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Journal of Cardiovascular Pharmacology... 2022The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease... (Review)
Review
Glucagon-Like Peptide-1 Receptor Agonists and Dual Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity/Metabolic Syndrome, Prediabetes/Diabetes and Non-Alcoholic Fatty Liver Disease-Current Evidence.
The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the "" and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Metabolic Syndrome; Prediabetic State; Glucagon-Like Peptide 1; Obesity; Glucose; Peptides
PubMed: 36546652
DOI: 10.1177/10742484221146371 -
Cardiovascular Diabetology Jan 2023Although a great deal of scientific evidence on the epidemiological risk factors for diabetes and prediabetes has been accumulated, there is still insufficient evidence...
BACKGROUND
Although a great deal of scientific evidence on the epidemiological risk factors for diabetes and prediabetes has been accumulated, there is still insufficient evidence to explore sex-related differences. The aim of this study was to examine sex-specific differences in the effect of the atherogenic index of plasma (AIP) on prediabetes and diabetes.
METHODS
This cross-sectional study included data from 10099 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included prediabetes and diabetes defined by the 2013 American Diabetes Association guidelines.
RESULTS
The median age (mean ± SD) was 48.51 ± 18.42 years, and the average value (SD) of the AIP was - 0.09 (0.34). The prevalence of prediabetes was 40.24%, and that of diabetes was 21.32%. Overall, there was a significant positive association between the AIP and prediabetes and diabetes (per 1-unit increment in the AIP: OR, 2.49; 95% CI 1.75, 3.54). The multivariate logistic regression model demonstrated that for each unit increment in the AIP, the prediabetes and diabetes prevalence increased 4.96-fold among female participants (OR 4.96, 95% CI 2.68, 9.18) but not among male participants. We found that the AIP was not related to the prevalence of prediabetes or diabetes (OR 1.41; 95% CI 0.87, 2.29) among males. There was an interaction between sex and the AIP (P for interaction < 0.0001).
CONCLUSIONS
This study showed that a higher AIP was significantly associated with an increased prevalence of prediabetes and diabetes, and the above relationships occurred only among women and not men.
Topics: Adult; Humans; Male; Female; Middle Aged; Aged; Prediabetic State; Cross-Sectional Studies; Nutrition Surveys; Atherosclerosis; Risk Factors; Triglycerides
PubMed: 36717829
DOI: 10.1186/s12933-023-01740-8 -
JAMA Dec 2023
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State
PubMed: 38038994
DOI: 10.1001/jama.2023.17846 -
Cardiovascular Diabetology Jun 2022Type 2 diabetes mellitus (T2DM) is often accompanied by undiagnosed dyslipidemia. Research on the association of unconventional lipid markers with prediabetes (pre-DM)...
Correlation between the triglyceride-to-high-density lipoprotein cholesterol ratio and other unconventional lipid parameters with the risk of prediabetes and Type 2 diabetes in patients with coronary heart disease: a RCSCD-TCM study in China.
OBJECTIVE
Type 2 diabetes mellitus (T2DM) is often accompanied by undiagnosed dyslipidemia. Research on the association of unconventional lipid markers with prediabetes (pre-DM) and T2DM simultaneously is limited in coronary heart disease (CHD) patients.
METHODS
This study included 28,476 patients diagnosed with CHD. Their lipid levels, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured, and non-traditional lipid parameters were calculated. The patients were divided into three groups based on the diabetic status including normoglycemic (NG), pre-DM, and T2DM. Multiple logistic regression was used to compare the association of TG/HDL-C and other non-traditional lipid parameters with pre-DM and T2DM. The tertiles of TG/HDL-C included T1 (TG/HDL-C < 1.10), T2 (1.10 ≤ TG/HDL-C ≤ 1.89) and T3 (TG/HDL-C > 1.89). Low and high TG/HDL-C was defined with sex-specific cutoff points.
