Euglycemic Participants Research Articles

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus.

BACKGROUND. Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum–filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D).METHODS. We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 μm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples.RESULTS. Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity.CONCLUSION. We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal “third space repository” for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.

Adults with Mycobacterium tuberculosis infection and pre-diabetes have increased levels of QuantiFERON interferon-gamma responses

BackgroundDiabetes is associated with increased prevalence of TB infection in the US. We assessed associations between diabetes and interferon-gamma (IFN-γ) TB antigen response among adults with TB infection using US representative data. MethodsNational Health and Nutrition Examination (NHANES) participants >19 years from 2011 to 2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) results were eligible. Diabetes was defined by combination of self-report and glycated hemoglobin (HbA1c). Quantitative IFN-γ TB antigen was classified as high (≥10 IU/mL), intermediate (1.01–9.99 IU/mL), or low (0.35–1.00 IU/mL). Analyses accounted for NHANES weighted design. ResultsAmong NHANES participants >19 years, n = 513 had positive QFT (5.9%). Among those with positive QFT, diabetes prevalence was 22.2% and pre-diabetes was 25.9%. Overall, 16.7% of positive QFT participants had high IFN-γ TB antigen levels including 21.7% among those with diabetes, 20.8% among those with pre-diabetes, and 12.6% among euglycemic participants. In adjusted analyses, high IFN-γ TB antigen response was more common among those with pre-diabetes (aOR 1.9, 95%CI 1.0, 3.6) compared to euglycemic participants. ConclusionHigher antigen responses may reflect immunopathy consistent with an exaggerated inflammatory but ineffectual response to TB or a reflection of more Mtb replication in participants with pre-diabetes or diabetes.

Differences in Acute Metabolic Responses to Bionic and Nonbionic Ambulation in Spinal Cord Injured Humans and Controls

ObjectivesTo (1) compare energy expenditure during seated rest, standing, and prolonged bionic ambulation or bipedal ambulation in participants with spinal cord injury (SCI) and noninjured controls, respectively, and (2) test effects on postbionic ambulation glycemia in SCI. DesignTwo independent group comparison of SCI and controls. SettingAcademic Medical Center. ParticipantsTen participants with chronic SCI (C7-T1, American Spinal Injury Association Impairment Scale A-C) and 10 controls (N=20). InterventionsA commercial bionic exoskeleton. Main Outcome MeasuresAbsolute and relative (to peak) oxygen consumption, perceived exertion, carbohydrate/fat oxidation, energy expenditure, and postbionic ambulation plasma glucose/insulin. ResultsAverage work intensity accompanying 45 minutes of outdoor bionic ambulation was <40% peak oxygen consumption, with negligible drift after reaching steady state. Rating of perceived exertion (RPE) did not differ between groups and reflected low exertion. Absolute energy costs for bionic ambulation and nonbionic ambulation were not different between groups despite a 565% higher ambulation velocity in controls and 3.3× higher kilocalorie per meter in SCI. Fuel partitioning was similar between groups and the same within groups for carbohydrate and fat oxidation. Nonsignificant (9%) lowering of the area under a glucose tolerance curve following bionic ambulation required 20% less insulin than at rest. ConclusionWork intensity during prolonged bionic ambulation for this bionic exoskeleton is below a threshold for cardiorespiratory conditioning but above seated rest and passive standing. Bionic ambulation metabolism is consistent with low RPE and unchanged fuel partitioning from seated rest. Bionic ambulation did not promote beneficial effects on glycemia in well-conditioned, euglycemic participants. These findings may differ in less fit individuals with SCI or those with impaired glucose tolerance. Observed trends favoring this benefit suggest they are worthy of testing.

Altered Extracellular Vesicle Concentration, Cargo, and Function in Diabetes.

Type 2 diabetes is a chronic age-associated degenerative metabolic disease that reflects relative insulin deficiency and resistance. Extracellular vesicles (EVs) (exosomes, microvesicles, and apoptotic bodies) are small (30-400 nm) lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids as part of intercellular communication systems. Recent studies in mouse models and in cell culture suggest that EVs may modulate insulin signaling. Here, we designed cross-sectional and longitudinal cohorts of euglycemic participants and participants with prediabetes or diabetes. Individuals with diabetes had significantly higher levels of EVs in their circulation than euglycemic control participants. Using a cell-specific EV assay, we identified that levels of erythrocyte-derived EVs are higher with diabetes. We found that insulin resistance increases EV secretion. Furthermore, the levels of insulin signaling proteins were altered in EVs from individuals with high levels of insulin resistance and β-cell dysfunction. Moreover, EVs from individuals with diabetes were preferentially internalized by circulating leukocytes. Cytokine levels in the media and in EVs were higher from monocytes incubated with diabetic EVs. Microarray of these leukocytes revealed altered gene expression pathways related to cell survival, oxidative stress, and immune function. Collectively, these results suggest that insulin resistance increases the secretion of EVs, which are preferentially internalized by leukocytes, and alters leukocyte function.

Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.

The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.

Impaired glucose metabolism moderates the course of illness in bipolar disorder

BackgroundThe longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population. MethodsFifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. ResultsThirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI). LimitationsCross-sectional design, small sample size. ConclusionsComorbid IGM may be a key moderator of illness progression in BD.

Association of Carotid Intima–media Thickness and Atherosclerotic Plaque with Periodontal Status

Studies have suggested an association between clinical/subclinical atherosclerosis and periodontal status. The purpose of this study was to investigate the association among maximal carotid intima–media thickness (cIMT), atherosclerotic plaque, and periodontal status in Chinese elderly patients. A cross-sectional study was conducted of 847 participants (age, 70.64 ± 9.03 yr) with ≥10 teeth. A questionnaire survey, routine biochemical tests, a periodontal examination, and maximal cIMT measurement were performed for each. Traditional risk factors for atherogenesis were considered in the statistical analysis. Mean plaque index, which reflects oral hygiene, was correlated with maximal cIMT and atherosclerotic plaque in the study sample overall (β = 0.068, p < .001; OR = 2.051, p < .001) and in euglycemic participants (β = 0.066, p = .008; odds ratio = 2.122, p = .009). In hyperglycemic participants, multiple linear regression analysis (p = .006) and multivariate logistic regression analysis (p = .025) revealed a linear and dose-dependent association between mean clinical attachment loss and maximal cIMT after adjustment for traditional risk factors. Each 1-mm increase in mean clinical attachment loss corresponded to a 0.018-mm increase in maximal cIMT. The risk of atherosclerotic plaque increased by 18.3% with each 1-mm increase in mean clinical attachment loss. Other indicators of periodontal exposure, including percentage of sites with attachment loss ≥ 3 to 5 mm (3%-5%), were also correlated with cIMT and atherosclerotic plaque in hyperglycemic patients. In this elderly population, a linear and dose-dependent association among mean clinical attachment loss, attachment loss 3% to 5%, maximal cIMT, and atherosclerotic plaque was verified in those with hyperglycemia. Poor oral hygiene was correlated with maximal cIMT and atherosclerotic plaque in all participants, including those with normal blood glucose.

Type 2 Diabetes Mellitus: A Potentially Modifiable Risk Factor for Neurochemical Brain Changes in Bipolar Disorders

BackgroundNeuroimaging changes in bipolar disorder (BD) may be secondary to the presence of certain clinical factors. Type 2 diabetes mellitus (T2DM) damages the brain and frequently co-occurs with BD. Studying patients with both T2DM and BD could help identify preventable risk factors for neuroimaging changes in BD. MethodsWe used 1.5T magnetic resonance spectroscopy to measure prefrontal N-acetylaspartate (NAA), which is mainly localized in neurons, and total creatine (tCr), an energy metabolite, in 19 BD patients with insulin resistance/glucose intolerance (BD + IR/GI), 14 BD subjects with T2DM (BD + T2DM), 15 euglycemic BD participants, and 11 euglycemic, nonpsychiatric control. ResultsThe levels of NAA and tCr were lowest among BD + T2DM, intermediate in the BD + IR/GI, and highest among the euglycemic BD and control subjects (F3,55 = 4.57, p = .006; F3,55 = 2.92, p = .04, respectively). Even the BD + IR/GI subjects had lower NAA than the euglycemic participants (t43 = 2.13, p = .04). Total Cr was associated with NAA (β = .52, t56 = 5.57, p = .000001). Both NAA and tCr correlated with Global Assessment of Functioning scores (r46 = .28, p = .05; r46 = .48, p = .0004, respectively). ConclusionsT2DM, but also prediabetes, may be risk factors for prefrontal neurochemical alterations in BD. These changes were associated with poor psychosocial functioning and could indicate impaired energy metabolism. The findings emphasize the importance of improving diabetes care in BD and suggest potential options for treatment of neuroimaging alterations.

Do colorectal cancer resections improve diabetes in long-term survivors? A case–control study

A clinical study was designed that aimed to analyze whether resection of the large bowel in cancer patients might benefit diabetes mellitus. This prospective case-control study included retrospective information. Patients (n = 247) included diabetic and euglycemic groups with colorectal cancer operations (n = 60), cancer gastrectomy (n = 72), exclusive chemoradiotherapy for rectal cancer (n = 46), and noncancer clinical controls (n = 69). Follow-up periods were, respectively, 79.2 ± 27.4, 86.8 ± 25.1, 70.0 ± 26.3, and 85.1 ± 18.2 months (NS). Diabetes groups included patients with prediabetes. Diabetes remission, defined as conversion from diabetes to prediabetes or from this condition to normal, was documented in, respectively, 32.4 % (11 of 34), 41.2 % (14 of 34), 7.1 % (1 of 14), and 7.7 % (3 of 39) in the four cohorts (P = 0.004). Within the same period, progression of euglycemic participants to diabetes occurred in 30.8 % (8 of 26), 63.2 % (24 of 38), 25.0 (8 of 32), and 20.0 % (6 of 30) (P = 0.028). Diabetes amelioration was associated with weight loss in gastrectomy patients but not in the other groups. Dietary intake, estimated in the two surgical populations, did not predict outcome. Diabetes amelioration after colorectal interventions was demonstrated, but progression of euglycemic patients toward prediabetes was not changed in comparison with nonsurgical controls. It is speculated that reshaping of the bowel microbiome or hormone changes after colorectal interventions underlay the improvement in diabetes. Body weight fluctuations could not be incriminated in this investigation.

