The impact of serum uric acid (SUA) levels on metabolic disorders, particularly concerning the development or reversal of prediabetes, is not well understood. While high uric acid is recognized for its association with metabolic disturbances, its specific influence on prediabetes progression and regression has been insufficiently explored. This study investigates how SUA levels correlate with the natural course of prediabetes, shedding light on its management.

A cohort of 3659 individuals diagnosed with prediabetes at Nanjing First Hospital was tracked over three years. Follow-up assessments included fasting plasma glucose and hemoglobin A1c (HbA1c) measurements. Serum uric acid was measured initially and categorized into quartiles (Q1 through Q4). To assess the impact of uric acid levels on shifting prediabetes status, methods such as restricted cubic spline, segmented regression, stratified analysis, and receiver operating characteristic curves were utilized in a multinomial logistic regression framework.

At baseline, all 3659 participants had prediabetes; by the three-year mark, 2626 remained in this category, 523 reverted to normal fasting glucose (NFG), and 510 advanced to diabetes. After adjustment for potential confounders, a positive correlation was found between higher SUA levels and progression to diabetes (Odds ratio [OR] 1.182, 95% confidence interval [CI]: 1.095-1.276), with no significant link to reversion to NFG (OR: 0.987, 95% CI: 0.909-1.073).

Elevated SUA levels are linked with a higher likelihood of progressing from prediabetes to diabetes but do not significantly forecast a regression to NFG.

With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour postload plasma glucose (1-h PG) for early hyperglycemia screening is emphasized.

This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose levels.

A total of 7504 participants were categorized into 3 groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour postload plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis.

At baseline, the composite insulin sensitivity index in the NGT and 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio, 5.47), followed by the NGT and 1-h PG ≥ 155 mg/dL group (hazard ratio, 2.74), compared to the NGT and 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG.

Even with normal fasting plasma glucose, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Prediabetes is a highly prevalent and increasingly common condition affecting a significant proportion of the global population. The heterogeneous nature of prediabetes presents a challenge in identifying individuals who particularly benefit from lifestyle or other therapeutic interventions aiming at preventing type 2 diabetes (T2D) and associated comorbidities. The phenotypic characteristics of individuals at risk for diabetes are associated with both specific risk profiles for progression and a differential potential to facilitate prediabetes remission and reduce the risk of future T2D. This review examines the current definition and global prevalence of prediabetes and evaluates the potential of prediabetes remission to reduce the alarming increase in the global burden of T2D.

Prediabetes, impacting a third of the adult Chinese population, is linked to a variety of detrimental health outcomes. However, scant research has delved into the factors that affect a regression from prediabetes to normal glucose regulation (NGR) in middle-aged and elderly Chinese adults.

We conducted a longitudinal analysis of 2,655 adults, aged 45 years and above, drawing data from wave 1 and wave 3 of the China Health and Retirement Longitudinal Study (CHARLS). We employed a stepwise logistic regression model to identify factors associated with the regression to NGR. Restricted Cubic Spline (RCS) analysis was used to evaluate the dose-response relationships between baseline fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) levels and the likelihood of regression to NGR. Attribution fraction (AF) analysis was conducted to measure the impact of modifiable factors on the regression of prediabetes. We further examined how changes in these factors were associated with regression to NGR.

During the 4-year follow-up, 570 of 2,655 prediabetes participants regressed to NGR. The stepwise logistic regression model identified older age, female sex, abdominal obesity (OR 0.70, 95% CI 0.57-0.86), elevated LDL-C (OR 0.69, 95% CI 0.48-0.97), higher FPG (OR 0.68, 95% CI 0.52-0.90), and higher HbA1c (OR 0.23, 95% CI 0.18-0.30) as factors associated with regression to NGR. AF analysis showed that a lower initial HbA1c was the most influential factor for regression to NGR. Additionally, evaluated blood lipid profiles reduced the odds of regression to NGR.

This study underscores the influence of age, gender, abdominal obesity, LDL-C levels, FPG, HbA1c, and blood lipid profiles on the likelihood of regressing from prediabetes to NGR. It suggests that adopting a healthy lifestyle and preemptively mitigating these risks may be more beneficial than addressing them after they have been identified in clinical settings.

To explore the effects of lifestyle interventions on the prevention of type 2 diabetes (T2D) and reversion to normoglycemia by prediabetes phenotype.

We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that evaluated the effects of lifestyle interventions in adults with prediabetes for a minimum duration of one year. Two reviewers independently screened articles, extracted data, and performed quality assessment. The relative effects were analyzed using a random-effects model, subgroup analysis was employed to explore the potential effects among subpopulations.

A total of 31 RCTs involving 23684 participants were analyzed. Compared with usual care, lifestyle interventions reduced the incident T2D by 41 % (RR 0.59 [95 % CI 0.52-0.68]) and increased the probability of reverting to normoglycemia by 44 % (RR 1.44 [95 % CI 1.15-1.81]) in adults with prediabetes. No significant difference was observed between the impaired fasting glucose (IFG5.6)/impaired glucose tolerance (IGT) and IFG6.1/IGT (P = 0.752). IGT + IFG benefited more than isolated IGT in prevention of T2D (RRIGT + IFG 0.47 [95 % CI 0.41-0.55]; RRisolatedIGT 0.77 [95 % CI 0.64-0.93]), whereas no benefit was found in isolated IFG (RR 0.77 [95 % CI 0.51-1.16]) or elevated HbA1c (RR 0.89 [95 % CI 0.74-1.07]).

Lifestyle intervention could help prevent T2D and revert to normoglycemia in adults with prediabetes, with significant benefit in people with IGT but not in those with isolated IFG or elevated HbA1c.

Ethnic disparities in the prevalence and pathophysiology of type 2 diabetes are well documented, but prospective data on insulin dynamics vis-à-vis pre-diabetes/early dysglycemia risk in diverse populations are scant.

