 1 diabetes should be managed in hospital or at home soon after diagnosis.
A systematic review identified two RCTs,24,25 three retrospective cohort studies26–28 and a prospective cohort study.29,30 [evidence level Ia] The systematic review found that owing to the low quality or limited applicability of the studies identified the results were inconclusive. However, the data suggested that home or outpatient management of type 1 diabetes in children at diagnosis did not lead to any disadvantages in terms of metabolic control, acute diabetes complications and hospitalisations, psychosocial variables and behaviour, or total costs.30 [evidence level Ia]
The two RCTs included in the systematic review compared home care packages to standard hospital inpatient care for the management of children and young people over the age of 2 years with newly diagnosed type 1 diabetes.24,25 [evidence level Ib] The trials were conducted in Finland and Canada, and the children and young people were followed for 2–5 years. The outcomes reported were HbA1c, diabetes-related adverse events, diabetes knowledge, adherence to treatment, family impact, stress, satisfaction, child behaviour, social cost, insulin dosage, family social variables and rate of re-admission. In the Finnish study, the two treatment groups received the same content and quantity of patient education, although few specific details were provided in the report. In the Canadian study, both treatment groups had 24-hour telephone access to a diabetologist or a diabetes nurse; the diabetes care team also included a psychologist and a social worker. Children and young people who lived more than 1 hour’s travelling time from the hospital were excluded from the study.
The Finnish study found no significant difference in HbA1c levels between the two treatment groups (n = 60).25 [evidence level Ib] The Canadian study reported improved glycaemic control in the home care group.24 [evidence level Ib] However, in this study the treatment groups differed in terms of continuity of care, and the home care group spent more hours with a diabetes nurse. These factors could explain the improved glycaemic control in the home care group.
Both studies examined diabetes-related hospital admissions in the post-initial management period. Neither study found a significant difference between home and hospital care groups. The Finnish study measured insulin dosage, and showed a statistically significant decrease in insulin use among children and young people treated as outpatients.31 [evidence level Ib] The Canadian study found no statistically significant differences between home and hospital care groups in terms of psychosocial outcomes, knowledge of diabetes, adherence to insulin therapy, family impact, satisfaction, child behavioural problems or social costs. This study did find significantly higher perceived stress levels among young people in the home care group after 1 month, although the difference was not significant at 12 months or 24 months. Perceived stress levels among parents did not differ significantly between home and hospital care groups at any time (n = 63).24 [evidence level Ib]
We did not identify any RCTs that investigated the location of initial management in the UK. A retrospective cohort study based in Leicester reported significantly fewer diabetes-related hospital re-admissions among children and young people who received home-based care.25 [evidence level IIb] However, glycated haemoglobin concentrations did not differ significantly between home and hospital care groups. In this observational study, the difference between the rates of hospital re-admission in the home and hospital care groups may have been due to differences between the two groups that were not related to the location of initial management.
