Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada.

BACKGROUND: In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements. METHODS: We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874. FINDINGS: 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred. INTERPRETATION: The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted. FUNDING: Juvenile Diabetes Research Foundation.

Type 1 diabetes care delivery in Yaoundé, Cameroon: Social and political representations.

BACKGROUND:  Increasing chronic diseases challenges the health systems of low- and middle-income countries, including Cameroon. Type 1 diabetes (T1D), among the most common chronic diseases in children, poses particular care delivery challenges. AIM:  We examined social representations of patients' roles and implementation of T1D care among political decision-makers, healthcare providers and patients within families. SETTING:  The study was conducted in Yaoundé, Cameroon. METHODS:  Eighty-two individuals were included in the study. The authors conducted semi-structured interviews with policy makers (n = 5), healthcare professionals (n = 7) and patients 'parents (n = 20). Questionnaires were administered to paediatric patients with T1D (n = 50). The authors also observed care delivery at a referral hospital and at a T1D-focused non-governmental organisation over 15 days. Data were analysed using thematic content analysis and descriptive statistics. RESULTS:  Cameroonian health policy portrays patients with T1D as passive recipients of care. While many practitioners recognised the complex social and economic determinants of adherence to T1D care, in practice interactions focused on specific biomedical issues and offered brief guidance. Cultural barriers and policy implementation challenges prevent patients and their families from being fully active participants in care. Parents and children prefer an ongoing relationship with a single clinician and interactions with other patients and families. CONCLUSION:  Patients and families mobilise experience and lay knowledge to complement biomedical knowledge, but top-down policy and clinical practice limit their active engagement in T1D care.Contribution: Children with T1D and their families, policy makers, healthcare professionals, and civil society have new opportunities to contribute to person-centred care, as advocated by the Sustainable Development Goals.

Socioeconomic Disparities in Glycemic Management in Children and Youth With Type 1 Diabetes: A Retrospective Cohort Study.

OBJECTIVE: In Canada, few studies have addressed health inequalities in type 1 diabetes (T1D) outcomes. In this study, we examined the relationship between socioeconomic status (SES) and glycemic management in children with T1D and determine whether technology use (insulin pumps or continuous glucose monitoring [CGM]), diabetes-related physician visits, and depressive symptoms modified the association. METHODS: This work was a retrospective cohort study using the Montréal Children's Hospital Pediatric Diabetes Database of children 0 to 18 years old, diagnosed with T1D for ≥1 year, and with a hospital visit between November 2019 and October 2020. Main exposure was SES measured by the Material and Social Deprivation Index (least, moderately, or most deprived). We determined the association between SES and mean glycated hemoglobin (A1C; main outcome) in the year after the index visit using multivariable linear regression, adjusting for age, sex, diabetes duration, technology use, diabetes-related physician visits, and depressive symptoms (subgroup). We examined interaction terms for technology use, diabetes-related physician visits, and depressive symptoms. RESULTS: The study cohort included 306 children (mean age 13.6 years, mean A1C 8.5%). Children in the most-deprived compared with least-deprived quintiles had higher mean A1C; effect modification was significant with CGM only. Children not using CGM in the most-deprived compared with least-deprived quintiles had higher mean A1C (0.52%; 95% confidence interval, 0.14% to 0.86%), whereas the association was not significant for children using CGM. CONCLUSIONS: Lower SES was associated with higher A1C; these disparities were not observed among CGM users. Further research is required to determine strategies to promote CGM access among children of lower SES in the Canadian health-care context.

Validation Study and Outcomes of the Diabetes Quality of Life in Youth Instrument in Haitian Youth With Type 1 Diabetes Residing in Haiti.

