Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

A comparative study of metabolic profile in pre-eclampsia and normotensive preterm pregnancy

Background: Hypertensive disorders of pregnancy are important and common cause of severe acute morbidity, long-term disability and death among mothers and babies. The metabolic characteristics (hypertriglyceridemia, hyperinsulinemia, hyperuricemia, low HDL2 cholesterol) in pregnancy-induced hypertension resemble the main features of the “insulin resistance syndrome”. This may result in endothelial cell dysfunction as evidenced by PGI2 suppression. We have designed this study with an objective to compare the metabolic parameters like fasting and post prandial blood glucose, fasting plasma insulin, HOMA-IR and lipid profile between pre-eclampsia and normotensive pregnant women at late preterm (32-36 weeks).Methods: Based on enrolment criteria and statistical analysis 224 patients were enrolled in study during study period and divided in to two groups, group 1- normotensive subjects, group2- pre-eclampsia subjects. Various biochemical parameters and obstetric profile was measured and compared with standard normotensive subjects.Results: The mean fasting plasma insulin was significant higher in group 2 than group 1 (18.36±6.48 mIU/dl versus 3.42±1.68 mIU/dl) (p=0.0001). The mean value of HOMA-IR was significant higher in group 2 than group 1 (3.82±1.68 versus 1.98±1.68) (p=0.0001). The mean value of HDL was significant higher in group 1 than group 2 (42.56±3.28 mg/dl versus 34.26±3.63 mg/dl) (p=0.0001). The mean concentration of LDL was significant higher in group 2 than group 1 (142.23±24.36 mg/dl vrsus 84.32±18.24 mg/dl) (p=0.0001).Conclusions: Systolic and diastolic blood pressure was significantly higher in preeclampsia patients and plasma fasting glucose was higher in normotensive subjects. In present study fasting plasma insulin and HOMA-IR are significantly higher in cases then control. Dyslipidemia is significantly evident in preeclampsia patients in our study.

Objectively Measured Physical Activity Is Associated With Body Composition and Metabolic Profiles of Pacific and New Zealand European Women With Different Metabolic Disease Risks

Objective: To assess associations between physical activity (PA), body composition, and biomarkers of metabolic health in Pacific and New Zealand European (NZE) women who are known to have different metabolic disease risks.Methods: Pacific (n = 142) or NZE (n = 162) women aged 18–45 years with a self-reported body mass index (BMI) of either 18.5–25.0 kg⋅m–2 or ≥30.0 kg⋅m–2 were recruited and subsequently stratified as either low (<35%) or high (≥35%) BF%, with approximately half of each group in either category. Seven-day accelerometery was used to assess PA levels. Fasting blood was analysed for biomarkers of metabolic health, and whole body dual-energy X-ray absorptiometry (DXA) was used to estimate body composition.Results: Mean moderate-to-vigorous physical activity (MVPA; min⋅day–1) levels differed between BF% (p < 0.05) and ethnic (p < 0.05) groups: Pacific high- 19.1 (SD 15.2) and low-BF% 26.3 (SD 15.6) and NZE high- 30.5 (SD 19.1) and low-BF% 39.1 (SD 18.4). On average Pacific women in the low-BF% group engaged in significantly less total PA when compared to NZE women in the low-BF% group (133 cpm); no ethnic difference in mean total PA (cpm) between high-BF% groups were observed: Pacific high- 607 (SD 185) and low-BF% 598 (SD 168) and NZE high- 674 (SD 210) and low-BF% 731 (SD 179). Multiple linear regression analysis controlling for age and deprivation showed a significant inverse association between increasing total PA and fasting plasma insulin among Pacific women; every 100 cpm increase in total PA was associated with a 6% lower fasting plasma insulin; no significant association was observed in NZE women. For both Pacific and NZE women, there was an 8% reduction in fasting plasma insulin for every 10-min increase in MVPA (p ≤ 0.05).Conclusion: Increases in total PA and MVPA are associated with lower fasting plasma insulin, thus indicating a reduction in metabolic disease risk. Importantly, compared to NZE, the impact of increased total PA on fasting insulin may be greater in Pacific women. Considering Pacific women are a high metabolic disease risk population, these pre-clinical responses to PA may be important in this population; indicating promotion of PA in Pacific women should remain a priority.

