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Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors Expert Forum

William T. Cefalu
Jan 1, 2018; 41:14-31
Diabetes Care Expert Forum




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Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial

W. Timothy Garvey
May 1, 2020; 43:1085-1093
Emerging Therapies: Drugs and Regimens




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Effects of Coffee Consumption on Fasting Blood Glucose and Insulin Concentrations: Randomized controlled trials in healthy volunteers

Rob M. van Dam
Dec 1, 2004; 27:2990-2992
Brief Reports




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Psychosocial Care for People With Diabetes: A Position Statement of the American Diabetes Association

Deborah Young-Hyman
Dec 1, 2016; 39:2126-2140
Psychosocial Research and Care in Diabetes




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Table 1-Systeme International (SI) units for plasma, serum, or blood concentrations


Aug 1, 1995; 18:1223-1224
Syst[egrave]me International (SI) Units




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2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

John B. Buse
Feb 1, 2020; 43:487-493
Consensus Report Update




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Redefining Hypoglycemia in Clinical Trials: Validation of Definitions Recently Adopted by the American Diabetes Association/European Association for the Study of Diabetes

OBJECTIVE

To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.

RESEARCH DESIGN AND METHODS

A post hoc analysis was performed of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and DEVOTE (n = 7,637, type 2 diabetes) trials utilizing the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2) IHSG level 2 (PG confirmed <3.0 mmol/L, independent of symptoms).

RESULTS

In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. Similar results were observed for the SWITCH 1 trial. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition.

CONCLUSIONS

The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials.




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Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance

OBJECTIVE

Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.

RESEARCH DESIGN AND METHODS

Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined.

RESULTS

Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ~30% and ~40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ~20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

CONCLUSIONS

In obese humans with microvascular insulin resistance, GLP-1’s vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.




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Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work

OBJECTIVE

Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality.

RESULTS

A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5–12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3–10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02–2.11], 2.28 [1.62–3.21], and 4.64 [3.39–6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15–2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09–3.42] and adjusted HR 1.49 [1.14–1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor.

CONCLUSIONS

Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.




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Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent?

OBJECTIVE

To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes.

RESEARCH DESIGN AND METHODS

People with type 1 diabetes (n = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.9, 3.45, and 3.0 mmol/L).

RESULTS

MDG was significantly higher, and %CV significantly lower (both P < 0.001), when comparing the 24-h glycemic profiles according to whether no time or a certain duration of time was spent below the thresholds. Univariate regression analyses showed that MDG and %CV were the two explanatory variables that entered the model with the outcome variable (time spent below the thresholds). The classification and regression tree procedure indicated that the predominant predictor for hypoglycemia was %CV when the threshold was 3.0 mmol/L. In people with mean glucose ≤7.8 mmol/L, the time spent below 3.0 mmol/L was shortest (P < 0.001) when %CV was below 34%.

CONCLUSIONS

In type 1 diabetes, short-term glycemic variability relative to mean glucose (i.e., %CV) explains more hypoglycemia than does mean glucose alone when the glucose threshold is 3.0 mmol/L. Minimizing the risk of hypoglycemia requires a %CV below 34%.




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Refugees and Asylees in the United States

The United States has historically been the top country for refugee resettlement, but was surpassed in 2018 by Canada amid record cuts to admissions by the Trump administration. Approximately 22,500 refugees were resettled in the United States during fiscal year 2018, as well as 26,500 asylees. This article examines where these newcomers came from and many other characteristics, including religious affiliation, age, and gender.




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As Governments Build Advanced Surveillance Systems to Push Borders Out, Will Travel and Migration Become Unequal for Some Groups?

As governments seek to push their borders out by amassing ever more data on travelers and migrants, their creation of increasingly complex border surveillance systems and use of risk-assessment technologies could ease mobility for some while rendering other groups immobile based on hypothetical risk profiles and decisions that are not publicly known and cannot be challenged, as this article explores.




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As the Trump Administration Seeks to Remove Families, Due-Process Questions over Rocket Dockets Abound

The U.S. government is operating accelerated dockets to handle the rising number of cases of families in immigration court. While it is essential to have timely, fair case processing and removal of those who have truly had their day in court and been found to be removable, using “rocket” dockets to speed up proceedings only heightens the breakdowns that are a recurring feature of the court system on its best day, as this commentary explains.




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As the United States Resettles Fewer Refugees, Some Countries and Religions Face Bigger Hits than Others

Even as refugee admissions have dropped sharply during the Trump administration, some countries and religions have been significantly more affected than others, as this commentary explores. In fiscal year 2019, 79 percent of refugees were Christian and 16 percent Muslim—as compared to 44 percent Christian and 46 percent Muslim in fiscal year 2016, which was the last full year of the Obama administration.




