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Tatti P, Singh P. Insulin Resistance: An Unresolved Riddle. J Clin Med 2023; 12:6394. [PMID: 37835038 PMCID: PMC10573251 DOI: 10.3390/jcm12196394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 10/15/2023] Open
Abstract
Insulin resistance (IR) is a rather common condition that is often diagnosed on the basis of an arbitrary "increased insulin value" or the presence of symptoms indicative of the Metabolic Syndrome [...].
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Cabiati M, Randazzo E, Guiducci L, Falleni A, Cecchettini A, Casieri V, Federico G, Del Ry S. Evaluation of Exosomal Coding and Non-Coding RNA Signature in Obese Adolescents. Int J Mol Sci 2022; 24:ijms24010139. [PMID: 36613584 PMCID: PMC9820564 DOI: 10.3390/ijms24010139] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Exosomes may contribute to the pathogenesis of obesity through their action as communication mediators. As we have previously demonstrated, in obese adolescents, some circulating miRNAs modified the C-type natriuretic peptide (CNP) expression and were associated with changes in metabolic functions. At present no data are available on miRNA transport by exosomes in this condition. To verify and compare the presence and the expression of CNP/NPR-B/NPR-C, and some miRNAs (miR-33a-3p/miR-223-5p/miR-142-5p/miRNA-4454/miRNA-181a-5p/miRNA-199-5p), in circulating exosomes obtained from the same cohort of obese (O, n = 22) and normal-weight adolescents (N, n = 22). For the first time, we observed that exosomes carried CNP and its specific receptors only randomly both in O and N, suggesting that exosomes are not important carriers for the CNP system. On the contrary, exosomal miRNAs resulted ubiquitously and differentially expressed in O and N. O showed a significant decrease (p < 0.01) in the expression of all miRNAs except for miR-4454 and miR-142-5p. We have found significant correlations among miRNAs themselves and with some inflammatory/metabolic factors of obesity. These relationships may help in finding new biomarkers, allowing us to recognize, at an early stage, obese children and adolescents at high risk to develop the disease complications in adult life.
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Affiliation(s)
- Manuela Cabiati
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, 56124 Pisa, Italy
| | - Emioli Randazzo
- Unit of Pediatric Endocrinology and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Letizia Guiducci
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, 56124 Pisa, Italy
| | - Alessandra Falleni
- Department of Experimental and Clinical Medicine, University of Pisa, 56126 Pisa, Italy
| | - Antonella Cecchettini
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, 56124 Pisa, Italy
- Department of Experimental and Clinical Medicine, University of Pisa, 56126 Pisa, Italy
| | - Valentina Casieri
- Scuola Superiore Sant’Anna, Unit of Translational Critical Care Medicine, 56126 Pisa, Italy
| | - Giovanni Federico
- Unit of Pediatric Endocrinology and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Silvia Del Ry
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, 56124 Pisa, Italy
- Scuola Superiore Sant’Anna, Unit of Translational Critical Care Medicine, 56126 Pisa, Italy
- Correspondence: ; Tel.: +39-050-3152793; Fax: +39-050-3152166
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Jawich K, Rocca MS, Al Fahoum S, Alhalabi M, Di Nisio A, Foresta C, Ferlin A, De Toni L. RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function. J Endocrinol Invest 2022; 45:1673-1682. [PMID: 35482214 DOI: 10.1007/s40618-022-01803-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/07/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function. METHODS 190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism. RESULTS Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P < 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P < 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P < 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007). CONCLUSIONS Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.
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Affiliation(s)
- K Jawich
- Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic
| | - M Santa Rocca
- Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy
- Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padua, Italy
| | - S Al Fahoum
- Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic.
| | - M Alhalabi
- Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic
| | - A Di Nisio
- Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy
| | - C Foresta
- Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy
| | - A Ferlin
- Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy
| | - L De Toni
- Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy
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Statins, gut microbiome, LDL-C, glucose intolerance: Personalized medicine timely? MED 2022; 3:355-357. [PMID: 35690054 DOI: 10.1016/j.medj.2022.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Statins are a mainstay in reducing cardiovascular disease risk by reducing circulating levels of plasma LDL-C. In this issue of Med, Wilmanski et al. demonstrate how the composition of the gut microbiome influences the pharmacological benefits and risks of statin therapy, an exciting additional step in personalized medicine.
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Amisi CA. Markers of insulin resistance in Polycystic ovary syndrome women: An update. World J Diabetes 2022; 13:129-149. [PMID: 35432749 PMCID: PMC8984569 DOI: 10.4239/wjd.v13.i3.129] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 09/14/2021] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.
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Affiliation(s)
- Chantal Anifa Amisi
- Endocrinology and Diabetes Unit, Department of Medicine, Universita Campus Bio-medico di Rome, Rome 00128, Italy
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Kavyani M, Saleh-Ghadimi S, Dehghan P, Abbasalizad Farhangi M, Khoshbaten M. Co-supplementation of camelina oil and a prebiotic is more effective for in improving cardiometabolic risk factors and mental health in patients with NAFLD: a randomized clinical trial. Food Funct 2021; 12:8594-8604. [PMID: 34338703 DOI: 10.1039/d1fo00448d] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This trial evaluated the effects of co-supplementing Camelina sativa oil (CSO) and a prebiotic as modulators of the gut microbiota on cardiometabolic risk factors and mental health in NAFLD patients. In all, 44 subjects with NAFLD were allocated to either an intervention (20 g d-1 CSO + resistant dextrin) or a placebo (20 g d-1 CSO + maltodextrin) group and received a calorie-restricted diet (-500 kcal d-1) for 12 weeks. Fasting plasma levels of gucose, insulin, hs-CRP, endotoxin, antioxidant enzyme activity, total antioxidant capacity (TAC), malondialdehyde (MDA), 8-iso-prostaglandin F2α, and uric acid were measured at the baseline and post-intervention. The depression, anxiety and stress scale (DASS) and the general health questionnaire (GHQ) were used to assess mental health. Co-supplementing CSO and resistant dextrin significantly decreased the level of insulin concentration (-0.84 μU ml-1, p = 0.011), HOMA-IR (-0.27, p = 0.021), hs-CRP (-1.25 pg ml-1, p = 0.023), endotoxin (-3.70 EU mL-1, p = 0.001), cortisol (-2.43, p = 0.033), GHQ (-5.03, p = 0.035), DASS (-9.01, p = 0.024), and MDA (-0.54 nmol mL-1, p = 0.021) and increased the levels of TAC (0.16 mmol L-1, p = 0.032) and superoxide dismutase (106.32 U g-1 Hb, p = 0.45) in the intervention group compared with the placebo group. No significant changes were observed in the levels of other biomarkers. Co-supplementing CSO and resistant dextrin in combination with a low-calorie diet may improve metabolic risk factors and mental health in NAFLD patients.
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Affiliation(s)
- Maryam Kavyani
- Student research committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sevda Saleh-Ghadimi
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Parvin Dehghan
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mahdieh Abbasalizad Farhangi
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. and Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manouchehr Khoshbaten
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Sharma VR, Matta ST, Haymond MW, Chung ST. Measuring Insulin Resistance in Humans. Horm Res Paediatr 2021; 93:577-588. [PMID: 33934092 PMCID: PMC8162778 DOI: 10.1159/000515462] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 02/25/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use. SUMMARY In this historical perspective, we explore the evolution of the term "insulin resistance" and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. Key Message: Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.
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Affiliation(s)
- Vandhna R. Sharma
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Samantha T. Matta
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | | | - Stephanie T. Chung
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA,*Stephanie T. Chung,
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Cabiati M, Randazzo E, Salvadori C, Peroni D, Federico G, Del Ry S. Circulating microRNAs associated with C-type natriuretic peptide in childhood obesity. Peptides 2020; 133:170387. [PMID: 32828851 DOI: 10.1016/j.peptides.2020.170387] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 12/13/2022]
Abstract
Circulating microRNAs (miRNAs) are potential biomarkers of metabolic disease implicated in the pathogenesis of obesity and at present, no data are available on a possible contribution of C-type natriuretic peptides (CNP)-linked miRNAs to childhood obesity. Our aims were to 1) perform an in silico-analysis to identify miRNAs targeting CNP gene; 2) recognize CNP-linked miRNAs associated with obesity; 3) characterize their circulating profiling in normal-weight (N) and obese adolescents (O). A clinical examination was performed in 25 N and 52 O adolescents. CNP plasma levels were detected by immunometric assay while miRNA expression was carried out on peripheral blood using Real-Time PCR. Plasma CNP resulted significantly lower in O than in N (5.58 ± 0.62 vs.14.78 ± 1.35 pg/mL, p < 0.0001). In silico-analysis disclosed several specific circulating CNP-linked miRNAs among which miR-33a-3p, miR-223-5p and miR-142-5p also associated with obesity. MiR-199-5p and miR-4454, known to be associated with obesity but not with CNP, were also studied. miR-223-5p and miR-33a-3p resulted significantly (p = 0.05) higher in O (0.97 ± 0.1; 0.85 ± 0.1, respectively) than in N (0.66 ± 0.11; 0.51 ± 0.08, respectively). Plasma CNP correlated inversely with miR-33a-3p (p = 0.036), miR-223-5p (p = 0.004), miR-199-5p (p = 0.003) and miR-4454 (p < 0.0001). Significantly positive correlations were observed between miR-33a-3p and miR-223-5p (p = 0.002) and between miR-199-5p and miR-4454 (p = 0.0001). Applying a multiple linear regression model, miR-142-5p, miR-199a-5p, miR-223-5p, miR33a-3p, diastolic blood pressure (DBP) and age were independent determinants of CNP. Our results underline the concept that expanding our knowledge on the behaviour of circulating miRNA profile may have a promising role for early identification of obese children at increased risk of cardiometabolic alterations.
