The role of autoimmune beta-cell damage in cystic fibrosis-related glucose abnormalities remains unclear. This study evaluates the prevalence of pancreatic islet autoantibodies (AABs) by glycemic status and age, and assesses the risk of developing cystic fibrosis-related diabetes (CFRD) in people with cystic fibrosis (pwCF).

A random-effects meta-analysis examined AABs against glutamic acid decarboxylase (GADA), insulin (IAA), islet cell (ICA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in pwCF (CRD42023482663). Prevalence, odds ratios (OR), and 95 % confidence intervals (CI) were calculated with subgroup analyses by glycemic status and age.

Analysis of 20 studies (2229 pwCF) found an overall islet AAB positivity rate of 4 % (CI: 2-9 %) and multiple positivity at 1 % (CI: 0-11 %). IAA had the highest prevalence at 6 % (CI: 3-14 %), and ICA the lowest at 1 % (CI: 0-9 %). Islet AAB prevalence trended higher in CFRD than non-CFRD patients and in children than adults. CFRD was significantly associated with islet AAB positivity, notably for GADA (OR 4.63, CI: 3.42-6.28), ICA (OR 3.57, CI: 1.05-12.18), and IA-2A (OR 2.36, CI: 1.29-4.34). Any and multiple AAB positivity were similarly correlated to CFRD (OR 2.82, CI: 1.22-6.51 and OR 2.71, CI: 1.49-4.93).

Pancreatic islet AABs are present in 1-6 % of pwCF and increase the risk of CFRD by 2.36 to 4.63 times. While there's a suggested link, limited study quality and inconsistent testing warrant cautious interpretation. Further robust studies are needed to confirm these findings and improve screening strategies.

To determine if, after adjusting for potential confounders, child health outcomes differ between children exposed to maternal gestational diabetes mellitus (GDM) and their unexposed peers.

Prospective cohort study. Recruitment took place between June 2022 and May 2024. The primary outcome was overweight or obesity. The secondary outcomes were other measures of size, eating behavior, behavioral and emotional problems, neurodevelopmental disorders, atopic disorders, and diabetes. Between-group differences were determined with generalized linear mixed models adjusted for gestational weight gain and socioeconomic status.

Of the 699 children who participated at a mean age of 5.6 years, 295 (42.2%) were exposed to GDM. There was no difference in the risk of being overweight or obese in children exposed to GDM compared with those unexposed (adjusted relative risk [95% CI]: 0.69 [0.44, 1.08]). Children exposed to GDM had lower body mass index z scores (adjusted relative risk [95% CI]: -0.30 [-0.53, -0.60]), enjoyment of food scores (adjusted relative risk [95% CI]: -0.17 [-0.31, -.04]), and risk of abnormal hyperactivity scores (adjusted relative risk [95% CI]: 0.23 [0.06, 0.87])] Other outcomes were similar between exposure groups.

After accounting for confounders, children exposed to treated GDM had a risk of being overweight or obese comparable with their unexposed peers. Our findings are reassuring for parents and health practitioners caring for women who experience GDM and their children.

It has been suggested that dietary factors correlated with red meat may contribute to its adverse health effects, while consuming red meat within a healthy diet may not necessarily increase disease risk.

Among 204,740 participants from three prospective cohorts, we examined the association between red meat consumption and risk of type 2 diabetes (T2D) across different levels of diet quality, measured by Alternative Healthy Eating Index (AHEI)-2010 (excluding red and processed meat component), using multivariable-adjusted Cox proportional hazards models. Dietary intake was assessed using repeated food frequency questionnaires.

During a median follow-up of 28 years, 18,868 cases were documented. Mean values were 47.3 (SD 8.5) for AHEI-2010 and 6.5 (SD 3.5), 1.8 (SD 1.5), and 4.8 (SD 2.5) servings/week for total, processed, and unprocessed red meat, respectively. Greater red meat consumption was consistently associated with a higher T2D risk across AHEI-2010 strata. Comparing the highest with the lowest quintile of red meat consumption in the highest diet quality quintile, the multivariable-adjusted HRs were 1.95 (1.72, 2.21) for total, 1.88 (1.67, 2.13) for processed, and 1.67 (1.47, 1.90) for unprocessed red meat. Substituting red meat with major food groups was associated with a lower T2D risk, particularly among those with high diet quality. The benefit of lowering red meat consumption was greater in participants with higher diet quality.

The risk associated with high red meat consumption persisted even among participants with a relatively high diet quality, underscoring the importance of limiting red meat consumption to prevent T2D.

Gestational diabetes mellitus (GDM) is regarded by many as maternal maladaptation to physiological insulin resistance during the second half of pregnancy. However, recent evidence indicates that alterations in carbohydrate metabolism can already be detected in early pregnancy. This observation, the increasing prevalence of GDM, and the significant short and long-term implications for the mother and offspring call for reevaluation of the conceptual paradigm of GDM as a syndrome. This review will present evidence for the syndromic nature of GDM and the controversies regarding screening, diagnosis, management, and treatment.