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USCIS Fee Increase Proposed Rule Could Represent the Latest Step in Reshaping Immigration to United States

While much attention has been given to the move by U.S. Citizenship and Immigration Services to raise its application fees—including an 83 percent hike to apply for U.S. citizenship—the policy changes embedded in the proposed rule have been less scrutinized. The changes, including the elimination of most fee waivers for lower-income applicants, would likely reduce the number and shift the profile of those getting a green card or other immigration status.




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As COVID-19 Slows Human Mobility, Can the Global Compact for Migration Meet the Test for a Changed Era?

The coronavirus pandemic dramatically reshaped how human mobility is managed just as the Global Compact for Safe, Orderly, and Regular Migration was beginning to move from paper to implementation. As governments face pressing public-health, economic, and other concerns in responding to COVID-19, this MPI Europe commentary explores whether the first comprehensive global agreement on migration can adjust to a changed reality.




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Interlocking Set of Trump Administration Policies at the U.S.-Mexico Border Bars Virtually All from Asylum

Through a set of interlocking policies, the Trump administration has walled off the asylum system at the U.S.-Mexico border, guaranteeing that only a miniscule few can successfully gain protection. While the Migrant Protection Protocols, more commonly known as Remain in Mexico, have been a key part of throttling asylum applications, two newer, far less visible programs hold the potential to complete the job, as this article explores.




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Soluciones estratégicas para afrontar la crisis migratoria en Estados Unidos y México

Dado el incremento de los flujos migratorios provenientes de Centroamérica, el pasado mes de junio de 2019, los Estados Unidos y México acordaron tomar una serie de medidas para reducir los flujos irregulares. Sin embargo, será muy difícil mantener estos esfuerzos de corto plazo, debido a una debilidad institucional crónica y a estructuras de política pública poco planificadas en ambos países. Este comentario ofrece cinco recomendaciones a ambos países considerando soluciones de mediano y largo plazo para disuadir la migración irregular y, al mismo tiempo, garantizar que aquellos que busquen protección tengan un proceso justo.




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HHS releases video tutorial for searching list of excluded individuals/entities

The Department of Health and Human Services released Nov. 25 a five-minute video explaining how to search its list of excluded individuals and entities, called LEIE.




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ADA asks Congress to pass Ensuring Lasting Smiles Act

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.




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Texas A&M dental school opens new clinic, education building

Texas A&M College of Dentistry announced Jan. 17 it opened it’s a new 160,000-square-foot, nine-story clinic, which enables the dental school to increase underserved patients’ access to care.




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2019 marks big year for Washington office

The Association’s Washington office covered a wide range of advocacy issues in 2019 — from vaping to student loan reform to making sure dentistry was exempt from the U.S. Mexico-Tourism Act.




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Dental Quality Alliance to help dentists make connection between everyday dentistry, quality measures

The Dental Quality Alliance will help dentists learn more about how quality measure domains can be best used to drive quality improvement at the practice level through a free webinar in March.




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ADA urges subcommittee to support Ensuring Lasting Smiles Act

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.




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Florida oral surgeon stays atop branding as practice expands

There is an art to conveying just who you are at every stage of your dental practice. One minute you could be a single-dentist practice with a hygienist and a receptionist, and then, the next thing you know, you could have a group practice and maybe even several locations.




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Missouri Dental Association notches win

Thanks to the advocacy efforts of the Missouri Dental Association, a managed care organization has agreed to remove an authorization tool it was requiring dentists to use prior to using sedation.




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Dental service leaders visit Washington

Dental service leaders met with the ADA Council on Government Affairs Jan. 25 in Washington to discuss legislative and regulatory issues.




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Dental Assistants Recognition Week set for March 1-7

The ADA Council on Dental Practice is encouraging dentists to acknowledge the dedication and contributions of their dental assistants during Dental Assistants Recognition Week.




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Journal of Public Health Dentistry study finds association between man-made chemical, childhood caries

Circulating levels of perfluorodecanoic acid, a type of perfluoroalkyl acid, may be associated with dental caries in children, according to a study published in the fall 2019 issue of the Journal of Public Health Dentistry.




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New dentists, ADA officers and Board members meet Feb. 9 to exchange ideas

Dr. Emily Mattingly, chair, New Dentist Committee, 6th District, shares her experience as a new dentist in a rural Missouri town. Three other NDC members also shared new dentist perspectives.




