Diabetes Risk Research Articles

Pregnancy as a challenge for a patient with schizophrenia

Introduction: Schizophrenia affects as many as 24 million people worldwide. Similar to the general population of women, it is estimated that every second woman with schizophrenia becomes a mother. The purpose of the article is to present the difficulties that pregnancy brings for women with schizophrenia in terms of physical and mental health and the course of the disease. Material and methods: The available literature in English and Polish languages was reviewed by searching the PubMed and Google Scholar databases. Articles published from 2009 to 2023 were selected using the following words: schizophrenia, pregnancy, hormones, treatment and outcomes. The analysis encompassed original studies, meta-analyses, randomized controlled trials, and review articles. Results: One of the most significant problems related to motherhood among patients with schizophrenia is the lack of access to knowledge about family planning, sexuality and parenting. Women with schizophrenia are more likely to engage in risky sexual contact, and usually their pregnancies are unplanned. The influence of schizophrenia on the course of pregnancy is still not clear. Studies show that changes in hormone levels during pregnancy, especially estrogen levels, play a protective role in the occurrence of schizophrenic episodes. Nonetheless, pregnant women with schizophrenia have higher risk of miscarriage, infant deaths, obesity, gestational diabetes, hypertension and other obstetric complications. Conclusions: Due to the fact that nowadays more women with schizophrenia may become mothers, it is crucial to provide patients with adequate knowledge about sexual and reproductive life and to ensure them professional, interdisciplinary medical and psychological care during pregnancy. Keywords: schizophrenia, pregnancy, hormones, treatment, outcomes

Engaging Students in a Bilingual Service-Learning Health Promotion Project.

Introduction: This service-learning, health promotion project used Leininger's Culture Care Theory to engage Baccalaureate Nursing students in a health promotion initiative specific to Hispanic community members. Methods: Thirty-seven students examined population health data, surveyed Hispanic community members to identify health priorities, and developed a population-specific intervention on diet and risk factors for diabetes. Students created a 5-min script focused on healthy eating plans with recognition of traditional foods associated with the Hispanic culture. Students delivered the script to community members attending an annual Hispanic Heritage Festival. Results: Seventy-six percent of the 488 community participants reported increased knowledge about diabetes risk factors and healthy eating habits. Each student completed a self-reflection on how the project impacted their transcultural skills and reported increased confidence related to engagement and communication with the Hispanic community. Discussion/Significance: Incorporating community-based service-learning into the undergraduate curricula is a powerful educational approach that can enhance students' ability to provide culturally congruent nursing care.

Adiposity and metabolic health in Asian populations: an epidemiological study using dual-energy x-ray absorptiometry in Singapore

Type 2 diabetes, cardiovascular disease, and related cardiometabolic disturbances are increasing rapidly in the Asia-Pacific region. We investigated the contribution of excess adiposity, a key determinant of type 2 diabetes and cardiovascular risk, to unfavourable cardiometabolic profiles among Asian ethnic subgroups. The Health for Life in Singapore (HELIOS) Study is a population-based cohort comprising multiethnic Asian men and women living in Singapore, aged 30-84 years. We performed a cross-sectional analysis of data from individuals who had assessment of body composition by dual-energy x-ray absorptiometry and metabolic characterisation. In a subset of participants on no medication for type 2 diabetes, hypertension, and hypercholesterolaemia, we tested the relationship of BMI and visceral fat mass index (vFMI) with cardiometabolic phenotypes (glycaemic indices, lipid levels, and blood pressure), disease outcomes (type 2 diabetes, hypercholesterolaemia, and hypertension), and metabolic syndrome score with multivariable regression analyses. Between April 2, 2018, and Jan 28, 2022, 10 004 individuals consented to be part of the HELIOS cohort, of whom 9067 were included in the study (5404 [59·6%] female, 3663 [40·4%] male; 6224 [68·6%] Chinese, 1169 [12·9%] Malay, 1674 [18·5%] Indian; mean age 52·8 years [SD 11·8]). The prevalence of type 2 diabetes, hypercholesterolaemia, and hypertension was 8·2% (n=744), 27·2% (n=2469), and 18·0% (n=1630), respectively. Malay and Indian participants had 3-4-times higher odds of obesity and type 2 diabetes, and showed adverse metabolic and adiposity profiles, compared with Chinese participants. Excess adiposity was associated with adverse cardiometabolic health indices including type 2 diabetes (p<0·0001). However, while vFMI explained the differences in triglycerides and blood pressure between the Asian ethnic groups, increased vFMI did not explain higher glucose levels, reduced insulin sensitivity, and increased risk of type 2 diabetes among Indian participants. Visceral adiposity is an independent risk factor for metabolic disease in Asian populations, and accounts for a large fraction of type 2 diabetes cases in each of the ethnic groups studied. However, the variation in insulin resistance and type 2 diabetes risk between Asian subgroups is not consistently explained by adiposity, indicating an important role for additional mechanisms underlying the susceptibility to cardiometabolic disease in Asian populations. Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, and National Medical Research Council, Singapore.

