Glycometabolic Parameters Research Articles

New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.

To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.

Effect of Verapamil on Glycemic Control in Type 2 Diabetic Hypertensive Patients in Saudi Arabia: A Quasi Experimental Study.

Type 2 diabetes is a common chronic disease that continues to increase in prevalence globally and is a major healthcare burden. Diabetes and hypertension frequently occur concurrently, and the use of antihypertensive agents is common in diabetic patients. One antihypertensive agent, verapamil, has tentatively shown potentially positive effects on glycemic control in assorted pre-clinical models. To evaluate the effect of verapamil on glycemic control in hypertensive type 2 diabetic patients. Type 2 diabetic hypertensive patients were recruited from King Fahad Medical City, Riyadh, KSA, to receive oral verapamil therapy. Blood pressure and glycometabolic parameters, including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), C-peptide, and homeostatic model assessment insulin resistance (HOMA-IR), were monitored at baseline and after 6 months of verapamil therapy. Thirty-five patients (16 male, 19 female) with a mean age of 57.2 years were recruited. The use of verapamil was associated with non-significant decreases in HbA1c, FPG, C-peptide, and HOMA-IR. However, a sub-group of 17 participants showed a decrease in HbA1c that was ≥0.5%. Univariate logistic regression showed that baseline BMI, HOMA-IR, and C-peptide were significantly (P < 0.05) associated with HbA1c reductions of ≥0.5%. Verapamil is metabolically neutral and allows the stabilization of glycometabolic parameters in type 2 diabetic individuals. Additional research exploring the mechanism behind the variable response to verapamil therapy is warranted.

3-Day food record: efficacy in patients with type 2 diabetes mellitus.

This study aimed to assess the efficacy of the 3-day food records in monitoring and enhancing dietary habits among patients with type 2 diabetes mellitus. A total of 49 patients with type 2 diabetes mellitus were enrolled, with 38 completing the study. Participants were instructed to record their food intake over 3 consecutive days every 2months. Key anthropometric and glycometabolic parameters, including body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar, were evaluated at baseline and after 6months. The introduction of the 3-day food records led to significant improvements in body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar. Additionally, there was a notable increase in the percentage of patients adhering to the LARN nutritional recommendations, especially concerning the intake of carbohydrates, simple sugars, proteins, fiber, and water. However, adherence to lipid and saturated fat recommendations remained a challenge. The 3-day food records emerges as a valuable tool in the dietary management of patients with type 2 diabetes mellitus. By facilitating real-time monitoring and feedback, it holds promise in enhancing patient adherence to nutritional guidelines, thereby improving key health outcomes.

Hookworm infection induces glycometabolic modulation in South Indian individuals with type 2 diabetes

ObjectivesA number of epidemiological studies have demonstrated that there is an inverse relationship between helminth infections and diabetes mellitus, suggesting that helminth infection may have a positive effect on type 2 diabetes mellitus (T2DM). However, the association between hookworm infection and T2DM has barely been studied. Hence, we aimed to investigate and analyze the interaction and association between hookworm infection and T2DM. MethodsWe examined the effect of hookworm infection on biochemical parameters, including plasma random blood glucose, glycated hemoglobin, and the plasma levels of pancreatic hormones, incretins, and adipokines in individuals with T2DM with (INF, n = 35) or without (UN, n = 35) hookworm infection. Moreover, we re-evaluated these analyte concentrations in a subset of INF individuals 6 months following anthelmintic therapy. ResultsCompared to UN individuals, INF individuals had significantly lowered levels of random blood glucose and glycated hemoglobin. INF individuals also exhibited significantly diminished levels of adiponectin, adipsin, C-peptide, insulin, and glucagon compared to UN individuals. In contrast, INF individuals displayed substantially elevated levels of visfatin and incretins compared to UN individuals. Interestingly, this effect was not seen following anthelmintic treatment. ConclusionOur study findings indicate that concomitant hookworm infection exerts a beneficial effect on glycometabolic parameters in T2DM.