OBJECTIVES: Health-related quality of life (HRQL) in type 1 diabetes is a critical health outcome but has not been studied in many low-income countries. In this study we evaluated the validity of 2 HRQL instruments, measured the HRQL and explored the association between HRQL and glycemic control. METHODS: This was a cross-sectional study of Haitian youth with diabetes between 0 and 25 years of age and living in Haiti. We administered the 51-item Diabetes Quality of Life for Youth (DQOLY) questionnaire and the EuroQol Visual Analogue Scale (EQ-VAS). Psychometric analyses evaluated internal consistency and construct validity of the DQOLY and its 21-item short form, the DQOLY-SF. Linear regression was used to identify predictors of HRQL and glycated hemoglobin (A1C). RESULTS: In 85 youth (59% female; mean age, 17.5 years; mean diabetes duration, 3.7 years; mean A1C, 11.3%), DQOLY and DQOLY-SF had adequate internal consistency with Cronbach's alpha values of 0.86 and 0.84, respectively. Confirmatory factor analysis revealed adequate validity for the DQOLY-SF and DQOLY Satisfaction subscale. HRQL, as measured using the DQOLY-SF, was 62±16 (mean ± standard deviation) out of 100. Mean EQ-VAS score was 78±24 out of 100. Older age (p=0.004), female sex (p=0.02) and lower socioeconomic status (SES) (p=0.03) were risk factors for lower DQOLY score, and older age (p=0.02) and marginally female sex (p=0.06) for lower DQOLY-SF score. No predictors of EQ-VAS were identified. HRQL measures were not associated with glycemic control. CONCLUSIONS: The DQOLY-SF and DQOLY Satisfaction subscale are valid measures of HRQL in Haitian youth with diabetes. HRQL is low and was worse in older, female and low-SES youth, but was not associated with glycemic control.

Alleviating carbohydrate counting with a FiASP-plus-pramlintide closed-loop delivery system (artificial pancreas): Feasibility and pilot studies.

AIM: To assess whether a FiASP-and-pramlintide closed-loop system has the potential to replace carbohydrate counting with a simple meal announcement (SMA) strategy (meal priming bolus without carbohydrate counting) without degrading glycaemic control compared with a FiASP closed-loop system. MATERIALS AND METHODS: We conducted a 24-hour feasibility study comparing a FiASP system with full carbohydrate counting (FCC) with a FiASP-and-pramlintide system with SMA. We conducted a subsequent 12-day outpatient pilot study comparing a FiASP-and-placebo system with FCC, a FiASP-and-pramlintide system with SMA, and a FiASP-and-placebo system with SMA. Basal-bolus FiASP-and-pramlintide were delivered at a fixed ratio (1 U:10 µg). Glycaemic outcomes were measured, surveys evaluated gastrointestinal symptoms and diabetes distress, and participant interviews helped establish a preliminary coding framework to assess user experience. RESULTS: Seven participants were included in the feasibility analysis. Time spent in 3.9-10 mmol/L was similar between both interventions (81%-84%). Four participants were included in the pilot analysis. Time spent in 3.9-10 mmol/L was similar between the FiASP-and-placebo with FCC and FiASP-and-pramlintide with SMA interventions (70%), but was lower in the FiASP-and-placebo with SMA intervention (60%). Time less than 3.9 mmol/L and gastrointestinal symptoms were similar across all interventions. Emotional distress was moderate at baseline, after the FiASP-and-placebo with FCC and SMA interventions, and fell after the FiASP-and-pramlintide with SMA intervention. SMA reportedly afforded participants flexibility and reduced mealtime concerns. CONCLUSIONS: The FiASP-and-pramlintide system has the potential to substitute carbohydrate counting with SMA without degrading glucose control.

Prevalence and perinatal outcomes of non-communicable diseases in pregnancy in a regional hospital in Haiti: A prospective cohort study.

