Paulina Przybysz, Adrian Kruszewski, Joanna Kacperczyk-Bartnik, et al. · (2023) · "The Impact of Maternal Plant-Based Diet on Obstetric and Neonatal Outcomes—A Cross-Sectional Study" · Nutrients · doi: 10.3390/nu15224717 · PMCID: PMC10675710 · PMID: 38004112

Question: What did the discussion section of the paper "The Impact of Maternal Plant-Based Diet on Obstetric and Neonatal Outcomes—A Cross-Sectional Study" cover?

Answer:
In this study, a plant-based diet was relatively common among pregnant women, with 5.7% of them being vegetarian and 2.5% being fully vegan based on reported dietary habits. The results showed that a plant-based diet—both during the preconception period and during pregnancy—was not associated with the incidence of anemia during pregnancy and gestational hypertension in univariate analysis. Multivariate analysis showed that prepregnancy BMI was a contributing factor to gestational hypertension incidence in the plant-based diet group, though the numbers are small. Additionally, a meat-free diet during the preconception period did not change the risk of developing GDM but during pregnancy was associated with a lower incidence of GDM. The GDM risk increased with the prepregnancy BMI increase in the omnivore group. There were fewer overweight women in the plant-based group than in the omnivore group, and the incidence of GDM was also affected by prepregnancy BMI, as shown by multivariate analysis.

The mechanism of plant-based-diet action on organisms is various. This diet has a beneficial effect on the microbiome by inducing the development of more diverse and stable microbial systems, hence supporting overall health [ 20 ]. The literature indicates that vegetarianism can increase nitric oxide bioavailability and decrease reactive oxygen species [ 6 ]. The semiquantitative review conducted by Jaworsky et al. of women with high risk for GDM pointed out that a plant-based diet and phytochemicals may reduce blood glucose and improve antioxidant activity to reduce the oxidative stress that is often associated with GDM [ 21 ]. Also, plant-rich meals significantly increase the serum levels of glucagon-like peptide-1 (GLP-1), a hormone that augments the secretion of insulin [ 6 ]. In our paper, we focused on the impact of diet on chosen maternal and neonatal outcomes, but further studies examining the impact and its mechanisms are needed.

The research by Yisahak et al. included 1948 low-risk pregnant women of four races in the USA, and the results showed that vegetarianism did not exhibit associations with maternal outcomes including GDM, hypertensive disorders, and anemia [ 22 ]. There is evidence that a higher intake of red and processed meat is a risk factor for developing GDM [ 23 ] and type 2 diabetes mellitus [ 24 , 25 ].

The study conducted by Carter et al. revealed that a vegan diet (low in arachidonic acid) might provide protection against preeclampsia and could alleviate most if not all of the signs and symptoms of preeclampsia [ 26 ]. Research performed by Pistollato et al. suggests that maternal nutritional patterns characterized by a low intake of plant-derived foods could increase the risk of gestation-related issues, such as preeclampsia and pregravid obesity, and contribute to the onset of pediatric diseases [ 27 ].

The result of our research showed that physical activity over 90 min a week is associated with a lower incidence of GDM. However, increasing physical activity among women on a plant-based diet does not affect the risk of GDM. On the other hand, among women on an omnivore diet, physical activity is associated with a lower incidence of GDM. We did not observe that the type of diet and increased physical activity were additional factors reducing the risk of gestational hypertension. The risk of gestational hypertension is strongly related to BMI, as mentioned above. The study conducted by Kruszewski A, Przybysz P., et al., which included over 960 women, showed that GDM is more common in women who did not exercise at all or had physical activity less than 90 min a week during the 6 months before pregnancy [ 17 ].

The previous studies on the impact of maternal diet on a newborn’s birth weight were limited and yielded inconsistent findings. Piccoli et al. in a systematic narrative review reported that five studies found lower birth weight in neonates of vegetarian mothers, whereas two analyses suggested higher birth weight [ 14 ]. Our findings showed no association between maternal diet and newborn birth weight. The percentage of newborns with too low body weight (<2500 g) was similar in both subgroups. Moreover, neonates of women on a plant-based diet had similar Apgar score results at the 5th minute after birth compared to neonates of omnivorous women. Newborns who received 8 or more points in the Apgar score constituted 98.8% and 96.6% of the above-mentioned groups, respectively. Moreover, multivariate analysis showed that women with higher prepregnancy BMI on an omnivore diet delivered children in worse condition (Apgar score less than 8 points). We did not observe an association between the type of delivery (vaginal or cesarean section) and maternal diet. In a multivariate analysis, a relationship was found between the newborn birth weight and the type of delivery.

According to a paper by Kesary et al., a maternal vegetarian diet was associated with a lower risk of excessive weight gain, and there was no statistical evidence for an association between maternal diet and preterm delivery or low birth weight [ 13 ]. We did not observe an increased risk of preterm birth in the group of women on a plant-based diet compared to omnivorous women in univariate analysis, but multivariate analysis revealed that prepregnancy BMI was a contributory factor influencing the pregnancy duration in diet type subgroups, i.e., overweight and obese women on an omnivore diet more frequently delivered prematurely and post-term. The study by Yisahak et al. also showed that diet-based full vegetarians had marginally increased odds of inadequate gestational weight gain during the second trimester [ 22 ]. Our univariate analysis of the Polish population showed that the type of diet 6 months before conception did not impact weight gain during pregnancy. Multivariate analysis revealed an influence of prepregnancy BMI on the relationship between diet type and gestational weight gain: overweight and obese women on an omnivore diet gained too much weight more frequently, and similarly, overweight women presented insufficient weight gain on an omnivore diet.

The questionnaire used in this study was self-composed by the authors and it had not been previously validated in a pregnant population. The limitation was that we could not verify all the answers. Some answers were subjective and self-reported by participants. The limitation of our survey was the fact that women could only choose the way of eating in closed questions distinguishing between a meat and a meatless diet, and women did not specify what type of food they consumed. We cannot rule out that a confounding bias and a misclassification bias may have occurred because of this. Unfortunately, we have no information on whether both types of diet were well-balanced and provided all the necessary micronutrients. An additional limitation was no information about the caloric content of the diet.

In a study by Marangoni F. et al., it was observed that even in the most industrialized countries, specific dietary intakes during pregnancy and lactation are often inadequate. This particularly applies to DHA, calcium, iron, folic acid, iodine, and vitamin D [ 28 ]. This result coincides with research on the Polish population that showed that none of the studied women managed adequate nutrition in terms of all tested macro- and micronutrients [ 29 ]. Particular attention should be paid to women of childbearing age following exclusion diets such as veganism because of the increased risk of inadequate supply of nutrients. Findings in the meta-analysis by Bhutta et al. confirm that supplementation during pregnancy reduces low birth weight in the population at risk [ 30 ]. Conclusions from the paper by Avnon et al. are that a vegan diet does not change the umbilical cord levels of B12, folic acid, ferritin, and hemoglobin. Moreover, at greater risk of B12 deficiency are vegans who do not take any vitamin supplementation compared with omnivores [ 31 ].

The WHO recommends initiation of breastfeeding within 1 h after birth, exclusive breastfeeding of infants till 6 months of age, and continued breastfeeding until 2 years of age or older [ 32 ]. Our research showed that a maternal plant-based diet before conception and during pregnancy is not associated with the occurrence of breastfeeding difficulties.

Our analysis showed that, despite the abundant evidence stating that a plant-based diet during pregnancy is safe for both the mother and the fetus, many women refrain from continuing this diet after conception. As many as one in seven women (14.5%) on a meat-free diet switched to an omnivore diet after becoming pregnant. It is worth considering why women adjust their dietary habits. Our study showed that only 36.8% of surveyed women received advice about nutrition during pregnancy from a healthcare professional such as a doctor, midwife, or dietician. Lack of adequate dietary counseling could be the reason for preference for extensive dietary changes during pregnancy, i.e., reintroducing meat after being vegan or vegetarian.

Our study stands out in that we examined nine associations (in heterogeneous groups, due to exclusions, Figure 1 , Materials and Methods) between the type of diet that women follow during the preconception period and the incidence of pregnancy-complicating diseases, premature birth, type of delivery, and neonatal parameters such as birth weight and Apgar score results. Furthermore, we also evaluated the association between diet and breastfeeding. Overweight women statistically significantly more often were on omnivore than plant-based diets, and this difference between subgroups could be the same limitation in our study. Another limitation could be the fact that the number of women on a plant-based diet is relatively small compared to the number of women in the omnivore group.

This study aimed to create a scientific paper that would be a compendium of knowledge for women planning pregnancy about the impact and safety of a properly balanced plant-based diet during pregnancy. Our findings are in line with the statements of the American Dietetic Association that well-planned vegetarian diets are appropriate during all stages of the life cycle including pregnancy [ 33 ]. We expect an increase in the population on a plant-based diet. In the coming years, the number of diet-related diseases will change.

— Source (discussion, peer-reviewed): Paulina Przybysz, Adrian Kruszewski, Joanna Kacperczyk-Bartnik, et al. · (2023) · "The Impact of Maternal Plant-Based Diet on Obstetric and Neonatal Outcomes—A Cross-Sectional Study" · Nutrients · doi: 10.3390/nu15224717 · PMCID: PMC10675710 · PMID: 38004112
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Nazihah Rasiwala, Gillian I. Bell, Nouran N. Al-Banaa, et al. · (2026) · "Therapeutic Activities of Multipotent Stromal Cells for Islet Regeneration" · Cells · doi: 10.3390/cells15060488 · PMCID: PMC13025508 · PMID: 41892279

Question: Summarize the abstract of the paper titled "Therapeutic Activities of Multipotent Stromal Cells for Islet Regeneration".

