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The relationships between thyroid-stimulating hormone level and insulin resistance, glucose effectiveness, first- and second-phase insulin secretion in Chinese populations.
Chuang, TJ, Lin, JD, Wu, CZ, Ku, HC, Liao, CC, Yeh, CJ, Pei, D, Chen, YL
Medicine. 2021;(19):e25707
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Abstract
Increased insulin resistance (IR); decreased glucose effectiveness (GE); and both first-and second phase of insulin secretion (FPIS, SPIS) have always been important factors for the development of type 2 diabetes. Therefore, in this study, we evaluated the relationships between thyroid-stimulating hormone (TSH) and these 4 factors in adult Chinese. We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured with the equations built by our group. IR = log (1.439 + 0.018 × sex - 0.003 × age + 0.029 × BMI - 0.001 × SBP + 0.006 × DBP + 0.049 × TG - 0.046 × HDLC - 0.0116 × FPG) × 10 3.333. FPIS = 10 [1.477 - 0.119 × FPG + 0.079 × BMI - 0.523 × HDLC]. SPIS = 10 [-2.4 - 0.088 × FPG + 0.072 × BMI]. GE = (29.196 - 0.103 × age - 2.722 × TG - 0.592 × FPG) ×10 −3. The t test was performed to evaluate the differences between normal and diabetic groups. To evaluate the differences of the mean values of the 4 groups, from the highest to the lowest levels of TSH, we used a one-way analysis of variance. Age, high density lipoprotein-cholesterol and GE were higher in women. On the other hand, body mass index, blood pressure, low density lipoprotein-cholesterol, triglyceride, FPIS, SPIS and IR were higher in men. TSH was positively related to IR, FPIS, and SPIS and negatively related to GE. According to the r values, the tightest relationship was between TSH and IR, followed by GE, FPIS and SPIS. In conclusion, our data showed that IR, FPIS, and SPIS were positively related to the TSH level in middle-aged Chinese, whereas GE was negatively related. In both genders, IR had the tightest association followed by GE, FPIS, and SPIS.
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Metabolite Changes After Metabolic Surgery - Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels.
Ahlin, S, Cefalo, C, Bondia-Pons, I, Trošt, K, Capristo, E, Marini, L, Romero, M, Zorzano, A, Gastaldelli, A, Mingrone, G, et al
Frontiers in endocrinology. 2021;:786952
Abstract
AIMS: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. MATERIALS AND METHODS This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). RESULTS Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. CONCLUSIONS Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.
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Hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada: a population-based retrospective cohort study.
Liu, SL, Columbus, MP, Peddle, M, Mahon, JL, Spaic, T
CMAJ open. 2021;(4):E1260-E1268
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Abstract
BACKGROUND People with diabetes mellitus commonly experience hypoglycemia, but they may not necessarily present to hospital after severe hypoglycemia requiring paramedic assistance. We sought to describe the incidence and characteristics of calls for hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada, and to determine predictors of hospital transport. METHODS This population-based retrospective cohort study used data extracted from ambulance call reports (ACRs) of 8 paramedic services of the Southwest Ontario Regional Base Hospital Program from January 2008 to June 2014. We described calls in which treatment for hypoglycemia was administered, summarized the incidence of hypoglycemia calls and performed logistic regression to determine predictors of hospital transport. RESULTS Out of 470 467 ACRs during the study period, 9185 paramedic calls occurred in which hypoglycemia treatment was administered to an adult (mean age 60.2 yr, 56.8% male, 81.1% with documented diabetes). Refusal of hospital transport occurred in 2243 (24.4%) of calls. Documented diabetes diagnosis (adjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69-0.96), higher capillary blood glucose (adjusted OR 0.31, 95% CI 0.22-0.44) and overnight calls (adjusted OR 0.80, 95% CI 0.72-0.91) were associated with lower odds of hospital transport. Higher-acuity calls (adjusted OR 2.05, 95% CI 1.58-2.66) were associated with higher odds of transport. The estimated annual incidence rate of hypoglycemia requiring paramedic assistance was 108 per 10 000 people with diabetes per year. INTERPRETATION Hypoglycemia requiring paramedic assistance in southwestern Ontario is common, and close to 25% of calls do not result in hospital transport. Physicians managing diabetes care may be unaware of patients' hypoglycemia requiring paramedic care, suggesting a potential gap in follow-up care; we suggest that paramedics play an important role in identifying those at high recurrence risk and communicating with their care providers.
