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  • 1
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    Online Resource
    The Effect of Ethnicity in the Rate of Beta-Cell Functional Loss in the First 3 Years After Type 1 Diabetes Diagnosis
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 12 ( 2020-12-01), p. e4393-e4406
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 12 ( 2020-12-01), p. e4393-e4406
    Abstract: We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis. Research Methods and Design We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14). Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa348
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 2
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    Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts
    American Diabetes Association ; 2021
    In:  Diabetes Care Vol. 44, No. 10 ( 2021-10-01), p. 2329-2336
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 44, No. 10 ( 2021-10-01), p. 2329-2336
    Abstract: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose & gt;30 min and time to peak C-peptide & gt;60 min (P & lt; 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P & lt; 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc21-0226
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 3
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    99-OR: An Inflection Point (IP) of C-Peptide (C-P) Decline during Progression to Type 1 Diabetes (T1D)
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: Evidence suggests the presence of an IP for accelerated β-cell loss during progression to T1D. Importantly, identification of an IP could guide subject selection for prevention trials. We used a 2-dimensional grid of area under the curve (AUC) glucose vs. AUC C-P to detect a C-P IP among Diabetes Prevention Trial-Type 1 (DPT-1; n=54) and TrialNet (TN; n=59) autoantibody positive (Ab+) participants. All analyzed were required to have OGTTs at baseline and every 6 months, then 2.0, 1.5, 1.0 and 0.5 yrs before diagnosis. In DPT-1, an IP was evident 1.5 yrs from diagnosis (Figure) (AUC C-P change from baseline to 1.5 yrs: 0.22±0.60 ng/ml, p=0.006; from 1.5 to 0.5 yrs: -0.42±1.23 ng/ml, p=0.026). In TN, a 1.5 yr IP was also evident (from baseline to 1.5 yrs: 0.18±0.95 ng/ml, p=0.184; from 1.5 to 0.5 yrs: -0.53±1.57 ng/ml, p=0.015), despite an older TN cohort (14.9±12.1 vs. 10.5±6.8 yrs, p=0.023) with higher AUC C-P (5.0±1.9 vs. 3.3±1.6 ng/ml, p & lt;0.001). There was no IP in non-progressors. In summary, an IP occurred 1.5 yrs before diagnosis when C-P began to decline as glucose continued to increase in DPT-1 and TN, suggesting that a 1.5 yr IP of C-P decline is consistent among Ab+ populations. These findings emphasize the importance of identifying at risk individuals as potential participants in prevention trials prior to the IP, when the loss of insulin secretion becomes more severe. Disclosure H.M. Ismail: None. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. J. Sosenko: None. J.P. Palmer: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb. L. DiMeglio: None. M.J. Redondo: None. A. Steck: None. M.A. Atkinson: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. B.M. Nathan: None. Funding National Institutes of Health
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-99-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 4
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    Slowed Metabolic Decline After 1 Year of Oral Insulin Treatment Among Individuals at High Risk for Type 1 Diabetes in the Diabetes Prevention Trial–Type 1 (DPT-1) and TrialNet Oral Insulin Prevention Trials
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. 8 ( 2020-08-01), p. 1827-1832
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. 8 ( 2020-08-01), p. 1827-1832