A descriptive observational study from Birmingham showed that 14% of children and young people with diabetes could be fully managed at home from the time of diagnosis. The mean length of inpatient hospital-based care for children and young people with newly diagnosed type 1 diabetes was 2 days.32 [evidence level III]
Another descriptive observational study from the USA reported that 35% of children and young people with newly diagnosed type 1 diabetes were treated as outpatients.33 [evidence level III]
Three non-experimental descriptive studies reported outcomes for children and young people receiving initial management at home or in hospital.26,29,34 [evidence level III] However, these studies were likely to have been affected by bias because children and young people who receive hospital-based initial management usually have severe symptoms which may be associated with long-term outcomes. The first study showed that the incidence of severe hypoglycaemia, diabetic ketoacidosis, diabetes-related complications and HbA1 did not differ significantly between children and young people receiving home- and hospital-based care.26 [evidence level III] The second study reported that hospitalisation episodes and ketoacidotic episodes were more common in children and young people treated initially as inpatients than in children and young people managed initially as outpatients (hospitalisation episodes: RR 3.7, 95% CI 1.5 to 9.0; ketoacidotic episodes: RR 3.1, 95% CI 1.5 to 6.3). However, there was no significant difference in the incidence of severe hypoglycaemia between the two treatment groups.34 [evidence level III] The third study found no significant differences in re-admission and emergency room visits, knowledge, responsibility of care, coping skills or quality of life between children and young people who received home- and hospital-based education. However, there were small differences in adherence to blood glucose regulation, emergency precautions and family functioning.29 [evidence level III]
Two further studies investigated the effects of reducing the length of hospital-based care. An RCT compared early discharge, care in a hospital-based family apartment, and conventional hospital-based care.35 [evidence level Ib] There was no significant difference in glycaemic control or readmission rates between the three groups. A non-randomised controlled trial that compared short (average 9 days) and long (approximately 23 days) initial hospital stays found no significant differences in metabolic control, percentage of children and young people that tested positive for C-peptide (an indicator of endogenous insulin production) after 2 years, insulin dosage31,36 or psychosocial function31,36 between the two treatment groups. [evidence level IIa]
We found an economic study based on a Canadian RCT.37 This study was based on data from one hospital and home care programme. The home care programme consisted of two nurse visits a year and a 24-hour telephone support service. Home care patients were offered psychosocial support and counselling and were offered an additional clinic visit with a diabetologist. Overall, the cost of home care was found to be higher. The increased cost of home care was attributable to increased specialist diabetes nursing care and increased psychosocial counselling, although the cost to parents was lower.
Diabetes care teams
The clinical management of children and young people with type 1 diabetes is normally organised by a team of healthcare professionals.
A 1998 survey of consultant paediatricians who provide care for children and young people with diabetes aged under 16 years in the UK found variation across the country on who provided care for children and young people with diabetes (n = 244 paediatricians, n = 17 192 children and young people).18 [evidence level III] Of these consultant paediatricians, 78% expressed a specialist interest in diabetes, and 91% saw children in a designated diabetes clinic. There was a specialist nurse in 93% of the clinics, 66% of whom were trained to care for children and 47% of whom had a caseload of more than 100 children. A paediatric dietitian was present in 65% of the clinics, and in 25% of clinics some form of specialist psychology or counselling was available.
The young people’s consultation day organised for this guideline in collaboration with the NCB found that:38 [evidence level IV]
Young people with type 1 diabetes felt that healthcare professionals should be skilled in gaining the confidence of young people by educating them about diabetes in accessible language, treating them as individuals and with respect, and ensuring that they are given the opportunity to contribute to decisions about their diabetes care.
Young people with type 1 diabetes and their parents felt they should have 24-hour access to a named specialist nurse with whom they could speak confidentially and who they could contact between clinic appointments.
Some young women with type 1 diabetes stated a preference for a female doctor with whom they felt they would be more comfortable.
Young people with type 1 diabetes and their parents felt that it was important to see the same members of the
diabetes care team wherever possible.
Young people with type 1 diabetes liked age-banded clinics.
Young people with type 1 diabetes were happy to miss school in order to attend clinic appointments, but their parents would prefer clinic appointments to be available outside of school hours.
Parents of young people with type 1 diabetes suggested that clinic appointments should be flexible enough to take into account school terms, timetables and examination schedules.
parents of young people with type 1 diabetes felt that there should be easy access to psychology services and suggested that paediatric diabetes care teams should include a psychologist.
RECOMMENDATIONS
Children and young people with type 1 diabetes should be offered an ongoing integrated package of care by a multidisciplinary paediatric diabetes care team. To optimise the effectiveness of care and reduce the risk of complications, the diabetes care team should include members with appropriate training in clinical, educational, dietetic, lifestyle, mental health and foot care aspects of diabetes for children and young people.
[GPP]
Children and young people with type 1 diabetes and their families should be offered 24-hour access to advice from the diabetes care team.
[GPP]
Children and young people with type 1 diabetes and their families should be involved in making decisions about the package of care provided by the diabetes care team.
[GPP]
At the time of diagnosis, children and young people with type 1 diabetes should be offered home-based or inpatient management according to clinical need, family circumstances and wishes, and residential proximity to inpatient services.
[A]
Home-based care with support from the local paediatric diabetes care team (including 24-hour telephone access to advice) is safe and as effective as inpatient initial management.