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Association of Triglyceride-Glucose Index and Lung Health: A Population-Based Study.
Wu, TD, Fawzy, A, Brigham, E, McCormack, MC, Rosas, I, Villareal, DT, Hanania, NA
Chest. 2021;(3):1026-1034
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Abstract
BACKGROUND Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.
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High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: An observational study.
Al-Disi, D, Ansari, MGA, Sabico, S, Wani, K, Hussain, SD, Elshafie, MM, McTernan, P, Al-Daghri, NM
Medicine. 2020;(46):e23211
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Abstract
Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ± 1.1 mmol/L) as compared to control (2.0 ± 0.5 mmol/L) and T2DM (2.7 ± 1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ± 1.1 vs 4.2 ± 1.4 mmol/L; P < .05), 4 hours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.
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Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.
Rouhard, S, Buysschaert, M, Alexopoulou, O, Preumont, V
Diabetes & metabolic syndrome. 2020;(2):65-69
Abstract
We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.
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Dialysate glucose response phenotypes during peritoneal equilibration test and their association with cardiovascular death: A cohort study.
Wang, Z, Yu, D, Cai, Y, Ma, S, Zhao, B, Zhao, Z, Simmons, D
Medicine. 2020;(21):e20447
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Abstract
Different measures of rates of transfer of glucose during the peritoneal equilibrium test (PET), undertaken during peritoneal dialysis (PD) might provide additional information regarding a patient's risk of future cardiovascular mortality. This study aimed to characterize the heterogeneity of dialysate glucose (DG) response phenotypes during the PET and compare the cardiovascular mortality rates associated with the different phenotypes. Our cohort was derived from Henan peritoneal dialysis registry. A total of 3477 patients initiating PD in 2007 to 2014 had the DG measured at 0, 2-hour and 4-hour (D0, D2, and D4 respectively) during the PET for estimation of D2/D0 and D4/D0. Deaths mainly due to CVD within 2 years since the initiation of PD were defined as the outcome. Latent class mixed-effect models were fitted to identify distinct phenotypes of the DG response during the PET. Multivariable unconditional Logistic regression models with adjustment for cardiometabolic risk factors were used to compare the 2-year risk of cardiovascular mortality among patients in the different latent classes. Three distinct DG response phenotypes during the PET were identified. Those with consistently high D2/D0 and D4/D0 ratios had a 1.22 [95% confidence interval: 1.02, 1.35] excess risk of a cardiovascular death within 2 years of commencing PD compared with patients with the lowest D2/D0 ratio and decreased D4/D0 ratio after adjustment for cardiometabolic risk factors. Consistently elevated D2/D0 and D4/D0 ratios during the PET are associated with an increased risk of 2-year cardiovascular mortality independent of other cardiometabolic risk factors. In view of the potential bias due to unmeasured confounders (eg, Family history of cardiovascular diseases, and dietary patterns), this association should be further validated in other external cohorts.
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Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort.
Mengozzi, A, Tricò, D, Nesti, L, Petrie, J, Højlund, K, Mitrakou, A, Krebs, M, Mari, A, Natali, A, ,
Metabolism: clinical and experimental. 2020;:154185
Abstract
BACKGROUND/AIMS: Uncertainty still exists on the earliest beta-cell defects at the bases of the type 2 diabetes. We assume that this depends on the inaccurate distinction between fasting and post-load glucose homeostasis and aim at providing a description of major beta-cell functions across the full physiologic spectrum of each condition. METHODS In 1320 non-diabetic individuals we performed an OGTT with insulin secretion modeling and a euglycemic insulin clamp, coupled in subgroups to glucose tracers and IVGTT; 1038 subjects underwent another OGTT after 3.5 years. Post-load glucose homeostasis was defined as mean plasma glucose above fasting levels (δOGTT). The analysis was performed by two-way ANCOVA. RESULTS Fasting plasma glucose (FPG) and δOGTT were weakly related variables (stβ = 0.12) as were their changes over time (r = -0.08). Disruption of FPG control was associated with an isolated and progressive decline (approaching 60%) of the sensitivity of the beta-cell to glucose values within the normal fasting range. Disruption of post-load glucose control was characterized by a progressive decline (approaching 60%) of the slope of the full beta-cell vs glucose dose-response curve and an early minor (30%) decline of potentiation. The acute dynamic beta-cell responses, neither per se nor in relation to the degree of insulin resistance appeared to play a relevant role in disruption of fasting or post-load homeostasis. Follow-up data qualitatively and quantitatively confirmed the results of the cross-sectional analysis. CONCLUSION In normal subjects fasting and post-load glucose homeostasis are largely independent, and their disruption is sustained by different and specific beta-cell defects.
