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  • 1
    Online Resource
    Online Resource
    The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes
    Oxford University Press (OUP) ; 2019
    In:  European Journal of Endocrinology Vol. 180, No. 2 ( 2019-02), p. 99-107
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 180, No. 2 ( 2019-02), p. 99-107
    Abstract: A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study. Methods We evaluated carriers ( n  = 72) and non-carriers ( n  = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic–hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (β = −0.164, P   =  0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) ( P   =  0.02) and of 7.34 U/L in gamma-glutamyltransferase (GGT) ( P   =  0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher ( P   〈  0.001). Conclusions Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-18-0677
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1485160-X
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  • 2
    Online Resource
    Online Resource
    Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance
    Springer Science and Business Media LLC ; 2010
    In:  Cardiovascular Diabetology Vol. 9, No. 1 ( 2010-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2010-12)
    Abstract: Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (S A index) for the identification of IR and related metabolic conditions. Methods A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the S A index were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated. Results The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 vs . 0.669, P = 0.74), obesity (0.592 vs . 0.610, P = 0.32), hypertriglyceridemia (0.661 vs . 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624 vs . 0.633, P = 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%. The area under the ROC curve of the S A index for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689] , hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677] . Conclusions Total adiponectin, HMWA and the S A index had similar utility for the identification of IR and metabolic disturbances.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/1475-2840-9-26
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2093769-6
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  • 3
    Online Resource
    Online Resource
    METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes
    Oxford University Press (OUP) ; 2018
    In:  European Journal of Endocrinology Vol. 178, No. 5 ( 2018-05), p. 533-544
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 178, No. 5 ( 2018-05), p. 533-544
    Abstract: We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic–hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D). Design and methods The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G 0 )+TG 0 )*BMI)/(Ln(HDL-c)) (G 0 : fasting glucose, TG 0 : fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects. Results METS-IR demonstrated the better correlation with the MFFM ( ρ  = −0.622, P   〈  0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78–0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53–0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels ( P   〈  0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile ( 〉 50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25–6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P   〈  0.001). Conclusion METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-17-0883
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1485160-X
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  • 4
    Online Resource
    Online Resource
    Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels
    Oxford University Press (OUP) ; 2010
    In:  European Journal of Endocrinology Vol. 163, No. 3 ( 2010-09), p. 469-477
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 163, No. 3 ( 2010-09), p. 469-477
    Abstract: Fibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This study investigates independent factors associated with serum FGF21 levels. Design Cross-sectional study done in healthy blue-collar workers. Methods A medical history was taken, and FGF21 (measured using an ELISA commercial kit), glucose, uric acid, plasma lipids, total/high-molecular weight (HMW) adiponectin, and retinal-binding protein 4 (RBP4) were measured in 210 individuals with ( n =81) and without ( n =129) metabolic syndrome. Results The median of serum FGF21 levels were higher in subjects with metabolic syndrome (339.5 vs 276.4 ng/l, P =0.01). Serum FGF21 levels correlated positively with body mass index (BMI; r =0.23, P =0.001) and age ( r =0.17, P =0.01). After adjusting for age and BMI, a significant positive correlation persisted for fasting glucose, uric acid, and physical activity in both males ( r =0.21, r =0.11, and r =0.19, all P 〈 0.05) and females ( r =0.20, r =0.19, and r =0.14, all P 〈 0.05). In addition, FGF21 also correlates negatively with RBP4 ( r =−0.27, P =0.02), total ( r =−0.26, P =0.03), and HMW adiponectin ( r =−0.30, P =0.01) in women. A multiple linear regression model analysis identified that BMI (standardized β (SB)=0.247; P =0.008), glucose (SB=0.226; P =0.003), uric acid (SB=0.191; P =0.04), and physical activity (SB=0.223; P =0.004) are independent factors influencing serum FGF21 levels ( F =10.05, r 2 =0.19, P 〈 0.001). In addition, fasting hyperglycemia ≥100 mg/dl, excess body weight with BMI ≥25 kg/m 2 , and uric acid ≥5.5 mg/dl predicted higher serum FGF21 levels. Conclusion Serum FGF21 levels are influenced by BMI, fasting glycemia, uric acid, and physical activity.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-10-0454
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1485160-X
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