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Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles




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Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM

Guenther Boden
Jan 1, 1997; 46:3-10
Perspectives in Diabetes




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Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies




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Role of Insulin Resistance in Human Disease

Gerald M Reaven
Dec 1, 1988; 37:1595-1607
Banting Lecture 1988




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Taxis complying with social-distancing protocol

Many taxi and bus operators in sections of Kingston and St Andrew are seemingly adhering to social-distancing guidelines outlined by the Government for the sector, in terms of the number of passengers they are allowed to transport at a time. These...




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World Bank predicts sharpest decline of remittances to Caribbean

WASHINGTON, CMC – The World Bank has predicted the sharpest decline of remittances to Latin America and the Caribbean, saying that global remittances on a whole are projected to fall by about 20 percent in 2020 due to the economic crisis...




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Haiti receives US$16.1 million in assistance from US to fight COVID-19

PORT AU PRINCE, Haiti, CMC – The Government of Haiti has received funds amounting to US$16.1 million from the United States to help the country respond to the COVID-19 pandemic. The funds from the United States Agency for International...




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Use of antiviral drug in poultry is blamed for drug resistant strains of avian flu




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Importance of creative industries

In 2020, when information is literally glued to our fingertips, technological innovations fill the stratosphere, the economy is reeling. Under the catastrophic effects of the coronavirus pandemic, one has no choice but to be creative – be creative...




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Bariatric Surgery Rapidly Decreases Cardiac Dietary Fatty Acid Partitioning and Hepatic Insulin Resistance Through Increased Intra-abdominal Adipose Tissue Storage and Reduced Spillover in Type 2 Diabetes

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.




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Understanding Diabetic Neuropathy--From Subclinical Nerve Lesions to Severe Nerve Fiber Deficits: A Cross-Sectional Study in Patients With Type 2 Diabetes and Healthy Control Subjects

Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (A fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and A-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.




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EUTR Workshop: Substantiated Concerns and Producer Country Cooperation

Invitation Only Research Event

28 October 2014 - 9:00am to 29 October 2014 - 12:00pm

Food and Agriculture Organization of the UN, Rome, Italy

This meeting will focus on standards for NGOs wishing to submit 'substantiated concerns' in the EUTR context, and best practice in cooperation with enforcement agents in forest producer countries. The workshop will be attended by representatives from EU member states as well as officials from the US and Australia.  

This workshop is the next in a series of EUTR/Lacey/Australian ILPA enforcement workshops co-organized by Chatham House and Forest Trends. Please note this event will be held in Rome.

Attendance at this event is by invitation only.

Event attributes

External event

Adelaide Glover

Digital Coordinator, Energy, Environment and Resources Programme




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Head-to-Head Comparison of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in Staging Prostate Cancer Using Histopathology and Immunohistochemical Analysis as a Reference Standard

18F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)–based radiopharmaceutical for imaging prostate cancer (PCa). The aim of this study was to compare the diagnostic accuracy of 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk PCa. Methods: Sixteen patients with intermediate- or high-risk PCa underwent 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT within 15 d. PET findings were compared between the 2 radiotracers and with reference-standard pathologic specimens obtained from radical prostatectomy. The Cohen -coefficient was used to assess the concordance between 18F-PSMA-1007 and 68Ga-PSMA-11 for detection of intraprostatic lesions. The McNemar test was used to assess agreement between intraprostatic PET/CT findings and histopathologic findings. Sensitivity, specificity, positive predictive value, and negative predictive value were reported for each radiotracer. SUVmax was measured for all lesions, and tumor-to-background activity was calculated. Areas under receiver-operating-characteristic curves were calculated for discriminating diseased from nondiseased prostate segments, and optimal SUV cutoffs were calculated using the Youden index for each radiotracer. Results: PSMA-avid lesions in the prostate were identified in all 16 patients with an almost perfect concordance between the 2 tracers ( ranged from 0.871 to 1). Aside from the dominant intraprostatic lesion, similarly detected by both radiotracers, a second less intense positive focus was detected in 4 patients only with 18F-PSMA-1007. Three of these secondary foci were confirmed as Gleason grade 3 lesions, whereas the fourth was shown on pathologic examination to represent chronic prostatitis. Conclusion: This pilot study showed that both 18F-PSMA-1007 and 68Ga-PSMA-11 identify all dominant prostatic lesions in patients with intermediate- or high-risk PCa at staging. 18F-PSMA-1007, however, may detect additional low-grade lesions of limited clinical relevance.




