Diabetes (type 1 and type 2) in children and young people: diagnosis and management

National Institute for Health and Care Excellence

This updated guideline covers the diagnosis and management of type 1 and type 2 diabetes in children and young people aged under 18. The guideline recommends how to support children and young people and their families and carers to maintain tight control of blood glucose to reduce the long-term risks associated with diabetes.

In May 2023, NICE reviewed the evidence and made new recommendations on blood glucose monitoring and management for children and young people with type 2 diabetes. For more details, see the update information.

Full guideline: Diabetes (type 1 and type 2) in children and young people: diagnosis and management

Diabetes in adults: updated quality standards

National Institute for Health and Care Excellence (NICE)

NICE has updated and replaced the quality standard on diabetes in adults (published March 2011). The quality standard on diabetes in adults is now split into separate quality standards on type 1 diabetes in adults and type 2 diabetes in adults.

Type 1 diabetes in adults. Quality standard [QS208]
This quality standard covers care and treatment for adults (aged 18 and over) with type 1 diabetes. It describes high-quality care in priority areas for improvement. It does not cover diabetes in children and young people, diabetes in pregnancy or other types of diabetes in adults.

Type 2 diabetes in adults. Quality standard [QS209]
This quality standard covers prevention of type 2 diabetes in adults (aged 18 and over) and care and treatment for adults with type 2 diabetes. It describes high-quality care in priority areas for improvement. It does not cover diabetes in children and young people, diabetes in pregnancy and other types of diabetes in adults.

Diabetes guidance: NICE updates

National Institute for Health and Care Excellence | updated 31st March

Type 1 diabetes in adults: diagnosis and management
This guideline covers care and treatment for adults (aged 18 and over) with type 1 diabetes. It includes advice on diagnosis, education and support, blood glucose management, cardiovascular risk, and identifying and managing long-term complications.

In March 2022, NICE reviewed the evidence and updated the recommendations on diagnosis and continuous glucose monitoring (CGM), replacing existing recommendations on diagnosis and CGM.

Type 2 diabetes in adults: management
This guideline covers care and management for adults (aged 18 and over) with type 2 diabetes. It focuses on patient education, dietary advice, managing cardiovascular risk, managing blood glucose levels, and identifying and managing long-term complications.

In March 2022, NICE reviewed the evidence and made new recommendations on continuous glucose monitoring (CGM).

Diabetes (type 1 and type 2) in children and young people: diagnosis and management
This guideline covers the diagnosis and management of type 1 and type 2 diabetes in children and young people aged under 18. The guideline recommends how to support children and young people and their families and carers to maintain tight control of blood glucose to reduce the long-term risks associated with diabetes.

In March 2022, NICE reviewed the evidence and updated the recommendations on continuous glucose monitoring (CGM), replacing existing recommendations on CGM.

A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial

Background

Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for adolescents and young adults with type 1 diabetes.

Methods

In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation [FLAIR]), individuals aged 14–29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA _1c) levels of 7·0–11·0% (53–97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA _1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete.

Findings

Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] −3·00% [95% CI −3·97 to −2·04]; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] −0·06% [95% CI −0·11 to −0·02]; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group.

Interpretation

Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology

Funding

National Institute of Diabetes and Digestive and Kidney Diseases.

Reference: The Lancet, VOLUME 397, ISSUE 10270, P208-219, JANUARY 16, 2021

Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes

BACKGROUND

Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor α that has already been approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown.

METHODS

In this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration–time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile.

RESULTS

A total of 84 participants underwent randomization — 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose–adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies.

CONCLUSIONS

Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545. opens in new tab.)

Reference: N Engl J Med 2020; 383:2007-2017

Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes

BACKGROUND

Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes.

METHODS

In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring.

RESULTS

A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was −0.88 percentage points (95% CI, −1.19 to −0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was −0.33 percentage points (95% CI, −0.53 to −0.13; P=0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group.

CONCLUSIONS

In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313. opens in new tab.)

Reference: N Engl J Med 2019; 381:1707-1717

Continuous subcutaneous insulin infusion versus multiple daily injection regimens in children and young people at diagnosis of type 1 diabetes: pragmatic randomised controlled trial and economic evaluation

Objective To compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people.

Design Pragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation.

Setting 15 paediatric National Health Service (NHS) diabetes services in England and Wales. The study opened to recruitment in May 2011 and closed in January 2017.

