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Diabetes/metabolism Research and Reviews May 2024Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity,...
BACKGROUND
Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension.
AIMS
To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM).
METHODS
We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression.
RESULTS
In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001).
CONCLUSIONS
MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Male; Female; Middle Aged; Cross-Sectional Studies; Adult; Glomerular Filtration Rate; Aged; Young Adult; Adolescent; Blood Glucose; Risk Factors; Prevalence; Non-alcoholic Fatty Liver Disease; Prognosis; Follow-Up Studies; Biomarkers; Diabetic Nephropathies
PubMed: 38757431
DOI: 10.1002/dmrr.3810 -
Nutrients Nov 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM).... (Randomized Controlled Trial)
Randomized Controlled Trial
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Prediabetic State; Carnosine; Pulse Wave Analysis; Dietary Supplements; Double-Blind Method; Lipids; Vascular Stiffness
PubMed: 38004228
DOI: 10.3390/nu15224835 -
Scientific Reports Apr 2024Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such...
Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pβf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pβf.
Topics: Humans; Metformin; Gastrointestinal Microbiome; Prediabetic State; Male; Female; Middle Aged; Cross-Sectional Studies; Linagliptin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Insulin Resistance; Adult; Insulin-Secreting Cells; Aged
PubMed: 38678119
DOI: 10.1038/s41598-024-60081-y -
Cardiovascular Diabetology Oct 2023We investigated the association of high-sensitivity cardiac troponin (Hs-cTn) with all-cause and cardiovascular mortality in non-diabetic individuals.
Association between high sensitivity cardiac troponin and mortality risk in the non-diabetic population: findings from the National Health and Nutrition Examination Survey.
OBJECTIVE
We investigated the association of high-sensitivity cardiac troponin (Hs-cTn) with all-cause and cardiovascular mortality in non-diabetic individuals.
METHODS
This study included 10,393 participants without known diabetes and cardiovascular disease from the US National Health and Nutrition Examination Survey (NHANES). Serum Hs-cTnI and Hs-cTnT concentrations were measured. Prediabetes was defined as fasting blood glucose between 100 and 125 mg/dL or HbA1c between 5.7 and 6.4%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality risk. Time-dependent receiver operating characteristics (tROC) curves were utilized to measure the predictive performance of the biomarkers. Net Reclassification Improvement (NRI) were calculated to estimate the improvement in risk classification for adding Hs-cTnT or Hs-cTnI to the standard models based on Framingham risk factors.
RESULTS
The mean age of the participants was 48.1 ± 19.1 years, with 53.3% being female and 25.8% being prediabetic. After multivariable adjustment, compared to those with Hs-cTnI concentration less than the limit of detection, the HRs (95% CIs) of the participants with Hs-cTnI concentration higher than the 99th upper reference limit were 1.74 (1.35, 2.24) for all-cause mortality and 2.10 (1.36, 3.24) for cardiovascular mortality. The corresponding HRs (95% CIs) for Hs-cTnT were 2.07 (1.53, 2.81) and 2.92 (1.47, 5.80) for all-cause and cardiovascular mortality. There was a significant interaction between prediabetes and Hs-cTnI on the mortality risk; a positive relationship was only observed in prediabetic individuals. No interaction was observed between prediabetes and Hs-cTnT on mortality risk. The Areas Under tROC indicated both Hs-cTnT and Hs-cTnI show better predictive performance in cardiovascular mortality than in all-cause mortality. NRI (95% CI) for adding Hs-cTnT to the standard model were 0.25 (0.21, 0.27) and 0.33 (0.26, 0.39) for all-cause and cardiovascular mortality. The corresponding NRI (95% CI) for Hs-cTnI were 0.04 (0, 0.06) and 0.07 (0.01, 0.13).
CONCLUSIONS
Elevated blood levels of Hs-cTnI and Hs-cTnT are associated with increased mortality. Measurement of Hs-cTnT in non-diabetic subjects, particularly those with prediabetes, may help identify individuals at an increased risk of cardiovascular disease and provide early and more intensive risk factor modification.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Cardiovascular Diseases; Nutrition Surveys; Prediabetic State; Biomarkers; Troponin I; Troponin T
PubMed: 37904214
DOI: 10.1186/s12933-023-02003-2 -
Diabetes Care Dec 2023To investigate the relationship between blood glycated hemoglobin (HbA1c) and cerebral cortical thickness (CT) and identify potential cellular mechanisms involved.
OBJECTIVE
To investigate the relationship between blood glycated hemoglobin (HbA1c) and cerebral cortical thickness (CT) and identify potential cellular mechanisms involved.
RESEARCH DESIGN AND METHODS
A cohort of 30,579 adults age 45 to 81 (mean ± SD: 64 ± 7.5) years with available data on brain MRI and blood HbA1c levels was analyzed. The relationship between HbA1c and CT was probed using independent spatial profiles of cell-specific gene expression. Lastly, a genome-wide association study was conducted on the shared variance between HbA1c and CT.
