Non-diabetic Participants Research Articles

Identification of key genes and mechanisms of epicardial adipose tissue in patients with diabetes through bioinformatic analysis.

BackgroundIn recent years, peri-organ fat has emerged as a diagnostic and therapeutic target in metabolic diseases, including diabetes mellitus. Here, we performed a comprehensive analysis of epicardial adipose tissue (EAT) transcriptome expression differences between diabetic and non-diabetic participants and explored the possible mechanisms using various bioinformatic tools.MethodsRNA-seq datasets GSE108971 and GSE179455 for EAT between diabetic and non-diabetic patients were obtained from the public functional genomics database Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using the R package DESeq2, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Next, a PPI (protein–protein interaction) network was constructed, and hub genes were mined using STRING and Cytoscape. Additionally, CIBERSORT was used to analyze the immune cell infiltration, and key transcription factors were predicted based on ChEA3.ResultsBy comparing EAT samples between diabetic and non-diabetic patients, a total of 238 DEGs were identified, including 161 upregulated genes and 77 downregulated genes. A total of 10 genes (IL-1β, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1RN, and SPP1) were selected as hub genes. GO and KEGG analysis showed that DEGs were mainly enriched in the inflammatory response and cytokine activity. Immune cell infiltration analysis indicated that macrophage M2 and T cells CD4 memory resting accounted for the largest proportion of these immune cells. CSRNP1, RELB, NFKB2, SNAI1, and FOSB were detected as potential transcription factors.ConclusionComprehensive bioinformatic analysis was used to compare the difference in EAT between diabetic and non-diabetic patients. Several hub genes, transcription factors, and immune cell infiltration were identified. Diabetic EAT is significantly different in the inflammatory response and cytokine activity. These findings may provide new targets for the diagnosis and treatment of diabetes, as well as reduce potential cardiovascular complications in diabetic patients through EAT modification.

Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose.

It is not determined whether serum visfatin levels are related to the presence and severity of coronary artery disease (CAD) in non-diabetic subjects. In this study, a total of 65 consecutive non-diabetic participants who underwent coronary angiography were enrolled. Serum visfatin and fasting glucose, as well as the serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride, were measured in all participants before the procedure. The extent of coronary artery lesions was determined by Gensini score. Serum visfatin levels were significantly lower in patients with CAD compared to participants with normal coronary arteries. Inversely, the circulating levels of fasting glucose were found to be elevated in patients with CAD compared with the control subjects. Multivariable logistic regression analysis demonstrated that visfatin and impaired fasting glucose (IFG) were independently associated with the presence of CAD in non-diabetics. No significant relationship was found between serum visfatin and fasting glucose levels in IFG subjects. However, there was a negative association between visfatin concentrations and Gensini score in participants with IFG. Both circulating visfatin concentrations and IFG are independently associated with CAD in non-diabetics. Serum visfatin levels are negatively related to the angiographic severity of CAD in subjects with IFG.

Association of Islet Amyloid Polypeptide to C-Peptide Ratio With Cystic Fibrosis–Related Diabetes

Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes. Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n = 16] and CFRD [n = 18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers. The median (interquartile range) IAPP:C-peptide ratio was significantly (P = 0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2 = 0.399, P < 0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r = 0.683, P = 0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF. Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

Predicting Diabetes in Patients with Metabolic Syndrome Using Machine-Learning Model Based on Multiple Years’ Data

