Search

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

OBJECTIVE We evaluated blinded continuous glucose monitoring (CGM) profiles in a subset of adults with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study to characterize the frequency of glycemic excursions and contributing factors. RESEARCH DESIGN AND METHODS CGM-derived metrics were compared for daytime and nighttime periods using blinded CGM for a minimum of 6.5 days (average 11.9 days) and correlated with HbA1c levels, routine use of diabetes devices, and other characteristics in 765 participants. RESULTS Participants were 58.9 ± 6.5 years of age with diabetes duration 36.8 ± 4.9 years and HbA1c 7.8 ± 1.2%; 58% used insulin pumps, and 27% used personal, unblinded CGM. Compared with daytime, nighttime mean sensor glucose was lower, percent time in range 70–180 mg/dL (TIR) was similar, and hypoglycemia was more common. Over the entire recording period, only 9% of the 765 participants achieved >70% TIR and only 28% achieved CONCLUSIONS In adults with long-standing type 1 diabetes, short-term blinded CGM profiles revealed frequent clinically significant hypoglycemia (

OBJECTIVE This study evaluated the effects of continuous glucose monitoring (CGM) combined with family behavioral intervention (CGM+FBI) and CGM alone (Standard-CGM) on glycemic outcomes and parental quality of life compared with blood glucose monitoring (BGM) in children ages 2 to RESEARCH DESIGN AND METHODS This was a multicenter (N = 14), 6-month, randomized controlled trial including 143 youth 2 to RESULTS Approximately 90% of participants in the CGM groups used CGM ≥6 days/week at 6 months. Between-group TIR comparisons showed no significant changes: CGM+FBI vs. BGM 3.2% (95% CI −0.5, 7.0), Standard-CGM vs. BGM 0.5% (−2.6 to 3.6), CGM+FBI vs. Standard-CGM 2.7% (−0.6, 6.1). Mean time with glucose level CONCLUSIONS CGM used consistently over a 6-month period in young children with type 1 diabetes did not improve TIR but did significantly reduce time in hypoglycemia. The FBI benefited parental well-being.

OBJECTIVE: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia. METHODS: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week). Weekly bonuses were given for maintaining at least 70% of the time in auto mode, which were increased for persistent auto mode use from $3/week to a maximum of $13/week. If a participant failed to maintain auto mode for a week, the rewards were reset to baseline. Data from 17 participants aged 15.9 years ± 2.5 years (baseline hemoglobin A1c [HbA1c] 8.6% ± 1.1%) were collected at 6, 12, and 16 weeks. The reinforcers were withdrawn at 16 weeks, with a follow-up assessment at 24 weeks. RESULTS: With reinforcers, the participants administered an average of at least 3 mealtime insulin boluses per day and wore the sensor over 70% of the time. However, auto mode use waned. HbA1c levels decreased by 0.5% after 6 weeks, and this improvement was maintained at 12 and 16 weeks (P < .05). Upon withdrawal of reinforcers, HbA1c levels increased back to baseline at 24 weeks. CONCLUSION: Compensation for diabetes-related tasks was associated with lower HbA1c levels, consistent administration of mealtime insulin boluses, and sustained sensor use. These results support the potential of financial rewards for improving outcomes in youth with type 1 diabetes.

BACKGROUND: This a unique case of late-onset endocrinopathies after stem cell transplant in a girl with Griscelli syndrome. Griscelli syndrome is a rare disorder characterized by partial albinism, silver hair and immune failure with alteration in genes necessary for melanin transport, which is curative by stem cell transplant. Although late endocrinopathies are quite common in other disorders after stem cell transplant, these complications have not been reported in Griscelli syndrome. CLINICAL CASE: A 7-year old female who received a stem cell transplant as a toddler and subsequently developed graft-versus-host-disease (GvHD) at 2 years of age presented for evaluation of growth failure. Patient had severe short stature along with mild hyperthyroxinemia with subsequent diagnosis of Graves’ disease which was treated with methimazole. Although hypothyroidism is more commonly seen after stem cell transplant, rare cases of hyperthyroidism have been reported. Despite normal GH and IGF-1 levels, GH therapy was commenced due to persistent growth failure. She showed a robust increase in growth parameter from -6 to -2 SD below the mean. She started spontaneous puberty, however, biochemical evaluation showed hypergonadotropic hypogonadism with undetectable anti-mullerian hormone (AMH) which is consistent with low ovarian reserve most likely related to total body irradiation prior to stem cell transplant. CONCLUSION: Our patient demonstrates that growth failure, thyroid disease and ovarian dysfunction can be complications of stem cell transplants in young children with Griscelli syndrome. This can be a result of the underlying disease leading to transplant, conditioning regimen prior to transplant or complications thereafter. GvHD may also be a risk factor for future autoimmune endocrine complications in this syndrome and in other syndromes treated with stem cell transplant. REFERENCES: (1) Griscelli C, Prunieras M. Pigment dilution and immunodeficiency: a new syndrome. Int J Dermatol. 1978;10:788–91. (2) Sağ E, Gönç N, Alikaşifoğlu A, et al. Hyperthyroidism after allogeneic hematopoietic stem cell transplantation: A Report of Four Cases. J Clin Res Pediatr Endocrinol. 2015;4:349–54.

