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  1. Article ; Online: Diabetic kidney disease 2.0: the treatment paradigm shifts.

    Gilbert, Richard E

    The lancet. Diabetes & endocrinology

    2019  Volume 7, Issue 11, Page(s) 820–821

    MeSH term(s) Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Humans ; Renal Insufficiency ; Sodium-Glucose Transporter 2 Inhibitors
    Chemical Substances Sodium-Glucose Transporter 2 Inhibitors
    Language English
    Publishing date 2019-09-05
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2213-8595
    ISSN (online) 2213-8595
    DOI 10.1016/S2213-8587(19)30253-0
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  2. Article ; Online: Finerenone in diabetic kidney disease - So far, so good.

    Gilbert, Richard E

    Journal of diabetes and its complications

    2017  Volume 31, Issue 4, Page(s) 651–652

    MeSH term(s) Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Heart Failure ; Humans ; Naphthyridines
    Chemical Substances Naphthyridines ; finerenone
    Language English
    Publishing date 2017-01-20
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1105840-7
    ISSN 1873-460X ; 1056-8727
    ISSN (online) 1873-460X
    ISSN 1056-8727
    DOI 10.1016/j.jdiacomp.2016.12.012
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  3. Article: Neurophysiological and Autonomic Dynamics of Threat Processing During Sustained Social Fear Generalization.

    Pouliot, Jourdan J / Ward, Richard T / Traiser, Caitlin M / Chiasson, Payton / Gilbert, Faith E / Keil, Andreas

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Survival in rapidly changing environments requires that organisms learn to predict noxious outcomes based on situational cues. One key facet of successful threat prediction is generalization from a specific predictive cue to similar cues, ensuring that a ...

    Abstract Survival in rapidly changing environments requires that organisms learn to predict noxious outcomes based on situational cues. One key facet of successful threat prediction is generalization from a specific predictive cue to similar cues, ensuring that a cue-outcome contingency is applied beyond the original learning environment. Generalization has also been observed in laboratory studies of human aversive conditioning: Most behavioral and physiological processes generalize responses from a stimulus paired with threat, (the CS+), to unpaired stimuli, with response magnitudes varying as a function of stimulus similarity. In contrast, work focusing on sensory responses in visual cortex has found a sharpening pattern, in which responses to stimuli closely resembling the CS+ are maximally suppressed, potentially reflecting lateral inhibitory interactions with the CS+ representation. Originally demonstrated with simple visual cues, changes in visuocortical tuning have also been observed in threat generalization learning across facial identity cues. It is however unclear to what extent these visuocortical changes represent transient or sustained effects and if generalization learning requires prior conditioning to the CS+. The present study addressed these questions using EEG and pupillometry in a paradigm involving several hundreds of trials of aversive generalization learning along a gradient of facial identities. Visuocortical ssVEP sharpening occurred after dozens of trials of generalization learning without prior differential conditioning, but diminished as learning progressed further. By contrast, generalization of EEG alpha power suppression, pupil dilation, and self-reported valence and arousal ratings was seen throughout the experimental session. Findings are consistent with models of threat processing emphasizing the role of changing visucocortical and attention dynamics in the formation, curation, and shaping of fear memories as observers continue learning about stimulus-outcome contingencies.
    Language English
    Publishing date 2024-04-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.16.589830
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  4. Article ; Online: SGLT2 inhibitors: β blockers for the kidney?

    Gilbert, Richard E

    The lancet. Diabetes & endocrinology

    2016  Volume 4, Issue 10, Page(s) 814

    Language English
    Publishing date 2016-10
    Publishing country England
    Document type Letter
    ISSN 2213-8595
    ISSN (online) 2213-8595
    DOI 10.1016/S2213-8587(16)30237-6
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  5. Article ; Online: Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease.

    Gilbert, Richard E

    Diabetes

    2017  Volume 66, Issue 4, Page(s) 791–800

    Abstract: The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great ... ...

    Abstract The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of renal prognosis in diabetes and may not be the primary event in the development of diabetic kidney disease either. Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current "glomerulocentric" paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state. Such findings raise important issues for therapeutic advances specifically targeting the pathophysiological perturbations that develop in this part of the nephron.
    MeSH term(s) Apoptosis ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/physiopathology ; Disease Progression ; Fibrosis ; Humans ; Hypoxia/metabolism ; Hypoxia/physiopathology ; Ischemia/metabolism ; Ischemia/physiopathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/physiopathology ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/physiopathology ; Mitochondria/metabolism ; Oxygen Consumption ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology
    Language English
    Publishing date 2017-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db16-0796
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    Uh III Zs.175: Show issues Location:
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  6. Article: GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials.