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Affiliation(s)
- Manuela Cabiati
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, Pisa, Italy
| | - Emioli Randazzo
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Costanza Salvadori
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, Pisa, Italy
| | - Diego Peroni
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Giovanni Federico
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Silvia Del Ry
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, Pisa, Italy.
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Derosa G, D'Angelo A, Martinotti C, Valentino MC, Di Matteo S, Bruno GM, Maffioli P. Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial. INT J VITAM NUTR RES 2020; 92:91-100. [PMID: 32795167 DOI: 10.1024/0300-9831/a000673] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.
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Affiliation(s)
- Giuseppe Derosa
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.,Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Angela D'Angelo
- Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Chiara Martinotti
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Centre, Milan, Italy
| | | | - Sergio Di Matteo
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Centre, Milan, Italy
| | - Giacomo M Bruno
- Department of Management information and production Engineering, University of Bergamo, Bergamo, Italy.,Drug Science Department, University of Pavia, Pavia, Italy
| | - Pamela Maffioli
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
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So A, Sakaguchi K, Okada Y, Morita Y, Yamada T, Miura H, Otowa-Suematsu N, Nakamura T, Komada H, Hirota Y, Tamori Y, Ogawa W. Relation between HOMA-IR and insulin sensitivity index determined by hyperinsulinemic-euglycemic clamp analysis during treatment with a sodium-glucose cotransporter 2 inhibitor. Endocr J 2020; 67:501-507. [PMID: 32023587 DOI: 10.1507/endocrj.ej19-0445] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
We had aimed to determine whether homeostasis model assessment-insulin resistance (HOMA-IR) reflects insulin resistance-sensitivity during treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Hyperinsulinemic-euglycemic clamp analysis was performed in 22 patients with type 2 diabetic patients taking dapagliflozin (5 mg/day before or after breakfast). Propensity score matching of these individuals (SGLT2i group) for age, sex, body mass index, and clamp-derived tissue glucose uptake rate with 44 type 2 diabetic patients who had undergone clamp analysis without SGLT2i treatment (control group) identified 17 paired subjects in each group for further analysis of the relation between HOMA-IR and a clamp-derived insulin sensitivity index (ISI). Natural log-transformed HOMA-IR was negatively correlated with ISI in both SGLT2i (r = -0.527, p = 0.030) and control (r = -0.534, p = 0.027) groups. The simple regression lines for log-transformed HOMA-IR and ISI in the two groups showed similar slopes but differed in their intercepts. Multivariate analysis revealed that HOMA-IR for patients with the same ISI in the two groups was related by the formula: HOMA-IRcontrol = HOMA-IRSGLT2i × 2.45. In conclusion, HOMA-IR was well correlated with ISI during SGLT2i treatment, but values corresponding to the same ISI were lower in the SGLT2i group than in the control group.
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Affiliation(s)
- Anna So
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazuhiko Sakaguchi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of General Internal Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuko Okada
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yasuko Morita
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoko Yamada
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroshi Miura
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Natsu Otowa-Suematsu
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoaki Nakamura
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Diabetes and Endocrinology, Akashi Medical Center, Akashi, Japan
| | - Hisako Komada
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yushi Hirota
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshikazu Tamori
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of Creative Health Promotion, Department of Social/Community Medicine and Health Science, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wataru Ogawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
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Del Ry S, Cabiati M, Bianchi V, Randazzo E, Peroni D, Clerico A, Federico G. C-type natriuretic peptide plasma levels and whole blood mRNA expression show different trends in adolescents with different degree of endothelial dysfunction. Peptides 2020; 124:170218. [PMID: 31794787 DOI: 10.1016/j.peptides.2019.170218] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/15/2019] [Accepted: 11/26/2019] [Indexed: 12/13/2022]
Abstract
C-type natriuretic peptide (CNP) is an endogenous adipogenesis regulator whose plasma levels in childhood are known, while no data are available on its expression. Our aim was to evaluate both CNP plasma levels and CNP system expression in whole blood obtained from normal-weight (N, n = 24) and obese (O, n = 16) adolescents (age:13.5 ± 0.4 years). Endothelial function was assessed measuring reactive hyperemia index (RHI). CNP plasma levels, evaluated with specific RIA, resulted significantly lower in O than in N (6.1 ± 0.8 vs.15.2 ± 1.3 pg/mL; p < 0.0001), while CNP/NPR-B/NPR-C mRNA, measured by Real-Time PCR, resulted similar in N (4.1 ± 1.7; 5.0 ± 1.6; 2.2 ± 0.9) and in O (4.3 ± 1.6; 3.5 ± 1.1; 2.3 ± 0.8). RHI was significantly lower in O than in N (1.4 ± 0.08 vs.2.1 ± 0.04, p < 0.0001). Dividing all subjects according to the RHI median value, irrespective of the presence or absence of obesity (Group 1 > 1.9, n = 23, Group 2 < 1.9, n = 17), CNP plasma concentrations resulted significantly (p = 0.014) higher in Group 1 (14.6 ± 1.6) than in Group 2 (7.5 ± 1.0), showing a significant correlation with RHI (p = 0.0026), while CNP mRNA expression was, surprisingly, higher in Group 2 (7.0 ± 2.3) than in Group 1 (1.8 ± 0.4; p = 0.02). NPR-B mRNA resulted similar in both Groups (4.3 ± 1.6; 4.7 ± 1.3) and NPR-C significantly higher in Group 2 (p = 0.02). Our data suggest different trends between CNP plasma levels and expression, assessed for the first time in whole blood, that could reflect changes occurring both at CNP transcriptional level in activated leukocytes due to inflammation, and at circulating levels, due to CNP paracrine/autocrine activities. This could represent an interesting area for new therapies able to modulate endothelial dysfunction.
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Affiliation(s)
- Silvia Del Ry
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, Pisa, Italy; Institute of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy.
| | - Manuela Cabiati
- Laboratory of Biochemistry and Molecular Biology, Institute of Clinical Physiology, CNR, Pisa, Italy
| | - Vanessa Bianchi
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Emioli Randazzo
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Diego Peroni
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
| | - Aldo Clerico
- Institute of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Giovanni Federico
- Unit of Pediatric Endocrinology and Diabetes, Dep. Clinical and Experimental Medicine, University of Pisa, Italy
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Keenan DM, Veldhuis JD, Basu A, Basu R. A novel measure of glucose homeostasis (or loss thereof) comprising the joint dynamics of glucose, insulin, glucagon, and cortisol. Am J Physiol Endocrinol Metab 2019; 316:E998-E1011. [PMID: 30860881 PMCID: PMC6620575 DOI: 10.1152/ajpendo.00078.2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Quantification of disturbances in glucose-insulin homeostasis has been the cornerstone of appraising insulin resistance and detecting early-stage diabetes. Metabolic homeostasis arises from feedback and feed-forward interactions among (at least) all four of glucose, insulin, glucagon, and cortisol. Quantifying such tetrapartite interactions in the fasting (endogenously regulated) state overnight could elucidate very early regulatory disruption. In the present study, healthy subjects without diabetes (ND; n = 20) and patients with Type 2 diabetes (T2D; n = 21) were investigated by repeated overnight blood sampling of all four of glucose, insulin, glucagon, and cortisol concentrations. To obviate confounding by hormone-specific disappearance rates, analyses were performed at the level of production (glucose) or secretion (insulin, glucagon, and cortisol) rates estimated by regularized deconvolution analysis. Then, a novel method for quantifying the loss of homeostasis among glucose, insulin, and glucagon (and, when available, cortisol) secretion patterns was developed. Potential early stage prediabetic candidates were identified. The new methodology avoids many of the difficulties encountered in the conventional estimation of insulin-glucose sensitivity or resistance, while incorporating the dynamics of the key coregulators under fasting conditions.
