Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

Association between Vitamin D Deficiency and Prediabetes Phenotypes: A Population-Based Study in Henan, China.

The evidence remains inconsistent regarding whether vitamin D deficiency (VDD) increases the risk of prediabetes. This study aimed to examine whether there is sex-specific association between VDD and impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) in Henan. The data were sourced from the survey of chronic diseases and nutrition in Henan. Multinomial logistic regression models based on complex sampling design and weight were developed to estimate the odds ratio (OR) and confidence interval (95%CI) for measuring the association between VDD and IFG/IGT. The prevalence rate of IGT in men was 20.1% in the VDD group, significantly higher than that in the non-VDD group (10.5%), but no significant difference was observed in women between the VDD and non-VDD groups; there were no significant differences in IFG prevalence between the VDD and non-VDD groups in either men or women. It was found that the association between VDD and IGT was statistically significant in men. The adjusted OR (95%CI) of VDD was 1.99 (1.24-3.19) for IGT in men and 14.84 (4.14-53.20) for IGT in men having a family history of DM. Thus, men with VDD were more likely to live with IGT than those without VDD, especially for men having a family history of diabetes.

Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study.

AIM: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). METHODS: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). RESULTS: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. CONCLUSIONS: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Normalization of impaired glucose tolerance after kidney transplantation is associated with improved beta-cell function.

Our previous study revealed over 50% of recipients with pre-transplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with beta-cell function and insulin resistance in Japanese kidney transplant recipients with pre-transplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pre-transplant IGT were included. We divided the recipients into improvement and non-improvement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). Beta-cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2, DI increased significantly after transplantation in the improved group (P<0.01, P<0.05, respectively), but not in the non-improved group. ΔISSI-2 and ΔDI were significantly and positively associated with pre-transplant 60-minute OGTT plasma glucose levels (both P<0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pre-transplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient: -0.48, P<0.05). In pre-transplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in beta-cell function. The higher the 60-minute OGTT plasma glucose level, the greater the improvement in post-transplant beta-cell function. Improvements in BUN after transplantation were associated with improvements in beta-cell function.

Amisulpride as the antipsychotic of choice in severe psychotic disorder with comorbid impaired glucose tolerance.

Antipsychotics are the mainstay treatment for the majority of severe mental illnesses. Such patients are also more prone to develop medical comorbidities, which complicate the treatment decisions. It is estimated that up to 40% of individuals with schizophrenia have impaired glucose tolerance (IGT) or diabetes, which can be attributed to a combination of genetic, lifestyle, and medication-related factors. Some widely used antipsychotic medications like olanzapine, risperidone, and clozapine have been associated with an increased risk of weight gain, insulin resistance, and other metabolic abnormalities, which can worsen IGT and increase the risk of developing diabetes. Among second-generation antipsychotics (SGAs), amisulpride, aripirazole, and ziprasidone have a fairly low potency to cause obesity and hyperglycemia. In this context, clinicians must balance the benefits and risks of different antipsychotic medications and consider the individual's specific needs and preferences. Here, we shall discuss three cases, to ascertain how the use of amisulpride helped in glycemic control, and also reflect on probable etiologies leading to deranged glucose levels.

Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.

Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO2-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO2-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO2-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO2-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO2-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO2-OA for 48 days), both HFD-fed Nrf2fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO2-OA treatment, no distinction was observed between Nrf2fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2fl/fl and ANKO compared to LFD-fed Nrf2fl/fl mice. Notably, NO2-OA treatment improved glucose tolerance in HFD-fed Nrf2fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO2-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.

Autosomal Dominant, Long-Standing Dysglycemia in 2 Families with Unique Phenotypic Features.