    Gilbert, Matthew P / Pratley, Richard E

    Frontiers in endocrinology

    2020  Volume 11, Page(s) 178

    Abstract: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in response to the presence of nutrients in the small intestines. These homones facilitate glucose ... ...

    Abstract The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in response to the presence of nutrients in the small intestines. These homones facilitate glucose regulation by stimulating insulin secretion in a glucose dependent manner while suppressing glucagon secretion. In patients with type 2 diabetes (T2DM), an impaired insulin response to GLP-1 and GIP contributes to hyperglycemia. Dipeptidyl peptidase-4 (DPP-4) inhibitors block the breakdown of GLP-1 and GIP to increase levels of the active hormones. In clinical trials, DPP-4 inhibitors have a modest impact on glycemic control. They are generally well-tolerated, weight neutral and do not increase the risk of hypoglycemia. GLP-1 receptor agonists (GLP-1 RA) are peptide derivatives of either exendin-4 or human GLP-1 designed to resist the activity of DPP-4 and therefore, have a prolonged half-life. In clinical trials, they have demonstrated superior efficacy to many oral antihyperglycemic drugs, improved weight loss and a low risk of hypoglycemia. However, GI adverse events, particularly nausea, vomiting, and diarrhea are seen. Both DPP-4 inhibitors and GLP-1 RAs have demonstrated safety in robust cardiovascular outcome trials, while several GLP-1 RAs have been shown to significantly reduce the risk of major adverse cardiovascular events in persons with T2DM with pre-existing cardiovascular disease (CVD). Several clinical trials have directly compared the efficacy and safety of DPP-4 inhibitors and GLP-1 RAs. These studies have generally demonstrated that the GLP-1 RA provided superior glycemic control and weight loss relative to the DPP-4 inhibitor. Both treatments were associated with a low and comparable incidence of hypoglycemia, but treatment with GLP-1 RAs were invariably associated with a higher incidence of GI adverse events. A few studies have evaluated switching patients from DPP-4 inhibitors to a GLP-1RA and, as expected, improved glycemic control and weight loss are seen following the switch. According to current clinical guidelines, GLP-1RA and DPP-4 inhibitors are both indicated for the glycemic management of patients with T2DM across the spectrum of disease. GLP-1RA may be preferred over DPP- 4 inhibitors for many patients because of the greater reductions in hemoglobin A1c and weight loss observed in the clinical trials. Among patients with preexisting CVD, GLP-1 receptor agonists with a proven cardiovascular benefit are indicated as add-on to metformin therapy.
    MeSH term(s) Clinical Trials as Topic/methods ; Clinical Trials as Topic/statistics & numerical data ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Glucagon-Like Peptide 1/analogs & derivatives ; Glucagon-Like Peptide 1/therapeutic use ; Humans ; Hypoglycemic Agents/therapeutic use
    Chemical Substances Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemic Agents ; Glucagon-Like Peptide 1 (89750-14-1)
    Language English
    Publishing date 2020-04-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2020.00178
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  7. Article ; Online: Acute kidney injury with sodium-glucose co-transporter-2 inhibitors: A meta-analysis of cardiovascular outcome trials.

    Gilbert, Richard E / Thorpe, Kevin E

    Diabetes, obesity & metabolism

    2019  Volume 21, Issue 8, Page(s) 1996–2000

    Abstract: Three, multicentre, large-scale, randomized, placebo-controlled trials of cardiovascular outcomes with sodium-glucose co-transporter-2 (SGLT2) inhibitors have each shown substantial reductions in rates of hospitalization for heart failure and progression ...