RESULTS
Multiple logistic regression results showed that the non-traditional lipid parameters, including non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C and TG/HDL-C, were all correlated with the risk of pre-DM and T2DM. Meanwhile TG/HDL-C showed the strongest correlation (odds ratio [OR]: 1.19; 95% confidence interval [CI] 1.16-1.23), (OR: 1.36; 95% CI 1.33-1.39). When dividing TG/HDL-C into tertiles, using T1 as a reference, T3 was observed to have the highest association with both pre-DM and T2DM (OR: 1.60; 95% CI 1.48-1.74), (OR: 2.79; 95% CI 2.60-3.00). High TG/HDL-C was significantly associated with pre-DM and T2DM (OR: 1.69; 95% CI 1.52-1.88), (OR: 2.85; 95% CI 2.60-3.12). The association of TG/HDL-C with T2DM and pre-DM existed across different sex, age, smoking, and drinking statuses.
CONCLUSION
Elevated non-traditional lipid parameters were significantly associated with pre-DM and T2DM in CHD patients, especially TG/HDL-C. High TG/HDL-C was the risk factor with a strong correlation with the risk of pre-DM and T2DM.
Topics: Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diabetes Mellitus, Type 2; Female; Humans; Male; Prediabetic State; Risk Factors; Triglycerides
PubMed: 35659300
DOI: 10.1186/s12933-022-01531-7 -
The Journal of Clinical Endocrinology... Dec 2022The preventive effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors for new-onset diabetes was investigated in secondary analyses of several randomized controlled... (Meta-Analysis)
Meta-Analysis
CONTEXT
The preventive effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors for new-onset diabetes was investigated in secondary analyses of several randomized controlled trials (RCTs). However, the results were inconsistent.
OBJECTIVE
This work aimed to synthesize available evidence and evaluate whether SGLT2 inhibitors are effective in preventing new-onset diabetes.
METHODS
In this systematic review and meta-analysis of RCTs, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched through February 11, 2022. Two independent authors screened the search results and extracted summary data from eligible RCTs (including original and post hoc analyses) comparing SGLT2 inhibitors and placebo for the risk of new-onset diabetes among adults with prediabetes. Meta-analysis was conducted using random-effects models to calculate risk ratios and 95% CIs.
RESULTS
We included 4 RCTs with 5655 participants who had prediabetes. Based on the random-effects meta-analysis, SGLT2 inhibitors were significantly associated with a lower risk of new-onset diabetes (relative risk, 0.79; 95% CI, 0.68-0.93). The relative risks of new-onset diabetes in dapagliflozin and empagliflozin were 0.68 (95% CI, 0.52-0.89) and 0.87 (95% CI, 0.72-1.04), respectively (P-for-heterogeneity = .14). The frequency of severe hypoglycemia was not elevated in the SGLT2 inhibitors group compared to the placebo group.
CONCLUSION
In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of new-onset type 2 diabetes among adults with prediabetes and heart failure or chronic kidney disease. These findings indicate the potential usefulness of SGLT2 inhibitors in preventing diabetes among high-risk populations with prediabetes.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Prediabetic State; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Glucose; Sodium
PubMed: 36217306
DOI: 10.1210/clinem/dgac591 -
Diabetes Dec 2021Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with... (Randomized Controlled Trial)
Randomized Controlled Trial
Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years' follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was -0.29 mmol/L [95% CI -0.54; -0.04], = 0.025. Liver fat (-1.34 percentage points [95% CI -2.17; -0.50], = 0.002) and cardiovascular risk (-1.82 percentage points [95% CI -3.13; -0.50], = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance ( = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype-based LI may be beneficial for the prevention of diabetes.
Topics: Adolescent; Adult; Aged; Behavior Therapy; Blood Glucose; Diabetes Mellitus, Type 2; Female; Germany; Glucose Tolerance Test; Humans; Life Style; Male; Middle Aged; Patient Acuity; Prediabetic State; Risk Assessment; Risk Reduction Behavior; Treatment Outcome; Young Adult
PubMed: 34531293
DOI: 10.2337/db21-0526 -
Metabolism: Clinical and Experimental Sep 2023The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among...
Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States.
BACKGROUND
The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among individuals with pre-diabetes (PreD) and metabolically healthy and metabolically unhealthy individuals without T2D are not known. Our aim was to assess prevalence and mortality of NAFLD among these four groups.
METHODS
The Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) with mortality data (follow up to 2019) via linkage to the National Death Index was utilized. NAFLD was defined by ultrasound and absence of other liver diseases and excess alcohol use. Pre-D was defined as fasting plasma glucose values of 100-125 mg/dL and/or HbA1c level between 5.7 %-6.4 % in the absence of established diagnosis of T2D. Metabolically healthy (MH) was defined if all of the following criteria were absent: waist circumference of ≥102 cm (men) or ≥ 88 cm (women) or BMI of ≥30; blood pressure (BP) ≥ 130/85 mmHg or using BP-lowering medication; triglyceride level ≥ 150 mg/dL or using lipid-lowering medication; lipoprotein cholesterol level of <40 mg/dL (men) or < 50 mg/dL (women); homeostasis model assessment of insulin resistance (HOMA-IR) score ≥ 2.5; C-reactive protein (CRP) level of >2 mg/L; Pre-D and T2D. Metabolically unhealthy (MU) individuals were defined as the presence of any component of metabolic syndrome but not having Pre-D and T2D. Competing risk analyses of cause-specific mortality were performed.
FINDINGS
11,231 adults (20-74y) were included: mean age 43.4 years; 43.9 % male; 75.4 % white, 10.8 % Black, and 5.4 % Mexican American, 18.9 % NAFLD, 7.8 % T2D; 24.7 % PreD; 44.3 % MU; and 23.3 % in MH individuals. In multivariable adjusted logistic model, as compared to MH individuals, the highest risk of having NAFLD were in T2D individuals (Odd Ratio [OR] = 10.88 [95 % confidence interval: 7.33-16.16]), followed by Pre-D (OR = 4.19 [3.02-5.81]), and MU (OR = 3.36 [2.39-4.71]). During a median follow up of 26.7 years (21.2-28.7 years), 3982 died. NAFLD subjects had significantly higher age-adjusted mortality than non-NAFLD (32.7 % vs. 28.7 %, p < .001). Among subjects with NAFLD, the highest age-standardized cumulative mortality was observed among those with T2D (41.3 %), followed by with Pre-D (35.1 %), MU subjects (30.0 %), and MH subjects (21.9 %) (pairwise p-values<.04 vs. MH). Multivariable adjusted cox models showed that NAFLD with T2D had a higher risk of all-causes and cardiac-specific deaths (Hazard Ratio [HR] = 4.71 [2.23-9.96] and HR = 20.01 [3.00-133.61]), followed by NAFLD with Pre-D (HR = 2.91 [1.41-6.02] and HR = 10.35 [1.57-68.08]) and metabolically unhealthy NAFLD (HR = 2.59 [1.26-5.33] and HR = 6.74 [0.99-46.03]) compared to metabolically healthy NAFLD. In addition to older age, independent predictors of mortality among NAFLD with T2D included high CRP, CVD, CKD, high FIB-4, and active smoking. Similarly, among NAFLD with PreD, high CRP, CKD, CVD, hypertension, and active smoking were associated with mortality. Finally, CVD and active smoking were predictors of mortality among metabolically unhealthy NAFLD, and active smoking was the only mortality risk among metabolically healthy NAFLD subjects.
INTERPRETATION
Metabolic abnormality impacts both prevalence and outcomes of subjects with NAFLD.
