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A study of changes in insulin requirements related to the menstrual cycle in Japanese women with type 1 diabetes using the advanced hybrid closed‐loop system

Open access
Takagi, Eri, Kaga, Hideyoshi, Mori, Ryoki, Fujikawa, Shohei, Nagashima, Haruki, Kogai, Toshiki, Koshibu, Mami, Sato, Junko +4 more·2026·Journal of Diabetes Investigation
DOI 10.1111/jdi.70463PMC PMC13647956
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Abstract

Aims/Introduction: In type 1 diabetes (T1D), insulin requirements and glycemic control may vary across the menstrual cycle. We examined phase‐related differences in insulin requirements, glycemic metrics, and recorded carbohydrate amounts in women using an advanced hybrid closed‐loop (AHCL) system and their associations with menstrual symptoms and premenstrual dysphoric disorder (PMDD) screening status. Materials and Methods: Fifteen premenopausal women with T1D using the MiniMed 780G without hormonal therapy were analyzed. Cycles with ≥2 eligible days (SmartGuard ≥70%) in both early follicular (d1–7) and late‐luteal (d‐7 to −1) phases were included. Phase differences were assessed using linear mixed‐effects models. Associations between phase‐related changes and menstrual symptom scores and PMDD screening status were evaluated using Spearman correlation and the Mann–Whitney U test, respectively. Results: Eighty cycles were analyzed. Compared with the early follicular phase, the late‐luteal phase showed a higher total daily insulin dose (49.2 ± 3.7 vs 45.1 ± 3.7 U/day), basal insulin dose, total bolus insulin, and recorded carbohydrate amount (197.9 ± 18.2 vs 186.1 ± 18.2 g/day), with lower Time in Range (70.0 ± 3.2% vs 72.9 ± 3.2%) and higher Time above Range (TAR). Most phase‐related differences persisted after adjustment for recorded carbohydrate amount. No clear associations between menstrual symptom scores or PMDD screening status and phase‐related changes were detected. Conclusion: During AHCL therapy, insulin requirements increased and glycemic control modestly worsened in the late‐luteal phase. No clear associations between phase‐related metabolic changes and menstrual symptom scores or PMDD screening status were detected in this small cohort.

AI snapshot

Written from the paper’s full text.

TL;DR

In 15 premenopausal Japanese women with type 1 diabetes using the MiniMed 780G advanced hybrid closed-loop system, the late-luteal phase showed higher insulin requirements and modestly worse glycemic control than the early follicular phase across 80 menstrual cycles. No clear associations were detected between these phase-related metabolic changes and menstrual symptom scores or PMDD screening status.

Key findings

  • Late-luteal vs early follicular phase: total daily insulin dose was higher (49.2 ± 3.7 vs 45.1 ± 3.7 U/day, P < 0.001), as were basal insulin dose (18.0 ± 1.3 vs 17.0 ± 1.3 U/day, P = 0.007), total bolus dose (31.0 ± 2.1 vs 28.0 ± 2.1 U/day, P < 0.001), auto-correction bolus dose (7.2 ± 0.8 vs 6.1 ± 0.8 U/day, P = 0.003), and recorded carbohydrate amount (197.9 ± 18.2 vs 186.1 ± 18.2 g/day, P = 0.013).
  • Glycemic metrics worsened in the late-luteal phase: Time in Range was lower (70.0 ± 3.2% vs 72.9 ± 3.2%, P = 0.006) and Time above Range level 2 was higher (6.9 ± 1.6% vs 5.1 ± 1.6%, P = 0.003); no statistically significant differences were observed in TAR level 1 or Time below Range level 1 or 2.
  • After adjustment for recorded carbohydrate amount, most phase-related differences persisted: total daily dose, basal insulin dose, total bolus dose, auto-correction bolus dose, TAR, and TIR remained statistically significant, while the meal bolus dose difference was no longer significant.
  • No significant associations were found between mMDQ scores and luteal-to-follicular ratios of TIR, insulin doses, or recorded carbohydrate amount, and no significant differences were observed according to PMDD screening status.

Methods

  • Retrospective, single-center observational study of 15 premenopausal women with type 1 diabetes using the MiniMed 780G without hormonal therapy; 80 menstrual cycles met eligibility criteria, requiring ≥2 eligible days with SmartGuard ≥70% in both the early follicular phase (days 1–7) and late-luteal phase (days −7 to −1).
  • Data were extracted from CareLink reports between February 1, 2024, and October 30, 2025; menstrual onset dates were self-reported, and the mMDQ and PMDD screening questionnaires were administered once at informed consent.
  • Phase differences were assessed using linear mixed-effects models with menstrual phase as a fixed effect and participant and cycle nested within participant as random effects; adjusted models included recorded carbohydrate amount as a covariate. Associations with mMDQ scores used Spearman correlation, and comparisons by PMDD screening status used the Mann–Whitney U test; no adjustment for multiple comparisons was applied.

