Elizabeth Seaquist
· Nesbitt Chair and HeadVerifiedUniversity of Minnesota · Internal Medicine
Active 1960–2026
About
Dr. Takako Araki is an Associate Professor in the Division of Endocrinology, Diabetes and Metabolism at the University of Minnesota. Her research is dedicated to quality improvement of pituitary perioperative patient care and the management of pituitary disorders. She is actively involved in research related to pituitary development and disorders, with a focus on improving clinical outcomes for patients with these conditions. Her work contributes to advancing understanding and treatment of pituitary-related health issues, supporting the broader mission of the Araki Lab to investigate endocrine and metabolic disorders.
Research topics
- Endocrinology
- Medicine
- Internal medicine
- Pediatrics
- Pathology
- Intensive care medicine
Selected publications
Journal of Clinical Investigation · 2026-02-19 · 1 citations
articleOpen accessBACKGROUNDRecurrent hypoglycemia in type 1 diabetes (T1D) may culminate in impaired awareness of hypoglycemia (IAH). While neuroimaging studies identified affected brain regions, more complex perspectives integrating vascular dynamics with endocrine profile are needed.METHODSHere, 26 healthy adults, 30 T1D patients with normal hypoglycemia awareness (NAH), and 25 T1D patients with IAH underwent a hyperinsulinemic stepped clamp (euglycemia → hypoglycemia 50 mg/dL) combined with pseudo-continuous arterial spin-labeling MRI. Cerebral blood flow (CBF) and sympathetic vasomotor range (0.02-0.05 Hz) CBF oscillations were modeled against serially sampled plasma cortisol, epinephrine, norepinephrine, and glucagon.RESULTSIn healthy individuals treated as controls, hypoglycemia evoked robust thalamo-striatal and salience-interoceptive CBF increases (mean Cohen's d across significant clusters = 0.93) and suppression of vasomotor oscillations (d = 0.71). T1D retained CBF response but failed to attenuate oscillations (dT1D>controls = 0.43). IAH further blunted hypoglycemia-associated CBF increase, especially in thalamus, striatum, and insula (dNAH>IAH = 0.51). Hormone-CBF coupling differed quantitatively: cortisol/epinephrine-CBF correlations were positive in controls (r = 0.37/0.26), negative in NAH (-0.16/-0.40), and strongly positive in IAH (0.42/0.46).CONCLUSIONThus, our findings indicate that T1D disrupts dynamic, sympathetic modulation of CBF, whereas IAH additionally impairs perfusion reserve and shows maladaptive catecholamine-dependent CBF regulation, suggesting a qualitatively distinct neurovascular phenotype.TRIAL REGISTRATIONClinicalTrials.gov: NCT02747680 and NCT02866435.FUNDINGNIH (P41-EB-015894, P30-NS-076408, R01-DK-099137, R56-DK-099137, and DP1 AG093028); National Center for Advancing Translational Sciences of the NIH (KL2-TR-000113 and UL1-TR-000114); DP1 AG093028; Charles University, Czech Republic (Cooperatio Program, research area NEUR), Brain Dynamics (grant number CZ.02.01.01/00/22_008/0004643); General University Hospital in Prague (MH CZ-DRO-VFN64165).
