Severity: Warning
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Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: models/Detail_model.php
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Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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Line: 143
Function: file_get_contents
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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File: /var/www/html/application/controllers/Detail.php
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Objective: Observations of a metabolically unhealthy normal weight phenotype suggest that a lack of favorable adiposity contributes to an increased risk of type 2 diabetes. We aimed to identify causal blood biomarkers linking favorable adiposity with type 2 diabetes risk for use in cardiometabolic risk assessments.
Research Design And Methods: A weighted polygenic risk score (PRS) underpinning metabolically favorable adiposity was validated in the UK Biobank ( = 341,872) and the Outcome Reduction With Initial Glargine Intervention (ORIGIN Trial) ( = 8,197) and tested for association with 238 blood biomarkers. Associated biomarkers were investigated for causation with type 2 diabetes risk using Mendelian randomization and for its performance in predictive models for incident major adverse cardiovascular events (MACE).
Results: Of the 238 biomarkers tested, only insulin-like growth factor-binding protein (IGFBP)-3 concentration was associated with the PRS, where a 1 unit increase in PRS predicted a 0.28-SD decrease in IGFBP-3 blood levels ( < 0.05/238). Higher IGFBP-3 levels causally increased type 2 diabetes risk (odds ratio 1.26 per 1 SD genetically determined IGFBP-3 level [95% CI 1.11-1.43]) and predicted a higher incidence of MACE (hazard ratio 1.13 per 1 SD IGFBP-3 concentration [95% CI 1.07-1.20]). Adding IGFBP-3 concentrations to the standard clinical assessment of metabolic health enhanced the prediction of incident MACE, with a net reclassification improvement of 11.5% in normal weight individuals ( = 0.004).
Conclusions: We identified IGFBP-3 as a novel biomarker linking a lack of favorable adiposity with type 2 diabetes risk and a predictive marker for incident cardiovascular events. Using IGFBP-3 blood concentrations may improve the risk assessment of cardiometabolic diseases.
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Source |
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http://dx.doi.org/10.2337/dc18-2444 | DOI Listing |
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