Metals link to diabetes: Insights from a national cross‐sectional investigation

Diabetes and impaired fasting glucose (IFG) are significant global health concerns. However, the potential effects of mixed heavy metal exposure on these conditions remain underexplored. This study aims to investigate the combined effects of multiple metals on diabetes risk and explore the mediating role of Body Mass Index (BMI) in rural China. A cross-sectional analysis involved 2313 adults from 12 provinces in rural China. Urinary levels of zinc (Zn), chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were quantified using inductively coupled plasma mass spectrometry. Fasting blood glucose (FBG) levels were measured with an automatic biochemical analyzer. Logistic regression models and the Bayesian Kernel Machine Regression (BKMR) model were used to examine associations and interactions. Mediation analysis was performed to assess the role of BMI. The results of our study indicate that there is a significant association between urinary Zn (OR = 2.38, 95 % CI: 1.57, 3.60), Cr (OR = 1.24, 95 % CI: 1.31, 1.61), and Ni (OR = 1.51, 95 % CI: 1.05, 2.18) and the diabetes risk. The study revealed that exposure to Ni amplified the associations between Zn, Cr and diabetes/IFG risk. Additionally, BMI was identified as a significant mediator in the relationship between metal exposure, particularly Cr/Cd, and diabetes risk. These findings reveal a complex link between multiple metals, such as Zn, Cr, and Ni, and diabetes risk, and emphasize the potential opposite mediating effects of BMI in different metal-induced diabetes mechanisms. Further investigation of these mechanisms is warranted.

Chronic Work Discrimination, Allostatic Load, and HbA1c in Older Workers.

Work discrimination is an important public health problem with consequences for health. This study examined the effect of chronic work discrimination on 4-year changes in HbA1c, as a reflection of glucose control and type 2 diabetes risk in older workers and assessed whether allostatic load (AL) affected the strength of this association. We used Health and Retirement Study data (2010-2016, n = 3,246). Conditional change multinomial logistic regression examined the association between chronic work discrimination, high AL (4 or more out of 8 high-risk biomarkers), and HbA1c, while accounting for relevant covariates. Black participants had the highest rates of baseline (22.7%) and follow-up (28%) HbA1c levels, AL (38%), and chronic work discrimination (39%; p < .01). Severe chronic work discrimination was associated with elevated HbA1c (relative risk ratio [RRR] = 1.61, 95% confidence interval [CI] = 1.07, 2.43). AL was associated with elevated HbA1c (RRR = 1.49, 95% CI = 1.04, 2.14). Relative to White participants, Hispanic (RRR = 1.52, 95% CI = 1.07, 2.16, RRR = 1.81, 95% CI = 1.051, 3.12), and Black (RRR = 2.42, 95% CI = 1.82, 3.23; RRR = 3.00, 95% CI = 1.97, 4.56) participants had an increased risk of intermediate and elevated HbA1c, respectively. Among those with long job tenure (≥5 years), both moderate (RRR = 1.81, 95% CI = 1.11, 2.96) and severe (RRR = 1.90, 95% CI = 1.15, 3.12) chronic work discrimination was associated with elevated HbA1c. Chronic work discrimination was associated with HbA1c; however, no moderating effects of AL were observed. Findings underscore a need for organizational and public health measures to establish strong anti-discrimination laws in the workplace to improve the work environment of older workers and reducediabetes risk.

Comparison of Absolute and Relative Grip Strength to Predict Incidence of Diabetes Mellitus in Korea: A Prospective Cohort Study.