Limitations

  • Stated in the paper: this was a retrospective, single-center study with a small cohort of Japanese women with relatively good glycemic control, limiting generalizability; menstrual phase was classified from self-reported onset rather than biochemical confirmation of ovulation or sex hormone measurements, with no prespecified numerical criterion for cycle regularity, so phase misclassification cannot be excluded; physical activity was not assessed; recorded carbohydrate amounts were patient-entered and not independently validated, and could not distinguish actual intake from “phantom carbohydrate entries”; insulin sensitivity was not directly assessed; no adjustment for multiple comparisons was performed; and menstrual symptoms/PMDD screening were evaluated only once, so scores may not reflect symptom severity during all analyzed cycles.
  • Evident from the text: the very small sample (15 participants, 80 cycles) and exploratory design limit precision and causal inference, and the reliance on self-reported cycle dates and a single questionnaire administration may introduce bias.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/jdi.70463

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

25 of 44 cited sources checked · 12 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Fluctuations in insulin sensitivity associated with the female menstrual cycle occur due to changes in the balance between estrogen and progesterone.

    “Fluctuations in insulin sensitivity associated with the female menstrual cycle occur due to changes in the balance between estrogen and progesterone.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [1] Yeung EH, Zhang C, Mumford SL, et al. Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: The BioCycle study. J Clin Endocrinol Metab 2010; 95: 5435– 5442. PMC2999972 20843950 source

      The Discussion reports that insulin and HOMA-IR fluctuate over the menstrual cycle and says these changes are most likely explained by their associations with estradiol and progesterone. It does not establish that a changing balance between the two hormones causes changes in insulin sensitivity; the study measured insulin resistance using HOMA-IR. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [2] Gaete X, Vivanco M, Eyzaguirre FC, et al. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril 2010; 94: 1822– 1826. 19796762 source

      The discussion under TABLE 2 links insulin dose and HbA1c to menstrual-cycle irregularities in adolescents with type 1 diabetes, but does not address menstrual-cycle fluctuations in insulin sensitivity. Searches for insulin sensitivity and estrogen–progesterone balance found no passage establishing the claimed mechanism; page numbers were unavailable in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
  • Premisecitation

    Elhenawy et al. investigated an adolescent and young adult cohort (14-21 years).

    “Elhenawy et al. 9 investigated an adolescent and young adult cohort (14–21 years), whereas Monroy et al. 10 examined individuals with relatively high baseline glycemic control (TIR in the 80% range).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Elhenawy YI, Abdel Kader MS, Thabet RA. Performance of the MiniMed 780G system on mitigating menstrual cycle‐dependent glycaemic variability. Diabetes Obes Metab 2024; 26: 4916– 4923. 39248215 source
  • Interpretationcitation

    Our results are broadly aligned with prior investigations using the MiniMed 780G system.

    “Furthermore, our results are broadly aligned with those of prior investigations using the MiniMed 780G system 9 , 10 .”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [9] Elhenawy YI, Abdel Kader MS, Thabet RA. Performance of the MiniMed 780G system on mitigating menstrual cycle‐dependent glycaemic variability. Diabetes Obes Metab 2024; 26: 4916– 4923. 39248215 source
    • cites [10] Monroy G, Picón‐César MJ, García‐Alemán J, et al. Glycemic control across the menstrual cycle in women with type 1 diabetes using the MiniMed 780G advanced hybrid closed‐loop system: The 780MENS prospective study. Diabetes Technol Ther 2025; 27: 395– 401. 39898554 source
  • Interpretationcitation

    Our findings are consistent with previous studies on women with T1D treated with MDI or CSII, which consistently reported reduced insulin sensitivity and deterioration of glycemic control during the luteal phase.

    “Our findings are consistent with those of previous studies on women with T1D treated with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), which consistently reported reduced insulin sensitivity and deterioration of glycemic control during the luteal phase 4 , 5 , 16 .”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [4] Brown SA, Jiang B, McElwee‐Malloy M, et al. Fluctuations of hyperglycemia and insulin sensitivity are linked to menstrual cycle phases in women with T1D. J Diabetes Sci Technol 2015; 9: 1192– 1199. PMC4667305 26468135 source

      The Discussion reports increased hyperglycemia risk and lower insulin sensitivity in the luteal phase among women with T1D. But this study enrolled women using CSII, not MDI, and the Discussion reports that insulin sensitivity decreased in only 42% of individual cycles; the source therefore does not support the claim that studies consistently found both effects across women treated with MDI or CSII. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [5] Barata DS, Adan LF, Netto EM, et al. The effect of the menstrual cycle on glucose control in women with type 1 diabetes evaluated using a continuous glucose monitoring system. Diabetes Care 2013; 36: e70. PMC3631835 23613610 source

      In the paper’s main text (page not provided), the six women with type 1 diabetes included one using an insulin pump and five using multiple insulin doses. The study reports more hyperglycemia in the luteal than the follicular phase, but it does not report a measured reduction in insulin sensitivity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [16] Herranz L, Saez‐de‐Ibarra L, Hillman N, et al. Glycemic changes during menstrual cycles in women with type 1 diabetes. Med Clin (Barc) 2016; 146: 287– 291. 26897501 source
  • Study design and conductnone given

    Physical activity was not assessed.