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Affiliation(s)
- Daniel M Keenan
- Department of Statistics, University of Virginia , Charlottesville, Virginia
| | - Johannes D Veldhuis
- Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic , Rochester, Minnesota
| | - Ananda Basu
- Division of Endocrinology, Center of Diabetes Technology, University of Virginia School of Medicine , Charlottesville, Virginia
| | - Rita Basu
- Division of Endocrinology, Center of Diabetes Technology, University of Virginia School of Medicine , Charlottesville, Virginia
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13
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Huerta-Ávila EE, Ramírez-Silva I, Torres-Sánchez LE, Díaz-Benítez CE, Orbe-Orihuela YC, Lagunas-Martínez A, Galván-Portillo M, Flores M, Cruz M, Burguete-García AI. High Relative Abundance of Lactobacillus reuteri and Fructose Intake are Associated with Adiposity and Cardiometabolic Risk Factors in Children from Mexico City. Nutrients 2019; 11:nu11061207. [PMID: 31141963 PMCID: PMC6627236 DOI: 10.3390/nu11061207] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/10/2019] [Accepted: 05/10/2019] [Indexed: 01/04/2023] Open
Abstract
In Mexico, 3 of 10 children are overweight. Fructose intake and relative abundance (RA) of Lactobacillus reuteri (L. reuteri) in the intestinal microbiota are associated with obesity and diabetes in adults, but studies in children are limited. This study evaluates the association between fructose intake and L. reuteri RA with adiposity and cardiometabolic risk markers in Mexican children dietary information, microbiota profiles, adiposity indicators (Body Mass Index, BMI and Waste Circumference, WC), and cardiometabolic markers were analyzed in 1087 children aged 6–12 years. Linear regression and path analysis models were used. High-tertile fructose intake and L. reuteri RA were positively associated with BMI (βTertil 3 vs. Tertil 1= 0.24 (95% CI, 0.04; 0.44) and βT3 vs. T1 = 0.52 (95% CI, 0.32; 0.72)) and WC (βT3 vs. T1 = 2.40 (95% CI, 0.93; 3.83) and βT3 vs. T1 = 3.40 (95% CI, 1.95; 4.90)), respectively. Also, these factors mediated by adiposity were positively correlated with high triglycerides and insulin concentrations and HOMA-IR (p ≤ 0.03) and negatively associated with HDL-C concentration (p < 0.01). High-tertile fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated though adiposity with metabolic disorders in children. In conclusion, fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated with metabolic disorders in children, mediated by adiposity.
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Affiliation(s)
- Eira E Huerta-Ávila
- Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Ivonne Ramírez-Silva
- Centro de Investigación sobre Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Luisa E Torres-Sánchez
- Centro de Investigación Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Cinthya E Díaz-Benítez
- Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Yaneth C Orbe-Orihuela
- Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Alfredo Lagunas-Martínez
- Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Marcia Galván-Portillo
- Centro de Investigación Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Mario Flores
- Centro de Investigación sobre Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
| | - Miguel Cruz
- Unidad de Investigación Médica en Bioquímica, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Ciudad de México, CDMX 06600, México.
| | - Ana I Burguete-García
- Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, México.
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14
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Saha S, Schwarz PEH. Impact of glycated hemoglobin (HbA1c) on identifying insulin resistance among apparently healthy individuals. J Public Health (Oxf) 2017. [DOI: 10.1007/s10389-017-0805-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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15
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Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor. Mol Cell Biochem 2016; 419:185-92. [PMID: 27426490 DOI: 10.1007/s11010-016-2772-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Accepted: 07/09/2016] [Indexed: 10/21/2022]
Abstract
The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.
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Masuyama H, Mitsui T, Eguchi T, Tamada S, Hiramatsu Y. The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters. Am J Physiol Endocrinol Metab 2016; 311:E236-45. [PMID: 27245335 DOI: 10.1152/ajpendo.00095.2016] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 05/26/2016] [Indexed: 11/22/2022]
Abstract
Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.
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Affiliation(s)
- Hisashi Masuyama
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Takashi Mitsui
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Takeshi Eguchi
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Shoko Tamada
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yuji Hiramatsu
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Gao X, Zhang W, Wang Y, Pedram P, Cahill F, Zhai G, Randell E, Gulliver W, Sun G. Serum metabolic biomarkers distinguish metabolically healthy peripherally obese from unhealthy centrally obese individuals. Nutr Metab (Lond) 2016; 13:33. [PMID: 27175209 PMCID: PMC4865032 DOI: 10.1186/s12986-016-0095-9] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 05/03/2016] [Indexed: 12/11/2022] Open
Abstract
Background Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals. Methods A two-stage case–control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR > 4.27 (90th percentile), 2) high-density lipoprotein cholesterol < 1.03 mmol/L in men and < 1.30 mmol/L in women, 3) fasting blood glucose ≥ 5.6 mmol/L, and 4) waist circumference > 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites. Results In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage. Conclusions Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity. Electronic supplementary material The online version of this article (doi:10.1186/s12986-016-0095-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiang Gao
- College of Food Science and Engineering, Ocean University of China, No.5, Yu Shan Road, Qingdao, Shandong Province China ; Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Weidong Zhang
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Yongbo Wang
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada ; Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000 Liaoning China
| | - Pardis Pedram
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Farrell Cahill
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Guangju Zhai
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Edward Randell
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Wayne Gulliver
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
| | - Guang Sun
- Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada
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Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats. Int J Biol Macromol 2016; 83:126-32. [DOI: 10.1016/j.ijbiomac.2015.11.045] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 10/29/2015] [Accepted: 11/16/2015] [Indexed: 11/22/2022]
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19
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Treviño S, Waalkes MP, Flores Hernández JA, León-Chavez BA, Aguilar-Alonso P, Brambila E. Chronic cadmium exposure in rats produces pancreatic impairment and insulin resistance in multiple peripheral tissues. Arch Biochem Biophys 2015; 583:27-35. [PMID: 26253262 DOI: 10.1016/j.abb.2015.07.010] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 06/17/2015] [Accepted: 07/10/2015] [Indexed: 12/20/2022]
Abstract
Previous studies have linked cadmium exposure to disturbances in carbohydrate and lipid metabolism. In this study we investigate the effects in Wistar rats of an oral cadmium exposure in drinking water on carbohydrates, lipids and insulin release. Also, using mathematical models we studied the effect of cadmium on insulin resistance and sensitivity in liver, muscle, adipose and cardiovascular tissue. Cadmium exposure induced hyperglycemia, increased insulin release after a glucose load, and caused increases in serum triglycerides, cholesterol, LDL-C and VLDL-C, and a decrease of HDL-C. In addition, there was an accumulation of cadmium in pancreas and an increase of insulin. After exposure, HOMA-IR was increased, while the HOMA-S%, QUICKI and Matsuda-DeFronzo indexes showed decreases. A decrease of insulin sensitivity was shown in muscle and liver. Additionally, cadmium increases insulin resistance in the liver, adipose tissue and cardiovascular system. Finally, β-cell functioning was evaluated by HOMA-B% index and insulin disposition index, which were decreased, while insulin generation index increased. In conclusion, cadmium increases insulin release, induces hyperglycemia and alters lipid metabolism. These changes likely occur as a consequence of reduced sensitivity and increased insulin resistance in multiple insulin-dependent and non-dependent tissues, producing a biochemical phenotype similar to metabolic syndrome and diabetes.
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Affiliation(s)
- Samuel Treviño
- Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico
| | - Michael P Waalkes
- Stem Cell Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
| | - José Angel Flores Hernández
- Departamento de Análisis Clínicos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico
| | - Bertha Alicia León-Chavez
- Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico
| | - Patricia Aguilar-Alonso
- Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico
| | - Eduardo Brambila
- Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
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The Frequent Adiponutrin (PNPLA3) Variant p.Ile148Met Is Associated with Early Liver Injury: Analysis of a German Pediatric Cohort. Gastroenterol Res Pract 2015; 2015:205079. [PMID: 26346943 PMCID: PMC4539481 DOI: 10.1155/2015/205079] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Revised: 03/05/2015] [Accepted: 03/05/2015] [Indexed: 01/23/2023] Open
Abstract
Introduction. The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. Here, we investigate the association of this polymorphism with hepatic and metabolic traits in a pediatric cohort. Patients and Methods. The study cohort comprised 142 German children (age 5-9 years, 98 overweight, 19 children with NAFLD). Results. Overweight children presented with increased serum ALT (P = 0.001) and GGT (P < 0.001) activities. ALT activities differed significantly (P = 0.02) between carriers of different PNPLA3 genotypes in the entire study cohort, in normal weight children (P = 0.02) and in children younger than 7 years (P = 0.02). Carriers of the prosteatotic PNPLA3 genotype p.148Met/Met displayed higher ALT activities as compared to children with the frequent genotype p.148Ile/Ile (P = 0.01). The BMI was however a stronger predictor of ALT activities compared to the PNPLA3 genotype (P < 0.001 and P = 0.06, resp.). The variant was associated with increased serum glucose levels (P = 0.01) and HOMA index (P = 0.02) in carriers of the p.148Ile/Met genotype but did not affect other metabolic traits or the presence of NAFLD. Discussion. The frequent PNPLA3 variant p.Ile148Met is associated with serum ALT activities already at a young age.
