The past, present, and future of basal insulins Pettus, Jeremy; Santos Cavaiola, Tricia; Tamborlane, William V. ...
Diabetes/metabolism research and reviews,
September 2016, Letnik:
32, Številka:
6
Journal Article
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.
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 (<47 mg/dL) hypoglycemia; percentage of time in mild (145-180 mg/dL) and severe (>180 mg/dL) hyperglycemia; and glucose variability.
Neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs 68%,
< .001) and decreased time spent in mild (
= .04) and severe (
= .007) hypoglycemia and in severe hyperglycemia (
= .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,
= .01; coefficient of variation: 22.8% ± 4.2% vs 27.9% ± 5.0%;
< .001).
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.
Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, ...insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated.
Participants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed.
A total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was -0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, -0.85%; 95% CI -1.51, -0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose -21.6 mg/dL (-49.0, 5.7; P = 0.119), systolic blood pressure -2.8 mmHg (-8.0, 2.4; P = 0.284), and body weight -1.22 kg (-3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively.
In youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated.
OBJECTIVE:--The most promising β-cell replacement therapy for children with type 1 diabetes is a closed-loop artificial pancreas incorporating continuous glucose sensors and insulin pumps. The ...Medtronic MiniMed external physiological insulin delivery (ePID) system combines an external pump and sensor with a variable insulin infusion rate algorithm designed to emulate the physiological characteristics of the β-cell. However, delays in insulin absorption associated with the subcutaneous route of delivery inevitably lead to large postprandial glucose excursions. RESEARCH DESIGN AND METHODS--We studied the feasibility of the Medtronic ePID system in youth with type 1 diabetes and hypothesized that small manual premeal "priming" boluses would reduce postprandial excursions during closed-loop control. Seventeen adolescents (aged 15.9 ± 1.6 years; A1C 7.1 ± 0.8%) underwent 34 h of closed-loop control; 8 with full closed-loop (FCL) control and 9 with hybrid closed-loop (HCL) control (premeal priming bolus). RESULTS:--Mean glucose levels were 135 ± 45 mg/dl in the HCL group versus 141 ± 55 mg/dl in the FCL group (P = 0.09); daytime glucose levels averaged 149 ± 47 mg/dl in the HCL group versus 159 ± 59 mg/dl in the FCL group (P = 0.03). Peak postprandial glucose levels averaged 194 ± 47 mg/dl in the HCL group versus 226 ± 51 mg/dl in the FCL group (P = 0.04). Nighttime control was similar in both groups (111 ± 27 vs. 112 ± 28 mg/dl). CONCLUSIONS:--Closed-loop glucose control using an external sensor and insulin pump provides a means to achieve near-normal glucose concentrations in youth with type 1 diabetes during the overnight period. The addition of small manual priming bolus doses of insulin, given 15 min before meals, improves postprandial glycemic excursions.
The prevalence and magnitude of childhood obesity are increasing dramatically. We examined the effect of varying degrees of obesity on the prevalence of the metabolic syndrome and its relation to ...insulin resistance and to C-reactive protein and adiponectin levels in a large, multiethnic, multiracial cohort of children and adolescents.
We administered a standard glucose-tolerance test to 439 obese, 31 overweight, and 20 nonobese children and adolescents. Baseline measurements included blood pressure and plasma lipid, C-reactive protein, and adiponectin levels. Levels of triglycerides, high-density lipoprotein cholesterol, and blood pressure were adjusted for age and sex. Because the body-mass index varies according to age, we standardized the value for age and sex with the use of conversion to a z score.
The prevalence of the metabolic syndrome increased with the severity of obesity and reached 50 percent in severely obese youngsters. Each half-unit increase in the body-mass index, converted to a z score, was associated with an increase in the risk of the metabolic syndrome among overweight and obese subjects (odds ratio, 1.55; 95 percent confidence interval, 1.16 to 2.08), as was each unit of increase in insulin resistance as assessed with the homeostatic model (odds ratio, 1.12; 95 percent confidence interval, 1.07 to 1.18 for each additional unit of insulin resistance). The prevalence of the metabolic syndrome increased significantly with increasing insulin resistance (P for trend, <0.001) after adjustment for race or ethnic group and the degree of obesity. C-reactive protein levels increased and adiponectin levels decreased with increasing obesity.
The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity. Biomarkers of an increased risk of adverse cardiovascular outcomes are already present in these youngsters.
Continuous glucose monitoring (CGM) has potential to address challenges of type 1 diabetes (T1D) management for young children. CGM use is increasing, yet remains underutilized. Characterizing ...parents' experiences with CGM can inform clinical strategies to help parents make decisions about diabetes management, overcome obstacles to initiating and sustaining CGM use, and maximize benefits of CGM use in their children's diabetes care.