    “Physical activity, a known determinant of insulin requirements 25 , 26 , was not assessed.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [25] Salem MA, AboElAsrar MA, Elbarbary NS, et al. Is exercise a therapeutic tool for improvement of cardiovascular risk factors in adolescents with type 1 diabetes mellitus? A randomised controlled trial. Diabetol Metab Syndr 2010; 2: 47. PMC3238209 20618996 source
    • cites [26] Ostman C, Jewiss D, King N, et al. Clinical outcomes to exercise training in type 1 diabetes: A systematic review and meta‐analysis. Diabetes Res Clin Pract 2018; 139: 380– 391. 29223408 source
  • Classified as probably not a substantial claim. 35
  • May combine two claims. 25
  • The quote only partly states this claim. 8

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    East Asian populations are characterized by distinct metabolic and anthropometric profiles compared to Western populations, including lower body mass index, differences in body composition, and unique dietary patterns.

    “East Asian populations are characterized by distinct metabolic and anthropometric profiles compared to Western populations, including lower body mass index (BMI), differences in body composition, and unique dietary patterns 11 , 12 .”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [11] Kodama K, Tojjar D, Yamada S, et al. Ethnic differences in the relationship between insulin sensitivity and insulin response: A systematic review and meta‐analysis. Diabetes Care 2013; 36: 1789– 1796. PMC3661854 23704681 source

      The Conclusions report that East Asians have lower mean BMI and less mean total visceral fat volume than Caucasians, supporting the anthropometric and body-composition comparisons. The paper mentions novel diets in a general discussion of human migration, but does not establish distinct East Asian dietary patterns compared with Western populations. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [12] do Vale Moreira NC, Ceriello A, Basit A, et al. Race/ethnicity and challenges for optimal insulin therapy. Diabetes Res Clin Pract 2021; 175: 108823. 33887353 source

      Section 2.5 reports that East Asians have lower mean BMI and less visceral fat than Caucasians, supporting the anthropometric and body-composition comparisons. The section on glycaemic response to carbohydrates contrasts Asian and Western diets, but describes Asian diets broadly rather than establishing a dietary pattern specific to East Asian populations. No page numbers are available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous studies have reported increased insulin requirements and deterioration of glycemic control from the mid- to late-luteal phases in women with type 1 diabetes.

    “Several previous studies have reported increased insulin requirements and deterioration of glycemic control from the mid‐ to late‐luteal phases in women with type 1 diabetes (T1D) 3 , 4 , 5 , 6 , 7 .”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [3] Trout KK, Rickels MR, Schutta MH, et al. Menstrual cycle effects on insulin sensitivity in women with type 1 diabetes: A pilot study. Diabetes Technol Ther 2007; 9: 176– 182. 17425444 source
    • cites [4] Brown SA, Jiang B, McElwee‐Malloy M, et al. Fluctuations of hyperglycemia and insulin sensitivity are linked to menstrual cycle phases in women with T1D. J Diabetes Sci Technol 2015; 9: 1192– 1199. PMC4667305 26468135 source

      The paper’s background passage reports that earlier small studies found more frequent hyperglycemia during the luteal phase in women with T1D, and says insulin requirements can change across the cycle. It does not establish increased insulin requirements specifically from mid- to late-luteal phases. Its own Results report no significant fluctuation in total daily insulin and a hyperglycemia risk that rose until early luteal phase, then returned to initial levels (Abstract; Glycemic Risks, page unavailable). (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [5] Barata DS, Adan LF, Netto EM, et al. The effect of the menstrual cycle on glucose control in women with type 1 diabetes evaluated using a continuous glucose monitoring system. Diabetes Care 2013; 36: e70. PMC3631835 23613610 source

      The paper’s main text reports more hyperglycemia in the luteal than the follicular phase in six women with type 1 diabetes, supporting the glycemic-control portion of the claim. It does not report increased insulin requirements or a progression from mid- to late-luteal phases; its measurements compare days 18–22 with days 4–8. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Menstrual-associated symptoms were assessed using the Japanese version of the modified Menstrual Distress Questionnaire (mMDQ), a validated instrument comprising 54 items scored 1-4 (total score range 54-216).