We analyzed insulin secretion, sensitivity, and clearance among participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The POP-ABC study followed initially normoglycemic offspring of parents with type 2 diabetes for 5.5 years, the primary outcome being incident dysglycemia. Assessments included anthropometry, oral glucose tolerance test, insulin sensitivity (hyperinsulinemic euglycemic clamp, HEC), insulin secretion (intravenous glucose tolerance test, IVGT), and disposition index (DI). Insulin clearance was derived as the molar ratio of plasma C peptide to insulin and by calculating the metabolic clearance rate during HEC.

POP-ABC participants who completed IVGT and HEC at baseline (145 African American, 123 European American; 72% women; mean age 44.6±10.1 years) were included in the present analysis. The baseline fasting plasma glucose was 91.9±6.91 mg/dL (5.11±0.38 mmol/L) and 2-hour plasma glucose was 123±25.1 mg/dL (6.83±1.83 mmol/L). African American offspring of parents with type 2 diabetes had higher insulin secretion and DI, and lower insulin sensitivity and clearance, than their European American counterparts. During 5.5 years of follow-up, 91 of 268 participants developed incident dysglycemia and 177 maintained normoglycemia. In Cox proportional hazards models, insulin secretion (HR 0.997 (95% CI 0.996 to 0.999), p=0.005), insulin sensitivity (HR 0.948 (95% CI 0.913 to 0.984), p=0.005), DI (HR 0.945 (95% CI 0.909 to 0.983), p=0.005) and basal insulin clearance (HR 1.030 (95% CI 1.005 to 1.056), p=0.018) significantly predicted incident dysglycemia.

Insulin sensitivity, secretion, and clearance differ significantly in normoglycemic African American versus European American offspring of parents with type 2 diabetes and are associated with the risk of incident dysglycemia.

We assessed the impact of a 3-year change-percent in adiposity measures on regression and pre-diabetes (Pre-DM) progression among Iranian adults.

Three-year change-percent in body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and visceral adiposity index (VAI) were calculated for 1458 Pre-DM subjects (mean age of 53.0 ± 13.7, 46.8% men), participated in the third examination of the Tehran Lipid and Glucose Study (2006-2008). Multinomial logistic regression models were used to estimate relative risk ratios (RRRs) of the outcomes [i.e., regression to normal glucose regulation (NGR), persistence in Pre-DM, and progression to newly diagnosed type 2 diabetes (T2D)] across 3-year change categories of adiposity measures (i.e., ≥ 5% decrease, 0-5% decrease, increase).

Over nine years of follow-up, 37.7 and 39.0% returned to NGR and progressed to T2D, respectively. Decreased BW (0-5 and ≥ 5%) was associated with regression to NGR (RRRs = 1.44, 95% CIs = 1.05-1.98, and 2.64, 1.63-4.28, respectively). Decreased BMI and WC ≥ 5% were also associated with regression to NGR (RRRs = 1.63, 95% CI = 1.01-2.64; 1.69, 1.20-2.37, respectively). Changes in WHR and VAI were not associated with Pre-DM regression or progression. Pre-DM subjects with ≥ 5% BW loss had a constant FSG level overtime and a lower overall mean of FSG (116 vs. 111 and 112 mg/dL, P = 0.023 and 0.009, respectively) and 2 h-SG (154 vs. 165 and 168 mg/dL) compared to those had 0-5% BW loss or BW gain.

Short-term management of adiposity measures increases the regression probability to NGR. Targeting BW loss seems a more potent predictor of Pre-DM reversion among the adiposity measures.

Current recommendations for weight loss in individuals with prediabetes come from individual trials and are derived from older data.

To elucidate the dose-dependent impacts of weight loss on participants with prediabetes to determine the optimal magnitude of weight loss required for the implementation of the most effective diabetes prevention program.

We searched PubMed, Scopus, CENTRAL, CINAHL, and gray literature sources to September 2023 for randomized trials ≥6 mo that evaluated the efficacy of a lifestyle weight loss intervention on participants with prediabetes. We conducted random-effects pairwise meta-analyses to calculate relative and absolute effects. We performed a 1-stage weighted mixed-effects meta-analysis to elucidate the dose-response curves.

Forty-four randomized trials with 14,742 participants with prediabetes [intervention duration range: 6-72 mo (median: 24 mo), mean weight loss range: 1%-9%] were included. Lifestyle weight loss interventions increased regression to normoglycemia by 11/100 participants (95% confidence interval [CI]: 8 more, 17 more; risk ratio: 1.51; 95% CI: 1.27, 1.80; n = 20 trials, grading of recommendations assessment, development, and evaluation = moderate], and reduced progression to type 2 diabetes by 8/100 participants (95% CI: 11 fewer, 6 fewer; risk ratio: 0.59; 95% CI: 0.51, 0.67; n = 37, grading of recommendations assessment, development, and evaluation = moderate). There were no significant or credible differences between subgroups categorized by the type and duration of intervention. Dose-response meta-analyses indicated that the risk of regression to normoglycemia increased, and the risk of progression to type 2 diabetes declined in a linear pattern within the range of weight loss from 1% to 9%.

Over a median duration of 24 mo, with weight loss ranging from 1% to 9%, the relationship between weight loss and the progression to type 2 diabetes, as well as the regression to normoglycemia, follows a linear pattern. Any form of lifestyle weight loss intervention, including diet, exercise, or a combination of both, can have beneficial impacts on participants with prediabetes. This trial was registered at PROSPERO as CRD42023465322.

We investigated the association of a 3-year change in body weight (BW) and regression to normal glucose regulation (NGR) among different phenotypes of pre-diabetes (Pre-DM), i.e., isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG) and combined IFG-IGT.

1458 Pre-DM subjects (iIFG = 618, iIGT = 462, and IFG-IGT = 378) were assessed for 3-year change-percent in BW (2006-2008 to 2009-2011) and then followed up to 2015-2017, within the national cohort of Tehran Lipid and Glucose Study (TLGS). Binary logistic regression models were used to estimate the probability (odds ratio, ORs) of regression to NGR across categories of 3-year BW change (i.e., ≥5% BW loss, <5% BW loss, BW gain) in different phenotypes of Pre-DM.