Diabetes mellitus is characterized by the loss of pancreatic insulin-secreting β-cells in the Islets of Langerhans. Understanding the regenerative potential of human islet cells is relevant in the context of putative restoration of islet function after damage and novel islet cell replacement therapies. Adult human pancreatic tissue can be cultured as three-dimensional organoids with the capacity for long-term expansion and the promise of endocrine cell formation. Here, we characterize the endocrine differentiation potential of human adult pancreatic organoids. Because exocrine-to-endocrine differentiation is dependent on the expression of Neurogenin 3 (NEUROG3), we first generated NEUROG3-inducible organoid lines. We show that doxycycline-induced NEUROG3 expression in the organoids leads to the formation of chromogranin A positive (CHGA+) endocrine progenitor cells. The efficiency of this differentiation was improved with the addition of thyroid hormone T3 and the AXL inhibitor R428. Further, compound screening demonstrated that modifying the pivotal embryonic endocrine pancreas signalling pathways driven by Notch, YAP, and EGFR led to increased NEUROG3 expression in organoids. In a similar fashion to embryonic development, adult ductal cells delaminated from the organoids after NEUROG3 induction. Thus, mechanisms in islet (re)generation including the initiation of endocrine differentiation and delamination can be achieved by NEUROG3 induction.

Existing evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.

We used data from 51,290 women in the Nurses' Health Study (1990-2016), 61,703 women in the Nurses' Health Study II (1991-2017) and 29,497 men in the Health Professionals Follow-up Study (1990-2016). Using food frequency questionnaires and food composition tables, we calculated MUFA-P and MUFA-A intakes every 4 years and modelled their associations with type 2 diabetes using Cox regression models.

During 3,268,512 person-years of follow-up, we documented 13,211 incident type 2 diabetes cases. After multivariate adjustment, total MUFA intake was associated with higher type 2 diabetes risk, with HR for Q5 vs Q1 of 1.10 (95% CI 1.01, 1.22). MUFA-Ps and MUFA-As demonstrated divergent associations, with HRs of 0.87 (95% CI 0.81, 0.94) and 1.34 (1.23, 1.45), respectively. In substitution analyses, HRs were 0.92 (95% CI 0.86, 0.99) for replacing 2% of energy from trans fatty acids or 0.72 (0.66, 0.78) and 0.82 (0.77, 0.88) for replacing 5% from MUFA-As and 5% from the sum of saturated fatty acids and MUFA-As with MUFA-Ps, respectively. Substituting MUFA-As for saturated fatty acids and refined carbohydrates was associated with a 43% and 33% higher risk, respectively.

Higher intake of MUFA-Ps was associated with lower type 2 diabetes risk, whereas increased intake of MUFA-As was associated with higher risk. Replacing saturated fatty acids, trans fatty acids and MUFA-As with MUFA-Ps may be beneficial for type 2 diabetes prevention.

Recent research has highlighted the significance of succinate and its receptor in gestational diabetes (GDM) pathogenesis. However, a clear interconnection between placenta metabolism, succinate levels, SUCNR1 signalling and pregnancy pathologies remains elusive. Here, we set out to investigate the potential role of succinate on labour and placental mechanisms by combining clinical and functional experimental data at the same time as exploring the specific SUCNR1-mediated effects of succinate on placenta vascularization, addressing its specific agonist actions. According to our data, succinate levels vary throughout pregnancy and postpartum, with a natural increase during the peripartum period. We also show that SUCNR1 activation in the umbilical cord endothelium promotes angiogenesis under normal conditions. However, in GDM, excessive succinate and impaired SUCNR1 function may weaken this angiogenic response. In conclusion, the present study underlines succinate as an emerging signalling molecule in the placenta, regulating labour and placental processes. The reduced sensitivity of the succinate/SUCNR1 pathway in the GDM environment may serve as a protective physiological mechanism or could have a pathogenic effect. KEY POINTS: Succinate levels increase at delivery in maternal and fetal circulation. Gestational diabetes (GDM) induces succinate accumulation and SUCNR1 downregulation in umbilical cords. GDM compromises angiogenic gene profile modulation by SUCNR1 in umbilical cord endothelium. SUCNR1 activation stimulates sprouting and tube-forming capacity of human umbilical vein endothelial cells from healthy, but not GDM pregnancies.

Background and Aims: Emerging evidence suggests adverse pregnancy outcomes (APOs) may increase future cardiovascular risk. This study aimed to assess in a Spanish cohort the long-term risk of cardiovascular disease in women with APOs compared to those without such complications. Methods: A retrospective longitudinal cohort study was conducted at Hospital Vall d'Hebron (Barcelona, Spain), including pregnant women delivering between January 2010 and December 2015. Women with pre-existing medical conditions were excluded. APOs included preeclampsia, gestational diabetes, preterm birth, late miscarriage, and stillbirth. Cardiovascular events were defined as acute myocardial infarction or stroke. Both APO and non-APO groups were compared for their risk of cardiovascular events in the years following delivery, using unadjusted and adjusted models. Results: Out of 12,071 pregnant women delivered at Hospital Vall d'Hebron during the study period. 10,734 met the inclusion criteria (8234 in the non-APO group and 2500 in the APO group). The adjusted model revealed a significant association between APOs and cardiovascular events post-delivery (HR 2.5; 95% CI 1.4-4.4). Furthermore, an increased number of APOs (≥2) correlated with a higher risk of post-delivery cardiovascular events (HR 8.6; 95% CI 2.8-26.8). Conclusions: Women with adverse pregnancy outcomes (APOs), particularly those experiencing preeclampsia, preterm birth, and late miscarriage, exhibit an elevated long-term risk of cardiovascular events. Our findings highlight that these associations persist even after adjusting for traditional cardiovascular risk factors, indicating that APOs may independently influence long-term cardiovascular health. This underscores the importance of recognizing pregnancy as a critical window for early cardiovascular health interventions and counseling. Addressing these risks proactively could improve long-term health outcomes for women with a history of APOs.