Dynapenia, Muscle Quality, and Hepatic Steatosis in Patients with Obesity and Sarcopenic Obesity

Accumulating evidence supports a connection between sarcopenic obesity (SO) and NAFLD. The extent to which fatty liver contributes to impaired muscle contractility is not yet well established. The aim of our study was to investigate the effect of NAFLD on dynapenia in patients with SO. In this study, 71 non-diabetic subjects (age 55 (7.8) years, BMI 35.2 kg/m2 (32.6-38.8)) were classified as having SO and non-sarcopenic obesity (NSO). SO patients displayed worse serum lipid profiles, higher body fat, and lower skeletal muscle mass (both total and appendicular) than NSO patients, despite the absence of any significant differences in body weight, glycometabolic parameters, and hepatic steatosis prevalence. A positive correlation between disposition index and muscle quality index (MQI) (r = 0.393, p = 0.013) emerged after controlling for menopause and body fat percentage. Based on multiple linear regression analysis, MQI was significantly positively associated with the disposition index (β: 0.059, SE: 0.002, p = 0.006) after adjustment for menopause, body fat percentage, and the presence of hepatic steatosis according to the hepatorenal index (HRI). Similar findings emerged when including liver enzyme levels in place of hepatic steatosis. Muscle quality was positively associated with β-cell function corrected for insulin resistance among patients with obesity and sarcopenic obesity, irrespective of the presence of fatty liver disease.

Gluten-Free Diet and Metabolic Syndrome: Could Be a Not Benevolent Encounter?

Celiac disease is a rising disorder and is becoming frequently diagnosed in recent years. To date, the only available treatment is the gluten-free diet (GFD). The role of gluten on components of metabolic syndrome and on related inflammatory response is still unclear due to controversial results. In recent years, scientific focus on this topic has been growing up, in particular regarding the role of the GFD on glycometabolic parameters and diabetes. In addition, studies on the remaining components showed discordant results, which was likely due to heterogeneous and large celiac disease populations and to the lack of prospective studies. Furthermore, knowledge about the role of the GFD on inflammatory cytokines and the relationship among vitamin D and celiac disease, metabolic syndrome (MS) and GFD is needed. In this narrative review, we provided evidence regarding the role of the GFD on glycometabolic parameters, cholesterol, triglycerides, waist circumference, blood pressure and inflammatory cascade, also evaluating the role of vitamin D, trying to summarize whether this nutritional pattern may be a value-added for subjects with dysmetabolic conditions. Finally, due to the limited findings and very low-certainty evidence, predominantly based on observational studies, the real effects of a GFD on different components of MS, however, are unclear; nevertheless, an improvement in HDL levels has been reported, although data on glycemic levels are discordant.

The Efficacy of Tadalafil and Tadalafil + Dapoxetine in Managing Sexual Dysfunction in Individuals with Type-2 Diabetes Mellitus

Objective: The present study was aimed to evaluate effect of metabolic parameters on erectile dysfunction (ED) in individuals with type-2 diabetes mellitus (T2DM) and to assess the efficacy of Tadalafil and Tadalafil + Dapoxetine combination. Materials and Methods: A prospective, observational, cross-sectional, bicentric study included 216 males with T2DM who are not treated with phosphodiesterase 5 inhibitors and without chronic kidney disease. The data were obtained from demographic questionnaire, clinical laboratory reports of glycometabolic parameters namely body mass index (BMI), hemoglobin A1c (HbA1c), testosterone, vitamin B12 (VitB12), and lipid profile and analyses of the International Index of Erectile Function (IIEF) questionnaire. The effect of physical and metabolic parameters on IIEF sub-domains namely erectile function; orgasmic function; sexual desire (SD); intercourse satisfaction; and overall satisfaction was evaluated. A statistical significance was evaluated using χ 2 test or t-test. Result: SD is most significantly lower in subjects with imbalanced physiological and metabolic characteristics including BMI, HbA1c, testosterone, VitB12, triglyceride, high-density lipoprotein, and low-density lipoprotein. Both Tadalafil and Tadalafil + Dapoxetine significantly improved almost all IIEF parameters without any pronounced effect of either. Similarly, both the treatments improved all the IIEF parameters for subjects with high BMI except for SD. In subjects with cardiac comorbidities, the use of either treatment significantly enhanced all the IIEF scores. Conclusion: The findings of this study outline the need of careful examination of sexual dysfunction in healthcare clinics for diabetic individuals. An imbalanced physiological and metabolic profile leads to ED in individuals with T2DM. Additionally, the presence of co-morbidities further elevates the odds of ED prevalence. The treatment with Tadalafil and Tadalafil + Dapoxetine drug combination shows promising results in improving the ED but a study with larger pool of subjects is needed to determine the additional benefits of Dapoxetine.

