Diabetic Subjects Research Articles

Assessment of lip and finger print patterns in patients with type 2 diabetes mellitus and dental caries: A cross-sectional study

Abstract Background and Objectives: Globally, the prevalence of diabetes and dental caries has been soaring high in recent times. There is a constant effort in the scientific community to develop a reliable and economic early predictor which can serve the purpose of mass screening of genetically vulnerable populations. The present study attempts to evaluate the different types of lip prints and finger prints in diabetes mellitus and dental caries and to see association between the most common diseases (diabetes mellitus and dental caries) if any. Materials and Methods: Study subjects included 100 subjects (50 uncontrolled Type II diabetes mellitus patients and 50 healthy controls) in the age group of 30–80 years among the population of Lucknow. Lip prints were obtained using lipstick and cellophane paper, analysed, and classified using Suzuki and Tsuchihashi’s classification. Finger prints were obtained using inkpad, analysed, and classified using Henry’s system of classification. Results: We found loop-type fingerprints and type IV lip prints associated with diabetic patients. Non-diabetics showed loop-type fingerprints and type I lip prints. We found increased dental caries incidence (DMFT scores) in diabetics. Diabetic subjects with caries showed loop fingerprints, which reiterated our earlier findings but are not associated with type IV lip prints. Non-diabetics with caries showed arch fingerprints, but they are not associated with type I lip prints. We found that DMFT scores that we used to assess caries did not associate well with lip prints. Conclusion: The results from our study strongly suggest that dermatoglyphics can be used as a non-invasive technique to mass screen for diabetes as well as dental caries as both diseases are predominantly associated with loop-type fingerprints. Type IV lip prints could be used to screen for diabetes, but no association of lip prints was seen in patients with caries.

The Role of Aldose Reductase in Polyol Pathway: An Emerging Pharmacological Target in Diabetic Complications and Associated Morbidities.

The expression of aldose reductase leads to a variety of biological and pathological effects. It is a multifunctional enzyme which has a tendency to reduce aldehydes to the corresponding sugar.alcohol. In diabetic conditions, the aldose reductase enzyme converts glucose into sorbitol using nicotinamide adenine dinucleotide phosphate as a cofactor. It is a key enzyme in polyol pathway which is a surrogate course of glucose metabolism. The polyol pathway has a significant impact on the aetiology of complications in individuals with end-stage diabetes. The exorbitant level of sorbitol leads to the accumulation of intracellular reactive oxygen species in diabetic heart, neurons, kidneys, eyes and other vasculatures, leading to many complications and pathogenesis. Recently, the pathophysiological role of aldose reductase has been explored with multifarious perspectives. Research on aldose reductase suggest that besides implying in diabetic complications, the enzyme also turns down the lipid-derived aldehydes as well as their glutathione conjugates. Although aldose reductase has certain lucrative role in detoxification of toxic lipid aldehydes, its overexpression leads to intracellular accumulation of sorbitol which is involved in secondary diabetic complications, such as neuropathy, cataractogenesis, nephropathy, retinopathy and cardiovascular pathogenesis. Osmotic upset and oxidative stress are produced by aldose reductase via the polyol pathway. The inhibition of aldose reductase alters the activation of transcription factors like NF-ƙB. Moreover, in many preclinical studies, aldose reductase inhibitors have been observed to reduce inflammation-related impediments, such as asthma, sepsis and colon cancer, in diabetic subjects. Targeting aldose reductase can bestow a novel cognizance for this primordial enzyme as an ingenious strategy to prevent diabetic complications and associated morbidities. In this review article, the significance of aldose reductase is briefly discussed along with their prospective applications in other afflictions.

Effects of Helicobacter pylori Infection on Insulin Resistance in Type 2 Mellitus Diabetics and Non-Diabetics Subjects at Brazzaville University Hospital