Consumption of coffee has been consistently associated with lower risk of type 2 diabetes (T2D). However, it is unknown whether the use of additives may modify the association.

This study aimed to analyze the association between coffee consumption and risk of T2D by considering the addition of sugar, artificial sweeteners, cream, or a nondairy coffee whitener.

We used 3 large prospective cohorts-Nurses' Health Study (NHS; 1986-2020), NHS II (1991-2020), and the Health Professionals Follow-up Study (HPFS 1991-2020). Self-reported coffee consumption, additive use, and T2D incidence were confirmed using validated questionnaires. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with multivariable adjustment.

During 3,665,408 person-years of follow-up, we documented 13,281 incident T2D cases. After multivariable adjustment, each additional cup of coffee without any additive was associated with 10% lower risk of T2D (HR: 0.90; 95% CI: 0.89, 0.92) in the pooled analysis of the 3 cohorts. The inverse association did not change among participants who added cream. Among participants who added sugar to coffee (on average 1 teaspoon per cup), the association was significantly weakened (HR: 0.95; 95% CI: 0.93, 0.97; interaction term HR: 1.17; 95% CI: 1.07, 1.27). A similar pattern was observed among those who used artificial sweeteners (HR: 0.93; 95% CI: 0.90, 0.96; interaction term HR: 1.13; 95% CI: 1.00, 1.28). The association between coffee consumption and T2D risk among those who used coffee whitener was also attenuated, although the interaction was not significant (HR: 0.95; 95% CI: 0.91, 1.00; interaction term HR: 1.16; 95% CI: 0.66, 2.06).

Adding sugar or artificial sweetener significantly attenuates the magnitude of the inverse association between higher coffee consumption and T2D risk, whereas the use of cream do not alter the inverse association.

An abnormal level of alkaline phosphatase (ALP) in serum is related to many diseases, such as breast cancer, prostate cancer, hepatitis, and diabetes. The level of glucose in the blood is related to diabetes or hypoglycemia. Given the close correlation between ALP and glucose in various diseases, it is essential to establish an accurate, sensitive, and selective assay for monitoring the levels of ALP and glucose in serum. As luminescent materials, upconversion nanoparticles (UCNPs) stand out in the design of biosensors because of their high photostability, large anti-Stokes shifts and low background interference. Additionally, metal organic frameworks (MOFs) are a class of functional porous materials, and their adjustable pore size structure and high specific surface area expose many catalytic sites, making MOFs excellent catalysts and ideal materials for constructing artificial enzymes. Herein, a fluorescent and colorimetric dual-mode probe based on a multifunctional composite (UCNP@MOF) with upconversion luminescence and peroxidase-like activity was proposed for the detection of ALP and glucose. Under the optimal conditions, the detection limits of ALP and glucose by the fluorescence method were 0.046 U/L and 0.079 μM, respectively. Furthermore, the method was used to determine ALP and glucose in serum samples, and the detection results were similar to those of commercial kits; moreover, the recoveries were in the range of 92.7-105.4 %, indicating great potential for accurate and sensitive detection of ALP and glucose in biological samples.

Background: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from six hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. The secondary outcomes were composite adverse outcomes, including pregnancy complications, delivery complications, and neonatal complications. The cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1543 pregnant individuals in the standard screening group and 2197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs. 6.9%, respectively; p < 0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs. 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in the composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8%) vs. 15/151 (9.9%). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in the composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment, and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

Gestational diabetes mellitus (GDM) is defined by one or more abnormal values in an oral glucose tolerance test (OGTT). The significance/importance of the number of abnormal values in relation to adverse perinatal and neonatal outcomes is unclear. We assessed the association of these outcomes with the number of abnormal glucose values in a 2-h 75 g OGTT in a large register-based cohort.

This sub-study of the Finnish Gestational Diabetes Study was based on the Finnish Medical Birth Register 2009 supplemented with OGTT laboratory data of 4869 pregnant women from six Finnish hospitals. The diagnostic cut-offs in OGTT according to the Finnish guidelines for plasma samples were ≥5.3 mmol/L (fasting), ≥10.0 mmol/L 1 h or ≥8.6 mmol/L 2 h after the glucose load. As per the guidelines, women with one or several abnormal OGTT values received diet and lifestyle counseling in the primary care, self-monitored their glucose values and received pharmacological therapy as needed. Women with GDM were categorized according to the number of abnormal glucose values. The primary outcomes, composites of adverse perinatal (pre-eclampsia, preterm delivery, macrosomia or primary cesarean section) and neonatal outcomes (birth trauma, neonatal hypoglycemia, hyperbilirubinemia or stillbirth/perinatal mortality), were analyzed by logistic regression adjusted for maternal age, pre-pregnancy body mass index, parity, socio-economic status and smoking.