Low Skeletal Muscle Mass Accompanied by Abdominal Obesity Additively Increases the Risk of Incident Type 2 Diabetes.

Low skeletal muscle mass often accompanies abdominal obesity in the aging process. We aimed to investigate the effect of reduced skeletal muscle mass and its interaction with abdominal obesity on incident type 2 diabetes. This retrospective longitudinal study included 36 304 diabetes-free Koreans who underwent 2 or more health checkups annually or biannually. Appendicular skeletal muscle mass was measured by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI) adjusted for body weight. Presarcopenia was defined as an SMI less than 1 SD of the sex-specific mean for a healthy young reference group. Abdominal obesity was defined using waist circumference greater than or equal to 90 cm for men and greater than or equal to 85 cm for women. Participants were classified into 4 groups of normal, presarcopenia alone, abdominal obesity alone, and presarcopenic obesity according to initial body composition. The cumulative incidence of diabetes was 9.1% during the 7-year follow-up. Compared with the highest tertile, the lowest sex-specific SMI tertile was significantly associated with a greater risk of incident type 2 diabetes (adjusted hazard ratio [HR] = 1.31; 95% CI, 1.18-1.45) in a fully adjusted model. Presarcopenic obesity significantly increased incident diabetes risk (adjusted HR = 1.57; 95% CI, 1.42-1.73) compared with normal body composition, presarcopenia alone, or abdominal obesity alone. Low skeletal muscle mass and its coexistence with abdominal obesity additively increased the risk of incident type 2 diabetes independent of the glycometabolic parameters.

Olea Europaea Effects on Glyco-Metabolic Parameters and on Glycemic Status in Patients with Impaired Fasting Glucose

Aim: the aim of this study was to evaluate the effects of a food supplement based on an infusion of olive leaves and marigold (Olife®) on glyco-metabolic parameters and glycemic status in patients with impaired fasting glucose (IFG). Material and methods: 148 patients were randomized to follow a standardized diet or a standardized diet plus Olife® for 3 months, in an open label, randomized, controlled study design. Olife® was self-administered, once a day, 70 ml/die (about half water glass), during breakfast in addition to diet. Results: in the group treated with Olife® plus diet there was a significant decrease of fasting and post-prandial plasma glucose after 3 months, both compared to baseline, and to diet group. There was a significant decrease of HOMA index in the group treated with Olife® plus diet, both compared to baseline and to diet. At baseline, all patients were affected by IFG. At the end of the study, 21 of 74 patients (28.3 %) returned to a condition of euglycemia according to OGTT in the Olife® plus diet vs 3 of 74 patients (4.1 %) in the diet group. The group treated with Olife® plus diet had an improvement of LDLox and Hs-CRP levels after 3 months, both compared to baseline, and to diet. Conclusions: the study showed the effects of a food supplement based on an infusion of olive leaves and marigold (Olife®) on glyco-metabolic parameters and glycemic status in patients with IFG.

Long Term Metabolic Effects of Sacubitril/Valsartan in Non-Diabetic and Diabetic Patients With Heart Failure Reduced Ejection Fraction: A Real Life Study.

Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF). HF and type 2 diabetes mellitus (T2DM) frequently coexist, with a prevalence of T2DM of 35%–40% in patients with HF. T2DM is the third co-morbidities in patients with HF and a strong independent risk factor for the progression of HF. In a post hoc analysis of PARADIGM-HF, improved glycemic control was shown in patients with T2DM and HFrEF receiving sac/val compared to enalapril at 12 months of follow-up. The aim of the present study was to evaluate, in a series of repeated observations in 90 HFrEF patients, the long term effect of sac/val treatment on renal function, glycometabolic state and insulin sensitivity parameters, according to diabetic status. We studied 90 patients (74 men and 16 women, mean age 68 ± 10 years, 60 diabetics and 30 non-diabetics) suffering from HFrEF and still symptomatic despite optimal pharmacological therapy. Patients with left ventricular ejection fraction (LVEF) <35% and II-III NYHA functional class were enrolled. All patients underwent clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 30 months to evaluate benefits and adverse events. After 30 months follow-up, we observed a significant improvement in glycometabolic parameters including HbA1c, fasting glucose and insulin, insulin-like growth factor-1 (IGF-1), HOMA index, and LDL cholesterol. Moreover, renal function, NTpro-BNP levels and echocardiographic parameters significantly improved. In diabetic patients a significant reduction in use of oral antidiabetic drugs and insulin was observed after 30 months of sac/val treatment. In the whole population, multivariate analysis shows that the evolution of cardiac index (CI) was significantly associated to simultaneous changes in HOMA, IGF-1 and visit; per each visit and for 1 ng/ml increase in IGF-1 there was an increase in CI of 64.77 ml/min/m2 (p < 0.0001) and 0.98 ml/min/m2 (p = 0.003), respectively, whereas 1 point increase in HOMA was associated with a −7.33 ml/min/m2 (p = 0.003) reduction in CI. The present data confirm persistent metabolic improvement in patients with HFrEF after treatment with sac/val and highlights its potential therapeutical role in patients with metabolic comorbidities.

