Non-diabetic Volunteers Research Articles

Effects of Intranasal Naloxone on Hypoglycemia-Associated Autonomic Failure (HAAF) in Susceptible Individuals.

Hypoglycemia-associated autonomic failure (HAAF), defined as blunting of counter-regulatory hormone and symptom responses to recurrent hypoglycemia, remains a therapeutic challenge in diabetes treatment. The opioid system may play a role in HAAF pathogenesis since activation of opioid receptors induces HAAF. Blockade of opioid receptors with intravenous naloxone ameliorates HAAF experimentally, yet is not feasible therapeutically. To investigate the effects of opioid receptor blockade with intranasal naloxone on experimentally-induced HAAF. Randomized, double-blinded, placebo-controlled crossover study. Academic research center. Healthy non-diabetic volunteers. Paired two-day studies, 5-10 weeks apart, each consisting of three consecutive hypoglycemic episodes (hyperinsulinemic hypoglycemic clamps, glucose nadir: 54 mg/dL): two on day 1 with administration of intranasal naloxone vs. placebo, followed by the third episode on day 2. Differences in counter-regulatory hormones responses and hypoglycemia symptoms between first and third hypoglycemic episodes in naloxone vs. placebo studies. Out of 17 participants, 9 developed HAAF, confirming variable inter-individual susceptibility. Among participants susceptible to HAAF, naloxone maintained some hormonal and symptomatic responses to hypoglycemia and prevented the associated requirement for increased glucose infusion. Unexpectedly, naloxone reduced plasma epinephrine and growth hormone responses to the first hypoglycemic episode but prevented further reduction with subsequent hypoglycemia. This is the first study to report that intranasal naloxone, a widely used opioid receptor antagonist, may ameliorate some features of HAAF. Further investigation is warranted into mechanisms of variable inter-individual susceptibility to HAAF and the effects of intranasal naloxone in people with diabetes at risk for HAAF.

Evaluation of glycemic response of ten local meals commonly consumed from Chad

Diabetes mellitus is a metabolic disorder characterized by the presence of chronic hyperglycaemia accompanied by greater or lesser impairment in the metabolism of carbohydrates, lipids and proteins, including defects in either insulin secretion or response. The function of pancreatic cells gradually declines before the onset of clinical hyperglycemia. Its prevalence is increasing everywhere, especially in the developing countries due to the consumption of unknown glycemic index (GI) foods. Thus, the present study aimed to determine the GI of some local meals from Chad. In this purpose, ten meals were investigated and 60 non-diabetic volunteers were recruited in the present study. The proximate composition and the GI of these meals were determined. Results showed that 5 main ingredients (Hibiscus esculentus, Ipomea batata, Hibiscus sabdariffa, Corchorus oletorius and seeds of Parkia biglobosa) differentiate the meals. Soluble sugars and total carbohydrates levels showed a significant (p < 0.05) difference between meals (staples and sauces). The highest value of total carbohydrate of staples was found in Peeled dried sorghum ((BD); 31.80 %) while Cooked rice ((RZ); 19.82 %) has the lowest amount. Then, total carbohydrate content of sauces was in the range of 3.95 % (Leaves of Corchorus oletorius (MLK)) and 8.76 % (Dried okra + Fresh meat (GSV)) while, Sorrel leaves + Smoked fish ((OSP); 2.51 %) and Dried okra + Smoked fish ((GSP); 1.31 %) recorded the highest and lower values of soluble sugars, respectively. Moreover, Peeled dried maize + Dried okra + Fresh meat (MD/GSV) meal showed the highest GI (115.76 %) while the lowest value was found with Cooked rice + Sorrel leaves + Smoked fish (RZ/OZP) meal (31.08 %). The GI of Peeled dried maize + Fresh okra + Fresh meat (MD/GFV) attained a peak of 140 at 40 min while the peak of 130 was obtained with Peeled dried maize + Fresh okra + Smoked fish (MD/GFP) meal at the same time compared to glucose (160 at 40 min). Five meals (OSP/RZ; MD/GFP; MD/GFV; BD/GFP and BD/MLK) were low GI foods and were the best meals for human-being in terms of preventing diabetes mellitus. The consumption of such meals can provide a substantial contribution to the improvement of the Chadian diets.