    Abstract: We assessed whether oral insulin slowed metabolic decline after 1 year of treatment in individuals at high risk for type 1 diabetes. Two oral insulin trials that did not show efficacy overall and had type 1 diabetes as the primary end point were analyzed: the Diabetes Prevention Trial–Type 1 (DPT-1) and the TrialNet oral insulin trials. Oral glucose tolerance tests at baseline and after 1 year of treatment were analyzed. Among those at high risk (with a Diabetes Prevention Trial–Type 1 Risk Score [DPTRS] ≥6.75), the area under the curve (AUC) C-peptide increased significantly from baseline to 1 year in each oral insulin group, whereas the AUC glucose increased significantly in each placebo group. At 1 year, the AUC C-peptide/AUC glucose (AUC Ratio) was significantly higher in the oral insulin group than in the placebo group in each trial (P & lt; 0.05; P = 0.057 when adjusted for age in the TrialNet trial) and in both trials combined (P & lt; 0.01 with or without adjustment for age). For a DPTRS & lt;6.75, oral insulin groups did not differ from placebo groups in the AUC Ratio. The findings suggest that 1 year of treatment with oral insulin slows metabolic deterioration in individuals at high risk for type 1 diabetes. Moreover, the findings further suggest that metabolic end points can be useful adjuncts to the diagnostic end point in assessments of preventive treatments for the disorder.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-0166
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 5
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    Index60 as an additional diagnostic criterion for type 1 diabetes
    Springer Science and Business Media LLC ; 2021
    In:  Diabetologia Vol. 64, No. 4 ( 2021-04), p. 836-844
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 64, No. 4 ( 2021-04), p. 836-844
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-020-05365-4
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1458993-X
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  • 6
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    Phenotypes Associated With Zones Defined by Area Under the Curve Glucose and C-peptide in a Population With Islet Autoantibodies
    American Diabetes Association ; 2023
    In:  Diabetes Care Vol. 46, No. 5 ( 2023-05-01), p. 1098-1105
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 46, No. 5 ( 2023-05-01), p. 1098-1105
    Abstract: Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies. RESEARCH DESIGN AND METHODS Baseline 2-h oral glucose tolerance test data from 6,620 TrialNet Pathway to Prevention Study (TNPTP) autoantibody-positive participants (relatives of individuals with type 1 diabetes) were used to form 25 zones from five area under the curve glucose (AUCGLU) rows and five area under the curve C-peptide (AUCPEP) columns. Zone phenotypes were developed from demographic, metabolic, autoantibody, HLA, and risk data. RESULTS As AUCGLU increased, changes of glucose and C-peptide response curves (from mean glucose and mean C-peptide values at 30, 60, 90, and 120 min) were similar within the five AUCPEP columns. Among the zones, 5-year risk for type 1 diabetes was highly correlated with islet antigen 2 antibody prevalence (r = 0.96, P & lt; 0.001). Disease risk decreased markedly in the highest AUCGLU row as AUCPEP increased (0.88–0.41; P & lt; 0.001 from lowest AUCPEP column to highest AUCPEP column). AUCGLU correlated appreciably less with Index60 (an indicator of insulin secretion) in the highest AUCPEP column (r = 0.33) than in other columns (r ≥ 0.78). AUCGLU was positively related to “fasting glucose × fasting insulin” and to “fasting glucose × fasting C-peptide” (indicators of insulin resistance) before and after adjustments for Index60 (P & lt; 0.001). CONCLUSIONS Phenotypes of 25 zones formed from AUCGLU and AUCPEP were used to gain insights into type 1 diabetes heterogeneity. Zones were used to examine GCRC changes with increasing AUCGLU, associations between risk and autoantibody prevalence, the dependence of glucose as a predictor of risk according to C-peptide, and glucose heterogeneity from contributions of insulin secretion and insulin resistance.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc22-2236
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1490520-6
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  • 7
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    The Transition From a Compensatory Increase to a Decrease in C-peptide During the Progression to Type 1 Diabetes and Its Relation to Risk
    American Diabetes Association ; 2022
    In:  Diabetes Care Vol. 45, No. 10 ( 2022-10-01), p. 2264-2270
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 10 ( 2022-10-01), p. 2264-2270