AIM: To assess the associations between demographic and clinical characteristics and sensor glucose metrics in young children with type 1 diabetes, using masked, continuous glucose monitoring data from children aged 2 to < 8 years. RESEARCH DESIGN AND METHODS: The analysis included 143 children across 14 sites in the USA, enrolled in a separate clinical trial. Eligibility criteria were: age 2 to 10.0 mmol/l) and a median of ~1 h/day in hypoglycaemia (

Background Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood. Methods and findings Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = −0.36, 95% CI −0.53 to −0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < −0.29, 95% CIs −0.47 to −0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = −0.22, 95% CI −0.41 to −0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI −0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown. Conclusions These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted., Lars C. Foland Ross and colleagues investigate executive brain function in children with Type 1 diabetes., Author summary Why was this study done? Maintaining optimal levels of blood glucose in children with type 1 diabetes (T1D) is difficult. Because childhood and adolescence are periods of major neurodevelopmental change, there has been growing interest in whether T1D is associated with variations in the brain. No studies to date, to our knowledge, have examined brain function in children with T1D as they engaged in a cognitively demanding task. What did the researchers do and find? Brain function was examined in 150 children with or without T1D as they performed an executive function paradigm, the go/no-go task. This task requires that participants respond as quickly and accurately as possible, using a button press, to a high number of “go” stimuli (e.g., when they see any letter except “X”), and suppress a prepotent response on a smaller subset of “no-go” stimuli (e.g., when they see the letter “X”). Despite equivalent performance on the go/no-go task, children with T1D exhibited increased activation in task-positive networks (e.g., in executive control regions), as well as reduced suppression of activation in the default mode network (DMN). Increased hyperactivation in task-positive networks was associated with better executive functioning, improved go/no-go task performance, and reduced suppression of the DMN in children with T1D. Reduced suppression of the DMN, in turn, was associated with an earlier age of onset of T1D. What do these findings mean? These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN and cognitive function. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes. ispartof: DIABETES CARE vol:42 issue:6 pages:1147-1154 ispartof: location:United States status: published

Background: In type 1 diabetes (T1D), closed-loop systems provide excellent overnight fasting blood glucose control by adjusting the insulin infusion rate based on corresponding changes in sensor glucose levels. In patients on multiple daily insulin (MDI) injections, such control in overnight glucose levels has not been possible due to the inability to alter the absorption rate of long-acting insulin after injection. In this study, we tested the hypothesis that increases/decreases of fasting glucose levels could be achieved by cooling/warming the skin around the injection site, which would result in lower/higher Glargine absorption rates from its subcutaneous depot. Methods: Fourteen subjects with T1D (4 females; age 39.6 ± 16.7 years, HbA1c 7.8 ± 1.1%, BMI 25.4 ± 2.8 kg/m2) on MDI therapy underwent fasting pharmacokinetic and pharmacodynamic studies that started at ~8 am and lasted 240 min on 3 separate days in random order: a control day without warming or cooling of the injection site and two experimental days, one day with injection site warming and the other with cooling. Results: Cooling the skin around the glargine injection site reduced insulin concentrations by >40% ( P < .01 versus the warming study, P = .21 versus the control study), accompanied by a 55 mg/dL increase in serum glucose ( P < .01 versus the control study). Conversely, skin warming prevented the fall in serum insulin ( P = .2 versus the control study; P < .01 versus the cooling study), resulting in a 40 mg/dL reduction in serum glucose ( P < .001 versus the cooling study, P = .11 versus the control study). Conclusions: This proof of concept study has shown that cooling and warming the skin around the injection site provides a means to decrease and increase the rate of absorption and action of insulin glargine from its subcutaneous depot.

With this January 2017 issue, our editorial team celebrates its 5-year anniversary at the helm of Diabetes Care . In 2012, when we accepted the assignment to oversee the scientific aspects of the journal, we envisioned that the editorial for this January 2017 issue would be our opportunity to thank the American Diabetes Association (ADA) for allowing us to lead this effort, to thank our reviewers and associate editors for their tireless efforts, and to thank the readers for their valuable suggestions and ideas. However, we are now writing to inform you that those plans have been put on hold. Our editorial team has been given the opportunity to continue to guide Diabetes Care for another 2-year period. We have accepted the invitation primarily because our “team” (including the editorial committee, editorial office, and publications staff) feels we still have creative ideas to make the journal better and considerable energy to bring these ideas to fruition. Therefore, suffice it to say, we remain honored to continue to lead Diabetes Care for this extended period. It has been our custom to summarize our productivity and achievements in both the January and June issues of each year. This year we believe the trajectory of quality continues to rise. We hope you will also agree when reading the summary presented in this narrative. We feel each year’s monthly issues have surpassed the prior year’s work, and year 2016 is no exception! As we described in July of 2016, we aim to provide the readers with lagniappe—“a little something extra”! (1). This past year the editorial team took our initiative to another level devoting several monthly issues to specific clinical or research topics. A current summary of all thematic monthly issues can be found in our Diabetes Care Online Collections (http://care.diabetesjournals.org/content/diabetes-care-online-collections). In the …

