SynthesisPloS one2014

Lower intensified target LDL-c level of statin therapy results in a higher risk of incident diabetes: a meta-analysis.

Rongrong Cai, Yang Yuan, Yi Zhou, Wenqing Xia, Pin Wang, Haixia Sun, Yue Yang, Rong Huang, Shaohua Wang

Open access · goldFull text readMeta-Analysis
In one paragraph

Synthesis in PloS one, 2014. The graph read 3 numbers from its abstract, feeding 1 cell of the map: it finds no clear difference in 1. Cited by 19 papers, 1 of them a synthesis that pooled it.

3numbers the graph read from it
1cell of the map it votes in
19citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the comparatorfavours the treatment →
1 · no effect
Lipidsfavours the treatment · against placebo · dyslipidemia, t2dfeeds one cell of the map
OR 1.331.14 to 1.56
A noticeable effect of statin therapy on new-onset diabetes was observed when their intensified target LDL-c level was lower than 1.8 mmol/L (OR 1.33, 95% CI 1.14 to 1.56; I 2 = 7.7%) and within 1.8 mmol/L to 2.59 mmol/L (OR 1.16, 95% CI 1.06 to 1.28; I 2 = 0.0%) (Figure 2).
Lipidsno clear difference · against placebo · dyslipidemia, t2dfeeds one cell of the map
OR 0.990.89 to 1.11
In the combined data set, no clear association was found between standard LDL-c lowering with statin therapy and incident diabetes compared with placebo or standard care control therapy (OR 0.99, 95% CI 0.89 to 1.11) (Figure 3).
Lipidsno clear difference · against placebo · dyslipidemia, t2dfeeds one cell of the map
OR 0.950.83 to 1.08
For analysis that targets LDL-c higher than 2.59 mmol/L, the result restricted to placebo-controlled trials (OR 0.95, 95% CI 0.83 to 1.08, I 2 = 0%), and the result without ALLHAT-LLT for its biggest weight (OR 0.97, 0.87 to 1.07, I 2 = 0%) was similar to the primary analysis.

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Statins×lipids

InconclusiveOpen on the map →What to test next →

38 readable studies in this cell: 26 favour the treatment, 5 find no difference, 7 favour the comparator.

Belief with this paper
0.50contested · 21 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ -13.2-16.8 to -9.60
reduced -66.0-73.0 to -58.0
NCT02546323543 enrolled · 2015
Δ -35.5-40.2 to -30.7
NCT01678820299 enrolled · 2012
Δ 0.50-4.80 to 5.80
NCT01218204287 enrolled · 2010
Δ 5.47-15.7 to 26.7
NCT0093525931 enrolled · 2009
Δ -51.7
reductions -33.6-38.8 to -28.4

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Statin Use and Hyperglycemia: Do Statins Cause Diabetes?Current atherosclerosis reports · 2024
    Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Diabetic dyslipidaemia.Practical laboratory medicine · 2021
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Diabetogenic Action of Statins: Mechanisms.Current atherosclerosis reports · 2019
    Review
  17. Article
  18. Review
  19. Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Rongrong CaiDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Yang YuanDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Yi ZhouDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Wenqing XiaDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Pin WangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Haixia SunDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Yue YangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Rong HuangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Shaohua WangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.
Zhongda Hospital Southeast University · CN

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundA recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. However, doubling of the statin dose generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL-c) on average. This study aimed to determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes.

methodsMedline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials of statins conducted from 1966 to 2012. We included trials with more than 1000 participants who were followed up for at least 2 years. The included trials were stratified by the target LDL-c level. I2 statistic was used to measure heterogeneity between trials. We further calculated risk estimates with random-effect meta-analysis. Meta-regression was used to identify the potential risk factors of statin-induced diabetes.

resultsFourteen trials with a total of 95 102 non-diabetic participants were included. The risks elevated by 33% [odds ratio (OR)  = 1.33; 95% confidence interval (CI) 1.14-1.56; I(2) = 7.7%] and 16% (OR = 1.16; 95% CI 1.06-1.28; I(2)= 0.0%) when the intensified target LDL-c levels were ≤ 1.8 mmol/L and 1.8-2.59 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level was ≥ 2.59 mmol/L. Apart from age, female, and baseline level of total cholesterol, meta-regression analysis showed that the target and baseline levels of LDL-c and relative LDL-c reduction were predictors of statin-induced diabetes.

conclusionA lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes.

Indexed as

Cholesterol, LDLDiabetes MellitusHumansHydroxymethylglutaryl-CoA Reductase InhibitorsRisk FactorsCholesterol, LDLHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID25122464
PMCPMC4133238
OpenAlexW2081050005

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.