Analysis of an Indian diabetes prevention programme on association of adipokines and a hepatokine with incident diabetes

AbstractTo study the association and possible predictive role of visfatin, resistin, fetuin-A and chemerin with incident type 2 diabetes (T2DM) among Asian Indians with prediabetes. Their association with insulin resistance, β-cell function, glycaemia and anthropometry were also studied. This is a nested case–control study of a large 2-year prospective prevention trial in persons at high risk of developing T2DM. Baseline HbA1c values between 6.0% (42 mmol/mol) and 6.2% (44 mmol/mol) were chosen for this analysis (n = 144). At follow-up, persons with incident T2DM (HbA1c ≥ 6.5%, 48 mmol/mol) were grouped as cases (n = 72) and those reverted to normoglycaemia, (HbA1c < 5.7% (39 mmol/mol) as controls (n = 72). Insulin resistance showed the strongest association with incident T2DM ((Odds Ratio (OR): 23.22 [95%CI 6.36–84.77]; p < 0.0001). Baseline visfatin (OR: 6.56 [95%CI 2.21–19.5]; p < 0.001) and fetuin-A (OR: 1.01 [95%CI (1.01–1.04)]; p < 0.0001) independently contributed to the conversion of prediabetes to T2DM. The contribution was significantly higher when their elevated levels coexisted (OR: 12.63 [95%CI 3.57–44.63]; p < 0.0001). The area under the curve was 0.77 ± SE 0.4 (95%CI 0.69–0.85) and 0.80 ± SE 0.04 (95%CI 0.73–0.88) for visfatin (median 17.7 ng/ml, sensitivity and specificity: 75%, p < 0.0001) and fetuin-A (mean 236.2 µg/ml, sensitivity: 71%, specificity: 75%, p < 0.0001) respectively. Higher baseline visfatin and fetuin-A concentrations are strongly associated with incident T2DM and are predictive of future diabetes.

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Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case–control study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000802 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000802 ◽

Cited By ~ 1

Author(s):

Chuyao Jin ◽

Lizi Lin ◽

Na Han ◽

Zhiling Zhao ◽

Zheng Liu ◽

...

Keyword(s):

Insulin Resistance ◽

Case Control Study ◽

Cell Function ◽

Dynamic Change ◽

First Trimester ◽

Second Trimester ◽

Fetuin A ◽

Β Cell Function ◽

Nested Case Control ◽

Control Study

ObjectiveTo examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.Research design and methodsA total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case–control study. Fasting venous blood samples were collected at the prenatal visit of the first trimester and during OGTT of the second trimester. Plasma concentration of fetuin-A and insulin was determined.ResultsThe plasma fetuin-A concentration in women with GDM was significantly higher than NGT controls in both the first trimester (medians: 403.0 pg/mL vs 273.4 pg/mL; p<0.05) and the second trimester (medians: 475.7 pg/mL vs 290.8 pg/mL; p<0.05) and notably increased from the first to the second trimester. Multivariate linear regression analysis showed that the change in fetuin-A concentration was associated with the changes in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, and HOMA of β-cell function (HOMA-β) (p<0.05). The highest quartile of the increase in fetuin-A concentration from the first to the second trimester was associated with a higher risk of developing GDM compared with the lowest quartile (OR 2.14; 95% CI 1.05 to 4.37).ConclusionsThe dynamic change in fetuin-A levels was associated with the changes in insulin resistance and β-cell function from the first to the second trimester, and was associated with an increased risk of the development of GDM, indicating that fetuin-A could be a biomarker to predict the risk of GDM.Trial registration numberNCT03814395.