PurposeTo evaluate the performance of machine-learning models based on multiple years of continuous data to predict incident diabetes among patients with metabolic syndrome.Patients and MethodsThe dataset comprises the health records from 2008 to 2020 including 4510 nondiabetic participants with metabolic syndrome (MetS) at baseline and with at least 6 years of records. MetS was defined according to the International Diabetes Federation (IDF) criteria. Overall, 332 patients developed incident diabetes during the 7±1.4 years of follow-up. Three popular classification algorithms were evaluated on the dataset: logistic regression, random forest, and Xgboost. Five models including single-year models (year 1, year 2, and year 3) and multiple-year models (year 1–2 and year 1–3) were developed for each algorithm.ResultsThe model performances improved with the increasing longitudinal dataset as the area under the receiver operating characteristic curve (AUROC) was boosted for both random forest (year 1–3: AUROC=0.893; year 3: AUROC=0.862; year 1–2: AUROC=0.847; year 2: AUROC=0.838) and Xgboost (year 1–3: AUROC=0.897; year 3: AUROC=0.833; year 1–2: AUROC=0.856; year 2: AUROC=0.823) model. In the multiple-year models, the highest fasting plasma glucose, followed by the mean or lowest level of HbA1c and BMI had the most important predictive value for the onset of diabetes. In the “1–3” year model, “delta weight” which reflects the fluctuations of yearly change of weight was the fourth-most important feature.ConclusionThis study demonstrated improved performance with the accumulation of longitudinal data when using machine learning for diabetes prediction in MetS patients. For individuals with similar clinical parameters, the variation trends of these parameters could change the risk of future diabetes. This result indicated that models based on longitudinal multiple years’ data may provide more personalized assessment tools for risk evaluation.

Serum triglycerides concentration in relation to total and cardiovascular mortality in an elderly Chinese population.

To investigate serum triglycerides in relation to all-cause, cardiovascular, and non-cardiovascular mortality in an elderly Chinese population. The study participants (n = 3565) were elderly (≥ 60 years) community dwellers living in a suburban town of Shanghai. Hypertriglyceridemia was defined as a serum triglycerides concentration ≥ 2.30 mmol/L (definite) and ≥ 1.70 mmol/L (borderline), respectively. The prevalence of definite and borderline hypertriglyceridemia at baseline was 7.5% and 29.5%, respectively. It was higher in women (n = 1982, 9.0% and 33.8%, respectively) than men (n = 1583, 6.2% and 27.9%, respectively), in obese and overweight participants (n = 1566, 10.5% and 36.4%, respectively) than normal weight participants (n = 1999, 5.6% and 27.1%, respectively), and in diabetic participants (n = 177, 11.9% and 39.0%, respectively) than non-diabetic participants (n = 3388, 7.5% and 30.8%, respectively). During a median of 7.9 years follow-up, all-cause, cardiovascular and non-cardiovascular deaths occurred in 529, 216 and 313 participants, respectively. In analyses according to the quintile distributions of serum triglycerides concentration, the sex- and age-standardized mortality rate was lowest in the middle quintile for all-cause, cardiovascular and non-cardiovascular mortality (18.6, 7.8 and 11.9 per 1000 person-years, respectively, versus 21.5, 10.5 and 12.7 per 1000 person-years, respectively, in the two lower quintiles and 21.7, 9.5 and 14.0 per 1000 person-years, respectively, in the two higher quintiles). The fully adjusted hazard ratios (95% CI) for the middle quintile versus the combined two lower with two higher quintiles were 0.85 (95% CI: 0.67-1.07, P = 0.17), 0.81 (95% CI: 0.54-1.19, P = 0.28) and 0.87 (95% CI: 0.64-1.17, P = 0.35) for all-cause, cardiovascular and non-cardiovascular mortality, respectively. Our study showed high prevalence of hypertriglyceridemia, especially when defined as borderline and in obese and overweight participants, and mildly but non-significantly elevated risks of cardiovascular mortality relative to the middle level of serum triglycerides.

