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Background: Physical activity of any amount results in substantial health benefits. However, public awareness of physical activity benefits in chronic diseases is inadequate in India. Prediabetes is a significant health issue on a global scale. Visceral fat (VF) is considered as an early predictor of prediabetes. Ethnicity and race have a substantial impact on VF. Hence, this study intended to evaluate the effect of a customized physical activity promotion program on VF and glycemic parameters in individuals with prediabetes. Methods: In the current, parallel group randomized controlled trial, a total of 158 participants were recruited: 79 in intervention and 79 in control group. The study included the prediabetes individuals based on American Diabetes Association criteria. Participants from the intervention group received the customized physical activity promotion program for 24 weeks. The primary outcome measures of the study were VF level and glycemic parameters that included fasting blood sugar and glycosylated hemoglobin. Two-way mixed analysis of variance was used to study the mean difference of an outcome between 2 groups over time. Results: The study found a statistically significant interaction between the intervention and times on VF level, F1,136 = 23.564, fasting blood sugar levels, F1,136 = 8.762, and glycosylated hemoglobin levels, F1,136 = 64.582 at the end of 24 weeks (P <.05). Conclusions: This study concluded that a customized physical activity promotion program was effective in reducing VF in individuals with prediabetes as compared with controls. It improved glycemic control by reducing fasting blood sugar and glycosylated hemoglobin levels. [ABSTRACT FROM AUTHOR]

Limited observational evidence suggests that a higher intake of high-fat dairy may be associated with lower prediabetes risk, while opposite associations have been observed for low-fat milk intake. This study aimed to examine associations between baseline and changes in dairy consumption, risk of prediabetes, and glycaemic status. 7521 participants from the prospective UK Fenland study were included (mean age 48.7 ± 2.0 years, 51.9 % female). Dairy intake was measured using self-reported food frequency questionnaires. Associations with prediabetes risk and glycaemic status were analysed using Poisson regression models adjusted for social demographics, health behaviours, family history of diabetes and food group intake. At a mean follow-up of 6.7 ± 2.0 years, 290 participants developed prediabetes (4.3 %). Most dairy products were not significantly associated with prediabetes risk. A higher baseline intake of high-fat dairy (RR servings/day 1.20, 95%CI 1.03–1.39) and high-fat milk (RR servings/day 1.22, 1.01–1.47) were associated with higher prediabetes risk. Conversely, low-fat milk was associated with lower prediabetes risk (RR servings/day 0.86, 0.75–0.98). In the analyses evaluating dietary changes over time, increases in high-fat milk were inversely associated with risk of progressing from normoglycaemia to prediabetes or type 2 diabetes (RR servings/day 0.86, 95%CI 0.75–0.99). This population-based study showed that most dairy products are not associated with prediabetes risk or progression in glycaemic status. Positive associations of high-fat dairy, high-fat milk, and the inverse association of low-fat milk with prediabetes risk found were inconsistent with prior literature and suggestive of the need for future research on environmental, behavioural, and biological factors that explain the available evidence. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population. Participants: Ninety-eight young, healthy, underweight women participated in this study. Design: To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively. Results: Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR. Conclusions: Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels. [ABSTRACT FROM AUTHOR]

Background: No study has investigated the association between ultra-processed food (UPF) and pre-diabetes development. Furthermore, prior investigations on the association between UPF and the risk of type 2 diabetes (T2D) were primarily conducted in Europe and America, and studies in other regions are lacking. We investigated the association between ultra-processed foods and the risk of pre-diabetes and T2D in a cohort of Iranians. Methods: This prospective study, with a sample size of 1954 for pre-diabetes and 2457 for T2D, was conducted among adults' participants (aged ≥ 18 years) from the Tehran Lipid and Glucose Study (TLGS). We defined UPF intake using NOVA calcification as a proportion of total energy, and calculated its average intake during the follow-ups. The hazard ratios (HR) and 95% confidence intervals (95% CI) for pre-diabetes/T2D across tertiles of total UPF and per 10% of its increment were examined using Cox proportional hazards models. We also investigated the possibility of non-linear association using a restricted cubic spline regression. Results: We identified 766 and 256 cases of pre-diabetes and T2D, respectively, during a median follow-up of 7 years for pre-diabetes and 8.6 years for T2D. In the multivariable adjusted model, a 10% increase in total UPF intake was associated with a 12% higher risk of pre-diabetes (HR = 1.12; 95% 1.02, 1.23). The incidence of pre-diabetes was also higher in those in tertile 3 than those in tertile 1 (HR = 1.28; 95% CI = 1.07, 1.52). Following additional adjustment for diet quality, the results remained unchanged. Spline regression demonstrated a J-shaped association between UPF and the risk of pre-diabetes; the risk of pre-diabetes did not increase until UPF consumption exceeded about 24% of total energy intake. Of the individual UPF, hydrogenated fat/mayonnaise/ margarine group was related to an increased risk of pre-diabetes. The total UPF and its individual items were not associated with T2D. Conclusions: This study found a positive, non-linear relationship between total UPF and the risk of pre-diabetes in Iranian adults. Our data could not show any significant association between UPF and T2D risk. [ABSTRACT FROM AUTHOR]