[D]
Children and young people who present with diabetic ketoacidosis should have their diabetic ketoacidosis treated in hospital according to the guidance outlined in this document.
[GPP]
Children with type 1 diabetes who are younger than 2 years of age and children and young people who have social or emotional difficulties, or who live a long way from hospital should be offered inpatient initial management.
[GPP]
Children and young people with type 1 diabetes and their families should be offered appropriate emotional support following diagnosis, which should be tailored to emotional, social, cultural and age-dependent needs.
[GPP]
3.3. Natural history of type 1 diabetes
Although considerably decreased, significant endogenous insulin production is often present at diagnosis of type 1 diabetes. For many patients this endogenous insulin production is a major factor in the occurrence of a ‘partial remission phase’ or ‘honeymoon period’.
The partial remission phase has been defined as a period when an insulin dosage of less than 0.5 units/kg body weight/day results in an HbA1c level of less than 7%,39 or when an insulin dosage of less than 0.3 units/kg body weight/day results in an HbA1c level of less than 6%.40 [evidence level III]
There is a wide variation in the prevalence of a partial remission phase in children and young people with type 1 diabetes. An observational study found that 80% of children and young people with newly diagnosed type 1 diabetes experienced a partial remission phase that lasted at least 3 months.39 [evidence level III] A second study found that 65% of children and young people experienced a partial remission phase.41 [evidence level III] However, a consensus guideline suggested that 30–60% of children and young people experience a partial remission phase.15 [evidence level IV]
Factors determining the length of the partial remission phase
Two observational studies found no association between the sex of children and young people and the presence or duration of a partial remission phase.39,40 [evidence level III] However, a third observational study found that males with type 1 diabetes were more likely to experience a partial remission phase than females (occurrence of remission: 73% in males versus 53% in females, RR 1.38, 95% CI 1.08 to 1.76; duration of remission: 279 ± 22 days in males versus 210 ± 25 days in females, p < 0.01).41 [evidence level III]
Four observational studies found that younger children were less likely than older children to experience a remission phase, and that younger children had shorter remission phases than older children. One study compared children diagnosed before the age of 5 years to those diagnosed after the age of 5 years (remission phase of at least 3 months: 50% under 5 years versus 90% over 5 years, p < 0.0005; average duration of remission phase: 7.3 ± 8.4 months versus 13.1 ± 8.6 months, p < 0.05).39 [evidence level III] A second study found that a remission phase occurred in 0%, 16%, 5% and 23% of children aged 5 years or younger, 5.1–9 years, 9.1–12 years and over 12 years, respectively (p = 0.01).40 [evidence level III] The same study found that residual C-peptide secretion was significantly reduced during the first year of disease in children with disease onset before the age of 5 years (p < 0.001).40 [evidence level III] Another study found that the age of onset of type 1 diabetes was greater in children who experienced a partial remission phase than in other children (7.6 ± 0.4 years versus 6.3 ± 0.5 years, p < 0. 05).41 [evidence level III]
Insulin treatment during the partial remission phase
We found no studies relating to the optimisation of insulin treatment during the partial remission phase. However, one study evaluated guidance aimed at reducing insulin dosage in response to self-monitoring of blood glucose levels in young people with newly diagnosed type 1 diabetes who presented with ketosis.42 [evidence level III] This study showed that, on average, the insulin dosage was reduced from 62 units/day to 33 units/day while maintaining preprandial blood glucose levels of 4–7 mmol/l.42 [evidence level III]
Insulin regimens for prolonging the partial remission phase
We found two RCTs that compared the effectiveness of continuous subcutaneous insulin infusion (CSII), or ‘insulin pump therapy’, with once-/twice-daily insulin injection therapy in children and young people with newly diagnosed type 1 diabetes. One study in which the children and young people were followed up for 2 years found CSII was associated with lower HbA1c levels from 2 months after diagnosis, but that it did not prolong endogenous insulin production (n = 30).43,44 [evidence level Ib] An earlier RCT in young people aged 13–19 years found no difference in HbA1c levels 1 year after the start of CSII compared with once-/twice-daily insulin injection therapy (n = 14).45 [evidence level Ib]