Answer:
Diabetes mellitus is a global healthcare issue of epidemic proportions. At the root of these disorders, characterized by poor glucose regulation and insulin deficiencies, is the pancreatic beta cell and insufficient insulin signal transduction in peripheral tissues. Residual c-peptide secretion and persisting beta cells have been found in patients who have been living with type 1 diabetes for over 50 years. Thus, beta cell regeneration has been vastly studied in rodents, and many agents to expand beta cell mass are under rigorous investigation for the treatment of diabetes. Multipotent stromal cells (MSC), isolated from human bone marrow, have an immunomodulatory and pro-regenerative secretome that can aid in repairing damaged tissues, including pancreatic islets. MSC transplantation has been shown to reduce hyperglycemia and orchestrate islet repair in experimental diabetes models and is currently being assessed in clinical trials. While the immunomodulatory mechanisms of MSC are well-studied, the beta-cell-regenerative mechanisms are unknown. MSC likely play a regenerative role by signaling to resident progenitor or precursor cells in the pancreas; however, the decades-long controversy surrounding the origin of regenerated adult beta cells remains unresolved. Herein, we take a deep dive into the role of MSC in the treatment of diabetes and the potential cellular mechanisms behind the MSC stimulation of beta cell regeneration.

— Source (abstract, peer-reviewed): Nazihah Rasiwala, Gillian I. Bell, Nouran N. Al-Banaa, et al. · (2026) · "Therapeutic Activities of Multipotent Stromal Cells for Islet Regeneration" · Cells · doi: 10.3390/cells15060488 · PMCID: PMC13025508 · PMID: 41892279
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Seiko Mizuno, Machiko Minatoya, Satoshi Osaga, et al. · (2024) · "Investigation of Severe Hypoglycemia Risk Among Patients with Diabetes Treated with Ultra-Rapid Lispro in Japan" · Advances in Therapy · doi: 10.1007/s12325-024-03050-1 · PMCID: PMC11782313 · PMID: 39570544

Question: What is the published background on "Investigation of Severe Hypoglycemia Risk Among Patients with Diabetes Treated with Ultra-Rapid Lispro in Japan"? Cite a peer-reviewed source.

Answer:
The Japanese Clinical Practice Guidelines for Diabetes 2019 recommend treating type 1 diabetes (T1D) with insulin therapy, and type 2 diabetes (T2D) with oral hypoglycemic agents, insulin therapy, or glucagon-like peptide 1 receptor agonists [ 1 ]. Ultra-rapid lispro (URLi), a novel ultra-rapid insulin lispro formulation launched on June 17, 2020, in Japan [ 2 ], improves post-prandial glucose control by closely matching physiological insulin secretion [ 3 ].

Hypoglycemia, i.e., a blood glucose level of < 70 mg/dL, is a major side effect of insulin therapy (including URLi); it is classified into non-severe and severe hypoglycemia based on the level of assistance required [ 1 , 4 ]. Non-severe hypoglycemia can be resolved by self-administering oral carbohydrates; however, severe hypoglycemia requires assistance from others to administer glucagon, glucose, or other medical treatments [ 1 , 4 ]. Since severe hypoglycemia can lead to loss of consciousness, seizures, coma, or death [ 5 , 6 ], it is listed as an important identified risk in URLi’s Japan risk management plan (data on file).

In clinical trials, the incidence rate of severe hypoglycemia in URLi-treated patients ranged from 2.4 to 17.6 per 100 person-years, and the incidence proportion ranged from 0.9 to 7.3% [ 7 – 13 ], due to differences in diabetes type, study period, and drug administration. Among insulin-treated patients with diabetes, the incidence rate of severe hypoglycemia differs in the real world (0.0–1.6 episodes/patient/year) and in controlled clinical trials (0.0–0.5 episodes/patient/year) [ 14 ]. Hence, it is necessary to evaluate the real-world risk of hypoglycemia by analyzing health records or medical claims, as conducted in the past [ 15 , 16 ].

To our knowledge, there is no information on the incidence of severe hypoglycemia in patients receiving URLi in the real-world setting. Furthermore, no study to date has compared the risk of severe hypoglycemia after treatment with URLi versus other rapid-acting insulin analogs (RAIAs). Hence, this post-marketing safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit for URLi-treated patients (i.e., a descriptive analysis). This study also compared the risk of severe hypoglycemia among patients treated with URLi or other RAIAs (i.e., a comparative analysis). Considering the diverse treatment regimens in the real world, this study also evaluated the aforementioned objectives in multiple subgroups as described later.

— Source (introduction, peer-reviewed): Seiko Mizuno, Machiko Minatoya, Satoshi Osaga, et al. · (2024) · "Investigation of Severe Hypoglycemia Risk Among Patients with Diabetes Treated with Ultra-Rapid Lispro in Japan" · Advances in Therapy · doi: 10.1007/s12325-024-03050-1 · PMCID: PMC11782313 · PMID: 39570544
License: CC-BY-NC. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Natalia A. Frankevich, Alisa O. Tokareva, Anna A. Derenko, et al. · (2026) · "Amino Acid Dysregulation in the Mother–Fetus Unit: Multi-Compartment Metabolomic Signatures of Gestational Diabetes Mellitus and Fetal Macrosomia" · International Journal of Molecular Sciences · doi: 10.3390/ijms27083346 · PMCID: PMC13116625 · PMID: 42073989

Question: What did the discussion section of the paper "Amino Acid Dysregulation in the Mother–Fetus Unit: Multi-Compartment Metabolomic Signatures of Gestational Diabetes Mellitus and Fetal Macrosomia" cover?

Answer:
The main risk factors for GDM in the studied cohort were high risk of PE (OR ≈ 6.75), family history of diabetes (OR ≈ 3.9), and elevated pre-pregnancy and delivery BMI. The heterogeneity of GDM is supported by the substantial proportion of women with normal weight (54%). Shared pathogenetic mechanisms with PE, evidence of systemic inflammation, and residual metabolic imbalance despite treatment underscore the need for improved therapeutic strategies. The absence of differences in most obstetric outcomes reflects the effectiveness of timely diagnosis and therapy.

These findings are fully consistent with the contemporary concept of GDM as a heterogeneous condition requiring a personalized approach. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study [ 23 ] demonstrated that the long-term consequences of GDM for mothers (risk of type 2 diabetes mellitus, cardiovascular disease) and offspring (obesity, impaired glucose tolerance) depend not only on the degree of hyperglycemia but also on baseline metabolic status, gestational weight gain, and genetic factors. The differences observed between subgroups 3 and 4 in the present study confirm the existence of distinct GDM phenotypes: “compensated” (with weight control and dietary therapy) and “decompensated” (with pathological weight gain, elevated glucose levels, and FM). This aligns with recent work in this area [ 24 , 25 ].

Current international guidelines (NICE, ACOG, FIGO) emphasize the need for a comprehensive approach to managing pregnant women with GDM, including not only glycemic control but also monitoring of gestational weight gain, screening for urinary tract infections, assessment of coagulation status, and consideration of risk factors such as history of macrosomia and family history of diabetes. The data obtained in this study confirm the importance of each of these components and justify the need for further prospective studies with larger sample sizes to develop more accurate prognostic models and therapeutic strategies.

This study revealed significant differences in the amino acid profiles of maternal serum, umbilical cord blood, and amniotic fluid between GDM and physiological pregnancies, and established an association between these alterations and the development of FM, opening new perspectives for understanding the pathogenesis of metabolic disturbances and their prediction. The findings demonstrate that GDM is accompanied by profound remodeling of amino acid metabolism, affecting not only the maternal organism but also the fetoplacental unit, with the pattern of these changes differing according to the presence or absence of FM. This allows for consideration of specific amino acids as potential biomarkers for different clinical outcomes. Analysis of maternal serum identified glycine, 1-methylhistidine, γ-aminobutyric acid, lysine, and tryptophan as the most informative GDM markers, with all except tryptophan showing statistically significant concentration decreases during GDM development. This finding aligns with the current understanding of enhanced amino acid consumption by the fetoplacental complex and impaired amino acid synthesis under conditions of insulin resistance [ 26 , 27 ].

Of particular note is the observed differential dynamics of lysine and 1-methylhistidine, which not only decreased in GDM overall but also exhibited specific alterations in the subgroup of women delivering normal-weight newborns, indicating the existence of distinct metabolic phenotypes within the GDM group and underscoring the heterogeneity of this condition. Analysis of the amino acid profile in umbilical cord blood revealed a substantially broader spectrum of alterations, including glutamine, glycine, asparagine, methionine, aspartic acid, γ-aminobutyric acid, glutamic acid, β-alanine, proline, citrulline, and alanine, all of which also showed decreased concentrations in GDM. These processes reflect impaired placental transport and altered metabolism in fetal tissues under conditions of hyperglycemia and hyperinsulinemia [ 28 ]. Of particular interest is the identified association between levels of branched-chain amino acids, specifically leucine and allo-isoleucine, in cord blood and the development of FM, confirming the key role of these compounds in stimulating insulin secretion and activating anabolic processes in the fetal organism, leading to excessive adipose tissue accumulation and increased birth weight [ 14 ].

Analysis of amniotic fluid identified lysine, threonine, 1-methylhistidine, and histidine as GDM markers; however, a different dynamic was observed here: lysine and 1-methylhistidine levels were significantly increased in GDM, which may be related to enhanced excretion of these amino acids by the fetal kidneys or to alterations in amniotic fluid composition resulting from polyuria characteristic of fetal hyperglycemia [ 29 , 30 ]. Interestingly, the GDM group subsequently delivering macrosomic infants was characterized by low levels of homocitrulline, asparagine, aminobutyric acid, and lysine, alongside high histidine concentrations, whereas the opposite pattern predominated in the GDM group without macrosomia. This suggests distinct metabolic trajectories leading to excessive fetal weight gain and opens opportunities for early risk stratification.

Correlation analysis revealed a complex network of relationships between clinical parameters and amino acid profiles, with the strongest negative correlations observed between total protein and fibrinogen concentrations in maternal blood and the levels of numerous amino acids in both maternal and umbilical cord serum. This reflects the tight integration of protein and amino acid metabolism and their coordinated regulation under conditions of metabolic stress [ 31 ].