    “Menstrual‐associated symptoms during the premenstrual, menstrual, and postmenstrual periods were assessed using the Japanese version of the modified Menstrual Distress Questionnaire (mMDQ), which comprises 54 items scored from 1 to 4 (total score range: 54–216) 13 .”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Yoshino O, Takahashi N, Suzukamo Y. Menstrual symptoms, health‐related quality of life, and work productivity in Japanese women with dysmenorrhea receiving different treatments: Prospective observational study. Adv Ther 2022; 39: 2562– 2577. PMC9123075 35362862 source

      The Methods (Study Outcomes; page unavailable) identify the mMDQ as a measure used in the study, and the Results (Changes in Menstrual Symptoms Over Time; page unavailable) report scores before and during menstruation. Our copy does not establish assessment after menstruation, a Japanese-language version, validation, or the stated item count and scoring range; Methods directs readers to supplementary material for measure details. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Advanced hybrid closed-loop systems continuously adjust basal insulin delivery every five minutes based on real-time continuous glucose monitoring data and automatically administer correction boluses in response to hyperglycemia, facilitating maintenance of glucose levels near predefined targets.

    “AHCL systems continuously adjust basal insulin delivery every five minutes based on real‐time continuous glucose monitoring (CGM) data and automatically administer correction boluses in response to hyperglycemia, thereby facilitating the maintenance of glucose levels near predefined targets 8 .”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Silva JD, Lepore G, Battelino T, et al. Real‐world performance of the MiniMed™ 780G system: First report of outcomes from 4120 users. Diabetes Technol Ther 2022; 24: 113– 119. PMC8817690 34524003 source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Reduced insulin sensitivity begins around ovulation and peaks during the progesterone-dominant luteal phase.

    “Reduced insulin sensitivity is known to begin around ovulation and to peak during the progesterone‐dominant luteal phase 1 , 2 .”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [1] Yeung EH, Zhang C, Mumford SL, et al. Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: The BioCycle study. J Clin Endocrinol Metab 2010; 95: 5435– 5442. PMC2999972 20843950 source
    • cites [2] Gaete X, Vivanco M, Eyzaguirre FC, et al. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril 2010; 94: 1822– 1826. 19796762 source

      The discussion accompanying Table 2 links insulin dose to menstrual-cycle variability and proposes effects of insulin on ovarian function. It does not describe insulin sensitivity beginning to fall around ovulation or reaching its lowest point in the luteal phase. Searches for ovulation, progesterone, luteal phase, and cyclic insulin resistance found no passage addressing that timing; page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Studies evaluating transitions from open-loop therapy to advanced hybrid closed-loop have demonstrated that luteal phase reductions in Time in Range observed under open-loop therapy disappeared after switching to advanced hybrid closed-loop, accompanied by algorithm-driven increases in basal and correction insulin delivery during the luteal phase.

    “Indeed, studies evaluating transitions from open‐loop therapy (OLP) to AHCL have demonstrated that luteal phase reductions in Time in Range (TIR) observed under OLP disappeared after switching to AHCL, accompanied by algorithm‐driven increases in basal and correction insulin delivery during the luteal phase 9 .”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Elhenawy YI, Abdel Kader MS, Thabet RA. Performance of the MiniMed 780G system on mitigating menstrual cycle‐dependent glycaemic variability. Diabetes Obes Metab 2024; 26: 4916– 4923. 39248215 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This finding may be consistent with previous evidence that menstrual-associated symptoms are more closely related to altered central nervous system sensitivity to hormonal fluctuations than to absolute hormone concentrations.

    “This finding may be consistent with previous evidence suggesting that menstrual‐associated symptoms are more closely related to altered central nervous system sensitivity to hormonal fluctuations than to absolute hormone concentrations 20 , 21 , 22 , 23 , 24 .”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [20] Reed SC, Levin FR, Evans SM. Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder). Horm Behav 2008; 54: 185– 193. PMC2491904 18413151 source
    • cites [21] Yen JY, Lin HC, Lin PC, et al. Early‐ and late‐luteal‐phase estrogen and progesterone levels of women with premenstrual dysphoric disorder. Int J Environ Res Public Health 2019; 16: 4352. PMC6888463 31703451 source

      The Introduction suggests that women with PMDD may have altered sensitivity to ovarian hormone dynamics, supporting the sensitivity-to-fluctuations part of the claim. But Discussion §4.1 reports lower early-luteal estrogen concentrations in women with PMDD, and §4.2 says serum concentration and dose may also matter. The paper therefore does not support the contrast that sensitivity is more closely related to symptoms than absolute concentrations. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [22] Bäckström T, Haage D, Löfgren M, et al. Paradoxical effects of GABA‐A modulators may explain sex steroid induced negative mood symptoms in some persons. Neuroscience 2011; 191: 46– 54. 21600269 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Elhenawy et al. observed that menstrual phase-related differences in TIR disappeared after AHCL initiation.

    “Elhenawy et al. observed that menstrual phase‐related differences in TIR disappeared after AHCL initiation 9 , whereas Monroy et al. reported increased mean glucose levels and TAR during the luteal phase 10 .”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Elhenawy YI, Abdel Kader MS, Thabet RA. Performance of the MiniMed 780G system on mitigating menstrual cycle‐dependent glycaemic variability. Diabetes Obes Metab 2024; 26: 4916– 4923. 39248215 source

  • May combine two claims.