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Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies




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Will a Devastating Bushfire Season Change Australia’s Climate Stance?

23 January 2020

Madeleine Forster

Richard and Susan Hayden Academy Fellow, International Law Programme

Professor Tim Benton

Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme
With Australians experiencing first-hand the risks of climate change, Madeleine Forster and Tim Benton examine the influencers, at home or abroad, that could push the government towards more action.

2020-01-23-FireNSW.jpg

Residents look on as flames burn through bush on 4 January 2020 in Lake Tabourie, NSW. Photo: Getty Images.

The 2019–20 fire season in Australia has been unprecedented. To date, an estimated 18 million hectares of fire has cut swathes through the bush – an area greater than that of the average European country and over five times the size of blazes in the Amazon.

This reflects previous predictions of Australian science. Since 2008 and as recently as 2018, scientific bodies have warned that climate change will exacerbate existing conditions for fires and other climatic disasters in Australia. What used to be once-in-a-generation fires now re-appear within 10–15 years with increased ferocity, over longer seasons.

In a country known for climate denial and division, debate has erupted around bushfire management and climate change. One of these is whether controlled burns are the answer to Australia’s climate-affected fire conditions.

There is no single risk reduction strategy. Controlled burning remains key, if adapted to the environment and climate

But when three out of four seasons in a year can support destructive bushfires, there are clear limits to what controlled burning and other fire management techniques can achieve. Other ‘adaptation’ measures are also likely to provoke intense debate – including bush clearance. As one Australian expert offered to highlight where Australia has got to, families should probably not go on holiday to bush and beach during the height of summer when temperatures and fire risk peaks. 

So, unless Australia is prepared to debate radical changes to where people live and how land is used, the limits to adaptation imply the need for mitigation. This means supporting ambitious global greenhouse emissions reductions targets. As research from Victoria, one fire-prone state in Australia, highlights, ‘the emissions pathway we follow is the largest determinant of change to many variables [such as temperature] beyond the next few decades.’

Can Australia become a more active global partner on emissions?

Australia accounts for just over one per cent of global emissions, so reducing domestic emissions – even though on a per capita basis they are the highest in the world – will not reduce Australia’s climate risk. Showing international leadership and supporting a powerful coalition of the willing to tackle climate change is the only way ahead. By showing a willingness to adopt climate ambition, Australia can help more constructive worldwide action, and thereby reduce its own risk exposure. 

Leading by example is a politically difficult issue for Australia. Prime Minister Scott Morrison was re-elected in May 2019 on an economic stability platform, and a promise not to imperil employment growth through climate action. Australia has contested UN estimates that it will not meet its existing modest goals for domestic emissions, by seeking to rely on carryover credits from action under the Kyoto Protocol as proof of progress.

It has also distanced itself from concerns over global supply and demand in fossil fuels. Australia remains a global supplier for fossil fuels, including coal – the nation’s coal exports accounted for $67 billion in revenues in 2019 in an expanding but changing Asian market, supplying ‘some of the cheapest electricity in the world’.

Possible influencers of change

With Australians experiencing first-hand the risks of climate change, there is already pressure to do more. Many are sceptical this will translate into domestic targets or export policies that give Australia the moral authority to ask for more action on the global stage.

Here, diverse groups who share a common interest in seeing Australia recover from the bushfires and address future climate risks could be key.

Importantly this includes rural and urban-fringe communities affected by the bushfires. They were part of Morrison’s traditional supporter-base but are angry at the government’s handling of the crisis and increasingly see how tiptoeing around emissions (including exports) has also ‘buried’ open discussion at home on climate-readiness.

Australian states could also find themselves taking a lead role. Virtually all jurisdictions have now committed to their own goals, most based on zero-carbon goals by 2050 (as has New Zealand). These can support modelling for Australia’s energy transition from coal, through gas, to market competitive renewables, while also help to ensure this reflects community expectations on jobs, electricity prices and other costs. 