Of particular interest are the observed correlations between newborn birth weight and concentrations of specific amino acids. Interestingly, maternal BMI both before pregnancy and at delivery showed weak but statistically significant correlations with a limited spectrum of amino acids, predominantly 3-aminoisobutyric acid and 2-aminoadipic acid, whereas gestational weight gain was associated with a broader range of metabolites, including proline, tyrosine, phenylalanine, and methionine. This underscores the importance of dynamic changes in body weight, rather than baseline anthropometric measures alone, in shaping the amino acid profile [ 32 ]. Summary Table S4 presents alterations in amino acid levels across the three biological compartments (maternal serum, umbilical cord serum, amniotic fluid) in GDM, as well as features characteristic of GDM cases complicated by FM.

The metabolic pathway enrichment analysis using the SMPDB identified key biochemical processes disrupted in GDM and in GDM with FM. Markers of GDM in maternal serum were primarily associated with biotin metabolism, glutamate metabolism, and carnitine synthesis, whereas markers in cord blood enriched a broader spectrum of pathways, including amino acid metabolism, purine metabolism, and amino sugar metabolism, reflecting the systemic nature of metabolic disturbances in the fetus. In amniotic fluid, GDM markers were associated with biotin metabolism, phenylacetate metabolism, aspartate metabolism, and the ammonia cycle, whereas in GDM with FM, the methylhistidine metabolism pathway was additionally enriched. This may be directly related to altered muscle metabolism and changes in body composition in macrosomic newborns. Summary data are presented in Table S5 .

The observed changes in the amino acid profiles within the maternal–fetal dyad provide critical insights into the mechanistic links between maternal metabolic dysregulation and excessive fetal growth [ 33 ]. These findings can be interpreted within the framework of key signaling pathways that integrate nutrient sensing with cellular growth and metabolism. The mammalian target of rapamycin (mTOR) pathway serves as a central nutrient sensor, particularly sensitive to amino acid availability, and plays a critical role in placental function and fetal growth [ 34 ]. Our observation of decreased branched-chain amino acid (BCAA; leucine, isoleucine, valine) levels in umbilical cord blood in gestational diabetes mellitus (GDM), alongside elevated leucine and allo-isoleucine, particularly in cases of macrosomia, is highly relevant to mTOR signaling. Leucine is a potent activator of mTOR complex 1 (mTORC1) through its interaction with sestrin 2, which relieves inhibition of mTORC1 [ 35 ]. In the placenta, mTORC1 activity regulates system A and system L amino acid transporters, establishing a positive feedback loop in which amino acid availability modulates transporter expression, which in turn determines nutrient delivery to the fetus [ 36 , 37 ]. The elevated leucine levels observed in fetal macrosomia may reflect hyperactivation of placental mTORC1, driving increased amino acid transport and subsequent fetal insulin secretion, thereby promoting anabolic growth. The insulin signaling pathway intersects with amino acid metabolism at multiple levels. Maternal hyperinsulinemia in GDM directly suppresses hepatic gluconeogenesis while simultaneously stimulating protein synthesis in maternal tissues, potentially contributing to the observed reduction in maternal amino acid concentrations. Fetal hyperinsulinemia, a hallmark of fetal macrosomia, further promotes amino acid uptake and protein accretion in fetal tissues [ 38 ]. Our correlation analysis, demonstrating positive associations between fetal weight and lysine (R = 0.45), isoleucine (R = 0.46), and leucine (R = 0.34), supports this mechanism. Conversely, the negative correlation with homocitrulline (R = −0.41) suggests that impaired urea cycle function may accompany excessive anabolic activity.

The amino acid profile undergoes systemic changes across compartments (mother, umbilical cord, AF); however, these changes are not mirror-like. For example, 1-methylhistidine decreases in maternal blood but increases in AF, highlighting the importance of investigating multiple compartments to understand the complete picture. Decreases in glycine and GABA indicate oxidative stress, inflammation, and impaired neuro/metabolic regulation. Reduced levels of glutamine, asparagine, and citrulline in umbilical cord blood reflect fetoplacental unit dysfunction, including impaired nutrient transport, endothelial dysfunction, and possibly intrauterine fetal metabolic stress.

Amniotic fluid serves as a unique “window” into fetal status. Alterations in AF (increased 1-methylhistidine and lysine) may reflect not so much placental transport as fetal renal function, skin and lung condition, and meconium composition [ 33 ]. This makes AF a valuable specimen for assessing the fetal response to maternal hyperglycemia. The observed changes (particularly glycine and glutamine deficiency) point to potential targets for nutritional intervention or biochemical monitoring aimed at reducing fetal risks. However, this requires further investigation.

Thus, the compartment-specific changes we observed reflect differential regulation of amino acid metabolism in maternal and fetal tissues. Decreased glycine and glutamine levels in maternal serum indicate enhanced utilization of gluconeogenic substrates and possible disruption of one-carbon metabolism, with glycine serving as a methyl donor in the methionine cycle and potentially influencing fetal epigenetic programming [ 39 , 40 ]. The significant enrichment of glutamate metabolism pathways among maternal markers is consistent with the role of glutamate as a key nitrogen carrier and precursor for glutathione synthesis, pointing to involvement of oxidative stress [ 41 ]. In umbilical cord blood, the widespread decrease in amino acids, including glutamine, asparagine, and methionine, suggests either impaired placental transport or enhanced fetal utilization, with methionine being critically important for methylation reactions and polyamine synthesis required for rapid fetal growth [ 39 , 42 ]. Enrichment of amino sugar metabolism pathways in umbilical cord blood markers may reflect alterations in glycosylation patterns or remodeling of the extracellular matrix in fetal tissues. Analysis of amniotic fluid reveals unique aspects of fetal excretory function: increased lysine and 1-methylhistidine suggests either fetal polyuria with concentration of these amino acids or altered tubular reabsorption. Histidine, which shows differential patterns in macrosomia, is a precursor of histamine and carnosine involved in antioxidant and anti-inflammatory mechanisms, and the specific enrichment of the methylhistidine metabolism pathway in GDM with macrosomia is particularly interesting, as 3-methylhistidine serves as a marker of myofibrillar protein breakdown [ 43 ], and its elevated level may reflect either increased muscle protein turnover in macrosomic fetuses or subclinical myopathy resulting from chronic hyperglycemic exposure. The distinct metabolic signatures in GDM with and without macrosomia support the concept of GDM heterogeneity: women who develop macrosomia, despite similar glycemic control, exhibit differences in amino acid metabolism that may reflect genetic variations in transporter efficiency or insulin sensitivity. Elevated branched-chain amino acid levels in umbilical cord blood in macrosomia may directly contribute to β-cell hyperplasia and hyperinsulinemia, as leucine allosterically activates glutamate dehydrogenase, potentiating glucose-stimulated insulin secretion, thereby establishing a direct link between maternal amino acid dysregulation and development of the fetal endocrine pancreas [ 44 ]. The inverse correlation of homocitrulline with fetal weight across all compartments warrants particular attention. Homocitrulline is formed by carbamylation of lysine under conditions of oxidative stress, and its low level may indicate either less oxidative protein modification or alterations in urea cycle function [ 45 ]. Amniotic fluid analysis, given its clinical accessibility, has the potential to provide prognostic information regarding the risk of excessive fetal growth. The involvement of specific metabolic pathways such as biotin metabolism, carnitine synthesis, and methylhistidine metabolism may point to potential therapeutic targets in the future, enabling a transition from mere biomarker identification to mechanistic understanding that can serve as a foundation for developing interventional strategies.

An important methodological limitation for interpretation: all conclusions drawn from this study are preliminary (hypothesis-generating) in nature due to the small sample size. They indicate interesting trends and biological mechanisms that should be confirmed in an independent, larger-scale cohort. It is important to note that in 2025, we published an article entitled “Amino Acid Profile Alterations in the Mother-Fetus System in Gestational Diabetes Mellitus and Macrosomia” [ 15 ], based on the results of a two-center study (Moscow + Tomsk) conducted from January 2024 to March 2025, which included 94 mother–fetus dyads (GDM group: 53, control group: 41; GDM + FM: 23, GDM + normosomia: 30, control: 36). Comparative analysis of data from the Tomsk patient cohort and the Moscow cohort (the present publication) revealed high consensus on key markers: glutamine, histidine, and asparagine were consistently decreased in GDM in maternal blood; isoleucine, leucine, and serine were consistently increased in FM in cord blood and AF; GABA decrease was confirmed in both studies (marker of metabolic dysregulation). Both studies confirm the involvement of amino acid transport, glutamate metabolism, and the urea cycle. Lysine and isoleucine were the most consistent positive correlates of fetal weight; homocitrulline was a consistent negative correlate of fetal weight. Both studies demonstrate high consistency of results, despite different cohorts and sample sizes. The identified markers (glutamine, histidine, asparagine in maternal blood; isoleucine, leucine, serine in cord blood and AF) can be considered valid candidates for the development of diagnostic panels. The differential dynamics of amino acids across different biological compartments underscore the need for a comprehensive approach to assessing the mother–fetus system and open prospects for early diagnosis and personalized correction of metabolic disturbances in GDM and FM.

— Source (discussion, peer-reviewed): Natalia A. Frankevich, Alisa O. Tokareva, Anna A. Derenko, et al. · (2026) · "Amino Acid Dysregulation in the Mother–Fetus Unit: Multi-Compartment Metabolomic Signatures of Gestational Diabetes Mellitus and Fetal Macrosomia" · International Journal of Molecular Sciences · doi: 10.3390/ijms27083346 · PMCID: PMC13116625 · PMID: 42073989
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Emily Salas-Groves, Shannon Galyean, Michelle Alcorn, et al. · (2023) · "Behavior Change Effectiveness Using Nutrition Apps in People With Chronic Diseases: Scoping Review" · JMIR mHealth and uHealth · doi: 10.2196/41235 · PMCID: PMC9883741 · PMID: 36637888

Question: What is the published background on "Behavior Change Effectiveness Using Nutrition Apps in People With Chronic Diseases: Scoping Review"? Cite a peer-reviewed source.

