Study analysis · The Journal of Clinical Endocrinology and Metabolism · 2015
This stress hormone could be predicting your diabetes—before you even have high blood sugar.
Older men with high levels of a stress hormone called copeptin are nearly twice as likely to get type 2 diabetes over 13 years, even if their blood sugar looks normal right now.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
In simple terms
This study found that men with higher levels of a substance called copeptin were more likely to get diabetes later on, but it didn’t prove that copeptin causes diabetes. It’s like noticing that people who eat more ice cream also get more sunburns — they’re linked, but ice cream doesn’t cause sunburns.
What’s the bottom line?
Scientists found that older men with higher levels of a stress-related hormone called copeptin were more likely to get type 2 diabetes later, even if they didn’t have high blood sugar yet.
How strong is this study?
This study did a really good job tracking a lot of men for over 10 years and checking many health details, which makes the results trustworthy. But since they didn’t change anything on purpose (like giving people copeptin), we can’t be sure if copeptin itself is the problem — maybe something else, like stress, is causing both.
0 / 100
- COI disclosureconflicts of interest not disclosed
- Data availabilitydata not shared
- Code availabilitycode not shared
56 / 100
- Randomizationnot randomized
- Blindingblinding unclear
- Control group+15/15
- Sample size (n=3226)+20/20
- Follow-up+10/10
100 / 100
77 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervals+15/15
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 559 / 100
Probability of being correct
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
This design cannot establish causation — the findings describe an association, not a cause. This is an observational cohort study with no randomization or intervention; therefore, it can identify associations but cannot prove that copeptin causes diabetes due to potential confounding factors.
No Conflicts
No conflicts of interest identified
No conflicts of interest or funding disclosures were reported in the study text. The study appears to be independently conducted with no indication of industry influence.
The study lacks any declared funding source or conflict of interest statement. While this absence does not confirm independence, there is no evidence of industry involvement, author affiliations with commercial entities, or funder control over study design, analysis, or publication.
Key takeaways
- 01
Men with copeptin above 6.79 pmol/L had a 78% higher chance of getting diabetes over 13 years.
- 02
This dropped to 47% higher risk after accounting for insulin resistance.
- 03
Yes — even men with normal blood sugar and no kidney disease showed this link, suggesting copeptin may signal early metabolic stress before diabetes develops.
Surprising findings
- Copeptin was not correlated with fasting glucose or HbA1c, yet still predicted future diabetes.Everyone assumes blood sugar is the earliest warning sign—but this study shows a stress hormone rises before glucose does, suggesting a new early pathway.
- The link was stronger in men without impaired fasting glucose (IFG) than in those with it.You’d expect the hormone to matter most in people already showing pre-diabetes—but it mattered more in those with normal glucose, meaning it may signal the very earliest stage.
Practical takeaways
If you're a man over 60 with high stress, poor sleep, or abdominal fat, consider this a red flag—even if your blood sugar is normal.
Copeptin isn’t routinely tested, and this study doesn’t prove reducing copeptin will prevent diabetes. Lifestyle changes are still your best bet.
medium confidenceWhy this study matters
Copeptin = Early Warning Sign
Men with copeptin levels above 6.79 pmol/L had a 78% higher risk of developing type 2 diabetes over 13 years—even after adjusting for obesity, blood pressure, and inflammation. This link held even in men with normal fasting glucose.
Most people think diabetes is predicted by high blood sugar, but this shows a hidden biological stress signal can warn you years in advance—before glucose spikes.
It’s Not Just Insulin Resistance
Insulin resistance (measured by HOMA-IR) explained only 17% of the risk. Even after accounting for it, copeptin still predicted diabetes with a 47% higher risk (HR=1.47).
This suggests stress hormones like AVP might trigger diabetes through pathways beyond just insulin—like inflammation, blood vessel damage, or even kidney stress.
It Doesn’t Help Predict Diabetes—But Still Matters
Adding copeptin to standard risk models didn’t improve prediction accuracy—the C-statistic stayed at 0.779. So it’s not useful for screening, but it reveals a biological mechanism.
A biomarker can be scientifically important without being clinically useful. This is like finding a smoke detector that doesn’t save lives—but tells you the house is on fire.