BACKGROUND: The prevalence of non-communicable diseases (NCDs) is rising in low and middle-income countries (LMIC). We aimed to report on the prevalence of NCDs in pregnancy and their associated perinatal outcomes in a regional hospital in Haiti. METHODS: We conducted the "Diabète et hYpertension Artéerielle et leurs issues MAternelles et Néonatales" (DYAMAN) prospective cohort study in a regional hospital in Haiti. Pregnant women presenting to care at 24-28 weeks were screened and treated for diabetes (DM) and hypertensive disorders of pregnancy (HDP) using setting-adapted protocols. Prevalence of NCDs and associated maternal-neonatal outcomes were described. RESULTS: 715 women were included, of which 51 (7.1%) had DM, 90 (12.6%) had HDP, and 30 (4.2%) had both DM and HDP (DM/HDP). Of 422 (59%) women delivered in hospital, 58 (13.7%) had preeclampsia, including 5 (8.6%) with eclampsia. Preterm birth <32 weeks was more common in the HDP than the control, DM, and DM/HDP groups. More low birth weight babies (n = 20, 25.6%) were born to the HDP group than to the control (n = 20, 7.1%), DM (n = 1, 2.7%), and DM/HDP (n = 3, 12%) groups (P < 0.001). Macrosomia and hypoglycemia affected 5 (8%) neonates of women with DM. Perinatal mortality, affecting 36/1000 births, was mainly driven by maternal NCDs. CONCLUSIONS: NCDs in pregnancy led to adverse maternal and perinatal outcomes. This study will help to prepare future refinements aimed at optimizing the management of NCDs in pregnancy in LMIC. Research is required to understand barriers to patient attendance at antenatal follow-up, treatment escalation for hyperglycemia, and in-hospital delivery.

A Meal Detection Algorithm for the Artificial Pancreas: A Randomized Controlled Clinical Trial in Adolescents With Type 1 Diabetes.

OBJECTIVE: We developed a meal detection algorithm for the artificial pancreas (AP+MDA) that detects unannounced meals and delivers automatic insulin boluses. RESEARCH DESIGN AND METHODS: We conducted a randomized crossover trial in 11 adolescents aged 12-18 years with HbA1c ≥7.5% who missed one or more boluses in the past 6 months. We compared 1) continuous subcutaneous insulin infusion (CSII), 2) artificial pancreas (AP), and 3) AP+MDA. Participants underwent three 9-h interventions involving breakfast with a bolus and lunch without a bolus. RESULTS: In AP+MDA, the meal detection time was 40.0 (interquartile range 40.0-57.5) min. Compared with CSII, AP+MDA decreased the 4-h postlunch incremental area under the curve (iAUC) from 24.1 ± 9.5 to 15.4 ± 8.0 h ⋅ mmol/L (P = 0.03). iAUC did not differ between AP+MDA and AP (19.6 ± 10.4 h ⋅ mmol/L, P = 0.21) or between AP and CSII (P = 0.33). The AP+MDA reduced time >10 mmol/L (58.0 ± 26.6%) compared with CSII (79.6 ± 27.5%, P = 0.02) and AP (74.2 ± 20.6%, P = 0.047). CONCLUSIONS: The AP+MDA improved glucose control after an unannounced meal.

From toy to tool: Using water beads for insulin storage in Haiti.

Diabetes prevalence within the global population has nearly doubled since 1980, with the most rapid growth occurring in low- and middle-income countries. Diabetes management in resource-limited settings such as Haiti presents many challenges, including the storage of insulin. Despite a lack of published data on insulin thermostability, storage at 2-8°C or at room temperature (25°C) is recommended. In Haiti, access to refrigeration and thereby proper insulin storage is severely limited. Commercial storage devices such as the FRIO cooling wallet are cost-prohibitive and not available locally, and alternatives such as small clay pots are fragile and nonportable. Here, we designed and tested the cooling efficacy of a homemade wallet made of acrylate polymer beads and a hand-sewn cotton pouch compared to a FRIO wallet and a clay pot. All studies were conducted over a ten-day period at the Kay Mackenson Clinic in Montrouis, Haiti. Temperature and humidity values were continuously collected using wireless monitors placed inside each device, and hourly ambient temperature and humidity values were manually recorded. Evaporative cooling efficacy was calculated using collected data. The homemade wallet and FRIO cooling wallet demonstrated comparable cooling efficacy with an average of 71% and 73%, respectively. The clay pot demonstrated significantly decreased efficacy with an average of 27% (p < 0.05). The homemade insulin wallet is a promising alternative for the storage of insulin in low-resource settings without the financial and physical barriers of commercial and locally sourced devices. Additionally, this wallet could be readily adapted for the storage of other perishable medical supplies in low-income countries.

