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  • 1
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    109-OR: Physiologic Subtypes of Gestational Glucose Intolerance and Risk of Future Prediabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Background: Gestational glucose intolerance (GGI, abnormal initial gestational diabetes [GDM] screen) conveys an increased risk of future diabetes (DM) , even when GDM criteria is not met. We previously defined subtypes of GGI/GDM according to the underlying mechanism leading to hyperglycemia (insulin resistance vs. deficiency) . We aimed to determine if GGI subtypes are at differential risk for future prediabetes/DM; we hypothesized increased risk with insulin deficient subtypes. Methods: We defined GGI as glucose loading test 1-hr glucose ≥ 140 mg/dL at & gt; 22 weeks’ gestation. We applied homeostasis model assessment (HOMA) to fasting glucose and insulin at 16-20 weeks’ gestation and classified pregnancies with GGI without GDM into subtypes according to the presence of insulin resistance and/or deficiency. We used Cox proportional-hazards models with time-varying exposures to assess risk of preDM/DM (HbA1c ≥ 5.7% at ≥ 3 months after delivery) in each GGI subtype compared to pregnancies with normal glucose tolerance after adjustment for age, race/ethnicity, health insurance, and first trimester BMI. Women were censored at the time of last HbA1c or GDM diagnosis. Results: Of 671 women with a median 9.9 years of follow-up, 29% (n=196) developed preDM/DM. Among pregnancies in 113 women with GGI, 54% had the insulin resistant subtype (IR) , 25% had the insulin deficient subtype (ID) , and 16% had the mixed pathophysiology subtype (MP) . Subtypes with insulin deficiency (ID + MP) and insulin resistance (IR) were both associated with increased risk of preDM/DM (ID + MP hazard ratio [HR]=1.8 [1.1-2.9] , p=0.02 and IR HR=1.7 [1.1-2.6], p=0.01) . Each insulin deficient subtype also appeared to carry increased risk: ID HR=1.7 (0.9-3.1, p=0.12) and MP HR=2.1 (1.0-4.2, p=0.048) . Conclusions: GGI confers an increased risk of future prediabetes/DM, regardless of the mechanism leading to glucose intolerance. A combination of insulin resistance and deficiency may convey the highest risk of future prediabetes/DM. Disclosure D.J. Selen: None. T. Thaweethai: None. K. James: None. J.L. Ecker: None. J.B. Meigs: Consultant; Quest Diagnostics. C.E. Powe: None. Funding National Institutes of Health (T32DK007028) , Massachusetts General Hospital (Physician Scientist Development Award and Claflin Distinguished Scholar’s Award)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-109-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 2
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    Racial/ethnic and socioeconomic disparities in achievement of treatment goals within a clinical trial: a secondary analysis of the ACCORD trial
    Springer Science and Business Media LLC ; 2023
    In:  Diabetologia
    Details
    In: Diabetologia, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-023-05997-2
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1458993-X
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  • 3
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    Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors
    Springer Science and Business Media LLC ; 2022
    In:  Diabetologia Vol. 65, No. 3 ( 2022-03), p. 541-551
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 65, No. 3 ( 2022-03), p. 541-551
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-021-05622-0
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458993-X
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  • 4
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    Gestational Glucose Intolerance and Birth Weight–Related Complications
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Obstetrics & Gynecology Vol. 142, No. 3 ( 2023-09), p. 594-602
    Details
    In: Obstetrics & Gynecology, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. 3 ( 2023-09), p. 594-602
    Abstract: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight–related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight–related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23–1.49, P 〈 .001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08–1.35, P 〈 .001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52–2.08, P 〈 .001). The odds of birth weight–related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight–related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.