Diabetes · 2025-06-13 · 1 citations
articleIntroduction and Objective: Mechanisms of impaired awareness of hypoglycemia (HG) after exposure to recurrent HG are unknown. We sought to determine if recurrent HG alters metabolite responses to HG in individuals with type 1 diabetes (T1D) and normal HG awareness. Methods: Participants with T1D (N=43) who self-reported normal HG awareness (using Cox/Clarke and Gold questionnaires) underwent four 2-hour HG clamps over 2 days to induce impaired awareness of HG. The 1st and 4th clamps were conducted in a 7T scanner. Metabolite concentrations in the prefrontal cortex (PFC) and hypothalamus (HTL) were measured during eu- and hypoglycemia using proton MR spectroscopy. Epinephrine samples and the Towler symptom questionnaire were collected during each clamp. Results: Complete PFC datasets were collected from 35 individuals for Clamp 1 and 29 individuals for Clamp 4 (Table). HG targets were achieved consistently in each clamp, with corresponding reduction in brain glucose levels. Hormone and symptom responses were blunted at Clamp 4 vs. Clamp 1. PFC glutamate and lactate levels decreased with HG at Clamp 1, indicating a slowing of the TCA cycle rate, but not at Clamp 4. Similar trends were observed for HTL. Conclusion: Exposure to recurrent HG blunted glutamate and lactate decrease in response to HG in individuals with T1D and normal HG awareness, indicating a metabolic adaptation to recurrent HG. Disclosure Y. Park: None. B.M. Payne: None. A. Kumar: None. A.C. Alvear: None. A. Moheet: Other Relationship; Sanofi-Aventis U.S. L.E. Eberly: None. E.R. Seaquist: None. G. Oz: Research Support; Biogen. Consultant; Servier Laboratories, UCB Biopharma SRL / Lacerta Therapeutics Inc, Sanofi. Funding National Institutes of Health (R01NS035192)
Diabetes Care · 2025-12-10
articleOpen accessOBJECTIVE: To test the effect of substituting plain water (the ideal standard) for habitual artificial sweetened beverage (ASB) intake by people with type 2 diabetes (T2D) on primary measures of diabetes control. RESEARCH DESIGN AND METHODS: The Study of Drinks with Artificial Sweeteners in People with T2D (SODAS) was conducted at two academic health centers and was a randomized, two-arm, parallel trial with a 2-week run-in period and a 24-week active intervention period. Adults with T2D (n = 181; HbA1c 6.5-8.5%; aged ≥35 years) who regularly consumed commercial ASBs were randomized to receive and consume 24 oz daily for 24 weeks of either 1) a commercial ASB of choice (control) or 2) an unflavored, sparkling or still, bottled or canned water of choice in place of ASBs. The outcomes measures were collected at baseline, 12, and 24 weeks and included the primary measure (HbA1c) and related secondary measures (fructosamine, fasting glucose and insulin, body weight, and continuous glucose monitor metrics). RESULTS: A total of 179 participants provided complete data over 24 weeks. From baseline to 24 weeks, the mean difference in change of HbA1c was 0.29% (SE 0.12; P = 0.013) higher in the water arm compared with the ASB arm. There were no significant effects on secondary clinical measures, but data were directionally consistent with the primary results. CONCLUSIONS: For people with T2D and HbA1c <8.5% who regularly consume ASBs, this trial provided no evidence that substituting water would improve glycemic-related clinical care measures over 24 weeks.
Diabetes · 2025-06-13
articleIntroduction and Objective: To describe the prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG evidence of cardiovascular (CV) autonomic neuropathy (CAN) by treatment group in the GRADE cohort of adults with type 2 diabetes (T2D) for &lt;10 years. Methods: The GRADE trial enrolled individuals with T2D &lt;10 years on metformin alone, randomized to insulin glargine, glimepiride, liraglutide, or sitagliptin, and followed for an average of five years. Resting ECGs were completed at baseline, 2-, and 4-years in 5029 participants (baseline mean ± SD age 57.2 ± 10.0 years; diabetes duration 4.2 ± 2.7 years; HbA1c 7.5 ± 0.5%; 36.4% women) and analyzed for overall, major, and minor abnormalities and heart rate variability (HRV), a measure of CAN. Incidence of new ECG abnormalities and CAN by treatment group were analyzed at years 2 and 4 using logistic repeated measures models, adjusted for baseline risk factors. As liraglutide is associated with CV outcomes benefit, ECG changes in the liraglutide vs. all other groups were also compared. Results: Participants with ECG abnormalities (57.1%) and ECG-defined CAN (52.8%) at baseline had longer diabetes duration, higher systolic blood pressure, more hyperlipidemia and lipid-lowering treatment, and beta blocker use. Across years 2 and 4, there were no