Metabolic signatures of insulin resistance in non-diabetic individuals

BackgroundInsulin resistance (IR) evolved from excessive energy intake and poor energy expenditure, affecting the patient's quality of life. Amino acid and acylcarnitine metabolomic profiles have identified consistent patterns associated with metabolic disease and insulin sensitivity. Here, we have measured a wide array of metabolites (30 acylcarnitines and 20 amino acids) with the MS/MS and investigated the association of metabolic profile with insulin resistance.MethodsThe study population (n = 403) was randomly chosen from non-diabetic participants of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS 2016). STEPS 2016 is a population-based cross-sectional study conducted periodically on adults aged 18–75 years in 30 provinces of Iran. Participants were divided into two groups according to the optimal cut-off point determined by the Youden index of HOMA-IR for the diagnosis of metabolic syndrome. Associations were investigated using regression models adjusted for age, sex, and body mass index (BMI).ResultsPeople with high IR were significantly younger, and had higher education level, BMI, waist circumference, FPG, HbA1c, ALT, triglyceride, cholesterol, non-HDL cholesterol, uric acid, and a lower HDL-C level. We observed a strong positive association of serum BCAA (valine and leucine), AAA (tyrosine, tryptophan, and phenylalanine), alanine, and C0 (free carnitine) with IR (HOMA-IR); while C18:1 (oleoyl L-carnitine) was inversely correlated with IR.ConclusionsIn the present study, we identified specific metabolites linked to HOMA-IR that improved IR prediction. In summary, our study adds more evidence that a particular metabolomic profile perturbation is associated with metabolic disease and reemphasizes the significance of understanding the biochemistry and physiology which lead to these associations.

One-hour plasma glucose as a long-term predictor of cardiovascular events and all-cause mortality in a Chinese older male population without diabetes: A 20-year retrospective and prospective study.

IntroductionElevated one-hour plasma glucose (1 h-PG) during oral glucose tolerance test predicts the development of type 2 diabetes mellitus and its complications. However, to date, there have been no studies investigating the predictive values of 1 h-PG for the risk of cardiovascular diseases (CVDs) and all-cause mortality in the elderly population in China. This study aimed to evaluate and compare the effectiveness of 1 h-PG and two-hour plasma glucose (2 h-PG) to predict the risk of CVD and all-cause mortality in the Chinese elderly population.Materials and methodsThis retrospective and prospective cohort study was conducted using data obtained from the Chinese People’s Liberation Army General Hospital. All the non-diabetic elderly participants, who had plasma glucose measured at 0, 1, and 2 h during an OGTT (75 g glucose), were followed for 20 years. The primary outcomes were all-cause mortality, myocardial infarction, unstable angina, and stroke. Multivariate-adjusted Cox proportional hazard regression models were performed to examine the association between risk factors and outcomes and to estimate the risk of CVD and all-cause mortality based on 1 h-PG levels.ResultsA total of 862 non-diabetic male individuals were included. The median age was 74.0 (25th–75th percentile: 68.0–79.0) years. There were 480 CVD events and 191 deaths during 15,527 person-years of follow-up. The adjusted hazard ratio (HR) of 1 h-PG as a continuous variable was 1.097 (95% CI 1.027–1.172; P = 0.006) for CVD events and 1.196 (95% CI 1.115–1.281; P < 0.001) for higher risk of mortality. When compared with the lowest 1 h-PG tertile, the other tertiles were associated with CVD events (HR 1.464, 95% CI 1.031–2.080; P = 0.033 and HR 1.538, 95% CI 1.092–2.166; P = 0.014, for tertile 2 and tertile 3 compared with tertile 1, respectively), and the highest 1 h-PG tertile had a significantly higher risk of mortality (HR 2.384, 95% CI 1.631–3.485; P < 0.001) after full adjustment. Compared with 1 h-PG, 2 h-PG had similar abilities to predict all-cause mortality. However, 2 h-PG was less closely associated with CVD when examined in the fully adjusted model, neither as a continuous variable nor as a categorical variable. Conversely, 1 h-PG remained an independent predictor of CVD and all-cause mortality after adjusting for various traditional risk factors.ConclusionPatients with higher 1 h-PG had a significantly increased risk of CVD and all-cause mortality regardless of prediabetes status or development of diabetes at follow-up. The 1 h-PG level might be a better predictor of cardiovascular risk than the 2 h-PG level for the Chinese elderly population.