Of all the women, 877 (18.0%) had one, 278 (5.7%) two and 79 (1.6%) three abnormal OGTT values, while 3635 (74.7%) women were normoglycemic. Women with at least two abnormal OGTT values had higher proportions of adverse perinatal composite (35.0% vs. 27.5%, adjusted odds ratio 1.36; 95% confidence interval 1.03-1.81) and neonatal composite outcomes (31.1% vs. 18.9%, adjusted odds ratio 1.88; 95% confidence interval 1.40-2.52) compared to women with one abnormal value. The risks of delivery induction and neonatal hypoglycemia were increased regardless of the number of abnormal values when compared with normoglycemic women.

The risk of adverse perinatal and neonatal outcomes is significantly higher in women with two or more abnormal OGTT values than in those with one abnormal value.

High birth weight increases the risk of obstetric anal sphincter injury. Macrosomia is a well-known complication in pregnancies complicated by gestational diabetes mellitus. The aim of this study was to investigate whether gestational diabetes is a risk factor for obstetric anal sphincter injury. We hypothesized that women with gestational diabetes have an increased risk of obstetric anal sphincter injury.

We performed a systematic review and meta-analysis using the PubMed and Embase databases. Studies including numbers on women with and without gestational diabetes and with and without obstetric anal sphincter injury were included. Studies were assessed using the SIGN-methodology checklist to evaluate the quality and risk of bias. Extracted data was analyzed using RevMan 5.4 and the statistical software R.

Twelve cohort studies were included for the meta-analyses. Overall, we found a slightly increased prevalence of obstetric anal sphincter injury among the women with gestational diabetes of 2.40% (95% CI; 2.37-2.43) compared to 2.31% (95% CI; 2.30-2.32) in women without diabetes. The meta-analysis revealed increased risk of obstetric anal sphincter injury in the gestational diabetes-group (RR 1.24 [95% CI; 1.12-1.37]) with a high level of heterogeneity (I2 = 94%). Primiparous women with gestational diabetes had an increased risk of obstetric anal sphincter injury 6.65% (95% CI; 6.18-7.14) compared to 4.98% (95% CI; 4.89-5.08) in the control group, whereas the risk was not significantly increased in multiparous women.

The risk of obstetric anal sphincter injury is increased in primiparous women with gestational diabetes mellitus compared to women without gestational diabetes.

Postprandial glucose concentration 1-h (1 h-PG) after an oral glucose tolerance test (OGTT) has similar or superior performance to 2 h-PG in predicting type-2 diabetes mellitus (T2DM) in several populations, and is simpler to obtain in clinical practice. However, studies in Asians are scarce. We investigated the utility of elevated baseline 1 h-PG in predicting T2DM incidence within three years, and its relationship with β-cell function in 1250 non-diabetic Asian participants.

Participants underwent an OGTT, an intravenous glucose challenge and a hyperinsulinemic-euglycemic clamp to determine glucose tolerance, acute insulin response (AIR) and insulin sensitivity at baseline. OGTTs were repeated every six months until study completion to monitor T2DM conversion.

The area under the receiver operating characteristic curve of 1 h-PG was not significantly different from 2 h-PG (AUC1h-PG = 0.883 vs. AUC2h-PG = 0.907; ΔAUC = -0.024, P = 0.124) and the optimal 1 h-PG cut-off was ≥10.7 mmol/L. When groups of high/low 1 h-PG and 2 h-PG at baseline were compared, AIR and disposition index were significantly lower in groups with high 1 h-PG, and both had a stronger correlation with 1 h-PG, indicating that impaired β-cell function was more strongly associated with elevated 1 h-PG than 2 h-PG.

The ability of 1 h-PG to detect Asians at risk of developing T2DM within three years is on par with 2 h-PG and the optimal cut-off is 10.7 mmol/L. Elevated 1 h-PG is associated with β-cell dysfunction. We conclude that 1 h-PG can be considered as a primary OGTT time point to identify Asians at risk for T2DM, allowing for screening at a reduced time and cost, and with lower patient burden.

National Medical Research Council (NMRC), Ministry of Health (MOH; Singapore) Industry Alignment Fund [NMRC/MOHIAFCat1/0048/2016] and Janssen Pharmaceuticals Inc. (USA).

The link between Type 2 Diabetes (T2DM) and Parkinson's Disease (PD) dates back to the early 1960s, and ongoing research is exploring this association. PD is linked to dysregulation of dopaminergic pathways, neuroinflammation, decreased PPAR-γ coactivator 1-α, increased phosphoprotein enriched in diabetes, and accelerated α-Syn amyloid fibril production caused by T2DM. This study aims to comprehensively evaluate the T2DM-PD association and risk factors for PD in T2DM individuals. The study reviews existing literature using reputable sources like Scopus, ScienceDirect, and PubMed, revealing a significant association between T2DM and worsened PD symptoms. Genetic profiles of T2DM-PD individuals show similarities, and potential risk factors include insulin-resistance and dysbiosis of the gut-brain microbiome. Anti-diabetic drugs exhibit neuroprotective effects in PD, and nanoscale delivery systems like exosomes, micelles, and liposomes show promise in enhancing drug efficacy by crossing the Blood-Brain Barrier (BBB). Brain targeting for PD uses exosomes, micelles, liposomes, dendrimers, solid lipid nanoparticles, nano-sized polymers, and niosomes to improve medication and gene therapy efficacy. Surface modification of nanocarriers with bioactive compounds (such as angiopep, lactoferrin, and OX26) enhances α-Syn conjugation and BBB permeability. Natural exosomes, though limited, hold potential for investigating DM-PD pathways in clinical research. The study delves into the underlying mechanisms of T2DM and PD and explores current therapeutic approaches in the field of nano-based targeted drug delivery. Emphasis is placed on resolved and ongoing issues in understanding and managing both conditions.

