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Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
Afghahi, H, Nasic, S, Peters, B, Rydell, H, Hadimeri, H, Svensson, J
PloS one. 2022;(1):e0262880
Abstract
BACKGROUND The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD. METHODS 325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses. RESULTS During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death. CONCLUSION The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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Alternative pre-analytic sample handling techniques for glucose measurement in the absence of fluoride tubes in low resource settings.
Nakanga, WP, Balungi, P, Niwaha, AJ, Shields, BM, Hughes, P, Andrews, RC, Mc Donald, TJ, Nyirenda, MJ, Hattersley, AT
PloS one. 2022;(2):e0264432
Abstract
INTRODUCTION Sodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda. METHODS Random (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis. RESULTS Rapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours. CONCLUSION In low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity.
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Precision Nutrition Model Predicts Glucose Control of Overweight Females Following the Consumption of Potatoes High in Resistant Starch.
Nolte Fong, JV, Miketinas, D, Moore, LW, Nguyen, DT, Graviss, EA, Ajami, N, Patterson, MA
Nutrients. 2022;(2)
Abstract
Individual glycemic responses following dietary intake result from complex physiological processes, and can be influenced by physical properties of foods, such as increased resistant starch (RS) from starch retrogradation. Predictive equations are needed to provide personalized dietary recommendations to reduce chronic disease development. Therefore, a precision nutrition model predicting the postprandial glucose response (PPGR) in overweight women following the consumption of potatoes was formulated. Thirty overweight women participated in this randomized crossover trial. Participants consumed 250 g of hot (9.2 g RS) or cold (13.7 g RS) potatoes on two separate occasions. Baseline characteristics included demographics, 10-day dietary records, body composition, and the relative abundance (RA) and α-diversity of gut microbiota. Elastic net regression using 5-fold cross-validation predicted PPGR after potato intake. Most participants (70%) had a favorable PPGR to the cold potato. The model explained 32.2% of the variance in PPGR with the equation: 547.65 × (0 [if cold, high-RS potato], ×1, if hot, low-RS potato]) + (BMI [kg/m2] × 40.66)-(insoluble fiber [g] × 49.35) + (Bacteroides [RA] × 8.69)-(Faecalibacterium [RA] × 73.49)-(Parabacteroides [RA] × 42.08) + (α-diversity × 110.87) + 292.52. This model improves the understanding of baseline characteristics that explain interpersonal variation in PPGR following potato intake and offers a tool to optimize dietary recommendations for a commonly consumed food.
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Association of Serum Alkaline Phosphatase with the TG/HDL Ratio and TyG Index in Korean Adults.
Son, DH, Ha, HS, Lee, YJ
Biomolecules. 2021;(6)
Abstract
Alkaline phosphatase (ALP) has long been considered a marker of hepatobiliary and bone disorders, but recent studies have shown that increased ALP activity is correlated with various cardio-metabolic diseases. Thus, we investigated the association of serum ALP level with surrogate markers of insulin resistance such as triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C ratio) and triglyceride and glucose (TyG) index in the general population. The study included 12,868 men and women aged 19 years and older. Participants were categorized into four groups based on serum ALP level (U/L) as follows: Q1: 55-190 U/L, Q2: 191-224 U/L, Q3: 225-265 U/L, and Q4: 266-923 U/L for men, Q1: 48-161 U/L, Q2: 162-198 U/L, Q3: 199-245 U/L, Q4: 246-790 U/L for women. The insulin resistance cut-off levels were defined corresponding to the 75th percentile of the TyG index and TG/HDL-C ratio in the current samples. Odds ratios (ORs) with 95% confidence intervals (CIs) of insulin resistance according to quartile of serum ALP level were calculated using weighted multivariate logistic regression analysis. Compared with Q1, the adjusted OR (95% CI) for insulin resistance of the Q4 serum ALP group was 1.517 (1.234-1.866) in men and 1.881 (1.399-2.528) in women using the TG/HDL-C ratio and 1.374 (1.093-1.728) in men and 2.047 (1.468-2.855) in women using the TyG index after adjusting for confounding variables. Serum ALP levels are independently and positively associated with surrogate markers of insulin resistance in Korean adults.