Other emerging voices include the insurance and banking sectors (the Reserve Bank of Australia warned of the long-term financial stability risks of climate change before the fires) and indigenous Australians (one group of Torres Strait Islanders have filed a complaint to the UN Human Rights Committee which, if heard, will place Australia’s emissions record under the spotlight again). Their challenge now is finding a common language on what a cohesive approach to addressing climate change risk looks like. 

The international picture is mixed. The United States’ poor federal climate policy is a buffer for Australia. French President Emmanuel Macron has tried to raise the cost of inaction for Australia in current EU–Australia trade negotiations, but many large emitters in the Indo-Pacific region remain key Australian trading partners, investors and buyers of Australian coal. 

In the meantime, the United Kingdom is preparing for the meeting of parties to the Paris Agreement in Glasgow in November. A key global event following Brexit, the UK will no doubt be hoping to encourage a leadership circle with national commitments that meet global need to make the Glasgow meeting a success.

The UK public has expressed enormous sympathy for Australia in the bushfires and outrage over ‘climate denialism.’ Australia’s experience will be a cautionary tale of the effects of climate change at the meeting. Could the UK also support Australia to become a less reluctant partner in global climate action?




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Healthcare comes to standstill in east Aleppo as last hospitals are destroyed




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State and Local Labor Standards Enforcement in Immigrant-Dense Industries

Marking the release of an MPI report, this discussion focuses on the dynamics in low-wage workplaces and immigration law that have contributed to systematic violations of labor standards and explores new and effective enforcement strategies that state and local governments across the United States are utilizing.




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State and Local Labor Standards Enforcement in Immigrant-Dense Industries

This discussion, featuring California's Labor Commissioner and the head of the Tennessee Bureau of Workers' Compensation, launched a report that examines state innovations in labor standards enforcement in low-wage, immigrant-dense industries. With wage underpayment, payroll fraud, and other violations widespread in industries such as construction and car-washing, the discussion focused on how targeted enforcement can deter practices that hurt native-born and immigrant workers alike, cost state tax revenue, and disadvantage law-abiding employers. 




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Labor Migration from Myanmar: Remittances, Reforms, and Challenges

Having emerged from a long era of military rule, Myanmar's leaders and many citizens are looking outward. In particular, with Burmese labor migration abroad on the rise, policymakers are examining ways in which to harness remittances as a vehicle for economic development, particularly in impoverished rural areas. This article explores Burmese labor migration flows, financial reforms, and challenges on migration and development.




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Understanding the Policy Context for Migrant Return and Reintegration

In advance of the December 2018 adoption of the Global Compact for Safe, Orderly, and Regular Migration and its commitment to facilitate the return, readmission, and reintegration of migrants, this webinar examines the policies, practices, and contextual factors that make compulsory returns such a difficult issue for international cooperation, and the programs that are being implemented to make reintegration of returnees sustainable.




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Afghanistan: Displacement Challenges in a Country on the Move

Nearly 6 million Afghans fled after violence erupted in the late 1970s, primarily to Iran and Pakistan. While millions returned after the collapse of the Taliban in 2001, the security situation has since deteriorated and the government struggles to meet the needs of vulnerable populations, particularly the internally displaced. This country profile explores Afghanistan’s complex migration and displacement history as well as ongoing challenges.




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La Situación de Cambio Constante entre EE UU y México: Tendencias y Políticas de Migración, Incluyendo Menores No Acompañados

Una llamada en español que analiza las dinámicas cambiantes y las cuestiones políticas relacionadas con la migración a través de México a los Estados Unidos.




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La Situación de Cambio Constante entre EE UU y México: Tendencias y Políticas de Migración, Incluyendo Menores No Acompañados

Durante este seminario, ponentes presentaron hallazgos de un reciente informe que utiliza datos de agencias gubernamentales mexicanas, entrevistas con funcionarios clave y relatos de la sociedad civil para examinar el marco legal para la protección de menores no acompañados y su aplicación, al igual que las brechas entre este marco y su aplicación durante los procesos de detención, interrogación y alojamiento. El presidente de MPI, Andrew Selee, también expuso cómo el cambio en la dinámica política en Estados Unidos puede afectar las cuestiones migratorias con México, así como los efectos en la relación bilateral en medio de tensiones sobre el muro fronterizo, la renegociación del acuerdo del TLCAN y una cifra significativa de repatriaciones de migrantes mexicanos.




