Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

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Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity -- a problem that is no longer restricted to minority groups

Acta Endocrinologica ◽

10.1530/eje.0.1510199 ◽

2004 ◽

pp. 199-206 ◽

Cited By ~ 125

Author(s):

S Wiegand ◽

U Maikowski ◽

O Blankenstein ◽

H Biebermann ◽

P Tarnow ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Children And Adolescents ◽

Fasting Glucose ◽

Sensitivity Index ◽

Model Assessment ◽

Abnormal Glucose Tolerance

BACKGROUND: The incidence of childhood obesity and type 2 diabetes is an increasing problem in Europe. We determined the prevalence of impaired glucose regulation in a predominantly Caucasian cohort of 491 children and adolescents with obesity. METHODS: Fasting glucose and insulin levels were determined in all 491 subjects. Patients with an abnormal fasting glucose or with additional risk factors (positive family history of type 2 diabetes, acanthosis nigricans, hyperlipidemia; n=102) underwent an oral glucose tolerance test (OGTT; 1.75 g glucose/kg body weight). Homeostasis model assessment was used to estimate insulin resistance in all subjects. The insulin sensitivity index was determined in those subjects who underwent an OGTT. Screening for mutations in the melanocortin 4 receptor (MC4R) gene and the coding region of the brain-derived neutrophic factor (BDNF) in 37 patients with an impaired glucose tolerance was performed by WAVE analysis. RESULTS: Out of the total of 491 patients, 12 had an abnormal fasting glucose level. Of the 102 patients who underwent an OGTT, 37 had impaired glucose tolerance; 6 out of the 102 patients were diagnosed with type 2 diabetes. Eighty-eight per cent of patients with abnormal glucose tolerance and 66% of patients with type 2 diabetes were Caucasian. Insulin resistance indices correlated well with the degree of abnormal glucose tolerance. Using the screening algorithm for type 2 diabetes as advocated by the American Diabetes Association, 68% of patients with impaired glucose tolerance and 66% of patients with type 2 diabetes would have been missed. No abnormalities in the MC4R and BDNF genes were detected. CONCLUSIONS: Impaired glucose tolerance and type 2 diabetes are far more common in obese European children of Caucasian origin than previously thought. Using fasting glucose levels as the main screening tool appears to be insufficient in detecting these children.

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Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I

Acta Endocrinologica ◽

10.1530/eje.1.02219 ◽

2006 ◽

Vol 155 (2) ◽

pp. 293-296 ◽

Cited By ~ 14

Author(s):

Adrienne A M Zandbergen ◽

Steven W J Lamberts ◽

Joop A M J L Janssen ◽

Aart H Bootsma

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fasting Glucose ◽

Serum Levels ◽

Model Assessment ◽

Angiotensin Receptor ◽

Angiotensin Receptor Antagonist ◽

Igf I ◽

Igfbp 3

Objective: Blocking the renin–angiotensin system (RAS) may reduce the risk of developing type-2 diabetes, but data are inconclusive and the mechanisms involved are unclear. RAS and RAS inhibition also influence the IGF-I system, which is important in glucose homeostasis. We investigated the effects of the angiotensin-receptor antagonist, losartan, on insulin resistance and IGF-I levels Design and methods: In this hypothesis-generating study, five individuals with impaired fasting glucose received 100 mg losartan during 8 weeks. Before and after the treatment period, insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA), as well as the 2-h continuous infusion of glucose with model assessment (CIGMA). Furthermore, serum levels of free and total IGF-I, IGF-binding protein-3 (IGFBP-3), lipids and HbAlc were measured. Results: After the treatment period, the HOMA score for insulin resistance had decreased from 5.3 ± 1.1 to 3.7 ± 0.9 (P = 0.004) and the 2-h CIGMA score from 23.4 ± 3.1 to 15.9 ± 2.1 (P = 0.07). The serum levels of free IGF-I had increased from 57 ± 18.8 to 134 ± 31.3 pmol/l (P = 0.04). In terms of percentage, the decrease of HOMA correlated with the increase in free IGF-I levels (Pearson’s correlation coefficient r = −0.8; P = 0.07). A trend in the same direction was observed with 2-h CIGMA. No differences were observed in lipids, total IGF-I, IGFBP-3 or HbAlc. Conclusions: Losartan raised serum levels of free IGF-I, which might contribute to the improvement of insulin resistance associated with losartan treatment. These observations, if confirmed in broader studies, will help our understanding of the pathogenesis of type-2 diabetes mellitus, as well as the role of angiotensin-receptor antagonists in its prevention.

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Effects of Micronutrient Supplementation on Glucose and Hepatic Lipid Metabolism in a Rat Model of Diet Induced Obesity

Cells ◽

10.3390/cells10071751 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1751

Author(s):

Saroj Khatiwada ◽

Virginie Lecomte ◽

Michael F. Fenech ◽

Margaret J. Morris ◽

Christopher A. Maloney

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Glucose Tolerance ◽

Antioxidant Capacity ◽

Fasting Glucose ◽

Oral Glucose ◽

Model Assessment ◽

Micronutrient Supplementation ◽

Sprague Dawley ◽

Triglyceride Accumulation

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.