Ameliorating Metabolic Profiles After Kidney Transplantation: A Protocol for an Open-Label, Prospective, Randomized, 3-Arm, Controlled Trial.

Aim: High prevalence of metabolic disorders causes higher risk of cardiovascular diseases after kidney transplantation (KT), which remains the main burden impairing short-term and long-term survival. This open-label, prospective, randomized, 3-arm, controlled trial will evaluate the safety, tolerability and efficacy of metformin and empagliflozin in ameliorating metabolic profiles after KT.Methods: After a screening assessment, eligible patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 are randomly assigned to standard triple immunosuppression alone, standard immunosuppression plus metformin (500 mg twice daily), standard immunosuppression plus empagliflozin (25 mg once daily) from discharge. The primary endpoint is the differences in the visceral-to-subcutaneous fat area ratio over 12 months, evaluated by magnetic resonance imaging (MRI). Secondary outcomes include kidney graft function, glycometabolism, lipid metabolism, and inflammatory parameters. The trial will enroll 105 kidney transplant recipients, providing 90% power to detect the difference at 5% significance.

Abnormal glucose metabolism is associated with clinical symptoms of adolescent-onset patients with first-episode drug-naive schizophrenia.

Extensive studies have reported alterations in glucose metabolism in adult-onset patients with schizophrenia, but less attention has been paid to adolescent-onset patients with first-episode drug-naive (FEDN) schizophrenia. The purpose of this study was to compare glucose metabolism between adolescent-onset patients with FEDN schizophrenia and healthy controls and to investigate the relationship between glucose metabolism and clinical symptoms in patients with schizophrenia. This study compared the glycometabolism parameters between 51 adolescents-onset patients with FEDN schizophrenia and 51 age- and sex-matched healthy controls. The Chinese version of the Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale were used to assess patients' psychiatric, anxiety, and depressive symptoms. The results showed that compared with healthy controls, the patients had a significantly higher prevalence of impaired fasting glucose and insulin resistance, as well as higher fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and triglycerides, but lower high-density lipoprotein cholesterol levels. Moreover, HOMA-IR was negatively associated with PANSS general psychopathology, while glucose was positively correlated with depressive symptoms among patients. In sum, adolescent-onset patients with FEDN schizophrenia are more likely to have abnormal glucose metabolism and dyslipidemia than their healthy counterparts. Moreover, abnormal glucose metabolism may be closely related to the psychopathological symptoms of schizophrenia in the early stage of the disease.

Postprandial glucose and HbA1c are associated with severity of obstructive sleep apnoea in non-diabetic obese subjects

IntroductionObstructive sleep apnoea (OSA) is an underdiagnosed condition frequently associated with glycaemic control impairment in patients with type 2 diabetes.AimTo assess the relationship between glycometabolic parameters and OSA in obese non-diabetic subjects.MethodsNinety consecutive subjects (mean age 44.9 ± 12 years, mean BMI 42.1 ± 9 kg/m2) underwent polysomnography and a 2-h oral glucose tolerance test (OGTT).ResultsOSA was identified in 75% of subjects, with a higher prevalence of males compared to the group of subjects without OSA (62% vs 32%, p = 0.02). Patients with OSA had comparable BMI (42.8 kg/m2 vs 39.4 kg/m2), a higher average HbA1c (5.8% vs 5.4%, p < 0.001), plasma glucose at 120 min during OGTT (2 h-PG; 123 mg/dl vs 97 mg/dl, p = 0.009) and diastolic blood pressure (81.1 mmHg vs 76.2 mmHg, p = 0.046) than obese subjects without OSA. HbA1c and 2 h-PG were found to be correlated with the apnoea-hypopnoea index (AHI; r = 0.35 and r = 0.42, respectively) and with percent of sleep time with oxyhaemoglobin saturation < 90% (ST90; r = 0.44 and r = 0.39, respectively). Further, in a linear regression model, ST90 and AHI were found to be the main determinants of 2 h-PG (β = 0.81, p < 0.01 and β = 0.75, p = 0.02, respectively) after controlling for age, sex, waist circumference, physical activity, and C-reactive protein. Similarly, ST90 and AHI persisted as independent determinants of HbA1c (β = 0.01, p = 0.01 and β = 0.01, p = 0.01, respectively).ConclusionBeyond the traditional clinical parameters, the presence of a normal-high value of 2 h-PG and HbA1c should raise suspicion of the presence of OSA in obese subjects.

