John B. Buse's research while affiliated with Microbiome Core Facility USA and other places

Publications (618)

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Objective: The concentrations of endogenous metabolites in saliva can be altered based on the systemic condition of the hosts and may, in theory, serve as a reflection of systemic disease progression. Hemoglobin A1C is used clinically to measure long-term average glycemic control. The aim of the study was to demonstrate if there were differences i...
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Background: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effecti...
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Sodium Glucose Co-Transporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to not only control blood glucose but to improve cardiovascular and kidney outcomes. Diabetic Ketoacidosis (DKA) is an uncommon but a serious complication of type 2 diabetes which has a high case fatality rate. The absolute risk of DKA...
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OBJECTIVE Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to t...
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Continuous, real‐time monitoring of biomarkers associated with local regions of the body can enhance both temporal and dimensional accuracy of proactive treatment to acute syndromes for critical illnesses, especially peripheral artery diseases. Conventional health monitors often face grand challenges in leveraging deep‐tissue sensing capability wit...
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The hemoglobin glycation index (HGI) is the difference between observed HbA1c and predicted HbA1c from FPG using linear regression. HGI is an important biomarker of clinical management/drug treatment outcomes and can identify individuals at high risk for multiple adverse events and outcomes before the appearance of clinical symptoms. Here, we sough...
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RADIANT is an NIH study of people with uncharacterized forms of atypical diabetes mellitus (DM) in the US. RADIANT participants consent online and progress through three sequential stages of study procedures, as eligible. DM in underrepresented minorities (URM) is rapidly increasing in incidence and has worse outcomes than DM in non-Hispanic whites...
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Background: At least two-thirds of people with hemodialysis-dependent kidney failure have comorbid diabetes which associates with higher mortality. Some GLP-1 receptor agonists (RA) do not require renal dosing and could uniquely benefit dialysis patients, individuals with tremendous cardiovascular disease burden. Methods: Using data from a national...
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Identification of adjunctive, oral pharmacotherapies to treat T1D has been limited by risk of DKA. TTP399, an oral hepatoselective GKA, significantly improves glycemia in individuals with T1D compared to placebo. This double-blind, randomized, placebo-controlled, Phase 1 mechanistic study examined whether TTP399 decreases ketogenesis during insulin...
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SEPRA (NCT03596450) is a 2-yr, multicenter, open-label, randomized pragmatic clinical trial comparing the long-term effects of once-weekly subcutaneous semaglutide vs. standard of care (both added to ≤2 oral antidiabetic medications) in US health-insured adults with T2D and physician-determined inadequate glycemic control. SEPRA will assess glycemi...
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The DAWN and SEED trials demonstrate the potential of glucokinase activators for the treatment of type 2 diabetes, but how they fit in the overall treatment algorithm remains to be determined.
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Background: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). Objective: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combi...
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Aims: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). Materials and methods: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. Aft...
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OBJECTIVE The purpose of the study is to evaluate the relationship between HbA1c and severity of coronavirus disease 2019 (COVID-19) outcomes in patients with type 2 diabetes (T2D) with acute COVID-19 infection. RESEARCH DESIGN AND METHODS We conducted a retrospective study using observational data from the National COVID Cohort Collaborative (N3C...
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Background Data conflict on whether vaccination decreases severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. The objective of this analysis was to compare baseline viral load and symptoms between vaccinated and unvaccinated adults enrolled in a randomized trial of outpatient COVID-19 treatment. Methods Baseline data from the...
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Background Randomized trials demonstrate the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). We evaluated their relative cardiovascular effectiveness in routine care populations with a broad spectrum of atherosclerotic cardiovascular diseases (CVDs) or heart fai...
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Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has no...
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Background: We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Methods: Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persisten...
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Introduction: Metabolic substrate utilization is central to metabolic disease. Metabolic pathways linking type 2 diabetes (T2D) to major adverse cardiac events (MACE) and heart failure (HF) remain poorly understood and T2D drug effects on metabolite biomarkers could improve biological understanding and support precision medicine approaches. Hypothe...