Answer:
Cardiovascular disease (CVD), cancer, diabetes mellitus (DM), and obesity are common chronic diseases [ 1 ], and their prevalence is reaching a substantial epidemic level internationally [ 2 ]. Chronic diseases are defined by the Centers for Disease Control and Prevention broadly as “conditions that last one year or more and require ongoing medical attention or limit activities of daily living or both” [ 3 ]. Chronic diseases affect hospitalization, mortality rates, and people’s overall health and quality of life (QOL) [ 1 ]. For example, CVD remains the most prevalent cause of morbidity and mortality in high-income countries despite significant advances in treatment over the last 5 decades. Recent epidemiological data show that CVD mortality is no longer declining and is indeed rising in some communities [ 4 ], and hospitalization rates are universally increasing [ 5 ]. Furthermore, chronic conditions such as cancer, CVD, DM, and chronic respiratory diseases caused approximately 33.2 million deaths worldwide in 2019 [ 6 ]. The prevalence of obesity has increased in all World Health Organization regions since 2000, which affects other chronic conditions as it is a risk factor for the development of CVD, DM, and several cancers [ 6 ].

As the impact of chronic diseases continues to increase, finding strategies to improve care, access to care, and patient empowerment becomes increasingly essential. Therefore, mobile health (mHealth) technology is rapidly gaining popularity among health care providers and consumers [ 7 ]. mHealth technology is defined as mobile devices (ie, mobile phones or monitoring devices) intended to be worn, carried, or accessed by patients or health care providers to monitor health status or improve health outcomes [ 8 ]. Among mobile devices, the most used are smartphones, with more than three-quarters of Americans having one, and at least one-third of smartphone owners use a health app [ 7 , 9 ]. Health care providers use mHealth to access clinical information, collaborate with care teams, communicate over long distances with patients, and facilitate real-time monitoring and interventions. These apps provide an opportunity to increase health care access for vulnerable populations [ 10 ]. Patients use mHealth to track their health data, access their clinical records, and communicate with their providers [ 11 ].

Furthermore, a meta-analysis [ 12 ] reported promising results for mHealth interventions in the improvement of patient outcomes such as body measurements (ie, weight and waist circumference), metabolic and physiological measurements (ie, blood pressure and glucose levels), adherence to and safe use of medication, physical activity performance, meal management, and awareness of health conditions and treatment options. Mobile apps that provide tools intended to facilitate nutrition care via smartphone technologies provide patients with more autonomy, thus empowering them and offsetting patient disengagement [ 13 ]. Moreover, mobile app–based interventions effectively improve diet and diet-related health outcomes, and effect sizes are comparable with those of traditional nondigital interventions [ 14 ]. For example, mHealth interventions can help improve lifestyle behaviors related to CVD [ 15 , 16 ]. A recent meta-analysis [ 17 ] found that using mHealth interventions for CVD was associated with improved blood pressure and hospitalization rates. In addition, mHealth apps have emerged as supportive tools in managing cancer as they reduce the financial burden, provide access to information, and facilitate communication [ 18 ]. Different studies and meta-analyses of patients with cancer have shown the benefits of mHealth, which include reducing fatigue or pain [ 19 , 20 ], providing distance physical activity programs [ 21 , 22 ], the use of social networks to improve QOL [ 23 ], and monitoring of symptoms [ 24 ]. mHealth offers improved and cost-effective care to people with type 2 DM (T2DM) through improved diabetes self-management [ 25 , 26 ]. These apps seem to increase the perception of self-care by contributing to better knowledge among people with T2DM [ 10 ]. Individuals with DM also become more confident in dealing with their illness, primarily because of decreased fear resulting from a lack of information [ 27 , 28 ]. For obesity, a systematic review [ 29 ] has found that technology-based interventions can provide a moderately effective way of facilitating lifestyle changes and weight loss. New technologies could help reduce economic costs, improve accessibility and adherence to treatment, and increase patient motivation and weight control [ 30 ].

The use of mobile apps for mHealth and of general health apps is increasing rapidly. However, these apps focus on improving general health care concerns, with limited apps focusing on specific chronic diseases and their nutritional intervention. The available evidence on the effectiveness of mHealth apps toward behavior change to improve chronic disease outcomes is also limited. Systematic reviews to date regarding nutrition apps have focused on healthy participants or examined the effects of dietary apps on diet improvement but not on chronic diseases [ 31 ]. Most reviews were inconclusive, with the authors recommending further research in this area to demonstrate possible benefits [ 32 - 34 ]. From a clinical point of view, it is essential to know if an app designed for chronic diseases produces behavior changes to improve an individual’s chronic disease outcomes. From an app creator’s point of view, it is crucial to see what needs to be done when developing an app directed toward people with chronic diseases to enhance the app’s effectiveness on behavior change and produce positive outcomes. The goal of this review was to define behavioral theories associated with mHealth use, evaluate behavior change techniques (BCTs), and describe the behavior change effectiveness using mHealth nutrition interventions in people with chronic diseases (ie, CVD, DM, cancer, and obesity).

— Source (introduction, peer-reviewed): Emily Salas-Groves, Shannon Galyean, Michelle Alcorn, et al. · (2023) · "Behavior Change Effectiveness Using Nutrition Apps in People With Chronic Diseases: Scoping Review" · JMIR mHealth and uHealth · doi: 10.2196/41235 · PMCID: PMC9883741 · PMID: 36637888
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Ayman F. Sabry, Patrick D. Evers, Erin J. Madriago · (2025) · "Association Between Sphericity and Ventricular Function in Fetus of Diabetic Mother: A Longitudinal Study from Fetal to Neonatal Period" · Pediatric Cardiology · doi: 10.1007/s00246-025-03882-w · PMCID: PMC12901260 · PMID: 40418292

Question: What is the published background on "Association Between Sphericity and Ventricular Function in Fetus of Diabetic Mother: A Longitudinal Study from Fetal to Neonatal Period"? Cite a peer-reviewed source.

Answer:
Diabetes mellitus (DM) is a relatively common medical disorder of pregnancy affecting about 7% of the pregnant population and it includes pregestational diabetes (PGD) and gestational diabetes mellitus (GDM) [ 1 , 2 ]. DM not only leads to maternal complications in later life of mother but also immediate and later fetal complications [ 2 , 3 ]. In all the diabetic pregnancies GDM accounts for more than 80% and the rest are PGD (type I and type II) [ 1 ]. In PGD, high maternal glucose level appears before pregnancy; in contrast to GDM, abnormal maternal glucose level starts from second to third trimester [ 2 , 3 ].

DM is a systemic chronic metabolic disorder characterized by increased insulin resistance and/or β-cell defects [ 4 , 5 ]. Intrauterine exposure to high level of maternal blood glucose significantly increases the insulin secretion in fetal pancreas, leading to fetal hyperinsulinemia, and the fetal heart is one of the major organs affected by hyperinsulinemia [ 3 – 5 ]. The rapid cell proliferation and differentiation during fetal growth are very sensitive to any changes in environment leading to permanent alteration in the cardiac structural and functional constitution [ 5 – 7 ].

Cardiac function impairment in the fetus of the diabetic mother during the second and third trimester is well established and the timing and severity of hyperglycemia in relation to gestational age are a critical factor that determines these effects [ 8 , 9 ]. The diastolic dysfunction represents the earliest manifestation of diabetic cardiomyopathy, preceding the systolic dysfunction [ 9 , 10 ]. Ventricular remodeling encompasses alternation in ventricular mass, shape, and geometry as a result of an increased hemodynamic load, neurohormonal activation, and genetic factors [ 11 – 13 ]. The sphericity index (SI) is used to evaluate the change of the shape of the right and left ventricles [ 11 , 12 ]. Less is known about changes in ventricular geometry and remodeling during fetal life among different diabetic levels and its association with cardiac dysfunction and the persistence of these changes in neonatal period.

Therefore, the purpose of this study was to provide a detailed overview of the fundamental mechanism of ventricular remodeling and its relation to cardiac function for different types and levels of DM during pregnancy and postnatally.

— Source (introduction, peer-reviewed): Ayman F. Sabry, Patrick D. Evers, Erin J. Madriago · (2025) · "Association Between Sphericity and Ventricular Function in Fetus of Diabetic Mother: A Longitudinal Study from Fetal to Neonatal Period" · Pediatric Cardiology · doi: 10.1007/s00246-025-03882-w · PMCID: PMC12901260 · PMID: 40418292
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Mona Hassan, Mahmoud ElHelaly, Nora Badawi, et al. · (2025) · "Impact of tailored diabetes education on adherence and glycemic control in children and adolescents on continuous subcutaneous insulin infusion, prospective interventional study in a tertiary center" · BMC Pediatrics · doi: 10.1186/s12887-025-06018-4 · PMCID: PMC12400561 · PMID: 40887640

Question: Summarize the abstract of the paper titled "Impact of tailored diabetes education on adherence and glycemic control in children and adolescents on continuous subcutaneous insulin infusion, prospective interventional study in a tertiary center".

Answer:
Structured diabetes education plays a crucial role in the management of Type 1 Diabetes (T1D), especially with advanced technologies such as continuous subcutaneous insulin infusion (CSII). This study evaluates the impact of tailored education on adherence and glycemic control among pediatric CSII users.

This interventional analytical study included 30 patients diagnosed with T1D with age ranged from 5 to 18 years, recruited from Diabetes & Endocrinology Clinic at tertiary university-based children’s hospital. Patients were recruited for one year duration. Patients who were on multiple daily injection (MDI) for 2 to 10 years were shifted to CSII after receiving comprehensive diabetes education. Their education level was assessed individually using a questionnaire to assess patients’ knowledge and application skills at the time of insulin pump insertion, 3 and 6 months later. Twenty-five patients were on mini-med 715, 10 patients used flash glucose monitoring, and 15 patients used self-monitoring blood sugar, while five patients were on mini-med 780G and continuous glucose monitoring (CGM) using guardian 4 (G4).