With the increasing availability of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII), the artificial pancreas (AP) (the commonly accepted term for closed-loop control [CLC] of blood glucose [BG] levels in diabetes) has become a hot area in translational research and industrial development. After a prolonged period of inpatient, clinical research center trials using cumbersome systems, the field has progressed rapidly over the past 2 years to long-term, free-living studies running AP algorithms on smartphones. Although it is still not a cure, the AP is the most promising advance in the treatment of diabetes at this time. This issue of Diabetes Care presents today’s AP state of the art, including reports on multinational home-use AP trials, studies in young children, the use of multihormonal approaches to mitigate meal-related hyperglycemia, and discussions of AP study designs and outcome measures. This collection of articles establishes the AP as a new diabetes treatment paradigm—not a single-function CGM or CSII device but an adaptable wearable network encompassing the patient in a digital treatment ecosystem. In its May 2014 issue, Diabetes Care featured the progress in the AP field in a series of articles labeled “Advances in Artificial Pancreas Development.” In addition to an editorial discussing the state of the art of AP development in 2014 (1), the issue included original articles that covered a broad range of topics including analyses of the possible physiological inputs to CLC (2), real-time estimation of insulin sensitivity from CGM and insulin pump data (3), engineering of the AP algorithms (4), reports of predictive low-glucose suspend (LGS) systems (5), studies of overnight CLC at home (6), feasibility of the AP in type 2 diabetes (7), and the first around-the-clock outpatient CLC running a model predictive control (MPC) algorithm on a portable AP system (8). Since then, …

OBJECTIVE Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3–4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16–23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-μg pramlintide (CL + P), after a 3–4-week outpatient dose escalation. Eleven subjects (age 18–27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3–4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.

Objective: We have shown that “euglycemic DKA” in patients with type 1 diabetes receiving a sodium–glucose cotransporter 2-inhibitor (SGLT2i) is due to normal increases in rates of ketogenesis but blunted increases in plasma glucose levels. In this analysis, we assessed whether rescue treatment of early ketoacidosis with insulin is altered by SGLT2i use. Research Design and Methods: Participants received 0.2 U/kg of aspart insulin after two 6-h interruptions of basal insulin that increased beta-hydroxybutyrate (BHB) by 1.2 ± 0.7 mmol/L before and by 1.5 ± 0.2 mmol/L during canagliflozin treatment. BHB and free fatty acid (FFA) were monitored every 30 min for 120 min after receiving a 0.2 U/kg subcutaneous injection of aspart insulin. Results: Ten adults (23 ± 5 years) were studied. During the 120 min after rescue therapy with insulin, the reductions in BHB and FFA were nearly identical between the pre- and during canagliflozin treatment studies, respectively (−1.27 ± 0.76 and −1.13 ± 0.69, P = 0.671 for BHB and −0.50 ± 0.35 vs. −0.41 ± 0.41, P = 0.603 for FFA). Conclusion: These data indicate that turning ketogenesis off, as well as on, does not appear to be affected by SGLT2i use.

OBJECTIVE The Diabetes Prevention Program (DPP) demonstrated that weight loss from intensive lifestyle intervention (ILI) in adults with prediabetes could decrease progression to type 2 diabetes. Inner-city, low-income Hispanic women are at high risk for developing type 2 diabetes; however, this type of intervention is not well established in this group. We hypothesized that a DPP intervention modified for a community health center (CHC) setting would decrease weight and improve metabolic measures in Hispanic women with prediabetes. RESEARCH DESIGN AND METHODS Women diagnosed with prediabetes on a screening oral glucose tolerance test were recruited from a CHC. Participants (90% of whom were Hispanic) were randomized to either usual care (age 43 ± 9.7 years, BMI 35.2 ± 7.3 kg/m2) or ILI (age 43.8 ± 10.8 years, BMI 35.4 ± 8.5 kg/m2), structured as 14 weeks of group sessions focused on food choices, behavior change, physical activity, and weight loss. One year after enrollment, 122 women repeated baseline measures. RESULTS Groups had similar baseline weight, BMI, and fasting and 2-h glucose. One year later, the ILI group had lost 3.8 kg (4.4%), while the usual care group had gained 1.4 kg (1.6%, P < 0.0001). Two-hour glucose excursion decreased 15 mg/dL (0.85 mmol/L) in the ILI and 1 mg/dL (0.07 mmol/L) in the usual care group (P = 0.03). Significant decreases favoring the ILI group were noted in BMI, percent body fat, waist circumference, and fasting insulin. CONCLUSIONS A 14-week ILI program based on the DPP can effectively be translated into a predominantly Hispanic CHC setting, resulting in decreased weight, improved fasting insulin, and smaller glucose excursions 1 year after enrolling in the program.

Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to

Early markers of diabetic kidney disease (DKD), including hyperfiltration and elevated albumin excretion, are common in youth with type 2 diabetes (T2D) (1). Despite the morbidity associated with the development of future DKD in youth-onset T2D, pharmacotherapeutic options to lower hyperglycemia are limited to metformin and insulin, the only drugs approved for use in pediatric patients. Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce blood pressure, weight, and hyperglycemia in adults with T2D. Furthermore, a 38% reduction in cardiovascular death and a 39% reduction in incident or worsening nephropathy have been demonstrated with the selective SGLT2 inhibitor empagliflozin in patients with established cardiovascular disease (2,3). In young adults with type 1 diabetes, treatment with the SGLT2 inhibitor empagliflozin for 8 weeks was associated with natriuresis, increased renal vascular resistance, and reductions in glomerular filtration rate (GFR) (using inulin clearances) and renal blood flow (assessed by p -aminohippuric acid clearance) in those with baseline hyperfiltration (4). This renal hemodynamic profile suggested that the 20% reduction in hyperfiltration observed in this trial was due to afferent vasoconstriction and a decline in intraglomerular hypertension (4). In adults with T2D, the reduction in intraglomerular hypertension is typically reflected by a mean reduction in estimated GFR (eGFR) of 2–4 mL/min/1.73 m2 after treatment initiation, followed by a stabilization of eGFR decline compared …

As the saying goes, time flies when you are having fun! So, our editorial team was surprised to find that with this issue of Diabetes Care we are celebrating our fourth year guiding the scientific aspects of Diabetes Care . It seems like just yesterday that we were introducing the team and our vision for the direction of the journal. We saw immediately that we had “issues” to address—we could easily fail to keep pace with the rapid advances in our field unless we introduced changes in our format and tactics. By this time you are very familiar with many of the changes we have put in place as we have been diligent in updating you in both the July and January issues (1,2). Thus, with this commentary, we will not review details previously provided. We will, however, focus on two initiatives that continue to grow and flourish and have exceeded our expectations. We are referring to the Diabetes Care Symposia that we coordinate and our special monthly thematic issues. Our Diabetes Care Symposium, held each year during the American Diabetes Association’s (ADA’s) Scientific Sessions, has become our editorial team’s signature event. In June 2015, we held our fourth annual symposium, which consisted of two 1-h sessions and a selected overarching theme. The first segment—in a format used for the past 2 years—was entitled “Best of Diabetes Care .” This provided brief overviews of several articles felt by the associate editors to be some of the most noteworthy original research reports published in Diabetes Care during the past year, and it has received rave reviews. The second segment of this year’s program had presentations from four selected original …

OBJECTIVE To evaluate the effectiveness of monetary reinforcement to increase the frequency of self-monitoring blood glucose (SMBG). RESEARCH DESIGN AND METHODS Ten adolescents with poorly controlled diabetes enrolled in a 12-week program in which they earned monetary reinforcers based on SMBG frequency ($0.10 per test, with bonuses for ≥4 tests per day, and $251.40 maximum). RESULTS SMBG increased from 1.8 ± 1.0 to 4.9 ± 1.0 tests per day (P < 0.001) with 90% completing four or more tests per day. Mean A1C fell from 9.3 ± 0.9% to 8.4 ± 1.5% (P = 0.05). Adolescents and parents reported high satisfaction with procedures. CONCLUSIONS Reinforcing adolescents for SMBG may increase testing and improve A1C.

BACKGROUND AND OBJECTIVES: Impaired glucose control in very preterm infants is associated with increased morbidity, mortality, and poor neurologic outcome. Strategies based on insulin titration have been unsuccessful in achieving euglycemia in absence of an increase in hypoglycemia and mortality. We sought to assess whether glucose administration guided by continuous glucose monitoring (CGM) is more effective than standard of care blood glucose monitoring in maintaining euglycemia in very preterm infants. METHODS: Fifty newborns ≤32 weeks’ gestation or with birth weight ≤1500 g were randomly assigned (1:1) within 48-hours from birth to receive computer-guided glucose infusion rate (GIR) with or without CGM. In the unblinded CGM group, the GIR adjustments were driven by CGM and rate of glucose change, whereas in the blinded CGM group the GIR was adjusted by using standard of care glucometer on the basis of blood glucose determinations. Primary outcome was percentage of time spent in euglycemic range (72–144 mg/dL). Secondary outcomes were percentage of time spent in mild (47–71 mg/dL) and severe (180 mg/dL) hyperglycemia; and glucose variability. RESULTS: Neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs 68%, P < .001) and decreased time spent in mild (P = .04) and severe (P = .007) hypoglycemia and in severe hyperglycemia (P = .04) compared with the blinded CGM group. Use of CGM also decreased glycemic variability (SD: 21.6 ± 5.4 mg/dL vs 27 ± 7.2 mg/dL, P = .01; coefficient of variation: 22.8% ± 4.2% vs 27.9% ± 5.0%; P < .001). CONCLUSIONS: CGM-guided glucose titration can successfully increase the time spent in euglycemic range, reduce hypoglycemia, and minimize glycemic variability in preterm infants during the first week of life.