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β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study

Open Medicine ◽

10.1515/med-2021-0376 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1583-1590

Author(s):

Jidong Liu ◽

Dongqing Yu ◽

Mingyue Xu ◽

Ruiying Feng ◽

Yujing Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cell Function ◽

Area Under The Curve ◽

Multivariate Linear Regression Analysis ◽

Middle Aged ◽

Β Cell ◽

Β Cell Function ◽

Nonobese Patients

Abstract Type 2 diabetes mellitus (T2DM) is a strong risk tfactor for osteosarcopenia. The relationship between musculoskeletal index and β-cell function remains controversial. We aimed to describe the clinical characteristics of osteosarcopenia and to explore the association between osteosarcopenia and β-cell function, as well as insulin resistance in patients with T2DM. A total of 150 middle-aged and older nonobese patients with T2DM were recruited. Bone mineral density (BMD) and body composition were measured by the dual-energy X-ray absorptiometry scanner. The homeostasis model assessment of insulin resistance and Matsuda index were used to evaluate insulin resistance status. β-Cell function was estimated by the area under the curve insulin/glucose (AUC-Ins/Glu) and the area under the curve C-peptide/glucose (AUC-CP/Glu). T2DM patients with osteosarcopenia had lower body mass index, waist circumference, body fat percentage, AUC-Ins/Glu, and AUC-CP/Glu. Both AUC-Ins/Glu (OR = 0.634, P = 0.008) and AUC-CP/Glu (OR = 0.491, P = 0.009) were negatively associated with the presence of osteosarcopenia. Multivariate linear regression analysis showed that β-cell function was positively associated with the skeletal muscle mass index, whereas it showed no correlation with lumbar or hip BMD. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with T2DM. These findings suggest that β-cell function might be a protective factor against osteosarcopenia.

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Association of Insulin Resistance, β-Cell Function Impairment and Calcium, Magnesium, and Fetuin-A Concentrations in Women with Type 2 Diabetes Mellitus

Acta Facultatis Medicae Naissensis ◽

10.1515/afmnai-2016-0020 ◽

2016 ◽

Vol 33 (3) ◽

pp. 187-197

Author(s):

Shatha Rouf Moustafa

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cell Function ◽

Serum Levels ◽

Control Group ◽

Β Cell ◽

Fetuin A ◽

Function Impairment ◽

Β Cell Function

SummaryInsulin resistance and β-cell function impairment play a role in the pathogenesis of type 2 diabetes (T2DM). Insulin signaling is inhibited by fetuin-A, an abundant plasma protein. Fetuin-A is also a candidate marker of the T2DM risk. This case-control study aimed to determine whether fetuin-A serum level is related to insulin resistance, β-cell function impairment, and total and ionized Ca and Mg serum levels in Erbil patients with T2DM.A total of 60 patients with T2DM were recruited, and 30 healthy persons were included in the control group. Fetuin-A and insulin concentrations were measured through ELISA. Other biochemical parameters were determined spectrophotometrically. Insulin resistance (HOMA2IR), insulin sensitivity (HOMA2%S), and β-cell function were examined by using a homeostatic model assessment 2 (HOMA2).Fasting serum insulin, fetuin-A serum levels, and HOMA2IR were significantly increased. HOMA2%S of the patients with diabetes was significantly lower than that of the control group. The total serum and ionized Ca and Mg contents and the Ca/Mg ratio were reduced in the patients.Therefore, fetuin-A is related to T2DM pathogenesis and is strongly associated with insulin resistance and glycemic control in T2DM patients. Future large-scale studies are necessary to validate fetuin-A as an indicator of IR in T2DM patients.

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Clinical Significance of the Fetuin-A-to-Adiponectin Ratio in Obese Children and Adolescents with Diabetes Mellitus

Children ◽

10.3390/children8121155 ◽

2021 ◽

Vol 8 (12) ◽

pp. 1155

Author(s):

Moon-Bae Ahn ◽

Seul-Ki Kim ◽

Shin-Hee Kim ◽

Won-Kyoung Cho ◽

Jin-Soon Suh ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Children And Adolescents ◽