Introduction: H.pylori infection is the most common bacterial infection worldwide and is associated with gastrointestinal diseases and extra-gastrointestinal pathologies such as diabetes mellitus and insulin resistance. Objective: To evaluate insulin resistance in diabetics and non-diabetics infected with H. pylori. Methods: We conducted a descriptive cross-sectional study. 90 patients were selected and divided into two groups, 44 patients with T2DM and 46 non-diabetic patients. All information concerning the age and sex of subjects was collected from medical records. Insulin levels were determined by ELISA, blood glucose and HbA1C levels by Cobas c 311, and the HOMA-IR index was calculated. Results: The mean age of T2DM patients was 51 ± 11 years, and that of NDT patients 40±15 years. Women (68) predominated over men (22), with a sex ratio of 0.32. The mean values for T2DM patients were: glycemia 12.6±2.3 mmol/l, HbA1C 10.37±2.9%, HOMA-IR 2.69±1.35 (p<0.001), Insulinemia 8.71±3.14 μU/ml (p= 0.801). Univariate logistic regression analysis showed: Glycemia OR 2.29 [95% IC 1.80-4.5], HbA1C OR 3.08 [95% IC 0.87-1.02], Insulin OR 1.02 [95% IC 1.0-0.16] and HOMA-IR OR 4.4 [95% IC 0.55-0.95]. Means for NDT infections were: blood glucose 9.7±1.0 mmol/l, insulin 9.7±1.64 μU/ml, HOMA-IR 1.45±0.42, HbA1C 8.6±0.9%. Univariate logistic regression analysis showed: Blood glucose OR1.1 [95% IC1.01-2.14], HbA1C OR 1.35 [95% IC 0.08-1.34], Insulin OR 0.51 [95% IC 0.12-1.08], HOMA-IR OR 2.4 [95% IC 0.32-1.45]. Conclusion: Our study showed a statistical significant difference between H.pylori infection and Insulin resistance, also confirms the link of both.Abbreviations: T2DM: Type two diabetes of mellitus, NDT: No-Diabetics, OR: Odd ratio.

Quantitative Analysis of Different Foveal Avascular Zone Metrics in Healthy and Diabetic Subjects

The primary aim of this study was to assess the size and shape of the Foveal Avascular Zone (FAZ) in patients with type 2 diabetes mellitus compared to healthy subjects. The study used 80 OCTA images from the FAZID dataset. The FAZ size was measured by its area, perimeter, and maximum/minimum Feret diameters. The shape was assessed using the axial ratio, circularity, roundness, and solidity. These metrics were calculated automatically using Matlab® R2020b. Statistical analysis was performed using SPSS statistical software version 28.0, with a p-value of less than 0.01 considered significant. The results showed that the FAZ area was significantly larger in diabetic eyes (mean = 0.50 mm2) compared to control eyes (mean = 0.37 mm2), with a p-value of less than 0.01. Both the maximum and minimum diameters of the FAZ were also significantly larger in diabetic groups compared to the control group. Parameters associated with FAZ’s shape were significantly smaller in the diabetic groups than in the control group, except for the axial ratio. The main finding of this study is that diabetic eyes without clinically detectable diabetic retinopathy exhibit morphological changes and irregularities at the FAZ border.

Adiponectin and TNFα in relation to glucometabolic control in patients with type 2 diabetes mellitus.

The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM). We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables. Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin. Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.

Radial artery pulse wave age-related assessment for diabetic patients based on multiple linear regression time domain analysis method

The global incidence of diabetes increases yearly. About 10 % of adults are affected. This study established a multiple linear regression (MLR) time domain analysis model of radial artery pulse wave characteristic parameters in CUN, GUAN and CHI based on traditional Chinese medicine (TCM) to assess diabetes. Pulse signals of diabetic subjects were collected by a pulse instrument. The locations of CUN, GUAN and CHI were determined by a TCM practitioner, and all pulse signals were normalized. Measurement data from 100 male and 100 female patients were used to establish a new time domain analysis method for extracting pulse wave characteristic parameters called equal pressure pulse transit time (EP-PTT). For these mentioned samples, the EP-PTT is different for male and female diabetic subjects, it was smaller for male diabetic subjects than those of female diabetic subjects. EP-PTT1 and EP-PTT6 are relevant to predicting age based on CUN, GUAN and CHI signals, which showed a linear negative correlation (P < 0.05). The EP-PTTi (i = 2, 3, 4) of female diabetic subjects are linearly correlated with age, and all of these are positively correlated (P < 0.05). These observations were clearly different from observations in healthy controls. The pulse waveform of CUN, GUAN and CHI of diabetic subjects can explore the relationship between the age of diabetic subjects and EP-PTT. The preliminary findings will provide foundational data for type 2 diabetes assessment based on CUN, GUAN and CHI pulse signals of radial artery, and the proposed new analysis method can be used for assessing type 2 diabetes.