Liver enzymes, alcohol consumption and the risk of diabetes: the Suita study.

We aimed to investigate the combined impact of liver enzymes and alcohol consumption on the diabetes risk. Data on 5972 non-diabetic participants aged 30-79years from the Suita study were analyzed. Diabetes incidence was surveyed every 2years. Current daily alcohol consumption was defined as light drinking (< 23.0g ethanol/day in men and < 11.5g in women), moderate drinking (23.0-45.9g and 11.5-22.9g), and heavy drinking (≥ 46.0g and ≥ 23.0g). The nondrinkers category included both never-drinkers and former drinkers. During the median follow-up of 13years, 597 incident diabetes cases were diagnosed. Higher levels of γ-glutamyltransferase (GGT), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT) were associated with an increased diabetes risk, and current light drinkers had a lower risk of diabetes than nondrinkers. No sex differences were observed in these associations. Compared to nondrinkers having the lowest quartiles of liver enzymes, nondrinkers and current moderate/heavy drinkers having the highest quartiles had an increased risk of diabetes. However, no association was observed for current light drinkers having the highest quartiles of liver enzymes; the multivariable hazard ratios (95% CIs) in current light drinkers with the highest quartile of liver enzymes were 1.27 (0.68-2.37) for GGT, 1.05 (0.59-1.89) for GPT, and 0.76 (0.40-1.47) for GOT, respectively. High liver enzymes were associated with an increased diabetes risk. No increased diabetes risk was observed in current light drinkers, even in these who had high levels of liver enzymes.

Consistent Inverse Associations of Total, "Bioavailable", Free, and "Non-Bioavailable" Vitamin D with Incidence of Diabetes among Older Adults with Lower Baseline HbA1c (≤6%) Levels.

Background: Serum 25-hydroxyvitamin (25(OH)D) levels are inversely associated with risk of diabetes. The “free hormone hypothesis” suggests potential effects to be mainly related to concentrations of “bioavailable” and free rather than total 25(OH)D. We assessed associations of serum concentrations of vitamin D-binding protein (VDBP), as well as total “bioavailable”, complementary “non-bioavailable”, and free 25(OH)D, with the risk of developing diabetes among non-diabetic older adults in a large population-based cohort study in Germany. Methods: We included 4841 non-diabetic older adults aged 50–75 years at the baseline exam from the ESTHER cohort conducted in Saarland, Germany, in 2001–2002. Concentrations of “bioavailable” and free 25(OH)D were derived from serum concentrations of VDBP, total 25(OH)D, and albumin. Incidence of diabetes was ascertained during up to 14 years of follow-up. Associations were quantified by multivariable Cox proportional hazards regression models with comprehensive confounder adjustment. Results: During a median follow-up of 10.6 years, 837 non-diabetic participants developed diabetes. We observed similar inverse associations with developing diabetes for VDBP (hazard ratio (HR) for lowest versus highest quintile: 1.37, 95% confidence interval (CI): 1.09, 1.72), total 25(OH)D (HR: 1.31, 95% CI: 1.03, 1.66), and “non-bioavailable” 25(OH)D (HR: 1.30, 95% CI: 1.02, 1.65). Associations were smaller and statistically insignificant for “bioavailable” and free 25(OH)D. However, associations of total “non-bioavailable”, “bioavailable”, and free 25(OH)D with incidence of diabetes were much stronger among, and essentially restricted to, participants with lower baseline HbA1c (≤6%) levels. Conclusions: This large prospective cohort study of older Caucasian adults, in agreement with results from randomized trials and Mendelian randomization studies, supports a protective effect of vitamin D against development of diabetes. The “free hormone theory” may not be relevant in this context. However, our results underline the importance of adequate vitamin D status among those who have not yet shown any sign of impaired glucose tolerance.