The mean age of the participants was 53.0 ± 13.7, and 46.8% were men. Over a median of 6 years of follow-up, the rate of regression to normoglycemia was 50.6, 43.2, and 12.7% in iIGT, iIFG, and combined IFG-IGT, respectively. The baseline-adjusted mean of 3-year BW change was not significantly different across Pre-DM phenotypes (0.68 ± 0.19, 0.32 ± 0.22, and 0.23 ± 0.24 kg, in iIFG, iIGT, and IFG-IGT). Three-year BW loss ≥5% was associated with a greater NGR probability in iIGT than other phenotypes (OR = 4.29 vs. 3.90 and 2.84 in IFG-IGT and iIFG, respectively). A modest reduction (<5% of initial BW) resulted in an increased chance of Pre-DM regression among subjects with iIGT (OR = 1.61, 95% CI = 1.03-2.52) but not iIFG or IFG-IGT phenotypes.

Short-term intensive BW loss (≥5% of initial BW) increased NGR probability in all Pre-DM phenotypes, with an order of iIGT > combined IFG-IGT > iIFG. Only iIGT takes advantage of moderate BW loss (<5% of initial BW) to increase the chance of Pre-DM regression.

Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes.

Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center.

The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance.

IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character.

Prediabetes is an intermediate state of glucose homeostasis whereby plasma glucose concentrations are above normal but below the threshold of diagnosis for diabetes. Over the last several decades, criteria for prediabetes have changed as the cut points for normal glucose concentration and diagnosis of diabetes have shifted. Global consensus does not exist for prediabetes criteria; as a result, the clinical course and risk for type 2 diabetes vary. At present, we can identify individuals with prediabetes based on three glycemic tests (hemoglobin A1c, fasting plasma glucose, and 2-h plasma glucose during an oral glucose tolerance test). The majority of individuals diagnosed with prediabetes meet only one of these criteria. Meeting one, two, or all glycemic criteria changes risk for type 2 diabetes, but this information is not widely known and does not currently guide intervention strategies for individuals with prediabetes. This review summarizes current epidemiology, prognosis, and intervention strategies for individuals diagnosed with prediabetes and suggests a call for more precise risk stratification of individuals with prediabetes as elevated (one prediabetes criterion), high risk (two prediabetes criteria), and very high risk (three prediabetes criteria). In addition, the roles of oral glucose tolerance testing and continuous glucose monitoring in the diagnostic criteria for prediabetes need reassessment. Finally, we must reframe our goals for prediabetes and prioritize intensive interventions for those at high and very high risk for type 2 diabetes.

We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D).

Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006-2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption.

The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00-2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20-2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D.

Regular dairy consumption may increase the chance of Pre-DM regression to NG.

The monocyte-to-high-density lipoprotein cholesterol (MHR) ratio has been linked to metabolic disorders. However, there is limited research on the predisposition to MHR and prediabetes. Hence, we conducted a study to investigate the relationship between MHR and the prevalence of prediabetes.

In total, 85,293 participants were included in our cross-sectional observational study. Multivariable regression analysis, subgroup analyses, and interaction testing were used to determine the relationship between MHR and prediabetes. To explore the non-linear association of MHR with prediabetes risk, generalized additive model (GAM) and smoothing splines were applied. The threshold effect analysis of MHR on the risk of prediabetes was further employed to identify the turning point.

After controlling for covariates, the results indicated that a positive correlation persisted between MHR and prediabetes (odds ratio (OR) =1.64, 95% confidence interval (CI), 1.48-1.82), and subgroup analyses found a more robust correlation between MHR and prediabetes in individuals with lower age, SBP, DBP, TG, TC and higher values of BMI and LDL-C than in their counterparts. Additionally, the correlation between MHR and the risk of prediabetes was found to be non-linear, with a turning point of -0.4 (Log-Likelihood Ratio, P< 0.001). The impact of variables on the two sides of the turning point were 1.94 (1.72, 2.19) and 0.88 (0.69, 1.14).

The positive correlation between MHR and the risk of prediabetes in Chinese participants was observed to be non-linear, and MHR ≤ -0.4 was strongly positively correlated with prediabetes risk.

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA1c) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG.

The present body of evidence regarding the correlation between the estimated glomerular filtration rate (eGFR) and the reversal of impaired fasting glucose (IFG) to normoglycemia remains constrained. Consequently, the objective of our study is to examine the relationship between eGFR and the restoration of normoglycemia in individuals with IFG.

This retrospective cohort study consecutively collected data from 24,541 non-selective participants with IFG at Rich Healthcare Group in China from January 2010 to 2016. We aimed to investigate the association between baseline eGFR and reversion to normoglycemia using the Cox proportional-hazards regression model. Through the utilization of a Cox proportional hazards regression model featuring cubical spline smoothing, we were able to ascertain the non-linear correlation between eGFR and the return to normoglycemia. Furthermore, various sensitivity and subgroup analyses were carried out, and a competing risk multivariate Cox regression was employed to examine the progression to diabetes as a competing risk for the reversal of normoglycemic events.

In our study, comprising 24,541 participants, the average age was 49.25 ± 13.77 years, with 66.28% being male. The baseline eGFR mean was 104.16 ± 15.78 ml/min per 1.73 m2. During a median follow-up period of 2.89 years, we observed a reversion rate to normoglycemia of 45.50%. Upon controlling for covariates, our findings indicated a positive correlation between eGFR and the probability of returning to normoglycemia (HR = 1.008, 95% CI 1.006-1.009). In addition, a non-linear association was observed between eGFR and the likelihood of transitioning from IFG to normoglycemia. The inflection point of eGFR was found to be 111.962 ml/min per 1.73 m2, with HRs of 1.003 (95% CI 1.001, 1.005) on the left side of the point and 1.019 (95% CI 1.015, 1.022) on the right side. Our robust results were supported by competing risks multivariate Cox's regression and sensitivity analysis.

The findings of our investigation indicate a favorable and non-linear correlation between eGFR and the restoration of normoglycemia in Chinese individuals with IFG. Specifically, a reduction in renal function at an early stage in these patients may considerably diminish the likelihood of attaining normoglycemia.