Study included 19 females (63.3%) and 11 males (36.7%) with age ranged from 7 to 11 with mean ± SD of 10.74 ± 1.86. Patients’ education level was assessed before pump insertion, and 3 months later which shows significant improvement in patients’ diabetes knowledge and technical skills with P-value 0.038. Also, time in range (TIR) improved significantly in well-educated patients at 3 and 6 months with P-values 0.048 and 0.025 respectively. There was highly significant improvement of HbA1c after 6 months (8.82 ± 1.5 vs. 7.18 ± 0.56) with P-value 0.000 after receiving diabetes education.

Tailored diabetes education significantly improves adherence and glycemic outcomes in pediatric patients using CSII. Integrating structured educational programs with diabetes technology is essential to achieve optimal metabolic control in youth.

— Source (abstract, peer-reviewed): Mona Hassan, Mahmoud ElHelaly, Nora Badawi, et al. · (2025) · "Impact of tailored diabetes education on adherence and glycemic control in children and adolescents on continuous subcutaneous insulin infusion, prospective interventional study in a tertiary center" · BMC Pediatrics · doi: 10.1186/s12887-025-06018-4 · PMCID: PMC12400561 · PMID: 40887640
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Rania Niri, Sofia Zahia, Alessio Stefanelli, et al. · (2025) · "Wound Segmentation with U-Net Using a Dual Attention Mechanism and Transfer Learning" · Journal of Imaging Informatics in Medicine · doi: 10.1007/s10278-025-01386-w · PMCID: PMC12572562 · PMID: 39849203

Question: Summarize the abstract of the paper titled "Wound Segmentation with U-Net Using a Dual Attention Mechanism and Transfer Learning".

Answer:
Accurate wound segmentation is crucial for the precise diagnosis and treatment of various skin conditions through image analysis. In this paper, we introduce a novel dual attention U-Net model designed for precise wound segmentation. Our proposed architecture integrates two widely used deep learning models, VGG16 and U-Net, incorporating dual attention mechanisms to focus on relevant regions within the wound area. Initially trained on diabetic foot ulcer images, we fine-tuned the model to acute and chronic wound images and conducted a comprehensive comparison with other state-of-the-art models. The results highlight the superior performance of our proposed dual attention model, achieving a Dice coefficient and IoU of 94.1% and 89.3%, respectively, on the test set. This underscores the robustness of our method and its capacity to generalize effectively to new data.

— Source (abstract, peer-reviewed): Rania Niri, Sofia Zahia, Alessio Stefanelli, et al. · (2025) · "Wound Segmentation with U-Net Using a Dual Attention Mechanism and Transfer Learning" · Journal of Imaging Informatics in Medicine · doi: 10.1007/s10278-025-01386-w · PMCID: PMC12572562 · PMID: 39849203
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Salvatore Monti, Beatrice Fazzalari, Valerio Renzelli, et al. · (2026) · "Effects of Lenvatinib treatment for advanced differentiated thyroid cancer on cortisol deficiency" · Frontiers in Endocrinology · doi: 10.3389/fendo.2025.1691740 · PMCID: PMC12812715 · PMID: 41561040

Question: What did the discussion section of the paper "Effects of Lenvatinib treatment for advanced differentiated thyroid cancer on cortisol deficiency" cover?

Answer:
Among the adverse events evaluated during Lenvatinib treatment, routine monitoring of adrenal function is not commonly performed in real life; however, recent evidence from relatively small series of patients with advanced thyroid cancer has suggested a potential impact of Lenvatinib on development of PAI and fatigue ( 5 – 9 ).

It is now recognized that PAI can occur with Lenvatinib treatment, but its clinical significance remains unclear. Consequently, PAI is not always investigated in patients receiving Lenvatinib, which may delay diagnosis.

PAI is a serious and potentially life-threatening condition, and its simultaneous occurrence in patients with RR-DTC could have a profoundly negative impact on the morbidity and mortality of those treated with Lenvatinib, by increasing drug-related toxicity. In this context, early diagnosis plays a crucial role.

In this prospective study, using the current Endocrine Society Clinical Practice Guideline ( 12 ), we observed a higher prevalence (77.4%) of PAI-18.1 in patients with peak cortisol levels below 500 nmol/L (18.1 mcg/dL) compared to previous reports. This is likely because we routinely monitor adrenal function with ACTH stimulation testing more frequently than other studies, which often assess adrenal function only when ACTH levels are elevated.

Our study design therefore allows early identification of mild PAI cases. Furthermore, repeated ACTH stimulation tests performed during follow-up consistently confirmed the diagnosis of PAI and demonstrated a progressive decline in cortisol response during Lenvatinib treatment.

The mechanisms underlying Lenvatinib-induced PAI remain unknown. Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI); notably, two of its targets—the vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptor alpha (PDGFRα)—may be involved in adrenal regulation ( 14 , 15 ). A key role seems to be played by the reduction of vascular density, mainly due to VEGF inhibition, causing ischemic damage to the adrenal cortex. Interestingly, a study in mice showed recovery of vascular damage following Lenvatinib withdrawal ( 16 ).

This experimental study supports the possibility that the adverse effect of Lenvatinib on adrenal function may be transient and dose-dependent, with recovery of adrenal function following drug discontinuation, as is common with other treatment-related adverse events. Notably, in one of our patients with PAI, Lenvatinib was interrupted for 34 days after one year of treatment due to surgical complications following laparoscopic cholecystectomy. After appropriate discontinuation of cortisone acetate, repeated ACTH stimulation test showed normal peak cortisol levels (597.9 nmol/L). Lenvatinib was then resumed at the previous dose (14 mg). However, after three months of reinitiation, two consecutive ACTH stimulation tests revealed a recurrence of PAI.

The strength of our study is the ability to evaluate adrenal function both before and during treatment with Lenvatinib. All our patients had normal adrenal function prior to starting Lenvatinib. Moreover, none of the patients presented with adrenal metastases or other adrenal gland abnormalities that could cause PAI, as confirmed by whole-body CT scans and whole-body 18F-FDG PET/CT during follow-up. Together, these findings support the conclusion that PAI is induced by Lenvatinib.

In recent years, there has been a proposal to lower the serum cortisol cut-off for the diagnosis of primary adrenal insufficiency (PAI) compared to the threshold established in the 2016 Endocrine Society Clinical Practice Guideline ( 12 ). While using an ACTH-stimulated peak cortisol threshold of 18 mcg/dL (500 nmol/L) to exclude adrenal insufficiency minimizes missed diagnoses, it may lead to overdiagnosis when more specific assays are employed. Consequently, several recent studies utilizing more specific (less cross-reactive) cortisol assays have suggested lowering the ACTH-stimulated peak cortisol cut-off to between 14 mcg/dL (386.2 nmol/L) and 15 mcg/dL (413.8 nmol/L) to reduce false-positive results in ACTH stimulation tests ( 13 , 17 ).

In this context, we applied an ACTH-stimulated peak cortisol cut-off of 14 mcg/dL as a diagnostic criterion for PAI (PAI-14). As expected, the prevalence of PAI-14 was lower than that of PAI-18.1; however, it remained substantial, with 14 out of 31 patients (45.2%) meeting the PAI-14 criterion.

The diagnosis of PAI-14 was preceded, on average, by an increase in ACTH levels 11.77 ± 8.38 months earlier in 92.3% of cases. This rise was greater, although not statistically significant (p = 0.054), compared to the increase observed before the diagnosis of PAI-18.1, which occurred in only 62.5% of cases and on average 6.28 ± 5.69 months earlier.

This observation indicates that cortisol deficiency is, as expected, more pronounced in PAI-14 than in PAI-18.1. Indeed, cortisol deficiency leads to reduced negative feedback on the hypothalamic-pituitary axis and a consequent compensatory increase in ACTH levels, reflecting greater biochemical and clinical impairment of PAI ( 12 ).

Treatment with cortisone acetate (CA) resulted in a significant improvement in fatigue, particularly during the first 3 months of therapy, with benefits persisting in the majority of cases, especially among patients with PAI-14.

Fatigue is one of the most common treatment-related adverse events, with a reported prevalence of up to 90–100% of cases ( 18 – 22 ). The wide variability in fatigue prevalence reported in the literature is partly due to the frequent underestimation and underdiagnosis of fatigue in clinical practice, despite it being a distressing and disabling condition.

Fatigue is a major cause of dose reduction, interruption, or discontinuation of Lenvatinib treatment, potentially leading to decreased treatment efficacy and shorter progression-free survival (PFS) ( 4 ). Managing fatigue effectively is critical to maintain optimal treatment adherence and maximize clinical benefit ( 23 ).

The mechanisms underlying fatigue are not yet fully elucidated. Fatigue arises from a complex interplay of multiple factors, including physical, psychological and biochemical conditions ( 24 ).

This study confirms that in the presence of fatigue, it is necessary to exclude PAI. If PAI is diagnosed, prompt initiation of glucocorticoid replacement therapy is essential to manage fatigue in Lenvatinib treatment.

Based on current evidence, we propose that all patients considered for Lenvatinib treatment undergo evaluation of adrenal function using a 250 μg ACTH stimulation test along with serum ACTH level measurement. A cortisol peak greater than 646.6 nmol/L indicates a low risk (approximately 30%) of developing PAI. In such cases, if ACTH levels are within the normal range, repeat ACTH stimulation testing is not mandatory; however, if ACTH levels are elevated beyond the upper limit of normal, ACTH stimulation testing should be repeated within 3 to 6 months.

Conversely, a cortisol peak below 646.6 nmol/L suggests a high risk (about 70%) of PAI development. For these patients, ACTH stimulation tests should be repeated according to ACTH concentrations: if ACTH is normal, retesting may be delayed but should occur within 6 to 12 months; if ACTH levels are elevated, repeat ACTH stimulation should be performed as soon as possible to guide timely diagnosis and management.

There are some limitations of our study that should be considered. It is a prospective single-center investigation conducted at a tertiary referral center, involving a relatively small sample size of 31 patients, which may limit the generalizability of the findings to broader populations of patients with RR-DTC treated with Lenvatinib. Additionally, the limited sample size may lack sufficient statistical power to detect weaker associations between PAI development, baseline clinical characteristics, and treatment parameters (e.g., initial dose, dose intensity, duration).