Context Sphingolipids are linked to the pathogenesis of type 2 diabetes. 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 study, a 5-year follow-up study. Setting Academic health center. Participants Normoglycemic adults enrolled in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included oral glucose tolerance test, insulin sensitivity, and insulin secretion. Participants with incident prediabetes were matched in age, sex, and ethnicity with nonprogressors. Interventions We assayed 58 sphingolipid species (ceramides, monohexosyl ceramides, sphingomyelins, and sphingosine) using liquid chromatography/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 years, body mass index 30.1 ± 5.78 kg/m2, fasting plasma glucose 92.7 ± 5.84 mg/dL, and 2-hour plasma glucose 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 =.015) and ceramide C18:0/C18:1 (OR, 1.236 [95% CI, 1.042-1.466], P =.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, body mass index, fasting plasma glucose, 2-hour plasma glucose, insulin sensitivity, and insulin secretion. Conclusion 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 type 2 diabetes. [ABSTRACT FROM AUTHOR]

Many preclinical reports have coalesced to identify a strong association between obesity and increased levels of uric acid (UA) in tissues and, importantly, in the circulation (hyperuricemia). Unfortunately, nearly all these studies were conducted with male mice or, in one case, female mice without a side-by-side male cohort. Therefore, the relationship between obesity and hyperuricemia in female mice remains undefined. This lack of clarity in the field has considerable impact as the downstream effects of obesity and allied hyperuricemia are extensive, resulting in many comorbidities including cardiovascular dysfunction, chronic kidney disease, and nonalcoholic fatty liver disease (NAFLD). Herein we begin to address this issue by revealing phenotypic and metabolic responses to diet-induced obesity (DIO) in a side-by-side male vs. female C57BL/6J study. Beginning at 6 weeks of age, mice were exposed to either an obesogenic diet (60% calories from fat) or control diet (10% calories from fat) for 19 weeks. Similar to numerous reported observations with the 60% diet, male mice experienced significant weight gain over time, elevated fasting blood glucose, impaired glucose tolerance and significantly elevated circulating uric acid levels (2.54 ± 0.33 mg/dL) compared to age-matched lean male controls (1.53 ± 0.19 mg/dL). As expected, the female mice experienced a slower rate of weight gain compared to the males; however, they also developed elevated fasting blood glucose and impaired glucose tolerance compared to age-matched lean controls. Countervailing our previous report whereby the control diet for the female-only study was vivarium standard chow (18% calories from fat), the obese female mice did demonstrate significantly elevated circulating UA levels (2.55 ± 0.15 mg/dL) compared to the proper control (1.68 ± 0.12 mg/dL). This affirms that the choice of control diet is crucial for reaching durable conclusions. In toto, these results, for the first time, reveal elevated circulating UA to be a similar long-term response to obesogenic feeding for both males and females and mirrors clinical observations demonstrating hyperuricemia in obesity for both sexes. [ABSTRACT FROM AUTHOR]