Transcripts from semistructured qualitative interviews with 55 parents of children aged 1 to <8 years, with T1D duration ≥6 months, and whose child currently or previously used CGM were coded and analyzed to derive themes about their experiences with CGM.
Participants were 88% mothers and the mean child age was 5.0 ± 1.5 years. Parents described benefits of CGM use: decreased worry about glucose excursions, improved sleep, increased sense of safety with children who cannot recognize or express symptoms of hypo- or hyperglycemia, and greater comfort with other caregivers, especially using remote monitoring functionality when away from children. Challenges included painful insertions, wearing multiple devices on small bodies, disruptive alerts, data gaps due to lost signals, skin/adhesive problems, and difficulty interpreting the amount of information generated by CGM. For some, the challenges outweighed potential benefits and they stopped CGM use.
CGM may address unique challenges of T1D in young children and increase parental comfort with diabetes management, yet there are multiple barriers to initiating or maintaining CGM use. Education and behavioral support to address these benefits and barriers may equip caregivers with skills to address challenges of CGM use.
Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are ...needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.
While the Type 1 Diabetes Exchange data noted that diabetic ketoacidosis (DKA) is more common in those utilizing injection regimens than insulin pumps, DKA remains a risk for pump users, as it can ...precipitously develop if insulin infusion is interrupted. We sought to obtain more recent DKA admission data in T1D youth using insulin pumps and the impact of CGM on DKA rates.
Methods: We characterized DKA data in insulin pump users from episodes between 12/20 and 6/2021 in an academic pediatric endocrine practice in which 68% were pump users.
Results: Among 591 pump patients aged <25 years (y) , 28 events occurred (3.16 events per 100 patient-y. Mean age was 13.6±3.4y; 85.7% were 12-19y old. More events were in males (60.7%) , 53.6% were white, 71.4% non-Hispanic. Mean HbA1c was 10.22.3%, diabetes duration 6.1±4.0y, and 57.1% used CGM; 28.6% of patients were new to pump therapy (<1y) .Admission pH levels ranged between 7.0-7.31, with 28.6% of events classified as “moderate” and 46.4% as “severe.” Average length of stay was 2.0±0.7 days. While there was no significant difference in pH levels, CGM wearers had higher admission bicarbonate values (11.8 vs. 9.3, p=0.04) . Clinicians assessed the cause of DKA to be related to concurrent illness (10.7%) , insulin omission (14.3%) , pump infusion site failure (57.1%) or other pump malfunctions (14.3%) . For most (60.7%) , this was the first documented DKA event. Alcohol consumption was a contributing factor in only one event.
Conclusions: DKA events were relatively uncommon; most episodes occurred in adolescents in poor diabetes control. Notably, most events could have been avoided if users followed standard trouble shooting guidelines. Thus, education on DKA prevention should be reinforced at each visit, particularly for teens on pumps with higher A1c levels. Moreover, while CGM wearers had higher admission bicarbonate values, over 50% of those hospitalized for DKA wore a CGM, suggesting even pump users using CGM require frequent reinforcement of DKA prevention education.
Disclosure
E.Doyle: None. S.A.Weinzimer: Consultant; Dompé, Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc. W.V.Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited.
Previous research has documented racial/ethnic disparities in diabetes treatments and outcomes. It remains controversial whether these disparities result from differences in socioeconomic status ...(SES) or other factors. We examined racial/ethnic disparities in therapeutic modalities and diabetes outcomes among the large number of pediatric participants in the T1D Exchange Clinic Registry.
The cohort included 10 704 participants aged <18 years with type 1 diabetes for ≥1 year (48% female; mean age: 11.9 ± 3.6 years; diabetes duration: 5.2 ± 3.5 years). Diabetes management and clinical outcomes were compared among 8841 non-Hispanic white (white) (83%), 697 non-Hispanic black (black) (7%), and 1166 Hispanic (11%) participants. The population included 214 high-income black and Hispanic families.
Insulin pump use was higher in white participants than in black or Hispanic participants (61% vs 26% and 39%, respectively) after adjusting for gender, age, diabetes duration, and SES (P < .001). Mean hemoglobin A1c was higher (adjusted P < .001) in black participants than in white or Hispanic participants (9.6%, 8.4%, and 8.7%). More black participants experienced diabetic ketoacidosis and severe hypoglycemic events in the previous year than white or Hispanic participants (both, P < .001). There were no significant differences in hemoglobin A1c, diabetic ketoacidosis, or severe hypoglycemia between white and Hispanic participants after adjustment for SES.
Even after SES adjustment, marked disparities in insulin treatment method and treatment outcomes existed between black versus Hispanic and white children within this large pediatric cohort. Barriers to insulin pump use and optimal glycemic control beyond SES should be explored in all ethnic groups.
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