Development of sensor system and data analytic framework for non-invasive blood glucose prediction

AbstractPeriodic quantification of blood glucose levels is performed using painful, invasive methods. The proposed work presents the development of a noninvasive glucose-monitoring device with two sensors, i.e., finger and wrist bands. The sensor system was designed with a near-infrared (NIR) wavelength of 940 nm emitter and a 900–1700 nm detector. This study included 101 diabetic and non-diabetic volunteers. The obtained dataset was subjected to pre-processing, exploratory data analysis (EDA), data visualization, and integration methods. Ambiguities such as the effects of skin color, ambient light, and finger pressure on the sensor were overcome in the proposed ‘niGLUC-2.0v’. niGLUC-2.0v was validated with performance metrics where accuracy of 99.02%, mean absolute error (MAE) of 0.15, mean square error (MSE) of 0.22 for finger, and accuracy of 99.96%, MAE of 0.06, MSE of 0.006 for wrist prototype with ridge regression (RR) were achieved. Bland–Altman analysis was performed, where 98% of the data points were within ± 1.96 standard deviation (SD), 100% were under zone A of the Clarke Error Grid (CEG), and statistical analysis showed p &lt; 0.05 on evaluated accuracy. Thus, niGLUC-2.0v is suitable in the medical and personal care fields for continuous real-time blood glucose monitoring.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.

Early Retinal Microvascular Changes Assessed with Swept-Source OCT Angiography in Type 1 Diabetes Patients without Retinopathy

Type 1 diabetes is a chronic disease that can lead to vision loss when diabetic retinopathy develops. Retinal microvascular alterations occur before the appearance of clinical signs on a fundus examination. This study aimed to analyze retinal vascular parameters on optical coherence tomography angiography (OCT-A) in patients with type 1 diabetes without diabetic retinopathy in comparison with non-diabetic volunteers. This cross-sectional study was conducted at Dijon University Hospital from 2018 to 2020. Vascular densities were measured using macular OCT-A. In total, 98 diabetes patients and 71 non-diabetic volunteers were enrolled. A statistically significant lower vascular density of the inner circle was found in the superficial capillary plexus (SCP) in the diabetes group (p < 0.01). There was a statistically significant correlation between central vascular density in the deep capillary plexus (DCP) and total daily insulin intake (p = 0.042); furthermore, use of the FreeStyle Libre (FSL) device was associated with higher vascular densities in both the SCP (p = 0.034 for outer circle density) and DCP (p < 0.01 for inner circle density and p = 0.023 for outer circle density). Retinal microvascularization was early-altered in type 1 diabetes, and using the FSL device seemed to preserve retinal microvascularization.

Increased level of plasma Cyclophilin A in early diabetic population suggesting it as a reliable pro inflammatory biomarker of coronary artery disease in diabetic patients