Abstract Background No study has investigated the association between ultra-processed food (UPF) and pre-diabetes development. Furthermore, prior investigations on the association between UPF and the risk of type 2 diabetes (T2D) were primarily conducted in Europe and America, and studies in other regions are lacking. We investigated the association between ultra-processed foods and the risk of pre-diabetes and T2D in a cohort of Iranians. Methods This prospective study, with a sample size of 1954 for pre-diabetes and 2457 for T2D, was conducted among adults’ participants (aged ≥ 18 years) from the Tehran Lipid and Glucose Study (TLGS). We defined UPF intake using NOVA calcification as a proportion of total energy, and calculated its average intake during the follow-ups. The hazard ratios (HR) and 95% confidence intervals (95% CI) for pre-diabetes/T2D across tertiles of total UPF and per 10% of its increment were examined using Cox proportional hazards models. We also investigated the possibility of non-linear association using a restricted cubic spline regression. Results We identified 766 and 256 cases of pre-diabetes and T2D, respectively, during a median follow-up of 7 years for pre-diabetes and 8.6 years for T2D. In the multivariable adjusted model, a 10% increase in total UPF intake was associated with a 12% higher risk of pre-diabetes (HR = 1.12; 95% 1.02, 1.23). The incidence of pre-diabetes was also higher in those in tertile 3 than those in tertile 1 (HR = 1.28; 95% CI = 1.07, 1.52). Following additional adjustment for diet quality, the results remained unchanged. Spline regression demonstrated a J-shaped association between UPF and the risk of pre-diabetes; the risk of pre-diabetes did not increase until UPF consumption exceeded about 24% of total energy intake. Of the individual UPF, hydrogenated fat/mayonnaise/ margarine group was related to an increased risk of pre-diabetes. The total UPF and its individual items were not associated with T2D. Conclusions This study found a positive, non-linear relationship between total UPF and the risk of pre-diabetes in Iranian adults. Our data could not show any significant association between UPF and T2D risk.

Aim. To assess the incidence of glucose metabolism disorders, administered hypoglycemic therapy and its effectiveness in a cohort of patients with previously diagnosed diabetes mellitus (DM) hospitalized for scheduled lower limb joint arthroplasty. Materials and methods. The study included 502 patients. Medical history, information about previously diagnosed DM and prescribed hypoglycemic therapy were collected in all patients according to medical documentation, as well as according to the patients’ survey. Within the preoperative examination, the glucose level was measured, and in patients with previously diagnosed diabetes, measuremaent of the HbA1c level was recommended. Results. The study population included 180 (35.9%) males and 322 females (64.1%). Among them, 99 (19.7%) patients had disorders of glucose metabolism [type 1 diabetes – 1 (0.2%) patient, type 2 diabetes – 90 (17.9%) patients, impaired glucose tolerance (IGT) – 8 (1.6%) patients]. In 8 patients, type 2 diabetes was newly diagnosed during the preoperative examination. HbA1c was measured before hospitalization in 26 patients with diabetes, the mean level was 7.0±1.4%. Regarding the analysis of hypoglycemic therapy, almost half of the patients with DM – 47 (47.5%) – received metformin monotherapy, 8 patients with IGT and 8 patients with newly diagnosed DM did not receive any drug therapy. Target glycemic levels during therapy were achieved in 36 (36.4%) patients, and target HbA1c levels were achieved in 21 patients. Conclusion. The cohort of patients hospitalized for elective lower limb joint arthroplasty is characterized by a relatively high incidence of glucose metabolism disorders, and in some patients, DM was newly diagnosed during the preoperative examination. Metformin is most often used as hypoglycemic therapy, and the target values of glycemia during treatment were achieved in less than half of the patients. The monitoring of the level of glycated hemoglobin is low and requires additional population analysis in order to determine the causes and optimize the strategy of patient management.

Abstract Background In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994–2019, assessing 5- and 10-year cancer risks. Methods Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1–5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. Results The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09–1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. Conclusions T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.

Our previous study revealed that over 50% of recipients with pretransplant 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 β-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). β-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 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min 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 pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = −0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in β-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Improvements in BUN after transplantation were associated with improvements in β-cell function. NEW & NOTEWORTHY: In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in β-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus. [ABSTRACT FROM AUTHOR]

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 (NO 2 -FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO 2 -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 NO 2 -OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO 2 -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 NO 2 -OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO 2 -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 NO 2 -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, NO 2 -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 NO 2 -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. [Display omitted] • Daily treatment of NO 2 -OA did not alter fat mass or body weight in high fat diet (HFD)-fed mice. • NO 2 -OA treatment improved HFD-mediated impaired glucose tolerance in Nrf2fl/fl mice. • The protective effects of improved glucose tolerance by NO 2 -OA are absent in mice with Nrf2 specifically ablated in adipocytes (ANKO mice). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. Methods: Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. Results: Over the 30‐year follow‐up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all‐cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. Conclusion: IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required. [ABSTRACT FROM AUTHOR]

