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Original investigation
Xianhui Qin
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7812-7982
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.
Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG <6.1mmol/L at baseline and ≥6.1 but <7.0mmol/L at the exit visit.
Results: Over a median of 4.5 years follow-up, 1,549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95%CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95%CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) <10μmol/L (adjusted OR, 1.24; 95%CI: 1.10, 1.40 vs. ≥10μmol/L: adjusted OR, 1.03; 95%CI: 0.96, 1.10; P-interaction=0.007) or FG ≥5.9mmol/L (adjusted OR, 1.16; 95%CI: 1.07, 1.27 vs. <5.9mmol/L: adjusted OR, 1.00; 95%CI: 0.93, 1.08; P-interaction =0.009)
Conclusions: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.
Clinical Trial Registration-URL: Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
Keywords
Alkaline phosphatase, New-onset diabetes, New-onset impaired fasting glucose, Total homocysteine, Hypertension
Figure 1
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile10824.docx
Additional file 1: Figure S1. Flow chart of the participants Figure S2. The association between baseline alkaline phosphatase (ALP) and new-onset diabetes in normal ALP levels (20-140 IU/L) Table S1. Concomitant medication usage during the treatment period by baseline serum alkaline phosphatase quartiles Table S2. The association between baseline serum alkaline phosphatase (ALP) and new-onset diabetes, with further adjustment for the use of calcium channel blockers, diuretics and antiplatelet drugs during the treatment period Table S3. The association between baseline serum alkaline phosphatase (ALP) and new-onset diabetes, with further adjustment for AST, ALT and GGT
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View the published article at Cardiovascular Diabetology.
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Editorial decision: Accept
On 14 Oct, 2020
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On 13 Oct, 2020
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On 13 Oct, 2020
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Received 05 Oct, 2020
Editorial decision: Major Revision
On 05 Oct, 2020
Review #1 received
Received 07 Sep, 2020
Reviewers invited
Invitations sent on 04 Sep, 2020
Reviewer #1 agreed
On 04 Sep, 2020
Reviewer #2 agreed
On 04 Sep, 2020
Editor assigned
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Editor invited
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A new preprint design is coming!
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See the published version of this preprint at Cardiovascular Diabetology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original investigation
Xianhui Qin
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7812-7982
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cardiovascular Diabetology.
Version 2
Posted 22 Oct, 2020
No community comments so far
Editor assigned
On 14 Oct, 2020
Editorial decision: Accept
On 14 Oct, 2020
Submission checks complete
On 13 Oct, 2020
Editor invited
On 13 Oct, 2020
No comments provided
Review #2 received
Received 05 Oct, 2020
Editorial decision: Major Revision
On 05 Oct, 2020
Review #1 received
Received 07 Sep, 2020
Reviewers invited
Invitations sent on 04 Sep, 2020
Reviewer #1 agreed
On 04 Sep, 2020
Reviewer #2 agreed
On 04 Sep, 2020
Editor assigned
On 03 Sep, 2020
Editor invited
On 02 Sep, 2020
Submission checks complete
On 30 Aug, 2020
First submitted
On 24 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cardiovascular Diabetology.
Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.
Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG <6.1mmol/L at baseline and ≥6.1 but <7.0mmol/L at the exit visit.
Results: Over a median of 4.5 years follow-up, 1,549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95%CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95%CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) <10μmol/L (adjusted OR, 1.24; 95%CI: 1.10, 1.40 vs. ≥10μmol/L: adjusted OR, 1.03; 95%CI: 0.96, 1.10; P-interaction=0.007) or FG ≥5.9mmol/L (adjusted OR, 1.16; 95%CI: 1.07, 1.27 vs. <5.9mmol/L: adjusted OR, 1.00; 95%CI: 0.93, 1.08; P-interaction =0.009)
Conclusions: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.
Clinical Trial Registration-URL: Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile10824.docx
Additional file 1: Figure S1. Flow chart of the participants Figure S2. The association between baseline alkaline phosphatase (ALP) and new-onset diabetes in normal ALP levels (20-140 IU/L) Table S1. Concomitant medication usage during the treatment period by baseline serum alkaline phosphatase quartiles Table S2. The association between baseline serum alkaline phosphatase (ALP) and new-onset diabetes, with further adjustment for the use of calcium channel blockers, diuretics and antiplatelet drugs during the treatment period Table S3. The association between baseline serum alkaline phosphatase (ALP) and new-onset diabetes, with further adjustment for AST, ALT and GGT
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