Participants Patients aged between 7 months and 15 years, with a new diagnosis of type 1 diabetes were eligible to participate. Patients who had a sibling with the disease, and those who took drug treatments or had additional diagnoses that could have affected glycaemic control were ineligible.

Interventions Participants were randomised, stratified by age and treating centre, to start treatment with CSII or MDI within 14 days of diagnosis. Starting doses of aspart (CSII and MDI) and glargine or detemir (MDI) were calculated according to weight and age, and titrated according to blood glucose measurements and according to local clinical practice.

Main outcome measures Primary outcome was glycaemic control (as measured by glycated haemoglobin; HbA1c) at 12 months. Secondary outcomes were percentage of patients in each treatment arm with HbA1c within the national target range, incidence of severe hypoglycaemia and diabetic ketoacidosis, change in height and body mass index (as measured by standard deviation scores), insulin requirements (units/kg/day), partial remission rate (insulin dose adjusted HbA1c <9), paediatric quality of life inventory score, and cost utility based on the incremental cost per quality adjusted life year (QALY) gained from an NHS costing perspective.

Results 294 participants were randomised and 293 included in intention to treat analyses (CSI, n=144; MDI, n=149). At 12 months, mean HbA1c was comparable with clinically unimportant differences between CSII and MDI participants (60.9 mmol/mol v 58.5 mmol/mol, mean difference 2.4 mmol/mol (95% confidence interval −0.4 to 5.3), P=0.09). Achievement of HbA1c lower than 58 mmol/mol was low among the two groups (66/143 (46%) CSII participants v 78/142 (55%) MDI participants; relative risk 0.84 (95% confidence interval 0.67 to 1.06)). Incidence of severe hypoglycaemia and diabetic ketoacidosis were low in both groups. Fifty four non-serious and 14 serious adverse events were reported during CSII treatment, and 17 non-serious and eight serious adverse events during MDI treatment. Parents (but not children) reported superior PedsQL scores for those patients treated with CSII compared to those treated with MDI. CSII was more expensive than MDI by £1863 (€2179; $2474; 95% confidence interval £1620 to £2137) per patient, with no additional QALY gains (difference −0.006 (95% confidence interval −0.031 to 0.018)).

Conclusion During the first year following type 1 diabetes diagnosis, no clinical benefit of CSII over MDI was identified in children and young people in the UK setting, and treatment with either regimen was suboptimal in achieving HbA1c thresholds. CSII was not cost effective.

Trial registration Current Controlled Trials ISRCTN29255275; European Clinical Trials Database 2010-023792-25.

Reference BMJ 2019;365:l1226

Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials

Objective To assess the efficacy and safety of dual sodium glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin in type 1 diabetes mellitus.

Design Meta-analysis of randomised controlled trials.

Data sources Medline; Cochrane Library; Embase; international meeting abstracts; international and national clinical trial registries; and websites of US, European, and Japanese regulatory authorities, up to 10 January 2019.

Eligibility criteria for selecting studies Randomised controlled trials evaluating the effect of sotagliflozin versus active comparators or placebo on glycaemic and non-glycaemic outcomes and on adverse events in type 1 diabetes in participants older than 18. Three reviewers extracted data for study characteristics, outcomes of interest, and risk of bias and summarised strength of evidence using the grading of recommendations assessment, development, and evaluation approach. Main outcomes were pooled using random effects models.

Results Of 739 records identified, six randomised placebo controlled trials (n=3238, duration 4-52 weeks) were included. Sotagliflozin reduced levels of glycated haemoglobin (HbA1c; weighted mean difference −0.34% (95% confidence interval −0.41% to −0.27%), P<0.001); fasting plasma glucose (−16.98 mg/dL, −22.1 to −11.9; 1 mg/dL=0.0555 mmol/L) and two hour-postprandial plasma glucose (−39.2 mg/dL, −50.4 to −28.1); and daily total, basal, and bolus insulin dose (−8.99%, −10.93% to −7.05%; −8.03%, −10.14% to −5.93%; −9.14%, −12.17% to −6.12%; respectively). Sotagliflozin improved time in range (weighted mean difference 9.73%, 6.66% to 12.81%) and other continuous glucose monitoring parameters, and reduced body weight (−3.54%, −3.98% to −3.09%), systolic blood pressure (−3.85 mm Hg, −4.76 to −2.93), and albuminuria (albumin:creatinine ratio −14.57 mg/g, −26.87 to −2.28). Sotagliflozin reduced hypoglycaemia (weighted mean difference −9.09 events per patient year, −13.82 to −4.36) and severe hypoglycaemia (relative risk 0.69, 0.49 to 0.98). However, the drug increased the risk of ketoacidosis (relative risk 3.93, 1.94 to 7.96), genital tract infections (3.12, 2.14 to 4.54), diarrhoea (1.50, 1.08 to 2.10), and volume depletion events (2.19, 1.10 to 4.36). Initial HbA1c and basal insulin dose adjustment were associated with the risk of diabetic ketoacidosis. A sotagliflozin dose of 400 mg/day was associated with a greater improvement in most glycaemic and non-glycaemic outcomes than the 200 mg/day dose, without increasing the risk of adverse events. The quality of evidence was high to moderate for most outcomes, but low for major adverse cardiovascular events and all cause death. The relatively short duration of trials prevented assessment of long term outcomes.