Topics: Adult; Humans; Male; Female; United States; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Nutrition Surveys; Prediabetic State; Hypertension; Body Mass Index; Renal Insufficiency, Chronic; Risk Factors
PubMed: 37380016
DOI: 10.1016/j.metabol.2023.155642 -
Hormone and Metabolic Research =... Feb 2022Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been... (Meta-Analysis)
Meta-Analysis
Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoarthritis. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Ten datasets from six observational studies were included, which involved 41 226 general adults and 10 785 (26.2%) of them were prediabetic. Pooled results showed that prediabetes was not independently associated with osteoarthritis [risk ratio (RR): 1.07, 95% confidence interval (CI): 1.00 to 1.14, p=0.06, I=0%]. Sensitivity limited to studies with adjustment of age and body mass index showed consistent result (RR: 1.06, 95% CI: 0.99 to 1.14, p=0.09, I=0%). Results of subgroup analyses showed that prediabetes was not associated with osteoarthritis in cross-sectional or cohort studies, in studies including Asian or non-Asian population, or in studies with different quality scores (p for subgroup difference>0.10). Besides, prediabetes was not associated with osteoarthritis in men or in women, in studies with prediabetes defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c (approximately 39-46 mmol/mol). Moreover, prediabetes was not associated with overall osteoarthritis, and knee or hip osteoarthritis. Current evidence does not support that prediabetes is independently associated with osteoarthritis in adult population.
Topics: Adult; Blood Glucose; Cross-Sectional Studies; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Male; Observational Studies as Topic; Osteoarthritis; Prediabetic State; Risk Factors
PubMed: 35130571
DOI: 10.1055/a-1730-5251 -
Current Opinion in Pediatrics Aug 2023Glucose metabolism alterations in cystic fibrosis range from the classic cystic fibrosis-related diabetes (CFRD) to forms of glucose intolerance and prediabetes. The aim... (Review)
Review
PURPOSE OF REVIEW
Glucose metabolism alterations in cystic fibrosis range from the classic cystic fibrosis-related diabetes (CFRD) to forms of glucose intolerance and prediabetes. The aim of the present work is to review the most up-to-date novelties in terms of CFRD diagnosis and therapy. This review is timely and relevant because it allows an update for the early and correct classification of glucose abnormalities in cystic fibrosis and because it favours an appropriate therapeutic approach.
RECENT FINDINGS
Confirm that Oral Glucose Tolerance Test is still the diagnostic gold standard despite the advent of continuous glucose monitoring (CGM) systems; this latter is spreading very rapidly, however, to date, there is still no strong evidence to hypothesize the use of CGM for diagnostic purposes. CGM has indeed proven to be very useful in managing and guiding CFRD therapy.
SUMMARY
Tailored and personalized insulin therapy is still the recommended therapy for children and adolescents with CFRD, although nutritional intervention and oral hypoglycaemic treatment are equally important and efficacious. Finally CFTR modulators have allowed the increase of the life expectancy of cystic fibrosis patients and have proven effective not only in improving the pulmonary function and the nutritional status but also the glucose control.
Topics: Adolescent; Humans; Child; Prediabetic State; Cystic Fibrosis; Blood Glucose Self-Monitoring; Blood Glucose; Diabetes Mellitus; Insulin
PubMed: 37211992
DOI: 10.1097/MOP.0000000000001259 -
Advances in Experimental Medicine and... 2021Impaired glucose regulation, including diabetes and prediabetes, poses a huge global problem not only in health but also in the epidemiological and economic areas. These... (Review)
Review
Impaired glucose regulation, including diabetes and prediabetes, poses a huge global problem not only in health but also in the epidemiological and economic areas. These disorders are often detected too late or remain unrecognized. The article aims to provide a review of the prevalence, etiology, and natural history of impaired fasting glucose (IFG). We focus on the progression of isolated IFG to full-fledged type 2 diabetes and the factors conducive to the development of diabetes. The knowledge about it could help design an optimal management program for the prevention of diabetes in patients with IFG; a program that would be patient-tailored and based on the underlying pathophysiology.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Glucose Intolerance; Humans; Prediabetic State; Prevalence
PubMed: 32767267
DOI: 10.1007/5584_2020_571