We found one RCT that compared the effectiveness of continuous venous insulin infusion for the first 28–62 days of treatment with once-daily subcutaneous insulin injections in young people with newly-diagnosed type 1 diabetes. During the intervention period continuous venous insulin infusion was associated with lower HbA1c levels (10.9 ± 0.6% versus 14.6 ± 0.7%, p < 0.005), and lower fasting plasma glucose levels and urinary glucose excretion, but after the intervention period finished there was no difference in HbA1c (n = 14).46 [evidence level Ib]
We found one non-randomised intervention study that compared the effectiveness of a closed loop insulin delivery system (artificial pancreas) for around 5 days with CSII in young people with newly diagnosed type 1 diabetes 3 to 5 days after diagnosis. The closed loop insulin delivery system was associated with a higher proportion of patients who had a remission period (18/23 versus 3/10). There were no differences in duration of remission period or mean basal or postprandial blood glucose levels (n = 33).47 [evidence level IIa]
Immunotherapy for prolonging the partial remission phase
The use of immunotherapy in type 1 diabetes has been investigated over the past 20 years. We found studies that investigated eight different therapies.
Cyclosporin
The effectiveness of cyclosporin compared with placebo was investigated in two RCTs. One RCT investigated cyclosporin in combination with insulin therapy compared with a placebo with insulin therapy in patients with type 1 diabetes between the ages of 10 and 35 years.48 [evidence level Ib] The study found cyclosporin treatment to be associated with insulin-free remission at 6 and 12 months (38.7% versus 19.1%, p < 0.001, n = 54 at 6 months; 24.2% versus 9.8%, p < 0.002, n = 31 at 12 months). A follow-up to the study using matched pairs of patients found that at 6 months after discontinuation of the treatment HbA1c was higher in the cyclosporin-treated group than the placebo group. However, at 15 months after discontinuation of the treatment there was no difference between the cyclosporin-treated group and the placebo group.49 [evidence level IIa]
A second RCT compared cyclosporin plus insulin therapy with placebo plus insulin therapy in patients aged 15–40 years with type 1 diabetes (n = 122).50 [evidence level Ib] Cyclosporin treatment was associated with insulin-free remission at 9 months (24.1% versus 5.8%, p < 0.01) but not at 6 months (25.4% versus 18.6%).
A non-randomised intervention study investigated the effectiveness of two different doses of cyclosporin in children and young people (n = 28).51 [evidence level IIa] There was no difference between the average HbA1c levels in the groups of children and young people with different doses of cyclosporin. High-dose cyclosporin (target trough plasma levels of 200 ng/ml) was associated with a higher number of children and young people in insulin-free remission at 6 months compared with low-dose cyclosporin (target trough plasma levels of 100 mg/ml) (3/6 versus 5/14). A cohort study investigated the effectiveness of cyclosporin in children and young people, including some of the children and young people from the above non-randomised intervention study (n = 83 treated with cyclosporin, n = 47 not treated with cyclosporin).52 [evidence level IIa] Children and young people treated with cyclosporin had lower HbA1c levels than those not treated with cyclosporin (HbA1c approximately 1–1.5% lower in cyclosporin-treated children during the first 4 years of follow-up) and a lower frequency of hypoglycaemia/patient (0.03 ± 0.03 versus 0.23 ± 0.09, p < 0.05).
Nicotinamide
A meta-analysis53 of seven RCTs54–59 investigated the effectiveness of nicotinamide compared with placebo in children, young people and adults with type 1 diabetes (n < 211, exact number not reported). There was no difference in HbA1c levels between patients treated with nicotinamide and placebo (standardised difference 0.08% at 6 months, approximate 95% CI −0.67 to 0.83%). [evidence level Ia]
The effectiveness of nicotinamide compared with placebo was investigated in one RCT in young adults (n = 21, mean age 23 years in the nicotinamide group versus 26 years in the placebo group).60 [evidence level Ib] There were no differences in HbA1c levels at 6, 12 or 24 months (5.7 ± 0.5% versus 5.4 ± 0.9% at 6 months; 6.0 ± 0.6% versus 5.8 ± 0.9% at 12 months; 6.6 ± 0.9% versus 6.0 ± 0.4% at 24 months). In both groups, similar numbers of patients experienced an insulin-free remission or partial remission (2/11 versus 3/9 in insulin-free remission and 4/11 versus 4/10 in partial remission at 6 months; 3/11 versus 3/9 in partial remission at 12 months; 1/11 versus 1/9 in partial remission at 2 years).