We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years.

This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio.

Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (P time×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018).

A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.

The available evidence on the connection between high-density lipoprotein cholesterol (HDL-C) levels and the reversion from prediabetes (Pre-DM) to normoglycemia is currently limited. The present research sought to examine the connection between HDL-C levels and the regression from Pre-DM to normoglycemia in a population of Chinese adults. This historical cohort study collected 15,420 Pre-DM patients in China who underwent health screening between 2010 and 2016. The present research used the Cox proportional hazards regression model to investigate the connection between HDL-C levels and reversion from Pre-DM to normoglycemia. The Cox proportional hazards regression model with cubic spline functions and smooth curve fitting was employed to ascertain the nonlinear association between HDL-C and reversion from Pre-DM to normoglycemia. Furthermore, a set of sensitivity analyses and subgroup analyses were employed. Following the adjustment of covariates, the findings revealed a positive connection between HDL-C levels and the likelihood of reversion from Pre-DM to normoglycemia (HR 1.898, 95% CI 1.758-2.048, P < 0.001). Furthermore, there was a non-linear relationship between HDL-C and the reversion from Pre-DM to normoglycemia in both genders, and the inflection point of HDL-C was 1.540 mmol/L in males and 1.620 mmol/L in females. We found a strong positive correlation between HDL-C and the reversion from Pre-DM to normoglycemia on the left of the inflection point (Male: HR 2.783, 95% CI 2.373-3.263; Female: HR 2.217, 95% CI 1.802-2.727). Our sensitivity analysis confirmed the robustness of these findings. Subgroup analyses indicated that patients with SBP < 140 mmHg and ever smoker exhibited a more pronounced correlation between HDL-C levels and the reversion from Pre-DM to normoglycemia. In contrast, a less robust correlation was observed among patients with SBP ≥ 140 mmHg, current and never smokers. This study provides evidence of a positive and nonlinear association between HDL-C levels and the reversion from Pre-DM to normoglycemia in Chinese patients. Implementing intensified intervention measures to control the HDL-C levels of patients with Pre-DM around the inflection point may substantially enhance the likelihood of regression to normoglycemia.

The current body of evidence on the association between the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-c) and the reversal of prediabetes to normoglycemia remains limited. The aim of this study is to investigate the association between TG/HDL-c and the reversion to normoglycemia in patients with prediabetes.

This retrospective cohort study included 15,107 individuals with prediabetes from 32 Chinese districts and 11 cities who completed health checks from 2010 to 2016. The Cox proportional-hazards regression model examined baseline TG/HDL-c and reversion to normoglycemia from prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting determined the non-linear connection between TG/HDL-c and reversion to normoglycemia. We also ran sensitivity and subgroup analysis. By characterizing progression to diabetes as a competing risk for the reversal of prediabetes to normoglycemic event, a multivariate Cox proportional hazards regression model with competing risks was created.

Upon adjusting for covariates, the findings indicate a negative association between TG/HDL-c and the likelihood of returning to normoglycemia (HR = 0.869, 95%CI:0.842-0.897). Additionally, a non-linear relationship between TG/HDL-c and the probability of reversion to normoglycemia was observed, with an inflection point of 1.675. The HR on the left side of the inflection point was 0.748 (95%CI:0.699, 0.801). The robustness of our results was confirmed through competing risks multivariate Cox's regression and a series of sensitivity analyses.

The present study reveals a negative and non-linear correlation between TG/HDL-c and the reversion to normoglycemia among Chinese individuals with prediabetes. The findings of this study are anticipated to serve as a valuable resource for clinicians in managing dyslipidemia in prediabetic patients. Interventions aimed at reducing the TG/HDL-c ratio through the reduction of TG or elevation of HDL-c levels may substantially enhance the likelihood of achieving normoglycemia in individuals with prediabetes.

In youths with obesity, the gut hormone potentiation of insulin secretion - the incretin effect - is blunted. We explored the longitudinal impact of the incretin effect during pubertal transition on β cell function and insulin sensitivity. Youths with obesity and 2-hour glucose level ≥ 120 mg/dL underwent a 3-hour oral glucose-tolerance test (OGTT) and an isoglycemic i.v. glucose infusion to quantify the incretin effect. After 2 years, 30 of 39 participants had a repeated OGTT and were stratified into 3 tertiles according to the baseline incretin effect. The high-incretin effect group demonstrated a longitudinal increase in β cell function (disposition index, minimal model [DIMM]), with greater insulin sensitivity at follow-up and stable insulin secretion (φtotal). A lower incretin effect at baseline was associated with higher 1-hour and 2-hour glucose level at follow-up. The high-incretin effect group displayed a greater increase of GLP-17-36 than the moderate- and low-incretin group at baseline, while such a difference did not persist after 2 years. Glucagon suppression was reduced at follow-up in those with low-baseline incretin in respect to the high-incretin group. The incretin effect during pubertal transition affected the longitudinal trajectory of β cell function and weight in youths with obesity.

This study aimed to evaluate the effects of Glucagon-like peptide-1 receptor agonist (GLP-1RA) on prediabetes with overweight/obesity.

A search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed to identify randomised controlled trials (up to 4 July 2022) which evaluated the effect of GLP-1RA on prediabetes with overweight/obesity.

Eight hundred and nine articles were retrieved (80 from PubMed, 481 from Embase, 137 from Cochrane library, and 111 from Web of Science) and a total of 5 articles were included in this meta-analysis. More individuals in GLP-1RAs group regressed from prediabetes to normoglycemia than individuals in the placebo group (OR = 4.56, 95% CI:3.58, 5.80, P = 0.004); fewer individuals in GLP-1RAs group were diagnosed with diabetes than those in the placebo group (OR = 0.31, 95% CI:0.12,0.81, P = 0.017). Results from five studies showed that GLP-1RAs significantly reduced fasting glucose (mean difference = -0.41 mmol/L, 95% CI: -0.58, -0.25, P < 0.00001), with an acceptable heterogeneity (I2  = 42%).