Postprandial hyperglycaemia following insulin suspensions by the artificial pancreas: Implications for bolus calculators.

Conventional bolus calculators apply negative prandial corrections when premeal glucose levels are low. However, no study has evaluated the need for this negative correction with closed-loop systems. We analysed data retrospectively from a cohort study evaluating a closed-loop artificial pancreas system conducted in a diabetes camp over a period of 11 days. Meal boluses with negative correction (n = 98) of 47 participants aged 8 to 22 years were examined. If there was no insulin-on-board from previous boluses at mealtime, the postprandial hyperglycaemia rate increased with increased duration of insulin suspension (P = .03), with odds ratios being exaggerated by 17% per 10 minutes of suspension. However, if there was insulin-on-board from previous boluses, the hyperglycaemia rate did not change with increased duration of insulin suspension (P = .24). When there was no insulin-on-board, the rate of hyperglycaemia after meals preceded by no suspension was 21% (3/14), compared with 52% (12/23) and 64% (9/14) after meals preceded by suspensions of ≥50 and ≥70 minutes, respectively. Meal size did not influence these results. We conclude that, in the absence of insulin-on-board, negative prandial corrections may not be necessary following long insulin suspensions.

A pilot non-inferiority randomized controlled trial to assess automatic adjustments of insulin doses in adolescents with type 1 diabetes on multiple daily injections therapy.

BACKGROUND: Multiple daily injections (MDI) therapy for type 1 diabetes involves basal and bolus insulin doses. Non-optimal insulin doses contribute to the lack of satisfactory glycemic control. We aimed to evaluate the feasibility of an algorithm that optimizes daily basal and bolus doses using glucose monitoring systems for MDI therapy users. METHODS: We performed a pilot, non-inferiority, randomized, parallel study at a diabetes camp comparing basal-bolus insulin dose adjustments made by camp physicians (PA) and a learning algorithm (LA), in children and adolescents on MDI therapy. Participants wore a glucose sensor and underwent 11 days of daily dose adjustments in either arm. Algorithm adjustments were reviewed and approved by a physician. The last 7 days were examined for outcomes. RESULTS: Twenty-one youths (age 13.3 [SD, 3.7] years; 13 females; HbA1c 8.6% [SD, 1.8]) were randomized to either group (LA [n = 10] or PA [n = 11]). The algorithm made 293 adjustments with a 92% acceptance rate from the camp physicians. In the last 7 days, the time in target glucose (3.9-10 mmol/L) in LA (39.5%, SD, 20.7) was similar to PA (38.4%, SD, 15.6) (P = .89). The number of hypoglycemic events per day in LA (0.3, IQR, [0.1-0.6]) was similar to PA (0.2, IQR, [0.0-0.4]) (P = .42). There was no incidence of severe hypoglycemia nor ketoacidosis. CONCLUSIONS: In this pilot study, glycemic outcomes in the LA group were similar to the PA group. This algorithm has the potential to facilitate MDI therapy, and longer and larger studies are warranted.

Thyroid Storm in a Toddler Presenting as a Febrile Seizure.