Self-monitoring of blood glucose (SMBG) is the standard of care for women with gestational diabetes mellitus (GDM). This study aimed to review SMBG profiles in women with GDM and to examine how glucose metrics derived from SMBG relate to fetal overgrowth and infants born large for gestational age (LGA, >90th percentile).

This was a single-center, historical, observational cohort study of 879 GDM pregnancies in Sweden. The diagnosis of GDM was based on a universal 75 g oral glucose tolerance test at gestational week 28 or 12 in high-risk women. The glucose metrics derived from the SMBG profiles were calculated. Treatment targets for glucose were <5.3 mmol/L fasting, and ≤7.8 mmol/L 1-h postprandial. The median (interquartile range) number of glucose measurements in the analysis for each woman was 318 (216-471), including 53 (38-79) fasting glucose measurements. Associations between glucose metrics and LGA were analyzed using binary logistic regression analysis adjusted for maternal age, body mass index, smoking, nulliparity, and European/non-European origin. Receiver operating characteristic (ROC) curves were used to evaluate glucose levels for LGA prediction. Differences in means were tested using analysis of variance.

The proportion of LGA infants was 14.6%. Higher mean glucose levels and smaller proportion of readings in target (glucose 3.5-7.8 mmol/L) were significantly associated with LGA (odds ratio [95% confidence interval]: 3.06 [2.05-4.57] and 0.94 [0.92-0.96], respectively). The strongest association was found with mean fasting glucose (3.84 [2.55-5.77]). The ability of mean fasting glucose and overall mean glucose to predict LGA infants in the ROC curves was fair, with areas under the curve of 0.738 and 0.697, respectively (p < 0.001). The corresponding discriminating thresholds were 5.3 and 6.1 mmol/L, respectively. Mean glucose levels increased and readings in target decreased with increasing body mass index category and at each step of adding pharmacological treatment, from diet alone to metformin and insulin (p < 0.001).

Higher mean glucose levels and a smaller proportion of readings within the target range were associated with an increased risk of LGA. Suboptimal glucose control is associated with obesity and the need for pharmacological treatment.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Currently, there is a lack of standardized diagnostic criteria for gestational diabetes mellitus (GDM), making it a subject of ongoing debate. The optimal diagnostic method and screening strategy for GDM remain contentious. In this review, we summarize the criteria and methods for diagnosing GDM, and perform a comparison between universal and selective screening strategies. Therefore, this review aims to highlight the following: (1) The most widely adopted criteria for GDM are those established by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). (2) Evidence from cohort studies suggests that the one-step diagnostic method is associated with improved pregnancy outcomes and appears more cost-effective compared to the two-step method. (3) Universal screening is more cost-effective than selective screening, which may overlook a significant number of women with GDM. Additionally, various methods have been proposed for early pregnancy screening (before 14 weeks). Finally, an outlook is presented for the diagnosis of GDM, emphasizing the importance of large-scale randomized controlled trials (RCTs) to provide stronger evidence for future support.

Correction of decreased diversity of the gut microbiome, which is characteristic of menopause, by supplementation with a synbiotic may attenuate or prevent dysbiosis processes and preserve bone mass. We describe the rationale and design of the OsteoPreP trial aimed at evaluating the effects of 12 months of supplementation with a synbiotic on bone and metabolic health in postmenopausal Caucasian women.

This is a randomized, double-blinded, placebo-controlled trial among 160 Caucasian, postmenopausal women with no current diagnosis of osteoporosis or supplementation with pro- or prebiotics, and no medical treatment affecting bone turnover. Dual-energy X-ray absorptiometry scans will be conducted at screening to confirm absence of osteoporosis. The primary outcome is the relative change (%) in total bone mineral density of the distal tibia at 12 months post-treatment between the active and placebo groups, as determined via high-resolution peripheral quantitative computed tomography. Secondary outcomes are the effects on immune system modulation and cognition, gut microbiota composition, and musculoskeletal and metabolic functions, with particular emphasis on blood glucose regulation.

The trial will inform on the efficacy and safety of a synbiotic containing both aerobic and anerobic bacterial strains and a prebiotic fiber on reduction in bone loss and on indices of blood glucose regulation. This trial may pave the way for an exciting field of translational research and be the underpinnings of the prevention strategy of osteoporosis and the management of metabolic dysfunction in postmenopausal women. The trial is registered with clinicaltrials.gov (NCT05348694).

The aim of this study is to assess the use of metformin with or without insulin for the treatment of Gestational Diabetes Mellitus compared to insulin alone.

This article consists of a systematic review of randomized clinical trials. The searches were carried out on MEDLINE including 7 studies, between 2010 to 2021.

Randomized clinical trials comparing metformin and insulin written in English, Spanish or Portuguese, with no time limit, were included.

Data was extracted from all the 7 articles and compared statistically when possible. Whenever data was not available or couldn't be statistically compared, the main results were described in detail.

Insulin alone is not superior than metformin with or without insulin on gestational diabetes mellitus.

There is a potential viability of using metformin as an alternative compared to insulin alone in the treatment of Gestational Diabetes Mellitus. However, all assessed outcomes have a very low level of certainty of evidence and more studies are necessary to support these findings.