Low-grade albuminuria is associated with carotid atherosclerosis in normotensive and euglycemic Chinese middle-aged and elderly adults: The Shanghai Changfeng Study

BackgroundMicroalbuminuria is associated with cardiovascular disease (CVD). We investigated whether low-grade albuminuria (LGA) is independently associated with the carotid intima-media thickness (CIMT) and carotid plaques in normotensive and euglycemic Chinese middle-aged and elderly adults. MethodsA total of 1341 normotensive and euglycemic participants (489 males and 852 females; mean age, 57.7 years) with normal urinary albumin-to-creatinine ratios (UACRs) (＜30 μg/mg) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyzes were performed for each participant. Bilateral CIMTs were measured using ultrasonography, and the presence of carotid plaques was assessed. The urinary albumin excretion rate was measured using an early morning urine sample to determine the UACR. ResultsThe median UACRs were 4.2 (interquartile range, 2.9–6.0) μg/mg and 5.6 (interquartile range, 4.0–8.2) μg/mg for male and female subjects, respectively. Compared with subjects with UACRs in the first and second tertiles, subjects of both genders with UACRs in the third tertile had greater CIMTs. After adjusting for conventional CVD risk factors and the glomerular filtration rate (GFR), male and female participants with UACRs in the third tertile for each gender had a 1.696-fold and 1.911-fold increased risk, respectively, of carotid plaques relative to those in the lowest tertiles. The logUACR was positively associated with the CIMT (β = 0.068 in males, P = 0.001; and β = 0.034 in females, P = 0.012) after adjusting for conventional CVD risk factors and the GFR. The multiple logistic regression analysis showed that a 1-unit increase in the logUACR corresponded to an odds ratio (OR) of having a carotid plaque that was 1.875 (95% confidence interval (CI) 1.103–3.538; P = 0.022) and 2.389 (95% CI 1.244–4.391; P = 0.01) for male and female subjects, respectively, after adjusting for all potential confounders. ConclusionsThese results suggest that the UACR is independently associated with carotid atherosclerosis in normotensive and euglycemic Chinese individuals and that even when well below the current microalbuminuria threshold, LGA contributes to the risk of atherosclerosis.

Central Obesity, the Metabolic Syndrome, and Plasminogen Activator Inhibitor‐1 in Young Adults

To determine the association of central obesity with the components of the metabolic syndrome (i.e., hyperinsulinemia, hypertension, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol [HDL-C]) and plasma levels of plasminogen activator inhibitor-1 (PAI-1) in young adults. We hypothesized that central obesity as determined by waist circumference would be predictive of components of the metabolic syndrome and of PAI-1. Participants in this descriptive study consisted of 85 healthy young adults aged 19-22 years, 62% women who fasted for 12 h prior to data collection in the General Clinical Research Center at a major university hospital medical center in the southeastern United States. The majority of the participants had one or more components of the metabolic syndrome (n= 43, 51%). Central obesity was present in 14.1% and was more common in women than men (chi(2)= 5.11; p= 0.021). Central obesity was significantly and positively correlated with elevated blood pressure (BP) and levels of insulin and PAI-1 while being negatively correlated with HDL-C. In multiple regression analyses, diastolic BP, insulin, and HDL-C were predictors of waist circumference (R(2)= 0.615). In a separate multiple regression, PAI-1 was predicted by waist circumference (R(2)= 0.331). Many otherwise healthy young adults have one or more components of the metabolic syndrome. Assessment and institution of preventative measures for obesity and the components of the metabolic syndrome should begin in childhood. Furthermore, determination of waist circumference especially in young women may aid the practitioner to identify those at risk for the metabolic syndrome earlier in their disease trajectory. Furthermore, insulin resistance is believed to occur initially in the trajectory of the metabolic syndrome, making it a principal contender for suitable interventions to reduce risk for both type 2 diabetes and cardiovascular disease (CVD). Homeostatic model assessment for insulin resistance was used to assess for insulin resistance among the euglycemic participants. Recording the presence of insulin resistance will aid the practitioner in determining if a low-risk patient is in peril for development of type 2 diabetes and/or CVD. Early cardiovascular risk recognition is vital to clinical practice as it allows more time for the practitioner to counsel patients for the essential planning needed to make lifestyle changes.