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Masuyama H, Mitsui T, Nobumoto E, Hiramatsu Y. The Effects of High-Fat Diet Exposure In Utero on the Obesogenic and Diabetogenic Traits Through Epigenetic Changes in Adiponectin and Leptin Gene Expression for Multiple Generations in Female Mice. Endocrinology 2015; 156:2482-91. [PMID: 25853666 DOI: 10.1210/en.2014-2020] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Recent studies demonstrate that epigenetic changes under malnutrition in utero might play important roles in transgenerational links with metabolic diseases. We have previously shown that exposure to a high-fat diet (HFD) in utero may cause a metabolic syndrome-like phenomenon through epigenetic modifications of Adiponectin and Leptin genes. Because an association of obesity between mother and offspring endured in multiple generations, we examined whether HFD exposure in utero might affect the metabolic status of female offspring through multigenerational epigenetic changes of Adiponectin and Leptin genes and whether a normal diet in utero for multiple generations might abolish such epigenetic changes after exposure to a HFD in utero using ICR mice. We observed that the effect of maternal HFD on offspring over multiple generations in metabolic syndrome-like phenomenon such as weight and fat mass gain, glucose intolerance, hypertriglyceridemia, abnormal adiponectin and leptin levels, and hypertension, were accumulated with expression and epigenetic changes in Adiponectin and Leptin genes. A normal diet in utero in the subsequent generations after HFD exposure in utero diminished, and a normal diet in utero for 3 generations completely abolished, the effect of HFD in utero on weight and fat mass gain, insulin resistance, serum triglyceride, adiponectin, and leptin levels, with epigenetic changes of Adiponectin and Leptin genes. Exposure to a HFD in utero might affect glucose and lipid metabolism of female offspring through epigenetic modifications to Adiponectin and Leptin genes for multiple generations. Obesogenic and diabetogenic traits were abolished after a maternal normal diet for 3 generations.
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Affiliation(s)
- Hisashi Masuyama
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Takashi Mitsui
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Etsuko Nobumoto
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Yuji Hiramatsu
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Luong DQ, Oster R, Ashraf AP. Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome. J Pediatr Endocrinol Metab 2015; 28:649-55. [PMID: 25210757 DOI: 10.1515/jpem-2014-0201] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Accepted: 08/14/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND To determine the effects of metformin therapy in children with metabolic syndrome (MS). METHODS A retrospective electronic chart review in children aged 8-18 years, from 2000 to 2012 with a diagnosis code for MS (ICD 277.7) that met the modified NCEP ATPIII criteria for MS. RESULTS There were a total of 217 subjects, 150 in the non-metformin [untreated group (UTG)] and 67 in the metformin treated group (MTG). At baseline, the MTG had a body mass index (BMI) similar to UTG, but had higher total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high density lipoprotein cholesterol (non-HDL-C). At the end of 1 year, the MTG (n=28) had reduced weight percentile (99.4±0.7 vs. 98.9±1.7, p=0.03), BMI percentile (99.2±0.5 vs. 98.8±1.1, p=0.012), total cholesterol (194.9±45.8 vs. 177.9±32.5 mg/dL, p=0.04), LDL-C (128.3±44.7 vs. 113.8±36.0 mg/dL, p=0.04), and non-HDL-C (154.6±45.5 vs. 136.4±35.2 mg/dL, p=0.03) compared to their baseline. The UTG (n=56) did not have any significant change in those parameters. CONCLUSIONS Metformin treatment results in significant improvement in BMI, total cholesterol, LDL-C, and non-HDL-C in children with MS.
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Ozgu-Erdinc AS, Yilmaz S, Yeral MI, Seckin KD, Erkaya S, Danisman AN. Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices. J Matern Fetal Neonatal Med 2014; 28:1957-62. [PMID: 25283990 DOI: 10.3109/14767058.2014.973397] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To develop a predictive index based on high sensitivity C-reactive protein (hs-CRP), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) measurements for early diagnosis of gestational diabetes mellitus (GDM). METHODS Healthy pregnant women who were screened for GDM during their first antenatal visit were included in this retrospective cohort study. FPG, FPI and serum hs-CRP concentrations were measured between weeks 11 and 14. A two-step glucose challenge test was carried out between gestational weeks 24 and 28. Fasting glucose/insulin ratio (FIGR), Homeostatic Model Assessment Insulin Resistance (HOMA-IR), HOMA-β indices and Quantitative Insulin Sensitivity Check Index (QUICKI) were used to estimate insulin sensitivity and β-cell function. RESULTS Of the 450 women who were eligible for the study, 49 (11.2%) were diagnosed with GDM at weeks 24-28. The median FPG and hs-CRP levels were higher in the GDM diagnosed women compared to the others. Comparison of accuracy measures resulted in the highest specificity (87.2%; 95% CI 83.5-90.1) and diagnostic odds ratio (3.9; 95% CI 2.1-7.6) for hs-CRP. CONCLUSION FPG and hs-CRP in the first trimester are correlated with later development of GDM in the pregnancy. In our study, FPG provided a better sensitivity while hs-CRP exhibited a better specificity for prediction of GDM.
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Affiliation(s)
- A Seval Ozgu-Erdinc
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
| | - Saynur Yilmaz
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
| | - M Ilkin Yeral
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
| | - K Doga Seckin
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
| | - Salim Erkaya
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
| | - A Nuri Danisman
- a Zekai Tahir Burak Women's Health Care, Training and Research Hospital , Ankara , Turkey
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Timonen P, Saxlin T, Knuuttila M, Suominen AL, Jula A, Tervonen T, Ylöstalo P. Role of insulin sensitivity and beta cell function in the development of periodontal disease in adults without diabetes. J Clin Periodontol 2014; 40:1079-86. [PMID: 24192072 DOI: 10.1111/jcpe.12162] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2013] [Indexed: 01/22/2023]
Abstract
AIM The goal of this study was to explore whether insulin resistance and beta cell function are related to periodontal pocket formation, indicative of infectious periodontal disease in non-smoking adults without manifest diabetes. MATERIAL AND METHODS We analysed data from a Health 2000 Survey consisting of dentate subjects without any indication of diabetes, aged between 30 and 64, who had never smoked and who had participated in the Follow-up Study on Finnish Adults' Oral Health about 4 years later (n = 157). The Homeostasis Model Assessment Indices were used to measure insulin resistance (HOMA-IR) and β-cell function (HOMA-B). The development of periodontal disease was measured by means of the incidence of deepened periodontal pockets (4 mm deep or deeper) during the follow-up period. Incidence rate ratios (IRR) were estimated using Poisson regression models. RESULTS Both HOMA-IR and HOMA-B indices were associated with periodontal pocket formation during the 4-year follow-up. CONCLUSION The results of this follow-up study suggest that impaired glucose metabolism measured as insulin resistance and altered beta cell function predict the breakdown of periodontal tissues. Further studies about their role in the pathogenesis of periodontal diseases are needed.
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Affiliation(s)
- Petra Timonen
- Department of Periodontology and Geriatric Dentistry, Institute of Dentistry, University of Oulu, Oulu, Finland
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Haemer MA, Grow HM, Fernandez C, Lukasiewicz GJ, Rhodes ET, Shaffer LA, Sweeney B, Woolford SJ, Estrada E. Addressing prediabetes in childhood obesity treatment programs: support from research and current practice. Child Obes 2014; 10:292-303. [PMID: 25055134 PMCID: PMC4120814 DOI: 10.1089/chi.2013.0158] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) and prediabetes have increased in prevalence among overweight and obese children, with significant implications for long-term health. There is little published evidence on the best approaches to care of prediabetes among overweight youth or the current practices used across pediatric weight management programs. METHODS This article reviews the literature and summarizes current practices for screening, diagnosis, and treatment of prediabetes at childhood obesity treatment centers. Findings regarding current practice were based on responses to an online survey from 28 pediatric weight management programs at 25 children's hospitals in 2012. Based on the literature reviewed, and empiric data, consensus support statements on prediabetes care and T2DM prevention were developed among representatives of these 25 children's hospitals' obesity clinics. RESULTS The evidence reviewed demonstrates that current T2DM and prediabetes diagnostic parameters are derived from adult-based studies with little understanding of clinical outcomes among youth. Very limited evidence exists on preventing progression of prediabetes. Some evidence suggests that a significant proportion of obese youth with prediabetes will revert to normoglycemia without pharmacological management. Evidence supports lifestyle modification for children with prediabetes, but further study of specific lifestyle changes and pharmacological treatments is needed. CONCLUSION Evidence to guide management of prediabetes in children is limited. Current practice patterns of pediatric weight management programs show areas of variability in practice, reflecting the limited evidence base. More research is needed to guide clinical care for overweight youth with prediabetes.