    Interpretationcitation

    The observed increase in insulin demand during the luteal phase corresponds to reports of algorithm-driven increases in insulin delivery during AHCL therapy and increased TDD during the luteal phase.

    “The observed increase in insulin demand during the luteal phase corresponds to reports demonstrating algorithm‐driven increases in insulin delivery during AHCL therapy 9 and increased TDD during the luteal phase 10 .”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [9] Elhenawy YI, Abdel Kader MS, Thabet RA. Performance of the MiniMed 780G system on mitigating menstrual cycle‐dependent glycaemic variability. Diabetes Obes Metab 2024; 26: 4916– 4923. 39248215 source
    • cites [10] Monroy G, Picón‐César MJ, García‐Alemán J, et al. Glycemic control across the menstrual cycle in women with type 1 diabetes using the MiniMed 780G advanced hybrid closed‐loop system: The 780MENS prospective study. Diabetes Technol Ther 2025; 27: 395– 401. 39898554 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Population-specific differences in body composition and insulin sensitivity among Asian individuals, together with dietary carbohydrate patterns, may contribute to higher insulin requirements.

    “Additionally, population‐specific differences in body composition and insulin sensitivity among Asian individuals 12 , together with dietary carbohydrate patterns 18 , 19 , may also contribute.”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [12] do Vale Moreira NC, Ceriello A, Basit A, et al. Race/ethnicity and challenges for optimal insulin therapy. Diabetes Res Clin Pract 2021; 175: 108823. 33887353 source
    • cites [18] Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): A prospective cohort study. Lancet 2017; 390: 2050– 2062. 28864332 source
    • cites [19] Schmidhuber J, Sur P, Fay K, et al. The global nutrient database: Availability of macronutrients and micronutrients in 195 countries from 1980 to 2013. Lancet Planet Health 2018; 2: e353– e368. PMC6076406 30082050 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Regional differences in insulin requirements exist, with higher insulin doses observed in Asia, the Middle East, and African populations.

    “Regional differences in insulin requirements have been described, with higher insulin doses being observed in Asia, the Middle East, and African populations 17 .”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [17] Saiyed M, Hasnani D, Alonso GT, et al. Worldwide differences in childhood type 1 diabetes: The SWEET experience. Pediatr Diabetes 2021; 22: 207– 214. 33038056 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Menstrual-associated symptoms are more closely related to altered central nervous system sensitivity to hormonal fluctuations than to absolute hormone concentrations.

    “This finding may be consistent with previous evidence suggesting that menstrual‐associated symptoms are more closely related to altered central nervous system sensitivity to hormonal fluctuations than to absolute hormone concentrations 20 , 21 , 22 , 23 , 24 .”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [20] Reed SC, Levin FR, Evans SM. Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder). Horm Behav 2008; 54: 185– 193. PMC2491904 18413151 source
    • cites [21] Yen JY, Lin HC, Lin PC, et al. Early‐ and late‐luteal‐phase estrogen and progesterone levels of women with premenstrual dysphoric disorder. Int J Environ Res Public Health 2019; 16: 4352. PMC6888463 31703451 source

      The Introduction (page unavailable) suggests that women with PMDD may have altered sensitivity to ovarian hormone dynamics, and Discussion §4.3 describes increased sensitivity to a hormone metabolite’s GABA-receptor effect. But the paper does not establish that central nervous system sensitivity is more closely related to symptoms than absolute hormone concentrations; Discussion §§4.2–4.3 also identify hormone concentrations as relevant to symptom severity. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [22] Bäckström T, Haage D, Löfgren M, et al. Paradoxical effects of GABA‐A modulators may explain sex steroid induced negative mood symptoms in some persons. Neuroscience 2011; 191: 46– 54. 21600269 source

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, total daily insulin dose remained significantly higher in the late-luteal phase than in the early follicular phase.

    “Total daily dose, U/day | 46.2 ± 3.3 | 48.7 ± 3.3 | 2.57 (1.32 to 3.82) | <0.001”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, basal insulin dose remained significantly higher in the late-luteal phase than in the early follicular phase.

    “Total daily basal dose, U/day | 17.0 ± 1.3 | 18.0 ± 1.3 | 0.97 (0.23 to 1.71) | 0.011”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, time in range (TIR) remained significantly lower in the late-luteal phase than in the early follicular phase.

    “TIR, % | 72.9 ± 2.7 | 70.2 ± 2.7 | −2.71 (−4.93 to −0.48) | 0.018”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    A total of 80 menstrual cycles met the predefined eligibility criteria and were included.

    “A total of 80 menstrual cycles (range: 1–10 cycles per participant) met the predefined eligibility criteria (SmartGuard™ usage ≥70% and ≥2 valid days per phase) and were included.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, time above range level 2 was significantly higher in the late-luteal phase than in the early follicular phase.