The present meta-analysis suggested that GLP-1RA significantly improves glucose metabolism, reduces systolic blood pressure and body weight in prediabetes with overweight/obesity. It could also prevent the development of diabetes and reverse abnormal glucose metabolism.

In this work, we present an exploratory within-trial analysis of the changing prevalence of prediabetes in response to nutrition and lifestyle counselling provided as part of a randomized placebo-controlled supplement trial with follow-up. We aimed to identify factors associated with changing glycemia status.

Participants (n=401) in this clinical trial were adults with a body mass index (BMI) of ≥25 kg/m2 and prediabetes (defined by the American Diabetes Association as a fasting plasma glucose [FPG] of 5.6 to 6.9 mmol/L or a glycated hemoglobin [A1C] of 5.7% to 6.4%) within 6 months before trial entry. The trial consisted of a 6-month randomized intervention with 2 dietary supplements and/or placebo. At the same time, all participants received nutrition and lifestyle counselling. This was followed by a 6-month follow-up. Glycemia status was assessed at baseline and at 6 and 12 months.

At baseline, 226 participants (56%) met a threshold for prediabetes, including 167 (42%) with elevated FPG and 155 (39%) with elevated A1C. After the 6-month intervention, the prevalence of prediabetes decreased to 46%, driven by a reduction in prevalence of elevated FPG to 29%. The prevalence of prediabetes then increased to 51% after follow-up. Risk of prediabetes was associated with older age (odds ratio [OR], 1.05; p<0.01), BMI (OR, 1.06; p<0.05), and male sex (OR, 1.81; p=0.01). Participants who reverted to normoglycemia had greater weight loss and lower baseline glycemia.

Glycemia status can fluctuate over time and improvements can be gained from lifestyle interventions, with certain factors associated with a higher likelihood of reverting to normoglycemia.

The Ceramides and other Sphingolipids as Predictors of Incident Dysglycemia (CASPID) study tests the overall hypothesis that sphingolipids are pathophysiologic mediators of transition from normal glucose regulation (NGR) to prediabetes, type 2 diabetes (T2DM), and associated complications. The CASPID study utilizes two longitudinal cohorts - the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC)/Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) and the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). Normoglycemic POP-ABC/PROP-ABC were followed for 10 years for progression to prediabetes and offered lifestyle intervention to reverse prediabetes. The DPP/DPPOS participants had prediabetes at enrollment, were randomized to placebo, lifestyle intervention, or metformin treatment, and followed for 11 years for progression to T2DM. Using a case-control design, we analyze 76 targeted plasma sphingolipids as predictors of progression from NGR to prediabetes (Aim 1), prediabetes to T2DM (Aim 2), response to interventions (Aim 3), and development of diabetes complications (Aim 4). A sample size of 600 subjects provides >80% power to detect a 20% difference in sphingolipid profiles between comparison groups (alpha = 0.01). At enrollment, POP-ABC participants had a mean age of 47.7 ± 9.00 years, body mass index (BMI) 30.4 ± 6.10 kg/m2, fasting glucose 92.9 ± 6.90 mg/dL, and 2-h glucose 130 ± 28.8 mg/dL; DPP participants had a mean age of 51.9 ± 9.44 years, BMI 33.7 ± 6.33 kg/m2, fasting glucose 106 ± 7.88 mg/dL, and 2-h glucose 164 ± 16.9 mg/dL. Among normoglycemic participants, those with parental history of T2DM had significantly higher baseline levels of total sphingomyelins, and lower levels of total ceramides and sphingosine, compared with control subjects without familial diabetes history. As the first such study in longitudinal human cohorts, CASPID will elucidate the role of sphingolipids in the pathogenesis of dysglycemia and facilitate the discovery of novel predictive and prognostic biomarkers.

The possible association of habitual physical activity (PA) and the risk of pre-diabetes (Pre-DM) progression to type 2 diabetes (T2D) or the chance of returning to normoglycemia was investigated. This cohort study included 1167 Pre-DM individuals (mean age of 53.5 years, and 45.3% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006-2008) and followed up to a median of 9 years. PA, including leisure time and job activities, was measured using a reliable and validated Iranian version of the Modifiable Activity Questionnaire and reported as metabolic equivalent (MET)-minutes per week. The odds ratios (ORs) and 95% confidence intervals (CIs) of incident T2D and returning to normoglycemia were estimated in relation to PA levels (i.e., per every 500 MET-minutes/week, or across categories of PA levels < 600 as a reference, 600-1500 and > 1500 MET-minutes/week). During the study follow-up, 39.0 % progressed to T2D, and 37.8% returned to normoglycemia. Compared to subjects with a PA < 600 MET-minutes/week, the chance of regression to normoglycemia increased by 58% [OR = 1.58, 95% CI = 1.03-2.40 ∼ relative risk (RR) = 1.32, 95% CI = 1.02-1.63] among the participants who had a PA > 1500 MET-minutes/week. We further noted that each 500 MET-min/week activity corresponded to an elevated chance of returning to normoglycemia by 5% (OR = 1.05, 95% CI = 1.01-1.11). The study's findings provided evidence that higher daily PA levels may facilitate Pre-DM regression to normoglycemia. The beneficial effect of PA in Pre-DM subjects needs to exceed the recommended levels (i.e., 600 MET-minutes/week).

Among 96 million U.S. adults with prediabetes, adoption of evidence-based treatment to prevent diabetes remains low. Primary care represents an essential venue for preventing diabetes, yet providers in this setting have limited time to address prevention. This highlights the need for low-touch interventions that promote diabetes prevention and are not delivered by primary care providers. Text messaging and decision aids displaying disease risk and treatment information have improved outcomes in prior research. However, these approaches have not been definitively studied for managing prediabetes.

The Behavioral Nudges for Diabetes Prevention (BEGIN) trial is a pragmatic, cluster randomized trial testing the effectiveness of text messaging about diabetes prevention and a prediabetes decision aid. These interventions are being studied in 8 primary care clinics using a 2 × 2 factorial design, in which pairs of clinics are randomized in a 1:1:1:1 ratio to receive usual care, text messaging alone, prediabetes decision aid alone, or both interventions. A total of 656 patients are recruited to participate, receive the study interventions, and contribute data at baseline and 12 months. The primary outcome is 12-month weight change, and the secondary outcome is adoption of evidence-based treatment to prevent diabetes. Change in hemoglobin A1c is an exploratory outcome that will be assessed among participants with available values.

