Key biomarkers in type 2 diabetes patients: A systematic review.

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.

Correlation between fetal subcutaneous fat thickness and insulin resistance through cord blood analysis immediately after delivery.

OBJECTIVES: This study aimed to determine whether fetal subcutaneous tissue (SCT) thickness, measured using ultrasound immediately before and after delivery, can reflect changes in glucose metabolism immediately after delivery. We also evaluated the impact of insulin resistance changes during pregnancy by comparing pregnant women with well-controlled gestational diabetes mellitus (GDM) and those with normal glucose metabolism. STUDY DESIGN: The study participants were 117 pregnant women, including 97 controls and 20 patients with GDM who visited our obstetric clinic between February and December 2022. The participants were scheduled for cesarean delivery at a gestational age of ≥37 weeks. SCT thickness before delivery was measured using ultrasound and within 48 h after delivery using Holtain calipers. The glucose and insulin concentrations were quantified from cord blood collected immediately after delivery. Based on these results, a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was performed to assess insulin resistance. Independent t-test or Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables were used to compare the various parameters. Correlations among the variables in each group were assessed by calculating the correlation coefficient (Pearson's correlation). RESULTS: SCT thickness measured using ultrasound and calipers demonstrated a strong correlation where pregnant women with GDM exhibited thicker fetal SCT and neonate skinfolds than in those without GDM. Glucose and insulin levels in the cord blood were significantly elevated (p < 0.05) in the gestational diabetic group, along with remarkable differences (p < 0.001) in HOMA-IR. These variables indicated a higher prevalence of glucose intolerance in the neonates of mothers with GDM. In pregnant women with GDM, there was a statistically significant correlation between fetal abdominal SCT thickness and glucose levels (r = 0.64, p < 0.01) and HOMA-IR (r = 0.48, p < 0.05). CONCLUSIONS: Measuring the subcutaneous fat thickness of the fetus shortly before delivery is beneficial for predicting insulin resistance in neonates. This is considered particularly useful for women with effectively managed GDM, where the presence of conditions such as macrosomia may not be pronounced.

Association between neck circumference and glucose tolerance levels at 2-6 months postpartum in women with and without gestational diabetes.

Objective: To evaluate the association between neck circumference (NC) measured during pregnancy and markers of glucose metabolism measured 2-6 months postpartum in women with overweight/obesity with and without gestational diabetes (GDM). Subjects and methods: This prospective study enrolled 100 pregnant women (including 50 with GDM) with pregestational body mass index (BMI) ≥ 25 kg and < 40 kg/m². The cohort was stratified according to NC tertiles during pregnancy. Glucose metabolism was assessed in the postpartum period. The association between NC during pregnancy and markers of glucose metabolism postpartum was tested using linear regression analysis. Results: Participants with NC in the third tertile, compared with those with NC in the second and first tertiles, had higher levels of glycated hemoglobin (HbA1c; 5.6 ± 0.4% versus 5.4 ± 0.3% versus 5.3 ± 0.2%, respectively, p = 0.006), fasting insulin (13.2 ± 6.6 µIU/mL versus 11.1 ± 5.8 µIU/mL versus 9.5 ± 4.9 µIU/mL, respectively, p = 0.035), homeostasis model for insulin resistance (HOMA-IR; 3.1 ± 1.7 versus 2.5 ± 1.3 versus 2.1 ± 1.2, respectively, p = 0.035) and triglyceride-glucose index (TyG; 4.6 ± 0.2 versus 4.5 ± 0.2 versus 4.5 ± 0.3, respectively, p = 0.010). In crude linear regression analysis, NC measured during pregnancy was significantly associated with levels of fasting plasma glucose, 2-hour glucose, HbA1c, log HOMA-IR, and TyG index. The association remained after adjustment for age, family history of diabetes, and number of pregnancies. When adjusted for pregestational BMI and gestational weight gain, NC remained independently associated with fasting plasma glucose and HbA1c levels. Conclusion: The NC measured during pregnancy was positively associated with worse glucose metabolic profile in the postpartum among women with obesity/overweight with and without GDM. The NC measurement may be a feasible tool for early identification of women at a higher risk of developing type 2 diabetes mellitus.