Background: While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well‐established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up‐to‐date systematic review and meta‐analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. Methods: The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM‐complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow‐up of at least 12 months. Results: Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43–1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta‐analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48–0.97; p = 0.03; I2 = 31%). Conclusion: This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM‐complicated pregnancy and highlights the need for further studies, including pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: Krüppel-like 11 factor (KLF11) gene mutation has been implicated in the pathogenesis of maturity onset diabetes of the young type 7 (MODY7). Recently, this potential correlation has been questioned, suggesting the need for more comprehensive diagnostic approaches. Methods: The proband is a 30-years-old male who underwent next-generation sequencing (NGS). This was followed by whole-exon sequencing of the proband and his parents to screen for KLF11 variants. Results: A heterozygous KLF11 mutation c.793G>A (p.Glu265Lys) was identified in the proband and his non-diabetic mother. Conclusions: The novel KLF11 mutation documented in this study might exhibit incomplete penetrance in relation to impaired glucose tolerance, which could also contribute to the argument against the necessity of including KLF11 genetic testing for MODY diagnosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism (CHI) is the most common form of persistent hypoglycemia in infants, and diazoxide is the most widely used drug for its treatment. Diazoxide suppresses insulin secretion and attenuates hypoglycemia by binding to sulfonylurea receptor 1 and activating KATP channels. While the short-term side effects of this drug, such as edema and blood cell abnormalities, are well known, the clinical course after its long-term oral administration remains unclear. Furthermore, there are currently no case reports clearly demonstrating a causal relationship between diazoxide and impaired glucose tolerance. We herein describe the case of a 9-year-old girl with CHI complicated with Kabuki syndrome who presented with impaired glucose tolerance due to decreased initial insulin secretion and insulin resistance caused by obesity resulting from diazoxide medication. This is a rare case of the insufficient effects of insulin due to the oral administration of diazoxide, and provides insights for managing the long-term administration of diazoxide to children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.

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. [ABSTRACT FROM AUTHOR]

Objective This article aimed to develop a predictive model to identify persons with recent gestational diabetes mellitus (GDM) most likely to progress to impaired glucose tolerance postpartum. Study Design We conducted an observational study among persons with GDM in their most recent pregnancy, defined by Carpenter-Coustan criteria. Participants were followed up from delivery through 1-year postpartum. We used lasso regression with k-fold cross validation to develop a multivariable model to predict progression to impaired glucose tolerance, defined as HbA1c≥5.7%, at 1-year postpartum. Predictive ability was assessed by the area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Results Of 203 participants, 71 (35%) had impaired glucose tolerance at 1-year postpartum. The final model had an AUC of 0.79 (95% confidence interval [CI]: 0.72, 0.85) and included eight indicators of weight, body mass index, family history of type 2 diabetes, GDM in a prior pregnancy, GDM diagnosis<24 weeks' gestation, and fasting and 2-hour plasma glucose at 2 days postpartum. A cutoff point of ≥ 0.25 predicted probability had sensitivity of 80% (95% CI: 69, 89), specificity of 58% (95% CI: 49, 67), PPV of 51% (95% CI: 41, 61), and NPV of 85% (95% CI: 76, 91) to identify women with impaired glucose tolerance at 1-year postpartum. Conclusion Our predictive model had reasonable ability to predict impaired glucose tolerance around delivery for persons with recent GDM. Key Points We developed a predictive model to identify persons with GDM most likely to develop IGT postpartum. The final model had an AUC of 0.79 (95% CI: 0.72, 0.85) and included eight clinical indicators. If validated, our model could help prioritize diabetes prevention efforts among persons with GDM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a leading cause of global mortality and morbidity. Nearly 80% of individuals with diabetes live in low- and middle-income countries (LMICs), where nearly half of those with the condition remain undiagnosed. The majority of known cases have sub-optimal clinical outcomes. Moreover, large populations with impaired glucose tolerance and/or impaired fasting glucose contribute to the rapid increase in type 2 diabetes. Globally, priority should be given to limit the population with diabetes, especially in LMICs, alongside actions to optimise the care of people diagnosed with diabetes. Primary prevention studies in LMICs have generated evidence to show the efficacy and scalability of strategies to fully prevent or delay the development of diabetes in high-risk groups. However, these are mainly limited to certain countries in Asia, particularly China and India. The studies have indicated that prevention policies are effective in populations with a high risk of type 2 diabetes, and they also have long-term benefits, not only for the risk of type 2 diabetes but also for the risk of associated metabolic disorders, such as CVDs. For the effective conduct of national programmes, innovative mechanisms must be implemented, such as the use of information technology, joint efforts of multiple teams implementing similar programmes, and involvement of governmental and non-governmental partnerships. Continuous monitoring and long-term studies are required to assess the utility of these programmes. The effectiveness of such programmes in LMICs has not been proven over the longer term, except in China. Despite the available evidence, the feasibility of prevention strategies for type 2 diabetes in LMICs at population level remains an enigma. There remain challenges in the form of cultural, societal and economic constraints; insufficient infrastructure and healthcare capacity; and the non-fully elucidated natural history and determinants of type 2 diabetes in LMICs. [ABSTRACT FROM AUTHOR]

