Roger H Unger
Aug 1, 1995; 44:863-870
Perspectives in Diabetes

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

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

JC Henquin
Nov 1, 2000; 49:1751-1760
Articles

Michael Brownlee
Jun 1, 2005; 54:1615-1625
Banting Lecture 2004

PORT AU PRINCE, Haiti, CMC – The Ministry of Public Health has confirmed that a 20-year-old man has become the seventh person in Haiti to die of the coronavirus (COVID-19). It is urging the population to follow restriction measures, including...

HAMILTON, Bermuda, CMC –  Bermuda recorded its seventh COVID-19 death on Saturday as Finance Minister Curtis Dickinson announced that he would need to rewrite this year’s budget because of the battering from the global...

Parish Histories of Jamaica Project, a publication by the JN Foundation in collaboration with the Department of History and Archaeology at The University of the West Indies, Mona, was launched recently. Jenny Jemmott of Department of History and...

Schwann cell–derived exosomes communicate with dorsal root ganglia (DRG) neurons. The current study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on diabetic peripheral neuropathy (DPN). We found that intravenous administration of SC-Exos to type 2 diabetic db/db mice with peripheral neuropathy remarkably ameliorated DPN by improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity. These functional improvements were associated with the augmentation of epidermal nerve fibers and remyelination of sciatic nerves. Quantitative RT-PCR and Western blot analysis of sciatic nerve tissues showed that SC-Exo treatment reversed diabetes-reduced mature form of miRNA (miR)-21, -27a, and -146a and diabetes-increased semaphorin 6A (SEMA6A); Ras homolog gene family, member A (RhoA); phosphatase and tensin homolog (PTEN); and nuclear factor-B (NF-B). In vitro data showed that SC-Exos promoted neurite outgrowth of diabetic DRG neurons and migration of Schwann cells challenged by high glucose. Collectively, these novel data provide evidence that SC-Exos have a therapeutic effect on DPN in mice and suggest that SC-Exo modulation of miRs contributes to this therapy.

Diabetic retinopathy is the most common microvascular complication of diabetes, and in the advanced diabetic retinopathy appear vitreal fibrovascular membranes that consist of a variety of cells, including vascular endothelial cells (ECs). New therapeutic approaches for this diabetic complication are urgently needed. Here, we report that in cultured human retinal microvascular ECs, high glucose induced expression of p110, which was also expressed in ECs of fibrovascular membranes from patients with diabetes. This catalytic subunit of a receptor-regulated PI3K isoform is known to be highly enriched in leukocytes. Using genetic and pharmacological approaches, we show that p110 activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. Using a mouse model of oxygen-induced retinopathy, p110 inactivation was found to attenuate pathological retinal angiogenesis. p110 inhibitors have been approved for use in human B-cell malignancies. Our data suggest that antagonizing p110 constitutes a previously unappreciated therapeutic opportunity for diabetic retinopathy.

Diabetes triggers peripheral nerve alterations at a structural and functional level, collectively referred to as diabetic peripheral neuropathy (DPN). This work highlights the role of the liver X receptor (LXR) signaling pathway and the cross talk with the reactive oxygen species (ROS)–producing enzyme NADPH oxidase-4 (Nox4) in the pathogenesis of DPN. Using type 1 diabetic (T1DM) mouse models together with cultured Schwann cells (SCs) and skin biopsies from patients with type 2 diabetes (T2DM), we revealed the implication of LXR and Nox4 in the pathophysiology of DPN. T1DM animals exhibit neurophysiological defects and sensorimotor abnormalities paralleled by defective peripheral myelin gene expression. These alterations were concomitant with a significant reduction in LXR expression and increase in Nox4 expression and activity in SCs and peripheral nerves, which were further verified in skin biopsies of patients with T2DM. Moreover, targeted activation of LXR or specific inhibition of Nox4 in vivo and in vitro to attenuate diabetes-induced ROS production in SCs and peripheral nerves reverses functional alteration of the peripheral nerves and restores the homeostatic profiles of MPZ and PMP22. Taken together, our findings are the first to identify novel, key mediators in the pathogenesis of DPN and suggest that targeting LXR/Nox4 axis is a promising therapeutic approach.

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.

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H₂O₂) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H₂O₂ by high glucose, and H₂O₂ reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

Type 2 diabetes accounts for 90% of the population with diabetes, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. The aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of the population with type 2 diabetes and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed a 45% kcal as fat diet for 8 weeks before administering streptozotocin, 30 mg/kg body weight (T2D), and compared with age- and duration-matched type 1 diabetic rats (T1D) (60 mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared with age-matched T1D rats. While at 4 months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and Rac1 promoter DNA methylation was exacerbated. At 6 months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good lifestyle and BMI could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in patients with diabetes.

A rise in mortality is a price worth paying to restart the US economy, President Trump has said, as many states flout advice from scientists and reopen beaches, cinemas, or hair salons while new...

We aimed to assess the value of ¹¹C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on ^99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUV_max and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the ¹¹C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUV_max was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that ¹¹C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and ^99mTc-sestamibi imaging yield negative or discordant results.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging ¹⁸F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with ¹⁸F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of ^99mTc-sestamibi SPECT/CT, ^99mTc-sestamibi/pertechnetate subtraction imaging, and ^99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of ¹⁸F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: ¹⁸F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

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. SUV_max 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.