To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise.Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HRBaseline PG levels were similar for CL alone (164 ± 16 mg/dL) versus CL+snack (172 ± 11 mg/dL). During exercise, PG levels fell by 53 ± 10 mg/dL without snacking versus a modest 10 ± 13 mg/dL increase in PG with snacking (P = 0.0005); similar differences in the change in PG levels were observed at the end of recovery period. Hypoglycemia requiring rescue treatment (PG ≤60 mg/dL) during exercise occurred in three nonsnacking visits versus none with snacking. During the 75-min exercise period, insulin delivered was 1.8 ± 0.4 U for the CL+snack admission compared to 0.7 ± 0.1 U during CL alone (P = 0.002).These results support the use of a simple snacking strategy to avoid exercise-induced lowering of PG while on CL insulin delivery. Persistent insulin infusion during exercise with snacking also appears to be effective in limiting increases in PG at the end of exercise.

OBJECTIVE Continuous glucose monitoring (CGM) has been found to improve glucose control in type 1 diabetic patients. We estimated the cost-effectiveness of CGM versus standard glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS This societal cost-effectiveness analysis (CEA) was conducted in trial populations in which CGM has produced a significant glycemic benefit (A1C ≥7.0% in a cohort of adults aged ≥25 years and A1C RESULTS During the trials, CGM patients experienced an immediate quality-of-life benefit (A1C ≥7.0% cohort: 0.70 quality-adjusted life-weeks [QALWs], P = 0.49; A1C CONCLUSIONS Long-term projections indicate that CGM is cost-effective among type 1 diabetic patients at the $100,000/QALY threshold, although considerable uncertainty surrounds these estimates.

OBJECTIVE Clinicians who treat children with type 1 diabetes often try to minimize the number of daily injections to reduce treatment burden and improve compliance. Despite the manufacturer's cautions against mixing glargine with rapid-acting insulin analogs, clinical studies have failed to demonstrate deleterious effects of mixing on glucose excursions or A1C levels. However, no formal glucose clamp studies have been performed to determine whether mixing with glargine has an adverse effect on the early pharmacodynamic action of rapid-acting insulin in humans. RESEARCH DESIGN AND METHODS To examine this question, euglycemic glucose clamps were performed twice, in random order, in 11 youth with type 1 diabetes (age 15.1 ± 3 years, A1C 7.6 ± 0.6%) with 0.2 units/kg lispro and 0.4 units/kg glargine, given either as separate or as a single mixed injection. RESULTS Mixing the two insulins shifted the time action curve to the right, with significantly lower glucose infusion rate (GIR) values after the mixed injections between 60 and 190 min and significantly higher values between 270 and 300 min, lowered the GIRmax (separate 7.1 ± 1 vs. mix 3.9 ± 1, P = 0.03), and markedly delayed the time to reach GIRmax (separate 116 ± 8 min vs. mix 209 ± 15 min, P = 0.004). The GIR area under the curve was significantly lower after the mixed injections. Mixing had similar effects on plasma insulin pharmacokinetics. CONCLUSIONS These data demonstrate that mixing lispro with glargine markedly flattens the early pharmacodynamic peak of lispro and causes a shift to the right in the GIR curve changes that might lead to difficulties in controlling meal-related glucose excursions.

OBJECTIVE The aim of this study was to examine differences between adolescents and adults in persistence of the benefits of intensive therapy 10 years after completion of the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS During the Epidemiology of Diabetes Interventions and Complications (EDIC) study, progression of retinopathy from DCCT closeout to EDIC year 10 was evaluated in 1,055 adults and 156 adolescents. RESULTS During 10 years of follow-up, HbA1c (A1C) was similar between original intensive (INT) and conventional (CON) groups and between former adolescents and adults. At EDIC year 10, adults in the former INT group continued to show slower progression of diabetic retinopathy than those in the CON group (adjusted hazard reduction 56%, P < 0.0001), whereas in adolescents this beneficial effect had disappeared (32%, P = 0.13). Seventy-nine percent of observed differences in the prolonged treatment effect between adults and adolescents at year 10 were explained by differences in mean A1C during DCCT between adolescents and adults (8.9 vs. 8.1%), particularly between INT adolescents and adults (8.1 vs. 7.2%). CONCLUSIONS Prior glycemic control during DCCT is vital for the persistence of the beneficial effects of INT therapy 10 years later. Lowering A1C to as close to normal as safely possible without severe hypoglycemia and starting as early as possible should be attempted for all subjects with type 1 diabetes. These results underscore the importance of maintaining A1C at target values for as long as possible because the benefits of former INT treatment wane over time if A1C levels rise.