Background: Prediabetes is a metabolic condition characterized by blood glucose levels higher than normal but below the threshold for diabetes mellitus. It represents a critical stage in the progression towards type 2 diabetes mellitus (T2DM) and is associated with an increased risk of cardiovascular disease and other complications. The two major pathophysiologic defects responsible for losing glucose tolerance are insulin resistance and β-cell glucose insensitivity, both appearing in subjects of Intermediate Hyperglycaemia. In classical literature, Unani physicians have described the initial symptoms and factors leading to the pathology, the risk factors are described in terms of ‘Su-e-mizaj’ as per the concept of Tibb. So, it is considered in the context of Ziabetus which is described as a disease that develops due to Sue-mizaj haar (abnormal hot temperament). The symptoms mentioned in Unani medicine are increased frequency of micturition (ants and flies are attracted to urine), increased thirst, nocturia, dryness of mouth and whole body, fatigue, loss of weight, malaise, and cramps in lower extremities. The modern drug-based approach for the management of Intermediate Hyperglycaemia is associated with inherent drawbacks, including toxicity, tolerability, cost, and efficacy.Objective: The purpose of this review is to provide an in-depth understanding of prediabetes concerning the classical literature of Greek medicine based on the analysis of certain parameters like etiopathophysiology, current diagnostic criteria, risk factors, and evidence-based management strategies. By synthesizing findings from epidemiological studies, and clinical trials, this paper aims to enhance understanding of prediabetes and facilitate effective preventive measures and interventions [ABSTRACT FROM AUTHOR]

Objective We aimed to study the distribution of traditional Chinese medicine (TCM) constitution and related influencing factors in patients with impaired glucose tolerance (IGT). Methods A cross-sectional study method was used to enroll IGT patients who attended one of eight collaborating units across China between January and August 2021. Basic information was recorded, physical and laboratory examinations were completed, and the data on TCM constitution were collected according to the "classification and determination table of TCM constitution." Finally, patient information was entered into an Excel table, and the data were analyzed using SPSS 26.0. Results Among the 450 patients, a balanced constitution accounted for 37.3%, yang-deficiency constitution for 15.6%, phlegm-dampness constitution for 14.4%, and dampness-heat constitution for 10.9%. Among the biased constitutions, the proportion of men with dampness-heat constitution was higher than that of women, and the proportion of women with yang-deficiency constitution and blood stasis constitution was significantly higher than that of men (P < 0.05). The triglyceride level of patients with phlegm-dampness constitution was higher than that of patients with yang-deficiency constitution (P < 0.05); the HDL-cholestrol level of patients with yang-deficiency constitution was higher than that of patients with phlegm-dampness constitution (P < 0.05); and the uric acid level of patients with phlegm-dampness constitution, dampness-heat constitution, or yin-deficiency constitution was higher than that of patients with yang-deficiency constitution, and the UA level was the highest in patients with dampness-heat constitution (P < 0.05). Conclusion The distribution of TCM constitution in IGT patients was dominated by balanced constitution, followed by yang-deficiency constitution, phlegm-dampness constitution, and dampness-heat constitution. Gender, blood lipid levels, and UA levels were the main factors affecting the constitution status of IGT patients. [ABSTRACT FROM AUTHOR]