Findings from the BEGIN trial will provide evidence about the effectiveness of two novel, low-touch interventions focused on diabetes prevention in primary care, where patients are diagnosed with prediabetes and there is little prior research.

NCT04869917.

The term prediabetes describes a fasting blood glucose level that is elevated but not yet in the diabetic range, a blood glucose level that is elevated after 120 min in a standard 75‑g oral glucose tolerance test, or both. The American Diabetes Association definition also includes glycated hemoglobin A (HbA1c). The incidence of prediabetes is rapidly increasing. Progression from normal glucose tolerance to diabetes is a continuous process. Insulin resistance and insulin secretory dysfunction, the simultaneous presence of which characterizes manifest diabetes, are already present in the prediabetic stage. Prediabetes is associated with an increased risk of diabetes; however, by no means all people with prediabetes go on to develop diabetes. Nevertheless, the identification of an increased risk of diabetes is still relevant insofar as it requires the adoption of diabetes prevention measures. Structured lifestyle intervention has been shown to be the most effective strategy for treating prediabetes. To increase its efficiency, it should, as far as possible, be made exclusively available to those people on whom it is most likely to confer a benefit. This would make it necessary to stratify people with prediabetes according to their risk profile. In a population of people at increased risk of diabetes (Tübingen Diabetes Family Study), a cluster analysis was performed, resulting in six clusters/subgroups. Within these, three high-risk subgroups were identified: Two of these risk groups show predominant insulin secretory dysfunction or predominant insulin resistance and high diabetes and cardiovascular risk. The third group shows a high risk of nephropathy and high mortality, but a comparatively lower diabetes risk. In general, prediabetes cannot yet be treated in a targeted pathophysiologically oriented manner. The new classification of prediabetes-based on pathophysiology-is now opening up new avenues for diabetes prevention. Current and future studies should confirm the assumption that the effectiveness of established, or not yet established, preventive measures depends on the respective subgroup.

Diabetes can be prevented through lifestyle modification in the prediabetic phase. A group-based lifestyle intervention called 'Diabetes Prevention Education Program' (DiPEP) was tested recently in Nepal. The present study aimed to explore experiences of making lifestyle changes among people with prediabetes participating in the DiPEP. This qualitative study, with semi-structured interviews of 20 participants, was conducted 4-7 months following DiPEP intervention. Data analysis was performed by thematic analysis. The results included four themes, understanding that diabetes could be prevented, lifestyle changes made, hurdles to overcome, and experiencing benefits leading to sustained change. Some participants said they felt relieved to know that they had a chance to prevent diabetes. The participants talked mostly about making changes in diet (reducing carbohydrate intake) and physical activity (starting exercises). Obstacles mentioned included a lack of motivation and a lack of family support to implement changes. Experiencing benefits such as weight loss and reduced blood sugar levels were reported to lead them to maintain the changes they had made. Understanding that diabetes could be prevented was a key motivator for implementing changes. The benefits and hurdles experienced by the participants of the present study can be taken into consideration while designing lifestyle intervention programs in similar settings.

Evidence regarding the relationship between body mass index (BMI) and reversion to normoglycemia from prediabetes is still limited. The purpose of our study is to survey the link of BMI on reversion to normoglycemia among patients with impaired fasting glucose (IFG).

This study, a retrospective cohort, covered 32 regions and 11 cities in China and collected 258,74 IFG patients who underwent a health check from 2010 to 2016. We investigated the association between baseline BMI and reversion to normoglycemia in patients with IFG using the Cox proportional-hazards regression model. The nonlinear relationship between BMI and reversion to normoglycemia was determined using a Cox proportional hazards regression with cubic spline functions and smooth curve fitting. In addition, we also performed a series of sensitivity analyses and subgroup analyses. A competing risk multivariate Cox regression was performed using progression to diabetes as a competing risk for reversal of normoglycemic events.

After adjusting covariates, the results showed that BMI was negatively related to the probability of reversion to normoglycemia (HR=0.977, 95%CI:0.971-0.984). Compared with participants with normal BMI(<24kg/m²), overweight (BMI:24-28kg/m²) participants with IFG had a 9.9% lower probability of returning to normoglycemia (HR=0.901,95%CI:0.863-0.939), while obese patients (BMI ≥ 28kg/m²) had a 16.9% decreased probability of reverting from IFG to normoglycemia (HR=0.831,95%CI:0.780-0.886). There was also a nonlinear relationship between them, and the inflection point of BMI was 21.7kg/m². The effect sizes (HR) on the left sides of the inflection point were 0.972(95%CI:0.964-0.980). The competing risks multivariate Cox's regression and sensitivity analysis demonstrated the robustness of our results.

This study demonstrates a negative and nonlinear relationship between BMI and reversion to normoglycemia in Chinese patients with IFG. Minimizing BMI to 21.7 kg/m² in patients with IFG through aggressive intervention may significantly increase the probability of returning to normoglycemia.

The current method to diagnose impaired glucose tolerance (IGT) is based on the 2-h plasma glucose (2-hPG) value during a 75-g oral glucose tolerance test (OGTT). Robust evidence demonstrates that the 1-h post-load plasma glucose (1-hPG) ≥ 8.6 mmol/L in those with normal glucose tolerance is highly predictive of type 2 diabetes (T2D), micro and macrovascular complications and mortality. The aim of this study was to conduct a health economic analysis to estimate long-term cost-effectiveness of using the 1-hPG compared to the 2-hPG for screening and assessing the risk of diabetes over 35 years. The main outcome was cost per quality-adjusted life year (QALY) gained.

A Monte Carlo-based Markov simulation model was developed to forecast long-term effects of two screening strategies with regards to clinical and cost-effectiveness outcomes. The base case model included 20,000 simulated patients over 35-years follow-up. Transition probabilities on disease progression, mortality, effects on preventive treatments and complications were retrieved from landmark diabetes studies. Direct medical costs were sourced from published literature and inflated to 2019 Euros.