between-group differences in overall or minor ECG abnormalities, but major ECG abnormalities occurred less often in the liraglutide vs. all other treatment groups (p=0.03; 9% [95% CI: 7%, 12%] vs 13% [11%, 14%] at year 4). ECG-defined CAN did not differ between liraglutide vs. non-liraglutide groups across years 2 and 4 (p=0.42). Conclusion: ECG abnormalities, including those of CAN, are common in T2D &lt;10 years and are associated with certain CV risk factors. The development of major ECG abnormalities may differ by glucose lowering treatment, as fewer occurred with liraglutide vs. the other treatments. Disclosure R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. S. Rosin: None. N.M. Butera: None. H. Krause-Steinrauf: None. H. Abou Assi: Research Support; Novo Nordisk. Stock/Shareholder; Gilead Sciences, Inc, Regeneron Pharmaceuticals, Medtronic, Moderna, Inc, MannKind Corporation, Merck & Co., Inc, Pfizer Inc. R.K. Garg: None. S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. A. Katona: None. J.B. McGill: Advisory Panel; Bayer Pharmaceuticals, Inc. Consultant; Jaeb Center for Health Research. Advisory Panel; Boehringer-Ingelheim, Lilly Diabetes, Novo Nordisk, MannKind Corporation. Research Support; Diagnode, Lexicon Pharmaceuticals, Inc, Biomea Fusion. S. Mudaliar: Consultant; Sun Pharmaceutical Industries Ltd. D.S. Schade: None. E.R. Seaquist: None. M. Tiktin: None. E.Z. Soliman: None. J.B. Green: Consultant; BI Lilly NovoNordisk Bayer Anji Vertex Valo Mineralys AstraZeneca. Research Support; BI Lilly Merck Bluedrop Roche. Funding NIDDK (U01DK098246, U34-DK-088043); American Diabetes Association; National Heart, Lung, and Blood Institute; The Centers for Disease Control and Prevention
Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes
JAMA Internal Medicine · 2025-05-19 · 6 citations
letterOpen accessImportance: Type 2 diabetes (T2D) is a risk factor for cognitive impairment. Whether the choice of the second-line glucose-lowering treatment added to metformin or glycemic control affects cognitive performance in T2D of relatively short duration (<10 years) is not known. Objective: To compare the relative effect of 4 classes of glucose-lowering medications that were randomly added to metformin on cognitive performance and to examine the association of longitudinal glycemic levels with cognitive performance. Design, Setting, and Participants: This randomized clinical trial (the GRADE study) was conducted at 36 clinical centers in the US and included 3721 participants with T2D with baseline and follow-up cognitive performance data. GRADE was implemented 2013 to 2021, and data for this study were analyzed from February 2024 to February 2025. Interventions: For the primary objective, the exposure was randomization of metformin-treated participants to receive long-acting insulin (insulin glargine U-100), sulfonylurea (glimepiride), glucagon-like peptide-1 receptor agonist (liraglutide), or dipeptidyl peptidase-4 inhibitor (sitagliptin). The secondary objective assessed time-weighted hemoglobin A1c levels over the follow-up period. Main Outcomes and Measures: The primary cognitive outcome was the Digit Symbol Substitution Test score; the secondary cognitive outcomes were the immediate and delayed recall in the Spanish English Verbal Learning Test and letter and category fluency test scores. Results: At baseline, the mean (SD) duration of T2D was 4.3 (2.7) years, and the mean (SD) age was 57.1 (9.8) years. Most participants were male (2320 [62.3%]; 1401 female individuals [37.7%]) and non-Hispanic (3015 [81.6%]; 681 Hispanic individuals [18.4%]); 712 (19.1%) were Black and 2452 (65.9%) were White; 777 (20.9%) were recruited from Veterans Affairs medical centers. There were no statistically significant differences between treatment groups in the cognitive outcomes at follow-up. However, a 1-unit increase in time-weighted hemoglobin A1c levels was associated with modestly lower Digit Symbol Substitution Test scores (-0.94 points; 95% CI, -1.30 to -0.57), Spanish English Verbal Learning Test scores (immediate recall, -0.27 points; 95% CI, -0.49 to -0.06), and category fluency test scores (animal fluency, -0.28 points; 95% CI, -0.47 to -0.09) over the mean (SD) of 4.1 (0.1) years of follow-up. Severe hypoglycemia requiring assistance was uncommon in all 4 groups (34 participants [0.9%]). Conclusions and Relevance: The results of this randomized clinical trial suggest that choice of second-line glucose-lowering medication class added to metformin is not associated with change in cognitive performance in persons with early T2D. Worse glycemic control is associated with modestly worse cognitive performance. Trial Registration: ClinicalTrials.gov Identifier: NCT01794143.