We describe 2 families with 5 members from 2 generations whose clinical and laboratory characteristics over up to 15 years were consistent with dysglycemia/impaired glucose tolerance. In both families (2 probands and 3 family members), long-term follow-up excluded diabetes type 1 and type 2. Diabetes type 1 antibodies were persistently negative and C-peptide levels were normal. In Family 1, the proband, during a follow-up of 7 years (10.3-17.5 years of age), exhibited persistently high HbA1c (>5.7%) with fasting blood glucose levels mostly higher than 100 mg/dl and postprandial glucose levels up to 180 mg/dl. She eventually required oral anti-diabetics with an improvement in glycemic balance. The father and sister also had persistent mild hyperglycemia with borderline high HbA1c (mostly > 5.7%) levels over 15 and 6.2 years respectively. In Family 2, the proband exhibited borderline high fasting hyperglycemia (>100 mg/dl) at age 16.2 years with increasing HbA1c levels (from 5.6%-5.9%) and impaired glucose tolerance at age 18.3 years (2 h blood glucose 156 mg/dl after 75 g glucose). His sister also exhibited borderline hyperglycemia with borderline high HbA1c over 2 years (13.6-15.4 years). These subjects shared a unique phenotype. They are tall and slim with decreased BMI. Three subjects from Generation II failed to thrive during infancy. In view of the data from 2 generations suggesting maturity-onset diabetes of the young (MODY) with autosomal dominant inheritance, we sought to analyze the MODY genes. In Family 1, the molecular analysis by the MODY panel including 11 genes and whole exome sequencing did not detect any mutation in the proband. In Family 2, the MODY panel was also negative in the proband's sister. These families may represent a hitherto unidentified syndrome. Unique features described in this report may help to reveal additional families with similar characteristics and to decipher the molecular basis of this syndrome. In selected cases, oral antidiabetics in adolescents may improve the glycemic balance.

One-hour post-load plasma glucose level predicts future type 2 diabetes in a community-based study of Hong Kong Chinese workforce.

BACKGROUND: We compared performance of high 1-hour PG level, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in predicting type 2 diabetes in a longitudinal community-based cohort of Hong Kong Chinese. METHODS: Between 2001 and 2003, 472 adults aged 18-55 years without diabetes underwent 75-gram oral glucose tolerance test (OGTT). Between 2012 and 2014, progression to diabetes was ascertained by reviewing medical records or repeating OGTT and HbA1c. We defined high 1-hour PG as PG ≥ 8.6 mmol/L at 1-hour. RESULTS: In this cohort, 23.5% had normal glucose tolerance and high 1-hour PG, 10.0% had isolated IGT, 4.2% had isolated IFG. Over 12-year follow-up, 9.3% developed type 2 diabetes. In logistic regression, high 1-hour PG was associated with progression to type 2 diabetes with adjusted odds ratio (95% CI) of 4.20 (1.60, 12.40), independent of IFG, IGT and other clinical variables. Areas under ROC (95% CI) for type 2 diabetes were similar between 1-hour (0.84 [0.78, 0.89], 2-hour (0.79 [0.72, 0.86]) and fasting PG (0.79 [0.71, 0.86]). CONCLUSION: High 1-hour PG identified young Chinese with 5-fold increased risk of type 2 diabetes independent of other intermediate hyperglycaemia status and clinical factors. 1-hour PG is similar to fasting and 2-hour PG in predicting type 2 diabetes.

Frequency of prediabetes in individuals with increased adiposity and metabolically healthy or unhealthy phenotypes.

AIMS: To utilize the estimated glucose disposal rate (eGDR) index of insulin sensitivity, which is based on readily available clinical variables, namely, waist circumference, hypertension and glycated haemoglobin, to discriminate between metabolically healthy and unhealthy phenotypes, and to determine the prevalence of prediabetic conditions. METHODS: Non-diabetic individuals (n = 2201) were stratified into quartiles of insulin sensitivity based on eGDR index. Individuals in the upper quartiles of eGDR were defined as having metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW) or metabolically healthy obesity (MHO) according to their body mass index, while those in the lower quartiles were classified as having metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW) and metabolically unhealthy obesity (MUO), respectively. RESULTS: The frequency of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG + IGT status was comparable among the MHNW, MHOW and MHO groups, while it increased from those with MUNW status towards those with MUOW and MUO status. As compared with participants with MHNW, the odds ratio of having IFG, IGT, or IFG + IGT was significantly higher in participants with MUOW and MUO but not in those with MUNW, MHOW and MHO, respectively. CONCLUSIONS: A metabolically healthy phenotype is associated with lower frequency of IFG, IGT, and IFG + IGT status across all body weight categories.