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Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

10.2337/figshare.17122142 ◽

2022 ◽

Author(s):

Marta Garaulet ◽

Jesus Lopez-Minguez ◽

Hassan S Dashti ◽

Céline Vetter ◽

Antonio Miguel Hernández-Martínez ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Area Under The Curve ◽

Serum Levels ◽

Postprandial Glucose ◽

Oral Glucose ◽

Elevated Concentration ◽

Endogenous Melatonin

Objective: We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (MTNR1B). Research Design and Methods: In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant (n=845) underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime (“early dinner-timing”), and a late condition scheduled 1 hour prior to habitual bedtime (“late dinner-timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between early and late dinner-timing. Results: Melatonin serum levels were 3.5-fold higher in the late vs. early condition, with late dinner-timing resulting in 6.7% lower insulin area-under-the-curve (AUC) and 8.3% higher glucose AUC. In the late condition MTNR1B G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (Pint AUCgluc=0.009, Pint CIR=0.022, Pint DI=0.018). Conclusions: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in MTNR1B G-risk-allele carriers, attributable to insulin secretion defects.

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Pre-diabetes and Type 2 Diabetes Status in Overweight and Obese Children in a Tertiary Care Hospital of Bangladesh

Bangladesh Journal of Child Health ◽

10.3329/bjch.v44i3.52706 ◽

2021 ◽

Vol 44 (3) ◽

pp. 143-147

Author(s):

Monira Hossain ◽

Suraiya Begum ◽

Shahana A Rahman

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Tertiary Care ◽

Oral Glucose ◽

Care Hospital ◽

Obese Children ◽

Diabetes Status

Introduction: Obesity in childhood is associated with many co-morbid conditions; one of them is alteration of glucose metabolism. Materials and Methods:This cross-sectional study was conducted among 100 overweight and obese children aged 5-16 years to determine the status of pre-diabetes (IFG and IGT) and type 2 diabetes mellitus (T2DM), attending the OPD, BSMMU, Dhaka. All overweight/obese children were included according to BMI for age and sex using CDC growth chart. Children taking steroid for any cause or having any endocrine disorder or syndrome was excluded from the study. Anthropometry and blood pressure measurement were done and skin manifestations of insulin resistance were looked for. Fasting lipid profile and oral glucose tolerance test (OGTT) was done for each child. Result: Among the studied children 62% were male and 38% female, 77% were obese and 23% were over weight. Evidence of insulin resistance were found among most of the children and most common evidence was dyslipidemia (80%) followed by acanthosis nigricans(76%). Skin manifestation of polycystic ovary syndrome (PCOS) was found in 3% of children. Impaired fasting glucose (IFG) was found in 4% and Impaired Glucose Tolerance (IGT) was found in 7% of children among them 4% had both IGT and IFT. No child was found diabetic in this study. Conclusion:Altered glucose metabolism was present in overweight and obese children of our children, so screening is recommended. Bangladesh J Child Health 2020; VOL 44 (3) :143-147

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Risk of hypertension in middle-aged and elderly participants with newly diagnosed type 2 diabetes and prediabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001500 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001500

Author(s):

Nobuo Sasaki ◽

Ryoji Ozono ◽

Ryo Maeda ◽

Yukihito Higashi

Keyword(s):

Type 2 Diabetes ◽

Glucose Tolerance ◽

Fasting Glucose ◽

Early Stage ◽

Normal Glucose Tolerance ◽

Oral Glucose ◽

Newly Diagnosed ◽

Middle Aged ◽

Early Stages

IntroductionLittle is known about the risk of hypertension in patients with the early stage of type 2 diabetes. We investigated the risk of hypertension in participants with newly diagnosed type 2 diabetes and prediabetes.Research design and methodsThis is a retrospective cohort study consisting of 2136 middle-aged participants (1022 with normal fasting glucose/normal glucose tolerance (NFG/NGT), 418 with impaired fasting glucose (IFG), 466 with impaired glucose tolerance (IGT) and 230 with diabetes) and 3426 elderly participants (1762 with NFG/NGT, 599 with IFG, 781 with IGT, and 284 with diabetes). All participants underwent 75 g oral glucose tolerance tests at baseline.ResultsOver a median 59-month follow-up period, 459 middle-aged and 1170 elderly participants developed hypertension. In middle-aged participants, the odds of incident hypertension were significantly higher in those with IFG (OR 1.40; p=0.019), IGT (OR 1.49; p=0.004), and diabetes (OR 1.55; p=0.013) than those with NFG/NGT, which was no longer significant after adjustment for body mass index. Subgroup analysis showed that the risk of hypertension was significantly higher in diabetes than NFG/NGT only in participants without obesity. Conversely, obesity was a risk factor of hypertension only in those with IFG and NFG/NGT. In elderly participants, there was no difference in the risk of hypertension among the NFG/NGT, IFG, IGT and diabetes groups.ConclusionsThe risk of hypertension is modest in participants with newly diagnosed type 2 diabetes and prediabetes. Our findings suggest that the early stages of type 2 diabetes and prediabetes may be a key period for reducing hypertension, given the pronounced risk of hypertension in patients with diabetes reported in previous studies. In terms of reducing the risk for hypertension, obesity treatment might be advantageous in the early stages rather than the advanced stages of impaired glucose metabolism.