Potential triggers of atrial fibrillation in type 2 diabetes mellitus

Introduction. Atrial fibrillation is an irregular heartbeat that accelerates to form blood clots in the chambers of the heart and leads to stroke, heart failure, and other cardiovascular complications. Diabetes mellitus itself has been identified as a risk factor for atrial fibrillation, but the association between them is unclear. Material and methods. We analyzed 70 patients with type 2 insulin non-dependent diabetes mellitus. All patients were examined in parallel continuous glucose (CGM) and ECG for 14 days. The study population divided into documented atrial fibrillation (AF group, n = 16) and without atrial fibrillation (non-AF group, n = 54) groups. We assessed the relationship between hypoglycemia, fasting plasma insulin, insulin resistance using the homeostatic model assessment (HOMA-IR) equation, and the incidence of atrial fibrillation. Results. We found a total of 46 episodes of documented atrial fibrillation (AF be defined as an arrhythmia lasting ≥ 30 seconds) lasted on the whole 596.9 minute, which was the most significant by the number (2.87 ± 2.05 per patient, p < 0.0001) or the time (31.31 ± 16.57 min per patient, p < 0.0001). We also compared the incident rate of different types of atrial premature complexes between two groups. We found a maximum of 642.6 ± 567.2 single PACs per patient in the AF group, compared to 84.6 ± 87.9, p = 0.002. Despite this, there were significant differences by the following parameters: couplet PACs (p = 0.0015) and triplet or > 3 PACs (p = 0.0007). Over 14 days, a total of 263 hypoglycemic episodes or 5135 min hypoglycemic time were detected, the average number and time of hypoglycemic episodes were 8.0 ± 4.94 per person and 137.0 ± 63.17 min in AF group, and 2.5 ± 4.64 per person (p = 0.0001), 54.5 ± 67.3 min (p = 0.004) in the non-AF group. There was a statistically significant (p < 0.0001) association between FPI and incident AF, more exactly, the mean level of FPI was 31 ± 6.1 mlU/L in the AF group, whereas was 11.3 ± 4.07 in the non-AF group. When we measured the HOMA-IR index by using the homeostasis model, we found significant differences between AF and non-AF groups (11.2 ± 3.88 mmol/l vs. 4.3 ± 1.66 mmol/l, p < 0.0001). Conclusion. The parallel recording of continuous glucose and ECG are necessary to evaluate hypoglycemia-related atrial fibrillation in type 2 diabetes mellitus. Elevated fasting plasma insulin, as well as insulin resistance, are important predictors of atrial fibrillation development, but it needs further studies.

Evaluation of glycemic abnormalities in children and adolescents with β-thalassemia major

Background The quality of life of B-thalassemia major (β-TM) patients has improved with the use of frequent blood transfusions. However, this leads to chronic iron overload with its sequelae, as prediabetes and diabetes mellitus. This study aimed to assess insulin resistance and glucose abnormalities in a sample of B-thalassemia major patients in Benha, Egypt. Results This case-control study included 40 B-thalassemia major patients on regular blood transfusion and iron chelation. Their ages ranged from 8 to 16 years, and 30 normal age and sex-matched controls. Thorough clinical examination was performed including weight (kg), height (m), body mass index (BMI) (kg/m2), and liver and spleen size. Laboratory investigations were done in the form of complete blood count, liver enzymes, serum ferritin, fasting plasma insulin, and fasting, and 2 h postprandial plasma glucose. Insulin resistance (IR) was calculated using the Homeostasis Model Assessment of insulin resistance (HOMA-IR) index. Insulin resistance was found in 27.5% of thalassemic patients; 18.2% of them had diabetes, 72.7% were prediabetics (with impaired fasting glycemia), and 9.1% had normal fasting and 2 h postprandial plasma glucose level. Insulin resistance increased significantly with increased blood transfusion duration, serum ferritin, liver enzymes, fasting plasma insulin, fasting plasma glucose, and 2 h postprandial plasma glucose (ROC). The curve analysis showed that the duration of blood transfusion, serum ferritin, fasting plasma insulin, fasting, and 2 h postprandial plasma glucose could significantly predict insulin resistance at a certain cut-off point. Conclusion Our data show that HOMA-IR can be used to detect insulin resistance in β-TM patients on long-term blood transfusions, especially patients with high serum ferritin and impaired liver enzymes.

Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM. Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM).The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlatted with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease.Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

The gut microbiome drives inter- and intra-individual differences in metabolism of bioactive small molecules

The origin of inter-individual variability in the action of bioactive small molecules from the diet is poorly understood and poses a substantial obstacle to harnessing their potential for attenuating disease risk. Epidemiological studies show that coffee lowers the risk of developing type 2 diabetes, independently of caffeine, but since coffee is a complex matrix, consumption gives rise to different classes of metabolites in vivo which in turn can affect multiple related pathways in disease development. We quantified key urinary coffee phenolic acid metabolites repeated three times in 36 volunteers, and observed the highest inter- and intra-individual variation for metabolites produced by the colonic microbiome. Notably, a urinary phenolic metabolite not requiring the action of the microbiota was positively correlated with fasting plasma insulin. These data highlight the role of the gut microbiota as the main driver of both intra- and inter-individual variation in metabolism of dietary bioactive small molecules.

An analysis of the correlation between thyroid nodules and metabolic syndrome

Objective: The purpose of this study was to explore the prevalence of thyroid nodules (TN) and metabolic syndrome (MS) and to analyze the correlation between TN and the components of MS. Methods: A total of 1526 subjects were divided into two groups: a TN group and a non-thyroid nodules (NTN) group. The height, weight, blood pressure, fasting blood glucose level, fasting plasma insulin level, serum lipid profile, uric acid level, serum thyroid-stimulating hormone (TSH) level, free triiodothyronine (FT3) level, and free thyroxine (FT4) level of each patient were measured. Insulin resistance (IR) was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Fatty liver and TN were detected by color Doppler ultrasonography. Results: (i) The overall prevalence of TN was 39.5%; it was significantly higher in women than in men (P < 0.01) and progressively increased with age in both sexes. (ii) The overall prevalence of MS was 25.6%; it was significantly higher in men than in women (P < 0.01) and progressively increased with age in both sexes. (iii) FT3 was significantly lower in the TN group than in the NTN group (P < 0.01). (iv) BMI, triglycerides, and HOMA-IR were higher in the TN group than in the NTN group (P < 0.05). (v) The existence of TN was significantly associated with overweight/obesity (OR = 1.03, 95% CI = 1.024–1.089), and with insulin resistance (IR) (OR = 1.98, 95% CI = 1.645–2.368), after adjusting for age and sex. Conclusions: The prevalence of thyroid nodules and metabolic syndrome in the Nanchang area increases with age, and overweight/obesity and IR in patients are associated with thyroid nodules.