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials.

BACKGROUND: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. METHODS: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. RESULTS: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. CONCLUSIONS: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Effects of Excessive High-fructose Corn Syrup Drink Intake in Middle-aged Mice.

BACKGROUND/AIM: The global prevalence of type 2 diabetes (T2D) continues to increase, necessitating the need for understanding the causes of its development. The widespread use of high-fructose corn syrup (HFCS) in drinks and diets is suspected to play a role in metabolic disorders. Although many studies have reported on the effects of excessive HFCS and excessive energy intakes in middle-aged individuals, few have focused on energy restriction. This study aimed to investigate the effects of excessive HFCS drink intake under energy restriction on developing T2D in early middle-aged mice. MATERIALS AND METHODS: Early middle-aged mice were divided in HFCS and control groups; they were provided either 10% HFCS water or deionized water ad libitum for 12 weeks, respectively. Total energy intake was controlled using a standard rodent diet. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), tissue weight measurements, serum parameter analyses, and mRNA expression assessments were performed. RESULTS: No increase in body and adipose tissue weight was observed with excessive HFCS intake under energy restriction. Moreover, serum lipid parameters did not differ from those of controls. However, in the OGTT and ITT, the HFCS group showed higher blood glucose levels than the control group. Moreover, the pancreatic weight and insulin II mRNA expression were reduced. CONCLUSION: The excessive HFCS drink intake under energy restriction did not induce obesity; however, it induced impaired glucose tolerance, indicating its negative effects on the pancreas in early middle-aged mice. When translated in human physiology, our results show that even if one does not become obese, excessive HFCS may affect the overall metabolic mechanism; these effects may vary depending on age.

Conceptual Overview of Prevalence of Prediabetes.

Prediabetes increases the risk of type 2 diabetes, metabolic syndrome, chronic renal disease, and cardiovascular disease in a person. In current practice, five alternative definitions of prediabetes are utilized, each based on different HbA1C, fasting glucose, and 2-hour glucose cut points. Prediabetes is a common condition that occurs between normal glycemia and diabetes. It is more common in elderly and obese people. The prevalence of prediabetes and diabetes can be influenced by a variety of individual, family, and societal variables. Additionally, as diabetes is the primary contributor to non-communicable diseases (NCD), it is crucial to identify the key temporal variables for diabetes early diagnosis. In turn, effective prediabetes and diabetes awareness, control, and preventive programs may be created by policymakers and public health professionals worldwide. Popular pathogenic pathways in prediabetes include insulin resistance, inflammation, and sensitivity to insulin. HBA1C, OGTT, and FPG are discussed as the diagnostic criteria in order of frequency. The most commonly researched therapies in the realm of prediabetes are metformin, exercise, and physical activity. Physiological markers including BMI, blood pressure, and waist circumference prompted relatively significant concern. Despite declining trends, the study demonstrates that prediabetes and diabetes are widely prevalent. In order to prevent non-communicable illnesses, the research suggests encouraging healthy lifestyles and regular screenings.

Pros and cons of live kidney donation in prediabetics: A critical review and way forward.