Conclusions In type 1 diabetes, sotagliflozin improves glycaemic and non-glycaemic outcomes and reduces hypoglycaemia rate and severe hypoglycaemia. The risk of diabetic ketoacidosis could be minimised by appropriate patient selection and down-titration of the basal insulin dose.

Reference BMJ 2019;365:l1328

Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset

Background

People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk.

Methods

We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National Diabetes Register and matched controls from the general population. We included patients with at least one registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration, we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0–10 years, 11–15 years, 16–20 years, 21–25 years, and 26–30 years.

Findings

27 195 individuals with type 1 diabetes and 135 178 matched controls were selected for this study. 959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0–10 years of age had hazard ratios of 4·11 (95% CI 3·24–5·22) for all-cause mortality, 7·38 (3·65–14·94) for cardiovascular mortality, 3·96 (3·06–5·11) for non-cardiovascular mortality, 11·44 (7·95–16·44) for cardiovascular disease, 30·50 (19·98–46·57) for coronary heart disease, 30·95 (17·59–54·45) for acute myocardial infarction, 6·45 (4·04–10·31) for stroke, 12·90 (7·39–22·51) for heart failure, and 1·17 (0·62–2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26–30 years were 2·83 (95% CI 2·38–3·37) for all-cause mortality, 3·64 (2·34–5·66) for cardiovascular mortality, 2·78 (2·29–3·38) for non-cardiovascular mortality, 3·85 (3·05–4·87) for cardiovascular disease, 6·08 (4·71–7·84) for coronary heart disease, 5·77 (4·08–8·16) for acute myocardial infarction, 3·22 (2·35–4·42) for stroke, 5·07 (3·55–7·22) for heart failure, and 1·18 (0·79–1·77) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1·9 (95% CI 1·71–2·11) per 100 000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 14·5–20·4) for women and 14·2 life-years (12·1–18·2) for men.

Interpretation

Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes.

Funding

Swedish Heart and Lung Foundation.

Reference: The Lancet, Volume 392, ISSUE 10146, P477-486, August 11, 2018

Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden

Objective To examine the association between maternal type 1 diabetes and the risk of major birth defects according to levels of glycated haemoglobin (HbA1C) within three months before or after estimated conception.

Design Population based historical cohort study using nationwide health registers.

Setting Sweden, 2003-15.

Participants 2458 singleton liveborn infants of mothers with type 1 diabetes and a glycated haemoglobin measurement within three months before or after estimated conception and 1 159 865 infants of mothers without diabetes.

Main outcome measures Major cardiac and non-cardiac birth defects according to glycated haemoglobin levels.

Results 122 cases of major cardiac defects were observed among 2458 infants of mothers with type 1 diabetes. Compared with 15 cases of major cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 33 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 2.17, 95% confidence interval 1.37 to 3.42), 49 per 1000 for 6.5% to <7.8% (3.17, 2.45 to 4.11), 44 per 1000 for 7.8% to <9.1% (2.79, 1.90 to 4.12), and 101 per 1000 for ≥9.1% (6.23, 4.32 to 9.00). The corresponding adjusted risk differences were 17 (5 to 36), 32 (21 to 46), 26 (13 to 46), and 77 (49 to 118) cases of major cardiac defects per 1000 infants, respectively. 50 cases of major non-cardiac defects were observed among infants of mothers with type 1 diabetes. Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for ≥9.1% (1.68, 0.85 to 3.33).

Conclusion Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.

Reference:  BMJ 2018;362:k2638