To prospectively investigate the associations between dark, milk, and total chocolate consumption and risk of type 2 diabetes (T2D) in three US cohorts.

Prospective cohort studies.

Nurses' Health Study (NHS; 1986-2018), Nurses' Health Study II (NHSII; 1991-2021), and Health Professionals Follow-Up Study (HPFS; 1986-2020).

At study baseline for total chocolate analyses (1986 for NHS and HPFS; 1991 for NHSII), 192 208 participants without T2D, cardiovascular disease, or cancer were included. 111 654 participants were included in the analysis for risk of T2D by intake of chocolate subtypes, assessed from 2006 in NHS and HPFS and from 2007 in NHSII.

Self-reported incident T2D, with patients identified by follow-up questionnaires and confirmed through a validated supplementary questionnaire. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals (CIs) for T2D according to chocolate consumption.

In the primary analyses for total chocolate, 18 862 people with incident T2D were identified during 4 829 175 person years of follow-up. After adjusting for personal, lifestyle, and dietary risk factors, participants consuming ≥5 servings/week of any chocolate showed a significant 10% (95% CI 2% to 17%; P trend=0.07) lower rate of T2D compared with those who never or rarely consumed chocolate. In analyses by chocolate subtypes, 4771 people with incident T2D were identified. Participants who consumed ≥5 servings/week of dark chocolate showed a significant 21% (5% to 34%; P trend=0.006) lower risk of T2D. No significant associations were found for milk chocolate intake. Spline regression showed a linear dose-response association between dark chocolate intake and risk of T2D (P for linearity=0.003), with a significant risk reduction of 3% (1% to 5%) observed for each serving/week of dark chocolate consumption. Intake of milk, but not dark, chocolate was positively associated with weight gain.

Increased consumption of dark, but not milk, chocolate was associated with lower risk of T2D. Increased consumption of milk, but not dark, chocolate was associated with long term weight gain. Further randomized controlled trials are needed to replicate these findings and further explore the mechanisms.

To create an objective framework to classify gestational diabetes mellitus diagnosed by routine antenatal 75 g diabetes testing results to provide an alternative to current treatment-based classification.

A framework was created to classify gestational diabetes according to the severity of glycemic abnormalities after routine antenatal 75 g GTT (classes 1 through 4, determined by fasting and post-test glycemic abnormalities). A retrospective cohort chart review was used to correlate clinically how often diet therapy alone maintained glycemic targets throughout pregnancy in each class. Chi-square analysis was used to assess inter-class differences in the success of diet therapy alone maintaining glycemic targets throughout pregnancy.

Seventy-four of 228 (33%), 35/228 (15%), 76/228 (33%), and 43/228 (19%) of the study population were classified as Class 1, 2, 3, or 4, respectively. Of eighty-nine patients who maintained glycemic targets throughout pregnancy with diet alone 51/89 (57%) were Class 1, 20/89 (22.5%) were Class 2, 11/89 (12.5%) were Class 3, and 7/89 (8%) were Class 4. Chi-square analysis showed statistically significant inter-class differences in the likelihood of diet therapy alone maintaining glycemic targets throughout pregnancy.

In this framework classifying gestational diabetes according to the severity of glycemic abnormalities after routine antenatal 75 g GTT (an objective proxy for disease severity), the higher the assigned class, the less likely that diet therapy alone maintained glycemic targets throughout pregnancy (a clinical proxy for disease severity).

Background and Objectives: Gestational diabetes mellitus (GDM) is one of the most common medical conditions in pregnancy, with adverse effects on maternal and neonatal outcomes. Evidence suggests a beneficial effect of plant-based dietary patterns, rich in foods derived from plant sources and low in animal foods, on type 2 diabetes; however, their effects on GDM remain unclear. We aimed to investigate the association between pre-pregnancy provegetarian food patterns and the incidence of GDM in a Spanish cohort. Materials and Methods: This subsample of the Seguimiento Universidad de Navarra (SUN) cohort analyzed 3589 Spanish university graduate pregnant women with a mean (standard deviation) age of 28 (±4.3) who were initially free of pre-existing diabetes at baseline. Dietary food consumption was evaluated through a validated, 136-item semi-quantitative food frequency questionnaire. The pre-pregnancy provegetarian food pattern was obtained by assigning positive scores to plant-based food groups and reverse scores to animal food groups. Energy-adjusted quintiles were applied to allocate points to construct the provegetarian food pattern, ranging from 12 to 60 points. Logistic regression models were performed to estimate the odds ratios (OR) of GDM across quintiles of a pre-pregnancy provegetarian food pattern, using the lowest quintile as the reference category. Results: We identified 178 incidence cases of GDM. Women in the highest quintile (Q5) of provegetarian food pattern before pregnancy exhibited a 42% relative reduction in the odds of GDM [adjusted OR (95% CI) Q5 vs. Q1: 0.58 (0.35, 0.97); p-trend = 0.109]. Higher consumption of meat and dairy before pregnancy was associated with a significantly increased risk of GDM [adjusted OR (95% CI) Q5 vs. Q1: 1.94 (1.19, 3.16); p-trend = 0.005] and [adjusted OR (95% CI) Q5 vs. Q1: 1.77 (1.07, 2.94); p-trend = 0.082], respectively. Conclusions: Higher pre-pregnancy consumption of a provegetarian food pattern was associated with a lower risk of developing GDM in Spanish women. Further studies are needed to confirm these findings.