In conclusion, based on our experience and supported by the literature, we recommend that adrenal function assessment be incorporated into the evaluation of patients treated with Lenvatinib, especially those experiencing fatigue. When PAI is confirmed, initiating glucocorticoid replacement therapy is advisable to manage fatigue and prevent unnecessary dose reduction or discontinuation of Lenvatinib treatment. This approach aligns with findings that PAI is a common and treatable cause of fatigue in this patient population, and that early intervention improves clinical outcomes and quality of life.

— Source (discussion, peer-reviewed): Salvatore Monti, Beatrice Fazzalari, Valerio Renzelli, et al. · (2026) · "Effects of Lenvatinib treatment for advanced differentiated thyroid cancer on cortisol deficiency" · Frontiers in Endocrinology · doi: 10.3389/fendo.2025.1691740 · PMCID: PMC12812715 · PMID: 41561040
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Julia Otten, Anna Tellström, Claudia Schien, et al. · (2025) · "eHealth versus face-to-face support for remission of type 2 diabetes by calorie restriction (eHealth DIabetes remission Trial): study protocol for a non-inferiority parallel group randomised controlled trial" · BMJ Open · doi: 10.1136/bmjopen-2024-095100 · PMCID: PMC12306309 · PMID: 40701606

Question: What is the published background on "eHealth versus face-to-face support for remission of type 2 diabetes by calorie restriction (eHealth DIabetes remission Trial): study…"? Cite a peer-reviewed source.

Answer:
A breakthrough in the treatment of type 2 diabetes is the recent Diabetes REmission Clinical Trial (DiRECT), which shows that long-term remission of type 2 diabetes can be achieved through calorie restriction. 1 2 The study found that of the people with type 2 diabetes who received total diet replacement with 850 kcal/day over a period of 3 to 5 months, 46% were in diabetes remission after 1 year, and 36% were still in remission after 2 years. 2 Diabetes remission is defined as haemoglobin A1c (HbA1c) below 48 mmol/mol (6.5%) without diabetes medication. 3 The HbA1c value reflects the average plasma glucose level of the last 2 months. In the DiRECT study, the diabetes remission rate was up to 70% in those who had maintained a weight loss of at least 15 kg. 2 Remarkably, the main motivator for study participants to lose weight was to achieve diabetes remission and thus avoid diabetes medication, 4 that is, remission was a much greater source of motivation than the promise that weight loss would reduce the risk of future complications and increase life expectancy.

According to a health economic evaluation of the DiRECT study, diabetes remission with total diet replacement is cost-saving after 5–6 years despite face-to-face meetings between patient and healthcare provider every 2 to 4 weeks. 5 Based on the results of the DiRECT study, calorie restriction with the goal of 15 kg weight loss and diabetes remission is now strongly recommended in the treatment guidelines of the European and American Diabetes Associations. 6

As far as we know, no dietary intervention with the overarching aim of remission of type 2 diabetes has yet been conducted comparing eHealth with face-to-face care. eHealth can have many benefits: It may be more effective than face-to-face care because it eliminates travel time for the patient, and it allows for a more flexible schedule for both the patient and the healthcare provider. In studies where eHealth was used to lower blood glucose levels in people with diabetes, eHealth was superior to conventional care. 7 In addition, a meta-analysis found that prevention of type 2 diabetes through eHealth via weight loss was successful in 63% of interventions in the short term and in 21% in the long term, that is, 12 months or longer. 8 However, only half of the studies were randomised controlled trials, and the control group usually received no intervention. The question of whether an intervention with eHealth support is more effective than face-to-face support is therefore still open.

After 3 months of total diet replacement and reaching the weight goal, food is gradually reintroduced for 6 weeks to reduce the risk of regaining weight. One meal at a time is reintroduced over about 2 weeks. During this time, participants receive guidance on how to prepare nutritious, low-calorie meals and snacks that meet the dietary recommendations. To allow flexibility for participants, the food reintroduction phase can be longer or shorter than 6 weeks.

— Source (introduction, peer-reviewed): Julia Otten, Anna Tellström, Claudia Schien, et al. · (2025) · "eHealth versus face-to-face support for remission of type 2 diabetes by calorie restriction (eHealth DIabetes remission Trial): study protocol for a non-inferiority parallel group randomised controlled trial" · BMJ Open · doi: 10.1136/bmjopen-2024-095100 · PMCID: PMC12306309 · PMID: 40701606
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Emna Jelloul, Manon Lomré, Pierre Kleynen, et al. · (2026) · "Low FT4 levels in early pregnancy are associated with higher insulin therapy need in women with gestational diabetes mellitus" · European Thyroid Journal · doi: 10.1530/ETJ-25-0206 · PMCID: PMC13138595 · PMID: 41439610

Question: What is the published background on "Low FT4 levels in early pregnancy are associated with higher insulin therapy need in women with gestational diabetes mellitus"? Cite a peer-reviewed source.

Answer:
Gestational diabetes mellitus (GDM) is a prevalent complication during pregnancy (11% in Europe doi: 10.3389/fendo.2021.691033.) and known to be associated with higher rates of preeclampsia, macrosomia, and other complications ( 1 ). Similarly, thyroid disorders during pregnancy, including (subclinical) hypothyroidism (SCH) and thyroid autoimmunity (TAI), are common and linked to various adverse pregnancy outcomes, of which some are the same as documented in case of GDM ( 2 ).

Thyroid disorders have been associated with a higher risk of GDM via different pathways, due to increased insulin resistance (IR) in case of thyroid dysfunction, and via common inflammatory pathways in case of the presence of TAI ( 3 , 4 ).

The initial treatment of GDM consists in dietary (Di) and lifestyle (LS) measures (DiLS), and when glycaemic targets as proposed by the international societies are not rapidly reached, insulin therapy (IT) is started ( 5 ).

Several factors have been associated with the need for IT in GDM, including advanced maternal age, body mass index (BMI) (obesity) and a history of GDM or familial diabetes ( 6 ).

Data on the impact of thyroid dysfunction on the IT need in women with GDM are limited to three studies ( 7 , 8 , 9 ). One in association with women who had hypothyroidism ( 7 ) and two others in case of hypothyroxinaemia ( 8 , 9 ).

We had two main aims in this study. The first was to compare all baseline data (demographic, obstetric and thyroid) and thyroid disorders between women with GDM in the DiLS group versus the IT group, and the second to determine in logistic regression analyses which independent variables (demographic, obstetric and thyroid parameters/disorders and treatment) were associated with IT need in women with GDM as dependent outcome.

— Source (introduction, peer-reviewed): Emna Jelloul, Manon Lomré, Pierre Kleynen, et al. · (2026) · "Low FT4 levels in early pregnancy are associated with higher insulin therapy need in women with gestational diabetes mellitus" · European Thyroid Journal · doi: 10.1530/ETJ-25-0206 · PMCID: PMC13138595 · PMID: 41439610
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Xinlu Li, Xiaojing Dong, Defei Feng, et al. · (2025) · "Establishment of a novel alloxan‐induced rabbit model exhibiting unique diabetic retinal neuropathy features assessed via ERG + VEP" · Animal Models and Experimental Medicine · doi: 10.1002/ame2.70032 · PMCID: PMC12710098 · PMID: 40536048

Question: What did the discussion section of the paper "Establishment of a novel alloxan‐induced rabbit model exhibiting unique diabetic retinal neuropathy features assessed via ERG + VEP" cover?

Answer:
DRN, the primary manifestation of ocular diabetic damage, is characterized by dysfunction of retinal neurons and glial cells. 16 , 17 Hyperglycemia initiates a cascade of biochemical events that lead to early neuronal apoptosis and glial activation. 34 These neuroretinal changes emerge before the onset of clinical DR in individuals with diabetes and precede DR microvascular pathology in diabetic mouse models. 57 However, a significant limitation of diabetic rabbit models remains the high mortality rate among experimental animals. 16 , 17

This study identified that a single 80 mg/kg injection of alloxan resulted in a low mortality rate and a high modeling success rate, indicating its suitability as an optimal dose for establishing diabetic rabbit models. Currently, no reports provide a standardized optimal dosage of alloxan for diabetes induction in rabbits. A notable increase in HbA1c levels was observed in diabetic rabbits following a single intravenous alloxan injection (80 mg/kg). Insulin deficiency caused by pancreatic beta‐cell destruction remains a defining feature of diabetes. HbA1c serves as a critical diagnostic indicator for diabetes and is regarded as more reliable than glucose levels, as it remains elevated despite fluctuations in BGLs in patients with diabetes. Consistent with these findings, Bem et al. 58 reported a similar increase in HbA1c levels in alloxan‐induced diabetic rabbits over 10 weeks. The developed model exhibited sustained hyperglycemia accompanied by a modest elevation in triglyceride levels. Dyslipidemia appeared at an early stage and was aligned with the pattern of diabetic dyslipidemia observed at week 6. Helfenstein et al. 16 demonstrated that rabbits with diet‐induced impaired glucose tolerance developed hypercholesterolemia by week 24. In contrast, the diabetic rabbit model was developed through a high‐sugar, high‐fat diet, resulting in a distinct pathophysiological profile. Hyperglycemia, lipid metabolism disorders, and abnormalities in the insulin signaling pathway are widely recognized as the initiating factors underlying various pathophysiological changes in DRN (Figure 3A–D ). Notably, progressive retinal changes in DRN are closely associated with elevated levels of HbA1C and TC. 58 , 59 These findings suggest the successful establishment of the rabbit model replicating key features of DRN.