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Affiliation(s)
- Matthew A. Haemer
- Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine, Aurora, CO
| | - H. Mollie Grow
- Department of Pediatrics, University of Washington School of Medicine, Seattle, WA
| | - Cristina Fernandez
- Department of Pediatrics, Creighton University School of Medicine, Omaha, NE
| | | | - Erinn T. Rhodes
- Division of Endocrinology, Boston Children's Hospital, Boston, MA
| | - Laura A. Shaffer
- Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY
| | - Brooke Sweeney
- Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY
| | | | - Elizabeth Estrada
- Division of Endocrinology, Connecticut Children's Medical Center, Hartford, CT
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26
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Affiliation(s)
- Jerry Radziuk
- Department of Medicine, University of Ottawa, Ottawa Hospital, Ottawa, Ontario, Canada
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Ader M, Stefanovski D, Richey JM, Kim SP, Kolka CM, Ionut V, Kabir M, Bergman RN. Failure of homeostatic model assessment of insulin resistance to detect marked diet-induced insulin resistance in dogs. Diabetes 2014; 63:1914-9. [PMID: 24353184 PMCID: PMC4876683 DOI: 10.2337/db13-1215] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Accurate quantification of insulin resistance is essential for determining efficacy of treatments to reduce diabetes risk. Gold-standard methods to assess resistance are available (e.g., hyperinsulinemic clamp or minimal model), but surrogate indices based solely on fasting values have attractive simplicity. One such surrogate, the homeostatic model assessment of insulin resistance (HOMA-IR), is widely applied despite known inaccuracies in characterizing resistance across groups. Of greater significance is whether HOMA-IR can detect changes in insulin sensitivity induced by an intervention. We tested the ability of HOMA-IR to detect high-fat diet-induced insulin resistance in 36 healthy canines using clamp and minimal model analysis of the intravenous glucose tolerance test (IVGTT) to document progression of resistance. The influence of pancreatic function on HOMA-IR accuracy was assessed using the acute insulin response during the IVGTT (AIRG). Diet-induced resistance was confirmed by both clamp and minimal model (P < 0.0001), and measures were correlated with each other (P = 0.001). In striking contrast, HOMA-IR ([fasting insulin (μU/mL) × fasting glucose (mmol)]/22.5) did not detect reduced sensitivity induced by fat feeding (P = 0.22). In fact, 13 of 36 animals showed an artifactual decrease in HOMA-IR (i.e., increased sensitivity). The ability of HOMA-IR to detect diet-induced resistance was particularly limited under conditions when insulin secretory function (AIRG) is less than robust. In conclusion, HOMA-IR is of limited utility for detecting diet-induced deterioration of insulin sensitivity quantified by glucose clamp or minimal model. Caution should be exercised when using HOMA-IR to detect insulin resistance when pancreatic function is compromised. It is necessary to use other accurate indices to detect longitudinal changes in insulin resistance with any confidence.
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Affiliation(s)
- Marilyn Ader
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Darko Stefanovski
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Joyce M. Richey
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Stella P. Kim
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Cathryn M. Kolka
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Viorica Ionut
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Morvarid Kabir
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Richard N. Bergman
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
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Anti-Obesity Effects of Poly-γ-glutamic Acid with or without Isoflavones on High-Fat Diet Induced Obese Mice. Biosci Biotechnol Biochem 2014; 77:1694-702. [DOI: 10.1271/bbb.130253] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Onopchenko OV, Kosiakova HV, Horid'ko TM, Klimashevskyĭ VM, Hula NM. [The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity]. UKRAINIAN BIOCHEMICAL JOURNAL 2014; 86:101-10. [PMID: 24834723 DOI: 10.15407/ubj86.01.101] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
We used alimentary obesity-induced insulin resistance (IR) model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic) and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic) fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight) caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influence of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.
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Additive effects of maternal high fat diet during lactation on mouse offspring. PLoS One 2014; 9:e92805. [PMID: 24664181 PMCID: PMC3963955 DOI: 10.1371/journal.pone.0092805] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Accepted: 02/26/2014] [Indexed: 12/30/2022] Open
Abstract
Recent reports indicated that nutrition in early infancy might influence later child health outcomes such as obesity and metabolic syndrome. Therefore, we examined the effects of maternal high fat diet (HFD) during lactation on the onset of a metabolic syndrome in their offspring. All offspring were cross-fostered by dams on the same or opposite diet to yield 4 groups: offspring from HFD-fed dams suckled by HFD-fed dams (OHH) and by control diet (CD)-fed dams (OHC) and CD-fed dams suckled by HFD-fed dams (OCH) and by CD-fed dams (OCC) mice. We examined several metabolic syndrome-related factors including body weight, blood pressure, glucose tolerance and adipocytokines. Mean body weights of OHH and OCH mice were significantly higher than those of OHC and OCC mice, respectively, with elevated systolic blood pressure. Moreover, OHH and OCH mice revealed significantly worse glucose tolerance compared with the OHC and OCC mice, respectively. Triglyceride and leptin levels were significantly increased and adiponectin levels were significantly reduced by the maternal HFD during lactation, with similar changes in leptin and adiponectin mRNA expression but without histone modifications in adipose tissues. In addition, maternal obesity induced by HFD during lactation increased and prolonged the leptin surge in the offspring and the gender differences of leptin surge were observed. Our data suggested that maternal HFD during lactation might have an additive effect on the onset of the metabolic syndrome in the offspring, irrespective of the nutritional status in utero through the modified leptin surge.
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Wiklund PK, Pekkala S, Autio R, Munukka E, Xu L, Saltevo J, Cheng S, Kujala UM, Alen M, Cheng S. Serum metabolic profiles in overweight and obese women with and without metabolic syndrome. Diabetol Metab Syndr 2014; 6:40. [PMID: 24650495 PMCID: PMC3998195 DOI: 10.1186/1758-5996-6-40] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 03/11/2014] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To identify serum biomarkers through metabolomics approach that distinguishes physically inactive overweight/obese women with metabolic syndrome from those who are metabolically healthy, independent of body weight and fat mass. METHODS We applied nuclear magnetic resonance spectroscopy-based profiling of fasting serum samples to examine the metabolic differences between 78 previously physically inactive, body weight and fat mass matched overweight/obese premenopausal women with and without MetS. MetS was defined as the presence of at least three of the following five criteria: waist circumference ≥88 cm, serum triacylglycerol ≥1.7 mmol/L, and high density lipoprotein cholesterol (HDL-C) <1.30 mmol/L, blood pressure ≥ 130/85 mmHg and fasting glucose ≥5.6 mmol/L). Principal component analysis was used to reduce the large number of correlated variables to fewer uncorrelated factors. RESULTS Two metabolic factors were associated with MetS independent of BMI, fat mass, waist circumference and physical activity/fitness. Factor comprising branched-chain amino acids (BCAA) and aromatic amino acids (AAA) and orosomucoid was associated with all clinical risk factors (p < 0.01 for all). CONCLUSION Two metabolic factors distinguish overweight/obese women with metabolic syndrome from those who are metabolically healthy independent of body weight, fat mass and physical activity/fitness. In particular, factor comprising BCAA, AAA and orosomucoid seems auspicious biomarker determining metabolic health as it was associated with all clinical risk factors. Further research is needed to determine the public health and clinical significance of these results in terms of screening to identify those at greatest cardio-metabolic risk for whom appropriate intervention strategies should be developed.