    “TAR level 2, % | 5.3 ± 2.0 | 6.8 ± 2.0 | 1.46 (0.31 to 2.60) | 0.013”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Two of the 15 study participants had slowly progressive insulin-dependent diabetes mellitus (SPIDDM).

    “Among the 15 study participants, two had slowly progressive insulin‐dependent diabetes mellitus (SPIDDM).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The mean menstrual cycle length across all evaluable cycles was 30.9 ± 6.5 days.

    “The mean menstrual cycle length across all evaluable cycles was 30.9 ± 6.5 days (Table 1).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Carbohydrate entry frequency was significantly higher in the late-luteal phase than in the early follicular phase (5.5 vs 5.2 entries/day, P = 0.036).

    “Carbohydrate entry frequency was also significantly higher during the late‐luteal phase than during the early follicular phase.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, auto-correction bolus dose remained significantly higher in the late-luteal phase than in the early follicular phase.

    “Total daily auto‐correction dose, U/day | 6.1 ± 0.9 | 7.2 ± 0.9 | 1.10 (0.45 to 1.75) | 0.001”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, total bolus dose remained significantly higher in the late-luteal phase than in the early follicular phase.

    “Total daily bolus dose, U/day | 29.2 ± 2.5 | 30.8 ± 2.5 | 1.56 (0.66 to 2.47) | <0.001”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SmartGuard auto-mode usage rate and infusion set replacement frequency were comparable between the early follicular and late-luteal phases.

    “SmartGuard™ auto‐mode usage rate, % | 93.7 ± 1.0 | 93.7 ± 1.0 | −0.03 (−1.86 to 1.81) | 0.978”
    • Also stated in: § Phase differences in insulin dose, CGM metrics, and recorded carbohydrate amount · plain
      “Infusion set replacement frequency, changes/week | 1.7 ± 0.1 | 1.8 ± 0.1 | 0.10 (−0.08 to 0.28) | 0.270”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    After adjustment for recorded carbohydrate amount, time above range level 1 was significantly higher in the late-luteal phase than in the early follicular phase.

    “TAR level 1, % | 19.5 ± 2.4 | 21.1 ± 2.4 | 1.53 (0.05 to 3.02) | 0.044”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Exploratory analyses of individual mMDQ subscales identified several nominal associations with TIR or recorded carbohydrate amount.

    “Exploratory analyses of individual mMDQ subscales identified several nominal associations with TIR or recorded carbohydrate amount.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Recorded carbohydrate amount and carbohydrate entry frequency increased during the late-luteal phase.

    “From a behavioral perspective, both the recorded carbohydrate amount and carbohydrate entry frequency increased during the late‐luteal phase, consistent with prior observations of increased carbohydrate intake during this phase 10 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Monroy G, Picón‐César MJ, García‐Alemán J, et al. Glycemic control across the menstrual cycle in women with type 1 diabetes using the MiniMed 780G advanced hybrid closed‐loop system: The 780MENS prospective study. Diabetes Technol Ther 2025; 27: 395– 401. 39898554 source

  • May combine two claims.

    Findingown data

    TIR decreased and TAR increased during the late-luteal phase despite automated algorithm-based insulin adjustment.

    “Despite automated algorithm‐based insulin adjustment, TIR decreased and TAR increased during the late‐luteal phase, indicating that glycemic control deteriorated even under automated management.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    A sensitivity analysis excluding the single participant receiving an SGLT2 inhibitor (14 participants, 74 cycles) showed findings consistent with the primary analysis, and the main findings remained statistically significant.

    “To assess the potential impact of SGLT2 inhibitor use, a sensitivity analysis excluding the single participant receiving an SGLT2 inhibitor was performed (14 participants, 74 cycles). The findings were consistent with those of the primary analysis, and the main findings remained statistically significant.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Higher scores on both instruments indicate a greater symptom burden.

    “Higher scores on both instruments indicate a greater symptom burden.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Written informed consent was obtained from all 31 participants.

    “Written informed consent was obtained from all 31 participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    11 participants were excluded due to the use of hormonal contraception or hormone therapy.

    “Among these, 11 participants were excluded due to the use of hormonal contraception or hormone therapy, one due to pregnancy during the study period, one due to menopause during follow‐up, and three due to missing data.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Only days with SmartGuardTM auto‐mode usage ≥70% were included in the analysis.

    “Only days with SmartGuard™ auto‐mode usage ≥70% were included in the analysis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    No adjustment for multiple comparisons was applied.

    “No adjustment for multiple comparisons was applied; therefore, the findings should be interpreted as exploratory.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    PMDD screening-positive status was defined as a total score ≥ 28 on Item 1 of a validated PMDD assessment scale (12 items scored 1-4, total score 12-48).