Metabolic and Immune Parameters in Pregnant Women with Impaired Glucose Metabolism-A Pilot Study.

Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third trimesters of pregnancy, including 13 pregnant women with GDM, 14 pregnant women with elevated glucose in the first trimester and 34 healthy pregnant women. A number of metabolic and immunological parameters were measured, including glucose, insulin, lipid status, fatty acids, lymphocyte profile, adiponectin, IL-6, IL-10 and TNF-a. A higher number of T-helper lymphocytes and a higher ratio of helper/cytotoxic lymphocytes was found in the control group in the first trimester of pregnancy. Pregnant women whose glucose threshold values were measured in the first trimester, but who did not develop GDM, showed a higher percentage of neutrophils and a lower percentage of lymphocytes in the third trimester. Differences in polyunsaturated fatty acids levels were observed between healthy pregnant women and those with glucose metabolism disorders in the first trimester of pregnancy. The results of this pilot study demonstrate that there are differences in the profiles of T lymphocytes, NK cells and polyunsaturated fatty acids between the examined groups of pregnant women, which can serve as a direction for future research.

Zinc Deficiency Presenting With Diverse Symptoms in a Young Patient: A Case Report.

Despite its prevalence, zinc deficiency often goes undiagnosed due to nonspecific symptoms. This study examined the case of an 18-year-old woman who presented with urinary tract infection, anemia, and insulin dysfunction and was ultimately diagnosed with zinc deficiency. Oral zinc supplementation significantly improved the patient's condition. Zinc is essential for the activity of numerous enzymes and affects immune function, protein structure, and endocrine regulation, but the cause is often unknown because symptoms and data abnormalities are nonspecific. The patient's diet was high in foods that inhibited zinc absorption, likely exacerbating the deficiency. This case illustrates the importance of considering zinc deficiency in patients with diverse and unexplained symptoms. Prompt recognition and treatment with zinc supplementation can lead to rapid and complete recovery. We hope that this case will contribute to the future diagnosis of zinc deficiency for clinicians.

Animal Models of Haploinsufficiency Revealed the Isoform-Specific Role of GSK-3 in HFD-Induced Obesity and Glucose Intolerance.

Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (α and ß) is implicated in the pathogenesis of Type 2 diabetes mellitus (T2D). Recently, we reported the isoform-specific role of GSK-3 in T2D using homozygous GSK-3α/ß Knock-Out mice. While the homozygous inhibition models are idealistic in a preclinical setting, they do not mimic the inhibition seen with pharmacological agents. Hence, in this study, we sought to investigate the dose-response effect of GSK-3α/ß inhibition in the pathogenesis of obesity-induced T2D. Specifically, to gain insight into the dose-response effect of GSK-3 isoforms in T2D, we generated tamoxifen-inducible global GSK-3α/ß heterozygous mice. GSK-3α/ß heterozygous and control mice were fed a high-fat diet (HFD) for sixteen weeks. At baseline, the body weight and glucose tolerance of GSK-3α heterozygous and controls were comparable. In contrast, at baseline, a modest but significantly higher body weight (higher lean mass) was seen in GSK-3ß heterozygous compared to controls. Post-HFD, GSK-3α heterozygous and controls displayed a comparable phenotype. However, GSK-3ß heterozygous were significantly protected against obesity-induced glucose intolerance. Interestingly, the improved glucose tolerance in GSK-3ß heterozygous animals was dampened with chronic HFD-feeding, likely due to significantly higher fat mass and lower lean mass in the GSK-3ß animals. These findings suggest that GSK-3ß is the dominant isoform in glucose metabolism. However, to avail of the metabolic benefits of GSK-3ß inhibition, it is critical to maintain a healthy weight.

Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion: Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet.

BACKGROUND: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice. METHODS: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage. RESULTS: During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed. CONCLUSION: Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes.

Bidirectional link between periodontitis and systemic inflammation in diabetic retinopathy.

Periodontitis is independently associated with numerous lifestyle diseases. Diabetic patients have approximately threefold increased odds of periodontitis, which in turn increases the risk of systemic inflammation. The study by Thazhe Poyil et al is an effort to establish the inflammatory link between diabetic re-tinopathy (DR) and periodontitis based on the periodontal inflamed surface area in diabetic patients with and without DR. To further advance the study, we suggest refining the eligibility criteria to explicitly state the clinical correlates of periodontitis and DR, larger sample size and improved sampling methodology, matching of baseline characteristics of the two groups, as well as improved statistical approach and interpretation of the study findings. Measurement of hemoglobin A1c (HbA1c) in studies comparing type 2 diabetes mellitus patients with DR of matched severity with and without periodontitis could provide a clearer picture of whether HbA1c level is indeed influenced by periodontitis.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial.

PURPOSE: Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS: We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS: The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION: MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity.

Introduction: Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity. In the present work we report a novel endothelial-mediated mechanism essential for regulation of metabolic homeostasis, driven by c-Myc. Methods: We used conditional knockout (EC-Myc KO) and overexpression (EC-Myc OE) mouse models to investigate the endothelial-specific role of c-Myc in metabolic homeostasis during aging and high-fat diet exposure. Body weight and metabolic parameters were collected over time and tissue samples collected at endpoint for biochemical, pathology and RNA-sequencing analysis. Animals exposed to high-fat diet were also evaluated for cardiac dysfunction. Results: In the present study we demonstrate that EC-Myc KO triggers endothelial dysfunction, which precedes progressive increase in body weight during aging, under normal dietary conditions. At endpoint, EC-Myc KO animals showed significant increase in white adipose tissue mass relative to control littermates, which was associated with sex-specific changes in whole body metabolism and increase in systemic leptin. Overexpression of endothelial c-Myc attenuated diet-induced obesity and visceral fat accumulation and prevented the development of glucose intolerance and cardiac dysfunction. Transcriptome analysis of skeletal muscle suggests that the protective effects promoted by endothelial c-Myc overexpression are associated with the expression of genes known to increase weight loss, energy expenditure and glucose tolerance. Conclusion: Our results show a novel important role for endothelial c-Myc in regulating metabolic homeostasis and suggests its potential targeting in preventing obesity and associated complications such as diabetes type-2 and cardiovascular dysfunction.

Molecular Aspects in the Development of Type 2 Diabetes and Possible Preventive and Complementary Therapies.

The incidence of diabetes, including type 2 diabetes (T2DM), is increasing sharply worldwide. To reverse this, more effective approaches in prevention and treatment are needed. In our review, we sought to summarize normal insulin action and the pathways that primarily influence the development of T2DM. Normal insulin action involves mitogenic and metabolic pathways, as both are important in normal metabolic processes, regeneration, etc. However, through excess energy, both can be hyperactive or attenuated/inactive leading to disturbances in the cellular and systemic regulation with the consequence of cellular stress and systemic inflammation. In this review, we detailed the beneficial molecular changes caused by some important components of nutrition and by exercise, which act in the same molecular targets as the developed drugs, and can revert the damaged pathways. Moreover, these induce entire networks of regulatory mechanisms and proteins to restore unbalanced homeostasis, proving their effectiveness as preventive and complementary therapies. These are the main steps for success in prevention and treatment of developed diseases to rid the body of excess energy, both from stored fats and from overnutrition, while facilitating fat burning with adequate, regular exercise in healthy people, and together with necessary drug treatment as required in patients with insulin resistance and T2DM.

Sex- and Age-Specific Differences in Mice Fed a Ketogenic Diet.