The term prediabetes describes blood glucose levels above the normal range but below the threshold to diagnose type 2 diabetes. Several population health initiatives encourage a test and treat approach for prediabetes. In this approach, screening and identification of individuals with prediabetes should be followed by prompt referral to structured lifestyle modification programs or pharmacologic interventions that have been shown to prevent or delay the progression to type 2 diabetes in clinical trials. Here we provide a critical review of evidence for this test and treat approach by examining health outcomes associated with prediabetes and the availability and effectiveness of lifestyle modification approaches that target prediabetes. We also describe current limitations to the reach and uptake of evidence-based treatment options for prediabetes. Finally, we highlight lessons learned from identifying and labeling other preconditions to consider challenges and opportunities that may arise with increasing awareness of prediabetes as part of routine preventive care. [ABSTRACT FROM AUTHOR]

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed. [ABSTRACT FROM AUTHOR]

The pathogenesis involved in glucose metabolism disorders (GMDs) in patients with liver cirrhosis remains unclear. We investigated the effects of acute-on-chronic liver failure (ACLF) development and bacterial infections (BIs) on pancreatic β-cell function and glucose homeostasis in individuals with liver cirrhosis. A retrospective analysis was conducted on 327 patients experiencing acute deterioration of liver cirrhosis. Oral glucose tolerance tests (OGTTs) and OGTT-based β-cell function indices were employed to assess β-cell function and glucose homeostasis. Univariate and multivariate logistic regression analyses were employed to identify GMD-associated risk factors. Both the development of ACLF and BIs significantly increased the prevalence of GMDs. Both ACLF and BIs markedly elevated the homeostasis model of assessment 2-insulin resistance (HOMA2-IR). ACLF significantly impaired glucose-stimulated insulin secretion, as evidenced by reduced insulinogenic index (IGI). Patients with GMDs exhibited significantly lower IGI levels than those without GMDs. Independent risk factors associated with GMDs were prothrombin activity (odds ratio [OR]=0.981, 95% confidence interval [CI]: 0.960–0.995), HOMA2-IR (OR=1.749, 95% CI: 1.130–2.707), and IGI (OR=0.963, 95% CI: 0.947–0.978). In liver cirrhosis, the onset of ACLF impairs glucose-stimulated insulin secretion from β-cells. Both liver impairment and BIs contribute to increased insulin resistance, ultimately disturbing glucose homeostasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dysmetabolic states, such as type 2 diabetes (T2D), characterized by insulin resistance (IR), are associated with fatty liver, increased cardiovascular disease (CVD) risk, and decreased functional exercise capacity (FEC). Rosiglitazone (RO) improves exercise capacity and IR in T2D. However, the effects of RO on FEC and other markers of CVD risk in prediabetes are unknown. We hypothesized that insulin sensitization with RO would improve exercise capacity and markers of CVD risk in participants with impaired glucose tolerance (IGT). Exercise performance (peak oxygen consumption and oxygen uptake kinetics), IR (homeostasis model assessment of IR and quantitative insulin sensitivity check index), and surrogate cardiovascular endpoints (coronary artery calcium (CAC) volume and density and C-reactive protein (CRP)) were measured in participants with IGT after 12 and 18 months of RO or placebo (PL). RO did not significantly improve exercise capacity. Glycemic measures and IR were significantly lower in people on RO compared to PL at 18 months. CAC volume progression was not different between PL and RO groups. RO did not improve exercise capacity during an 18-month intervention despite improved IR and glycemia in people with IGT. Future studies should explore why effects on FEC with RO occur in T2D but not IGT. Understanding these questions may help in targeting therapeutic approaches in T2D and IGT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. Methods Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. Results Over the 30‐year follow‐up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all‐cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. Conclusion IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

Abstract Background While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well‐established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up‐to‐date systematic review and meta‐analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. Methods The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM‐complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow‐up of at least 12 months. Results Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43–1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta‐analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48–0.97; p = 0.03; I2 = 31%). Conclusion This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM‐complicated pregnancy and highlights the need for further studies, including pharmacotherapy.