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Institute of Cardiovascular disease, Madras Medical Mission Background Type 2 Diabetes (DM) is a pro-inflammatory state in the pathogenesis of Atherosclerosis with the presence of many active proteins, of which CyclophilinA (CypA) has been shown to have a positive correlation with the presence and severity of vascular diseases. As Cyp A is proven to be secreted in varying levels from cells, in response to inflammatory stimuli, viz., hypoxia, infection, and oxidative stress, it is found ideal, to study it further as one of a reliable pro-inflammatory biomarker responsible for the progression of Coronary Artery Disease (CAD) in early DM. Purpose A prospective cross-sectional study was conducted to quantify CypA in the early phase of DM before the onset of CAD, in comparison to non-diabetic volunteers and to review it as one of the pro-inflammatory biomarkers of CAD, in association with hsCRP and other proven biomarkers (Insulin, Lipid profile, HBA1C, and Glucose). Methods The study subject comprised 299 patients with DM and 50 healthy volunteers. History of duration of DM and other co-morbidities was obtained. A comprehensive clinical examination and non-invasive evaluation of atherosclerotic vascular disease were done to rule out CAD. CypA was analyzed by ELISA kit in serum. P-value of &amp;lt;0.05 was considered statistically significant. Results The average age group of study population is 51­ with an SD of 9.4(Male 206; Female 143). The observed range of CypA in our study is 50–1974 ng/ml, which is much higher than the values obtained in other studies (2–200 ng/ml). An increased level of CYP A is seen in DM than control group with a significant P Value of &amp;lt;0.001 [DM - Mean 462.5 ; Median of 328 ng/ml; Control group(Non diabetic) - Mean 273 ; Median 190 ng/ml]. CypA value in early diabetics (&amp;lt;5 years) is higher than patients with &amp;gt;5 years of DM (one-way ANOVA). Review of hsCRP shows statistically different levels between DM and the control group (p=0.012). Scatter plots of CypA and hsCRP concentration showed values within 500 ng/ml of CypA distributed in the mid to average risk category of hsCRP (&amp;lt;1–3 mg/l). The probability of proposing CypA as a pro-inflammatory biomarker compared to hsCRP in DM is reviewed by the ROC curve (AUC 0.684 with a sensitivity of 80% and specificity of 50%). Increased CypA and hsCRP are observed in females than males (CypA: p=0.04 and hsCRP: p&amp;lt;0.001). No significant difference is observed between the two groups in other variables (Insulin (P=0.69), Cholesterol (P= 0.33), TGL (P=0.77), HDL (P=0.17), LDL (P=0.06). Conclusion In our study CypA level is increased in the early stage of DM when compared with non-Diabetes. The range obtained is higher than the previous study values. CypA value of &amp;lt;500 ng/ml is observed to be related to CAD when reviewed along with the hsCRP cardiac risk stratification range. The scope of CypA as a reliable pro-inflammatory biomarker of CAD in early DM is more promising and its edge over hsCRP as an early biomarker is to be reviewed further.

The study of electrocardiographic changes in type II diabetes mellitus

Background: The predictions of the silent ischemia in the asymptomatic patients were done with the Electrocardiographic (ECG) abnormalities findings. The high risk of the cardiac morbidity and mortality was statistically associated with abnormal ECG findings. Aims and Objectives: To reduce patient mortality and morbidity, the current analysis was performed on diabetes patients to look for ECG alterations. Materials and Methods: A total of 100 people were used, 50 of whom had type-2 diabetes mellitus and 50 of whom were healthy, non-diabetic volunteers whose ages and sexes matched the patients with type-2 diabetes. The 12-lead ECG instrument was used to record the electrographic markings. For fasting blood sugar blood was collected after a minimum 8 h overnight fasting and for PP2BS blood was collected 2 h after lunch. Results: In people with type II diabetes mellitus, the P wave’s amplitude significantly decreased. When compared to controls, type II diabetics’ QRS complex duration was noticeably longer. When compared to controls, (type II DM) Type 2 diabetes mellitus sufferers had a significantly longer QT and QTC interval. When type II diabetics were compared to controls, the ST segment alterations were significantly different. When compared to controls, type II diabetes showed a considerable T-wave alteration. Conclusion: The ST segment deviation from the isoelectric line is a predictor of coronary events in an asymptomatic diabetic population. The incidence of sudden mortality due to cardiovascular disease in diabetics is reduced as a result of early detection of QT and QTC alterations, which are good indicators of cardiovascular disease risk in diabetics.

PANCREATIC FAT CONTENT PLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS SIMILAR TO THAT OF LIVER FAT CONTENT.

Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk factors for T2DM. The aim of the present study was to demonstrate the relationship between PFC, LFC and T2DM. A total of 70 T2DM subjects and 30 non-diabetic volunteers who underwent Dixon-based magnetic resonance imaging (MRI) method at Yixing People's Hospital between December 2018 to December 2020 were included in the study. The three-point Dixon (3p-Dixon) method was used to measure the fat content in the pancreas and liver. Clinical indices including gender, age, body mass index (BMI), total cholesterol, triglyceride, glucose and C peptide levels were collected. The association between PFC, LFC, and OGTT-derived parameters was examined by Pearson and Spearman correlation analyses. T2DM subjects had higher PFC and LFC than those measured in the non-diabetic subjects (p <0.05). PFC and LFC were associated positively with OGTT-derived parameters such as insulin secretion, insulin resistance, and early- and late-phase insulin secretion in the male T2DM subjects(p <0.05), but not in the non-diabetic and female T2DM subjects. The relationship between PFC and OGTT-derived parameters was also more obvious than that for LFC in overweight and obese male patients with T2DM whose BMI was >24 kg/m2. PFC and LFC were both associated with β-cell dysfunction and insulin resistance in males with T2DM. The relationship between PFC and β-cell dysfunction and insulin resistance was more obvious than that observed for LFC in overweight and obese male T2DM patients. More attention should therefore be paid to PFC in clinical settings.

LEP G2548A polymorphism is associated with increased serum leptin and insulin resistance among T2DM Malaysian patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome that is rapidly increasing across the world, especially in Malaysia. Leptin plays a vital role in the regulation of metabolism through its effect on peripheral tissues. G2548A polymorphism in the LEP gene promoter has been associated with insulin resistance, leptin, and type 2 diabetes mellitus across different population, but has not been inclusively reported within the Malaysian population. Thus, our study aimed to investigate the impact of G2548A polymorphism on serum leptin levels and insulin resistance among Malaysian T2DM patients. This case-control study involved 150 T2DM patients and 150 non-diabetic volunteers from ethnic Malays, Chinese and Indians. Genotyping of G2548A polymorphism was carried out using PCR-RFLP. Serum leptin and insulin levels were determined via ELISA. ANOVA and Chi-square tests were used to determine the distribution of genotypes and allelic frequencies based on serum leptin and insulin levels. Frequency of AA genotype and A allele of G2548A variant were significantly (P < 0.05) higher in T2DM patients of Malay and Indian ethnicities (4%, 35%, and 36%, 57%, respectively) as compared to the control groups (0%, 22%, and 18%, 35%, respectively). Fasting serum leptin levels were significantly (P < 0.001) higher in T2DM patients compared to non-diabetic subjects (166.78 pg/ml, 101.94 pg/ml, respectively). Additionally, elevated serum leptin, insulin levels, and BMI in diabetic patients were found to be associated with the AA genotype of this variant, compared to GG, and GA genotypes (P < 0.05). Our findings suggest a significant association between G2548A polymorphism among Malaysian T2DM subjects, particularly among Malay and Indian ethnic groups. Moreover, the A allele frequency of the G2548A variant significantly increased the risk of T2DM and is significantly associated with increased serum leptin, insulin levels, and elevated BMI.

New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation

BackgroundGlucose cotransporter (SGLT) 2 suppression provides potent renal protective effect during diabetic kidney disease (DKD). This work aimed to explore how empagliflozin (EMPA, the selective and strong inhibitor of SGLT2) affected renal lipid deposition among patients undergoing type 2 diabetes mellitus (T2DM), a T2DM mouse model and human renal proximal tubular epithelial (HK-2) cells.MethodsThis work divided subjects as 3 groups: non-diabetic volunteers, patients treated with metformin and those treated with metformin plus EMPA. In an in vivo study, EMPA was adopted for treating db/db mice that were raised with the basal diet or the high-advanced glycation end products (AGEs) diet. In addition, AGEs and/or EMPA was utilized to treat HK-2 cells in vitro.ResultsResults showed that diabetic patients treated with metformin plus EMPA had lower AGEs levels and renal fat fraction (RFF) than those treated with metformin. Moreover, a significant and positive association was found between AGEs and RFF. Results from the basic study showed that EMPA decreased cholesterol level, tubular lipid droplets, and protein levels related to cholesterol metabolism in AGEs-mediated HK-2 cells, kidneys of db/db mice and those fed with the high-AGEs diet. Additionally, EMPA decreased AGEs levels in serum while inhibiting the expression of receptor of AGEs (RAGE) in vitro and in vivo.ConclusionEMPA inhibited the AGEs-RAGE pathway, thereby alleviating diabetic renal tubular cholesterol accumulation.

