Estrogen and Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Estrogen and Diabetes (NCT03436992), a randomized na study. The primary outcome is FMD/Shear.

2. Clinical Question

The study’s broader motivation is the registry’s statement that women with type 1 diabetes have a greater risk of cardiovascular disease than men with type 1 diabetes, while the reason for that difference is unknown. That rationale is not itself a finding from this trial. The listed study groups include men as well as women, but the registry’s stated purpose focuses on premenopausal women with diabetes and estrogen. It does not report a formal primary comparison, a treatment-by-sex analysis, or a specific hypothesis about differences among all of the groups. The clinical question can therefore be described from the stated purpose and outcome, but the precise statistical contrast intended to answer it is not reported in the registry record.

3. Trial Design

The registry describes a randomized, double-masked, parallel study with an enrollment of 143. The status is completed. The recorded start date is 2018-04-17 and the primary completion date is 2023-09-01. The listed phase is NA. The sponsor is Augusta University.

Women with type 1 diabetes and men with type 1 diabetes are each described as being randomly assigned to an antioxidant cocktail, resveratrol, or placebo. Healthy control women receive no intervention and serve as controls. This creates a distinction between randomized comparisons among participants with type 1 diabetes and comparisons involving the untreated healthy controls. The registry does not report how many participants were assigned to each intervention, whether assignment was stratified, or whether the healthy controls were enrolled under the same allocation process.

The record labels the study double-masked but does not identify which people were masked, how masking was maintained, or whether it applied to every group and assessment. It also does not describe the randomization procedure, allocation concealment, treatment duration beyond the outcome timeframe, or intervention administration. These details are not reported in the registry record.

The primary outcome timeframe is approximately 2 weeks, with acquisition at menses and in the late follicular phase. This indicates that the listed outcome is assessed at two menstrual-cycle phases, rather than at a single unspecified time. The record does not state how those measurements were combined into an analysis, whether all participants contributed observations at both phases, or how differences between phases were intended to enter the primary comparison. Enrollment describes the overall study, not the number of participants with complete outcome data.

Although the study is marked completed, that status does not establish that results were posted or that the planned comparisons were completed. The registry lists one outcome measure and zero analyses. Numerical outcome results, analysis populations, and a detailed statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: These results were based on a subset (n=57) of the total enrollment of 143.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as FMD/Shear, measured over ~ 2 weeks. Acquired at Menses and Late Follicular phase..

The primary outcome is titled FMD/Shear and is described as flow-mediated dilation controlled for shear. Flow-mediated dilation is a measure of how a blood vessel changes in response to increased blood flow. The shear component represents the stimulus associated with that response; accounting for it can help distinguish a change in dilation from a change in the stimulus that produced it. This is a general explanation of the measurement, not a description of the study’s specific calculation, which is not reported in the registry record.

The outcome is continuous, with the registry specifying a mean and standard deviation as its summary form. Its listed unit is %/s^-1. The timeframe is approximately 2 weeks, with measurements acquired at menses and in the late follicular phase. The record does not explain whether the endpoint is a phase-specific value, a change between phases, or a combined measure. It also does not provide a numerical mean, standard deviation, treatment contrast, confidence interval, or test result.

Using a vascular measure is relevant to the study’s stated aim of investigating possible estrogen-related vascular dysfunction. Measuring at the stated menstrual-cycle phases may describe vascular function at different points in that cycle. As a general statistical consideration, repeated measurements from the same participant are related, so their analysis should account for that relationship. The registry does not report how the repeated measurements were analyzed or whether the primary question concerned a phase-specific comparison, a phase change, or an interaction with treatment or participant group. Without those details and results, the endpoint can be described, but its observed pattern cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary endpoint as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the central value of observed measurements, while a standard deviation describes their spread around that mean. Those summaries can help describe a group’s outcome distribution, but they do not by themselves show the estimated difference between groups or the uncertainty around that difference. No means or standard deviations for the outcome are reported in the registry record.

What does randomization contribute?

In general, random assignment helps make intervention groups comparable on average with respect to both measured and unmeasured characteristics at the start of a study. This supports causal interpretation of a difference between randomized groups, subject to the study’s conduct, follow-up, and analysis. Here, random assignment is described for women and men with type 1 diabetes across the antioxidant cocktail, resveratrol, and placebo. The registry does not provide the assignment procedure, group counts, or evidence about whether the groups remained comparable after enrollment.

The healthy control women are described as receiving no intervention. Their role is therefore distinct from that of the randomized intervention groups. In general, a comparison between an enrolled control group and participants with a condition can reflect differences beyond the intervention, especially when the groups are not described as randomized against one another. The record does not report a design or analysis that would make a comparison involving healthy controls equivalent to a randomized treatment contrast.