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Social Distancing

Social Distancing (date: 5/9/2020 - Rank: 6)




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Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

RESEARCH DESIGN AND METHODS

We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK).

RESULTS

Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively.

CONCLUSIONS

Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.




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Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease--A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V

OBJECTIVE

Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects.

RESEARCH DESIGN AND METHODS

The European Society of Cardiology’s European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016–2017) included 8,261 CAD patients, aged 18–80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated.

RESULTS

A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium–glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small.

CONCLUSIONS

Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.




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Treatment Approach to Patients With Severe Insulin Resistance

Timothy J. Church
Apr 1, 2016; 34:97-104
Feature Articles




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Standards of Medical Care in Diabetes--2018 Abridged for Primary Care Providers

American Diabetes Association
Jan 1, 2018; 36:14-37
Position Statements




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Standards of Medical Care in Diabetes--2019 Abridged for Primary Care Providers

American Diabetes Association
Jan 1, 2019; 37:11-34
Position Statements




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Standards of Medical Care in Diabetes--2020 Abridged for Primary Care Providers

American Diabetes Association
Jan 1, 2020; 38:10-38
Standards of Care




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Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland

OBJECTIVE

To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications.

RESEARCH DESIGN AND METHODS

We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications.

RESULTS

The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21–1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37–2.03]), and worse renal function (1.96 [1.03–3.74] for estimated glomerular filtration rate levels <30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66–0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78–2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications.

CONCLUSIONS

Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.




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Loss of Incretin Effect Is a Specific, Important, and Early Characteristic of Type 2 Diabetes

Jens J. Holst
May 1, 2011; 34:S251-S257
Diabetes Treatments




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National Standards for Diabetes Self-Management Education and Support

Linda Haas
Jan 1, 2014; 37:S144-S153
National Standards




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Consensus Development Conference on Insulin Resistance: 5-6 November 1997

American Diabetes Association
Feb 1, 1998; 21:310-314
Consensus Development Conference Report




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Breaking Up Prolonged Sitting With Standing or Walking Attenuates the Postprandial Metabolic Response in Postmenopausal Women: A Randomized Acute Study

Joseph Henson
Jan 1, 2016; 39:130-138
IDF-ADA Translational Symposium




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Acute Effects of Insulin in the Control of VLDL Production in Humans: Implications for the insulin-resistant state

Gary F Lewis
Apr 1, 1996; 19:390-393
Symposium On Insulin Resistance




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Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endo

Gina Agiostratidou
Dec 1, 2017; 40:1622-1630
Continuous Glucose Monitoring and Risk of Hypoglycemia




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Psychological Insulin Resistance in Patients With Type 2 Diabetes: The scope of the problem

William H. Polonsky
Oct 1, 2005; 28:2543-2545
BR Epidemiology/Health Services/Psychosocial Research




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India police: Security forces kill top militant commander in Kashmir

Police in India said security forces killed a top Hizbul Mujahideen commander amid a series of gunfights in the disputed Jammu and Kashmir region on Wednesday.




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Israeli High Court permits Benjamin Netanyahu to form government despite indictments

A panel of 11 judges ruled that Israeli Prime Minister Benjamin Netanyahu can form a government after reaching a deal with rival Benny Gantz.




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Professional Practice Committee: Standards of Medical Care in Diabetes--2019


Jan 1, 2019; 42:S3-S3
Professional Practice Committee




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Disclosures: Standards of Medical Care in Diabetes--2020


Jan 1, 2020; 43:S205-S206
Disclosures




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2017 National Standards for Diabetes Self-Management Education and Support

Joni Beck
Oct 1, 2017; 40:1409-1419
National Standards




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Professional Practice Committee: Standards of Medical Care in Diabetes--2020


Jan 1, 2020; 43:S3-S3
Professional Practice Committee




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Steroid Metabolomic Signature of Insulin Resistance in Childhood Obesity

OBJECTIVE

On the basis of urinary steroidal gas chromatography-mass spectrometry (GC-MS), we previously defined a novel concept of a disease-specific "steroid metabolomic signature" and reclassified childhood obesity into five groups with distinctive signatures. The objective of the current study was to delineate the steroidal signature of insulin resistance (IR) in obese children.