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March JADA finds past incarceration associated with oral health issues

Formerly incarcerated people in the U.S. have worse oral health outcomes than those who have never been in prison, according to a study published in the March issue of The Journal of the American Dental Association.




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ADA releases coronavirus handout for dentists based on CDC guidelines

The handout covers strategies for helping prevent the transmission of suspected respiratory disease in the dental health care setting and answers frequently asked questions related to the virus, based on guidelines from the Centers for Disease Control and Prevention.




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ADA technical report on age assessment by dental analysis available for review

The ADA Standards Committee on Dental Informatics has approved the technical report for circulation and comment.




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Vaping bill passes House

The U.S. House of Representatives Feb. 28 passed a comprehensive bill designed to address the youth tobacco epidemic.




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American Dental Board of Anesthesiology recognized as national certifying board for dental specialty

The National Commission on Recognition of Dental Specialties and Certifying Boards announced March 4 it recognizes the American Dental Board of Anesthesiology as the national certifying board for dental anesthesiology.




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Oral medicine recognized as a dental specialty

Oral medicine becomes the 11th dental specialty recognized by the National Commission on Recognition of Dental Specialties and Certifying Boards. The recognition comes after the National Commission on March 2 adopted a resolution based on an application from the American Academy of Oral Medicine to recognized oral medicine as a dental specialty.




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Howard dental school celebrates GKAS

The Howard University College of Dentistry treated 35 students from Washington’s Raymond Elementary School at a Feb. 7 Give Kids A Smile event.




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Study: Evidence does not support classifying fluoride as cognitive neurodevelopmental hazard

The National Academies of Sciences, Engineering, and Medicine announced March 5 that it does not find that the National Toxicology Program adequately supported its conclusion that fluoride is “presumed” to be a cognitive neurodevelopmental hazard to humans.




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Association launches new ADA Science & Research Institute

The American Dental Association launched the new ADA Science & Research Institute LLC on Jan. 1, bringing together the Science Institute in Chicago and research group in Gaithersburg, Maryland, that previously reported to the ADA Foundation.




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ADA adds frequently asked questions from dentists to coronavirus resources

With the coronavirus disease now deemed a pandemic by the World Health Organization, the American Dental Association updated its webpage on the disease March 11 to include a link to frequently asked questions from member dentists covering topics such as personal protective equipment and patient communications.




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Association warns members on potential coronavirus-related phishing emails

The Association is asking member dentists and their dental teams to increase their vigilance over phishing emails as a result of the coronavirus, known as COVID-19.
Attackers often use emergencies as an opportunity to send fake emails tailored to that situation, the association said.




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Association provides coronavirus infection control resources for dentists

The ADA is sharing with members the CDC guidelines on the use of personal protective equipment on its website dedicated to COVID-19.




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Senate passes coronavirus legislative package

The Senate and House have passed a coronavirus legislation package that includes three issues important to dentistry that will next head to the White House where President Donald Trump is expected to sign it into law.




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Treasury, IRS delay federal tax filing, payments until July 15

Taxpayers do not need to file or pay their federal income taxes until July 15, after the U.S. Department of the Treasury and Internal Revenue Service extended both deadlines from April 15.




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ADA, other dental organizations ask Labor Department to help small businesses

The ADA, along with a large group of other dental organizations, told the U.S. Department of Labor that they are concerned about provisions in HR 6201, the Families First Coronavirus Response Act as related to family and medical leave and paid sick leave.




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ADA urges Congress to increase relief for small businesses, dentist owners

As Congress works on a third legislation package in response to the coronavirus pandemic, the ADA is asking lawmakers to include provisions on how to assist dental practices and other small businesses facing economic burdens.




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ADA initiates grassroots campaign in response to CARES Act

The ADA is calling on dentists everywhere to contact their legislators today ahead of the Senate’s vote on the Coronavirus Aid, Relief and Economic Security Act.




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ADA president thanks dentists for grassroots efforts in response to CARES Act

As the Senate works to pass a stimulus package aimed at granting relief to the millions of Americans affected by the COVID-19 pandemic, the ADA is thanking dentists across the nation for making their voices heard in Washington on that same legislation.




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Senate passes CARES Act

The ADA sent out an Issues Alert March 25 from ADA President Chad P. Gehani following the Senate's passing of a $2 trillion stimulus package to help the people, states and businesses nationwide devastated by the coronavirus pandemic.




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EPA releases expanded list of SARS-CoV-2 disinfectants

Washington — The Environmental Protection Agency announced March 13 that it was adding nearly 200 additional products that have qualified for use against SARS-CoV-2, the novel coronavirus that causes the disease COVID-19.