COL1A1 as a potential new biomarker and therapeutic target for type 2 diabetes

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC–MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

Change in skeletal muscle mass is associated with lipid profiles in female rheumatoid arthritis patients -TOMORROW study-

To examine the relationship between changes in skeletal muscle mass and lipid metabolism and glycometabolism in patients with rheumatoid arthritis (RA). Data were analyzed from 148 female RA patients and 145 age-matched non-RA (control) female subjects from a prospective cohort study (TOMORROW; TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality study). Appendicular skeletal muscle mass (ASM) was assessed using dual-energy x-ray absorptiometry and skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. The reference value for SMI in Asian women, 5.4kg/m2, was used to define low SMI. Data were assessed using cross-sectional (2010 baseline data) and longitudinal (change in value from 2010 to 2013) methods from the retrospective cohort. At baseline in RA patients, the low SMI group showed significantly higher low-density lipoprotein cholesterol (LDL-chol) (p=0.015), apolipoprotein (Apo)B (p=0.046), and ApoB-to-A1 (ApoB/A1) (p=0.025) than the normal SMI group. In multiple regression analysis of RA patients, sequential changes from 2010 to 2013 (Δ) in SMI and ApoB and ApoC2 showed significant negative relationships (β=-0.19,-0.18, respectively) even after adjusting for age, RA duration, exercise habits, medication for RA, disease severity, activities of daily living (ADL) and body fat mass. No significant relation was evident between ΔSMI and various glycometabolism parameters in RA patients. Skeletal muscle mass might be related to lipid metabolism in RA patients. This relationship is independent of factors such as disease severity and body fat mass.

Impact of Genetic Predisposition on Glyco-Metabolic Side Effects of TKIs in CML

Introduction: since the introduction of tyrosine kinase inhibitors (TKIs), the survival of chronic myeloid leukemia (CML) patients has sharply increased. Three generation of TKIs with different toxicity profiles, including glyco-metabolic alterations (i.e. diabetes mellitus [DM] and impaired fasting glucose [IFG]), are currently available in clinical practice. The risk of developing type 2 diabetes (T2D) reflects the joint effect of genetic predisposition and relevant environmental exposure; genome-wide association studies (GWAS) have identified more than sixty single nucleotide polymorphisms (SNPs) associated with this risk. Aim: to explore the impact of different TKIs on the development of T2D, especially in relation to the presence of those SNPs showed to have a major involvement in T2D insurgence. Methods: the study includes 25 consecutive patients affected by CML, who have been treated in first line with continuous TKI therapy (imatinib, dasatinib, or nilotinib) for at least 6 months (mean 54 months, range 8-86). Anthropometric and glyco-metabolic parameters were collected at start of therapy and during last follow-up visit or at switch of therapy. Moreover, we genotyped 17 SNPs in which one of the two alleles has been associated with greater susceptibility to T2D (rs10490072, BCL11A; rs10811661, CDKN2A/2B; rs10923931, NOTCH2; rs1111875, HHEX; rs1801282, PPARG; rs4402960, IGFBP2, rs4607103, ADAMTS9; rs5219, KCNJ11; rs7578597, THADA; rs7903146, TCF7L2; rs7961581, TSPAN8/LGR5; rs864745, JAZF1, rs9472138, VEFGA; rs9939609, FTO; rs1153188, DCD; rs12779790, CDC123/CAMK1D; rs7754840, CDKAL). The Wilcoxon singed-rank test was used to determine the impact of each TKI on glyco-metabolic parameters, whereas the comparison among imatinib, dasatinib, and nilotinib was studied through the Kruskal-Wallis test with post-hoc pairwise comparisons. The latter was also used to analyze the impact of risk alleles of each SNPs on clinical parameters. Statistical analyses were conducted using IBM SPSS Statistics for Macintosh, Version 26.0. Armonk, NY: IBM Corp. Results: among our study population, 13 (52%) patients were males and the median age at CML diagnosis was 57 years (range, 33-86). Nine (36%) were taking imatinib, 8 (32%) dasatinib, and 8 (32%) nilotinib. Our analysis showed that all TKIs significantly increased glycemic levels (Figure 1), however without reaching the criteria for T2D onset. Furthermore, when analyzing SNPs associated with greater T2D susceptibility (Lyssenko V et al. N Engl J Med 2008), most of the patients (22/25, 88%) had been found to bear more than 12 risk alleles (median 16, range 11-20), so being at higher risk of T2D insurgence. Nevertheless, the effect of the analyzed TKIs on T2D development was not worsened by the presence of these risk alleles. Besides, nilotinib interestingly demonstrated an effect on total cholesterol and LDL level increase (p=0.012 and p=0.017, respectively). Conclusions: despite the limited size of the cohort, our data suggest that imatinib, dasatinib, and nilotinib similarly does not influence the emergence of T2D, neither when considering the several SNPs known to be clinically related to this comorbidity. Besides, a significant correlation between TKIs administration and glycemic level increase has emerged together with nilotinib influence on other metabolic parameters (i.e. total cholesterol and LDL), confirming similar results of previous studies. Therefore, in clinical practice, glycemic state should not preclude the use of any TKIs, but close monitoring of glyco-metabolic alterations is fundamental to promptly identify any glycemic or lipidic alteration. Updated data with new analyses will be presented later. Disclosures No relevant conflicts of interest to declare.