2025-12-10
articleOpen access<p dir="ltr">Objective: To test the effect of substituting plain water (the ideal standard) for habitual artificial sweetened beverage (ASB) intake in people with type 2 diabetes (T2D) on primary measures of diabetes control. Research Design and Methods: The Study Of Drinks with Artificial Sweeteners in People With T2D (SODAS) was conducted at two academic health centers; and was a randomized, two-arm parallel trial with a 2-week run-in period and a 24-week active intervention period. 181 adults with T2D (HbA1c 6.5-8.5%), age 35+ years, who regularly consumed commercial ASB were randomized to receive and consume 24 oz. daily for 24-weeks of either: 1) Commercial ASB of choice (control); or 2) Unflavored, sparkling or still, bottled/canned water of choice in place of ASB. The outcomes measures were collected at baseline, 12, and 24 weeks and include the primary (HbA1c%) and related secondary measures (Fructosamine, fasting glucose and insulin, body weight and continuous glucose monitor metrics). Results: 179 participants provided complete data over 24 weeks. From baseline to 24 weeks, the mean difference in change of HbA1c% was 0.29% (SE 0.12; P value = 0.013) higher in the water arm compared to the ASB arm. There were no significant effects on secondary clinical measures, but data were directionally consistent with the primary results. Conclusion: For people with T2D and HbA1c% < 8.5% who regularly consume ASB, this trial provided no evidence that substituting water would improve glycemic-related clinical care measures over 24 weeks.</p>
Diabetes · 2025-06-13
article1st authorCorrespondingIntroduction and Objective: Mechanisms of impaired awareness of hypoglycemia (IAH) upon exposure to recurrent hypoglycemia (HG) in people with T1D are unknown. We tested the hypothesis that brain glucose transport is upregulated in response to recurrent HG, obviating the need to mount a counterregulatory response during subsequent HG. Methods: Glucose concentrations in the hypothalamus (HTL) and prefrontal cortex (PFC) were measured during hyperglycemic clamps in 45 people with T1D who were aware of HG using 1H MRS at 3T before and after the induction of IAH by exposure to 3 two-hour HG clamps over 2 days. Steady state brain glucose transport kinetics were determined using reversible Michaelis-Menton model. Epinephrine samples and the Towler symptom questionnaire were collected at the 1st and 3rd HG clamp. We present data from 30 who completed the entire study (14 males, age 30.4(±9.3), A1c 6.8(±0.7)). Results: Data collected during HG clamps 1 and 3 are in table. During hyperglycemia, brain glucose concentrations increased as a function of the target glycemia, but no differences were found in steady state glucose transport kinetics before vs after IAH-induction (Tmax/CMRgluc, before vs after, HTL:1.81±0.14 vs 1.88±0.13; PFC: 1.94±0.07 vs 1.91±0.06). Conclusion: We conclude that exposure to recurrent HG did not alter glucose transport kinetics in the HTL or PFC in subjects with T1D. Disclosure E.R. Seaquist: None. Y. Park: None. A. Kumar: None. L. Zhang: None. B. Strong: None. L.E. Eberly: None. A. Moheet: Other Relationship; Sanofi-Aventis U.S. P. Henry: None. G. Oz: Research Support; Biogen. Consultant; Servier Laboratories, UCB Biopharma SRL / Lacerta Therapeutics Inc, Sanofi. Funding National Institutes of Health (NS035192)
The Journal of Clinical Pharmacology · 2025-06-29
articleOpen accessAbstract Impaired awareness of hypoglycemia (IAH) impacts 25%‐30% of individuals with type 1 diabetes mellitus (T1D), potentially leading to severe outcomes due to reduced symptom perception. Naloxone, a mu‐opioid receptor antagonist, shows promise as a preventive measure against IAH. This study explored intranasal (IN) naloxone as a potential therapy to preserve counterregulatory and symptom responses to hypoglycemia following exercise in T1D patients. Participants included adults with T1D for 2‐20 years. The study aimed to develop a population pharmacokinetic (PopPK) model of IN naloxone and assess exposure–response relationships. The study was conducted as a single‐center, single‐blinded, placebo‐controlled crossover study. It involved collecting blood samples at 12 intervals before, during, and after exercise. Plasma naloxone concentrations were analyzed using high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS). Utilizing nonlinear mixed effects modeling, the PopPK model simulated individual naloxone maximum concentrations (C max ) and total area under the curve (AUC) to evaluate exposure–response relationships. A two‐compartment model with combined zero‐ and first‐order absorption best described the naloxone's pharmacokinetics. Allometric scaling based on weight was applied to volume and clearance parameters, with a combined additive and proportional error model describing residual unexplained variability. Clearance and volume estimates were: central: 6.82 L/min/70 kg and 171 L/70 kg, peripheral: 2.97 L/h/70 kg and 278 L/70 kg. The absorption rate constant and zero‐order absorption duration were 0.0272 min −1 and 7.33 min, respectively. While a strong correlation was observed between simulated exposures (C max and AUC), no statistically significant correlation was found between exposures and responses. This is the first PopPK model of IN naloxone in T1D offering insights for future clinical pharmacokinetic studies.