A controlled study (unknown if randomised) investigated the effectiveness of nicotinamide compared with placebo in children, young people and young adults (n = 16, age range 10–35 years).61 [evidence level IIa] Nicotinamide was associated with an increase in patients experiencing an insulin-free remission (5/7 versus 2/9 at 6 months; 3/7 versus 0/9 at 1 year) and a decrease in HbA1c levels (7%, SE 0.46% versus 7.7%, SE 0.7% at 6 months; 6.4%, SE 0.6% versus 8.6%, SE 0.5% at 1 year).
Nicotinamide and cyclosporin
The effectiveness of cyclosporin and nicotinamide combined compared with nicotinamide alone and a control group was investigated in children, young people and young adults in an RCT (n = 90, age range 7–40 years).62 [evidence level Ib] There was no difference in the total number who experienced a remission period by 1 year (7/30 versus 5/30 versus 2/30). However, at 3 months the cyclosporin and nicotinamide combination was associated with an increased number of clinical remissions (6/30 versus 1/30 versus 0/30, p = 0.05) and nicotinamide alone was associated with a longer duration of clinical remission than was the cyclosporin plus nicotinamide and control (7 ± 3 months, p < 0.02).
Methylprednisolone
The effectiveness of methylprednisolone has been investigated in two studies. One controlled study without randomisation investigated children and young people treated with intravenous methylprednisolone pulse therapy in combination with multiple subcutaneous insulin injections compared with a control group receiving only multiple subcutaneous insulin injections (n = 31).63 [evidence level IIa] At 12 months, methylprednisolone treatment was associated with an increase in the number of children and young people having had a remission period (4/16 versus 1/11 with complete remission where no insulin required; 9/16 versus 1/11 with partial remission involving 50% reduction in insulin dosage, p < 0.01), an increase in the duration of remission (6.6 ± 4.6 months versus 3.1 ± 2.3 months, p < 0.01), and a decrease in HbA1c levels (9.2 ± 3.6% versus 10.5 ± 1.9%, p < 0.01). A controlled study without randomisation in children, young people and adults investigated oral methylprednisolone with insulin therapy compared with insulin therapy alone (n = 25).64 [evidence level IIa] All patients in the study underwent a remission period. Oral methylprednisolone was associated with an increased duration of remission (p < 0.001), although there were no differences in HbA1c levels. The study discussed several adverse effects that may be associated with oral methylprednisolone.
Prednisone
One RCT has investigated the effectiveness of prednisone in adults (n = 25).65 [evidence level Ib] Prednisone was associated with an increase in partial remission compared with placebo (6/9 versus 2/10). Adverse events (facies lunaris and epigastralgia) were reported.
Indometacin
One RCT has investigated the effectiveness of indometacin in adults (the same RCT as above, n = 25).66 [evidence level Ib] No association was seen between indometacin and partial remission compared with placebo (1/4 versus 2/10). An adverse event (headache) was reported.
Theophylline
One RCT has investigated the effectiveness of theophylline in adults (the same RCT as above, n = 10).66 [evidence level Ib] Theophylline was associated with an increase in partial remission compared with placebo (4/5 versus 2/4).
Thymopentin
One RCT has investigated the effectiveness of thymopentin in young people and young adults (n = 48, age range 12–31 years).67 [evidence level Ib] Thymopentin was associated with an increase in partial remission compared with control (7/16 versus 3/30 at 6 months; 9/16 versus 2/30 at 1 year; p range ≤ 0.05–0.01). There were no differences in HbA1c levels (8.8 ± 0.4% versus 8.7 ± 0.3% at 1 month; 6.2 ± 0.2% versus 6.5 ± 0.1% at 6 months; 6.4 ± 0.4% versus 7.5 ± 0.5% at 1 year).