Obesity Does Not Modulate the Glycometabolic Benefit of Insoluble Cereal Fibre in Subjects with Prediabetes-A Stratified Post Hoc Analysis of the Optimal Fibre Trial (OptiFiT).

Obesity does not modulate the glycometabolic benefit of insoluble cereal fibre in subjects with prediabetes—a stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT). Background: OptiFiT demonstrated the beneficial effect of insoluble oat fibres on dysglycemia in prediabetes. Recent analyses of OptiFiT and other randomised controlled trials (RCTs) indicated that this effect might be specific for the subgroup of patients with impaired fasting glucose (IFG). As subjects with IFG are more often obese, there is a need to clarify if the effect modulation is actually driven by glycemic state or body mass index (BMI). Aim: We conducted a stratified post hoc analysis of OptiFiT based on the presence or absence of obesity. Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomised in a double-blinded fashion to either twice-a-day fibre or placebo supplementation for 2 years (n = 89 and 91, respectively). Once a year, they underwent fasting blood sampling, an oral glucose tolerance test (oGTT) and full anthropometry. At baseline, out of 136 subjects who completed the first year of intervention, 87 (62%) were classified as OBESE (BMI >30) and 49 subjects were NONOBESE. We performed a stratified per-protocol analysis of the primary glycemic and secondary metabolic effects attributable to dietary fibre supplementation after 1 year of intervention. Results: Neither the NONOBESE nor the OBESE subgroup showed significant differences between the respective fibre and placebo groups in metabolic, anthropometric or inflammatory outcomes. None of the four subgroups showed a significant improvement in either fasting glucose or glycated haemoglobin (HbA1c) after 1 year of intervention and only OBESE fibre subjects improved 2 h glucose. Within the NONOBESE stratum, there were no significant differences in the change of primary or secondary metabolic parameters between the fibre and placebo arms. We found a significant interaction effect for leukocyte count (time × supplement × obesity status). Within the OBESE stratum, leukocyte count and gamma-glutamyl transferase (GGT) levels decreased more in the fibre group compared with placebo (adjusted for change in body weight). Comparison of both fibre groups revealed that OBESE subjects had a significantly stronger benefit with respect to leukocyte count and fasting C-peptide levels than NONOBESE participants. Only the effect on leukocyte count survived correction for multiple comparisons. In contrast, under placebo conditions, NONOBESE subjects managed to decrease their body fat content significantly more than OBESE ones. Intention-to-treat (ITT) analysis resulted in similar outcomes. Conclusions: The state of obesity does not relevantly modulate the beneficial effect of cereal fibre on major glycometabolic parameters by fibre supplementation, but leukocyte levels may be affected. Hence, BMI is not a suitable parameter to stratify this cohort with respect to diabetes risk or responsiveness to cereal fibre, but obesity needs to be accounted for when assessing anti-inflammatory effects of fibre treatments. Targeted diabetes prevention should focus on the actual metabolic state rather than on mere obesity.