Tongue image fusion and analysis of thermal and visible images in diabetes mellitus using machine learning techniques

The study aimed to achieve the following objectives: (1) to perform the fusion of thermal and visible tongue images with various fusion rules of discrete wavelet transform (DWT) to classify diabetes and normal subjects; (2) to obtain the statistical features in the required region of interest from the tongue image before and after fusion; (3) to distinguish the healthy and diabetes using fused tongue images based on deep and machine learning algorithms. The study participants comprised of 80 normal subjects and age- and sex-matched 80 diabetes patients. The biochemical tests such as fasting glucose, postprandial, Hba1c are taken for all the participants. The visible and thermal tongue images are acquired using digital single lens reference camera and thermal infrared cameras, respectively. The digital and thermal tongue images are fused based on the wavelet transform method. Then Gray level co-occurrence matrix features are extracted individually from the visible, thermal, and fused tongue images. The machine learning classifiers and deep learning networks such as VGG16 and ResNet50 was used to classify the normal and diabetes mellitus. Image quality metrics are implemented to compare the classifiers’ performance before and after fusion. Support vector machine outperformed the machine learning classifiers, well after fusion with an accuracy of 88.12% compared to before the fusion process (Thermal-84.37%; Visible-63.1%). VGG16 produced the classification accuracy of 94.37% after fusion and attained 90.62% and 85% before fusion of individual thermal and visible tongue images, respectively. Therefore, this study results indicates that fused tongue images might be used as a non-contact elemental tool for pre-screening type II diabetes mellitus.

Evaluating the outcome of screening for glaucoma using colour fundus photography-based referral criteria in a teleophthalmology screening programme for diabetic retinopathy

AimsTo evaluate the effectiveness of glaucoma screening using glaucoma suspect (GS) referral criteria assessed on colour fundus photographs in Singapore’s Integrated Diabetic Retinopathy Programme (SiDRP).MethodsA case–control study. This study included...

1786-LB: Twenty-Four-Hour Ambulatory Blood Pressure and Vascular Complications in Type 1 Diabetes Subjects—Systematic Review and Meta-analysis of Prospective Studies

1786-LB: Twenty-Four-Hour Ambulatory Blood Pressure and Vascular Complications in Type 1 Diabetes Subjects—Systematic Review and Meta-analysis of Prospective Studies

Above-ankle Reamputation and Mortality following Transmetatarsal Amputation in Diabetic and Nondiabetic Peripheral Artery Disease

The risk of above-ankle reamputation following a transmetatarsal amputation is around 30%. Patient selection may be crucial to achieve good outcomes, and to avoid futile operations and suffering. We are aware of no previous comparison between the two largest patient groups that undergo lower extremity amputations: patients with diabetes, and patients with non-diabetic peripheral artery disease. Patients with diabetes or non-diabetic peripheral artery disease who had undergone a transmetatarsal amputation from 2004 through 2018 at our institution were included. Patient characteristics and peri-operative details were analyzed retrospectively. Subjects with diabetes were compared with subjects with non-diabetic peripheral artery disease regarding above-ankle reamputation, reamputation level, and mortality. Five-hundred-and-sixty transmetatarsal amputations in 513 subjects were included. The majority of transmetatarsal amputations (86%) occurred in diabetic subjects. Subjects with non-diabetic PAD had a higher risk of above-ankle reamputation (p = .008), and death (p < .001). At the time of data collection, only multiple-ray amputation (vs. single-ray) was an independent risk factor for above-ankle reamputation. Only age, medical comorbidity in general, and chronic heart failure were independent risk factors of death. To our knowledge, this study is the first to report marked differences in above-ankle reamputation rates and mortality following transmetatarsal amputation, comparing diabetics with non-diabetic patients with peripheral artery disease. However, the differences may be attributed to non-diabetics being older, having more medical comorbidities, and having more advanced foot ulcers at the time of transmetatarsal amputation. In patients exhibiting several of these risk factors, transmetatarsal amputation may be futile. Level of Clinical EvidencePrognostic Level 2: Retrospective study.

Dexamethasone-Induced Insulin Resistance Attenuation by Oral Sulfur-Oxidovanadium(IV) Complex Treatment in Mice.

Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound-[VIVO(octd)]-and effects associated with glucocorticoid-induced insulin resistance in mice. The effects of [VIVO(octd)] were evaluated in a female Swiss mice model of insulin resistance induced by seven days of dexamethasone treatment in comparison with groups receiving metformin treatment. Biological assays such as hematological, TyG index, hepatic lipids, glycogen, oxidative stress in the liver, and oral glucose tolerance tests were evaluated. [VIVO(octd)] was characterized with 51V NMR, infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR), electronic absorption spectroscopy, and mass spectrometry (ESI-FT-MS). The [VIVO(octd)] oral treatment (50 mg/kg) had an antioxidant effect, reducing 50% of fast blood glucose (p < 0.05) and 25% of the TyG index, which is used to estimate insulin resistance (p < 0.05), compared with the non-treated group. The oxidovanadium-sulfur compound is a promising antihyperglycemic therapeutic, including in cases aggravated by insulin resistance induced by glucocorticoid treatment.

Serum Fructosamine and Glycosylated Haemoglobin in Diabetic Subjects and their Non-Diabetic First-Degree Relatives

Serum Fructosamine and Glycosylated Haemoglobin in Diabetic Subjects and their Non-Diabetic First-Degree Relatives

Neuroprotective Effects of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors (Gliflozins) on Diabetes-Induced Neurodegeneration and Neurotoxicity: A Graphical Review.

Diabetes is a chronic endocrine disorder that negatively affects various body systems, including the nervous system. Diabetes can cause or exacerbate various neurological disorders, and diabetes-induced neurodegeneration can involve several mechanisms such as mitochondrial dysfunction, activation of oxidative stress, neuronal inflammation, and cell death. In recent years, the management of diabetes-induced neurodegeneration has relied on several types of drugs, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, also called gliflozins. In addition to exerting powerful effects in reducing blood glucose, gliflozins have strong anti-neuro-inflammatory characteristics that function by inhibiting oxidative stress and cell death in the nervous system in diabetic subjects. This review presents the molecular pathways involved in diabetes-induced neurodegeneration and evaluates the clinical and laboratory studies investigating the neuroprotective effects of gliflozins against diabetes-induced neurodegeneration, with discussion about the contributing roles of diverse molecular pathways, such as mitochondrial dysfunction, oxidative stress, neuro-inflammation, and cell death. Several databases-including Web of Science, Scopus, PubMed, Google Scholar, and various publishers, such as Springer, Wiley, and Elsevier-were searched for keywords regarding the neuroprotective effects of gliflozins against diabetes-triggered neurodegenerative events. Additionally, anti-neuro-inflammatory, anti-oxidative stress, and anti-cell death keywords were applied to evaluate potential neuronal protection mechanisms of gliflozins in diabetes subjects. The search period considered valid peer-reviewed studies published from January 2000 to July 2023. The current body of literature suggests that gliflozins can exert neuroprotective effects against diabetes-induced neurodegenerative events and neuronal dysfunction, and these effects are mediated via activation of mitochondrial function and prevention of cell death processes, oxidative stress, and inflammation in neurons affected by diabetes. Gliflozins can confer neuroprotective properties in diabetes-triggered neurodegeneration, and these effects are mediated by inhibiting oxidative stress, inflammation, and cell death.

IDENTIFICATION OF SIGNIFICANT TEMPORAL FEATURES FROM PHOTO PULSE PLETHYSMOGRAM FOR PREDICTION OF HYPERGLYCEMIA

The increase in diabetic class population is witnessed every year and hence frequent need of checking blood glucose levels is highly required in both diabetic and healthy subjects. This requirement has led many researchers to develop efficient, accurate and easy estimation of blood glucose level without painful blood pricking or extraction. In line with this objective, this study is an effort for waveform analysis of autonomic response of photo pulse plethysmogram (PPG) and to evaluate PPG features that may provide better non-invasive detection of the disease. A total of 300 (150 diabetic and 150 control) subjects aged more than 18 years are considered for this study. Relevant patient details were obtained, and finger PPG recording in digital form was performed for 5 min with the digitization sampling rate of 200 sample points per second. After signal baseline correction, features are calculated from averaged normalized PPG and its first and second derivatives. A total of 41 features were derived from normalized PPG pulse and its derivatives for the assessment of hyperglycemia. But in practice, computation of many features is time-consuming and truly a tedious job for any model design. Further, model performance and accuracy are affected significantly. Applying six different statistical and machine learning methods for the identification of important features, 20 features were identified out of 41 features whose values are highly significantly different for control and study (diabetic) groups. This work was focused on feature extraction stage for a PPG-based diagnostic system. Though our study is aimed to identify significant features that can discriminate between diabetic and control groups non-invasively, these features have the potential for much clinical assessment and other pathological disorders without any doubt.