Increase in glycemic set point, alongside a decrease in waist circumference, in the non-diabetic population during the Japanese National Intervention Program for metabolic syndrome: A single-center, large-scale, matched-pair analysis.

BackgroundIn 2008, the Japanese government implemented a National Intervention Program for metabolic syndrome. Low-risk individuals were not direct targets of this intervention. Nevertheless, they were indirectly enlightened by this massive campaign. Documentation of the metabolic shifts in low-risk individuals following the program launch may inform public health policy regarding approaches to metabolic risks in the general population.MethodsWe conducted a cross-sectional analysis of data from non-diabetic participants who underwent general health check-ups at the Physical Check-up Center of Sumitomo Hospital. Participants during 2007–2008 were pair-matched with those during 2015–2016 with respect to sex, age, smoking status, hemoglobin level, and red blood cell (RBC) count. Each participant was included only once in the study.ResultsTotals of 3,140 men and 2,048 women were pair-matched. The non-diabetic participants showed lower waist circumference, blood pressure, heart rate, and serum lipid concentrations during the second study period. In contrast, the entire distributions of fasting plasma glucose (FPG) concentration in both sexes and glycated hemoglobin (HbA1c) in women were shifted upwards. In men, Δ FPG was +1.6 mg/dL (P < 0.001) and Δ HbA1c was ±0% (P = 0.6). In women, Δ FPG was +3.0 mg/dL (P < 0.001), and Δ HbA1c was +0.1% (P < 0.001). Δ Homeostasis model assessment of β-cell function was −6.6 in men (P < 0.001) and −10.3 in women (P < 0.001). The homeostasis model assessment of insulin resistance did not change significantly.ConclusionsThe “glycemic set point” has increased in non-diabetic people in Japan during recent years. Lifestyle or environmental changes may have caused this metabolic shift through obesity-independent pathways, possibly through effects on pancreatic β-cell function. The underlying mechanism awaits further investigation.

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study.

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; P Interaction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years.

Sonographic Comparison of Atherosclerotic Changes in Carotid Arteries of Diabetic and Non-Diabetic Individuals

Objective: To compare the sonographic findings of atherosclerotic changes in carotid arteries of diabetic and non-diabetic individuals. Material &amp; Methods: A cross-sectional study of 62 diabetic and non-diabetic individuals was conducted from 11 November 2021 to 20 March 2022 at the Radiology Department of District Head Quarter Hospital, Faisalabad, Pakistan. The ultrasound of carotid arteries with a TOSHIBA MX Doppler ultrasound machine, using a linear probe with transducer frequency of 5-12.5MHz was performed in both diabetic and non-diabetic participants. Results: The mean value of CIMT in diabetic patients was 0.6839 ± 0.29178mm while the mean value of CIMT in Non- diabetic patients was 0.8000 ± 0.08563mm. The mean value of peak systolic velocity (PSV) of CCA in diabetic patients was 41.4194 ± 6.60189mm and the mean value of PSV of CCA in Non- diabetic patients was 41.7742 ± 6.52538mm. The mean value of PSV of ICA in diabetic patients was 58.4839 ± 12.03293mm and in Non- diabetic patients was 59.0323 ±10.03489mm. Similarly, the mean value of ICA/CCA ratio in diabetic patients was 1.4097 ± 0.39442 while in non-diabetic patients was 1.4323 ± 0.30374. Conclusion: The diagnostic accuracy of ultrasonography of common carotid artery, and internal carotid artery is very high for atherosclerosis. The use of sonography for measurement of IMT and plaque area act as a vital tool for the detection of atherosclerosis changes due to diabetes. Keywords: carotid artery, diabetes mellitus, intima-media thickness

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension.

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: −4.0; −2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls.