How should repeated measurements be considered?

The primary outcome is acquired at menses and in the late follicular phase. As a general statistical matter, two measurements from the same person are usually correlated because they share participant characteristics. An analysis that treats those observations as independent can misstate uncertainty. Methods for repeated measurements can account for within-person dependence and can estimate phase-specific patterns, average patterns, or differences in changes across groups. The record does not identify the method used, the planned estimand, or whether missing measurements were expected or observed.

Because FMD/Shear is continuous, an analysis might estimate means or contrasts in means, but the exact method cannot be inferred from the endpoint type alone. A confidence interval would communicate the precision of an estimated contrast; a p-value would address compatibility with a specified null model under its assumptions. Neither should be interpreted without knowing the contrast, analysis population, and model. The registry does not report an analysis method, model terms, covariate adjustments, confidence intervals, or p-values.

What can be inferred from the planning assumptions?

The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. The numerical effect fraction and planning outputs are not reported in the registry record. The stated assumptions are not enough to reconstruct a sample-size estimate or to establish what design the investigators actually used. The illustration is explicitly distinct from the trial’s own design, and any sample-size values derived from such assumptions are planning illustrations, not observed power.

In general, a planning calculation relates a target effect, variability, significance level, allocation, and desired power to a proposed sample size. Its result depends on those assumptions. A calculation based on an observed effect can be especially sensitive to uncertainty in that estimate. It should not be treated as a retrospective probability that the study detected an effect. The registry does not report a sample-size justification, target power, assumed variability, or an original protocol calculation.

Why does over-dispersion matter in general?

Over-dispersion occurs when observed variability is greater than a model assumes. In general, a model that understates variability may produce uncertainty estimates that are too small, making results appear more precise than warranted. This concept is most relevant to outcomes modeled with distributions that impose a particular variance structure. The listed primary outcome is continuous and summarized by a mean and standard deviation; no model or evidence of over-dispersion is reported. It would therefore be inappropriate to claim that over-dispersion occurred in this study.

What does the record establish about the analysis?

The registry lists one outcome measure and zero analyses. It does not report which outcome timepoint or phase was designated as primary for a particular contrast, how multiple phases or intervention groups were handled, or whether any adjustment for covariates was planned. It also does not report the analysis population, exclusions, handling of missing measurements, or any interim analysis. The statistical plan is not reported in the registry record. These absences limit interpretation: the endpoint definition and broad design are available, but the inferential method and numerical findings are not.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, FMD/Shear, and zero analyses. The outcome is acquired at menses and in the late follicular phase, while participants with type 1 diabetes are assigned to three interventions and the study also includes healthy control women. These features create the possibility of multiple comparisons or analytic choices, but the record does not state which comparisons were prespecified, which were primary, or whether any adjustment for multiplicity was planned. No multiplicity procedure is reported in the registry record.

In general, evaluating several outcomes, timepoints, groups, or contrasts can increase the chance of a seemingly notable result arising by chance if the analysis does not account for the number of tests. That general concern does not establish that the study conducted multiple tests or that its results are false; the record contains no analysis results. A reader would need the prespecified statistical plan and complete results to distinguish confirmatory analyses from exploratory ones.

Missing-data handling and analysis populations are also not reported in the registry record. It is not stated whether all enrolled participants contributed outcome measurements, whether any observations were excluded, how incomplete phase measurements were handled, or whether the analysis used all randomized participants or another defined group. In general, missingness can affect estimates when the availability of measurements is related to participant characteristics or outcomes. The direction and extent of any such effect cannot be determined without information about missing observations and the analysis strategy.

The registry does not report interim analyses, stopping rules, or a detailed statistical plan. Their absence from this record should be read as missing documentation, not as proof that a particular procedure was or was not used.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious adverse event listing identifies T1M Women and Controls. For T1M Women, 32 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. For Controls, 25 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. No serious adverse event terms are listed.

These figures describe the groups and event categories present in the registry record. They do not provide safety results for the antioxidant cocktail, resveratrol, or placebo groups, and they should not be treated as covering every study participant. The record does not report the duration or method of adverse event collection, the definition used for other adverse events, or whether all participants in the named groups had complete safety follow-up.

Zero events in the listed groups means that no events are recorded for those categories in this listing. It does not establish that no events occurred outside the recorded groups or observation period, and it does not quantify the possibility of an event that was not observed. Without fuller safety follow-up information, the figures are a limited registry summary rather than a complete account of comparative safety.

12. What the Result Does, and Does Not, Mean

The registry record documents a completed randomized, double-masked, parallel study focused on vascular function in the context of type 1 diabetes and estrogen. It identifies the intervention groups for participants with type 1 diabetes, healthy control women, and a primary continuous outcome measured at two menstrual-cycle phases. These details describe the study’s question and broad design; they do not reveal what the outcome showed.