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Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study

Public Health Nutrition ◽

10.1017/s1368980016001233 ◽

2016 ◽

Vol 19 (16) ◽

pp. 3017-3026 ◽

Cited By ~ 8

Author(s):

Preet K Dhillon ◽

Liza Bowen ◽

Sanjay Kinra ◽

Ankalmadugu Venkatsubbareddy Bharathi ◽

Sutapa Agrawal ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Large Scale ◽

Fasting Glucose ◽

Epidemiological Studies ◽

Model Assessment ◽

Dietary Intakes ◽

Migration Status

AbstractObjectiveLegume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap.DesignFasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ.SettingLucknow, Nagpur, Hyderabad and Bangalore, India.SubjectsMen and women (n 6367) aged 15–76 years – urban residents, urban migrants and their rural siblings.ResultsIn multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes.ConclusionsAlthough legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.

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The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

International Journal of Endocrinology ◽

10.1155/2015/836941 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Alexis Elias Malavazos ◽

Emanuele Cereda ◽

Federica Ermetici ◽

Riccardo Caccialanza ◽

Silvia Briganti ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Lipid Accumulation ◽

Fasting Glucose ◽

Tolerance Test ◽

Continuous Variable ◽

Oral Glucose ◽

Model Assessment ◽

Lipid Accumulation Product ◽

Adult Age

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006andP=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

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Dipeptidyl-Peptidase-IV Inhibitors, Imigliptin and Alogliptin, Improve Beta-Cell Function in Type 2 Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.694390 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xu Liu ◽

Yang Liu ◽

Hongzhong Liu ◽

Haiyan Li ◽

Jianhong Yang ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Dipeptidyl Peptidase ◽

Chinese Patients ◽

Oral Glucose ◽

Model Assessment

ObjectsImigliptin is a novel dipeptidyl peptidase-4 inhibitor. In the present study, we aimed to evaluate the effects of imigliptin and alogliptin on insulin resistance and beta-cell function in Chinese patients with type-2 diabetes mellitus (T2DM).MethodsA total of 37 Chinese T2DM patients were randomized to receive 25 mg imigliptin, 50 mg imigliptin, placebo, and 25 mg alogliptin (positive drug) for 13 days. Oral glucose tolerance tests were conducted at baseline and on day 13, followed by the oral minimal model (OMM).ResultsImigliptin or alogliptin treatment, compared with their baseline or placebo, was associated with higher beta-cell function parameters (φs and φtot) and lower glucose area under the curve (AUC) and postprandial glucose levels. The changes in the AUC for the glucose appearance rate between 0 and 120 min also showed a decrease in imigliptin or alogliptin groups. However, the insulin resistance parameter, fasting glucose, was not changed. For the homeostatic model assessment (HOMA-β and HOMA-IR) parameters or secretory units of islets in transplantation index (SUIT), no statistically significant changes were found both within treatments and between treatments.ConclusionsAfter 13 days of treatment, imigliptin and alogliptin could decrease glycemic levels by improving beta-cell function. By comparing OMM with HOMA or SUIT results, glucose stimulation might be more sensitive for detecting changes in beta-cell function.

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Plasma C1q/TNF-Related Protein-3 (CTRP-3) and High-Mobility Group Box-1 (HMGB-1) Concentrations in Subjects with Prediabetes and Type 2 Diabetes

Journal of Diabetes Research ◽

10.1155/2016/9438760 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Huili Wei ◽

Hua Qu ◽

Hang Wang ◽

Huacong Deng

Keyword(s):

Type 2 Diabetes ◽

Glucose Tolerance ◽

Linear Regression Analysis ◽

High Mobility ◽

Multiple Linear Regression Analysis ◽

High Mobility Group ◽

Oral Glucose ◽

Model Assessment ◽

Related Protein

Aims. To detect the association of C1q/TNF-related protein-3 (CTRP-3) and high-mobility group box-1 (HMGB-1) in subjects with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (nT2DM).Methods. 224 eligible participants were included. The 75 g oral glucose tolerance test (OGTT) and several clinical parameters of metabolic disorders and cytokines were measured. All participants were divided into three groups: normal glucose tolerance (NGT,n=62), pre-DM (n=111), and nT2DM group (n=56).Results. Plasma CTRP-3 concentrations were significantly lower in subjects with pre-DM and nT2DM than that of the NGT group, while plasma HMGB-1 levels were higher in pre-DM and nT2DM group compared with the NGT group (P<0.05). A multiple linear regression analysis showed both plasma CTRP-3 and HMGB-1 concentrations were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR) and interleukin-6 (IL-6) (P<0.05for all). Further multiple logistical regression analyses revealed that both plasma CTRP-3 and HMGB-1 levels were significantly associated with pre-DM and nT2DM after adjusting for several confounders (P<0.001for all).Conclusions. Circulating CTRP-3 and HMGB-1 concentrations might be promising biomarkers to predict prediabetes and type 2 diabetes.

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