    “PMDD screening‐positive status was defined as a total score ≥ 28 on Item 1 of a validated PMDD assessment scale (12 items scored 1–4, total score 12–48) 14 , 15 .”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Steiner M, Macdougall M, Brown E. The premenstrual symptoms screening tool (PSST) for clinicians. Arch Womens Ment Health 2003; 6: 203– 209. 12920618 source
    • cites [15] Miyaoka Y, Akimoto Y, Ueda K, et al. The reliability and validity of the newly developed PMDD scale. J JP Soc Psychosom Obstet Gynecol 2009; 14: 194– 201.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Regular menstrual cycles were determined based on participant self-report, without a prespecified numerical criterion for cycle length or cycle-to-cycle variability.

    “Regular menstrual cycles were therefore determined based on participant self‐report, without a prespecified numerical criterion for cycle length or cycle‐to‐cycle variability.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    15 participants were included in this retrospective analysis.

    “Consequently, 15 participants were included in this retrospective analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    This questionnaire-based classification was used as a screening measure and did not represent a formal clinical diagnosis of PMDD.

    “This questionnaire‐based classification was used as a screening measure and did not represent a formal clinical diagnosis of PMDD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    1 participant was excluded due to pregnancy during the study period.

    “Among these, 11 participants were excluded due to the use of hormonal contraception or hormone therapy, one due to pregnancy during the study period, one due to menopause during follow‐up, and three due to missing data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    These fasting C-peptide levels indicate markedly impaired endogenous insulin secretion.

    “Their fasting C‐peptide levels were <0.02 ng/mL and 0.007 ng/mL, respectively, indicating markedly impaired endogenous insulin secretion.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Only menstrual cycles with at least two valid days in each phase were included.

    “Only menstrual cycles with at least two valid days in each phase were included.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Automated insulin delivery may attenuate menstrual cycle-dependent glycemic instability while enabling more accurate characterization of cycle-related insulin requirements.

    “These findings suggest that automated insulin delivery may attenuate menstrual cycle‐dependent glycemic instability while enabling more accurate characterization of cycle‐related insulin requirements.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    AHCL utilization and infusion set management were similar during the early follicular and late-luteal phases.

    “SmartGuard™ auto‐mode usage rate and infusion set replacement frequency were comparable between the early follicular and late‐luteal phases, indicating similar AHCL utilization and infusion set management during both phases (Table 2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Although advanced hybrid closed-loop technology can mitigate cycle-related metabolic fluctuations, it may not eliminate them uniformly, highlighting potential limitations of current algorithms.

    “Collectively, these findings suggest that although AHCL technology can mitigate cycle‐related metabolic fluctuations, it may not eliminate them uniformly, highlighting the potential limitations of the current algorithms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    These factors may influence insulin sensitivity and, consequently, the performance of advanced hybrid closed-loop algorithms.

    “These factors may influence insulin sensitivity and, consequently, the performance of the AHCL algorithms.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    3 participants were excluded due to missing data.

    “Among these, 11 participants were excluded due to the use of hormonal contraception or hormone therapy, one due to pregnancy during the study period, one due to menopause during follow‐up, and three due to missing data.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Recorded carbohydrate amount was included as a covariate in the linear mixed-effects model.

    “Given the observed phase difference in recorded carbohydrate amount, this variable was included as a covariate in the linear mixed‐effects model (Table 2B).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    No single primary outcome was prespecified because of the exploratory nature of this retrospective observational study.

    “No single primary outcome was prespecified because of the exploratory nature of this retrospective observational study.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    1 participant was excluded due to menopause during follow-up.

    “Among these, 11 participants were excluded due to the use of hormonal contraception or hormone therapy, one due to pregnancy during the study period, one due to menopause during follow‐up, and three due to missing data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Most phase-related differences persisted after statistical adjustment for recorded carbohydrate amount, whereas the difference in meal bolus dose was attenuated.

    “These findings indicate that most phase‐related differences persisted after statistical adjustment for recorded carbohydrate amount, whereas the difference in meal bolus dose was attenuated.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Menstrual symptoms and PMDD screening status were evaluated only once at the time of informed consent, whereas the analyzed menstrual cycles included data collected both before and after questionnaire administration.

    “Finally, menstrual symptoms and PMDD screening status were evaluated only once at the time of informed consent, whereas the analyzed menstrual cycles included data collected both before and after questionnaire administration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study had a modest sample size and performed multiple comparisons.

    “However, given that menstrual symptoms were assessed only once while the analyzed cycles included periods both before and after questionnaire administration, together with the modest sample size and multiple comparisons performed, these findings should be considered hypothesis‐generating and require confirmation in larger prospective studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Menstrual phase classification was based on self-reported menstrual onset dates rather than biochemical confirmation of ovulation or sex hormone measurements, and no prespecified numerical criterion for menstrual cycle regularity was applied.

    “Menstrual phase classification was based on self‐reported menstrual onset dates rather than biochemical confirmation of ovulation or sex hormone measurements, and no prespecified numerical criterion for menstrual cycle regularity was applied; therefore, some degree of phase misclassification cannot be excluded.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Recorded carbohydrate amounts were based on patient-entered pump records and were not independently validated.