RESULTS
The HbA1c-CT association was noncontinuous, emerging negatively within the prediabetic range (39.6 mmol/mol). This association was strongest in brain regions with higher expression of genes specific to excitatory neurons and lower expression of genes specific to astrocytes and microglia. A significant locus implicated mitochondrial maintenance and ATP generation.
CONCLUSIONS
Effective glycemia control at prediabetic levels is warranted to preserve brain health and prevent prediabetes-related neurobiologic perturbations.
Topics: Adult; Humans; Middle Aged; Aged; Aged, 80 and over; Prediabetic State; Glycated Hemoglobin; Blood Glucose; Genome-Wide Association Study; Neurobiology; Atrophy
PubMed: 37824790
DOI: 10.2337/dc23-1105 -
Journal of Translational Medicine Sep 2023Triglyceride glucose index (TyG index) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG and regression from...
OBJECTIVE
Triglyceride glucose index (TyG index) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG and regression from prediabetes to normoglycemia remains to be elucidated.
METHODS
This retrospective cohort study involved 25,248 subjects with prediabetes at baseline conducted from 2010 to 2016. A Cox proportional hazard regression model was designed to evaluate the role of TyG in identifying people at converting from prediabetes to normoglycemia. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was used to dig out the nonlinear relationship between them. Detailed evaluations for TyG were also performed using sensitivity and subgroup analyse.
RESULTS
Among the included prediabetes subjects (n = 25,248), the mean age was 49.27 ± 13.84 years old, and 16,701 (66.15%) were male. The mean TyG was 8.83 ± 0.60. The median follow-up time was 2.96 ± 0.90 years. 11,499 (45.54%) individuals had a final diagnosis of normoglycemia. After adjusting for covariates, TyG was negatively affecting the results of glucose status conversion in prediabetes people (HR 0.895, 95% CI 0.863, 0.928). There was a nonlinear connection between TyG and normoglycemia in prediabetes people, and the inflection point was 8.88. The effect sizes (HR) on the left and right sides of the inflection point were 0.99 (0.93, 1.05) and 0.79 (0.74, 0.85), respectively. Sensitivity analysis confirmed the robustness of these results. Subgroup analysis showed that TyG was more strongly associated with incident glucose status conversion in male, BMI ≥ 25. In contrast, there was a weaker relationship in those with female, BMI < 25.
CONCLUSION
Based on sample of subjects evaluated between 2010 and 2016, TyG index appears to be a promising marker for predicting normoglycemic conversion among prediabetes people in China. This study demonstrates a negative and non-linear association between TyG and glucose status conversion from prediabetes to normoglycemia. TyG is strongly related to glucose status conversion when TyG is above 8.88. From a therapeutic point of view, it is meaningful to maintain TyG levels within the inflection point to 8.88.
Topics: Adult; Female; Humans; Male; Middle Aged; Cohort Studies; East Asian People; Glucose; Longitudinal Studies; Prediabetic State; Retrospective Studies; Triglycerides; Blood Glucose; Insulin Resistance
PubMed: 37715242
DOI: 10.1186/s12967-023-04402-1 -
The Journal of Clinical Psychiatry Aug 2023Certain atypical antipsychotics, while efficacious as adjunctive treatments in major depressive disorder (MDD), are associated with metabolic adverse effects and weight... (Randomized Controlled Trial)
Randomized Controlled Trial
Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies.
Certain atypical antipsychotics, while efficacious as adjunctive treatments in major depressive disorder (MDD), are associated with metabolic adverse effects and weight gain. This analysis determined the effect of adjunctive brexpiprazole on metabolic parameters and body weight in adults with MDD and prediabetes (ie, at risk of developing diabetes) based on pooled data from 3 short-term studies and 1 long-term study. The short-term studies were 6-week, randomized, double-blind, placebo-controlled studies of adjunctive oral brexpiprazole 1-3 mg/d in outpatients with MDD ( criteria) and inadequate response to antidepressant treatment, conducted between June 2011 and May 2016. The long-term study was a 26- to 52-week, open-label extension study conducted between October 2011 and May 2017. was defined based on fasting serum glucose and glycated hemoglobin (HbA1c) levels. Shifts in diabetes status and shifts/changes in fasting metabolic parameters and body weight were determined. Most patients receiving adjunctive brexpiprazole maintained their baseline diabetes status in the short term (568/751; 75.6%) and long term (1,919/2,746; 69.9%). The incidence of categorical shifts in fasting metabolic parameters generally did not differ between treatment groups or between prediabetes and non-diabetes subgroups. Mean changes from baseline in metabolic parameters were small in the short term (all < 5 mg/dL) and long term (all < 6 mg/dL, except < 20 mg/dL for triglycerides). Moderate weight gain was observed in the short term (1.5 kg) and long term (3.4-4.1 kg). Adjunctive brexpiprazole had a limited impact on the metabolic profile of patients with MDD, regardless of diabetes status (prediabetes/non-diabetes). Data used in this post hoc analysis came from studies with ClinicalTrials.gov identifiers NCT01360645, NCT01360632, NCT02196506, and NCT01360866.