Interferon
One RCT has investigated the effectiveness of interferon in young people and young adults with type 1 diabetes (n = 16, age range 15–25 years).68 [evidence level Ib] No difference was seen in the number of patients experiencing a remission phase at 1 year (6/20 versus 12/23), nor in HbA1c levels (8.9 ± 0.3% versus 9.1 ± 0.4% at 1 month; 8.1 ± 0.5% versus 7.9 ± 0.5% at 6 months; 8.6 ± 0.6% versus 9.7 ± 0.7% at 12 months; 9.8 ± 0.6%, n = 9 versus 9.5 ± 0.7%, n = 9 at 30–36 months).
Methotrexate
One RCT has investigated the effectiveness of methotrexate in children and young people (n = 10).69 [evidence level Ib] No difference was seen in the number of patients experiencing a remission phase at 18 months (1/5 versus 3/5). Adverse effects were investigated and found to be minimal.
Azathioprine
One RCT has investigated the effectiveness of azathioprine in children and young people (n = 49).70 [evidence level Ib] No difference was seen in the number of patients experiencing a remission phase (7/24 versus 10/25 at 6 months; 4/24 versus 4/25 at 1 year), nor in HbA1c levels (7.2 ± 0.4% versus 6.6 ± 0.2% at 6 months; 7.7 ± 0.3% versus 7.1 ± 0.3% at 12 months). Adverse effects were investigated and no difference was found in the number of infections between the two groups. However, there was a greater number of skin lesions reported in the azathioprine-treated children and young people.
Healthcare professionals may find it useful to refer to the recommendations in Section 4.1 (education) when offering information about the natural history of type 1 diabetes.
RECOMMENDATIONS
Children and young people with newly diagnosed type 1 diabetes should be informed that they may experience a partial remission phase (or ‘honeymoon period’) during which a low dosage of insulin (0.5 units/kg body weight/day) may be sufficient to maintain an HbA1c level of less than 7%.
[D]
Children and young people with type 1 diabetes should be informed that the use of multiple daily insulin injection regimens or continuous subcutaneous insulin infusion (or insulin pump therapy) will not prolong the partial remission phase, although these forms of therapy may be appropriate for optimising glycaemic control, especially in young people.
[A]
3.4. Essential education at diagnosis
A consensus guideline has highlighted education as an essential part of the package of care at diagnosis.15 [evidence level III] The consensus guideline and Diabetes UK care recommendations suggested topics that could act as a template in which to develop an appropriate curriculum, with the proviso that the content and pace of education should be determined by the individual and the model of care utilised. Education for children and young people with newly diagnosed type 1 diabetes, their families and other carers should aim to cover the following topics:15,71 [evidence level IV]
explaining how the diagnosis has been made and reasons for symptoms, including a simple explanation of the uncertain cause of diabetes and that there is no cause for blame
identifying and addressing fears, anxieties and preconceived ideas of diabetes and other questions that children, young people or family members may have
risks associated with type 1 diabetes
the need for immediate insulin and how insulin works
practical skills in insulin injection
what glucose is, normal blood glucose levels, glucose targets, practical skills in self-monitoring of blood glucose and reasons for monitoring
basic dietetic advice and information about healthy eating
the advantages of physical activity and strategies to prevent adverse events occurring during or after physical activity
awareness of acute complications and how to deal with them, including
hypoglycaemia, stressing that glucose or sucrose must always be available
management of type 1 diabetes during intercurrent illness, including advice not to omit insulin
aspects of self-confidence needed for self-management
psychological adjustment to the diagnosis of type 1 diabetes
everyday issues such as diabetes at home and school, identification cards or bracelets and providing contacts for further advice
information about diabetes support groups and local services for people with diabetes, including contact telephone numbers
details of emergency telephone contacts.