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Affiliation(s)
- Petri K Wiklund
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
- Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland
| | - Satu Pekkala
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
| | - Reija Autio
- Department of Signal Processing, Tampere University of Technology, Tampere, Finland
| | - Eveliina Munukka
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
| | - Leiting Xu
- Ningbo University School of Medicine, Ningbo, China
| | - Juha Saltevo
- Central Hospital Central Finland, Jyväskylä, Finland
| | - ShuMei Cheng
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
| | - Urho M Kujala
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
| | - Markku Alen
- Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland
- Institute of Health Sciences, University of Oulu, Oulu, Finland
| | - Sulin Cheng
- Department of Health Sciences, University of Jyväskylä, Jyväskylä FIN-40014, Finland
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Ashraf AP, Huisingh C, Alvarez JA, Wang X, Gower BA. Insulin resistance indices are inversely associated with vitamin D binding protein concentrations. J Clin Endocrinol Metab 2014; 99:178-83. [PMID: 24170105 PMCID: PMC3879668 DOI: 10.1210/jc.2013-2452] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT We hypothesized that, similar to the coordinated homeostatic regulation of most hormones, the concentration of free and bioavailable 25-hydroxyvitamin D [25(OH)D] will be tightly controlled by total 25(OH)D and vitamin D binding protein (VDBP) and that the VDBP concentrations will be associated with insulin resistance status. OBJECTIVE Our primary objective was to investigate associations between total, free, and bioavailable 25(OH)D and VDBP. We also evaluated the relationships of VDBP with insulin resistance indices. STUDY DESIGN The study design was cross-sectional in the setting of a university children's hospital. The relative concentration of bioavailable 25(OH)D to total 25(OH)D [bioavailable 25(OH)D/total 25(OH)D was expressed as a percentage [percentage bioavailable 25(OH)D]. RESULTS Subjects were 47, postmenarchal, female adolescents, with a mean age of 15.8±1.4 years, a mean body mass index of 23.1±4.0 kg/m2. The total 25(OH)D was strongly associated with VDBP (rho=0.57, P<.0001). At lower total 25(OH)D concentrations, the concentration of bioavailable 25(OH)D relative to total 25(OH)D was higher (23.8% vs 14.9%, P<.0001), whereas the relative concentration of free 25(OH)D was similar (P=.44). VDBP was inversely associated with fasting insulin (rho=-0.51, P=.0003) and homeostatic model assessment of basal insulin resistance (rho=-0.45, P=.002) and positively with whole-body insulin sensitivity (rho=0.33, P=.02); these relationships persisted after adjusting for percentage fat and attenuated after adjusting for race. CONCLUSION Our data suggest that VDBP concentrations are regulated by total 25(OH)D levels to maintain adequate concentrations of bioavailable 25(OH)D. VDBP concentrations are inversely associated with hyperinsulinemia and insulin resistance.
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Affiliation(s)
- Ambika P Ashraf
- Division of Pediatric Endocrinology (A.P.A., X.W.), Department of Pediatrics, Center for Clinical and Translational Sciences (C.H.), and Department of Nutrition Sciences (B.A.G.), University of Alabama, Birmingham, Birmingham, Alabama 35233; and Division of Endocrinology (J.A.A.), Emory University School of Medicine, Atlanta, Georgia 30322
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33
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Patarrão RS, Wayne Lautt W, Paula Macedo M. Assessment of methods and indexes of insulin sensitivity. ACTA ACUST UNITED AC 2014. [DOI: 10.1016/j.rpedm.2013.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Onopchenko OV. The effect of N-stearoylethanolamine on the activity of antioxidant enzymes, content of lipid peroxidation products and nitric oxide in the blood plasma and liver of rats with induced insulin-resistance. UKRAINIAN BIOCHEMICAL JOURNAL 2013. [DOI: 10.15407/ubj85.05.088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Afsar B. The comparison of 24-hour urinary sodium, albumin, and protein excretion in chronic kidney disease patients with type 2 diabetes mellitus using insulin detemir or insulin glargine. Clin Drug Investig 2013; 33:773-8. [PMID: 23943142 DOI: 10.1007/s40261-013-0118-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND AND OBJECTIVE Insulin detemir induces bodyweight loss or less weight gain in patients with type 2 diabetes mellitus. However, in contrast to insulin detemir, insulin glargine has no weight loss effect. Increased sodium excretion has been speculated to be one of the mechanisms of weight loss by insulin detemir. However, there are no studies in the literature comparing sodium excretion between patients using insulin detemir and those using insulin glargine. There are also no studies comparing the excretion of urinary albumin and urinary protein in chronic kidney disease (CKD) patients using insulin detemir or insulin glargine. Thus, the aim of the current study was to compare the effects of insulin detemir and insulin glargine on sodium, albumin, and protein excretion in patients with various stages of CKD and concomitant type 2 diabetes. METHODS Demographic, clinical, and laboratory data were evaluated for all patients. Hypoglycemic attacks, appetite score, 24-h urinary sodium, albumin, and protein excretion were also measured. RESULTS A total of 47 patients (23 taking insulin detemir, 24 taking insulin glargine) were included in the study. There were no differences with respect to 24-h sodium (p = 0.694), albumin (p = 0.297), or protein excretion (p = 0.202) between patient groups. Appetite and hypoglycemic attacks also did not differ between groups. Use of insulin detemir or insulin glargine was not related to sodium, albumin, and protein excretion in stepwise regression analysis. CONCLUSION There was no difference between insulin detemir and insulin glargine with respect to sodium, albumin, and protein excretion in type 2 diabetic CKD patients. Studies are needed both in CKD patients and those with normal renal function to highlight mechanisms regarding the weight loss effect unique to insulin detemir.
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Affiliation(s)
- Baris Afsar
- Division of Nephrology, Department of Internal Medicine, Konya Numune State Hospital, Ferhuniye Mah. Hastane Cad., 42690, Konya, Turkey,
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36
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Hill NR, Levy JC, Matthews DR. Expansion of the homeostasis model assessment of β-cell function and insulin resistance to enable clinical trial outcome modeling through the interactive adjustment of physiology and treatment effects: iHOMA2. Diabetes Care 2013; 36:2324-30. [PMID: 23564921 PMCID: PMC3714535 DOI: 10.2337/dc12-0607] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To describe and make available an interactive, 24-variable homeostasis model assessment (iHOMA2) that extends the HOMA2 model, enabling the modeling of physiology and treatment effects, to present equations of the HOMA2 and iHOMA2 models, and to exemplify iHOMA2 in two widely differing scenarios: changes in insulin sensitivity with thiazolidinediones and changes in renal threshold with sodium glucose transporter 2 (SGLT2) inhibition. RESEARCH DESIGN AND METHODS iHOMA2 enables a user of the available software to examine and modify the mathematical functions describing the organs and tissues involved in the glucose and hormonal compartments. We exemplify this with SGLT2 inhibition modeling (by changing the renal threshold parameters) using published data of renal effect, showing that the modeled effect is concordant with the effects on fasting glucose from independent data. RESULTS iHOMA2 modeling of thiazolidinediones effect suggested that changes in insulin sensitivity in the fasting state are predominantly hepatic. SGLT2 inhibition modeled by iHOMA2 resulted in a decrease in mean glucose of 1.1 mmol/L. Observed data showed a decrease in glucose of 0.9 mmol/L. There was no significant difference between the model and the independent data. Manipulation of iHOMA2's renal excretion threshold variable suggested that a decrease of 17% was required to obtain a 0.9 mmol/L decrease in mean glucose. CONCLUSIONS iHOMA2 is an extended mathematical model for the assessment of insulin resistance and β-cell function. The model can be used to evaluate therapeutic agents and predict effects on fasting glucose and insulin and on β-cell function and insulin sensitivity.
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Affiliation(s)
- Nathan R Hill
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK
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Lunger F, Wildt L, Seeber B. Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations. Gynecol Endocrinol 2013; 29:541-4. [PMID: 23464983 DOI: 10.3109/09513590.2013.774362] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The aims of this cross-sectional study were to evaluate the relative agreement of both static and dynamic methods of diagnosing IR in women with polycystic ovary syndrome (PCOS) and to suggest a simple screening method for IR. All participants underwent serial blood draws for hormonal profiling and lipid assessment, a 3 h, 75 g load oral glucose tolerance test (OGTT) with every 15 min measurements of glucose and insulin, and an ACTH stimulation test. The prevalence of IR ranged from 12.2% to 60.5%, depending on the IR index used. Based on largest area under the curve on receiver operating curve (ROC) analyses, the dynamic indices outperformed the static indices with glucose to insulin ratio and fasting insulin (fInsulin) demonstrating the best diagnostic properties. Applying two cut-offs representing fInsulin extremes (<7 and >13 mIU/l, respectively) gave the diagnosis in 70% of the patients with high accuracy. Currently utilized indices for assessing IR give highly variable results in women with PCOS. The most accurate indices based on dynamic testing can be time-consuming and labor-intensive. We suggest the use of fInsulin as a simple screening test, which can reduce the number of OGTTs needed to routinely assess insulin resistance in women with PCOS.