BuZangTongLuo decoction improved hindlimb ischemia by activating angiogenesis and regulating gut microbiota in diabetic mice.

Seven traditional medicinal plants (including Astragalus membranaceus, Dioscorea hemsleyi, Salvia miltiorrhiza, Scrophularia ningpoensis, Ophiopogon japonicus, Panax ginseng and Fritillariae cirrhosae) and one insect leech (Whitmania pigra Whitman) were combined into BuZangTongLuo formula (BZTLF) under the guidance of traditional Chinese medicine. BZTLF is potentially effective against diabetic vascular complications. Previous studies failed to clarify the molecular mechanism through which BZTLF suppressed diabetic ischemia. In this study, we aimed to explore whether BZTLF treatment could prevent the occurrence of type 2 diabetic (T2D) hindlimb ischemia in mice. Further, we investigated the regulatory effect of BZTLF on angiogenesis-related VEGF signaling pathway and gut microbiota dysfunction in diabetic ischemia mice. C57BL/6J mice fed with high-fat diet (HFD) received STZ injection and femoral artery ligation to build T2D diabetic hindlimb ischemia model. Mice were gavaged with BZTLF (5 g [raw materials]/kg/d) or with metformin plus atorvastatin for three weeks. Laser doppler imaging system was utilized for the visualization of blood flow. Histochemistry analysis was performed for microvascular vessel staining. Western blot was applied to detect the protein changes of signaling molecules responsible for VEGF pathway. Finally, 16S rDNA gene sequencing was conducted for analysis of gut microbiota structure. BZTLF treatment remarkably restored blood flow and capillary density of diabetic hindlimb ischemia. And the protein changes of VEGF signaling molecules were reversed in BZTLF-treated diabetic ischemia mice, including the decreased VEGF and HIF-1α, and the increased NO, eNOS and p-ERK1/2. The gut microbiota analysis suggests that BZTLF treatment increased the abundances of several beneficial bacteria (Akkermansia, Bifidobacterium and Bacteroides), while decreased the populations of some harmful bacteria(Blautia, Weissella, Escherichia Shigella and Kurthia). By using Spearman's correlation analysis, these changed gut flora were positively/negatively correlated with VEGF signaling pathway or glycometabolic parameters. BZTLF displayed beneficial effects on diabetic hindlimb ischemia by reshaping the gut microbiota structure and stunning the VEGF/HIF-1α pathway.

Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and 18F-Fluorodeoxyglucose Accumulation Data.

Purpose:The aim of this study was to generate a multivariate model using various MRI markers of blood flow and vascular permeability and accumulation of 18F-fluorodeoxyglucose (FDG) to predict the extent of hypoxia in an 18F-fluoromisonidazole (FMISO)-positive region.Methods:Fifteen patients aged 27–74 years with brain tumors (glioma, n = 13; lymphoma, n = 1; germinoma, n = 1) were included. MRI scans were performed using a 3T scanner, and dynamic contrast-enhanced (DCE) perfusion and arterial spin labeling images were obtained. Ktrans and Vp maps were generated using the DCE images. FDG and FMISO positron emission tomography scans were also obtained. A model for predicting FMISO positivity was generated on a voxel-by-voxel basis by a multivariate logistic regression model using all the MRI parameters with and without FDG. Receiver-operating characteristic curve analysis was used to detect FMISO positivity with multivariate and univariate analysis of each parameter. Cross-validation was performed using the leave-one-out method.Results:The area under the curve (AUC) was highest for the multivariate prediction model with FDG (0.892) followed by the multivariate model without FDG and univariate analysis with FDG and Ktrans (0.844 for all). In cross-validation, the multivariate model with FDG had the highest AUC (0.857 ± 0.08) followed by the multivariate model without FDG (0.834 ± 0.119).Conclusion:A multivariate prediction model created using blood flow, vascular permeability, and glycometabolism parameters can predict the extent of hypoxia in FMISO-positive areas in patients with brain tumors.

Increased plasmatic NETs by-products in patients in severe obesity

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients’ systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET’s dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.