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Correlation between hyperglycemia and glycated albumin with retinopathy of prematurity.
Almeida, AC, Silva, GA, Santini, G, Brízido, M, Correia, M, Coelho, C, Borrego, LM
Scientific reports. 2021;(1):22321
Abstract
To determine the association between hyperglycemia, glycated albumin (GlyA) and retinopathy of prematurity (ROP). Prospective study of all infants under ROP screening from March 2017 to July 2019. All demographic, clinical and laboratory data were collected. Glucose was measured at birth and every 8 h for the first week and serum GlyA was evaluated at birth, 1st, 2nd and 4th weeks after birth. Reference range for GlyA was obtained. Univariate logistic regression was used to examine risk factors for ROP followed by multivariate regression. A total of 152 infants were included in the study. Median gestational age was 30 weeks and median birth weight 1240 g. Thirty-three infants (21.7%) had ROP. Hyperglycemia was present in 24 (72.7%) infants diagnosed with any ROP versus 6 (0.05%) in those without ROP. Median GlyA at birth, 1st, 2nd and 4th and respective reference ranges were 8.50% (6.00-12.65), 8.20% (5.32-11.67), 8.00% (5.32-10.00) and 7.90% (5.30-9.00) respectively. After multivariate logistic regression, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors (Exp (B) 28.062, 95% CI for Exp(B) 7.881-99.924 p < 0.001). In our cohort, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors.
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Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes.
Mezza, T, Ferraro, PM, Di Giuseppe, G, Moffa, S, Cefalo, CM, Cinti, F, Impronta, F, Capece, U, Quero, G, Pontecorvi, A, et al
The Journal of clinical investigation. 2021;(12)
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Abstract
BACKGROUNDThe appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of β cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting β cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of β cell mass, on the subsequent development of hyperglycemia.METHODSTo pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM).RESULTSAt baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes.CONCLUSIONDespite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM).TRIAL REGISTRATIONClinicalTrials.gov NCT02175459.FUNDINGUniversità Cattolica del Sacro Cuore; Italian Ministry of Education, University and Research; European Foundation for the Study of Diabetes.
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The acute effects of vinyasa flow yoga on vascular function, lipid and glucose concentrations, and mood.
Piña, AA, Shadiow, J, Tobi Fadeyi, A, Chavez, A, Hunter, SD
Complementary therapies in medicine. 2021;:102585
Abstract
While the chronic effects of certain styles of yoga on cardiometabolic factors have been investigated, little is known about the acute effects of a single yoga session on these outcomes. Moreover, vinyasa yoga's potential to modulate cardiometabolic outcomes has not been established. The purpose of this study is to determine the acute effects of a vinyasa yoga session on arterial stiffness, wave reflection, lipid and glucose concentrations, and mood in adults with prior yoga experience. Thirty yoga practitioners with a minimum of 3 months of practice experience were enrolled into the study. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), lipid profile, glucose concentrations, and mood (Positive and Negative Affect Scale) were assessed at baseline and immediately following a 1 -h vinyasa yoga session. After the yoga session, participants had significantly lower AIx (p < 0.001), non-HDL cholesterol (p < 0.05), and negative affect (p < 0.01) compared to baseline. These results highlight the efficacy of a single bout of yoga in altering wave reflection while improving mood and lipid concentrations in healthy adults with a history of yoga practice.
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Statins Are Associated With Increased Insulin Resistance and Secretion.
Abbasi, F, Lamendola, C, Harris, CS, Harris, V, Tsai, MS, Tripathi, P, Abbas, F, Reaven, GM, Reaven, PD, Snyder, MP, et al
Arteriosclerosis, thrombosis, and vascular biology. 2021;(11):2786-2797
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OBJECTIVE Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. APPROACH AND RESULTS We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). CONCLUSIONS In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.
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Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study.
Jeong, JH, Jung, S, Kim, KN
Scientific reports. 2021;(1):3333
Abstract
Emerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545-2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263-2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.
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First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas.
Fujimoto, H, Fujita, N, Hamamatsu, K, Murakami, T, Nakamoto, Y, Saga, T, Ishimori, T, Shimizu, Y, Watanabe, H, Sano, K, et al
Frontiers in endocrinology. 2021;:717101
Abstract
Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic β cells.