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Affiliation(s)
- Fabian Lunger
- Department of Gynecologic Endocrinology and Reproductive Medicine, Innsbruck Medical University, Innsbruck, Austria
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Moreno-Pérez O, Portilla J, Escoín C, Alfayate R, Reus S, Merino E, Boix V, Bernabeu A, Giner L, Mauri M, Sánchez-Paya J, Picó A. Impact of vitamin D insufficiency on insulin homeostasis and beta cell function in nondiabetic male HIV-infected patients. HIV Med 2013; 14:540-8. [DOI: 10.1111/hiv.12042] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2013] [Indexed: 12/14/2022]
Affiliation(s)
- O Moreno-Pérez
- Endocrinology and Nutrition Department; Alicante University General Hospital; Alicante Spain
| | - J Portilla
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - C Escoín
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - R Alfayate
- Hormone Laboratory; Alicante University General Hospital; Alicante Spain
| | - S Reus
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - E Merino
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - V Boix
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - A Bernabeu
- Magnetic Resonance Unit - Inscanner S.L.; Alicante University General Hospital; Alicante Spain
| | - L Giner
- Infectious Diseases Unit; Alicante University General Hospital; Alicante Spain
| | - M Mauri
- Hormone Laboratory; Alicante University General Hospital; Alicante Spain
| | - J Sánchez-Paya
- Preventive Medicine Department; Alicante University General Hospital; Alicante Spain
| | - A Picó
- Endocrinology and Nutrition Department; Alicante University General Hospital; Alicante Spain
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Ashraf AP, Alvarez J, Huisingh C, Casazza K, Gower B. Higher Serum Insulin Concentrations Positively Influence the Bone Mineral Density in African American Adolescents. ACTA ACUST UNITED AC 2013; 3:1050-1061. [PMID: 25258705 DOI: 10.9734/bjmmr/2013/2720#sthash.xsm9pvk7.dpuf] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Puberty is a developmental stage of increased insulin resistance that also is a critical period for bone mass accrual. Historically, African Americans (AA) have lesser risk for osteoporotic fractures compared to European Americans (EA). AA also have higher incidence of insulin resistance. The possibility that bone health and insulin secretion or concentrations are linked has not been investigated. AIMS We aimed to examine the associations of bone mineral density (BMD) and bone mineral apparent density (BMAD) with insulin sensitivity and secretion in healthy adolescent girls and healthy female adults and to evaluate ethnic differences in these associations. STUDY DESIGN Observational cohort design. PLACE AND DURATION OF THE STUDY University of Alabama at Birmingham, between January 2010 and September 2011. METHODOLOGY Healthy, female, non-smoking adolescents and young adults (14-55 years) were enrolled in this observational cohort study. RESULTS Adolescents had significantly higher fasting insulin (P=0.0002), insulin area under the curve [AUC] (P= 0.0004) and lower insulin sensitivity (P=0.0005) compared to adults. Among adolescents, AA race was significantly associated with BMD (β=0.086, P=0.01) and BMAD (β=0.0075, P=0.002); however, adjusting for insulin AUC explained this difference. Insulin AUC (β=0.0006, P=0.029) and fasting insulin (β=0.0005, P=0.01) were positively associated with BMAD only in AA adolescents. Insulin AUC and fasting insulin were not significant predictors of BMD for adults. CONCLUSION The higher insulin concentration among AA adolescents is associated with increased BMD and higher BMAD.
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Affiliation(s)
- Ambika P Ashraf
- Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, The Children's Hospital, University of Alabama Birmingham, Birmingham, USA
| | - Jessica Alvarez
- Division of Endocrinology, Emory University School of Medicine, Atlanta, USA
| | - Carrie Huisingh
- Center for Clinical and Translational Sciences, University of Alabama at Birmingham, USA
| | - Krista Casazza
- Department of Nutrition Sciences, University of Alabama Birmingham, Birmingham, USA
| | - Barbara Gower
- Department of Nutrition Sciences, University of Alabama Birmingham, Birmingham, USA
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Ashraf AP, Alvarez J, Huisingh C, Casazza K, Gower B. Higher Serum Insulin Concentrations Positively Influence the Bone Mineral Density in African American Adolescents. ACTA ACUST UNITED AC 2013. [PMID: 25258705 PMCID: PMC4172283 DOI: 10.9734/bjmmr/2013/2720] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Background Puberty is a developmental stage of increased insulin resistance that also is a critical period for bone mass accrual. Historically, African Americans (AA) have lesser risk for osteoporotic fractures compared to European Americans (EA). AA also have higher incidence of insulin resistance. The possibility that bone health and insulin secretion or concentrations are linked has not been investigated. Aims We aimed to examine the associations of bone mineral density (BMD) and bone mineral apparent density (BMAD) with insulin sensitivity and secretion in healthy adolescent girls and healthy female adults and to evaluate ethnic differences in these associations. Study Design Observational cohort design. Place and Duration of the Study University of Alabama at Birmingham, between January 2010 and September 2011. Methodology Healthy, female, non-smoking adolescents and young adults (14–55 years) were enrolled in this observational cohort study. Results Adolescents had significantly higher fasting insulin (P=0.0002), insulin area under the curve [AUC] (P= 0.0004) and lower insulin sensitivity (P=0.0005) compared to adults. Among adolescents, AA race was significantly associated with BMD (β=0.086, P=0.01) and BMAD (β=0.0075, P=0.002); however, adjusting for insulin AUC explained this difference. Insulin AUC (β=0.0006, P=0.029) and fasting insulin (β=0.0005, P=0.01) were positively associated with BMAD only in AA adolescents. Insulin AUC and fasting insulin were not significant predictors of BMD for adults. Conclusion The higher insulin concentration among AA adolescents is associated with increased BMD and higher BMAD.
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Affiliation(s)
- Ambika P Ashraf
- Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, The Children's Hospital, University of Alabama Birmingham, Birmingham, USA
| | - Jessica Alvarez
- Division of Endocrinology, Emory University School of Medicine, Atlanta, USA
| | - Carrie Huisingh
- Center for Clinical and Translational Sciences, University of Alabama at Birmingham, USA
| | - Krista Casazza
- Department of Nutrition Sciences, University of Alabama Birmingham, Birmingham, USA
| | - Barbara Gower
- Department of Nutrition Sciences, University of Alabama Birmingham, Birmingham, USA
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de Groot PCE, Hjeltnes N, Heijboer AC, Stal W, Birkeland K. Effect of training intensity on physical capacity, lipid profile and insulin sensitivity in early rehabilitation of spinal cord injured individuals. Spinal Cord 2012; 41:673-9. [PMID: 14639446 DOI: 10.1038/sj.sc.3101534] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
STUDY DESIGN Pre-post training intervention. OBJECTIVES To evaluate the effect of training intensity on physical capacity, lipid profile and insulin sensitivity in early rehabilitation of spinal cord injured (SCI) patients, and to assess the correlation between peak aerobic capacity (VO(2Peak)) and insulin sensitivity. SETTING Spinal Cord Rehabilitation Unit, Sunnaas Hospital, Nesoddtangen, Norway. METHOD Six recently injured SCI individuals participated in the arm training intervention and were randomly admitted to a high-intensity (HI; 70-80% heart rate reserve (HRR)) and low-intensity (LI; 40-50% HRR) group. The 1 h interval training consisted of 3 min exercise bouts interspersed with 2 min of rest, three times a week for 8 weeks. In addition, a correlation coefficient was obtained between VO(2Peak) and insulin sensitivity in 11 SCI patients. RESULTS The 8-week training program resulted in a significant increase in VO(2Peak) and maximal power output (PO(Max)) for the group as a whole (P<0.05). VO(2Peak) increased significantly more and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and triglycerids decreased significantly more in the HI group than in the LI group (P=0.05). Training-induced changes in insulin sensitivity were significantly different between the groups (P=0.05), which was due to a nonsignificant decline in insulin sensitivity in the HI group and a nonsignificant improvement in the LI group. A significant positive correlation was found between VO(2peak) and insulin sensitivity (r=0.68, P=0.02). CONCLUSION The interval arm training protocol as used in the present study enables recently injured SCI patients to do substantial work at a relatively high intensity. Results indicate that improvements in physical capacity and lipid profile were more pronounced in response to high-intensity training. The significant correlation between maximal oxygen consumption and insulin sensitivity indicates that, as in the able-bodied population, peak aerobic capacity is a predictive value with regard to insulin sensitivity in SCI. Future studies with larger groups assessing the role of exercise intensity on insulin sensitivity in SCI are suggested.
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Affiliation(s)
- P C E de Groot
- Department of Physiology, University Medical Centre Nijmegen, the Netherlands
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Nolan JJ, Færch K. Estimating insulin sensitivity and beta cell function: perspectives from the modern pandemics of obesity and type 2 diabetes. Diabetologia 2012; 55:2863-7. [PMID: 22911384 DOI: 10.1007/s00125-012-2684-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 05/18/2012] [Indexed: 12/25/2022]
Abstract
The 1985 manuscript describing the HOMA model, by Matthews and colleagues, is the most cited paper in the history of Diabetologia. In this edition of 'Then and now' we assess the impact of this seminal paper by considering the contribution of this elegant work in the context of the most rapidly changing period in the history of diabetes. HOMA was born in the middle of an 'era' of insulin resistance, and was subsequently nurtured and grew during the 'eras' of insulin sensitisers and diabetes prevention. From the modern era of insulin resistance onward, researchers have sought a convenient method for measuring insulin sensitivity and secretion, and found this in HOMA. However, the explosion in the prevalence of diabetes clearly underlines that an understanding of insulin resistance and how it can be measured has been insufficient to make any impact on the growing pandemic of diabetes. Knowledge of individual physiology is important, but the dramatic impact of the modern environment may be the factor that has escaped attention until very recently. An optimist can only state that the coming 'era' in diabetes research will be a period of true translation of scientific insight and implementation of effective disease prevention.