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that results in the elevation of serum ketone bodies, known as ketosis. This metabolic consequence has been suggested as a method for treating neurological conditions, improving exercise performance, and facilitating weight loss for overweight individuals. However, since most research primarily uses male populations, little is known about the potential sex differences during the consumption of the KD. In addition, the effects of the KD on aging are relatively unexplored. Therefore, the purpose of this study was to explore sex- and age-specific differences in mice fed the KD. Male and female C57BL/6N mice at either 12 wks or 24 wks of age were randomly assigned to a KD (90% fat, 1% carbohydrate) or chow (13% fat, 60% carbohydrate) group for 6 wks. KD induced weight gain, increased adiposity, induced hyperlipidemia, caused lipid accumulation in the heart and liver, and led to glycogen depletion in the heart, liver, and muscle with varying degrees of changes depending on age and sex. While younger and older male mice on the KD were prone to glucose intolerance, the KD acutely improved rotarod performance in younger females. Overall, this study highlights potential sex and aging differences in the adaptation to the KD.

Insights into the phytochemical profiling, antidiabetic and antioxidant potentials of Lepionurus sylvestris Blume extract in fructose/streptozotocin-induced diabetic rats.

In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1ß, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1ß, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant.

Postpartum glucose intolerance after gestational diabetes mellitus: tailored prediction according to data-driven clusters and BMI-categories.

Objectives: To account for the heterogeneity of gestational diabetes (GDM), this study investigated tailored predictors during pregnancy and at 6-8 weeks postpartum of glucose intolerance (GI) at 1-year postpartum. We identified predictors according to data-driven clusters, analogous to the newly proposed diabetes classification, and for clinical ease also based on BMI-categories. Methods: This is a secondary analysis of the MySweetheart trial. It included 179 women with GDM who underwent a 75g oral glucose tolerance test and HbA1c measurement at 1-year postpartum. Predictors were determined according to: a) cluster analysis based on age, BMI, HOMA-IR and HOMA-B; and b) BMI-categories (normal weight [NW], and overweight/obesity [OW/OB]). Results: We identified two clusters during pregnancy and at 6-8 weeks postpartum (for both time points an "insulin-resistant", and an "insulin-deficient" cluster). The "insulin-resistant" cluster was associated with a 2.9-fold (CI: 1.46-5.87; pregnancy) and 3.5-fold (CI: 1.63-7.52; at 6-8 weeks postpartum) increased risk of GI at 1-year postpartum. During pregnancy, the most relevant predictors of GI were history of previous GDM and fasting glucose for the "insulin-deficient" and NW category and HOMA-IR for the "insulin-resistant" and OW/OB category (all p ≤0.035). In the postpartum, predictors were more heterogenous and included the insulin-sensitivity-adjusted-secretion index and 1-h glucose in the "insulin-deficient" and NW women. Main conclusions: In women with GDM, we identified "insulin-resistant" and "insulin-deficient" clusters with distinct risks of future GI. Predictors varied according to clusters or BMI-categories emphasizing the need for tailored risk assessments.

Cocoa extract induces browning of white adipocytes and improves glucose intolerance in mice fed a high-fat diet.

Cocoa extract (CE) offers several health benefits, such as antiobesity and improved glucose intolerance. However, the mechanisms remain unclear. Adipose tissue includes white adipose tissue (WAT) and brown adipose tissue. Brown adipose tissue leads to body fat reduction by metabolizing lipids to heat via uncoupling protein 1 (UCP1). The conversion of white adipocytes into brown-like adipocytes (beige adipocytes) is called browning, and it contributes to the anti-obesity effect and improved glucose tolerance. This study aimed to evaluate the effect of CE on glucose tolerance in terms of browning. We found that dietary supplementation with CE improved glucose intolerance in mice fed a high-fat diet, and it increased the expression levels of Ucp1 and browning-associated gene in inguinal WAT. Furthermore, in primary adipocytes of mice, CE induced Ucp1 expression through ß3-adrenergic receptor stimulation. These results suggest that dietary CE improves glucose intolerance by inducing browning in WAT.