2025-09-23
articleOpen access<p dir="ltr">Objective: To describe prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG-derived cardiovascular autonomic neuropathy (CAN) in the GRADE cohort of adults with type 2 diabetes (T2D) <10 years.</p><p dir="ltr">Research Design and Methods: T2D individuals on metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at baseline, 2-, and 4-year study visits and analyzed for minor/major abnormalities and CAN assessed with heart rate variability (HRV) in 4769 participants. Incidence of new major/minor/any ECG abnormalities and CAN by treatment group was analyzed using logistic repeated measures models at years 2 and 4 adjusted for baseline risk factors.</p><p dir="ltr">Results: At baseline, participants were 57.2 ± 10.0 years old, 36.3% women, had diabetes duration 4.3 ± 2.8 years, and HbA1c 7.5 ± 0.5%. Participants with ECG abnormalities at baseline (57.1%) and ECG-derived CAN (52.8%) were older and had more severe cardiovascular risk factors. The incidence of minor and major ECG abnormalities was similar among all treatment groups. However, at year 4, major ECG abnormalities were fewer in liraglutide vs. non-liraglutide groups (9% vs. 13%; p=0.03). The incidence of CAN did not differ between liraglutide vs. non-liraglutide groups across visits (p=0.42); however, one measure of HRV (standard deviation of normal-to-normal R-R intervals) was higher at year 2 in liraglutide vs. non-liraglutide groups (p=0.02).</p><p dir="ltr">Conclusions: ECG abnormalities, including those reflecting CAN, are common in T2D <10 years, more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.</p><p><br></p>
2025-12-10
articleOpen access<p dir="ltr">Objective: To test the effect of substituting plain water (the ideal standard) for habitual artificial sweetened beverage (ASB) intake in people with type 2 diabetes (T2D) on primary measures of diabetes control. Research Design and Methods: The Study Of Drinks with Artificial Sweeteners in People With T2D (SODAS) was conducted at two academic health centers; and was a randomized, two-arm parallel trial with a 2-week run-in period and a 24-week active intervention period. 181 adults with T2D (HbA1c 6.5-8.5%), age 35+ years, who regularly consumed commercial ASB were randomized to receive and consume 24 oz. daily for 24-weeks of either: 1) Commercial ASB of choice (control); or 2) Unflavored, sparkling or still, bottled/canned water of choice in place of ASB. The outcomes measures were collected at baseline, 12, and 24 weeks and include the primary (HbA1c%) and related secondary measures (Fructosamine, fasting glucose and insulin, body weight and continuous glucose monitor metrics). Results: 179 participants provided complete data over 24 weeks. From baseline to 24 weeks, the mean difference in change of HbA1c% was 0.29% (SE 0.12; P value = 0.013) higher in the water arm compared to the ASB arm. There were no significant effects on secondary clinical measures, but data were directionally consistent with the primary results. Conclusion: For people with T2D and HbA1c% < 8.5% who regularly consume ASB, this trial provided no evidence that substituting water would improve glycemic-related clinical care measures over 24 weeks.</p>
Recent grants
NIH · $278k · 2015
NIH · $419k · 1994
NIH · $21.0M · 2010
NIH · $368k · 2014
NIH · $1.7M · 2010
Frequent coauthors
- 276 shared
E. Diaz
Medical University of South Carolina
- 262 shared
M. Mullen
- 194 shared
Naji Younes
Milken Institute
- 160 shared
Rodica Pop‐Busui
Oregon Health & Science University
- 155 shared
Melissa Lee
Otterbein University
- 151 shared
Mary Ann Banerji
- 145 shared
Emily B. Schroeder
- 144 shared
Richard M. Bergenstal
Park Nicollet Clinic
Labs
Awards & honors
- American Diabetes Association’s Transformative Woman in Diab…
- Albert Renold Award for Mentoring (2020)
- Inductee, AHC Academy for Excellence in Team Science, Univer…
- Bruce Zimmerman Diabetes Award, American Diabetes Associatio…
- Inductee, AHC Academy for Excellence in Health Research, Uni…
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