The effect of glucagon on local subcutaneous blood flow in non-diabetic volunteers; a proof-of-concept study

IntroductionGlucagon and insulin are the two most important hormones in glucose metabolism and have been incorporated in the dual-hormonal artificial pancreas, a device for automated glucose regulation for people with diabetes type 1. Currently the subcutis is the preferred site of hormone delivery for insulin-only as well as dual-hormonal artificial pancreas systems. The delay in glucose-lowering effect after subcutaneous injection of insulin is substantial, in contrast to the elevation of blood glucose values after subcutaneously injected glucagon which is occurs shortly after injection. We hypothesize that this is caused by properties of glucagon and have investigated the vasodilative effect of glucagon on subcutaneous blood flow in this proof-of-concept study. MethodsTwenty-two volunteers received subcutaneous injections of 0.1 mg and 0.01 mg glucagon, and saline on the abdomen. Blood flow was measured by a laser doppler blood flowmeter for 35 min after injections. ResultsInjection of 0.1 mg glucagon resulted in a significant increase in blood flow compared with baseline blood flow for all time intervals. Significant increase was also observed after the 0.01 mg glucagon injection, except between two- and five-min post injection. The inter-individual variance was large and a third of the subjects did not show an apparent increase in local subcutaneous blood flow after the 0.1 mg glucagon injection. ConclusionThis proof-of-concept study shows that micro-boluses of glucagon increases local subcutaneous blood flow on the abdomen of non-diabetic subjects. However, the vasodilative effect of glucagon is not observed in all subjects. The trial was not registered to protect intellectual property rights.

Employing an “aging paradox” to uncover effective measures for advancing productive longevity

Data gathered from healthy and non-diabetic volunteers who previously had participated in assorted clinical research trials, reveal that many medical risk factors primarily related to insulin resistance (IR) and the metabolic syndrome (MS) gradually intensify between ages 25 and 70 years. This phase here labeled “Continuum of risks” (CR) is a period whereby the metabolic changes that correlate with health situations adjust unfavorably but never exceed nor fall outside ranges that would diagnose established pathological diseases. The strengths of some of these risk factors unexpectedly reverted in an opposite and beneficial direction. This occurred somewhere beyond age 70 years. This phenomenon is defined as “Aging paradox” (AP). Because comparing data from the CR and AP periods did not reveal any significant differences in the glucose-insulin relationships with other components of MS, the beneficial happenings in AP were attributed to “Survivor bias.” The meaning behind this is that those volunteers possessing the more promising profile of risk factors can contribute to clinical studies, while participants with poorer profiles cannot take part as volunteers in later life due to medical debilities or even death. Health-wise, the average values of the following markers changed in a favorable direction when evaluated in the later AP period: Body weight, fat mass, fat free mass, levels of fasting blood glucose (FBG), triglycerides, HDL-cholesterol, and alanine aminotransferase enzyme. The lowering of FBG levels signifies the lessening of IR, the well accepted driving force behind MS. In contrast, total, LDL-, and non-HDL-cholesterol levels as well as systolic blood pressure essentially did not transform favorably over time. Health parameters associated with active survival should be at the center of attention in any developing schema to extend meaningful longevity. Thus, natural regimens involving nutrition, exercise, and dietary supplement usage exist to carry out necessary therapeutic measures to mitigate IR and its disabling components – thus potentially contributing to a longer healthier lifespan.