In the lifetime analysis, the 1-hPG was projected to increase the number of years free from disease (2 years per patient); to delay the onset of T2D (1 year per patient); to reduce the incidence of T2D complications (0·6 RR-Relative Risk per patient) and to increase the QALY gained (0·58 per patient). Even if the 1-hPG diagnostic method resulted in higher initial costs associated with preventive treatment, long-term diabetes-related costs as well as complications costs were reduced leading to a lifetime saving of - 31225719.82€. The incremental cost-effectiveness ratio was - 8214.7€ per each QALY gained for the overall population.

Screening prediabetes with the 1-hPG is feasible and cost-effective resulting in reduced costs per QALY. Notwithstanding, the higher initial costs of testing with the 1-hPG compared to the 2-hPG due to incremental preventive intervention, long-term diabetes and complications costs were reduced projecting an overall cost saving of - 8214.7€ per each QALY gained.

To estimate the prevalence of prediabetes and to assess the association of prediabetic stages with sociodemographic, lifestyle and clinical factors DESIGN: Cross-sectional study at the screening and inclusion stage of a Diabetes Prevention Education Program (DiPEP) trial SETTING: The study was conducted in two urban communities in Nepal (October 2019-March 2020).

A total of 6222 residents of two study sites, aged 18-64 years and without a history of diabetes, were eligible for prediabetes screening. Exclusion criteria were pregnancy, history of diabetes and critical illness. A total of 291 participants with prediabetes were included in this study.

Prevalence of prediabetes based on glycated haemoglobin (HbA1c) criteria (5.7%-6.4%) was the primary outcome of the study. Odds Ratio and 95% CI were estimated to assess the associations between the outcome prediabetic stages (5.7%-5.9% vs 6.0%-6.4%) and sociodemographic, lifestyle and clinical factors in both unadjusted and adjusted models.

Out of 6222 screened participants, 308 (5%, 95% CI: 4.4% to 5.5%) individuals were detected with prediabetes based on HbA1c. The mean age of 291 responded participants was 50.3±7.6 years and 67% were females. Among them, 78% aged 45-64 years, 97% had central obesity, 90% had high waist-hip ratio, 63% were hypertensive and 66% had no family history of diabetes. Approximately, 54% and 46% of individuals with prediabetes had HbA1c of 5.7%-5.9% and 6.0%-6.4%, respectively. Female gender was associated with prediabetes with HbA1c 6.0%-6.4% (OR, 1.98, 95% CI: 1.07 to 3.67) in the adjusted model.

The estimated prevalence of prediabetes was 5% among screened participants, and female gender was associated with the prediabetic stage. As a large proportion of the population with prediabetes were not aware of their status, this study demonstrates a need for regular community screening programmes to detect individuals with prediabetes and provide them a comprehensive lifestyle intervention for diabetes prevention.

NCT04074148, 2019/783.

T2DM heterogeneity affects responsiveness to lifestyle treatment. Beta-cell failure and nonalcoholic fatty liver disease (NAFLD) independently predict T2DM, but NAFLD inconsistently predicts metabolic response to lifestyle intervention.

We attempt to replicate a prediction model deducted from the Tübinger Lifestyle Intervention Program by assessing similar metabolic factors to predict conversion to normal glucose regulation (NGR) in a comparable lifestyle intervention trial.

In the Optimal Fiber Trial (OptiFiT), 131 Caucasian participants with prediabetes completed a one-year lifestyle intervention program and received a fiber or placebo supplement. We compared baseline parameters for responders and non-responders, assessed correlations of major metabolic changes and conducted a logistic regression analysis for predictors of remission to NGR.

NGR was achieved by 33 participants, respectively. At baseline, for the placebo group only, 1 h and 2 h glucose levels, glucose AUC and Cederholm index predicted conversion to NGR. HOMA-beta, HOMA-IR or liver fat indices did not differ between responders and non-responders of the placebo or the fiber group. Changes in waist circumference or fatty liver index correlated with changes in glycemia and insulin resistance, but not with changes in insulin secretion. Insulin-resistant NAFLD did not predict non-response. Differences in compliance did not explain the results.

Higher post-challenge glucose levels strongly predicted the metabolic non-response to complex lifestyle intervention in our cohort. Depending on the specific intervention and the investigated cohort, fasting glucose levels and insulin sensitivity might contribute to the risk pattern. Beta-cell function did not improve in accordance with other metabolic improvements, qualifying as a potential risk factor for non-response. We could not replicate previous data suggesting that an insulin-resistant fatty liver is a specific risk factor for treatment failure. Replication studies are required.

This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes.

STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc).

Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01).

STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.

Pancreatic β cell plasticity is the primary determinant of disease progression and remission of type 2 diabetes (T2D). However, the dynamic nature of β cell adaptation remains elusive. Here, we establish a mouse model exhibiting the compensation-to-decompensation adaptation of β cell function in response to increasing duration of high-fat diet (HFD) feeding. Comprehensive islet functional and transcriptome analyses reveal a dynamic orchestration of transcriptional networks featuring temporal alteration of chromatin remodeling. Interestingly, prediabetic dietary intervention completely rescues β cell dysfunction, accompanied by a remarkable reversal of HFD-induced reprogramming of islet chromatin accessibility and transcriptome. Mechanistically, ATAC-based motif analysis identifies CTCF as the top candidate driving dietary intervention-induced preservation of β cell function. CTCF expression is markedly decreased in β cells from obese and diabetic mice and humans. Both dietary intervention and AAV-mediated restoration of CTCF expression ameliorate β cell dysfunction ex vivo and in vivo, through transducing the lipid toxicity and inflammatory signals to transcriptional reprogramming of genes critical for β cell glucose metabolism and stress response.

In studies that enrolled people with prevalent pre-diabetes of unknown duration, lifestyle intervention (LI) delayed progression to type 2 diabetes (T2D) but did not reverse pre-diabetes in most participants. Here, we assessed the effects of LI among individuals with pre-diabetes of known duration to determine whether outcomes are related to duration of pre-diabetes.

