In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12 years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1clevels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37–63%)] compared to pre-T2D [36% (95% CI 31–48%), p = 0.01] and at-risk participants [34% (95% CI 27–39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA1csub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories.
To determine whether HbA1cmismatches (HbA1clevels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1clevels.
In a cross‐sectional study, 3106 participants without known diabetes underwent a 75‐g oral glucose tolerance test (fasting glucose and 2‐h glucose) and a 50‐g glucose challenge test (1‐h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1cwas determined from the linear regression modelling the relationship between observed HbA1cand average glucose (mean of fasting glucose and 2‐h glucose from the oral glucose tolerance test, and 1‐h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed – predicted HbA1c], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles.
Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher
Measuring only HbA1ccould lead to under‐diagnosis in people with low mismatches and over‐diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1cin diagnostic classification should be performed in most individuals.
- PAR ID:
- 10360239
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Diabetic Medicine
- Volume:
- 37
- Issue:
- 4
- ISSN:
- 0742-3071
- Page Range / eLocation ID:
- p. 689-696
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Methods We performed a retrospective case‐control study of 299 women with GDM and 204 women with normal glucose tolerance (NGT), using oral glucose tolerance test‐based indices performed at 24‐25 weeks of gestation. Women with GDM were classified into the following three physiologic subtypes: GDM with a predominant insulin‐secretion defect (GDM‐dysfunction), GDM with a predominant insulin‐sensitivity defect (GDM‐resistance), or GDM with both defects (GDM‐mixed). We then used a binary logistic regression model to evaluate the potential associations of GDM subtypes and pre‐BMI with newborn macrosomia or LGA.
Results Women with GDM‐resistance had a higher pre‐BMI (
P < 0.001), whereas women in the GDM‐dysfunction and GDM‐mixed groups had pre‐BMIs comparable to the NGT group. In the logistic regression model, women in the GDM‐mixed group exhibited an increased risk of bearing newborns with macrosomia and LGA, and women in the GDM‐dysfunction group tended to have newborns with LGA after adjusting for pre‐BMI and other potential confounders. Women who were overweight or obese prepregnancy manifested an increased risk of having newborns with macrosomia and LGA relative to normal‐weight women, regardless of whether values were unadjusted or adjusted for all potential confounders. There was no significant interaction between GDM subtype and pre‐BMI for any of the studied outcomes.Conclusions Heterogeneity of GDM (GDM‐dysfunction and GDM‐mixed) and prepregnancy overweight/obesity were independently associated with LGA in Chinese women. There was no significant interaction between GDM subtypes and pre‐BMI for LGA.
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Importance Continuous glucose monitoring (CGM) is associated with improvements in hemoglobin A 1c (HbA 1c ) in youths with type 1 diabetes (T1D); however, youths from minoritized racial and ethnic groups and those with public insurance face greater barriers to CGM access. Early initiation of and access to CGM may reduce disparities in CGM uptake and improve diabetes outcomes. Objective To determine whether HbA 1c decreases differed by ethnicity and insurance status among a cohort of youths newly diagnosed with T1D and provided CGM. Design, Setting, and Participants This cohort study used data from the Teamwork, Targets, Technology, and Tight Control (4T) study, a clinical research program that aims to initiate CGM within 1 month of T1D diagnosis. All youths with new-onset T1D diagnosed between July 25, 2018, and June 15, 2020, at Stanford Children’s Hospital, a single-site, freestanding children’s hospital in California, were approached to enroll in the Pilot-4T study and were followed for 12 months. Data analysis was performed and completed on June 3, 2022. Exposures All