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Cardiovascular Diabetology Dec 2023Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated...
BACKGROUND
Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored.
METHODS
We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan-Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes.
RESULTS
During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan-Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10-1.46], p = 0.001) and MACE (aHR 1.46 [1.27-1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04-3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06-1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14-1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5-6.0%: aHR 1.67 [1.39-2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76-2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation.
CONCLUSION
We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.
Topics: Adult; Humans; Male; Prediabetic State; Glycated Hemoglobin; Retrospective Studies; Blood Glucose; Diabetes Mellitus; Atrial Fibrillation; Risk Factors
PubMed: 38115080
DOI: 10.1186/s12933-023-02085-y -
The Journal of Clinical Endocrinology... Jul 2021
Topics: Humans; Insulin Resistance; Prediabetic State
PubMed: 33765140
DOI: 10.1210/clinem/dgab198 -
Environment International Jan 2022Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association.
OBJECTIVE
To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association.
DATA SOURCE
After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes.
STUDY ELIGIBILITY CRITERIA
We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only.
STUDY APPRAISAL AND SYNTHESIS METHODS
Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model.
RESULTS
In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine.
LIMITATIONS AND CONCLUSIONS
This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
Topics: Bias; Cadmium; Diabetes Mellitus, Type 2; Humans; Prediabetic State; Risk
PubMed: 34628255
DOI: 10.1016/j.envint.2021.106920 -
High Blood Pressure & Cardiovascular... Nov 2023The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the... (Review)
Review
The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the potential benefits of early identification and management of patients at risk. In this view, prediabetes represents a high-risk condition for the development of type 2 diabetes mellitus and cardiovascular diseases, and an ideal target to intercept patients before they develop type 2 diabetes gaining a prominent role even in international guidelines. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of about 50% relative risk reduction. Accumulating data also show potential benefits from pharmacotherapy. In this context, the only available data pertain to metformin as a pharmaceutical drug and vitamin D and L-arginine as nutraceuticals. L-arginine appears to be a very interesting tool in the clinical management of patients with pre-diabetes. In this review we summarize the current knowledge on the role of L-arginine in prediabetes as a potentially useful preventive strategy against the progression to type 2 diabetes, with a particular focus on the underlying molecular mechanisms and the past and ongoing trials. In this article we also report the interesting data about the perception of the prediabetic condition and its therapeutic management in the clinical practice in Italy. An early identification and a prompt management of people with prediabetes appears to be of paramount importance to prevent the progression to diabetes and avoid its cardiovascular consequences.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Metformin; Vitamins; Arginine
PubMed: 38060094
DOI: 10.1007/s40292-023-00613-1 -
BMC Medicine Dec 2023Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes...
BACKGROUND
Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes.
METHODS
Among 142,271 diabetes-free UK Biobank participants (aged 39-72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7-6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression.
RESULTS
During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group.
CONCLUSIONS
A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Incidence; Blood Glucose; Risk Factors; Diet
PubMed: 38049803
DOI: 10.1186/s12916-023-03190-1 -
The Journal of Pediatrics Apr 2020
Review
Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemoglobin; Humans; Male; Mass Screening; Obesity; Prediabetic State
PubMed: 32143933
DOI: 10.1016/j.jpeds.2019.12.061 -
Theranostics 2023Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood...
Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology. Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments. We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a. This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR. Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention.
Topics: Mice; Animals; Prediabetic State; Lipofuscin; NAD; Adipose Tissue; Hyperglycemia; Insulin Resistance
PubMed: 37441598
DOI: 10.7150/thno.82697 -
Cardiovascular Diabetology Sep 2023Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased...
BACKGROUND
Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.
METHODS
The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.
RESULTS
Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.
CONCLUSIONS
In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
Topics: Humans; Female; Male; Prediabetic State; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Prevalence; Sweden; Atherosclerosis; Plaque, Atherosclerotic
PubMed: 37759237
DOI: 10.1186/s12933-023-01982-6 -
Science Progress 2021Given that the complications of type 2 diabetes can start at an early stage, early detection and appropriate management of prediabetes are essential. We aimed to develop... (Review)
Review
Given that the complications of type 2 diabetes can start at an early stage, early detection and appropriate management of prediabetes are essential. We aimed to develop an expert opinion on prediabetes in Lebanon to pave the way for national guidelines tailored for the Lebanese population in the near future. A panel of seven diabetes experts conducted a thorough literature review and discussed their opinions and experiences before coming up with a set of preliminary recommendations for the detection and management of prediabetes in Lebanon. Lebanese physicians employ multiple tests for the diagnosis of prediabetes and no national cut-off values exist. The panel agreed that prediabetes screening should be focused on patients exceeding 45 years of age with otherwise no risk factors and on adults with risk factors. The panel reached that fasting plasma glucose (FPG) and HbA1c should be used for prediabetes diagnosis in Lebanon. FPG values of 100-125 mg/dL or HbA1c values of 5.7%-6.4% were agreed upon as indicative of prediabetes. For the management of prediabetes, a three-step approach constituting lifestyle modifications, pharmacological treatment and bariatric surgery is recommended. There should be more focus on research on prediabetes in Lebanon. This preliminary report will be further discussed with the Lebanese Society of Endocrinology, Diabetes and Lipids in 2021 in order to come up with the first Lebanese national guidelines for the detection and management of prediabetes in Lebanon.
Topics: Adult; Diabetes Mellitus, Type 2; Expert Testimony; Fasting; Humans; Lebanon; Prediabetic State
PubMed: 34261386
DOI: 10.1177/00368504211029439 -
Nephron 2021Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and... (Review)
Review
Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.
Topics: Diabetes Mellitus; Humans; Insulin Resistance; Kidney Transplantation; Prediabetic State; Transplant Recipients
PubMed: 33902027
DOI: 10.1159/000514288