RESEARCH DESIGN AND METHODS

Urinary samples of 87 children (44 girls) aged 8.5–17.9 years with obesity (BMI >97th percentile) were quantified for 31 steroid metabolites by GC-MS. Defined as HOMA-IR >95th percentile and fasting glucose-to-insulin ratio >0.3, IR was diagnosed in 20 (of 87 [23%]) of the examined patients. The steroidal fingerprints of subjects with IR were compared with those of obese children without IR (non-IR). The steroidal signature of IR was created from the product of IR – non-IR for each of the 31 steroids.

RESULTS

IR and non-IR groups of children had comparable mean age (13.7 ± 1.9 and 14.6 ± 2.4 years, respectively) and z score BMI (2.7 ± 0.5 and 2.7 ± 0.5, respectively). The steroidal signature of IR was characterized by high adrenal androgens, glucocorticoids, and mineralocorticoid metabolites; higher 5α-reductase (An/Et) (P = 0.007) and 21-hydroxylase [(THE + THF + αTHF)/PT] activity (P = 0.006); and lower 11βHSD1 [(THF + αTHF)/THE] activity (P = 0.012).

CONCLUSIONS

The steroidal metabolomic signature of IR in obese children is characterized by enhanced secretion of steroids from all three adrenal pathways. As only the fasciculata and reticularis are stimulated by ACTH, these findings suggest that IR directly affects the adrenals. We suggest a vicious cycle model, whereby glucocorticoids induce IR, which could further stimulate steroidogenesis, even directly. We do not know whether obese children with IR and the new signature may benefit from amelioration of their hyperadrenalism.




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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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Leukocyte Telomere Length, DNA Oxidation, and Risk of Lower-Extremity Amputation in Patients With Long-standing Type 1 Diabetes

OBJECTIVE

Telomere shortening and DNA oxidation are associated with premature vascular aging, which may be involved in lower-extremity amputation (LEA). We sought to investigate whether leukocyte telomere length (LTL) and plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation, were associated with LEA in subjects with type 1 diabetes at high vascular risk.

RESEARCH DESIGN AND METHODS

LTL (quantitative PCR) and plasma 8-OHdG concentrations (immunoassay method) were assessed at baseline in the GENEDIAB (Génétique de la Néphropathie Diabétique) type 1 diabetes cohort. Logistic and Cox proportional hazards regression models were fitted to estimate odds ratio (OR) (at baseline) and hazard ratio (HR) (during follow-up), with related 95% CI, by increasing biomarker tertiles (T1, T2, T3).

RESULTS

Among 478 participants (56% male, mean ± SD age 45 ± 12 years and diabetes duration 29 ± 10 years), 84 patients had LEA at baseline. Baseline history of LEA was associated with shorter LTL (OR for T2 vs. T1 0.62 [95% CI 0.32–1.22] and for T3 vs. T1 0.41 [0.20–0.84]) but not with plasma 8-OHdG (1.16 [0.56–2.39] and 1.24 [0.61–2.55], respectively). New cases of LEA occurred in 34 (12.3%) participants during the 10-year follow-up. LTL were shorter (HR T2 vs. T1 0.25 [95% CI 0.08–0.67] and T3 vs. T1 0.29 [0.10–0.77]) and plasma 8-OHdG higher (2.20 [0.76–7.35] and 3.11 [1.07–10.32]) in participants who developed LEA during follow-up compared with others. No significant interaction was observed between biomarkers on their association with LEA.

CONCLUSIONS

We report the first independent association between LTL shortening and excess risk of LEA in type 1 diabetes. High plasma 8-OHdG was also associated with incident LEA but partly dependent on cofounding variables.




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New ADA standard, technical report available for comment by Feb. 17

The American Dental Association Standards Committee on Dental Informatics has approved two documents for circulation and comment.




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ADA standards committees invite interested parties to upcoming meetings

Those interested in developing dental standards that ensure product safety and efficacy and offer useful information on new and emerging technologies can attend upcoming meetings of the American Dental Association's standards committees.




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ADA standard on treating biofilm in waterlines available for comment

The American Dental Association Standards Committee on Dental Products has approved the document for circulation and comment.