Axial Length, Anterior Chamber Depth, and Lens Thickness in Normal Libyan Eyes; Measured by the Aladdin Ocular Biometer

Background Ocular parameters as axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) are important for refractive and cataract surgeries, and its normal data are important to be identified. Aim This study was carried out to obtain data about AL, ACD, and LT parameters in normal Libyans. Methods A cross-sectional study (first of July to end of August, 2021) was done in Benghazi teaching eye hospital on 106 nondiabetic volunteers aged between 17 and 75 years with no ophthalmic disease. Ocular parameters were measured using the Aladdin optical biometer that is a noninvasive machine and without the use of drugs. Descriptive statistics and data analysis were done by using SPSS version 23.0, IBM Corporation. Results The mean age was 35.36 ± 13.35 years, the mean AL was 23.79 ± 0.91 mm, the mean ACD was 2.96 ± 0.62 mm, and the mean LT was 3.67 ± 0.62 mm. There was no statistically significant difference between these parameters regarding gender or age. Conclusion This is the first study done on Libyan population to report the AL, ACD, and LT. It showed a comparable result with studies from other populations and that age and gender have no effect on these ocular parameters.

Factors associated with brain white matter damage in type 2 diabetes mellitus: a tract-based spatial statistics study.

The pathogenesis and related factors of central nervous system abnormality in patients with type 2 diabetes mellitus (T2DM) have always been the focus of clinical research. To compare and analyze the area of white matter (WM) damage in patients with T2DM based on their level of hemoglobin A1C (HBA1c) and discuss any related factors. Based on their levels of HBA1c, 87 patients with T2DM were divided into three groups (Group B, C, or D), of which 29 non-diabetic volunteers served as the control group (Group A). DTI data analysis was based on tract-based spatial statistics (TBSS). The obtained parameters were compared among each group and the relevant clinical factors were analyzed. For age, sex, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MoCA) scores, there were no statistically significant differences among groups. For fractional anisotropy (FA) and radial diffusivity (RD) of WM, there were statistically significant differences (P < 0.05, two-tailed, FWE corrected) in the local area of corpus callosum, corona radiate, superior longitudinal fasciculus, etc. Most of these were significantly correlated with body mass index (BMI), left systolic blood pressure (SBP_L), and β2 microglobulin. Before the cognitive function was obviously impaired, abnormalities of FA and RD had been found in the corpus callosum, corona radiate, and upper fasciculus in patients with T2DM, which suggested that the damage mainly occurred in the myelin sheath of WM and may be related to systemic vascular damage.

Impact of type 2 diabetes mellitus on the immunoregulatory characteristics of adipose tissue-derived mesenchymal stem cells.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) represent an emerging type of MSCs with high plasticity and immunoregulatory capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs. We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and protein secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. those derived from non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups. Our data revealed comparable proliferative activities in both groups. Flow cytometric analysis results showed a lower expression of CD200 and CD276 on dAT-MSCs vs. ndAT-MSCs. qPCR demonstrated upregulation of IL-1β associated with a downregulation of IL-1RN in dAT-MSCs vs. ndAT-MSCs. IFN-γ priming induced an elevation in CD274 expression associated with IDO1 and ILRN overexpression and IL-1β downregulation in both groups. ELISA analysis uncovered elevated levels of secreted IL-1β, TNF, and visfatin/NAMPT in dAT-MSCs, whereas IL-1RA and IDO levels were reduced. ELISA results were also evident in the secretome of dAT-MSCs upon IFN-γ priming. This study suggests that the T2DM milieu alters the immunomodulatory characteristics of AT-MSCs with a shift towards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, our findings indicate that IFN-γ priming could be a useful strategy for enhancing dAT-MSC anti-inflammatory potential.