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Importance Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. Objective To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated em...
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Introduction Hemoglobin glycation index (HGI) is the difference between observed and predicted glycated hemoglobin A1c (HbA 1c ), derived from mean or fasting plasma glucose (FPG). In this secondary, exploratory analysis of data from DEVOTE, we examined: whether insulin initiation/titration affected the HGI; the relationship between baseline HGI te...
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Objective: Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. Research design and methods: We used data from the Trial Evaluating Ca...
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Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have r...
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Objective: To explore the effect of discontinuing continuous glucose monitoring (CGM) after 8 months of CGM use in adults with type 2 diabetes treated with basal without bolus insulin. Research design and methods: This multicenter trial had an initial randomization to either real-time CGM or blood glucose monitoring (BGM) for 8 months followed b...
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Frontal-midline theta (FMT) oscillations are increased in amplitude during cognitive control tasks. Since these tasks often conflate cognitive control and cognitive effort, it remains unknown if FMT amplitude maps onto cognitive control or effort. To address this gap, we utilized the glucose facilitation effect to manipulate cognitive effort withou...
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Throughout history, up to the early part of the 20th century, diabetes has been a devastating disorder, particularly when diagnosed in childhood when it was usually fatal. Consequently, the successful pancreatic extraction of insulin in 1921 was a miraculous, life-changing advance. In this review, the truly transformative effect that insulin has ha...
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Background: Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with...
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Importance The National COVID Cohort Collaborative (N3C) is a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools and inform clinical care and policy....
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Back Cover Caption: The cover image is based on the Research Article Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity by Carolyn T. Bramante et al., https://doi.org/10.1002/jmv.26873. Design Credit: Andy Grams.
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We sought to identify genome‐wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome‐wide antihypertensive drug‐SNP interaction tests for four drug classes (β‐block...
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The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. He...
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Objective: To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...
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Importance Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied. Objective To determine the effectiveness of CGM in adults with type 2 diabetes treated with bas...
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Aims: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and semaglutide appeared to reduce kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal-replacement therapy, or renal death) in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials, primarily driven by changes in albuminuria. We i...
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Objective: Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. Research design and methods: This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (n = 205) with type 2 diabetes and HbA1c 7...
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Objective: Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed...
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In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes (T2D). In this post hoc anal...
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Introduction The coronavirus disease 2019 (COVID-19) created major disruptions at academic centers and healthcare systems globally. Clinical and Translational Science Awards (CTSA) fund hubs supported by the National Center for Advancing Translational Sciences provideinfrastructure and leadership for clinical and translational research at manysuch...
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With the emergence of glycated hemoglobin as a diagnostic test for diabetes, oral glucose tolerance tests (OGTTs) have become rare in endocrinology practice. As they have moved out of favor, the importance of patient instructions on preparation prior to OGTT has faded from memory. Decades old literature, well known to endocrinologists a generation...
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Aims Although models exist to predict amputation among people with type 2 diabetes with foot ulceration or infection, we aimed to develop a prediction model for a broader range of major adverse limb events (MALE)—including gangrene, revascularization, and amputation—among individuals with type 2 diabetes. Methods In a post‐hoc analysis of data fro...
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Insulin therapy is the central component of treatment for type 1 and advanced type 2 diabetes; however, its narrow therapeutic window is associated with a risk of severe hypoglycemia. A glucose-responsive carrier that demonstrates consistent and slow basal insulin release under a normoglycemic condition and accelerated insulin release in response t...
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We are writing with great concern about the consequences of applying drug related regulations to allogeneic islets (allo‐islets). Currently, the Food and Drugs Administration (FDA) is reviewing a Biologics License Application (BLA) for the isolation of allogenic islets which, if approved, will effectively confer marketing rights to a private, for‐p...
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Introduction: The efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses evaluated outcomes by background medication and i...