Gestational Diabetes Mellitus (GDM) is the most frequent pregnancy-related medical issue and presents significant risks to both maternal and foetal health, requiring monitoring and management during pregnancy. The prevalence of GDM has surged globally in recent years, mirroring the rise in diabetes and obesity rates. Estimated to affect from 5% to 25% of pregnancies, GDM impacts approximately 21 million live births annually, according to the International Diabetes Federation (IDF). However, consensus on diagnostic approaches remains elusive, with varying recommendations from international organizations, which makes the comparison between research complicated. Compounding concerns are the short-term and long-term complications stemming from GDM for mothers and offspring. Maternal outcomes include heightened cardiovascular risks and a notable 70% risk of developing Type 2 Diabetes Mellitus (T2DM) within a decade postpartum. Despite this, research into the metabolic profiles associated with a previous GDM predisposing women to T2D remains limited. While genetic biomarkers have been identified, indicating the multifaceted nature of GDM involving hormonal changes, insulin resistance, and impaired insulin secretion, there remains a dearth of exploration into the enduring health implications for both mothers and their children. Furthermore, offspring born to mothers with GDM have been shown to face an increased risk of obesity and metabolic syndrome during childhood and adolescence, with studies indicating a heightened risk ranging from 20% to 50%. This comprehensive review aims to critically assess the current landscape of Gestational Diabetes Mellitus (GDM) research, focusing on its prevalence, diagnostic challenges, and health impacts on mothers and offspring. By examining state-of-the-art knowledge and identifying key knowledge gaps in the scientific literature, this review aims to highlight the multifaceted factors that have hindered a deeper understanding of GDM and its long-term consequences. Ultimately, this scholarly exploration seeks to promote further investigation into this critical area, improving health outcomes for mothers and their children.

To identify the proportion of patients with prediabetes who have prescribed metformin and factors related to doing so as a preventive measure for diabetes in primary care at a Family Medicine Unit in northeastern Mexico.

This retrospective observational study included 372 adults who met the criteria for prediabetes diagnosis according to the American Diabetes Association. Data was collected from medical records from January 2020 to December 2021. Possible associations between the variables of interest and the prescription of metformin were tested via hypothesis tests, furthermore, binary logistic regression was performed.

Nearly 85% of the patients met at least one criterion for receiving metformin according to ADA recommendations, but only 60% of them were prescribed this medication. Patients with metformin prescriptions differed from those without in aspects such as having a documented diagnosis of prediabetes in their medical records, a higher BMI, and higher glucose levels.

Almost one out of two patients with a high risk of type 2 diabetes are not treated with metformin as a preventive measure. Factors associated with metformin prescription included a high BMI, elevated baseline glucose levels, and a prediabetes diagnosis in the medical record. These findings suggest the need for studies to evaluate physicians' reasons for different treatments and implementation of recommendations for type 2 diabetes prevention in patients with prediabetes in primary health care.

In a previous study performed by our group, pregnant women with Gestational Diabetes (GDM) showed higher vitamin D (VitD) levels in the last trimester, particularly in those requiring insulin. This phenomenon was not linked to factors like season or supplementation. This study aimed to investigate if insulin treatment in GDM affects DNA methylation in VitD metabolism genes. Thirty-two pregnant women were selected, half of whom had GDM, and were divided into insulin-treated and lifestyle groups. The DNA methylation levels in CpGs from 47 VitD metabolism-related genes were analyzed at the diagnostic visit (24-28 weeks) and before delivery. At week 36-38 of pregnancy, twenty-six CpG sites were differentially methylated (DMPs) in the insulin-treated group compared with the control group and the lifestyle group. Twenty-two of these DMPs were not different at the diagnostic visit. Six CpGs (cg18276810 (CTNNB1), cg03919554 (FGFR3), cg03984919 (NCOA1), cg19218509 (ASIP), cg09922639 (SMAD3), and cg25356935 (PDZD3)) showed significant correlations with VitD levels, not only before childbirth, but also in the postpartum period and at one year later. This suggests that insulin treatment in GDM could influence DNA methylation in genes involved in vitamin D metabolism, affecting VitD levels during and after pregnancy. Further research is warranted to elucidate these findings' clinical implications.

Obesity is an epidemic associated with platelet and vascular disorders. Platelet O-GlcNAcylation has been poorly studied in obese subjects. We aimed to evaluate O-linked N-acetyl-glucosamine (O-GlcNAc) levels and platelet activity in obese insulin-resistant (ObIR) subjects. Six healthy and six insulin-resistant obese subjects with a body mass index of 22.6 kg/m2 (SD ± 2.2) and 35.6 kg/m2 (SD ± 3.8), respectively, were included. Flow cytometry was used to measure markers of platelet activity, expression of P-selectin (CD62P antibody), glycoprotein IIb/IIIa (integrins αIIbβ3 binding to PAC-1 antibody), and thrombin stimulation. O-GlcNAc was determined in the platelets of all test subjects by cytofluometry, intracellular calcium, percentage of platelet aggregation, and immunofluorescence microscopy and Western blot were used to assess O-GlcNAc and OGT (O-GlcNAc transferase) in platelets. Platelets from ObIR subjects had on average 221.4 nM intracellular calcium, 81.89% PAC-1, 22.85% CD62P, 57.48% OGT, and 66.62% O-GlcNAc, while platelets from healthy subjects had on average 719.2 nM intracellular calcium, 4.99% PAC-1, 3.17% CD62P, 18.38% OGT, and 23.41% O-GlcNAc. ObIR subjects showed lower platelet aggregation than healthy subjects, 13.83% and 54%, respectively. The results show that ObIR subjects have increased O-GlcNAc, and increased intraplatelet calcium associated with platelet hyperactivity and compared to healthy subjects, suggesting that changes in platelet protein O-GlcNAcylation and platelet activity might serve as a possible prognostic tool for insulin resistance, prediabetes and its progression to type 2 diabetes mellitus.