Cell Function ◽

Obese Children ◽

Metabolic Complications ◽

Fetuin A ◽

Diabetic Children ◽

Β Cell Function

Fetuin-A and adiponectin are inflammatory cytokines associated with obesity and insulin resistance. This study aimed to examine the fetuin-A-to-adiponectin ratio (FAR) in diabetic children and to determine the role of FAR. A total of 54 children and adolescents with diabetes mellitus (DM) and 44 controls aged 9–16 years were included in this study. Clinical characteristics, including plasma fetuin-A and adiponectin levels, were compared with respect to body mass index (BMI) and diabetes type. Of 98 children, 54.1% were obese, whereas 18.4% were obese and diabetic. FAR was higher in obese children with DM than in non-obese children and also in type 2 DM children than in type 1. FAR showed a stronger association with BMI than with fetuin-A and adiponectin individually, and its association was more prominent in diabetic children than in controls. BMI was a risk factor for increased FAR. Plasma fetuin-A was elevated in obese children, and its association with insulin resistance and β cell function seemed more prominent in diabetic children after adjustment for adiponectin. Thus, FAR could be a useful surrogate for the early detection of childhood metabolic complications in diabetic children, particularly those who are obese.

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Phosphorylation status of fetuin-A is critical for inhibition of insulin action and is correlated with obesity and insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00089.2018 ◽

2019 ◽

Vol 317 (2) ◽

pp. E250-E260 ◽

Cited By ~ 2

Author(s):

Guang Ren ◽

Teayoun Kim ◽

James B. Papizan ◽

Carl K. Okerberg ◽

Vishal M. Kothari ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Insulin Action ◽

Glycogen Synthesis ◽

Human Hepatoma Cells ◽

Fetuin A ◽

Incident Type ◽

Insulin Resistant ◽

Incident Type 2 Diabetes ◽

Zucker Diabetic Fatty Rats

Fetuin-A (Fet-A), a hepatokine associated with insulin resistance, obesity, and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin-resistant conditions and its functional significance are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin-resistant Zucker diabetic fatty rats, and in individuals with obesity who are insulin resistant. Unlike serum total fetuin-A, serum phosphofetuin-A was associated with body weight, insulin, and markers of insulin resistance. To characterize potential mechanisms, fetuin-A was purified from Hep3B human hepatoma cells. Hep3B Fet-A was phosphorylated (Ser312) and inhibited insulin-stimulated glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Furthermore, single (Ser312Ala) and double (Ser312Ala + Ser120Ala) phosphorylation-defective Fet-A mutants were without effect on glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Together, our studies demonstrate that phosphorylation status of Fet-A (Ser312) is associated with obesity and insulin resistance and raise the possibility that Fet-A phosphorylation may play a role in regulation of insulin action.

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HDL cholesterol is an independent predictor of β‐cell function decline and incident type 2 diabetes: A longitudinal study

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.3289 ◽

2020 ◽

Vol 36 (4) ◽

Cited By ~ 3

Author(s):

Teresa V. Fiorentino ◽

Elena Succurro ◽

Maria A. Marini ◽

Elisabetta Pedace ◽

Francesco Andreozzi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Longitudinal Study ◽

Cell Function ◽

Independent Predictor ◽

Hdl Cholesterol ◽

Β Cell ◽

Incident Type ◽

Incident Type 2 Diabetes ◽

Β Cell Function

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Effects of Ovariectomy on Insulin Resistance and β-Cell Function and Mass

Preventive Nutrition and Food Science ◽

10.3746/jfn.2004.9.4.367 ◽

2004 ◽

Vol 9 (4) ◽

pp. 367-373

Author(s):

Soo-Bong Choi ◽

Chun-Hee Park ◽

Dong-Wha Jun ◽

Jin-Sun Jang ◽

Sun-Min Park

Keyword(s):

Insulin Resistance ◽

Cell Function ◽

Β Cell ◽

Β Cell Function

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Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes: the PREVEND study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01348-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Sara Sokooti ◽

Jose L. Flores-Guerrero ◽

Hiddo J. L. Heerspink ◽

Margery A. Connelly ◽

Stephan J. L. Bakker ◽

...

Keyword(s):

Cell Function ◽

Cox Regression ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Β Cell ◽

Incident Type ◽

Particle Characteristics ◽

Ldl Size ◽

Triglyceride Rich Lipoprotein ◽

Β Cell Function

Abstract Background Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population. Methods We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function. Results In subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D. Conclusions Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.

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