There is shortage of organs, including kidneys, worldwide. Along with deceased kidney transplantation, there is a significant rise in live kidney donation. The prevalence of prediabetes (PD), including impaired fasting glucose and impaired glucose tolerance, is on the rise across the globe. Transplant teams frequently come across prediabetic kidney donors for evaluation. Prediabetics are at risk of diabetes, chronic kidney disease, cardiovascular events, stroke, neuropathy, retinopathy, dementia, depression and nonalcoholic liver disease along with increased risk of all-cause mortality. Unfortunately, most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period. There is lack of prospective long-term studies to know about the real risk of complications after donation. Furthermore, there are variations in recommendations from various guidelines across the globe for donations in prediabetics, leading to more confusion among clinicians. This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients. This review focuses on pathophysiological changes of PD in kidneys, potential complications of PD, other risk factors for development of type 2 diabetes, a review of guidelines for kidney donation, the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.

Plasma Ceramides and Other Sphingolipids in Relation to Incident Prediabetes in a Longitudinal Biracial Cohort.

CONTEXT: Sphingolipids are linked to the pathogenesis of type 2 diabetes (T2D). OBJECTIVE: To test the hypothesis that plasma sphingolipid profiles predict incident prediabetes. DESIGN: A case-control study nested in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study, a 5-year follow-up study. SETTING: Academic health center. PARTICIPANTS: Normoglycemic adults enrolled in the POP-ABC study. Assessments included OGTT, insulin sensitivity and insulin secretion. Participants with incident prediabetes were matched in age, sex, and ethnicity with non-progressors. INTERVENTIONS: We assayed 58 sphingolipid species (ceramides, monohexosyl ceramides, sphingomyelins, and sphingosine) using LC/tandem mass spectrometry in baseline plasma levels from participants and determined association with prediabetes risk. MAIN OUTCOME MEASURE: The primary outcome was progression from normoglycemia to prediabetes, defined as impaired fasting glucose or impaired glucose tolerance. RESULTS: The mean age of participants (N = 140; 50% Black, 50% female) was 48.1 ± 8.69 y, BMI 30.1 ± 5.78 kg/m2, fasting plasma glucose (FPG) 92.7 ± 5.84 mg/dl, and two-hour plasma glucose (2hrPG) 121 ± 23.3 mg/dl. Of the 58 sphingolipid species assayed, higher ratios of sphingomyelin C26:0/C26:1 (OR 2.73 [95% CI 1.172-4.408], P = 0.015) and ceramide C18:0/C18:1 (OR 1.236 [95% CI 1.042-1.466], P = 0.015) in baseline plasma specimens were significantly associated with progression to prediabetes during the 5-year follow-up period, after adjustments for age, race, sex, BMI, FPG, 2hPG, insulin sensitivity, and insulin secretion. CONCLUSIONS: We conclude that the saturated-to-monounsaturated ratios of long-chain ceramide C18:0/C18:1 and very-long-chain sphingomyelin C26:0/C26:1 are potential biomarkers of prediabetes risk among individuals with parental history of T2D.

Antenatal factors and risk of postpartum hyperglycemia in women with gestational diabetes mellitus: A central India prospective cohort study.

Introduction: Global prevalence of gestational diabetes mellitus (GDM) ranges from <1% to 28%. Risk of postpartum diabetes (PPDM) is 7 times higher in women with GDM. We aimed to identify antenatal risk factors associated with postpartum hyperglycemia so that these women may be subjected to targeted screening in a low resource setting. Methods: Screening for GDM was done with a 75gram GTT using IADPSG criteria in women between 28-29 weeks and post-partum screening for hyperglycemia was done using 75 gm 2hour OGTT. Results: Mixed effect linear regression model to assess PPDM as outcome against age, pre pregnancy weight, baby weight at birth, HbA1C and postpartum BMI as predictors was significant at overall level (p=0.00). HbA1C (p =0.00) and pre pregnancy weight (p=0.001) were significant at individual level. Same model for postpartum prediabetes was significant at overall level and assumed significance for pre pregnancy weight (p=0.00), baby birth weight (p= 0.001), postpartum BMI (p=0.00) and HbA1C (p= 0.05) at individual level. The same model for postpartum abnormal sugars (PPDM or prediabetes) was significant at overall level (p = 0.00). Conclusion: Women with GDM represent a vulnerable population that is likely to develop a chronic metabolic disease at a young age exposing them to morbidity associated with unrecognized untreated hyperglycemia. Easily detectable clinical and biochemical antenatal risk factors may help identify women eligible for targeted screening for early diagnosis and treatment as well as use of preventive interventions against type2 diabetes after GDM.