No numerical FMD/Shear results, group means, standard deviations, treatment contrasts, confidence intervals, or p-values are reported. The record therefore does not support a conclusion about the direction or size of any observed difference, how precisely a difference was estimated, or whether the data were compatible with a range of effects. Completed status does not fill that gap.

The randomized intervention groups and the healthy control women also answer different kinds of questions. A contrast among randomized interventions can be interpreted differently from a comparison with an untreated control group. The registry does not specify the primary contrast or analysis approach, so it is not possible to determine how the listed groups were used to address the stated estrogen-related question.

The serious adverse event figures report no events in the two named groups, but do not cover all intervention groups in the listing and lack details about ascertainment and follow-up. They cannot establish an overall safety profile.

In general, an absence of posted statistical results is not evidence that an intervention had no effect or that the groups were equivalent. Equivalence requires an appropriate design and analysis, with a prespecified margin and sufficiently precise results. Those details and results are not reported in the registry record. The most defensible interpretation is that the registry describes a study designed to investigate vascular function, while leaving its primary outcome findings and inferential conclusions unreported.

13. Why This Trial Matters Statistically

This study is statistically interesting because its stated question sits alongside several distinct sources of comparison: three randomized interventions for participants with type 1 diabetes, a healthy control group without intervention, and outcome acquisition at two menstrual-cycle phases. Each comparison can address a different scientific question. A clear prespecified contrast is important for interpreting what an estimated difference means, but the registry does not report that contrast or the analysis plan.

The endpoint also illustrates the distinction between measuring a physiological response and specifying an estimand. FMD controlled for shear is the listed continuous measure, but a reader still needs to know whether the target is a difference between interventions, a difference between groups, a change across phases, or a pattern involving both treatment and phase. Those choices affect the estimate and its interpretation. The registry defines the outcome’s general form and timing but not the inferential target.

Randomization is a valuable design feature for comparisons among assigned interventions, while the untreated healthy controls have a different role. Keeping those comparisons distinct prevents a nonrandomized group contrast from being interpreted as though it were a randomized treatment effect. The record’s sparse analysis information makes this distinction especially important.

Finally, the lack of posted outcome analyses shows why registry status and registry results are not interchangeable. A study can be marked completed without the record containing estimates needed to evaluate effect magnitude or precision. For researchers, the missing analysis details also underscore the value of reporting group counts, missingness, prespecified comparisons, methods for repeated measurements, and uncertainty alongside outcome estimates.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpretation is that the registry record contains no numerical primary outcome results and lists zero analyses. The effect size, direction, and precision of FMD/Shear are therefore unavailable. The record also does not identify the primary comparison, despite describing several intervention groups, participant groups, and measurement phases.

Important design and analysis details are not reported in the registry record. These include group-specific enrollment, randomization procedures, the identities of those masked, intervention dosing and adherence, the statistical model, covariate adjustment, and handling of repeated measurements. A detailed statistical plan, sample-size justification, and interim-analysis information are also not reported. It is not possible to infer these procedures from the study’s randomized or double-masked labels.

The timeframe is approximately 2 weeks, with acquisition at menses and in the late follicular phase. The record does not explain whether all participants completed both assessments, how the timing was assigned or verified, or how incomplete measurements were handled. It also does not report outcome distributions or an analysis population.

The healthy controls receive no intervention, so their comparisons with participants who have type 1 diabetes are distinct from randomized comparisons among interventions. The registry does not specify how those control data enter the primary question. The safety listing is limited to T1M Women and Controls and does not give ascertainment or follow-up details. These limitations concern what can be established from the registry record; they do not demonstrate that a particular method was absent from the full study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Estrogen and Diabetes — NCT03436992.
• Registry record last updated 2025-02-17; status last verified 2025-01.
• Results first posted 2025-02-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT03436992, titled “Estrogen and Diabetes,” with the official title “Estrogen-Mediated Impairments of Vascular Health in Diabetes.” Augusta University is listed as sponsor. The study is marked completed, randomized, double-masked, and parallel, with enrollment of 143. The recorded start date is 2018-04-17 and primary completion date is 2023-09-01; the phase is listed as NA.

Women and men with type 1 diabetes are described as randomly assigned to an antioxidant cocktail, resveratrol, or placebo. Healthy control women receive no intervention. The primary outcome is continuous FMD/Shear, described as flow-mediated dilation controlled for shear, acquired at menses and in the late follicular phase over approximately 2 weeks.

The registry lists one outcome measure and zero analyses. Numerical primary outcome findings, the statistical plan, and the primary comparison are not reported in the registry record. The serious adverse event listing gives figures only for T1M Women and Controls.