    “Recorded carbohydrate amounts were based on patient‐entered pump records and were not independently validated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Insulin pump records could not distinguish actual carbohydrate consumption from intentional carbohydrate entries used to facilitate insulin delivery (phantom carbohydrate entries), which may have influenced recorded carbohydrate amounts.

    “Furthermore, the insulin pump records could not distinguish actual carbohydrate consumption from intentional carbohydrate entries used to facilitate insulin delivery (so‐called “phantom carbohydrate entries”), which may have influenced the recorded carbohydrate amounts.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    No adjustment for multiple comparisons was performed because of the exploratory nature of the analyses.

    “In addition, no adjustment for multiple comparisons was performed because of the exploratory nature of the analyses; therefore, the statistically significant findings should be interpreted cautiously.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Differences in system utilization may partly contribute to between-study variation but are unlikely to be the sole explanation for the observed discrepancies.

    “Thus, while differences in system utilization may partly contribute to between‐study variation, they are unlikely to be the sole explanation for the observed discrepancies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    This was a retrospective, single-center study involving a relatively small cohort of Japanese women with relatively good glycemic control, potentially limiting its generalizability.

    “This was a retrospective, single‐center study involving a relatively small cohort of Japanese women with relatively good glycemic control, potentially limiting its generalizability.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Monroy et al. reported increased mean glucose levels and TAR during the luteal phase.

    “Elhenawy et al. observed that menstrual phase‐related differences in TIR disappeared after AHCL initiation 9 , whereas Monroy et al. reported increased mean glucose levels and TAR during the luteal phase 10 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Monroy G, Picón‐César MJ, García‐Alemán J, et al. Glycemic control across the menstrual cycle in women with type 1 diabetes using the MiniMed 780G advanced hybrid closed‐loop system: The 780MENS prospective study. Diabetes Technol Ther 2025; 27: 395– 401. 39898554 source
58 of 58

  • The paper relies on this without support.

    Evidence addressing menstrual cycle-related metabolic variability during advanced hybrid closed-loop therapy in East Asian women is scarce.

    “However, evidence addressing the menstrual cycle‐related metabolic variability during AHCL therapy in East Asian women is scarce.”

  • The paper relies on this without support.

    Limited data exist regarding whether menstrual-associated symptoms or premenstrual dysphoric disorder contribute to variability in insulin requirements or glycemic control.

    “Furthermore, limited data exist regarding whether menstrual‐associated symptoms or premenstrual dysphoric disorder (PMDD), both of which may affect eating behavior and daily functioning, contribute to variability in insulin requirements or glycemic control.”

  • The authors state this as an assumption.

    A compound symmetry covariance structure holds for repeated measurements within cycles.

    “A compound symmetry covariance structure was assumed for repeated measurements within cycles”

  • The paper relies on this without support.

    Self-reported menstrual onset dates accurately reflect true menstrual onset.

    “Menstrual onset dates were obtained by self‐report from each participant.”

  • The paper relies on this without support.

    AHCL algorithms primarily adapt insulin delivery based on glucose trends and recent insulin requirements and may not fully anticipate menstrual cycle-related changes in insulin requirements.

    “AHCL algorithms primarily adapt insulin delivery based on glucose trends and recent insulin requirements and may not fully anticipate menstrual cycle‐related changes in insulin requirements.”

  • The paper relies on this without support.

    Carbohydrate intake may itself be influenced by menstrual phase.

    “However, carbohydrate intake may itself be influenced by menstrual phase, and recorded carbohydrate amounts may not always represent actual food intake because of possible phantom carbohydrate entries.”
6 of 6

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Miyaoka Y, 2009, The reliability and validity of the newly developed PMDD scale, J JP Soc Psychosom Obstet Gynecol, 14, 194

Authors
Takagi, E., Kaga, H., Mori, R., Fujikawa, S., Nagashima, H., Kogai, T., Koshibu, M., Sato, J., Nishida, Y., Ikeda, F., Tamura, Y., & Watada, H.
Affiliations
Juntendo University (JP)
Corresponding author
Kaga, Hideyoshi
ORCID
Venue
Journal of Diabetes Investigation
Publisher
Wiley
Published
2026-10-08
ISSN
  • 2040-1116 (ISSN-L)
  • 2040-1124
DOI
10.1111/jdi.70463
PMC
PMC13647956
OpenAlex
W7221041491
Semantic Scholar
f4194031c984aac1d0bbf04f31351a6988bdd56d
Cited by
0
References
25
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes Investigation (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc)
Funders
Manpei Suzuki Diabetes Foundation
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
type 1 diabetes, menstrual cycle, insulin requirement, luteal phase, follicular phase, glycemic control, time in range, time above range, premenstrual dysphoric disorder, menstrual symptoms, carbohydrate intake, Japanese women

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-17.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-17.

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