ObjectiveDiabetes is a heterogeneous disease and a precise diagnosis of diabetes subgroups is necessary to initiate proper early treatment and clinical management of the disease. Circulating small RNAs (sRNAs) are potentially diagnostic biomarkers in diseases, including diabetes. Here we aimed to examine whether profiles of circulating sRNAs differed between patients with autoimmune and non-autoimmune diabetes and non-diabetic controls.DesignThis cross-sectional case–control study included participants from the third survey of the HUNT study.MethodsWe performed sRNA sequencing in serum from adult-onset type 1 diabetes (n = 51), type 2 diabetes (n = 50) and latent autoimmune diabetes in adult (LADA, n = 51), as well as non-diabetic HUNT3 participants as control group (n = 51). Differential expression analysis of the sRNAs was performed in R using limma-voom.ResultsWe identified differences in sRNA expression between autoimmune (type 1 diabetes and LADA) and non-autoimmune diabetes (type 2 diabetes) and between patients with diabetes and non-diabetic controls. Focusing on miRNA, we identified 10 differentially expressed mature miRNAs and 30 differentially expressed miRNA variants (isomiRs). We also identified significant changes within other sRNA classes, including a pronounced downregulation of a tRNA fragment in patients with diabetes compared to non-diabetic controls. We created cross-validated sRNA signatures based on the significant sRNAs that distinguished patients with diabetes from non-diabetic controls, and autoimmune from non-autoimmune diabetes, with high specificity and sensitivity. sRNA profiles did not distinguish between type 1 diabetes and LADA.ConclusionsCirculating sRNAs are differentially expressed between patients with diabetes and non-diabetic controls and between autoimmune and non-autoimmune diabetes.

Full-field and multifocal electroretinogram in non-diabetic controls and diabetics with and without retinopathy.

To compare retinal function assessed by full-field electroretinography (ffERG) and multifocal electroretinography (mfERG) in diabetes without retinopathy, diabetes with moderate non-proliferative diabetic retinopathy (NPDR) and in the absence of diabetes. Scotopic and photopic ffERG and mfERG was made in non-fasting volunteers, including 26 diabetic participants without retinopathy, 22 diabetic participants with moderate NPDR and 22 participants without diabetes using full International Society for Clinical Electrophysiology of Vision protocols. Of the ffERG responses, significant deviation (p ≤ 0.05, corrected for multiple sampling and other relevant confounders) from the non-diabetic participants was seen in the diabetic participants only for the OP1-OP3 oscillatory amplitudes and the OP2 implicit time. This finding was independent of whether retinopathy was present or not. For the mfERG, minor amplitude or implicit time deviations were found for a small number of rings (R2, R4 and R5). Receiver of operating characteristic analysis showed that the single most prominent abnormality of the ffERG in diabetes, regardless of whether retinopathy was present or not, was the OP2 implicit time (area under the curve ≥ 0.80). This bi-modal study of electroretinographic characteristics found that the most prominent anomaly associated with diabetes was a prolongation of the implicit time of the OP2 of the scotopic ffERG, while the most prominent added effect of non-proliferative diabetic retinopathy was a further prolongation of the OP2 implicit time. Although the variation in ERG characteristics is far too large for diagnostic purposes, the close association of the oscillatory potentials with the amacrine cells of the retina indicate that their function is particularly sensitive to diabetes.

1184-P: Adolescent Growth Spurt and Type 2 Diabetes Risk in an American Indian Population