eligible participants were offered CGM within 1 month of diabetes diagnosis. Main Outcomes and Measures To assess HbA 1c change over the study period, analyses were stratified by ethnicity (Hispanic vs non-Hispanic) or insurance status (public vs private) to compare the Pilot-4T cohort with a historical cohort of 272 youths diagnosed with T1D between June 1, 2014, and December 28, 2016. Results The Pilot-4T cohort comprised 135 youths, with a median age of 9.7 years (IQR, 6.8-12.7 years) at diagnosis. There were 71 boys (52.6%) and 64 girls (47.4%). Based on self-report, participants’ race was categorized as Asian or Pacific Islander (19 [14.1%]), White (62 [45.9%]), or other race (39 [28.9%]); race was missing or not reported for 15 participants (11.1%). Participants also self-reported their ethnicity as Hispanic (29 [21.5%]) or non-Hispanic (92 [68.1%]). A total of 104 participants (77.0%) had private insurance and 31 (23.0%) had public insurance. Compared with the historical cohort, similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were observed for Hispanic individuals (estimated difference, −0.26% [95% CI, −1.05% to 0.43%], −0.60% [−1.46% to 0.21%], and −0.15% [−1.48% to 0.80%]) and non-Hispanic individuals (estimated difference, −0.27% [95% CI, −0.62% to 0.10%], −0.50% [−0.81% to −0.11%], and −0.47% [−0.91% to 0.06%]) in the Pilot-4T cohort. Similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were also observed for publicly insured individuals (estimated difference, −0.52% [95% CI, −1.22% to 0.15%], −0.38% [−1.26% to 0.33%], and −0.57% [−2.08% to 0.74%]) and privately insured individuals (estimated difference, −0.34% [95% CI, −0.67% to 0.03%], −0.57% [−0.85% to −0.26%], and −0.43% [−0.85% to 0.01%]) in the Pilot-4T cohort. Hispanic youths in the Pilot-4T cohort had higher HbA 1c at 6, 9, and 12 months postdiagnosis than non-Hispanic youths (estimated difference, 0.28% [95% CI, −0.46% to 0.86%], 0.63% [0.02% to 1.20%], and 1.39% [0.37% to 1.96%]), as did publicly insured youths compared with privately insured youths (estimated difference, 0.39% [95% CI, −0.23% to 0.99%], 0.95% [0.28% to 1.45%], and 1.16% [−0.09% to 2.13%]). Conclusions and Relevance The findings of this cohort study suggest that CGM initiation soon after diagnosis is associated with similar improvements in HbA 1c for Hispanic and non-Hispanic youths as well as for publicly and privately insured youths. These results further suggest that equitable access to CGM soon after T1D diagnosis may be a first step to improve HbA 1c for all youths but is unlikely to eliminate disparities entirely. Trial Registration ClinicalTrials.gov Identifier: NCT04336969more » « less
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Methods A bolus of [2H7]glucose was injected through the tail vein at 1.95 g/kg into Sprague‐Dawley rats. A2H surface coil was placed on top of the head to record2H spectra of the brain every 1.3 minutes to measure glucose uptake and metabolism to HDO, lactate, and glutamate/glutamine. A two‐point Dixon method based on a gradient‐echo sequence was used to reconstruct deuterated glucose and water (HDO) images selectively.
Results The background HDO signal could be detected and imaged before glucose injection. The2H NMR spectra showed arrival of [2H7]glucose and its metabolism in a time‐dependent manner. A ratio of the HDO to glutamate/glutamine resonances demonstrates a pseudo–steady state following injection, in which cerebral metabolism dominates wash‐in of HDO generated by peripheral metabolism. Brain spectroscopy reveals that HDO generation is linear with lactate and glutamate/glutamine appearance in the appropriate pseudo–steady state window. Selective imaging of HDO and glucose is easily accomplished using a gradient‐echo method.
Conclusion Metabolic imaging of HDO, as a marker of glucose, lactate, and glutamate/glutamine metabolism, has been shown here for the first time. Cerebral glucose metabolism can be assessed efficiently using a standard gradient‐echo sequence that provides superior in‐plane resolution compared with CSI‐based techniques.
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Methods Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife.
Results Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory.
Discussion Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.
