Christine L. Chan

Continuous Glucose Monitoring and its Relationship to Hemoglobin A1c and Oral Glucose Tolerance Testing in Obese and Prediabetic Youth

CONTEXT The optimal screening test for diabetes and prediabetes in obese youth is controversial. OBJECTIVE We examined whether glycosylated hemoglobin (HbA1c) or the oral glucose tolerance test (OGTT) is a better predictor of free-living glycemia as measured by continuous glucose monitoring (CGM). DESIGN This was a cross-sectional study of youth 10-18 years old, body mass index (BMI) 85th percentile or greater, with diabetes risk factors. SETTING AND PARTICIPANTS Participants (n = 118) with BMI 85th percentile or greater, not on medications for glucose management, were recruited from primary care and pediatric endocrinology clinics around Denver, Colorado. INTERVENTION HbA1c, fasting plasma glucose, and 2-hour glucose were collected and all participants wore a blinded CGM for 72 hours. MAIN OUTCOME MEASURES CGM outcomes were determined and descriptive statistics calculated. Performance characteristics at current American Diabetes Association cutpoints were compared with CGM outcomes. RESULTS CGM data were successfully collected on 98 obese youth. Those with prediabetes had significantly higher average glucose, area under the curve (AUC), peak glucose, and time greater than 120 and greater than 140 mg/dL (P < .01) on CGM than youth with normal HbA1c or OGTT. HbA1c had a greater magnitude of correlation to CGM average glucose, AUC, and minimum glucose; 2-hour glucose had a greater magnitude of correlation to CGM SD, peak glucose, and time greater than 140 and greater than 200 mg/dL. However, there were no overall differences in the strength comparisons between 2-hour glucose and HbA1c correlations to CGM outcomes. CONCLUSIONS In obese youth, HbA1c and 2-hour glucose performed equally well at predicting free-living glycemia on CGM, suggesting that both are valid tests for dysglycemia screening.

Use of glycosylated hemoglobin increases diabetes screening for at-risk adolescents in primary care settings.

To examine rates of diabetes screening in obese adolescents in an ethnically diverse primary care health care system before and after an internal recommendation to use HbA1c‐based screening.

Screening for type 2 diabetes and prediabetes in obese youth: evaluating alternate markers of glycemia – 1,5‐anhydroglucitol, fructosamine, and glycated albumin

Hemoglobin A1c (HbA1c) is increasingly performed over the oral glucose tolerance test (OGTT) as the initial screening test for type 2 diabetes in youth. However, the optimal strategy for identifying type 2 diabetes in youth remains controversial. Alternate glycemic markers have been proposed as potentially useful tools for diabetes screening. We examined the relationships among fructosamine (FA), glycated albumin (GA), and 1,5‐anhydroglucitol (1,5‐AG) with traditional screening tests, HbA1c and OGTT. Youth 10–18 yrs, BMI ≥85th‰, and HbA1c <7.5% had a single visit with measurement of HbA1c, 1,5‐AG, FA, GA, and a standard OGTT. Distributions of FA, GA, and 1,5‐AG by HbA1c and 2‐hour glucose (2hG) categories were compared. Receiver operating characteristic (ROC)‐curves were generated to determine the cut points at which alternate markers maximized sensitivity and specificity for predicting prediabetes and diabetes. One hundred and seventeen, 62% female, 59% Hispanic, 22% White, 17% black, median 14.1 yr, and body mass index (BMI) z‐score 2.3 participated. Median values of each alternate marker differed significantly between prediabetes and diabetes HbA1c and 2hG categories (p < 0.017). Only GA medians differed (p = 0.006) between normal and prediabetes HbA1c. Area under the receiver operating characteristic curves (ROC‐AUCs) for alternate markers as predictors of prediabetes (0.5–0.66) were low; however, alternate marker ROC‐AUCs for identifying diabetes (0.82–0.98) were excellent. Although the alternate markers were poor predictors of prediabetes, they all performed well predicting diabetes by 2hG and HbA1c. Whereas the usefulness of these markers for identifying prediabetes is limited, they may be useful in certain scenarios as second line screening tools for diabetes in overweight/obese youth.

Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes

To determine whether the alternate glycemic markers, fructosamine (FA), glycated albumin (GA), and 1,5‐anhydroglucitol (1,5AG), predict glycemic variability captured by continuous glucose monitoring (CGM) in obese youth with prediabetes and type 2 diabetes (T2D).

Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate with pulmonary function decline

BACKGROUND To characterize glucose patterns with continuous glucose monitoring (CGM) in cystic fibrosis (CF) and assess relationships between CGM and clinical outcomes. METHODS 110 CF youth and healthy controls (HC), 10-18 years, wore CGM up to 7 days. Correlations between CGM and lung function and BMI z-score change over the prior year were determined. RESULTS Multiple CGM measures were higher in CF Normal Glycemic (CFNG) youth versus HC (peak glucose, excursions >140 mg/dl/day, %time > 140 mg/dl, standard deviation (SD) and mean amplitude of glycemic excursions (MAGE)). Hypoglycemia was no different among groups. In CF, decline in FEV1% and FVC% correlated with maximum CGM glucose, excursions >200 mg/dl/day, SD, and MAGE. CONCLUSIONS CFNG youth have higher glucoses and glucose variability than HC on CGM. Higher and more variable glucoses correlate with lung function decline. Whether earlier treatment of CGM abnormalities improves lung function in CF requires further study.

The role of glycemia in insulin resistance in youth with type 1 and type 2 diabetes

Hyperglycemia has traditionally been considered a major contributor to insulin resistance (IR) in type 1 diabetes (T1D), yet studies examining the relationship between HbA1c and IR are conflicting. Glucose measures captured by continuous glucose monitoring (CGM) (eg, peak glucose, standard deviation, hypoglycemia) in youth have not been explored as predictors of insulin sensitivity (IS).

Comparison of Metabolic Outcomes in Children Diagnosed with Type 1 Diabetes Through Research Screening (Diabetes Autoimmunity Study in the Young [DAISY]) Versus in the Community.

BACKGROUND Children with positive islet autoantibodies monitored prospectively avoid metabolic decompensation at type 1 diabetes (T1D) diagnosis. However, the effects of early diagnosis and treatment on preservation of insulin secretion and long-term metabolic control are unknown. We compared characteristics of children detected through research screening (Diabetes Autoimmunity Study in the Young [DAISY]) versus community controls at baseline and, in a subset, 6- and 12-month metabolic outcomes. MATERIALS AND METHODS This was a case-control study comparing DAISY children with T1D to children diagnosed in the general community. All participants underwent mixed-meal tolerance testing; a subset wore a continuous glucose monitoring (CGM) device. Fasting and stimulated C-peptide levels, insulin dose-adjusted hemoglobin A1c (IDAA1c), and CGM variables were compared. RESULTS Children (21 DAISY, 21 community) were enrolled and matched by age, time of diagnosis, and diabetes duration; 18 were enrolled within 2 months and 24 within 2.5 years on average from diagnosis. In the overall group and the subgroup of participants enrolled 2.5 years from diagnosis, there were no IDAA1c or C-peptide differences between DAISY versus community children. The subgroup of DAISY versus community children enrolled near diagnosis, however, had lower baseline hemoglobin A1c (6.5±1.4% vs. 9.2±2.9%; P=0.0007) and IDAA1c (7.4±2.1% vs. 11.2±3.5%; P=0.04) and higher stimulated C-peptide (2.5±0.5 vs. 1.6±0.2 ng/mL; P=0.02). In this subgroup, IDAA1c differences persisted at 6 months but not at 1 year. CGM analyses revealed lower minimum overnight glycemia in community children (72 vs. 119 mg/dL; P=0.01). CONCLUSIONS Favorable patterns of IDAA1c and C-peptide seen in research-screened versus community-diagnosed children with T1D within 2 months of diagnosis are no longer apparent 1 year from diagnosis.

Reduced insulin sensitivity is correlated with impaired sleep in adolescents with cystic fibrosis

Prevalence of cystic fibrosis‐related diabetes (CFRD) rises sharply in adolescence/young‐adulthood and is associated with increased morbidity/mortality. Sleep may be a modifiable risk factor for diabetes but its relationship with metabolic function has not been fully examined in youth with CF. The aim of the study was to examine the relationship between objectively measured sleep and glucose metabolism in youth with CF.

Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes and Hepatic Steatosis in Obese Girls

Abstract Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

Continuous glucose monitoring in youth with cystic fibrosis treated with lumacaftor-ivacaftor

BACKGROUND The effects of lumacaftor-ivacaftor therapy on glycemia have not been thoroughly investigated. Continuous glucose monitoring (CGM) provides detailed information about glycemic patterns and detects glucose abnormalities earlier than traditional screening tools for diabetes. METHODS CGM measures, HbA1c, and oral glucose tolerance test (OGTT) results were collected and within-subject results compared in F508del homozygous youth with CF before and after initiation of lumacaftor-ivacaftor using the Wilcoxon signed-rank test. RESULTS Nine youth with CF (6 males, median age 12.7 years) were enrolled. CGM was performed in all participants before (median 26 weeks) and after lumacaftor-ivacaftor (median 29 weeks). HbA1c and fasting plasma glucose increased (p = .02) after lumacaftor-ivacaftor initiation. No changes in OGTT 1 h or 2 h glucose nor CGM measures were observed overall. When analyzed by sex, males showed lower glycemic variability, as reflected by the mean amplitude of glycemic excursions, on the post-treatment CGM. CONCLUSIONS Glycemic abnormalities persisted in CF patients treated with lumacaftor-ivacaftor, although sex-dependent differences in glycemic response to treatment may exist.