    Abstract: To define the relationship between glucose and C-peptide during the progression to type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We longitudinally studied glucose and C-peptide response curves (GCRCs), area under curve (AUC) for glucose, and AUC C-peptide from oral glucose tolerance tests (OGTTs), and Index60 (which integrates OGTT glucose and C-peptide values) in Diabetes Prevention Trial–Type 1 (DPT-1) (n = 72) and TrialNet Pathway to Prevention Study (TNPTP) (n = 82) participants who had OGTTs at baseline and follow-up time points before diagnosis. RESULTS Similar evolutions of GCRC configurations were evident between DPT-1 and TNPTP from baseline to 0.5 years prediagnosis. Whereas AUC glucose increased throughout from baseline to 0.5 years prediagnosis, AUC C-peptide increased from baseline until 1.5 years prediagnosis (DPT-1, P = 0.004; TNPTP, P = 0.012) and then decreased from 1.5 to 0.5 years prediagnosis (DPT-1, P = 0.017; TNPTP, P = 0.093). This change was mostly attributable to change in the late AUC C-peptide response (i.e., 60- to 120-min AUC C-peptide). Median Index60 values of DPT-1 (1.44) and TNPTP (1.05) progressors to T1D 1.5 years prediagnosis (time of transition from increasing to decreasing AUC C-peptide) were used as thresholds to identify individuals at high risk for T1D in the full cohort at baseline (5-year risk of 0.75–0.88 for those above thresholds). CONCLUSIONS A transition from an increase to a decrease in AUC C-peptide ∼1.5 years prediagnosis was validated in two independent cohorts. The median Index60 value at that time point can be used as a pathophysiologic-based threshold for identifying individuals at high risk for T1D.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc22-0167
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 8
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    Online Resource
    1618-P: Insulin Secretion Variability According to the Specific Type 1 Diabetes (T1D) Risk Predictor
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: The risk for T1D, a major criterion for entry into disease prevention trials, can be assessed in various ways, but usually includes autoantibody (Ab) and/or metabolic measures. Given inherent variations in these biomarkers, it is possible that informative characteristics differ between populations selected by different risk measures. Thus, we assessed whether indices of insulin secretion [C-pep; first phase insulin response (FPIR)] vary between groups defined by distinctive risk measures. We used data from Diabetes Prevention Trial-Type 1 (DPT-1) participants, all being ICA positive subjects with or without biochemical Ab (bAb) positivity (GADA, IA-2A, mIAA). C-pep and FPIR values from baseline oral and intravenous glucose tolerance tests were compared between those who had 2-3 bAbs (≥2bAb) and those who had 0-1 bAb plus Index60≥0.40 (≤1bAb+Ind60). Index60 is a composite C-pep and glucose measure. These groups were chosen so that T1D risk would be similar (50% 5-year risk for both, log rank p=0.95). Ages (mean±SD) for ≥2bAb (n=289) and ≤1bAb+Ind60 (n=175) were 12.8±8.2 and 13.3±9.6 yrs, respectively (p=0.53). BMI Z-score was greater for ≥2bAb (0.42±1.12 vs. 0.15±1.09, p=0.01). C-pep levels were consistently higher for ≥2bAb than ≤1bAb+Ind60 [30-0 minute C-pep: 2.73±1.58 vs. 2.04±1.12 ng/mL, p & lt;0.0001; area under the curve (AUC) C-pep: 3.70±1.55 vs. 3.27±1.12 ng/ml, p=0.013; AUC C-pep/AUC glucose: 0.030±0.013 vs. 0.025±0.007 (ng/ml)/(mg/dl), p & lt;0.001]. FPIR was also higher for ≥2bAb (122.0±87.3 vs. 96.2±47.1 µU/ml, p & lt;0.01). All comparisons remained significant with adjustments for age and BMI Z-score. Of those with ≤1bAb+Ind60, 0 bAb did not differ from 1 bAb for C-pep indices or FPIR. In conclusion, C-pep and FPIR values can differ appreciably according to the measure that defines risk. This should be considered in choosing risk measures for prevention trials. Disclosure L.M. Jacobsen: None. B.M. Nathan: None. H.M. Ismail: None. M.J. Redondo: None. D. Schatz: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. E.K. Sims: None. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. J.P. Palmer: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. J. Sosenko: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-1618-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 9
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    The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study
    American Diabetes Association ; 2020
    In:  Diabetes Care Vol. 43, No. 11 ( 2020-11-01), p. 2668-2674