Although simple febrile seizures are relatively common and benign in toddlers, it is important to rule out any underlying critical disease that necessitates further intervention and treatment. Thyroid storm, the extreme manifestation of hyperthyroidism, is relatively rare and not often considered in the differential diagnosis of a febrile seizure despite its high mortality rate. Here, we report 1 of the youngest patients with thyroid storm, who initially presented with a febrile seizure. After reevaluation, the 2-year-9-month-old patient was discovered to have thyromegaly, which led to recognition that her persistent tachycardia and widened pulse pressure were likely signs of thyrotoxicosis. Laboratory results were consistent with primary hyperthyroidism due to Graves' disease. Thyroid storm was then diagnosed on the basis of clinical features including gastrointestinal and central nervous system disturbances. Treatment with methimazole, propranolol, hydrocortisone, and Lugol's iodine solution was used. This medication regimen was safe and effective with restoration of a euthyroid state after 2 months and no recurrence of seizures. Improved awareness of hyperthyroidism and thyroid storm can lead to prompt diagnosis and treatment of this endocrine emergency, thus reducing mortality and morbidity. Pediatricians should consider this diagnosis in children with febrile seizures and suggestive vital signs and physical examination findings.

The Efficacy of Basal Rate and Carbohydrate Ratio Learning Algorithm for Closed-Loop Insulin Delivery (Artificial Pancreas) in Youth with Type 1 Diabetes in a Diabetes Camp.

Background: Optimizing programmed basal rates and carbohydrate ratios may improve the performance of the artificial pancreas. We tested, in a diabetes camp, the efficacy of a learning algorithm that updates daily basal rates and carbohydrate ratios in the artificial pancreas. Materials and Methods: We conducted a randomized crossover trial in campers and counselors aged 8-21 years with type 1 diabetes on pump therapy. Participants underwent 2 days of artificial pancreas alone and 6 days of artificial pancreas with learning. During the artificial pancreas with learning, programmed basal rates and carbohydrate ratios were updated daily based on the learning algorithm's recommendations. All algorithm recommendations were reviewed for safety by camp physicians. The primary outcome was the time in target range (3.9-10 mmol/L) of the last 2 days of each intervention. Results: Thirty-four campers (age 13.9 ± 3.9, hemoglobin A1c 8.3% ± 0.2%) were included. Ninety-six percent of algorithm recommendations were approved by the camp physicians. Participants were in closed-loop mode 74% of the time. There was no difference between interventions in time in target (55%-55%; P = 0.71) nor in hypoglycemia events (0.8-0.9 events per day; P = 0.63). This was despite changes in programmed basal rate ranging from -21% to +117%, and changes in breakfast, lunch, and supper carbohydrate ratios from -17% to +40%, -36% to +37%, and -35% to +63%, respectively. Morever, postprandial hyperglycemia and hypoglycemia did not decrease in participants whose carbohydrate ratios were decreased (more insulin boluses) and increased (less insulin boluses), respectively. Conclusions: In camp settings, despite adjustments to programmed basal rates and carbohydrate ratios, the learning algorithm did not change glycemia, which may point toward limited effect of these adjustments in environments with large day-to-day variability in insulin needs. Longer randomized studies in real-world settings are required to further assess the efficacy of automatic adjustments of programmed basal rates and carbohydrate ratios.

Experience With Store-and-Forward Consultations in Providing Access to Pediatric Endocrine Consultations in Low- and Middle-Income Countries.

Pediatric specialists are often unavailable in low- and middle-income countries. As part of multiple professional associations' efforts to improve access to endocrine expertise globally, a pediatric endocrine teleconsultation network was established on a store-and-forward teleconsultation platform to facilitate focused, language-appropriate advice that can be kept for future reference while bypassing real-time video-conferencing, and obviating the need for a scheduled appointment. User information was recorded, and quality statistics on network performance and qualitative evaluation by referring physicians were analyzed. Over a 3-year period, 81 referrers (88% from Haiti) and 13 pediatric endocrinologists registered onto the network and discussed 47 pediatric endocrine cases, exchanging a total of 412 messages for a median of 7 messages (IQR 5, 11) per case. Diagnoses spanned the spectrum of pediatric endocrine disorders. According to referrers, an appropriate expert was consulted and an answer provided sufficiently quickly in 100% of cases. The answer was well-adapted to their environment in 86%, and referrers were able to follow the advice given in 72%. All but one referrer found the advice helpful, it clarified the diagnosis in 88%, assisted with management in 93%, improved patient's symptoms in 77%, improved function in 77%, and was considered cost-saving in 50%. Perceived benefits of the consultations were academic instruction, setting-adapted advice beyond the scope of guidelines or textbooks, and advancement in the diagnostic process. Pediatric endocrine remote store-and-forward consultations in low- and middle-income countries may provide a reasonable alternative to face-to-face visits, providing clinical and educational benefit, and a potential for cost-saving.