Topics: Adult; Humans; Depressive Disorder, Major; Prediabetic State; Body Weight; Weight Gain
PubMed: 37656180
DOI: 10.4088/JCP.23m14786 -
Cells Apr 2024Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors.... (Review)
Review
Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are hyperglycemia, hyperinsulinemia, and adipokines imbalance. The chronic stimulation related to these metabolic signatures can favor CRC onset and development, as well as negatively influence CRC prognosis. To date, the growing burden of prediabetes and CRC has generated a global interest in defining their epidemiological and molecular relationships. Therefore, a deeper knowledge of the metabolic impairment determinants is compelling to identify the pathological mechanisms promoting the onset of prediabetes and CRC. In this scenario, this review aims to provide a comprehensive overview on the metabolic alterations of prediabetes and CRC as well as an overview of recent preventive and therapeutic approaches for both diseases, focusing on the role of the metabolic state as a pivotal contributor to consider for the development of future preventive and therapeutic strategies.
Topics: Animals; Humans; Colorectal Neoplasms; Prediabetic State; Risk Factors
PubMed: 38667278
DOI: 10.3390/cells13080663 -
The Science of the Total Environment Nov 2023The association between air pollution and mental disorders has been widely documented in the general population. However, the evidence among susceptible populations,...
BACKGROUND
The association between air pollution and mental disorders has been widely documented in the general population. However, the evidence among susceptible populations, such as individuals with prediabetes or diabetes, is still insufficient.
METHODS
We analyzed data from 48,515 participants with prediabetes and 24,393 participants with diabetes from the UK Biobank. Annual pollution data were collected for fine particulate matter (PM), inhalable particulate matter (PM), nitrogen dioxide (NO), and nitrogen dioxides (NO) during 2006-2021. The exposure to air pollution and temperature for each participant were estimated by the bilinear interpolation approach and time-weighted method based on their geocoded home addresses and time spent at each address. We employed the generalized propensity score model based on the generalized estimating equation and the time-varying covariates Cox model to assess the effects of air pollution.
RESULTS
We observed causal links between air pollutants and mental disorders among both prediabetic and diabetic participants, with stronger effects among those with diabetes than prediabetes. The hazard ratios were 1.18 (1.12, 1.24), 1.15 (1.10, 1.20), 1.18 (1.13, 1.23), and 1.15 (1.11, 1.19) in patients with prediabetes, and 1.21 (1.13, 1.29), 1.17 (1.11, 1.24), 1.19 (1.13, 1.25), and 1.17 (1.12, 1.23) in patients with diabetes per interquartile range elevation in PM, PM, NO, and NO. Furthermore, the effects were more pronounced among people who were older, alcohol drinkers, and living in urban areas.
CONCLUSIONS
Our study indicates the potential causal links between long-term exposure to air pollution and incident mental disorders among those with prediabetes and diabetes. Reducing air pollution levels would significantly benefit this vulnerable population by reducing the incidence of mental disorders.
Topics: Humans; Prediabetic State; Nitrogen Dioxide; Prospective Studies; Environmental Exposure; Air Pollution; Air Pollutants; Particulate Matter; Diabetes Mellitus; Mental Disorders
PubMed: 37414192
DOI: 10.1016/j.scitotenv.2023.165235 -
Diabetic Medicine : a Journal of the... Mar 2024The aim of the study was to describe the association of prediabetes progression and regression with change in cognitive function.
AIM
The aim of the study was to describe the association of prediabetes progression and regression with change in cognitive function.
METHODS
Data from three waves (2011, 2015 and 2018) of the China Health and Retirement Longitudinal Study (CHARLS) were analysed. Diabetic statuses in 2011 and 2015 were ascertained using the American Diabetes Association criteria. Cognitive function was assessed and standardized at all three waves, where a total score and its two components (episodic memory and metal status) were calculated. We evaluated the association of prediabetes progression and regression (from 2011 to 2015) with changes in cognitive function from 2011 to 2015 and from 2015 to 2018.
RESULTS
Of 2590 participants (56% women, mean age 58.6 ± 8.4 years) with prediabetes, 12% progressed to diabetes and 41% regressed to normoglycaemia. Compared with participants who remained as prediabetes, those who progressed to diabetes showed a trend to have accelerated decline in episodic memory (β = -0.11, 95% confidence interval -0.22 to 0.003, p = 0.057). However, participants who regressed to normoglycaemia did not have less cognitive decline. Neither prediabetes progression nor regression predicted change in cognitive function from 2015 to 2018. In a separate group of participants who remained as normoglycaemia (n = 858), changes in cognitive function from 2011 to 2015 and from 2015 to 2018 were similar to those who remained as prediabetes.
CONCLUSION
In people with prediabetes, progression to diabetes may be associated with accelerated cognitive decline but regression to normoglycaemia does not retard cognitive decline. Prediabetes progression and regression may not be predictive of change in cognitive function.
Topics: Humans; Female; Middle Aged; Aged; Male; Prediabetic State; Longitudinal Studies; Retirement; Risk Factors; Diabetes Mellitus; Cognitive Dysfunction; Cognition
PubMed: 37454341
DOI: 10.1111/dme.15180