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Data‐driven tools are needed to inform individualized treatment decisions for people with type 2 diabetes (T2D). To demonstrate how treatment might be individualized, an interactive outline tool was developed to predict treatment outcomes. Individualized predictions were generated for change in glycated haemoglobin (HbA1c) and body weight after ini...
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Objective: Despite advances in exogenous insulin therapy, many patients with type 1 diabetes do not achieve acceptable glycemic control and remain at risk for ketosis and insulin-induced hypoglycemia. We conducted a randomized, controlled trial to determine whether TTP399, a novel hepatoselective glucokinase activator, improved glycemic control in...
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In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes (T2D) in both the ‘established CV disease’ (CVD) and ‘CV risk factor’ subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD than REWIND. This post hoc analysis assessed the effect of se...
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The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities an...
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Background: Observational studies suggest outpatient metformin use is associated with reduced mortality from COVID-19 disease. Metformin is known to decrease interleukin-6 (IL-6) and tumor-necrosis alpha (TNFα), which appear to contribute to morbidity in COVID-19. We sought to understand whether outpatient metformin use was associated with reduced...
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New findings: What is the central question of this study? Glucose is the dominant energy source for the brain. However, little is known about how glucose metabolism impacts the coordination of network activity in the brain in healthy adults. What is the main finding and its importance? We demonstrate that both alpha oscillations and the aperiodic...
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OBJECTIVE | Sodium–glucose cotransporter 2 (SGLT2) inhibitors are approved for type 1 diabetes in Europe and Japan, with off-label use in type 1 diabetes in the United States. Although there were no consistent approaches to risk mitigation in clinical trials of these agents, protocols have been developed to try to reduce the risk of diabetic ketoac...
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Glycated haemoglobin (HbA1c) is considered the gold standard for predicting glycaemia-associated risks for the microvascular and macrovascular complications of diabetes mellitus over 5–10 years. The value of HbA1c in the care of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) is unassailable, yet HbA1c targets rema...
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Introduction: The PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide. Research design and methods:...
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Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state‐of‐the‐art in clinical or technical practices. In the US, islets are considered biologic drugs and “mo...
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Introduction: People with type 2 diabetes mellitus (DM) have a large burden of cardiovascular (CV) morbidity and mortality, but the likelihood of these outcomes varies and existing risk calculators do not fully capture risk for individuals. Hypothesis: Circulating metabolites characterizing mitochondrial dysfunction may be novel predictors for CV o...
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Introduction: To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM). Hypothesis: Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with...
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Introduction Pilot programs are integral to catalyzing and accelerating research at Clinical and Translational Science Award (CTSA) hubs. However, little has been published about the structure and operationalization of pilot programs or how they impact the translational research enterprise at CTSAs. The North Carolina Translational and Clinical Sci...
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Significance The efficacy of current diabetes treatments designed to reverse insulin deficiency is often limited by the frequent occurrence of acute hypoglycemia. To this end, a hybrid glucose-responsive delivery patch is engineered to function as a synthetic artificial pancreas by delivering insulin and glucagon upon hyperglycemic and hypoglycemic...
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Aim To investigate risk factors associated with kidney disorders in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk. Methods In DEVOTE, a cardiovascular outcomes trial, 7637 patients were randomised to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100), with standard of care. In these exploratory post...
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Individuals with type 1 and advanced type 2 diabetes require daily insulin therapy to maintain blood glucose levels in normoglycemic ranges to prevent associated morbidity and mortality. Optimal insulin delivery should offer both precise dosing in response to real-time blood glucose levels as well as a feasible and low-burden administration route t...
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Cardiovascular outcome trials in patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of GLP-1 receptor agonists and SGLT2 inhibitors to reduce cardiorenal events. In 2019, the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), an...
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2020, The Author(s), under exclusive licence to Springer Nature Limited. Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsiv...
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Suggested Citation: Hale PM, Ali AK, Buse JB, McCullen MK, Ross DS, Sabol ME, Tuttle RM, Stemhagen A. Medullary thyroid carcinoma surveillance study: a case-series registry. Thyroid. October 2020;30(10):1397-1398.