Capacity Building and Innovation in Caring for Non-communicable Diseases in Maternal Global Health: The Example of Haiti.

Non-communicable diseases (NCDs) are important contributors to maternal morbidity and mortality worldwide. Yet, data on their prevalence and related outcomes in low-income countries are currently lacking. Additionally, screening and treatment protocols adapted for resource-limited settings are urgently required. This collaborative research initiative on the screening and management of hypertensive disorders of pregnancy and gestational diabetes was conducted in Saint-Nicolas Hospital in Saint-Marc, Haiti. The report discusses methods used to overcome several local challenges to implementation of care for NCDs. It also describes how collaborative research initiatives are efficient strategies to innovate and build research capacity for NCD care delivery during pregnancy in low-income countries.

Normal weight metabolically unhealthy phenotype in youth: Do definitions matter?

BACKGROUND: Normal weight metabolically unhealthy (NWMU) adults are at increased risk of cardiometabolic disease, however, little is known regarding NWMU children. OBJECTIVES: We examined the associations between existing definitions of NWMU in children aged 8 to 10 years and insulin sensitivity (IS) and secretion 2 years later. METHODS: Data stem from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of 630 Caucasian youth, 8 to 10 years old at baseline, with at least one obese biological parent. Of these, 322 normal weight children were classified as NWMU using four definitions. At 10 to 12 years, IS was measured with the Matsuda-insulin sensitivity index; insulin secretion was measured with the ratio of the area under the curve (AUC) of insulin to the AUC of glucose over a 2-hour oral glucose tolerance test. Multiple linear regression models were used. RESULTS: Because few children met the existing definitions of metabolic syndrome, associations were examined for less stringent definitions (eg, having two vs no risk factors). At baseline, IS was lower in NWMU children compared to children with no risk factors (virtually all definitions). Moreover, after 2 years, IS was 14.4-19.3% lower in NWMU children with one or more risk factors, and up to 29.7% lower in those with two or more risk factors compared to those with none. Insulin secretion was not predicted by components of the metabolic syndrome. CONCLUSION: Existing definitions of NWMU youth performed relatively similarly in predicting IS as youth entered puberty. Children with one or more components of metabolic syndrome-even when of normal weight-have significantly lower IS over time.

Levels of type 1 diabetes care in children and adolescents for countries at varying resource levels.

Optimal care for children and adolescents with type 1 diabetes is well described in guidelines, such as those of the International Society for Pediatric and Adolescent Diabetes. High-income countries can usually provide this, but the cost of this care is generally prohibitive for lower-income countries. Indeed, in most of these countries, very little care is provided by government health systems, resulting in high mortality, and high complications rates in those who do survive. As lower-income countries work toward establishing guidelines-based care, it is helpful to describe the levels of care that are potentially affordable, cost-effective, and result in substantially improved clinical outcomes. We have developed a levels of care concept with three tiers: "minimal care," "intermediate care," and "comprehensive (guidelines-based) care." Each tier contains levels, which describe insulin and blood glucose monitoring regimens, requirements for hemoglobin A1c (HbA1c) testing, complications screening, diabetes education, and multidisciplinary care. The literature provides various examples at each tier, including from countries where the life for a child and the changing diabetes in children programs have assisted local diabetes centres to introduce intermediate care. Intra-clinic mean HbA1c levels range from 12.0% to 14.0% (108-130 mmol/mol) for the most basic level of minimal care, 8.0% to 9.5% (64-80 mmol/mol) for intermediate care, and 6.9% to 8.5% (52-69 mmol/mol) for comprehensive care. Countries with sufficient resources should provide comprehensive care, working to ensure that it is accessible by all in need, and that resulting HbA1c levels correspond with international recommendations. All other countries should provide Intermediate care, while working toward the provision of comprehensive care.