OBJECTIVE The potential benefits of continuous glucose monitoring (CGM) in the management of adults and children with well-controlled type 1 diabetes have not been examined. RESEARCH DESIGN AND METHODS A total of 129 adults and children with intensively treated type 1 diabetes (age range 8–69 years) and A1C RESULTS At 26 weeks, biochemical hypoglycemia (≤70 mg/dl) was less frequent in the CGM group than in the control group (median 54 vs. 91 min/day), but the difference was not statistically significant (P = 0.16). Median time with a glucose level ≤60 mg/dl was 18 versus 35 min/day, respectively (P = 0.05). Time out of range (≤70 or >180 mg/dl) was significantly lower in the CGM group than in the control group (377 vs. 491 min/day, P = 0.003). There was a significant treatment group difference favoring the CGM group in mean A1C at 26 weeks adjusted for baseline (P < 0.001). One or more severe hypoglycemic events occurred in 10 and 11% of the two groups, respectively (P = 1.0). Four outcome measures combining A1C and hypoglycemia data favored the CGM group in comparison with the control group (P < 0.001, 0.007, 0.005, and 0.003). CONCLUSIONS Most outcomes, including those combining A1C and hypoglycemia, favored the CGM group. The weight of evidence suggests that CGM is beneficial for individuals with type 1 diabetes who have already achieved excellent control with A1C

OBJECTIVE—The purpose of this study was to examine the effect of type of insulin analog and age of insertion site on the pharmacodynamic characteristics of a standard insulin bolus in youth with type 1 diabetes receiving insulin pump therapy. RESEARCH DESIGN AND METHODS—Seventeen insulin pump–treated adolescents with type 1 diabetes underwent two euglycemic clamp procedures after a 0.2 unit/kg bolus of either insulin aspart or lispro on day 1 and day 4 of insulin pump site insertion. The glucose infusion rate (GIR) required to maintain euglycemia was the primary pharmacodynamic measure. RESULTS—There were no statistically significant differences in any of the pharmacodynamic parameters between aspart and lispro during day 1 and day 4. However, when the two groups were combined, time to discontinuation of exogenous glucose infusion, and time to half-maximal onset and offset of insulin action were observed significantly earlier during day 4 compared with day 1 (P = 0.03–0.0004), but the overall area under the GIR curve was similar on day 1 and day 4. CONCLUSIONS—With both insulin aspart and lispro, there is an earlier peak and shorter duration of action with increasing duration of infusion site use, but overall insulin action is not affected.

Background: Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. Methods: Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m2) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. Results: Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after the meal were significantly reduced ( P = .007 and P = .03, respectively) with skin warming around the injection site. Discussion and Conclusions: Use of the InsuPad to increase the rate of insulin absorption provides an effective means to achieve better control of postmeal glucose excursions in type 2 diabetic patients receiving premeal injections of rapid-acting insulin analogs.

OBJECTIVE To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids. RESEARCH DESIGN AND METHODS Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year. RESULTS American Diabetes Association HbA1c targets of CONCLUSIONS Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.

Seasonal variation in glycemic control has been postulated to occur in school-aged children with type 1 diabetes, with higher HbA1c levels during summer months than during the school year because of lack of structure and less stringent adherence to a prescribed medical regimen during summer vacation (1). To address this question, we used data obtained in 1,972 youth with type 1 diabetes enrolled in the T1D Exchange (T1DX) at 56 clinical centers in the U.S. between 2010 and 2012 (2). To be included in these analyses, participants had to be 8 to 3 years to minimize the influence of changes in residual endogenous insulin secretion over time, and have HbA1c measurements in each of three predefined periods: prior to the start of summer (March, April, May), end of summer vacation (August and September), and back in school (November and December). HbA1c values …

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented.

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10-11) and 8q12 (minimum p value 1.82×10-11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

OBJECTIVE To evaluate long-term effects of continuous glucose monitoring (CGM) in intensively treated adults with type 1 diabetes. RESEARCH DESIGN AND METHODS We studied 83 of 86 individuals ≥25 years of age with type 1 diabetes who used CGM as part of a 6-month randomized clinical trial in a subsequent 6-month extension study. RESULTS After 12 months, median CGM use was 6.8 days per week. Mean change in A1C level from baseline to 12 months was −0.4 ± 0.6% (P < 0.001) in subjects with baseline A1C ≥7.0%. A1C remained stable at 6.4% in those with baseline A1C CONCLUSIONS In intensively treated adults with type 1 diabetes, CGM use and benefit can be sustained for 12 months.