Background: This study aimed to investigate the association between absolute grip strength (AGS), relative grip strength (RGS) levels, and the risk of developing diabetes in middle-aged adults, utilizing longitudinal data. Methods: A total of 1935 participants, 51-81 years of age, were engaged in surveys both in 2017-2018 and during the subsequent follow-up survey in 2019-2020. Diabetes diagnosis and treatment were the criteria for categorizing individuals as "diabetic." Grip strength was measured using the JAMA-5030J1 equipment (SAEHAN, Korea), and AGS and RGS were also categorized into tertiles by gender. A proportional hazards Cox regression model was used to evaluate the relationship among AGS, RGS, and the risk of developing diabetes. Subsequently, we computed the hazard ratio (HR) and 95% confidence interval (95% CI) for the risk of developing diabetes. Results: After adjusting for various confounding variables, a significant reduction in diabetes risk was observed in the high grip strength group, adjusted for body mass index (RGS1) and body weight (RGS2), compared with the low RGS1 and RGS2 groups (RGS1 HR = 0.54, 95% CI = 0.36-0.80; RGS2 HR = 0.50, 95% CI = 0.34-0.73). However, there were no significant associations between AGS and diabetes risk. Furthermore, significant differences in the relationship among AGS, RGS levels, and the risk of developing diabetes were found across gender and insulin resistance levels. Conclusion: This study underscores the importance of RGS levels in predicting the incidence of diabetes, with AGS, RGS1, and RGS2 emerging as significant predictive indicators for assessing diabetes risk.

Automated Comprehensive CT Assessment of the Risk of Diabetes and Associated Cardiometabolic Conditions.

Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities. Materials and Methods This retrospective study included Korean adults (age ≥ 25 years) who underwent health screening with fluorine 18 fluorodeoxyglucose PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral and subcutaneous fat, muscle, bone density, liver fat, all normalized to height (in meters squared), and aortic calcification. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively. Results The cross-sectional and cohort analyses included 32166 (mean age, 45 years ± 6 [SD], 28833 men) and 27 298 adults (mean age, 44 years ± 5 [SD], 24 820 men), respectively. Diabetes prevalence and incidence was 6% at baseline and 9% during the 7.3-year median follow-up, respectively. Visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUC of 0.70 (95% CI: 0.68, 0.71) for men and 0.82 (95% CI: 0.78, 0.85) for women and C-index of 0.68 (95% CI: 0.67, 0.69) for men and 0.82 (95% CI: 0.77, 0.86) for women, respectively. Combining visceral fat, muscle area, liver fat fraction, and aortic calcification improved predictive performance, yielding C-indexes of 0.69 (95% CI: 0.68, 0.71) for men and 0.83 (95% CI: 0.78, 0.87) for women. The AUC for visceral fat index in identifying metabolic syndrome was 0.81 (95% CI: 0.80, 0.81) for men and 0.90 (95% CI: 0.88, 0.91) for women. CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores greater than 100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95. Conclusion Automated multiorgan CT analysis identified individuals at high risk of diabetes and other cardiometabolic comorbidities. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pickhardt in this issue.

Effect of trace elements and nutrients on diabetes and its complications: a Mendelian randomization study.

Multiple clinical studies have observed a close relationship between serum trace elements and nutrients and diabetes and its complications, but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients and diabetes and its complications. This study aims to investigate the causal effects of serum trace elements and nutrients on diabetes and its complications using Mendelian randomization methods. The single nucleotide polymorphisms of serum trace elements and vitamins, as exposure factors, were sourced from the published UK Biobank database and public databases of genome-wide association studies. The genome-wide association study data of diabetes and its complications, as outcome events, were sourced from the FinnGen Biobank database. Mendelian randomization methods were employed to explore the causal relationships between 9 trace elements and 6 nutrients and diabetes and its complications. The causal relationships were inferred using inverse variance weighting, MR Egger, weighted median, simple model, and weighted model methods. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, MR-PRESSO tests, and leave-one-out analysis, were conducted to evaluate the robustness of the study results. Finally, trace elements and nutrients with statistical significance in the IVW method and consistent Beta and OR directions in the five methods were selected as exposure factors with causal relationships with diabetes and its complications. This study also used multivariable Mendelian randomization methods to assess the combined effects of multiple exposure factors on the risk of diabetes and its complications. Mendelian randomization analysis revealed that selenium was linked to an elevated risk of T2D.Vitamin B6 was correlated with an increased risk of neurological complications in type 2 diabetes. Magnesium exhibited a negative causal relationship with the risk of T1D.Carotene was linked to a higher risk of renal complications in T1D.Vitamin B12 showed a negative causal relationship with renal complications in T1D.Carotene was connected to a higher risk of neurological complications in T1D.Potassium and vitamin B6 exhibited negative causal relationships with neurological complications in T1D.Vitamin E showed a negative causal relationship with peripheral circulation complications in T2D.Multivariable Mendelian randomization analysis suggested that vitamin B6 could independently influence neurological complications in both T1D and T2D, apart from other exposure factors. Vitamin B6 could also independently influence renal complications in T1D.Vitamin E could independently influence peripheral circulation complications in T1D, apart from other exposure factors. The findings from univariable and multivariable Mendelian randomization studies substantiate the causal relationships between trace elements and nutrients and different subtypes of diabetes and their complications. These findings hold significant clinical implications for developing targeted prevention and treatment strategies for diabetes and its complications.