Gestational diabetes (GDM), defined as glucose intolerance during pregnancy, affects one in six pregnancies globally and significantly increases a woman’s lifetime risk of type 2 diabetes mellitus (T2DM). Being a relatively young group, women with GDM are also at higher risk of developing diabetes related complications (e.g., cardiovascular disease, non-alcoholic fatty liver disease) later in life. Children of women with GDM are also likely to develop GDM and this perpetuates a cycle of diabetes, escalating our current pandemic of metabolic disease. The global prevalence of GDM has now risen by more than 30% over the last two decades, making it an emerging public health concern. Antepartum management of maternal glucose is unable to fully mitigate the associated lifetime cardiometabolic risk. Thus, efforts may need to focus on improving care for women with GDM during the postpartum period where prevention or therapeutic strategies could be implemented to attenuate progression of GDM to DM and its associated vascular complications. However, strategies to provide care for women in the postpartum period often showed disappointing results. This has led to a missed opportunity to halt the progression of impaired glucose tolerance/impaired fasting glucose to DM in women with GDM. In this review, we examined the challenges in the management of women with GDM after delivery and considered how each of these challenges are defined and could present as a gap in translating evidence to clinical care. We highlighted challenges related to postpartum surveillance, postpartum glucose testing strategies, postpartum risk factor modification, and problems encountered in engagement of patients/providers to implement interventions strategies in women with GDM after delivery. We reasoned that a multisystem approach is needed to address these challenges and to retard progression to DM and cardiovascular disease (CVD) in women with GDM pregnancies. This is very much needed to pave way for an improved, precise, culturally sensitive and wholistic care for women with GDM.

ObjectiveThis study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments.MethodsIn this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils.ResultsBased on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils.ConclusionDysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Abstract Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.

Abstract Purpose Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs. Methods HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function. Results Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function. Conclusions Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function.

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.

The aim. To study the impact of carbohydrate metabolism disorders on perioperative period in cardiac surgery pa-tients with post-infarction left ventricular (LV) aneurysms. Materials and methods. Retrospective analysis of perioperative period in random 132 patients with post-infarction LV aneurysms of various locations, who were operated on and discharged from the department of surgical treatment of ischemic heart disease of the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Disorders of carbohydrate metabolism (DCM) were detected in 98 (74.2%) patients, among whom type 2 diabetes mellitus (DM) was diagnosed in 34 (25.7%) patients, impaired glucose tolerance (IGT) in 64 (48.5%). All the patients underwent general clinical examination, electrocardiography, echocardiography, coronary angiography and surgical treatment. Results. When analyzing the clinical picture in patients with post-infarction LV aneurysms, painless myocardial isch-emia was diagnosed in 41 (31.06%) patients, among whom type 2 DM in 11 (26.8%) cases and IGT in 18 (43.9%). No statistically significant difference was found in patients with and without DCM in the LV contractile function, presence of LV thrombosis, atrial fibrillation, chronic kidney disease, stenosis of brachiocephalic arteries and arteries of the lower extremities, gouty arthritis, and body weight. Intraoperatively, diameter of the coronary arteries in patients with type 2 DM was slightly smaller compared to patients without DCM. Its increase in cases of calcification of coronary arteries and aorta among patients of the study group with DCM was statistically insignificant. A careful analysis of the postoperative period in patients with and without DCM showed a statistically significant occurrence of paroxysms of atrial fibrillation in 30 (90.9%) and 3 (9.1%) cases, respectively (p=0.0115). The patients with DCM had longer stay in the intensive care unit: 4.03 ± 2.3 vs. 3.2 ± 1.3 days (p=0.0483). Acute kidney injury in the early postoperative period occurred in 8 (6.06%) patients, including 5 (62.5%) with type 2 DM (p=0.0142). Sternal wound infection occurred in 2 (1.5%) patients with type 2 DM (p=0.0156). Conclusions. Among cardiac surgical patients with postinfarction LV aneurysms, the major part is formed by patients with DCM (74.2%), the presence of which complicates the course of the postoperative period with the development of paroxysms of atrial fibrillation (p=0.0115), acute kidney injury (p=0.0142), sternal wound infection (p=0.0156), a long stay in the intensive care unit (p=0.0483).