Increasing numbers of children and adolescents with type 1 diabetes (T1D) have been placed on insulin pump therapy. Nevertheless, data are limited regarding patterns of pump use during the first year of treatment and the clinical and socioeconomic factors associated with early use of pump therapy. Therefore, we sought to determine factors associated with pump therapy within the first year of diagnosis in youth enrolled in the Pediatric Diabetes Consortium (PDC) T1D New-Onset (NeOn) Study.The NeOn Study includes youth19 years old at T1D diagnosis who have been followed from the time of diagnosis at seven U.S. pediatric diabetes centers. Cox regression was used to determine factors associated with transition from injection to pump therapy during the first year of T1D in 1,012 participants.Twenty-seven percent (n=254) of participants began pump therapy within the first year of diagnosis, ranging from 18% to 59% among the seven centers. After adjusting for center effect, factors associated with pump use in multivariate analysis included private health insurance (37% vs. 7%; P0.001), having annual household income over $100,000 (50% vs. 15%; P0.001), and non-Hispanic white race (36% vs. 11%; P0.001). The hemoglobin A1c level did not appear to influence the decision to initiate pump use.Participants of non-Hispanic white race and higher socioeconomic status were more likely to be placed on pumps during the first year. Further investigations are needed to gain a better understanding of barriers to use of pumps in youth with T1D, especially in disadvantaged and minority families.

Behavioural economics refers to the study of psychological and cognitive factors that relate to decision-making processes. This field is being applied increasingly to health care settings, in which patients receive tangible reinforcers or incentives for meeting objective behavioural criteria consistent with healthy lifestyles. This article reviews the background and efficacy of reinforcement interventions in general, and then as applied to behaviours related to diabetes prevention and management. Specifically, reinforcement interventions have been applied with some notable success towards promoting greater attendance at medical appointments, enhancing weight loss efforts, augmenting exercising regimes, improving medication adherence and increasing blood glucose monitoring. Suggestions for promising areas of future research are provided, keeping in mind the controversial nature of these interventions.

AIMS AND HYPOTHESIS: The optimal duration and frequency of short-term continuous glucose monitoring (CGM) to reflect long-term glycemia have not been determined. The Juvenile Diabetes Research Foundation CGM randomized trials provided a large dataset of longitudinal CGM data for this type of analysis. METHODS: The analysis included 185 subjects who had 334 3-month intervals of CGM data meeting specific criteria. For various glucose indices, correlations (r(2)) were computed for the entire 3-month interval versus selected sampling periods ranging from 3 to 15 days. Other computed agreement measures included median relative absolute difference, values within ± 10% and ± 20% of full value, and median absolute difference. RESULTS: As would be expected, the more days of glucose data that were sampled, the higher the correlation with the full 3 months of data. For 3 days of sampling, the r(2) value ranged from 0.32 to 0.47, evaluating mean glucose, percentage of values 71–180 mg/dL, percentage of values >180 mg/dL, percentage of values ≤70 mg/dL, and coefficient of variation; in contrast, for 15 days of sampling, the r(2) values ranged from 0.66 to 0.75. The results were similar when the analysis intervals were stratified by age group (8–14, 15–24, and ≥25 years), by baseline hemoglobin A1c level (

Objective: The aim was to formulate practice guidelines for determining settings where patients are most likely to benefit from the use of continuous glucose monitoring (CGM). Participants: The Endocrine Society appointed a Task Force of experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, the Diabetes Technology Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: The Task Force evaluated three potential uses of CGM: 1) real-time CGM in adult hospital settings; 2) real-time CGM in children and adolescent outpatients; and 3) real-time CGM in adult outpatients...

Adiponectin, an adipokine secreted by the adipocyte, is inversely related to adiposity and directly related to insulin sensitivity. In type 1 diabetes mellitus (T1DM), however, data thus far are contradictory. We investigated the relationship between adiponectin and exercise inT1DM.Forty-nine children (14.5 +/- 2.0 yr, range 8-17 yr) with T1DM on an insulin pump were studied during two 75-min exercise sessions with and without continuation of the basal rate within 4 wk. Adiponectin and epinephrine concentrations were measured before and during exercise.Mean preexercise adiponectin concentration was 11.2 +/- 4.7 mg/L (range 2.7-23.0 mg/L) with a mean absolute difference of 1.7 mg/L between the 2 d. Adiponectin concentrations did not change meaningfully during exercise (mean change: -0.1 +/- 1.2 mg/L; p = 0.17). Adiponectin correlated inversely with body mass index percentile (p = 0.02) but not with age, gender, duration of diabetes, hemoglobin A1c, or preexercise glucose. However, those with higher baseline adiponectin concentrations were less likely to become hypoglycemic during exercise, 36% becoming hypoglycemic when baseline adiponectin concentration was10 mg/L, 42% when 10 to15 mg/L, and 15% whenor =15 mg/L (p = 0.02). Baseline epinephrine concentrations were not associated with adiponectin, and in those whose nadir glucose wasor =100 mg/dL, there was no correlation between epinephrine response and adiponectin (p = 0.16).Adiponectin concentrations are stable from day to day, are not affected by acute exercise or metabolic control, and vary inversely with adiposity. Higher adiponectin concentration appears to be associated with a decrease in hypoglycemia risk during exercise. Further studies are needed to examine whether adiponectin protects against exercise-induced hypoglycemia by directly enhancing the oxidation of alternate fuels.