A practical guide for the use of apalutamide for non-metastatic castration-resistant prostate cancer in Australia.

Studies of patients with castrate-resistant prostate cancer at high risk of developing overt metastases but with no current evidence of evaluable disease on computed tomography or bone scan non-metastatic castrate-resistant prostrate cancer have demonstrated increased metastasis-free survival and overall survival following treatment with the next-generation oral anti-androgen apalutamide (in addition to therapies that aim to lower testosterone to castrate levels) or luteinizing hormone-releasing hormone antagonist or surgical castration. Patients receiving apalutamide can be managed by medical oncologists, radiation oncologists, or urologists, preferably as part of a multidisciplinary team. However, the importance of additional safety monitoring for significant adverse effects and drug interactions should not be underestimated. The toxicities of apalutamide are manageable with experience and should be managed proactively to minimize their impact on patients. Monitoring of patients for apalutamide-specific toxicities, including skin rash, hypothyroidism, and QT prolongation should be carried out regularly, particularly in the first few months following initiation. Monitoring should continue alongside monitoring for toxicities of androgen deprivation, including cardiovascular risk, hot flashes, weight gain, bone health, muscle wasting, and diabetic risk. This review is a practical guide to the use of apalutamide describing the management of patients including dosing and administration, toxicities, potential drug interactions, and safety monitoring requirements.

Hypertension and diabetes risk in patients with previous pregnancy-related disorders and the time to onset of the disease

Hypertension and diabetes risk in patients with previous pregnancy-related disorders and the time to onset of the disease

Association of dietary and lifestyle inflammatory indices with type 2 diabetes risk in Iranian adults

BackgroundType 2 diabetes mellitus (T2DM) is often linked to chronic inflammation, which can be influenced by both lifestyle and dietary choices. However, the relationship between the inflammatory potential of diet and lifestyle factors and the risk of developing T2DM remains unclear. The present study aimed to investigate the associations of the empirical dietary inflammatory index (EDII), dietary inflammatory score (DIS), and lifestyle inflammatory score (LIS) with the risk of T2DM among Iranian adults.MethodsThe current study was conducted on 5714 individuals from Yazd Health Study (YaHS) who were followed up for a mean period of six years. YaHS is a prospective cohort study which has been conducted since 2014. Dietary intakes were collected at baseline using the food frequency questionnaire. The relative risk (RR) of T2DM was calculated by Cox regression analysis across tertiles of EDII, DIS, and LIS, adjusted for potential confounders.ResultsThe mean ± SD for the age and body mass index of the study population were 47.0 ± 9.2 years and 26.7 ± 5.1 Kg.m2, respectively. A significant association between LIS and the risk of T2DM was observed (RR: 4.05, 95% CI: 2.61–6.27 P-trend < 0.001). Individuals in the highest compared to the lowest tertile of EDII-LIS (RR: 3.07, 95%CI: 2.01–4.68; P for trend < 0.001) and DIS-LIS (RR: 2.42, 95%CI: 1.69–3.49; P for trend < 0.001) had a higher risk of T2DM. However, no significant association was found between EDII and DIS scores and the risk of T2DM.ConclusionGreater adherence to LIS, EDII-LIS, and DIS-LIS scores was associated with a higher risk of T2DM, while no significant association was found between EDII and DIS with T2DM risk.