Brain-derived neurotrophic factor (BDNF) and other neurotrophic factors in type2 diabetes mellitus and their association with neuropathy.

Diabetes mellitus (DM) is associated with increased risk of morbidity and premature mortality due to its various complications. In an Indian study, the prevalence of diabetic peripheral neuropathy (DPN) in type 2 diabetic subjects was shown to be 29.2%. There is increasing evidence that a deficiency of nerve growth factor (NGF) in diabetes, as well as the calcitonin gene-related peptide (CGRP), may also contribute to the development of DPN. The aim of the current study was to evaluate nerve growth factor levels with neuropathy in type2 DM. Forty healthy controls and 40 patients withtype2 DM were recruited; they were asked to report to Dept. of Physiology for initial history taking, general examination and neuropathy examination. A total of 5mL of blood was collected for neurotrophic factor estimation as well as glycemic profile estimation. The brain-derived neurotrophic factor (BDNF) valueswere significantly lower in the DM group whereas the insulin levels were also quite high in DM. The hot thresholds for both the upper limb and lower limb were greater in the DM group suggesting the impending neuropathy. Similarly, the Michigan scores were also greater in the DM group. The neuropathy parameters especially the Michigan A and B and the hot thresholds were positively correlated with duration of DM and glucose profile. The neurotrophic factors especially BDNF are drastically reduced in DM patients and are negatively associated with neuropathy, and hence, BDNF can be utilized as a therapeutic target to treat and prevent neuropathy.

Discovery of Free Glycated Amines and Glycated Urea in Diabetic Plasma: Potential Implications in Diabetes.

The role of protein glycation in the pathogenesis of diabetes has been well established. Akin to proteins, free amino acids and other small-molecule amines are also susceptible to glycation in hyperglycemic conditions and may have a role in the pathogenesis of the disease. However, information about glycation of free amino acids and other small-molecule amines is relatively obscure. In the quest to discover small-molecule glycated amines in the plasma, we have synthesized glycated amino acids, glycated creatine, and glycated urea, and by using a high-resolution accurate mass spectrometer, a mass spectral library was developed comprising the precursor and predominant fragment masses of glycated amines. Using this information, we report the discovery of the glycation of free lysine, arginine, and leucine/isoleucine from the plasma of diabetic patients. This has great physiological significance as glycation of these amino acids may create their deficiency and affect vital physiological processes such as protein synthesis, cell signaling, and insulin secretion. Also, these glycated amino acids could serve as potential markers of diabetes and its complications. While other amines, such as creatinine and urea, accumulate in the plasma and act as biomarkers of diabetic nephropathy. For the first time, we report the detection of glycated urea in diabetic plasma, which is confirmed by matching the precursor and fragment masses with the in vitro synthesized glycated urea by using 12C6 and 13C6-glucose. Further, we quantified glycated urea detected in two forms, monoglycated urea (MGU) and diglycated urea (DGU), by a targeted mass spectrometric approach in the plasma of healthy, diabetic, and diabetic nephropathy subjects. Both MGU and DGU showed a positive correlation with clinical parameters, such as blood glucose and HbA1c. Given that urea gets converted to glycated urea in hyperglycemic conditions, it is crucial to quantify MGU and DGU along with the urea for the diagnosis of diabetic nephropathy and study their physiological role in diabetes.

#771 Estimating glomerular filtration rate: does the diabetic status influence the performances of current equations?