Treatment of congenital hypothyroidism in a newborn with malabsorption after subtotal ileum resection.

Congenital hypothyroidism requires prompt treatment to prevent adverse health outcomes. Poor intestinal levothyroxine absorption can complicate management. We present a case of a term female newborn with necrotizing enterocolitis (NEC) requiring subtotal ileum resection. Congenital hypothyroidism was diagnosed by newborn screening. Treatment was complicated by intestinal malabsorption of levothyroxine. Intravenous levothyroxine substitution restored euthyroidism and supraphysiologic PO doses subsequently maintained a euthyroid state. After several months, the required levothyroxine dose was weaned down to typical recommended dosing. In conclusion, small bowel resection secondary to NEC may lead to malabsorption of oral levothyroxine. An intravenous levothyroxine dose of approximately 50% typical PO dosing is effective in providing rapid normalization of free T4 and TSH. High PO doses may be required to maintain euthyroidism. Close thyroid function monitoring and immediate therapy adjustment are essential as the individual absorption may vary widely. Normal absorption levels may be regained due to adaption of the neonatal intestines. LEARNING POINTS: In neonates with malabsorption after ileum resection intravenous levothyroxine replacement should be used to provide normalization of free T4 and TSH.Very high doses of up to 500% usual oral levothyroxine may be required to maintain euthyroidism. The estimated degree of malabsorption can be used to determine the initial dose.Close thyroid function monitoring and immediate therapy adjustment are essential as the absorption and intestinal adaption may vary widely.

Resolution of ketoacidosis in children with new onset diabetes: Evaluation of various definitions.

AIMS: Data are sparse concerning use of serum electrolyte parameters as compared to venous blood gas (VBG) measurements to monitor acid-base status during treatment of diabetic ketoacidosis (DKA). We explored the utility of various parameters to define DKA resolution by investigating the relationship of venous pH (vpH), anion gap (AG), serum bicarbonate (HCO3), and glucose concentration during management of DKA in children with new onset diabetes mellitus (NODM). METHODS: We included all patients with NODM presenting with DKA to Boston Children's Hospital from 10/1/07-7/1/13. DKA was defined as serum glucose ≥ 200 mg/dL (11.1 mmol/L) and vpH<7.30; severity as mild <7.30, moderate<7.20, severe<7.10; resolution of DKA as vpH≥7.30 and AG≤18 mmol/L. We used Cox regression to determine time to DKA resolution, and logistic regression to evaluate different serum HCO3 cut-off values as predictors of DKA resolution. RESULTS: 263 patients (133F, mean age 9.9±4.4 years, 74% White) were included. DKA was mild in 134 (51%), moderate in 75 (28%) and severe in 54 (20%). In mild DKA, AG closed after normalization of vpH; in moderate and severe DKA, AG closed before normalization of vpH. HCO3>15mmol/L correlated with vpH≥7.30, and had 76% sensitivity and 85% specificity to predict DKA resolution. Median times to DKA resolution were similar using two different definitions: vpH and AG (8.4h [IQR 6.3-11.9]) vs. HCO3>15 mmol/L (7.9 h [IQR 5.0-11.8]), p=.42. CONCLUSIONS: During management of pediatric DKA, HCO3 > 15 mmol/L reliably predicts resolution of DKA. In low-resource settings where VBG is unavailable, electrolyte parameters alone may be used to determine DKA resolution.