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Affiliation(s)
- J J Nolan
- Steno Diabetes Center A/S, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark.
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43
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Seclén S, Villena A, Larrad MT, Gamarra D, Herrera B, Pérez CF, Sánchez JLG, Ríos MS. Prevalence of the metabolic syndrome in the mestizo population of peru. Metab Syndr Relat Disord 2012; 4:1-6. [PMID: 18370764 DOI: 10.1089/met.2006.4.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND The metabolic syndrome (MS) has been shown to predict mortality due to cardiovascular disease. Currently, no population-based data on the prevalence of the MS is available in Peru. This study was aimed to assess the prevalence of the MS in urban Peruvian Mestizos, in the coastal districts of Lima, the capital of Peru. METHODS A cross-sectional, epidemiological survey was undertaken, including 612 unrelated subjects aged 30-92 years (68.3% females). Prevalence of the MS was defined by the National Cholesterol Education Program Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) criteria. Insulin resistance was estimated by the homeostasis model assessment (HOMA). RESULTS Age and sex standardized prevalence of the MS was 14.9% (13.2% in males, 16.5% in females). The MS was significantly more prevalent in females aged 45-59 years old (20.2% vs. 6.7%, p = 0.019). In individuals with the MS, the prevalence of insulin resistance (IR) was 45% in males/42% in females. Abdominal obesity (80% in males/92.8% in females), and low HDL cholesterol (55% males/75.4% females), but neither hypertriglyceridemia (85% in males/81.2% females) nor high fasting glucose (55% in males/36.2 % females) were more common in females. Prevalence of arterial hypertension was similar in both sexes. CONCLUSIONS In this Mestizo Peruvian population, prevalence of the MS is relatively low as compared to other ethnic groups; the higher prevalence in females is likely due to a higher prevalence of abdominal obesity. Overall, abdominal obesity and hypertriglyceridemia were the predominant combination of metabolic disorders in individuals fulfilling criteria for the diagnosis of the MS.
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Affiliation(s)
- Segundo Seclén
- Diabetes Clinic, Cayetano Heredia National Hospital, Universidad Peruana Cayetano Heredia, Lima, Peru
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Lim S, An JH, Shin H, Khang AR, Lee Y, Ahn HY, Yoon JW, Kang SM, Choi SH, Cho YM, Park KS, Jang HC. Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study. Clin Endocrinol (Oxf) 2012; 77:215-23. [PMID: 21955147 DOI: 10.1111/j.1365-2265.2011.04240.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug-naïve type 2 diabetic patients. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0-10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and β-cell function (HOMA-B), insulinogenic index (IGI, defined as 30-0 min insulin/30-0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test. RESULTS After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P < 0·01). HOMA-B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and HOMA-IR. No severe adverse events were observed. CONCLUSION These results suggest that drug-naïve type 2 diabetic patients with low β-cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Masuyama H, Hiramatsu Y. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice. Am J Physiol Endocrinol Metab 2012; 303:E293-300. [PMID: 22649068 DOI: 10.1152/ajpendo.00167.2012] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.
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Affiliation(s)
- Hisashi Masuyama
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Okayama 700-8558, Japan.
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Masuyama H, Hiramatsu Y. Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology 2012; 153:2823-30. [PMID: 22434078 DOI: 10.1210/en.2011-2161] [Citation(s) in RCA: 147] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.
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Affiliation(s)
- Hisashi Masuyama
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan.
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Abstract
The objective of this article is to systematically review the changes in insulin resistance after various types of bariatric surgical procedures. A Pubmed and EMBASE search for studies measuring insulin resistance before and after bariatric surgery was done and all original research articles from 1980 to present (2011) were included. Only the currently widely performed bariatric procedures were included. A meta-analysis of change in HOMA-IR was conducted, grouping studies with similar duration of follow-up. The percentage decrease in HOMA-IR at <=2 weeks, 1 month, 3 months, 6 months, 12 months and >16-18 months was found to be (mean ± standard error) -33.48 ± 5.78, -46.43 ± 6.99, -38.79 ± 9.64, -58.62 ± 7.38, -44.91 ± 7.98 and -67.04 ± 10.78%, respectively. RYGB (gastric bypass) and BPD (biliopancreatic diversion) produced a significant decrease in insulin resistance at 2 weeks after surgery, while LSG (sleeve gastrectomy) was strongly trending. LSG produced an earlier decrease in insulin resistance when compared to LAGB (gastric banding). RYGB, BPD and LSG produce an early decrease in insulin resistance through yet unknown mechanisms.
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Affiliation(s)
- R S Rao
- Department of Surgery, Division of Metabolic, Endocrine and Minimally Invasive Surgery, Diabetes and Bone Disease, Mount Sinai School of Medicine, 5 E. 98th St., New York, NY 10029, USA.
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Masuyama H, Hiramatsu Y. Treatment with a constitutive androstane receptor ligand ameliorates the signs of preeclampsia in high-fat diet-induced obese pregnant mice. Mol Cell Endocrinol 2012; 348:120-7. [PMID: 21839802 DOI: 10.1016/j.mce.2011.07.047] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2011] [Revised: 07/24/2011] [Accepted: 07/26/2011] [Indexed: 11/24/2022]
Abstract
Constitutive androstane receptor (CAR) has been reported to decrease insulin resistance, while obesity and insulin resistance may also be involved in the pathogenesis of preeclampsia. We examined whether a CAR ligand, 1,4-bis(2-(3,5-dichloropyridyloxy)) benzene (TCPOBOP), can ameliorate the signs of preeclampsia in high-fat diet (HFD)-induced obese pregnant mice to examine a possibility of CAR as a therapeutic target. We employed six groups including non-pregnant, HFD-fed or control diet-fed pregnant mice with or without TCPOBOP treatment (n=6). In HFD pregnant mice, insulin resistance increased with increasing expression of gluconeogenic and lipogenic genes and abnormal adipocytokine levels. TCPOBOP treatment, which was once-weekly intraperitoneal injections (0.5 mg/kg) and started at day 0.5 of pregnancy, improved glucose tolerance with significant changes of gluconeogenic, lipogenic and adipocytokine genes. HFD pregnant mice had hypertension and proteinuria, while TCPOBOP treatment ameliorated these signs. Our data suggested CAR might be a potential therapeutic target for obese preeclampsia patients with insulin resistance.
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Affiliation(s)
- H Masuyama
- Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Department of Obstetrics and Gynecology, Okayama, Japan.
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Kahveci C, Koldemir M, Cagatay P, Bayer H, Yildiz S, Bagriacik N, Duman BS. Relationship of transcription factor 7 like 2 gene rs7903146 variation with type 2 diabetes and obesity related parameters. Diabetes Metab Syndr 2012; 6:48-53. [PMID: 23014255 DOI: 10.1016/j.dsx.2012.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
AIMS The allele frequencies of transcription factor 7 like 2 (TCF7L2) gene rs7903146 polymorphism in type 2 diabetes mellitus (T2DM) and non-T2DM controls were determined. METHODS TCF7L2 rs7903146 genotypes were determined with qPCR. RESULTS The TCF7L2 gene rs7903146 genotype frequencies for homozygous wild type (C/C), heterozygous (C/T) and homozygous polymorphic (T/T) for T2DM patients were determined, respectively, as 71.4%, 14.3%, 14.3% and 72.5%, 11.8%, 15.7% for controls. The weight, length and lean body mass were higher in C/T+T/T compared to C/C carriers. Glucose, insulin, insulin resistance and homeostatic model assessment (HOMA) were nonsignificantly higher in rs7903146C/T+T/T in comparison to C/C. TCF7L2 gene rs7903146 genotypes were not found to interact with drugs. The absence of any difference between genotype frequencies among study groups indicates that no association persists with TCF7L2 gene rs7903146 polymorphism and T2DM. CONCLUSIONS The effects of rs7903146 variation over some obesity variables suggest that this variation may effect T2DM development via obesity.
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Affiliation(s)
- Cigdem Kahveci
- Marmara University, Faculty of Science and Arts, Department of Biology, Istanbul, Turkey
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Borai A, Livingstone C, Kaddam I, Ferns G. Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol 2011; 11:158. [PMID: 22112229 PMCID: PMC3258205 DOI: 10.1186/1471-2288-11-158] [Citation(s) in RCA: 162] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Accepted: 11/23/2011] [Indexed: 12/15/2022] Open
Abstract
Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study.
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Affiliation(s)
- Anwar Borai
- Department of Pathology, King Khalid National Guard Hospital, Jeddah, Saudi Arabia.
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