Want the whole report?
Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Scientists found that older men with higher levels of a stress-related hormone called copeptin were more likely to get type 2 diabetes later, even if they didn’t have high blood sugar yet.
Research results
Men with copeptin above 6.79 pmol/L had a 78% higher chance of getting diabetes over 13 years. This dropped to 47% higher risk after accounting for insulin resistance.
What this means - more context
Yes — even men with normal blood sugar and no kidney disease showed this link, suggesting copeptin may signal early metabolic stress before diabetes develops.
To examine whether plasma copeptin levels predict incident type 2 diabetes in older men over 13 years, independent of traditional risk factors.
In 3,226 older men without diabetes, those in the top fifth of copeptin levels (>6.79 pmol/L) had a 78% higher risk of developing diabetes over 13 years, even after adjusting for waist circumference, blood pressure, triglycerides, and inflammation. This association was partially mediated by insulin resistance (HOMA-IR), which explained about 17% of the risk, but copeptin remained significantly associated even after adjusting for fasting glucose and HbA1c. Copeptin did not improve diabetes risk prediction beyond standard clinical models.
Methods Used
Prospective cohort study of 3,226 men aged 60–79 without diabetes, followed for a mean of 13 years. Plasma copeptin was measured at baseline using an ultrasensitive assay. Incident diabetes was identified via GP records and medical notes. Hazard ratios were calculated using Cox proportional hazards models, adjusting for metabolic, inflammatory, and renal markers.
Main Finding
Men with copeptin >6.79 pmol/L had a 78% higher risk of incident diabetes (HR = 1.78, 95% CI: 1.34–2.37) after adjustment for traditional risk factors; this dropped to HR = 1.47 (95% CI: 1.11–1.97) after adjusting for HOMA-IR, indicating partial mediation by insulin resistance.
Confidence Level
High. Large, well-phenotyped prospective cohort with high follow-up (99%), comprehensive adjustment for confounders, validated biomarker assays, and consistent results across sensitivity analyses.
Study Flags
Red Flags
- •No direct measurement of insulin resistance (used HOMA-IR instead of gold-standard clamp)
- •Study limited to older white men — findings not generalizable to women or younger populations
- •Did not measure sleep, diet, or cortisol — potential unmeasured confounders
Surprising Findings
Copeptin was not correlated with fasting glucose or HbA1c, yet still predicted future diabetes.
Everyone assumes blood sugar is the earliest warning sign—but this study shows a stress hormone rises before glucose does, suggesting a new early pathway.
Practical Takeaways
If you're a man over 60 with high stress, poor sleep, or abdominal fat, consider this a red flag—even if your blood sugar is normal.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 559 / 100
Probability of being correct
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
Human Cohort Study
Subject
Moderate probability
on the GRADE evidence scale
This study found that men with higher levels of a substance called copeptin were more likely to get diabetes later on, but it didn’t prove that copeptin causes diabetes. It’s like noticing that people who eat more ice cream also get more sunburns — they’re linked, but ice cream doesn’t cause sunburns.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Large sample size (n=3226)
- Long follow-up period (mean 13 years)
- High follow-up rate (99%)
Weaknesses
- No randomization or intervention — observational design limits causal inference
- Blinding status unknown — potential for measurement bias
- Self-reported data for some variables (e.g., diet, physical activity)
Methodology
Evidence Keywords
Statistical Reporting
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Scientists found that older men with higher levels of a stress-related hormone called copeptin were more likely to get type 2 diabetes later, even if they didn’t have high blood sugar yet.
Research results
Men with copeptin above 6.79 pmol/L had a 78% higher chance of getting diabetes over 13 years. This dropped to 47% higher risk after accounting for insulin resistance.
What this means - more context
Yes — even men with normal blood sugar and no kidney disease showed this link, suggesting copeptin may signal early metabolic stress before diabetes develops.
To examine whether plasma copeptin levels predict incident type 2 diabetes in older men over 13 years, independent of traditional risk factors.