The serum uric acid to serum creatinine ratio is an independent risk factor for type 2 diabetes in community-dwelling elderly: A longitudinal analysis

Background and aimElevated serum uric acid (SUA) levels are an important marker of metabolic disorders. However, SUA levels largely depend on renal clearance function. This study aims to investigate the relationship between renal function-normalized SUA [SUA to serum creatinine (SCr) ratio] and the risk of developing type 2 diabetes in a community-dwelling elderly population. Methods and resultsA retrospective cohort study was conducted on elderly, non-diabetic individuals from the Kunshan community in China, who participated in annual health check-ups between January 2018 and December 2023. The relationship between the baseline SUA/SCr ratio and the risk of type 2 diabetes was examined using Cox regression models, restricted cubic splines (RCS), and subgroup analyses. After a median follow-up of 3.88 years, 778 cases of type 2 diabetes were identified among 7671 elderly non-diabetic individuals. Adjusting for confounding variables, the baseline SUA/SCr ratio was significantly linked to type 2 diabetes risk (P < 0.001). Individuals in the highest SUA/SCr ratio quartile had a 1.323 times higher risk of developing type 2 diabetes compared to those in the lowest quartile (HR = 1.323, 95% CI 1.053–1.661, P = 0.016). RCS analysis further confirmed this positive association. Additionally, subgroup analyses suggested that this relationship was particularly pronounced in female individuals. ConclusionsIn Chinese elderly community residents, the baseline SUA/SCr ratio is linked to the risk of type 2 diabetes. Monitoring this ratio could aid in predicting and assessing the risk of type 2 diabetes.

Protective Effects of Curcumin and its Analogues via the Nrf2 Pathway in Metabolic Syndrome.

Metabolic Syndrome (MetS) refers to a set of medical conditions including insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension. Due to these dysregulations, if not treated, MetS could increase the risk of CVA, CVD, and diabetes. As described by WHO, CVD is the leading cause of mortality in the world which motivates researchers to investigate the management of its risk factors, especially MetS. It is reported that oxidative stress secondary to the abundant generation of free radicals oxygen species (ROS) and the ensuing altered redox status play an important role as a mediator in MetS. As a result, using new antioxidant agents with higher bioavailability has been proposed as an efficient treatment. Curcumin (a polyphenol of the diarylheptanoids class), which is used as a traditional medicine for various diseases including cardiovascular diseases and diabetes, is characterized by its antioxidant properties which, at least in part, are mediated via the activation of the Nrf2/ARE signaling pathway. Nrf2 is a transcription factor that plays a key role in regulating internal defense systems and increases antioxidant levels to decrease oxidative damage and cell apoptosis. Nrf2 expression and stability are enhanced by curcumin, leading to a higher rate of Nrf2 migration to the cell nucleus to regulate ARE gene expression, thus protecting cells against oxidative stress. In this article, we provide a comprehensive review of the molecular effect of curcumin and its derivatives via Nrf2 regulation in several conditions, such as diabetes, hypertension, dyslipidemia, and obesity.

Interlinked Pathways: Exploring the Bidirectional Impacts of Periodontitis and Metabolic Syndrome.

Metabolic syndrome (MBS) and periodontitis are distinct conditions with overlapping and unique risk factors. Periodontitis is a chronic destructive disease of the periodontium, driven by alterations in the host immune-inflammatory response to virulent periodontal pathogens. MBS is characterized by various abnormalities, including visceral abdominal obesity, dyslipidemia (low high-density lipoprotein (HDL) and high triglyceride (TG) levels), hypertension, and hyperglycemia. These factors collectively increase the risk of atherosclerotic cardiovascular disease (CVD) and diabetes. Several pro-inflammatory mediators are involved in the pathogenesis of periodontitis and MBS, and the deleterious bidirectional effects of these mediators exacerbate the severity and progression of both conditions. This comprehensive review focuses on the intricate relationship between MBS and periodontitis. Specifically, it explores the pathophysiological mechanisms of each disease component of MBS and its impact on periodontitis, and vice versa.

Genotype-by-Environment Interactions in Nonalcoholic Fatty Liver Disease and Chronic Illness among Mexican Americans: The Role of Acculturation Stress.

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h2 = 0.52), marginalization (h2 = 0.30), AST (h2 = 0.25), ALT (h2 = 0.41), and BMI (h2 = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations.

Single-housing-induced islet epigenomic changes are related to polymorphisms in diabetic KK mice.