Sonographic Optic Nerve Diameter and Clinical Biomarkers in Patients With Poorly Controlled Diabetes: A Comparative Analysis With Nondiabetic Subjects

Objective: The study assessed optic nerve diameter (OND) and clinical biomarkers in patients with poorly controlled diabetes compared with healthy nondiabetic volunteers. Materials and Methods: There were 1320 adult participants recruited to the study. The cohort was divided into 600 Type 2 diabetic (DM II) patients and 720 apparently healthy, nondiabetic volunteers. The OND was measured using a high-resolution dedicated ultrasound device (Sonoace 5500; Medicol, Medison, Miami, FL, USA) with a 10-MHz linear array transducer. Subjects were examined in a supine position with their eyes closed. Three measurements of the OND were taken and the average recorded. Hemoglobin A1c concentration and lipid profiles were determined using Bio-Rad Diamat analyzer (Bio-Rad, Hercules, CA). Body mass index and age were matched for both cohorts for comparativeness. Results: The mean OND of the DM II patients was 3.10 ± 0.14 mm (range of 2.6–4.0 mm), which was significantly ( P &lt; .05) lower than the control volunteers (4.22 ± 0.15 mm). The OND demonstrated a negative significant correlation with HA1c, duration of diabetes and low-density lipoprotein cholesterol level ( P &lt; .05). Lipid profiles, blood urea, serum creatinine, and hemoglobin A1c showed statistical difference between diabetics and control subjects. Conclusion: Poorly controlled DM II patients may have significantly narrower OND than nondiabetic patients. This imaging biomarker has the potential to transform visual care for DM II patients.

Probing the Relationship Between Declining Renal Glomerular Filtration Over the Life Span and General Biological Aging: Does the Former Provide Means to Estimate the Latter?

Background: While a consistent, gradual decline in the renal glomerular filtration rate (GFR) is a characteristic occurrence over the human life span, the exact pathophysiology behind this event remains unresolved. Evidence to date suggests that the endogenous glucose-insulin system could be involved at some level. Diabetic-induced nephropathy, one of the most prevalent chronic renal diseases, is closely linked to a severe form of insulin resistance (IR). Nevertheless, it is less certain that the ubiquitous milder forms of IR in nondiabetics ascribed customarily to routine, poor choices in diet and exercise management can over time diminish GFR and adversely influence other renal functions to any perceptible extent. Methodology: Baseline data for cross-sectional analyses were obtained from a cohort of healthy, nondiabetic volunteers (fasting blood glucose [FBG] ≤ 125 mg/dL) involved in prior clinical studies. Slope-based rather than threshold analyses were mainly employed. These measurements were applied for the most part to correlate age, FBG levels used as an estimate of IR activity, and systolic blood pressure (SBP) to a variety of metabolic parameters during aging with a primary focus on GFR. Results: Considering cause and effect, FBG and SBP correlate positively with the diminishing GFR over a major part of the life span. The decline in GFR begins somewhere around the mid-20s and coincides with key temporal increases in FBG and SBP levels. Conclusions: A close time-based setting suggests that IR plays a prominent role in the declining GFR that occurs over the life span. This is perhaps due in part through deleterious effects of rising levels of insulin, glucose, and SBP individually or combined that are also popular proposed causative factors for human aging in general. On the philosophical side, the latter fact suggests that the declining GFR might provide a practical way to estimate the rate of overall human biological aging.

Insulin Resistance and Type 2 Diabetes in Asymptomatic Obstructive Sleep Apnea: Results of the PROOF Cohort Study After 7 Years of Follow-Up.

The aim of the study was to assess potential associations between obstructive sleep apnea (OSA) and the occurrence of diabetes mellitus and insulin resistance in the elderly. Nondiabetic volunteers (n = 549) with undiagnosed or untreated asymptomatic OSA (66.2+/−1 years at the inclusion) were evaluated as an ancillary study of the PROOF cohort study (n = 1,011). After 7 years follow-up, 494 subjects underwent assessment of fasting insulin and glucose levels. OSA was defined by an apnea-hypopnea index (AHI) of ≥15/h using polygraphy. Diabetes mellitus was defined by a fasting glucose ≥ 1.26 g/L and/or when requiring pharmacological treatment, while insulin resistance corresponded to HOMA-IR ≥ 2. Asymptomatic OSA subjects (men or women) did not display increased risk of incident diabetes (2.8 vs. 3.9%, p = 0.51). However, there was a greater frequency of insulin resistance in subjects with severe OSA (AHI > 30) [OR 2.21; 95% CI (1.22–4.02); p = 0.009]. Furthermore, multiple logistic regression showed that triglycerides levels [OR 1.61; 95% CI (1.10–2.36); p = 0.01] and fasting glycaemia [OR 4.69; 95% CI (1.12–192.78); p = 0.04], but not AHI or oxyhemoglobin desaturation index were independently associated with higher rate of insulin resistance. The deleterious metabolic effect of asymptomatic OSA in the population may be indirectly mediated via perturbations in lipids, and is particularly likely to become manifest in severe apneic subjects with higher glycemic levels.