    Type of Medium: Online Resource
    ISSN: 0029-7844
    URL: Article
    DOI: 10.1097/AOG.0000000000005278
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2012791-1
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  • 5
    Online Resource
    Online Resource
    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Abstract: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%] ) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.8823
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 6
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    1181-P: Substituting Protein for Fat Lowers Postprandial Glycemic Response in Gestational Diabetes
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: Background: Dietary guidelines in gestational diabetes mellitus (GDM) focus on carbohydrate without regard to other macronutrients. We tested the impact of fat and protein on postprandial glycemia in GDM and analyzed whether the physiology underlying GDM influenced this response. Methods: In a pilot crossover trial, participants ate two isocaloric breakfast meals with the same carbohydrate content and different protein and fat content (High protein meal: 390 kCal, 35 g protein, 9 g fat, 45 g carb, High fat meal: 411 kCal, 15 g protein, 19 g fat, 46 g carb) on subsequent days in a random order. We measured peak postprandial glucose (primary outcome) using continuous glucose monitors. We used homeostatic model assessment to determine if participants had insulin resistant (IR) or insulin deficient (ID) GDM. We used paired t-tests to test if glycemic response to the meals differed and linear regression to test if differential response to meals was influenced by having IR vs ID GDM. Results: We studied 16 women with diet-controlled GDM (median [IQR] 31 [30-33] weeks’ gestation). Mean [SD] peak glucose after the high fat meal (146 [20] mg/dl) was higher than after the high protein meal (137 [21] mg/dl) (P=0.03), but individuals varied in their differential response to the meals (range: 25 mg/dl higher after high protein meal to 35 mg/dl higher after high fat meal). Median time to peak glucose (IQR) was 72 (63-74) minutes after the high protein meal and 65 (60-73) minutes after the high fat meal (P=0.11). There was no difference in differential glycemic response to the meals in IR (n=8) vs ID (n=4) GDM (P=0.98); age (median [IQR] 36 [33-38] yrs) and BMI (median [IQR] 27 [24-30]) adjustment did not change results (P=0.82). Conclusion: On average, women with GDM have lower post prandial glucose levels after a high protein meal compared to a high fat meal with equivalent carbohydrate content. This may inform GDM dietary recommendations and motivate research on determinants of individual-level response to macronutrients. Disclosure E.A.Rosenberg: None. T.Thaweethai: None. K.James: None. E.Kelty: None. R.L.Azevedo: None. S.Nelson: None. J.L.Garry: None. E.W.Seely: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. Funding Robert Wood Johnson Foundation; National Institutes of Health (5F32DK12634302); Endocrine Fellows Foundation
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-1181-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1501252-9
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  • 7
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    1089-P: Gestational Glucose Intolerance and Risk of Childhood Overweight and Obesity
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: Infants of individuals with gestational glucose intolerance (GGI, abnormal glucose loading test [GLT] without gestational diabetes [GDM] ) have increased risk of large for gestational age birthweight, but an association between GGI and childhood adiposity has not been consistently observed. We studied the risk of overweight and obesity in 2-5-year-old children exposed to varying degrees of maternal glycemia in utero in a retrospective hospital-based cohort. We defined normal glucose tolerance (NGT) as a GLT & lt;140 mg/dl, GGI as GLT ≥ 140 mg/dl and zero (GGI-0) or 1 (GGI-1) abnormal values on a 3-hour 100-gram oral glucose tolerance test (OGTT), and gestational diabetes (GDM) as ≥2 abnormal values. We used logistic regression to investigate the risk of obesity, defined as body mass index (BMI) & gt; 95th percentile, in children born to individuals with GGI and GDM as compared to NGT. In model 1, we adjusted for maternal age, gestational weight gain, parity, insurance, race/ethnicity, marital status, gestational age at delivery and infant sex; in model 2, we further adjusted for maternal 1st trimester BMI. Of n=12728 children, 48.5% were female, the mean (SD) gestational age at delivery was 39.4 (1.7) weeks, and the mean birthweight was 3341 (519) grams. A total of 10567 children were exposed to NGT in utero, 1156 to GGI-0, 428 to GGI-1, and 577 to GDM. Obesity was present in 12.9% of children exposed to NGT, 12.5% exposed to GGI-0, 16.6% exposed to GGI-1, and 18.5% exposed to GDM, respectively. In model 