One-year postpartum weight retention and glucose intolerance in women with prediabetes after gestational diabetes.

AIMS: To determine risk factors for 1-year postpartum weight retention (PPWR) and glucose intolerance (prediabetes + diabetes) in women with a previous history of gestational diabetes (GDM) and prediabetes in early postpartum. METHODS: In this exploratory analysis of the MELINDA randomized controlled trial, we report data of 167 women with prediabetes at the 6-16 weeks (early) postpartum oral glucose tolerance test after a recent history of GDM. RESULTS: Of all participants, 45% (75) had PPWR >0 kg at 1-year postpartum. Compared to women without PPWR, women with PPWR had higher gestational weight gain [10.5 ± 6.4 vs. 6.5 ± 4.5 kg, p < 0.001], higher BMI (p < 0.01) and a worse metabolic profile (higher waist circumference, worse lipid profile and more insulin resistance) (all p < 0.05) both in early and late postpartum. Of all women with PPWR, 40.0% developed metabolic syndrome, compared to 18.9% of women without late PPWR (p = 0.003). The only independent predictor for late PPWR was weight retention in early postpartum (p < 0.001). Of all participants, 55.1% (92) had glucose intolerance (84 prediabetes, 8 diabetes) 1-year postpartum. Independent predictors for late postpartum glucose intolerance were lower gestational age at start insulin therapy in pregnancy and delivery by caesarean section (resp. p = 0.044 and 0.014). CONCLUSIONS: In women with a previous history of GDM and prediabetes in early postpartum, PPWR in early postpartum was a strong independent predictor for late PPWR, while earlier start of insulin therapy during pregnancy and delivery by caesarean section were independent predictors of glucose intolerance in late postpartum.

A framework to classify gestational diabetes diagnosed by routine antenatal 75g glucose tolerance testing.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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).

Bacteroides uniformis CECT 7771 requires adaptive immunity to improve glucose tolerance but not to prevent body weight gain in diet-induced obese mice.

BACKGROUND: The metabolic disturbances of obesity can be mitigated by strategies modulating the gut microbiota. In this study, we sought to identify whether innate or adaptive immunity mediates the beneficial metabolic effects of the human intestinal bacterium Bacteroides uniformis CECT 7771 in obesity. METHODS: We evaluated the effects of orally administered B. uniformis on energy homeostasis, intestinal immunity, hormone levels, and gut microbiota in wild-type and Rag1-deficient mice with diet-induced obesity. We also assessed whether B. uniformis needed to be viable to exert its beneficial effects in obesity and to directly induce immunoregulatory effects. RESULTS: The administration of B. uniformis to obese mice improved glucose tolerance and insulin secretion, restored the caloric intake suppression after an oral glucose challenge, and reduced hyperglycemia. The pre- and post-prandial glucose-related benefits were associated with restoration of the anti-inflammatory tone mediated by type 2 macrophages and regulatory T cells (Tregs) in the lamina propria of the small intestine. Contrastingly, B. uniformis administration failed to improve glucose tolerance in obese Rag1-/- mice, but prevented the increased body weight gain and adiposity. Overall, the beneficial effects seemed to be independent of enteroendocrine effects and of major changes in gut microbiota composition. B. uniformis directly induced Tregs generation from naïve CD4+ T cells in vitro and was not required to be viable to improve glucose homeostasis but its viability was necessary to prevent body weight gain in diet-induced obese wild-type mice. CONCLUSIONS: Here we demonstrate that B. uniformis modulates the energy homeostasis in diet-induced obese mice through different mechanisms. The bacterium improves oral glucose tolerance by adaptive immunity-dependent mechanisms that do not require cell viability and prevents body weight gain by adaptive immunity-independent mechanisms which require cell viability. Video Abstract.