Zheng Wang,1,&ast; Dahai Yu,1,2,&ast; Uchechukwu Levi Osuagwu,3,4 Karen Pickering,5 John Baker,5,6 Richard Cutfield,5,7 Yamei Cai,1 Brandon J Orr-Walker,5,6 Gerhard Sundborn,8 Zhanzheng Zhao,1 David Simmons1,4 1Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, ST5 5BG, UK; 3Translational Health Research Institute (THRI), Western Sydney University, Campbelltown, Sydney NSW, 2560, Australia; 4School of Medicine, Western Sydney University, Campbelltown, Sydney NSW, 2751, Australia; 5Diabetes Foundation Aotearoa, Otara, New Zealand; 6Department of Diabetes and Endocrinology, Counties Manukau Health, Auckland, New Zealand; 7Department of Diabetes and Endocrinology, Waitemata District Health Board, Auckland, New Zealand; 8Section of Pacific Health, The University of Auckland, Auckland, New Zealand&ast;These authors contributed equally to this workCorrespondence: David Simmons; Zhanzheng Zhao, Department of Nephrology, The First Affiliated Hospital Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Tel +6124620 3899 ; +86 13938525666, Fax +6124620 3890 ; +863716698 8753, Email Da.Simmons@westernsydney.edu.au; zhanzhengzhao@zzu.edu.cnPurpose: We aimed to examine socioeconomic inequality (SI) in cause-specific outcomes among adults with impaired glucose tolerance (IGT) and/or Impaired fasting glucose (IFG) in New Zealand (NZ) over 25 years.Patients and Methods: A population-based open cohort was derived from Diabetes Care Support Service in NZ with national databases linkage. Patients aged ≥ 18 years with IGT and/or IFG were enrolled between 01/01/1994 and 31/07/2018 and followed up until death or 31/12/2018. Incident outcomes (all-cause, premature, cardiovascular, and cancer death; cardiovascular, myocardial infarction, stroke, heart failure, and end-stage kidney disease hospitalization) by demographic, anthropometric, socioeconomic status, clinical measurements, enrol-time-periods, and IGT/IFG were evaluated. Adjusted incidence rate ratios, absolute risk difference, and SI measurements (slope and relative index of inequality) were estimated using Age-Period-Cohort models.Results: 29,894 patients (58.5 (SD 14.3) years mean age; 52.2% female) were enrolled with 5.6 (IQR: 4.4– 7.4) years of median follow-up. Mortality rates decreased, whereas hospitalization (except myocardial infarction) rates increased. SI was significant for each outcome. Higher mortality and hospitalization rates and worsened SI were common in men, older, the most deprived, and M&amacr;ori patients, as well as patients with obesity, current smoking, with both IFG and IGT, and greater metabolic derangement (higher systolic blood pressure, lipids, and HbA1c, and lower level of mean arterial pressure).Conclusion: Enhanced management strategies are necessary for people with IGT and/or IFG to address persisting SI, especially for men, older people, current smokers, NZ European and M&amacr;ori patients, patients with obesity, or with any abnormal metabolic measurements.Keywords: impaired glucose tolerance, impaired fasting glucose, New Zealand, M&amacr;ori, ethnic disparity, socioeconomic inequality, mortality, cardiovascular diseases, heart failure, cancer, end-stage renal disease

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. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha‐glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within‐trial medical resource use and costs, and quality‐adjusted life years (QALYs). Methods: Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health‐related quality of life was captured using the EuroQol‐5 Dimension‐3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Results: Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p =.009), but there were no significant differences in total inpatient days (rate ratio 1.04, p =.30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p < 0.001). QALYs reported by participants in the acarbose arm (3.96 QALYs) were marginally higher than in the placebo arm (3.95 QALYs), but the difference was not statistically significant (0.01 QALYs; p =.58). Conclusions: Acarbose, compared with placebo, participants cost more due to study drug costs and reported no statistically significant difference in QALYs. These higher within‐trial costs could potentially be offset in future by savings from the acarbose‐related lower incidence of diabetes. [ABSTRACT FROM AUTHOR]

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs. Methods: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function. Results: Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function. Conclusions: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function. [ABSTRACT FROM AUTHOR]