Epidemiologic evidence has emerged showing an association between exposure to air pollution and increased risks of gestational diabetes mellitus (GDM). This study examines the effect of low-level air pollution exposure on a subclinical biomarker of hyperglycemia (i.e., HbA1c) in pregnant people without diabetes before conception. We measured HbA1c in 577 samples repeatedly collected from 224 pregnant people in Rochester, NY, and estimated residential concentrations of PM2.5 and NO2 using high-resolution spatiotemporal models. We observed a U-shaped trajectory of HbA1c during pregnancy with average HbA1c levels of 5.13 (±0.52), 4.97 (±0.54), and 5.43 (±0.40)% in early-, mid-, and late pregnancy, respectively. After adjustment for the U-shaped trajectory and classic GDM risk factors, each interquartile range increase in 10 week NO2 concentration (8.0 ppb) was associated with 0.09% (95% CI: 0.02 to 0.16%) and 0.18% (95% CI: 0.08 to 0.28%) increases in HbA1c over the entire pregnancy and in late pregnancy, respectively. These associations remained robust among participants without GDM. Using separate distributed lag models, we identified a period between 8th and 14th gestational weeks as critical windows responsible for increased levels of HbA1c measured at 14th, 22nd, and 30th gestational weeks. Our results suggest that low-level air pollution contributes to hyperglycemia in medically low-risk pregnant people.

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis.

Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy.

We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality.

Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women.

Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility.

Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (-0.08 vs. 0.31, P = 2.3 × 10-11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05-2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15-0.49, P = 3.0 × 10-4). Although there was variation, a similar trend was observed across study cohorts.

In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.

Inadequate management of blood glucose levels in gestational diabetes mellitus (GDM) poses risks for both pregnant women and the developing fetus. Attaining appropriate blood glucose control is crucial to mitigate potential adverse outcomes. This study aimed to consolidate the latest guidelines from representative professional societies, providing insights into exercise therapy for GDM patients and suggesting potential avenues for future research. The review was conducted with up-to-date exercise guidelines from prominent societies, such as the American College of Obstetricians and Gynecologists (ACOG), the Society of Obstetricians and Gynecologists of Canada (SOGC), the Canadian Society for Exercise Physiology (CSEP), the American College of Sports Medicine, the American Diabetes Association (ADA), and the Korean Diabetes Association. The ACOG and SOGC/CSEP recommend 150 min of low to moderate intensity exercise, 3-4 times a week, combining aerobic and resistance exercises. All guidelines advise against activities involving sudden directional changes, physical contact, a risk of falling, and exercises performed lying down. Despite cautions from the ADA and ACOG on blood glucose fluctuations during physical activity, the lack of specific methods and recommendations from other societies reveals a notable gap in evidence-based guidelines for GDM. For effective and safe blood glucose management in GDM patients, further research should be conducted on the exercise-related precautions outlined for GDM patients. Establishing ample evidence would facilitate the development of customized exercise guidelines for GDM patients.

The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies.

This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up.

A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus.

Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively).

Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

Retinopathy is one of the most common microvascular complications of diabetes mellitus and is the leading cause of vision loss in the working middle-aged population.

This study aimed to investigate the value of neopterin and orexin-A levels in patients with diabetes mellitus with different stages of diabetic retinopathy and without diabetic retinopathy and to compare those findings with results from healthy individuals without diabetes mellitus.

In total, 65 patients with type 2 diabetes mellitus and 22 healthy individuals without diabetes mellitus were enrolled in this prospective study. The participants were separated into four subgroups. The first subgroup included 25 patients without diabetic retinopathy, the second subgroup included 20 patients non-proliferative diabetic retinopathy, the third subgroup included 20 patients with proliferative diabetic retinopathy, and the fourth subgroup included 22 healthy individuals without diabetes mellitus as controls. Serum neopterin and orexin-A levels were analysed and compared among the groups.

The age and gender of the participants between the four subgroups were not statistically significantly different (p > 0.05). The mean neopterin levels were significantly higher in patients included in the diabetes mellitus subgroups compared with the controls (p < 0.001). Neopterin levels significantly increased as diabetic retinopathy progressed within the diabetes mellitus subgroups. Mean orexin-A levels were significantly lower in the diabetes mellitus subgroups compared with the controls (p < 0.001); however, orexin-A levels were not significantly different within the diabetes mellitus subgroups (p > 0.05).

Patients with diabetes mellitus have higher serum neopterin and lower serum orexin-A levels compared with healthy individuals without diabetes mellitus. Moreover, serum neopterin levels increase with progression of diabetic retinopathy.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.