    Abstract Three, multicentre, large-scale, randomized, placebo-controlled trials of cardiovascular outcomes with sodium-glucose co-transporter-2 (SGLT2) inhibitors have each shown substantial reductions in rates of hospitalization for heart failure and progression of chronic kidney disease in people with type 2 diabetes. However, safety concerns remain for this ostensibly paradigm-shifting drug class. In particular, the US Food and Drug Administration has highlighted the risk of acute kidney injury (AKI), a condition associated with high morbidity and mortality. To investigate this further, we conducted a meta-analysis of the three trials to compare the frequency of AKI adverse event reports between participants treated with placebo and those who had received an SGLT2 inhibitor. Rather than an increase, we noted a consistent and robust reduction in the likelihood of AKI among those participants who had been randomized to receive an SGLT2 inhibitor (hazard ratio 0.66, 95% confidence interval 0.54-0.80). We further noted that the reports of AKI were similar in frequency to those of kidney disease progression. The caveats of the non-adjudicated reporting of AKI in the trials notwithstanding, these data suggest that SGLT2 inhibitors may protect vulnerable patients with type 2 diabetes from AKI and that prospective studies to evaluate this additional aspect of kidney protection are warranted.
    MeSH term(s) Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acute Kidney Injury/chemically induced ; Diabetes Mellitus, Type 2/drug therapy ; Hypoglycemic Agents/adverse effects ; Kidney/drug effects ; Proportional Hazards Models ; Randomized Controlled Trials as Topic ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Multicenter Studies as Topic
    Chemical Substances Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors
    Language English
    Publishing date 2019-05-24
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 1454944-x
    ISSN 1463-1326 ; 1462-8902
    ISSN (online) 1463-1326
    ISSN 1462-8902
    DOI 10.1111/dom.13754
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5442: Show issues Location:
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  8. Article ; Online: Heart failure: fatal, forgotten, and frequent in type 1 diabetes too.

    Gilbert, Richard E

    The lancet. Diabetes & endocrinology

    2015  Volume 3, Issue 11, Page(s) 832–834

    MeSH term(s) Diabetes Mellitus, Type 1/epidemiology ; Female ; Heart Failure/epidemiology ; Humans ; Male
    Language English
    Publishing date 2015-11
    Publishing country England
    Document type Comment ; Journal Article
    ISSN 2213-8595
    ISSN (online) 2213-8595
    DOI 10.1016/S2213-8587(15)00329-0
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  9. Article ; Online: Reduction in the incidence of myocardial infarction with sodium-glucose linked cotransporter-2 inhibitors: evident and plausible.

    Gilbert, Richard E / Connelly, Kim A

    Cardiovascular diabetology

    2019  Volume 18, Issue 1, Page(s) 6

    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/metabolism ; Evidence-Based Medicine ; Humans ; Incidence ; Myocardial Infarction/epidemiology ; Myocardial Infarction/metabolism ; Myocardial Infarction/prevention & control ; Protective Factors ; Risk Assessment ; Risk Factors ; Sodium-Glucose Transporter 2/drug effects ; Sodium-Glucose Transporter 2/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Treatment Outcome
    Chemical Substances SLC5A2 protein, human ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors
    Language English
    Publishing date 2019-01-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2093769-6
    ISSN 1475-2840 ; 1475-2840
    ISSN (online) 1475-2840
    ISSN 1475-2840
    DOI 10.1186/s12933-019-0812-6
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  10. Article ; Online: Preconception SGLT2 or DPP4 inhibitor use and adverse pregnancy outcomes.

    Ray, Joel G / Harel, Ziv / Gilbert, Richard E / Wald, Ron / Berger, Howard / Park, Alison L

    Diabetes research and clinical practice

    2023  Volume 205, Page(s) 110946

    Abstract: Aims: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies.!# ...

    Abstract Aims: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies.
    Methods: This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly - the latter two outcomes assessed using propensity score overlap weighting.
    Results: The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents.
    Conclusions: Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis.
    MeSH term(s) Infant, Newborn ; Pregnancy ; Female ; Humans ; Dipeptidyl-Peptidase IV Inhibitors/adverse effects ; Cohort Studies ; Diabetes Mellitus, Type 2/drug therapy ; Glycated Hemoglobin ; Pregnancy Outcome ; Sodium-Glucose Transporter 2/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Hypoglycemic Agents/therapeutic use ; Sulfonylurea Compounds/therapeutic use ; Retrospective Studies
    Chemical Substances Dipeptidyl-Peptidase IV Inhibitors ; Glycated Hemoglobin ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Hypoglycemic Agents ; Sulfonylurea Compounds
    Language English
    Publishing date 2023-10-07
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 632523-3
    ISSN 1872-8227 ; 0168-8227
    ISSN (online) 1872-8227
    ISSN 0168-8227
    DOI 10.1016/j.diabres.2023.110946
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    Zs.A 2047: Show issues Location:
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