Analyzing Blood Pressure Ascent during Aging in Non-Diabetics: Focusing on Links to Insulin Resistance and Body Fat Mass

Background A gradual upward progression of blood pressure (BP) occurs regularly in most humans during aging. This is unfortunate, because it is generally recognized that elevation of BP, even when relatively mild, is eventually detrimental to human health. Accordingly, considerably more understanding of the pathophysiology behind such a phenomenon is important in order to institute the correct remedies. Two components of the ubiquitous metabolic syndrome (MS) with nutritional implications, elevated insulin resistance (IR) and excess body fat mass (FM), are often postulated to be critical driving forces behind the elevated BP that is common with aging. The current study, therefore, focuses on the presence and importance of IR and/or body FM in BP regulation of non-diabetics over the lifespan. Methodology In cross sectional analyses, baseline data obtained from healthy, non-diabetic volunteers involved in prior clinical studies were analyzed by examining links between FBG measurements used as a surrogate for IR and body FM through their individual and combined effects on BP. Results A significant positive correlation was found between FBG and FM and also between each employed individually as independent variables to the dependent BP and heart rate (HR) variables. In volunteers with higher body FM compared to lower, average systolic BP (SBP) values are increased to some extent at the same FBG measurement suggesting that other factors related to FM in addition to IR are the basis for slight pressure differences. Considering quartiles based upon levels of FM and FBG, low FM-low FBG display significantly reduced average SBP, diastolic blood pressure (DBP), and HR compared to the upper FM-FBG quartiles. While readings of FBG and FM display a decline in elderly subjects after age 70 years (aging paradox), such does not occur with SBP. Conclusions IR is a major driving force behind BP regulation even in non-diabetics. FM influences BP substantially through its relationship with IR and also via other mechanisms directly linked to FM.

Assessing Genders Separately in Nondiabetic Persons Regarding Links Between Insulin Resistance and Fat Mass With Elements Related to the Metabolic Syndrome

Objective Initial results gathered from previously published observations dealing with nondiabetic volunteers reveal that both the fasting blood glucose (FBG) level employed as a surrogate for insulin resistance (IR) and the amount of body fat mass (FM) correlate significantly with the strength and pathological direction of many harmful elements making up the metabolic syndrome (MS). These initial results were obtained using combined data from both females and males. How the two markers correlate with specific metabolic parameters in each gender separately was not established. Method Baseline data from more than 700 volunteers were examined mainly using correlations to compare whether the breadth of IR estimated by FBG levels and/or the accumulation of body FM on the early development and progression of many chronic metabolic derangements differ to any meaningful extent between nondiabetic females and males. Results The following significant positive correlations were found in the data on females employing either FBG or FM as independent variables regarding development of elements associated with MS: in body composition (scale weight, fat free mass [FFM]); in blood chemistries (triglycerides, high-sensitivity C-reactive protein [hsCRP], alanine aminotransferase [ALT]); and in blood counts (white blood cells [WBC], neutrophils). Also consistent with MS, high-density lipoprotein cholesterol levels declined significantly. In males, findings with FBG as the independent variable differ from females in some respects. These major exceptions are lack of significant correlations with FFM and high-density lipoprotein cholesterol as well as a weaker link with ALT. Despite a positive hsCRP linkage, a poorer response of WBC and neutrophils appeared in males when correlations were made. The latter disassociations disappeared when FM replaced FBG as the independent variable. Conclusions Progression of many chronic metabolic derangements differ only slightly in females and males.