scholarly journals Microbiota-related metabolites and the risk of type 2 diabetes

2020 ◽  
Author(s):  
Jagadish Vangipurapu ◽  
Lilian Fernandes Silva ◽  
Teemu Kuulasmaa ◽  
Ulf Smith ◽  
Markku Laakso
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Oral Glucose ◽  
Microbial Metabolites ◽  
Cross Sectional ◽  
Metabolomics Data ◽  
Incident Type ◽  
Increased Risk

<b>OBJECTIVE: </b>Recent studies have highlighted the significance of microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes. <p> </p> <p><b>RESEARCH DESIGN AND METHODS: </b>5,181 participants from the cross-sectional METabolic Syndrome In Men (METSIM) study that included Finnish men (age 57 ± 7 years, body mass index 26.5 ± 3.5 kg/m<sup>2</sup>) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. Based on an oral glucose tolerance test, Matsuda ISI and Disposition index were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit and 522 participants developed type 2 diabetes.</p> <p><b> </b></p> <p><b>RESULTS: </b>Creatine, 1-palmitoleoylglycerol(16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol(18:1), 1-myristoylglycerol(14:0), dimethylglycine and 2-hydroxyhippurate(salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoyl-glycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.</p> <p><b> </b></p> <p><b>CONCLUSIONS: </b>Several novel and previously reported microbial metabolites related to gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes. </p>

scholarly journals Microbiota-related metabolites and the risk of type 2 diabetes

2020 ◽  
Author(s):  
Jagadish Vangipurapu ◽  
Lilian Fernandes Silva ◽  
Teemu Kuulasmaa ◽  
Ulf Smith ◽  
Markku Laakso
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Oral Glucose ◽  
Microbial Metabolites ◽  
Cross Sectional ◽  
Metabolomics Data ◽  
Incident Type ◽  
Increased Risk

<b>OBJECTIVE: </b>Recent studies have highlighted the significance of microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes. <p> </p> <p><b>RESEARCH DESIGN AND METHODS: </b>5,181 participants from the cross-sectional METabolic Syndrome In Men (METSIM) study that included Finnish men (age 57 ± 7 years, body mass index 26.5 ± 3.5 kg/m<sup>2</sup>) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. Based on an oral glucose tolerance test, Matsuda ISI and Disposition index were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit and 522 participants developed type 2 diabetes.</p> <p><b> </b></p> <p><b>RESULTS: </b>Creatine, 1-palmitoleoylglycerol(16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol(18:1), 1-myristoylglycerol(14:0), dimethylglycine and 2-hydroxyhippurate(salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoyl-glycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.</p> <p><b> </b></p> <p><b>CONCLUSIONS: </b>Several novel and previously reported microbial metabolites related to gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes. </p>

scholarly journals The relationship between insulin sensitivity and serum antithrombin 3 activity in patients with type 2 diabetes

2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xueqin Wang ◽  
Dong-mei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Relationship

Background: Antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and serum AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity indices and serum AT3 activity in patients with T2D. Methods: We conducted a cross-sectional study in patients with T2D who consented to participate in the study at the Endocrinology Department of Affiliated 2 Hospital of Nantong University from January 2015 to June 2018. All patients received serum AT3 activity test and 75-g oral glucose tolerance test (OGTT). Basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISIMatsuda), respectively, from the OGTT. And other relevant clinical data were also collected. Results: Total 1612 patients with T2D were enrolled in the study, with a mean age of 58.67±13.09 years and a median diabetes duration of 6 years (interquartile range, 1–10 years). Across ascending quartiles of serum AT3, HOMA-IR progressively decreased, while ISIMatsuda progressively increased (all p for trend <0.001). Moreover, serum AT3 was negatively correlated with HOMA-IR (r= –0.189, p<0.001) and positively correlated with ISIMatsuda (r=0.221, p<0.001). After adjusting for other metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β= −0.185, t= −5.960, p<0.001) and ISIMatsuda (β= 0.197, t=6.632, p<0.001) remained independently associated with the serum AT3 activity in patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased serum AT3 activity in patients with T2D.

scholarly journals The relationship between insulin sensitivity and serum AT3 activity in patients with type 2 diabetes

2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xue-qin Wang ◽  
Dong-mei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Relationship

Abstract Background: Serum antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity and serum AT3 activity in patients with T2D. Methods: We recruited 1612 patients with T2D for this cross-sectional study from the Second Affiliated Hospital of Nantong University. All patients performed 75-g oral glucose tolerance test (OGTT), and basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISI Matsuda ), respectively. Serum AT3, one of the hemostatic parameters, and the relevant clinical data were collected, as well as other laboratory indicators. Results: It is showed that HOMA-IR decreased, while ISI Matsuda notably increased, across ascending quartiles of serum AT3. Moreover, serum AT3 were was negatively correlated with (r = –0.189, p < 0.001) and positively correlated with ISI Matsuda (r = 0.221, p < 0.001). After adjusted for metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β = −0.179, t = −5.823, p < 0.001) and ISI Matsuda (β = 0.191, t = 6.395, p < 0.001) was remained independently associated with the serum AT3 activity patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased AT3 activity in patients with T2D.

Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort

2021 ◽  
pp. 153537022110094
Author(s):  
Ibiye Owei ◽  
Nkiru Umekwe ◽  
Frankie Stentz ◽  
Jim Wan ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Intravenous Glucose Tolerance Test ◽  
Cross Sectional ◽  
Parental History ◽  
Intravenous Glucose

The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

scholarly journals Eating Competence Is Associated with Lower Prevalence of Obesity and Better Insulin Sensitivity in Finnish Adults with Increased Risk for Type 2 Diabetes: The StopDia Study

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 104 ◽  
Author(s):  
Tanja Tilles-Tirkkonen ◽  
Kirsikka Aittola ◽  
Reija Männikkö ◽  
Pilvikki Absetz ◽  
Marjukka Kolehmainen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Cross Sectional Study ◽  
Healthy Diet ◽  
Lower Prevalence ◽  
Cross Sectional ◽  
Increased Risk ◽  
Eating Competence

A healthy diet prevents type 2 diabetes but is often difficult to adhere to. This cross-sectional study aimed to investigate whether eating competence is associated with diet or risk factors and prevalence of type 2 diabetes in individuals screened for type 2 diabetes risk. Eating competence is an indicator of food acceptance, positive attitudes, internal regulation and contextual skills related to food and eating. In total, 3147 Finnish adults aged 18–74 at an increased risk for type 2 diabetes identified via online risk screening participated in the baseline examinations of the Stop Diabetes (StopDia) study. The participants filled out the digital questionnaire on food intake, physical activity and sleep, and the Satter Eating Competence Inventory 2.0TM (ecSI 2.0TM). In addition, anthropometric and laboratory measurements were performed at primary healthcare centres. Eating competent individuals (37%, classified by ecSI 2.0TM) had a better quality of diet (p < 0.05 for all). Additionally, eating competence was associated with a lower prevalence of previously undiagnosed type 2 diabetes, abdominal obesity, metabolic syndrome and hypertriglyceridaemia, and with better insulin sensitivity (p < 0.05 for all). However, these associations, except for metabolic syndrome, were at least partly mediated by body mass index. Eating competence is associated with a healthy diet and could, thus, in the long term, support the prevention of type 2 diabetes.

scholarly journals Short Course of Insulin Treatment versus Metformin in Newly Diagnosed Patients with Type 2 Diabetes

2018 ◽  
Vol 7 (9) ◽  
pp. 235 ◽  
Author(s):  
Marta Seghieri ◽  
Eleni Rebelos ◽  
Andrea Mari ◽  
Luigi Sciangula ◽  
Carlo Giorda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Basal Insulin ◽  
Insulin Treatment ◽  
Oral Glucose ◽  
Newly Diagnosed ◽  
Insulin Group ◽  
Short Course

The ß-cell dysfunction of type 2 diabetes is partly reversible. The optimal time window to induce glycemic remission is uncertain; short courses of insulin treatment have been tested as a strategy to induce remission. In a pilot study in 38 newly-diagnosed patients, we assessed the time-course of insulin sensitivity and ß-cell function (by repeat oral glucose tolerance tests) following a 6-week basal insulin treatment compared to metformin monotherapy in equipoised glycemic control. At 6 weeks, insulin secretion and sensitivity were increased in both groups whilst ß-cell glucose sensitivity was unchanged. From this time onwards, in the insulin group glycemia started to rise at 3 months, and was no longer different from baseline at 1 year. The initial improvement in insulin secretion and sensitivity dissipated. In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group. A short course of basal insulin in newly-diagnosed patients does not appear to offer clinical advantage over recommended initiation with metformin.

scholarly journals Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

2014 ◽  
Vol 307 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Thomas P. J. Solomon ◽  
Steven K. Malin ◽  
Kristian Karstoft ◽  
Sine H. Knudsen ◽  
Jacob M. Haus ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Normal Glucose

Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.

scholarly journals The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans

2018 ◽  
Vol 103 (12) ◽  
pp. 4373-4383 ◽  
Author(s):  
Felicia Gerst ◽  
Benjamin A Jaghutriz ◽  
Harald Staiger ◽  
Anke M Schulte ◽  
Estela Lorza-Gil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Oral Glucose ◽  
Gene Variants ◽  
Mrna Levels ◽  
Hyperglycemic Clamp ◽  
Increased Risk

Abstract Context Reduced β-cell mass, impaired islet function, and dedifferentiation are considered causal to development of hyperglycemia and type 2 diabetes. In human cohort studies, changes of islet cell–specific expression patterns have been associated with diabetes but not directly with in vivo insulin secretion. Objective This study investigates alterations of islet gene expression and corresponding gene variants in the context of in vivo glycemic traits from the same patients. Methods Fasting blood was collected before surgery, and pancreatic tissue was frozen after resection from 18 patients undergoing pancreatectomy. Islet tissue was isolated by laser capture microdissection. Islet transcriptome was analyzed using microarray and quantitative RT-PCR. Proteins were examined by immunohistochemistry and western blotting. The association of gene variants with insulin secretion was investigated with oral glucose tolerance test (OGTT)-derived insulin secretion measured in a large cohort of subjects at increased risk of type 2 diabetes and with hyperglycemic clamp in a subset. Results Differential gene expression between islets from normoglycemic and hyperglycemic patients was prominent for the glycolytic enzyme ALDOB and the obesity-associated gene FAIM2. The mRNA levels of both genes correlated negatively with insulin secretion and positively with HbA1c. Islets of hyperglycemic patients displayed increased ALDOB immunoreactivity in insulin-positive cells, whereas α- and δ-cells were negative. Exposure of isolated islets to hyperglycemia augmented ALDOB expression. The minor allele of the ALDOB variant rs550915 associated with significantly higher levels of C-peptide and insulin during OGTT and hyperglycemic clamp, respectively. Conclusion Our analyses suggest that increased ALDOB expression in human islets is associated with lower insulin secretion.

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