DRN leads to retinal abnormalities that impair function before the onset of clinical DR, in some cases, even before diabetes is diagnosed. 17 , 60 In this study, a significant reduction in mean b‐wave amplitude was identified in the model rabbits ( p < 0.01), accompanied by a decrease in the amplitude of the OP wave (Figure 5 ). This reduction in amplitude strongly correlates with the extent of retinal damage, 5 suggesting delayed signal transmission in bipolar cells and Muller cell dysfunction. 61 These findings are consistent with previous studies involving streptozotocin‐induced diabetic rats and further support electrophysiological impairments as an early indicator of retinal neuropathy. 62 VEP provides an objective evaluation of visual system function. 53 In model rabbits, a significant reduction in mean P2 wave amplitudes ( p < 0.05) and a prolongation in P2 wave latency were observed (Figure 6 ), indicating optic nerve injury and disruption of the visual pathway. A decrease in amplitude combined with increased latency in VEP readings strongly suggests damage to the optic nerve. Miura 54 demonstrated that patients with diabetes mellitus may exhibit antecedent neuropathy despite the absence of clinically detectable ophthalmoscopic or morphological abnormalities. Moreover, VEP can detect such functional impairments before the appearance of visible changes during fundus examination. These findings are consistent with the results of this study. The present study represents the first assessment of visual impairment in DRN model rabbits using full‐field ERG and VEP recordings under scotopic and photopic conditions. The results suggest that early retinal dysfunction and retinopathy in DRN may initially manifest in the optic retina and central optic nerve.

Structural analyses through SD‐OCT and H&E staining provided complementary perspectives on retinal alterations in early diabetic rabbits. SD‐OCT was performed on conscious animals to assess retinal and choroidal thickness in superior and inferior regions (Figure 7B ). At 9 weeks, diabetic rabbits exhibited no significant retinal thinning compared to controls (Table S1 ). These findings align with the observations in a diabetic mouse model, which demonstrate impairments in a‐wave, b‐wave, and OPs despite preserved inner retinal thickness. 63 This evidence underscores the suitability of the DRN rabbit model for studying early neural retinal pathology while highlighting the advantage of OCT in awake animals to reduce use and support animal welfare.

In contrast, H&E staining revealed marked retinal edema in diabetic animals, characterized by disorganized cellular distribution from the retinal nuclear layer to the ganglion cell layer, reduced intercellular spacing, and increased vacuolization (Figure 8 ). 64 , 65 Comparable disruptions have been observed in STZ‐induced diabetic rats, including alterations in GCL, INL, and ONL at 8 weeks 66 and vacuolar degeneration of ganglion cells at 4 weeks. 67 Notably, histologically measured retinal thickness was significantly greater than that obtained via OCT, likely due to inherent differences between in vivo imaging and ex vivo histological processing. In vivo OCT, despite its high‐resolution capabilities, may underestimate diffuse edema because its resolution and segmentation algorithms—primarily optimized for human retinal architecture—are not fully attuned to detect subtle, uniformly distributed changes, particularly in rabbit models with distinct retinal layer definitions. Conversely, H&E staining of ex vivo sections offers exquisite cellular and subcellular detail but is susceptible to processing artifacts, such as those arising from fixation, dehydration, and embedding, which can exaggerate tissue swelling. Consequently, the full‐thickness edema observed histologically likely reflects both genuine pathological alterations and artifacts introduced during tissue processing, whereas OCT yields a more conservative estimate of retinal thickness. Future research should aim to refine OCT segmentation protocols and develop species‐specific criteria to enhance the correlation between these imaging modalities.

Furthermore, WF‐FFA and Optos UWF imaging revealed no vascular abnormalities or basement membrane thickening in the DRN model, with similar results between diabetic and control groups (Figure 7 ). Specifically, FFA is highly sensitive for detecting microvascular leakage, subtle perfusion defects, and early vascular abnormalities. By dynamically imaging the distribution of fluorescein dye in the retinal vasculature, FFA provides detailed visualization of vascular integrity, enabling the identification of even minor instances of leakage that might be missed by other modalities. 68 Although Ljubimov et al. 69 reported basement membrane thickening in diabetic retinopathy, such alterations were absent in our model. Notably, this study is the first to assess early DRN severity in rabbits using Optos UWF imaging, which, along with SD‐OCT, confirmed the presence of a well‐defined visual streak and clear optic bands in awake diabetic rabbits, supporting findings by Paulus et al. 70

This study identified pronounced glial activation and substantial neuronal loss in DRN retinas. This activation may intensify retinal damage by amplifying inflammatory signaling pathways, aligning with prior findings that associate glial activation with DRN. 71 , 72 Concurrently, the results revealed a marked reduction in ganglion and displaced amacrine cells within the GCL. Decreased RBPMS‐labeled ganglion cell density further supports the hypothesis that diabetic retinas undergo progressive neuronal loss, ultimately disrupting visual signaling.

This model effectively isolates early neurodegenerative events from subsequent microvascular pathology, establishing it as a valuable preclinical tool for investigating the mechanisms underlying DRN. Full‐field ERG and VEP emerged as highly sensitive screening tools, capable of detecting retinal nerve dysfunction before the onset of irreversible damage occurs. While early neuronal and glial alterations are evident in preclinical diabetes models, conventional diagnostic approaches typically identify neuropathy only during more advanced stages. Preclinical evidence indicates that retinal neuropathy, partially characterized by photoreceptor dysfunction, precedes overt vascular alterations, reinforcing the rationale for neuroprotective strategies to prevent or delay apoptotic neuronal cell death. These findings highlight the critical need for early detection and intervention targeting neurodegenerative processes in DR. In summary, this model elucidates the temporal progression of diabetic retinal alterations while emphasizing the therapeutic potential of early neuroprotective approaches to enhance clinical outcomes in individuals with diabetes.

This study has some limitations. First, using a rabbit model introduces physiological and anatomical disparities compared to humans, potentially limiting direct clinical applicability. Although the DRN model was successfully replicated, the short observation period restricted the comprehensive assessment of disease progression. Second, suboptimal housing conditions, including limited control over movement and dietary intake following induction, may have introduced confounding factors. Alloxan injection (80 mg/kg) yielded promising outcomes; however, the small sample size constrains statistical robustness and reproducibility. Future studies should employ larger cohorts and adopt a multidisciplinary strategy integrating in vitro, ex vivo, and clinical research to more precisely define the biological and pathophysiological mechanisms underlying DRN.

— Source (discussion, peer-reviewed): Xinlu Li, Xiaojing Dong, Defei Feng, et al. · (2025) · "Establishment of a novel alloxan‐induced rabbit model exhibiting unique diabetic retinal neuropathy features assessed via ERG + VEP" · Animal Models and Experimental Medicine · doi: 10.1002/ame2.70032 · PMCID: PMC12710098 · PMID: 40536048
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Emilee Kim Ming Ong, Carolyn Murray, Susan Hillier, et al. · (2025) · "Using Nominal Group Technique to Gather Recommendations in the Decision‐Making for Amputation Due to Diabetes" · Journal of Foot and Ankle Research · doi: 10.1002/jfa2.70095 · PMCID: PMC12582910 · PMID: 41184217

Question: What does the published research conclude about "Using Nominal Group Technique to Gather Recommendations in the Decision‐Making for Amputation Due to Diabetes"? Cite a peer-reviewed source.

Answer:
The outcomes of this study are the first steps towards establishing evidence‐based guidelines for making decisions for amputation. A person‐centred approach is required when making decisions for non‐emergency amputation. This is achieved by a mutual understanding of goals and priorities, and differing meanings of quality of life through systems that enable continuity of health practitioners. Identifying the optimal time for amputation may be facilitated through early discussions. Further research into how these recommendations can be implemented into multi‐disciplinary clinics across different settings is now required.

— Source (conclusions, peer-reviewed): Emilee Kim Ming Ong, Carolyn Murray, Susan Hillier, et al. · (2025) · "Using Nominal Group Technique to Gather Recommendations in the Decision‐Making for Amputation Due to Diabetes" · Journal of Foot and Ankle Research · doi: 10.1002/jfa2.70095 · PMCID: PMC12582910 · PMID: 41184217
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Ruiyu Wu, Xiao Yang, Xu Zhou, et al. · (2026) · "Maintained diabetes remission among normal BMI individuals achieved without ongoing intervention: a three-year follow-up study of intermittent calorie restriction" · Frontiers in Endocrinology · doi: 10.3389/fendo.2025.1733840 · PMCID: PMC12890618 · PMID: 41684452

Question: What did the discussion section of the paper "Maintained diabetes remission among normal BMI individuals achieved without ongoing intervention: a three-year follow-up study of intermittent calorie restriction" cover?

Answer:
This study demonstrates that diabetes remission achieved through a 3-month CMNT diet intervention can be maintained over 3 years without ongoing pharmacological or diet interventions. Notably, 64.7% (n = 17, of which 11 maintained remission) of participants in the CMNT group who had achieved remission by the 3rd-month post-intervention, maintained it for 3 years under ad libitum dietary conditions, highlighting the potential of this approach to alleviate the burden of long-term disease management. Different from previous studies, such as the DIRECT trial, which required ongoing support to mitigate weight regain and preserve remission, our findings underscore the feasibility of achieving long-term remission without structured maintenance strategies. Although this remission requires maintaining a normal BMI, the findings nonetheless challenge the conventional assumption that prolonged intervention is indispensable.

Long-term weight maintenance interventions have been used to support long-term diabetes remission due to the effects of weight regain, but their outcomes remain suboptimal ( 13 ). In the DIRECT follow-up study, for instance, even with low-intensity rescue programs provided over three to five years, many participants experienced weight regain, leading to a decline in remission rates from 51% to 13% ( 7 ). The CMNT diet intervention resulted in weight loss, while weight regain was also observed and primarily among participants who achieved remission. However, relapse was less frequent, even though only general dietary recommendations was provided. Linear regression analysis further revealed that maintenance of remission was not affected by weight changes during the follow-up. In energy-restricted diets, weight loss and weight regain are common phenomena, including participants from CMNT. However, given that the baseline BMI of the CMNT group was not elevated (approximately 25 kg/m²) and further decreased following the intervention, the average BMI remained below 24 kg/m² even after weight regain. In DIRECT study, a significant proportion of the participants exhibited a BMI greater than 30 kg/m², and even subsequent to the intervention, the BMI remained greater than 27 kg/m² ( 7 ). This may provide a reason for the high diabetes remission rate observed in the three-year follow-up after CMNT intervention in this study.