Type 1 diabetes is an autoimmune-mediated disease that culminates in the targeted destruction of insulin-producing β-cells. CD4 responses in NOD mice are dominated by insulin epitope B:9-23 (InsB_9-23) specificity, and mutation of the key T-cell receptor (TCR) contact residue within the epitope prevents diabetes development. However, it is not clear how insulin self-antigen controls the selection of autoimmune and regulatory T cells (Tregs). Here we demonstrate that mutation of insulin epitope results in escape of highly pathogenic T cells. We observe an increase in antigen reactivity, clonality, and pathogenicity of insulin-specific T cells that develop in the absence of cognate antigen. Using a single TCR system, we demonstrate that Treg development is greatly diminished in mice with the Y16A mutant epitope. Collectively, these results suggest that the tyrosine residue at position 16 is necessary to constrain TCR reactivity for InsB_9-23 by both limiting the development of pathogenic T cells and supporting the selection of Tregs.

Members Event

Event participants

Stephen Gethins, Candidate for Fife North East and Shadow Spokesperson for Foreign and Commonwealth Office (2018-19), Scottish National Party (remote)
Dominic Raab, Candidate for Esher & Walton, Foreign Secretary and First Secretary of State (2019), Conservative Party
Emily Thornberry, Candidate for Islington South & Finsbury and Shadow Foreign Secretary (2016-19), Labour Party
Chuka Umunna, Candidate for Cities of London & Westminster and Spokesperson for Foreign and Commonwealth Affairs (2019), Liberal Democrat Party
Chair: Ritula Shah, The World Tonight, BBC Radio 4
 

Research Event

With thousands more migrants potentially traveling through the Western Balkans this year, this MPI Europe webinar explores the implications of the buttressed EU border on the bloc’s neighbors, including the issues of outsourcing migration control, EU support for addressing irregular migration in neighboring countries, and considerations for EU policymakers.

With thousands migrants potentially traveling through the Western Balkans this year, this MPI Europe webinar explores the implications of the buttressed EU border on the bloc’s neighbors, the migrants transiting these routes, and the local communities. Experts also explored how the European Union can support efforts to address irregular migration in neighboring countries, and what are the tradeoffs and considerations that policymakers must weigh. 

Even as the 1.8 million number swirls in the discussion of how many DREAMers would be placed on a path to citizenship, proposals debated in the Senate in February 2018 would have resulted in the legalization of smaller numbers, as this commentary explains. It offers estimates of potential beneficiaries of several Senate proposals, including one backed by the White House, and analysis of key criteria.

In exchange for resolving the status of DREAMers, the White House and its congressional allies are demanding billions of dollars for a border wall and additional enforcement, sharp limits on asylum, cuts to legal immigration, and more. But what would the two bills expected to be voted on by the House do in terms of extending temporary or permanent status to DREAMers? This commentary offers estimates.

Although in many countries immigrants fill labor gaps in fields such as agriculture and construction, few legal migration pathways exist for low-skilled workers. As states meet to negotiate a Global Compact for Safe, Orderly, and Regular Migration, this policy brief takes stock of the channels available for such workers to move legally and take up work abroad, highlighting promising practices and policy gaps.

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development. 

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development.

The world’s first international agreement on migration was approved by 164 countries in December 2018, but not without turbulence. U.S. withdrawal from the nonbinding Global Compact on Safe, Orderly, and Regular Migration, on grounds it could impinge on sovereignty, triggered similar actions by others, particularly in Eastern Europe. Amid ongoing political ripple effects, attention now turns to implementation of the deal's goals.

Climate-related displacement is not hypothetical: An average of 21.5 million people per year have been displaced since 2008 by natural disasters, and thousands more have fled slow-onset environmental hazards. While migration can serve as a safety valve to adapt to changing conditions, few orderly, legal channels exist for climate migrants (also known as environmental migrants), as this article explores.

By Michael Pershan, St. Ann’s School I. What do primary/secondary math educators think of the teaching that happens in colleges? And — the other way around — what do mathematics professors think of primary and secondary math teaching? I’m nearing … Continue reading →

by Doug O’Roark Executive Director, Math Circles of Chicago The New York Times recently published an article entitled “The Right Answer? 8,186,699,633,530,061 (An Abacus Makes It Look Almost Easy)”. Its lead photograph features over 100 children seated at desks, facing … Continue reading →

By: Kristin Pfabe, Nebraska Wesleyan University “I am sad this class is going to be over,” said one student. “What am I going to do with myself?” asked another during the last week of an Intermediate Algebra class that I … Continue reading →

Vanessa J. Briscoe
Jul 1, 2006; 24:115-121
Feature Articles

Andrew J.M. Boulton
Jan 1, 2005; 23:9-15
Feature Articles

Warren Clayton
Mar 1, 2009; 27:52-58
Features

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.

A Florida TV station's weather radar detected a large mass between the state and Cuba that turned out to be something other than an unseasonable storm -- it was a flock of migrating birds.

Boris Draznin
Jul 1, 2013; 36:1807-1814
Perspectives in Care

Samy Suissa
Jan 1, 2018; 41:6-10
Perspectives in Care

TODAY Study Group
Jun 1, 2013; 36:1735-1741
TODAY Study

Mary M Tai
Feb 1, 1994; 17:152-154
Short Report

Catherine L. Martin
Jan 1, 2014; 37:31-38
DCCT/EDIC 30th Anniversary Summary Findings

Frederick S Fein
Nov 1, 1990; 13:1169-1179
Supplement 4: Diabetes 80 Black Populations: Current State of Knowledge

Henry N Ginsberg
Sep 1, 1991; 14:839-855
Diet and Diabetes