Abstract Background and Aims Diabetes is the first cause of chronic kidney disease (CKD) worldwide. The estimation of glomerular filtration rate (GFR) is one main tool to detect CKD. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equations is the most validated in Europe. More recently, another renal biomarker, cystatin C, has been proposed. In the current analysis, we studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. Method Four cohorts from the EKFC dataset were considered in which the diabetic status was available: Lund, Sweden (n = 2,780), Berlin, Germany (n = 654), Créteil, France (n = 466), and Paris, France (n = 2,258). Serum creatinine and cystatin C were measured with calibrated assays. GFR was measured by plasma clearances (mGFR) (iohexol in Lund, Berlin and Créteil and 51Cr-EDTA in Paris). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ±30% of mGFR). As the characteristics of diabetic patients were different, we matched diabetic and non-diabetic patients using the following matching criteria: age (±3 years), sex (equal), mGFR (±3 mL/min/1.73 m²), and BMI (±2.5 kg/m²). Results In the whole population (n = 6,158), median [IQR] age was 61 [47; 72] years, with 45.8% of women. Mean measured GFR (mGFR) was 60 [39; 82] mL/min/1.73 m². Compared to non-diabetic subjects (n = 5,124), diabetic patients (n = 1,034) were older, more frequently males, heavier, had lower mGFR (45 vs 64 mL/min/1.73 m²), and higher creatinine (1.44 vs 1.06 mg/dL; p &amp;lt; 0.0001) and cystatin C (1.67 vs 1.20 mg/L) concentrations. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than single-biomarker equations. Globally, P30 were substantially lower in diabetic patients than in non-diabetic patients (Table). We could match data for 289 females and 546 males. The results in the matched cohorts were quite similar between diabetics and non-diabetics subjects, and this is true for every equation. Conclusion In conclusion, in a large dataset of patients including diabetics and non-diabetics, we showed that the EKFC equations are accurate in diabetic and non-diabetic patients. Combining the creatinine and cystatin C-based equations presents an added value. If accuracy of all equations seems better in non-diabetic than in diabetic subjects, it is probably more due to differences in age and (still more) in GFR levels than to the diabetic status.

Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study

BackgroundThe neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status.MethodsData were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors.ResultsOver a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19–1.58) for all-cause mortality and 1.63 (95% CI, 1.29–2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03–1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08–2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively.ConclusionsThe findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR’s fluctuations over time should be further focused.

MitoTempo protects against nε-carboxymethyl lysine-induced mitochondrial dyshomeostasis and neuronal cells injury

Enhanced formation of advanced glycation end products (AGEs) is a pivotal factor in diabetes pathophysiology, increasing the risk of diabetic complications. Nε-carboxy-methyl-lysine (CML) is one of the most relevant AGEs found in several tissues including the peripheral blood of diabetic subjects. Despite recognizing diabetes as a risk factor for neurodegenerative diseases and the documented role of mitochondrial abnormalities in this connection, the impact of CML on neuronal mitochondria and its contribution to diabetes-related neurodegeneration remain uncertain. Here, we evaluated the effects of CML in differentiated SH-SY5Y human neuroblastoma cells. Due to the association between mitochondrial dysfunction and increased production of reactive oxygen species (ROS), the possible protective effects of MitoTempo, a mitochondria-targeted antioxidant, were also evaluated. Several parameters were assessed namely cells viability, mitochondrial respiration and membrane potential, ATP and ROS production, Ca2+ levels, mitochondrial biogenesis and dynamics, mito/autophagy, endoplasmic reticulum (ER) stress and amyloidogenic and synaptic integrity markers. CML caused pronounced mitochondrial defects characterized by a significant decrease in mitochondrial respiration, membrane potential, and ATP production and an increase in ROS production. An accumulation of individual mitochondria associated with disrupted mitochondrial networks was also observed. Furthermore, CML caused mitochondrial fusion and a decrease in mitochondrial mass and induced ER stress associated with altered unfolded protein response and Ca2+ dyshomeostasis. Moreover, CML increased the protein levels of β-secretase-1 and amyloid precursor protein, key proteins involved in Alzheimer's Disease pathophysiology. All these effects contributed to the decline in neuronal cells viability. Notable, MitoTempo was able to counteract most of CML-mediated mitochondrial defects and neuronal cells injury and death. Overall, these findings suggest that CML induces pronounced defects in neuronal mitochondria and ER stress, predisposing to neurodegenerative events. More, our observations suggest that MitoTempo holds therapeutic promise in mitigating CML-induced mitochondrial imbalance and neuronal damage and death.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case–control study

BackgroundLong-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. ObjectivesOur study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. MethodsThis is a prospective nested case–control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score–matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. ResultsThe majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18–26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. ConclusionsThese findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.