The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort study initiated LI in subjects with incident pre-diabetes during follow-up of initially normoglycemic African Americans and European Americans with parental T2D. Participants were stratified into those initiating LI after <3, 3-5, or >5 years of pre-diabetes diagnosis. Assessments included anthropometry, body fat, fasting and 2-hour plasma glucose (FPG, 2hPG), and insulin sensitivity and secretion. The outcomes were normal glucose regulation (NGR; ie, normal FPG and 2hPG), persistent pre-diabetes, or T2D. Participants who maintained normal FPG and normal 2hPG levels during follow-up served as the control. The control subjects did not receive lifestyle or other intervention to alter the course of glycemia or body weight.

Of 223 participants (age 53.3±9.28 years, body mass index 30.6±6.70 kg/m²), 72 (control) maintained normoglycemia during follow-up and 138 subjects with incident pre-diabetes initiated LI after 4.08±2.02 years (range 3 months-8.3 years) of diagnosis. Compared with control, LI participants showed decrease in glucose, weight, and body fat; 42.8% reverted to NGR, 50% had persistent pre-diabetes, and 7.2% developed T2D after 5 years. These outcomes were similar across race and pre-diabetes duration strata, but greater glycemic decrease occurred when LI was initiated within 5 years of pre-diabetes diagnosis.

Ninety-three per cent of adults with parental T2D who initiated LI within 3 months to 8.3 years of developing pre-diabetes did not progress to T2D; nearly half reverted to NGR.Trial registration number NCT02027571.

To examine the predictive factors associated with the progression of different prediabetic status to diabetes.

A two-year retrospective cohort study was conducted on 5741 participants aged 40 years or older. Finally, 1685 participants with prediabetes defined by IFG (impaired fasting glucose), IGT (impaired glucose tolerance) and CGI (combined IFG and IGT) were included. Logistic regression model was used to evaluate the risk of prediabetes progression to diabetes.

Of the 1685 subjects with prediabetes at baseline, 212 (12.6%) subjects progressed to diabetes and 1473 (87.4%) subjects did not. Logistic regression analysis demonstrated that people with CGI were associated with an increased risk of progressing to diabetes compared to those with IFG (OR, 95% CI: 3.127, 2.047-4.776). Moreover, males, obese people, people with increased BMI and WHR (Waist/ Hip ratio), and hypertension were positively associated with the progression to diabetes, while HOMA-β was negatively associated with the progression to diabetes.

Subjects with CGI are prone to progressed to diabetes compared to those with IFG or IGT in middle-aged and older person in China. More attention should be paid to male and obese prediabetic subjects, and measures should be taken to control the increase in their BMI and WHR.

To evaluate the short-term effect of lifestyle intervention in people with prediabetes.

A stratified multistage sampling method was used in the recruitment of residents of the Jiangsu Province, China in 2017, who had no previous diagnosis of diabetes. Physical examination and laboratory tests were performed, and questionnaires were completed. Those with a prediabetes diagnosis at baseline were included in the cohort and participants were randomized to the intervention group or the control group. The intervention group received a lifestyle intervention strategy, which included exercise, diet and peer educations. The control group received general health education. Participants were followed up in 2018.

A total of 2005 individuals were included in the analysis. At follow-up, there were 516 (36.7%) individuals in the intervention group and 207 (34.5%) individuals in the control group with normal blood glucose levels. The decline in waist circumference and fasting plasma glucose levels was significantly higher in the intervention group than in the control group. This was still observed after adjusting for variables (odds ratio 1.32, P = 0.02). Females or younger individuals who had lower body mass index and plasma glucose levels at baseline were more likely to reverse to normoglycemia at follow-up.

Compared with a strategy of general health education, a lifestyle intervention strategy could reverse glucose levels to normoglycemia in individuals with prediabetes.

We aimed to determine the predictors of regression to normoglycemia and progression to diabetes among subjects with pre-diabetes in a single model concurrently.

The present study included 1329 participants aged 20 to 70 years with prediabetes from the population-based cohort of the Tehran Lipid and Glucose Study, with a 10-year follow-up. Glycemic status at follow-up was categorized as regression to normoglycemia: fasting plasma glucose [FPG] of <5.55 and 2h-plasma glucose [PG] of <7.77 mmol/L, and not taking antidiabetic medications. Glycemic status at follow-up was categorized as progression to diabetes: FPG ≥7 or 2h-PG of ≥11.1 mmol/L, or taking antidiabetic medications. Glycemic status determined whether the patients remained in prediabetes category (isolated impaired fasting glycaemia [iIFG] [(5.55≤FPG<7 and 2h-PG<7.77 mmol/L); isolated impared glucose tolarence [iIGT] (7.77 ≤ 2h-PG<11.1 and FGP<5.55 mmol/L)]. With prediabetes as a reference, multinomial logistic regression was utilized to identify the determinants of glycemic changes.

Approximately 40% of participants returned to normoglycemia (n = 578), and similar percentage of participants progressed to diabetes (n = 518). Based on the multivariable multinomial model, regression to normoglycemia was associated with age (relative risk ratio [RRR] = 0.97; 95% CI, 0.95-0.99), female sex (RRR = 1.72; 95% CI, 1.18-2.50), high education level of ≥12 years (RRR = 2.10; 95% CI, 1.19-3.70), and combined IFG/impaired glucose tolerance (IGT) versus IFG (RRR = 0.45; 95% CI, 0.29-0.70). The risk of progression to diabetes increased with body mass index (RRR = 1.10; 95% CI, 1.05-1.15), waist circumference (RRR = 0.97; 95% CI, 0.96-0.99), positive familial history of diabetes (RRR = 1.62; 95% CI, 1.07-2.45), and combined IFG/IGT versus IFG (RRR = 2.54; 95% CI, 1.71-3.77).

A small percentage of patients with prediabetes remain in this condition, but the majority go on to develop diabetes or regress to normoglycemia. Both directions had distinct predictors.