A lack of social relationships is increasingly recognized as a type 2 diabetes (T2D) risk. To investigate the underlying mechanism, we used male KK mice, an inbred strain with spontaneous diabetes. Given the association between living alone and T2D risk in humans, we divided the non-diabetic mice into singly housed (KK-SH) and group-housed control mice. Around the onset of diabetes in KK-SH mice, we compared H3K27ac ChIP-Seq with RNA-Seq using pancreatic islets derived from each experimental group, revealing a positive correlation between single-housing-induced changes in H3K27ac and gene expression levels. In particular, single-housing-induced H3K27ac decreases revealed a significant association with islet cell functions and GWAS loci for T2D and related diseases, with significant enrichment of binding motifs for transcription factors representative of human diabetes. Although these H3K27ac regions were preferentially localized to a polymorphic genomic background, SNVs and indels did not cause sequence disruption of enriched transcription factor motifs in most of these elements. These results suggest alternative roles of genetic variants in environment-dependent epigenomic changes and provide insights into the complex mode of disease inheritance.

Gestational Diabetes Mellitus-Induced Milk Fat Globule Membrane Protein Changes of Human Mature Milk Based on TMT Proteomic Analysis

Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breastmilk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with GDM and without based on tandem mass tag (TMT) labeling and liquid chromatography tandem mass spectrometry (LC-MS) techniques. A total of 5402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis (GSEA) involving all genes.

Primary care providers’ perspectives on referrals to the Diabetes Prevention Programme: a qualitative comparative study across varied referral patterns

IntroductionDespite the effectiveness of Diabetes Prevention Programmes (DPP) in reducing diabetes risk, primary care provider (PCP) referrals remain low, especially among men and racial/ethnic minorities, exacerbating their under-representation in DPPs....

CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant

Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased enhancer discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system. Among the enhancers identified, we focused on an enhancer we named ONECUT1e-664kb, ∼664 kb from the ONECUT1 promoter. Previous studies have linked ONECUT1 coding mutations to pancreatic hypoplasia and neonatal diabetes. We found that homozygous deletion of ONECUT1e-664kb in hPSCs leads to a near-complete loss of ONECUT1 expression and impaired pancreatic differentiation. ONECUT1e-664kb contains a type 2 diabetes-associated variant (rs528350911) disrupting a GATA motif. Introducing the risk variant into hPSCs reduced binding of key pancreatic transcription factors (GATA4, GATA6, and FOXA2), supporting its causal role in diabetes. This work highlights the utility of unbiased enhancer discovery in disease-relevant settings for understanding monogenic and complex disease.

Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses following low-energy diet-induced weight loss: a PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) substudy

BackgroundWeight loss through lifestyle interventions, notably low-energy diets, offers glycemic benefits in populations with overweight-associated prediabetes. However, >50% of these individuals fail to achieve normoglycemia after weight loss. Circulating lipids hold potential for evaluating dietary impacts and predicting diabetes risk. ObjectivesThis study sought to identify serum lipids that could serve as evaluative or predictive biomarkers for individual glycemic changes following diet-induced weight loss. MethodsWe studied 104 participants with overweight-associated prediabetes, who lost ≥8% weight via a low-energy diet over 8 wk. High-coverage lipidomics was conducted in serum samples before and after the dietary intervention. The lipidomic recalibration was assessed using differential lipid abundance comparisons and partial least squares discriminant analyses. Associations between lipid changes and clinical characteristics were determined by Spearman correlation and Bootstrap Forest of ensemble machine learning model. Baseline lipids, predictive of glycemic parameters changes postweight loss, were assessed using Bootstrap Forest analyses. ResultsWe quantified 439 serum lipid species and 9 related organic acids. Dietary intervention significantly reduced diacylglycerols, ceramides, lysophospholipids, and ether-linked phosphatidylethanolamine. In contrast, acylcarnitines, short-chain fatty acids, organic acids, and ether-linked phosphatidylcholine increased significantly. Changes in certain lipid species (e.g., saturated and monounsaturated fatty acid-containing glycerolipids, sphingadienine-based very long-chain sphingolipids, and organic acids) were closely associated with clinical glycemic parameters. Six baseline bioactive sphingolipids primarily predicted changes in fasting plasma glucose. In addition, a number of baseline lipid species, mainly diacylglycerols and triglycerides, were predictive of clinical changes in hemoglobin A1c, insulin and homeostasis model assessment of insulin resistance. ConclusionsNewly discovered serum lipidomic alterations and the associated changes in lipid-clinical variables suggest broad metabolic reprogramming related to diet-mediated glycemic control. Novel lipid predictors of glycemic outcomes could facilitate early stratification of individuals with prediabetes who are metabolically less responsive to weight loss, enabling more tailored intervention strategies beyond 1-size-fits-all lifestyle modification advice.The PREVIEW lifestyle intervention study was registered at clinicaltrials.gov as NCT01777893 (https://clinicaltrials.gov/study/NCT01777893).