Attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurobehavioral disorders of childhood and can profoundly affect children's academic achievement, well-being, and social ...interactions. The American Academy of Pediatrics first published clinical recommendations for evaluation and diagnosis of pediatric ADHD in 2000; recommendations for treatment followed in 2001. The guidelines were revised in 2011 and published with an accompanying process of care algorithm (PoCA) providing discrete and manageable steps by which clinicians could fulfill the clinical guideline's recommendations. Since the release of the 2011 guideline, the
has been revised to the fifth edition, and new ADHD-related research has been published. These publications do not support dramatic changes to the previous recommendations. Therefore, only incremental updates have been made in this guideline revision, including the addition of a key action statement related to diagnosis and treatment of comorbid conditions in children and adolescents with ADHD. The accompanying process of care algorithm has also been updated to assist in implementing the guideline recommendations. Throughout the process of revising the guideline and algorithm, numerous systemic barriers were identified that restrict and/or hamper pediatric clinicians' ability to adopt their recommendations. Therefore, the subcommittee created a companion article (available in the Supplemental Information) on systemic barriers to the care of children and adolescents with ADHD, which identifies the major systemic-level barriers and presents recommendations to address those barriers; in this article, we support the recommendations of the clinical practice guideline and accompanying process of care algorithm.
In persons with type 1 diabetes, intermittently scanned continuous glucose monitoring led to significantly lower glycated hemoglobin levels than participant monitoring with fingerstick testing.
Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response that stimulates endogenous glucose production to maintain concentrations within an appropriate physiological range. ...Although the involvement of the brain in preserving normoglycemia has been established, the neurocircuitry underlying centrally mediated CR-responses remains unclear. Here we demonstrate that lateral parabrachial nucleus cholecystokinin (CCKLPBN) neurons are a population of glucose-sensing cells (glucose inhibited) with counterregulatory capacity. Furthermore, we reveal that steroidogenic-factor 1 (SF1)-expressing neurons of the ventromedial nucleus of the hypothalamus (SF1VMH) are the specific target of CCKLPBN glucoregulatory neurons. This discrete CCKLPBN→SF1VMH neurocircuit is both necessary and sufficient for the induction of CR-responses. Together, these data identify CCKLPBN neurons, and specifically CCK neuropeptide, as glucoregulatory and provide significant insight into the homeostatic mechanisms controlling CR-responses to hypoglycemia.
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•CCKLPBN neurons are glucose inhibited and activated by hypoglycemia•CCKLPBN neurons are necessary and sufficient for counterregulatory (CR)-responses•CCK neuropeptide is the key mediator of CCKLPBN neuron-mediated CR-responses•CCKLPBN neuron-induced CR-responses require downstream SF1VMH neurons
The counterregulatory response (CRR) to hypoglycemia is critical for the maintenance of normoglycemia and governed by the brain. Garfield et al. identify a population of brainstem CCK neurons that directly sense extracellular glucose concentrations and, via their connection to SF1 hypothalamic neurons, promote CRR.
In two randomized trials conducted under home conditions, investigators compared closed-loop insulin delivery with sensor-augmented pump therapy in adults and in children and adolescents for 12 ...weeks. The closed-loop approach improved glucose control and reduced hypoglycemia.
Intensive insulin therapy is the standard of care for type 1 diabetes but is limited by the risk of hypoglycemia,
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which leads to failure in achieving treatment goals for most patients in all age groups.
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,
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Among patients with type 1 diabetes, hypoglycemia is common, has a major effect on patients’ quality of life and psychological well-being,
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and may cause seizures, which is of particular concern during the overnight hours in children and adolescents.
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New approaches (e.g., continuous glucose monitoring) can improve glycemic control when the patient wears the sensors on a regular basis.
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,
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If insulin delivery is linked . . .
In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 ...adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol
(9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9-10.0 mmol l
). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0-42.6 percentage points; P < 0.001). Time > 10.0 mmol l
was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, -35.2 percentage points; 95% CI, -42.8 to -27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l
versus 12.6 ± 3.0 mmol l
, respectively; mean difference, -3.6 mmol l
; 95% CI, -4.6 to -2.5 mmol l
; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol
(7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol
(8.7% ± 1.2%); mean difference, -15 mmol mol
; 95% CI, -11 to -20 mmol l
(mean difference, -1.4%; 95% CI, -1.0 to -1.8%); P < 0.001). Time < 3.9 mmol l
was similar between treatments (a median of 0.44% (interquartile range, 0.19-0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00-1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).
In this trial involving hospitalized patients with type 2 diabetes, closed-loop insulin delivery (artificial pancreas) resulted in better glucose control than standard subcutaneous insulin therapy ...without an increased incidence of hypoglycemia.
The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with ...sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.
In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin HbA1c 7·5–10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9–10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.
From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change −0·83 percentage points, −1·40 to −0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change −10·3 percentage points, −13·2 to −7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change −0·4%, 95% CI −1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI −0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI −0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group.
Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes.
JDRF, NIHR, and Wellcome Trust.
In this recent 2019–2020 audit, 96% (168/173) of paediatric diabetes teams submitted data and included a total of 29,242 children and young people (CYP) up to the age of 24 years, and type 1 diabetes ...consisted of 27,653 CYP. One of the key findings was that CYP with type 1 diabetes from minority ethnic communities have higher HbA1 compared to white ethnicity and that significantly lower use of insulin pumps or real‐time continuous glucose monitoring systems was used among black children. There has been an increasing trend of widening health inequalities reported the past 6 years. As chairs of Diabetes UK Diabetes Research Study Groups, the authors urge that research into barriers of access to technology for T1D in CYP in the UK specifically looking at provider bias, systemic issues within the health system, and individual and family factors are conducted with urgency.
In the study, 181 adults (88 women and 93 men) with insulin-treated type 2 diabetes and sub optimal control (glycated haemoglobin HbA1c ≥7·5% 58 mmol/mol to ≤11% 97 mmol/mol) were randomly assigned ...(1:1) to the intervention group, in which patients used the d-Nav device in combination with health-care professional support, or the control group, in which patients continued with a standard meter for glucose monitoring but otherwise received identical health-care professional contact. The reported metabolic outcomes are similar to those reported in an earlier single-arm service evaluation assessment of the same device in a UK setting5 and a broadly similar system in which dose advice was fed back to health-care providers.6 As expected in the context of a clinical trial, both groups had frequent contact with study team members, with seven face-to-face or telephone contacts over the period of 6 months. ...importantly, how comfortable would patients and clinical teams be in allowing an algorithm to manage insulin dose titration?
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