In 3,226 older men without diabetes, those in the top fifth of copeptin levels (>6.79 pmol/L) had a 78% higher risk of developing diabetes over 13 years, even after adjusting for waist circumference, blood pressure, triglycerides, and inflammation. This association was partially mediated by insulin resistance (HOMA-IR), which explained about 17% of the risk, but copeptin remained significantly associated even after adjusting for fasting glucose and HbA1c. Copeptin did not improve diabetes risk prediction beyond standard clinical models.
Methods Used
Prospective cohort study of 3,226 men aged 60–79 without diabetes, followed for a mean of 13 years. Plasma copeptin was measured at baseline using an ultrasensitive assay. Incident diabetes was identified via GP records and medical notes. Hazard ratios were calculated using Cox proportional hazards models, adjusting for metabolic, inflammatory, and renal markers.
Main Finding
Men with copeptin >6.79 pmol/L had a 78% higher risk of incident diabetes (HR = 1.78, 95% CI: 1.34–2.37) after adjustment for traditional risk factors; this dropped to HR = 1.47 (95% CI: 1.11–1.97) after adjusting for HOMA-IR, indicating partial mediation by insulin resistance.
Confidence Level
High. Large, well-phenotyped prospective cohort with high follow-up (99%), comprehensive adjustment for confounders, validated biomarker assays, and consistent results across sensitivity analyses.
Study Flags
Red Flags
- •No direct measurement of insulin resistance (used HOMA-IR instead of gold-standard clamp)
- •Study limited to older white men — findings not generalizable to women or younger populations
- •Did not measure sleep, diet, or cortisol — potential unmeasured confounders
Surprising Findings
Copeptin was not correlated with fasting glucose or HbA1c, yet still predicted future diabetes.
Everyone assumes blood sugar is the earliest warning sign—but this study shows a stress hormone rises before glucose does, suggesting a new early pathway.
Practical Takeaways
If you're a man over 60 with high stress, poor sleep, or abdominal fat, consider this a red flag—even if your blood sugar is normal.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 559 / 100
Probability of being correct
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
Human Cohort Study
Subject
Moderate probability
on the GRADE evidence scale
This study found that men with higher levels of a substance called copeptin were more likely to get diabetes later on, but it didn’t prove that copeptin causes diabetes. It’s like noticing that people who eat more ice cream also get more sunburns — they’re linked, but ice cream doesn’t cause sunburns.
No conflicts of interest were detected in this study. No score impact.
Strengths
- Large sample size (n=3226)
- Long follow-up period (mean 13 years)
- High follow-up rate (99%)
Weaknesses
- No randomization or intervention — observational design limits causal inference
- Blinding status unknown — potential for measurement bias
- Self-reported data for some variables (e.g., diet, physical activity)
Methodology
Evidence Keywords
Statistical Reporting
Scoring
How strong is this study?
This study did a really good job tracking a lot of men for over 10 years and checking many health details, which makes the results trustworthy. But since they didn’t change anything on purpose (like giving people copeptin), we can’t be sure if copeptin itself is the problem — maybe something else, like stress, is causing both.
0 / 100
- COI disclosureconflicts of interest not disclosed
- Data availabilitydata not shared
- Code availabilitycode not shared
56 / 100
- Randomizationnot randomized
- Blindingblinding unclear
- Control group+15/15
- Sample size (n=3226)+20/20
- Follow-up+10/10
100 / 100
77 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervals+15/15
- Pre-registrationnot pre-registered
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 559 / 100
Probability of being correct
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
This design cannot establish causation — the findings describe an association, not a cause. This is an observational cohort study with no randomization or intervention; therefore, it can identify associations but cannot prove that copeptin causes diabetes due to potential confounding factors.
No Conflicts
No conflicts of interest identified
No conflicts of interest or funding disclosures were reported in the study text. The study appears to be independently conducted with no indication of industry influence.
The study lacks any declared funding source or conflict of interest statement. While this absence does not confirm independence, there is no evidence of industry involvement, author affiliations with commercial entities, or funder control over study design, analysis, or publication.
Standing
Who’s using this study?
The videos and claims on this site that lean on this study, and the researchers who wrote it.
1 video from Thomas DeLauer cite this study, drawing 2 claims from it.
Authored by
6 researchersIf this is your work, this is how we attribute it on Fit Body Science. S. Goya Wannamethee is listed as the lead author.