Application of Clinical Blood Metabogram to Type 2 Diabetes Mellitus.

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual's metabolic status in diabetes mellitus for diagnostic and treatment purposes.

Identification of claudin-2 as a promising biomarker for early diagnosis of pre-diabetes.

Introduction: Pre-diabetes, a high-risk metabolic state, is situated between normal glucose homeostasis and diabetes. Early identification of pre-diabetes offers opportunities for intervention and diabetes reversal, highlighting the crucial need to investigate reliable biomarkers for this condition. Methods: We conducted an in-depth bioinformatics analysis of clinical samples from non-diabetic (ND), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) categories within the GSE164416 dataset. Thereafter the HFD and STZ treated mice were used for validation. Results: This analysis identified several codifferentially expressed genes (Co-DEGs) for IGT and T2DM, including CFB, TSHR, VNN2, APOC1, CLDN2, SLPI, LCN2, CXCL17, FAIM2, and REG3A. Validation of these genes and the determination of ROC curves were performed using the GSE76895 dataset. Thereafter, CLDN2 was selected for further verification. Gene expression analysis and immunofluorescence analysis revealed a significant upregulation of CLDN2 expression in the pancreas islets of mice in the high-fat diet and T2DM groups compared to the control group. Similarly, serum level of CLDN2 in patients with IGT and T2DM were significantly higher than those in the healthy group. Discussion: These results suggest that CLDN2 can serve as a novel biomarker for pre-diabetes, providing a new direction for future research in the prevention of type 2 diabetes.

Association of Hepatic Steatosis and Fibrosis Indices With Insulin Sensitivity and Inflammation in the POP-ABC Study.

Context: The cardiometabolic significance of subclinical liver fat in otherwise healthy individuals is unclear. Objective: This work aimed to evaluate the association of hepatic steatosis/fibrosis with cardiometabolic risk markers and incident prediabetes among healthy adults. Methods: This is a post hoc analysis of data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The participants underwent assessments, including clinical examination, oral glucose tolerance test, insulin sensitivity, insulin secretion, plasma high-sensitivity C-reactive protein (hsCRP), and adiponectin levels, with the primary outcome of incident prediabetes during 5-year follow-up. Liver steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and the Fibrosis-4 (Fib-4) index, and participants were stratified by baseline quartiles (Q) of each index. Results: Among 343 (193 African American, 150 European American) participants (mean age 44.2 ± 10.6 years, body mass index 30.2 ± 7.28, fasting glucose 91.8 ± 6.80 mg/dL, and 2-hour glucose 125 ± 26.5 mg/dL), the mean baseline HSI was 39.7 ± 8.21 and Fib-4 index was 0.80 ± 0.41. Baseline HSI correlated with insulin sensitivity (r = -0.44; P < .0001), hsCRP (r = 0.37; P < .0001), and adiponectin (r = -0.24; P < .0001), as did Fib-4 index: insulin sensitivity (r = 0.14; P = .046), hsCRP (r = -0.17; P = .0021), adiponectin (r = -0.22; P < .0001). During 5 years of follow-up, prediabetes occurred in 16.2%, 21.6%, 31.5%, and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively (log-rank P = .02). The prediabetes hazard ratio was 1.138 (95% CI, 1.027-1.261) for baseline HSI. Conclusion: Among initially normoglycemic individuals, hepatic steatosis predicted progression to prediabetes, probably via mechanisms that involve insulin resistance and inflammation.