A UK health technology assessment has addressed aspects of education in children, young people and young adults with type 1 diabetes (age range 9–21 years).72 [evidence level Ia–II] The health technology assessment identified five studies that examined education of children and young people with type 1 diabetes. Three of the studies,36,73,74 [evidence level IIa–IIb] which concerned education offered in relation to the place of initial management, were discussed in Section 3.2. The two remaining studies27,75 [evidence level Ib–IIa] are summarised below, together with other studies that were identified in our searches. Further evidence and recommendations relating to education are presented in Section 4.1.
The young people’s consultation day organised for this guideline in collaboration with the NCB found that some young people with type 1 diabetes felt they were given too much information at the time of diagnosis. Young people with type 1 diabetes wanted information aimed at them rather than just at their parents, although they understood that their parents also needed to know how to manage type 1 diabetes.38 [evidence level IV]
An RCT in children and young people with newly diagnosed type 1 diabetes investigated the use of additional educational support at diagnosis in the form of a booklet called Improving compliance with treatment for diabetes. The study showed that there was a general tendency for lower glycated haemoglobin levels in the group given the booklet but a significantly lower glycated haemoglobin level was only seen at 10–13 months after diagnosis (p < 0.01, exact results not reported).76 [evidence level Ib]
Techniques for initiating insulin therapy
We found no systematic reviews, RCTs or observational studies that evaluated education for the initiation of insulin therapy for children and young people with newly diagnosed type 1 diabetes.
Techniques for monitoring blood glucose levels
We found one RCT that investigated education at diagnosis for self-monitoring of blood glucose levels.75 [evidence level Ib] The RCT was based on 36 children and young people with newly diagnosed type 1 diabetes. The intervention group received seven sessions of training that related specifically to self-monitoring of blood glucose for the purposes of adjusting diet, exercise and insulin administration. The intervention group was compared with a control group that received non-specific training sessions and another control group that received standard care. The group that received training in self-monitoring of blood glucose levels had lower HbA1 levels at 1 year (p < 0.01) and 2 years (p < 0.05) compared with the group that received standard care, but not compared with the group that received non-specific training.75 [evidence level Ib]
Avoiding and treating symptoms of hypoglycaemia
We found no studies that evaluated initial education for avoiding and treating hypoglycaemia in children and young people with newly diagnosed type 1 diabetes.
An RCT involving 332 children and young people with previously diagnosed type 1 diabetes (diagnosed 5 years earlier on average) investigated an education programme involving a video and brochure that reviewed skills for self-control and treatment with the aim of preventing hypoglycaemia. The study found no difference in the incidence of severe hypoglycaemia between the intervention and control groups after 1 year.77 [evidence level Ib]
A non-controlled intervention study involving 86 children and young people with previously diagnosed type 1 diabetes (diagnosed 4 years earlier on average), found no difference in the incidence of hypoglycaemia after the use of a video and brochure. However, HbA1c levels were lower after 1 year and 2 years than at baseline. In this study, 84% of respondents indicated that receiving a video for home use was valuable, and 84% of respondents anticipated using the videos in future.78 [evidence level III]
Psychological support
We found one study with a non-randomised control group that investigated the effects of intensive psychosocial education/support in the month following diagnosis.27 [evidence level IIa] This study was based on 223 children, young people and young adults with type 1 diabetes (age range 7–24 years) who were followed up for 3–15 years. The study reported better adherence to therapy (p < 0.001), better family relations (p < 0.02) and better sociability (p < 0.025) in the intervention group, although there was no significant difference in school work between the intervention and control groups, and the significant differences that were reported were specific to higher socio-economic groups.27 [evidence level IIa]
We found no studies that investigated education for parents and other carers, dietary management, exercise or protocols for the management of intercurrent illness (‘sick-day rules’) in relation to children and young people with newly diagnosed type 1 diabetes. General evidence relating to these topics is discussed in Sections 4.1, 4.7, 4.8 and 5.4 respectively.
RECOMMENDATION
Children and young people with newly diagnosed type 1 diabetes should be offered a structured programme of education covering the aims of insulin therapy, delivery of insulin, self-monitoring of blood glucose, the effects of diet, physical activity and intercurrent illness on glycaemic control, and the detection and management of hypoglycaemia.
[D]