Background: Some studies suggest that earlier pubertal development is associated with obesity and metabolic disorders in adulthood, but whether accelerated adolescent linear growth spurt influences type 2 diabetes (T2D) in populations at high risk of diabetes is unclear. Aim: To examine associations of age at initiation of the adolescent growth spurt (i.e., take-off) (ATO) , velocity at take-off (VTO) , and age at peak velocity (APV) with T2D incidence. Methods: Height measurements obtained from a longitudinal study of diabetes in American Indians were used to estimate biological growth parameters using the Preece-Baines growth model I, a parametric model of the human growth curve. Diabetes incidence was analyzed among individuals who had ≥ 4 height examinations at ages 5-17 years and who remained nondiabetic at first examination after age 18. Participants were followed until diabetes developed or last examination. Associations of growth parameters with diabetes incidence were analyzed by Poisson regression. Results: Among 649 originally nondiabetic participants, 135 females and 82 males developed diabetes in a median follow-up of years. With adjustment for age, birth date and maternal diabetes, younger ATO and APV were associated with T2D incidence in males (incidence rate ratio (IRR) =1.75 per year, 95% CI, 1.23, 2.50; and IRR=1.33, 95% CI, 1.01, 1.75, respectively) but not in females (IRR=0.93, 95% CI, 0.75, 1.16; and IRR=1.04, 95% CI, 0.86, 1.26, respectively) . Higher VTO was associated with T2D incidence in males (IRR=1.80 per cm/y, 95% CI, 1.15, 2.81) but not in females (IRR=1.15, 95% CI, 0.88, 1.50) . With further adjustment for adult and childhood BMI and fasting insulin, the associations were attenuated for APV and VTO but remained significant for ATO in males. Conclusion: Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for T2D, at least in males. These associations are only partially explained by measures of adiposity and insulinemia. Disclosure M.J.Ramirez-luzuriaga: n/a. S.Kobes: None. M.Sinha: None. W.C.Knowler: None. R.L.Hanson: None.

Sexual Dimorphism in the Association of Serum Retinol-Binding Protein-4 With Long-Term Dynamic Metabolic Profiles in Non-Diabetes.

ObjectivesWe aimed to investigate the association of circulating retinol-binding protein-4 (RBP4) levels with long-term cardiometabolic risk profiles and whether sex disparity mattered.MethodsWe included 784 non-diabetic participants aged 40 years and above from a well-defined community-based cohort at baseline in 2005 and they were invited to attend the on-site follow-up examination for two consecutive times with 3-year intervals in 2008 and 2011, respectively. Serum RBP4 was measured at baseline, and the anthropometry and biochemical measurements were performed at each visit. Generalized estimating equation models were used to assess the association of serum RBP4 levels with the dynamic changes in adiposity and glucolipid profile.ResultsBased on all the baseline and the 3- and 6-year follow-up data, baseline serum RBP4 levels (each 1-unit of log10RBP4) were significantly associated with waist circumference [β=3.12, 95% confidence interval (CI) (0.77, 5.47), P=0.01], fasting, and 2-h post-loading glucose [β=0.26 (0.05, 0.47), P=0.02, and 1.70 (1.29, 2.12), P< 0.0001], serum triglycerides [β=0.75, 95% CI (0.54, 0.96), P< 0.0001], total cholesterol [β=0.47, 95% CI [0.23 0.70], P<0.0001), and marginally with body mass index (β=0.97, 95% CI (0.02, 1.93), P=0.046], in total participants, after adjusting potential confounders. The association of RBP4 with 2-h post-loading glucose was stronger in women than that in men [β=1.99, 95% CI (1.49, 2.50) vs. 0.61 (-0.14, 1.36), P for interaction=0.001]. The analysis of change in Z-score of cardiometabolic profiles corresponding to each 1-unit increment in log10RBP4 showed consistent results.ConclusionsHigher RBP4 levels are associated with longitudinal increase in adiposity and deteriorated glucolipid profile defined by repeated measurements. The associations differ in sex regarding to the 2-h post-loading glucose.

Digital health in medicine: Important considerations in evaluating health economic analysis

Digital health in medicine: Important considerations in evaluating health economic analysis

The Negative Association Between NAFLD Severity and CKD in a Non-Diabetic Gouty Population.

Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors. We aim to evaluate the association between NAFLD and CKD in a non-diabetic gouty population. The retrospective cross sectional study was performed on 1049 non-diabetic gouty participants, who were hospitalized between 2014 and 2020, across 4 districts in Shandong, China. Demographic and clinical characteristics of the study population were collected. The odds ratios (OR) and corresponding 95% confidence intervals (CI) about the NAFLD severity determined by ultrasonography were obtained by multiple logistic regression analysis. An unexpectedly inverse relationship was found between NAFLD severity and the risk of CKD in people with gout. Multivariate logistic regression analysis demonstrated that a higher degree of NAFLD severity is independently associated with a lower risk of CKD in people with gout, after adjusted for age, sex, smoking, gout duration, and metabolic risk factors including obesity, hypertension, hyperglycemia, hyperuricemia, and dyslipidemia, with OR 0.392 (95% CI 0.248-0.619, p<0.001), 0.379 (95% CI 0.233-0.616, p<0.001) and 0.148 (95% CI 0.043-0.512, p=0.003) in participants with mild, moderate, and severe NAFLD, respectively, compared to those without NAFLD. We also observed a weakened association of serum uric acid (SUA) with metabolic risk factors and NAFLD under circumstances of CKD in people with gout (r=-0.054, p=0.466). In conclusion, the presence and severity of NAFLD were negatively associated with the risk of CKD in the non-diabetic gouty population.

Correlation between prediabetes, coronary artery calcification and cardiovascular risk factors: A 5-year retrospective case study

Objective was to evaluate the correlation between prediabetes, Hemoglobin A1c (HbA1c) 5.7 to 6.4%, cardiovascular risks (determined by Framingham Risk Score: FRS) and the coronary artery calcium score (CACS), by the retrospective analysis of 5 year data documents on PACS, Jan 2015 to Dec 2020. Method: There were 1,639 eligible cases, reviewed by certified radiologists via Picture Archiving and Communication System (PACS), with an asymptomatic condition in the check-up center, divided into two groups: - (1) the prediabetes group, with 756 cases and (2) the non-diabetes group, with 883 cases. The results of vital signs, BMI, CACS, blood test, HbA1c, fasting blood sugar (FBS), lipid profiles, and serum uric acid of all eligible cases were reviewed. Linear regression, t-test, chi-square, and Adjusted Odd ratio were used analyzed the significance and correlation between variables. Results: (1) Most of the prediabetes participants (456 cases, 60.31%) had an intermediate risk of Framingham Risk Score (FRS). While most of the non-diabetes participants (665 cases, 75.31%) had a low risk of FRS., with a statistical difference (Chi-square, P &lt; 0.05), (2) The prediabetes cases were significantly associated with coronary calcification at 2.38 times to the non-diabetic cases [Adjusted Odds Ratio = 2.38 [95% CI (1.98 – 14.98)]., (3) The intermediate cardiovascular risk (FRS) was associated with positive coronary artery calcification at 2.36 times to the low cardiovascular risk [Multivariate adjusted OR = 2.36 (95% CI (1.06 – 5.46)]., and (4) The high cardiovascular risk (FRS) was associated with positive coronary artery calcification at 8.64 times to the low cardiovascular risk [Multivariate adjusted OR = 8.64 (95% CI (2.65 – 18.58)]. Moreover, we found a significant higher serum uric acid in the prediabetes group than the non-diabetes group. Conclusions: Subclinical prediabetes, among 47 to 62-year-old individuals, with an intermediate risk of FRS was significantly associated with positive coronary calcification (atherosclerosis). The combination of CACS screening with a safety low dose radiation protocol and FRS are of complementary together to evaluate the potential risk of Atherosclerotic Cardiovascular Disease (ASCVD). The benefits of combining CACS and FRS are used for decision making of the statin therapy, according to the ACC/AHA primary prevention guidelines (2019). Moreover, a high serum uric acid (UA) is a new challenging ASCVD risk factor in the present that we found it in prediabetes. The association of UA, cardiometabolic disease, and coronary atherosclerosis needs further studies.