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 43, No. 11 ( 2020-11-01), p. 2668-2674
    Abstract: Glucose response curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of type 1 diabetes. We performed a longitudinal analysis in pancreatic autoantibody-positive individuals to assess 1) characteristic GRC changes during progression to type 1 diabetes and 2) GRC changes in relation to β-cell function changes and to combined glucose and C-peptide response curve (GCRC) changes. RESEARCH DESIGN AND METHODS Among antibody-positive individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors (n = 298) to type 1 diabetes and nonprogressors (n = 2,216). GRC changes from last OGTT before diagnosis to diagnostic OGTTs were studied in progressors. RESULTS GRCs changed more frequently from biphasic (two peaks) to monophasic (one peak) GRCs between first and last OGTTs in progressors than in nonprogressors (75.4% vs. 51.0%, respectively; P & lt; 0.001). In contrast, GRCs of progressors changed less frequently from monophasic to biphasic than those of nonprogressors (12.6% vs. 30.6%; P & lt; 0.001). Monotonic (continuous increase) GRCs were present in 47.7% of progressors at diagnosis. The early (30–0 min) C-peptide response decreased in progressors with GRCs changing from biphasic to monophasic between first and last OGTTs (P & lt; 0.001) and from monophasic to monotonic between last and diagnostic OGTTs (P & lt; 0.001). Conversely, the early C-peptide response increased among nonprogressors with GRCs changing from monophasic to biphasic (P & lt; 0.001). Changes in GRCs were related to changes in GCRCs. CONCLUSIONS Characteristic GRC changes, biphasic to monophasic to monotonic, occur during the progression to type 1 diabetes. These GRC changes correspond to decreasing β-cell function.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc20-0701
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 10
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    20-OR: Loss of Characteristic ß-Cell Function in Autoantibody-Positive (Ab+) Individuals during the Progression to Type 1 Diabetes (T1D)
    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: We used correlations of C-peptide secretion between follow-up time points (autocorrelation) of Ab+ relatives in the TrialNet Pathway to Prevention study to assess the loss of characteristic β-cell function during progression to T1D. Measures of β-cell function: AUC C-peptide; C-peptide Index (30-0 min C-peptide)/(30-0 min glucose); and Index60 (composite of glucose and C-peptide during first 60 minutes of OGTT)] were assessed (table 1). Spearman correlations of AUC C-peptide from baseline to pre-diagnosis (6 months before) OGTTs of progressors (Pro; Age=8.7±3.6 yrs; n=182) were lower than correlations of AUC C-peptide from baseline to last OGTTs of non-progressors (NPro; Age=9.6±3.8 yrs; n=3,137; p & lt;0.001 for all). Among Pro, correlations of AUC C-peptide from baseline to diagnosis OGTTs were considerably lower than correlations of AUC C-peptide from baseline to pre-diagnosis OGTTs (p= & lt;0.001 for all). In conclusion, the lower C-peptide autocorrelation from baseline to last OGTTs of Pro compared to NPro indicates that β-cell function is already appreciably altered 6 months before diagnosis. Among Pro, the substantial decline of C-peptide autocorrelation from 6 months before diagnosis to diagnosis suggests a marked loss of β-cell function in that interval. Autocorrelation offers another approach for providing insight into β-cell compromise. Disclosure H.M.Ismail: Consultant; Rise Therapeutics. D.D.Cuthbertson: None. J.S.Skyler: Advisory Panel; Adocia, Altheia Sciences, Arecor, Avotres Inc., Bayer Inc., COUR Pharmaceuticals, Dance Biopharm/Aerami, Diasome, Enthera, Immnomolecular Therapeutics, Kriya Therapeutics, Oramed Pharmaceuticals, Orgenesis Inc., Precigen, Inc., ViaCyte, Inc., Board Member; Applied Therapeutics Inc., Dexcom, Inc., Consultant; Novo Nordisk, Sanofi, Signos, 4Immune, Other Relationship; Imcyse, Provention Bio, Inc. C.Evans-molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics, Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics, Research Support; Lilly, Astellas Pharma Inc. J.Sosenko: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK129799-01A1)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-20-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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