The Dual-Cycle Hypothesis of T2DM suggests that the interaction between hepatic insulin resistance caused by liver fat accumulation and β-cell dysfunction induced by pancreatic exposure to hypertriglyceridemia drives the onset and progression of T2DM ( 14 ). Among participants in the CMNT group who maintained remission, the BMI was 23.9 kg/m² at baseline and 21.7 kg/m² after intervention. In the three newly added subjects whose diabetes was in remission, the intervention was followed by the use of only one hypoglycaemic agent and concomitant HbA1c of less than 6%. Although these participants’ weight had increased during the follow-up, all but one participant had a BMI below 25 kg/m²in the 3 -year follow-up. A BMI below 25 kg/m² is generally associated with a lower risk of developing T2DM and is often indicative of relatively limited hepatic fat accumulation ( 15 ). This phenotype may partly explain the favorable conditions that support diabetes remission maintenance in our cohort. However, this assumption requires further validation with direct measurements of hepatic steatosis, as the current study lacks corresponding liver fat data. Furthermore, the dietary recommendations stipulated within the Dietary Guidelines for Diabetes in China, which were to be adhered to by subjects during the follow-up period, including a low GL diet, management of staple foods, and increased vegetable intake, also demonstrated glycaemic control benefits. Overall, maintaining diabetes remission may be partly attributable to sustaining a normal BMI together with adherence to healthy dietary patterns.

As long as the pancreas can compensate by increasing insulin secretion, plasma glucose control can be maintained in both muscle and liver, even in the presence of insulin resistance ( 14 ). Some studies have demonstrated that in the absence of weight loss, such as in the context of intensive insulin therapy ( 16 ), GLP-1 therapy ( 17 ), or other interventions, diabetes remission can be achieved. In this follow-up study, we evaluated the impact of the CMNT diet intervention on participants’ use of insulinotropic agents and insulin. Results showed a 86.7% reduction in usage ( Supplementary Table 6 ) among participants in the CMNT group during the intervention period, with no subsequent increase observed throughout the follow-up period. These findings may reflect an improvement in the participants’ endogenous insulin secretory capacity, potentially reducing their reliance on insulin-secretagogue medications or exogenous insulin therapy. Furthermore, animal studies have demonstrated that CMNT can promote β-cell proliferation and enhance insulin secretion in mice, supporting a possible mechanistic basis for the observed clinical benefits ( 18 ). In addition, we observed that participants in the CMNT group who remained in remission in the 3-year follow-up exhibited higher HOMA-β levels compared with those who did not ( Figure 2C ). Although this observation is based on a relatively small sample size and requires confirmation in larger and more rigorous studies, it remains a noteworthy finding. Taken together, these observations may indicate a potential role of CMNT in supporting metabolic improvements that favor diabetes remission, possibly through modest enhancements in endogenous insulin secretion and β-cell function.

The majority of individuals with diabetes express a strong desire to achieve autonomy to live their lives as they choose, free from the need for medication, insulin, or restrictive diets, and without the requirement for strenuous exercise ( 19 , 20 ). This is a goal that their physicians had previously indicated unattainable, even if medication was ceased, particularly in individuals dependent on insulin ( 11 , 21 ). Nevertheless, the necessity of long-term disease management imposes varying degrees of psychological stress on patients ( 22 ). In this study, those who achieved remission in CMNT group were not only free from the need for antidiabetic medications, but also did not require interventions that differed from their normal routine. These benefits were reflected in the markedly superior quality of life in the CMNT group in comparison to the control group. Diabetes-related complications are common and can impact multiple organ systems, leading to increased mortality, blindness and renal failure ( 23 ). Despite the absence of ongoing intervention during the 3-year follow-up period, the CMNT group exhibited a five-fold reduction in hospitalisation rates and a three-fold reduction in complication rates compared to the control group ( Supplementary Table 7 ). In summary, CMNT-induced remission could enable some individuals to reduce their reliance on pharmacological therapy and may be associated with improvements in disease-related burden, although further studies are needed to confirm long-term effects without ongoing intervention.

It is important to acknowledge the limitations of this study. On the one hand, the sample size was relatively small, and the three-year follow-up period was not sufficiently long. Future research with larger cohorts and longer follow-up duration is needed to confirm these results and further explore the long-term impact of CMNT interventions on diabetes remission. On the other hand, CMNT needs to be validated for its effectiveness in remission diabetes in people with higher BMI, and its long-term benefits need to be explored. It should also be noted that remission status in the present study was defined solely on the basis of annual HbA1c measurements and thus reflects the remission status only at the time of assessment. Owing to the absence of additional day-to-day normoglycaemic data, the findings do not provide evidence for sustained metabolic stability.

In conclusion, this study highlights the CMNT diet as a promising intervention for achieving long-term diabetes remission. It is noteworthy that this remission was maintained without the requirement for ongoing pharmacological or dietary intervention, provided that a normal BMI was preserved. Meanwhile, the preservation of pancreatic β-cell function is also an important contributing factor. This diet-focused approach demonstrates the potential to reduce reliance on insulin and insulinotropic agents while improving quality of life and minimizing the burden of long-term management.

— Source (discussion, peer-reviewed): Ruiyu Wu, Xiao Yang, Xu Zhou, et al. · (2026) · "Maintained diabetes remission among normal BMI individuals achieved without ongoing intervention: a three-year follow-up study of intermittent calorie restriction" · Frontiers in Endocrinology · doi: 10.3389/fendo.2025.1733840 · PMCID: PMC12890618 · PMID: 41684452
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Anjali Kashyap, Alexander Mackay, Ben Carter, et al. · (2022) · "Investigating the Effectiveness of Very Low-Calorie Diets and Low-Fat Vegan Diets on Weight and Glycemic Markers in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis" · Nutrients · doi: 10.3390/nu14224870 · PMCID: PMC9695880 · PMID: 36432557

Question: What is the published background on "Investigating the Effectiveness of Very Low-Calorie Diets and Low-Fat Vegan Diets on Weight and Glycemic Markers in Type 2 Diabetes…"? Cite a peer-reviewed source.

Answer:
Type 2 Diabetes Mellitus (T2DM) is a global epidemic, driven by an increased prevalence of obesity in both children and adults [ 1 ]. Increased consumption of calorific foods including processed foods and beverages, meat and other animal products, sugary beverages, and refined grains are believed to play a key role in the growing rates of T2DM worldwide [ 2 ]. The International Diabetes Federation estimate that approximately 537 million adults (20–79 years) are living with diabetes. The total number of people living with diabetes is projected to rise to 643 million by 2030 and 783 million by 2045 [ 3 ], with the predominant type being T2DM. With fewer than 2% of people with T2DM entering a state of spontaneous remission [ 4 ], the present clinical paradigm is that T2DM is an irreversible condition.

The primary approach for management of T2DM is to achieve and maintain weight loss [ 5 ]. Evidence has shown a multifactorial intervention in the form of caloric restriction, exercise, and behavior change has optimal effects in improving glycemic control and weight [ 6 , 7 ]. Current dietary interventions for the management of T2DM include restricting carbohydrates, cholesterol, and fat intake, as well as caloric restriction [ 8 ]. Dietary restriction therapies for management and cessation of T2DM have mainly focused on weight loss through the implementation of either low-calorie diets (LCD) defined as 1200–1500 kcal/day [ 9 , 10 , 11 ] or very low-calorie diets (VLCD) ranging from 450–800 kcals/day [ 12 ]. Current literature supports VLCD diets, illustrating that such diets are superior in inducing/promoting rapid weight reductions, improving insulin secretion, and lowering hemoglobin A1c (HbA1c) to levels seen in pre-diabetes or normoglycemia [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].

Plant-based diets, focusing on inclusion of foods from plant sources and exclusion of animal-based products, have gained recognition in public heath for not only their potential in promoting sustainability, but also to curb the onset and assist in management of chronic disease [ 23 ], including cardiovascular disease, some cancers, and T2DM [ 24 , 25 , 26 , 27 ]. Clinical studies have demonstrated improvements in glycemic control, blood lipids and body weight. In some cases, this has been achieved to a greater degree than conventional dietary interventions [ 28 ]. Proposed mechanisms for this have been attributed to increased consumption of plant foods (naturally rich in minerals, vitamins, and antioxidants) and reduced intake of processed and red meats [ 29 , 30 , 31 ]. A study conducted to determine the nutritional adequacy of a low-fat vegan diet concluded that vegan diets have positive impacts on energy and plasma lipids [ 32 ]. The lipid lowering effects of plant-based diets can be attributed to negligible dietary cholesterol intake, reduced saturated fat content and cholesterol-lowering effects of soluble fiber [ 33 ]. These effects are important, as cardiovascular complications are one of the leading causes of worldwide morbidity and mortality in patients with T2DM.

A recently published systematic review and meta-analysis [ 34 ] confirmed that the consumption of vegan diets yields favorable results in some cardiometabolic health measures in overweight patients and those with T2DM. Despite there being an overlap in review content, our review is unique for several reasons: the most important being the current focus on patients with diabetes and the inclusion of VLCD diets. We included a side-by-side analysis by looking at both vegan and VLCD diets, being current popular approaches. Our inclusion criteria did not include individuals with pre-diabetes, but included studies of any length of intervention period, to facilitate a broader analysis for clinical relevance. This approach means that these results are translatable for patients, clinicians, and healthcare workers with an interest in dietary approaches to manage with type 2 diabetes and body weight control.

Our study assessed the evidence available to support very low-calorie diets (VLCD) and vegan diets for management of body weight and/glycemic control in patients with T2DM.

— Source (introduction, peer-reviewed): Anjali Kashyap, Alexander Mackay, Ben Carter, et al. · (2022) · "Investigating the Effectiveness of Very Low-Calorie Diets and Low-Fat Vegan Diets on Weight and Glycemic Markers in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis" · Nutrients · doi: 10.3390/nu14224870 · PMCID: PMC9695880 · PMID: 36432557
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.