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The Close Link of Pancreatic Iron With Glucose Metabolism and With Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study.
Pepe, A, Pistoia, L, Gamberini, MR, Cuccia, L, Peluso, A, Messina, G, Spasiano, A, Allò, M, Bisconte, MG, Putti, MC, et al
Diabetes care. 2020;(11):2830-2839
Abstract
OBJECTIVE We systematically explored the link of pancreatic iron with glucose metabolism and with cardiac complications in a cohort of 1,079 patients with thalassemia major (TM) enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. RESEARCH DESIGN AND METHODS MRI was used to quantify iron overload (T2* technique) and cardiac function (cine images) and to detect macroscopic myocardial fibrosis (late gadolinium enhancement technique). Glucose metabolism was assessed by the oral glucose tolerance test (OGTT). RESULTS Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with impaired fasting glucose, impaired glucose tolerance, and diabetes. A pancreas T2* <13.07 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for disturbances of glucose metabolism and for cardiac iron. Patients with myocardial fibrosis showed significantly lower pancreas T2* values. Patients with cardiac complications had significantly lower pancreas T2* values. No patient with arrhythmias/heart failure had a normal global pancreas T2*. CONCLUSIONS Pancreatic iron is a powerful predictor not only for glucose metabolism but also for cardiac iron and complications, supporting the close link between pancreatic iron and heart disease and the need to intensify iron chelation therapy to prevent both alterations of glucose metabolism and cardiac iron accumulation.
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AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism.
Randrianarisoa, E, Lehn-Stefan, A, Krier, J, Böhm, A, Heni, M, Hrabě De Angelis, M, Fritsche, A, Häring, HU, Stefan, N, Staiger, H
The Journal of clinical endocrinology and metabolism. 2020;(1)
Abstract
CONTEXT Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all 7 AMPK subunit genes on adiposity, glucose metabolism, and lipid metabolism has not yet been systematically studied. OBJECTIVE To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides. STUDY DESIGN AND METHODS A cohort of 2789 nondiabetic participants from the Tübingen Family study of type 2 diabetes, metabolically characterized by oral glucose tolerance test and genotyped by genome-wide SNP array, was analyzed. RESULTS We identified 6 largely nonoverlapping SNP sets across 4 AMPK genes (PRKAA1, PRKAA2, PRKAG2, PRKAG3) associated with adiposity, insulin sensitivity, insulin secretion, blood glucose, total/LDL cholesterol, or HDL cholesterol, respectively. A genetic score of body-fat-increasing alleles revealed per-allele effect sizes on body mass index (BMI) of +0.22 kg/m2 (P = 2.3 × 10-7), insulin sensitivity of -0.12 × 1019 L2/mol2 (P = 9.9 × 10-6) and 2-hour blood glucose of +0.02 mmol/L (P = 0.0048). Similar effects on blood glucose were observed with scores of insulin-sensitivity-reducing, insulin-secretion-reducing and glucose-raising alleles, respectively. A genetic cholesterol score increased total and LDL cholesterol by 1.17 mg/dL per allele (P = 0.0002 and P = 3.2 × 10-5, respectively), and a genetic HDL score decreased HDL cholesterol by 0.32 mg/dL per allele (P = 9.1 × 10-6). CONCLUSIONS We describe largely nonoverlapping genetic determinants in AMPK genes for diabetes-/atherosclerosis-related traits, which reflect the metabolic pathways controlled by the enzyme. Formation of trait-specific genetic scores revealed additivity of allele effects, with body-fat-raising alleles reaching a marked effect size. (J Clin Endocrinol Metab XX: 0-0, 2019).