1, there was an increased odds of obesity in those exposed to GGI-1 (1.37 [1.04, 1.78], P=0.02) and GDM (1.61 [1.28, 2.02] P & lt;0.001). After maternal BMI adjustment, we did not find a significant increased risk of obesity in any group compared to NGT (GGI-1: 1.15 [0.86, 1.51] P=0.33; GDM 1.24 (0.97, 1.57), P=0.08). After accounting for maternal BMI, children exposed to GGI and GDM in utero have a similar risk of obesity in early childhood to those born to NGT pregnancies. Disclosure J.Maya: None. S.Hsu: None. C.C.M.Schulte: None. K.James: None. T.Thaweethai: None. M.Hivert: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. Funding National Institutes of Health (T32DK007028-47S1)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-1089-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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  • 8
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    Psychological and Behavioral Predictors of Weight Loss in the Reach Ahead for Lifestyle and Health-Diabetes Lifestyle Intervention Cohort
    Elsevier BV ; 2023
    In:  Journal of the Academy of Nutrition and Dietetics Vol. 123, No. 7 ( 2023-07), p. 1033-1043.e1
    Details
    In: Journal of the Academy of Nutrition and Dietetics, Elsevier BV, Vol. 123, No. 7 ( 2023-07), p. 1033-1043.e1
    Type of Medium: Online Resource
    ISSN: 2212-2672
    URL: Article
    DOI: 10.1016/j.jand.2023.02.018
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2646137-7
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  • 9
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    Impact of selection bias on polygenic risk score estimates in healthcare settings
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine
    Details
    In: Psychological Medicine, Cambridge University Press (CUP)
    Abstract: Hospital-based biobanks are being increasingly considered as a resource for translating polygenic risk scores (PRS) into clinical practice. However, since these biobanks originate from patient populations, there is a possibility of bias in polygenic risk estimation due to overrepresentation of patients with higher frequency of healthcare interactions. Methods PRS for schizophrenia, bipolar disorder, and depression were calculated using summary statistics from the largest available genomic studies for a sample of 24 153 European ancestry participants in the Mass General Brigham (MGB) Biobank. To correct for selection bias, we fitted logistic regression models with inverse probability (IP) weights, which were estimated using 1839 sociodemographic, clinical, and healthcare utilization features extracted from electronic health records of 1 546 440 non-Hispanic White patients eligible to participate in the Biobank study at their first visit to the MGB-affiliated hospitals. Results Case prevalence of bipolar disorder among participants in the top decile of bipolar disorder PRS was 10.0% (95% CI 8.8–11.2%) in the unweighted analysis but only 6.2% (5.0–7.5%) when selection bias was accounted for using IP weights. Similarly, case prevalence of depression among those in the top decile of depression PRS was reduced from 33.5% (31.7–35.4%) to 28.9% (25.8–31.9%) after IP weighting. Conclusions Non-random selection of participants into volunteer biobanks may induce clinically relevant selection bias that could impact implementation of PRS in research and clinical settings. As efforts to integrate PRS in medical practice expand, recognition and mitigation of these biases should be considered and may need to be optimized in a context-specific manner.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291723001186
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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  • 10
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    Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response
    The Endocrine Society ; 2022
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 107, No. 2 ( 2022-01-18), p. e698-e707
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 2 ( 2022-01-18), p. e698-e707
    Abstract: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. Objective To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. Methods This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR] , D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. Results In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P  & lt; 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P  & lt; 0.001). Evidence of mediation was more pronounced in patients  & lt; 65 years (proportion mediated = 0.52 [P  & lt; 0.001] vs 0.44 [P = 0.180] ). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). Conclusion Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients  & lt; 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgab629
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    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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