OBJECTIVE—Strategies for preventing hypoglycemia during exercise in children with type 1 diabetes have not been well studied. The Diabetes Research in Children Network (DirecNet) Study Group conducted a study to determine whether stopping basal insulin could reduce the frequency of hypoglycemia occurring during exercise. RESEARCH DESIGN AND METHODS—Using a randomized crossover design, 49 children 8–17 years of age with type 1 diabetes on insulin pump therapy were studied during structured exercise sessions on 2 days. On day 1, basal insulin was stopped during exercise, and on day 2 it was continued. Each exercise session, performed from ∼4:00–5:00 p.m., consisted of four 15-min treadmill cycles at a target heart rate of 140 bpm (interspersed with three 5-min rest breaks over 75 min), followed by a 45-min observation period. Frequently sampled glucose concentrations (measured in the DirecNet Central Laboratory) were measured before, during, and after the exercise. RESULTS—Hypoglycemia (≤70 mg/dl) during exercise occurred less frequently when the basal insulin was discontinued than when it was continued (16 vs. 43%; P = 0.003). Hyperglycemia (increase from baseline of ≥20% to ≥200 mg/dl) 45 min after the completion of exercise was more frequent without basal insulin (27 vs. 4%; P = 0.002). There were no cases of abnormal blood ketone levels. CONCLUSIONS—Discontinuing basal insulin during exercise is an effective strategy for reducing hypoglycemia in children with type 1 diabetes, but the risk of hyperglycemia is increased.

Until two decades ago, children and adolescents were automatically assumed to have insulin-dependent type 1 diabetes. However, type 2 diabetes emerged as a “new type” of childhood diabetes in the 1990s in association with the epidemic of childhood obesity. It quickly became apparent that this new pediatric disease disproportionally affected disadvantaged minority children and was associated with comorbidities that increased the risk of future cardiovascular disease. After more than 20 years, the optimal approach to the treatment of childhood type 2 diabetes remains largely unknown. Besides insulin, metformin remains the only other antidiabetic medication that is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in youth with type 2 diabetes. Glimepiride and rosiglitazone failed noninferiority tests versus metformin as initial monotherapy in company-sponsored clinical trials. While the primary study results of the randomized phase of the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) study showed that combination therapy with metformin plus rosiglitazone was more effective than metformin plus intensive lifestyle intervention and metformin alone (1), rosiglitazone will not be used with any frequency in young patients with type 2 diabetes because of concerns about the cardiovascular and other adverse effects of this class of medications. Once again, pediatric diabetes practitioners are left with just metformin and insulin for adolescents with type 2 diabetes. Why haven’t glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors that have been approved for use in adults with type 2 diabetes been approved for the treatment of adolescents …

OBJECTIVE The workup of hypoglycemia requires frequent glucose sampling. We designed these studies to determine if the Continuous Glucose Monitoring System (CGMS) and the GlucoWatch G2 Biographer (GW2B) are sufficiently accurate to use in nondiabetic children. Study design Fifteen healthy children (aged 9-17 years, 11 boys) wore a GW2B and a CGMS during a 24-hour period, and reference serum glucose was measured hourly during the day and half-hourly overnight. RESULTS Compared with the reference glucose, the median absolute difference in concentrations measured by the GW2B (487 pairs) was 13 mg/dL, and the difference measured by the CGMS was 17 mg/dL (668 pairs), with 30% and 42% of values using the GW2B and CGMS, respectively, deviating >20 mg/dL from the reference value. The GW2B reported values

The ventromedial hypothalamic nucleus (VMH) is necessary for the integrated hormonal response to hypoglycemia. To determine the role of the VMH as a glucose sensor, we performed experiments designed to specifically prevent glucopenia in the VMH, while producing hypoglycemia elsewhere. We used awake chronically catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D-glucose) was combined with a sequential euglycemic-hypoglycemic clamp. In two control groups the VMH was perfused either with (a) an iso-osmotic solution lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic hypoglycemia glucagon and catecholamine concentrations promptly increased in the control animals perfused with either 100 mM L-glucose or the iso-osmotic solution lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release was inhibited in the animals in which the VMH was perfused with D-glucose; hormonal secretion was partially suppressed by the VMH perfusion with 15 mM D-glucose and suppressed by approximately 85% when the VMH was perfused with 100 mM D-glucose, as compared with the control groups. We conclude that the VMH must sense hypoglycemia for full activation of catecholamine and glucagon secretion and that it is a key glucose sensor for hypoglycemic counterregulation.