Studying progression from glucose intolerance to type 2 diabetes in obese children

Dubinina, Irina A.; Chistiakov, Dimitry A.; Еремина, Ирина Александровна; Brovkin, A. N.; Zilberman, L. I.; Никитин, А Г; Кураева, Тамара Леонидовна; Носиков, В. В.; Dedov, Ivan I.

doi:10.1016/j.dsx.2014.07.002

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…According to a recessive model analysis, similar to our results, the minor allele of the Pro12Ala PPARγ2 polymorphism has been associated with insulin levels in healthy men without obesity ( Helwig et al, 2007 ). Carriers of the Ala12Ala genotype showed increased HOMA compared to individuals with Pro12Pro + Ala12Pro genotypes also in diabetic obese children ( Dubinina et al, 2014 ). Li et al demonstrated significant lower fasting insulin levels and HOMA-IR with the presence of the Ala12 allele in adulthood and a similar trend, although not significant, in childhood ( Li et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

et al. 2021

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Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.

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Section: Discussionmentioning

confidence: 99%

PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

et al. 2021

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“…Meanwhile, Pro12Ala could predict BMI, overweight, and total cholesterol in females but not in male Taiwanese patients [31]. In children diagnosed with T2D the Pro12Ala polymorphism of PPARγ was significantly associated with obesity and T2D [32]. However, in a Japanese cohort, this polymorphism was not associated with BMI, and visceral and subcutaneous fat accumulation assessed by computed tomography [33].…”

Section: Human Aspects Of Pparγ In Metabolic Syndromementioning

confidence: 99%

Is the Mouse a Good Model of Human PPARγ-Related Metabolic Diseases?

Pap

Cuaranta-Monroy

Peloquin

et al. 2016

IJMS

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With the increasing number of patients affected with metabolic diseases such as type 2 diabetes, obesity, atherosclerosis and insulin resistance, academic researchers and pharmaceutical companies are eager to better understand metabolic syndrome and develop new drugs for its treatment. Many studies have focused on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in adipogenesis and lipid metabolism. These studies have been able to connect this transcription factor to several human metabolic diseases. Due to obvious limitations concerning experimentation in humans, animal models—mainly mouse models—have been generated to investigate the role of PPARγ in different tissues. This review focuses on the metabolic features of human and mouse PPARγ-related diseases and the utility of the mouse as a model.

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“…In contrast, Giannini et al identified a higher number of risk alleles ( TCF7L2 /rs7903146, IGF2BP2/ rs4402960, CDKAL1/ rs7754840, HHEX/ rs1111875, and HNF1A/ rs1169288) in individuals with progression from normal glucose tolerance to T2D in a multiethnic cohort in the United States. The Pro12Ala variant of PPARG influenced the progression from normal glucose tolerance to clinical T2D in obese Russian children, and the E23K polymorphism of the KCNJ11 gene conferred higher susceptibility to TD2 in Taiwanese children and adolescents …”

Section: Introductionmentioning

confidence: 99%

“…The Pro12Ala variant of PPARG influenced the progression from normal glucose tolerance to clinical T2D in obese Russian children, 12 and the E23K polymorphism of the KCNJ11 gene conferred higher susceptibility to TD2 in Taiwanese children and adolescents. 13 There is strong evidence for familial clustering and genetic predisposition to T2D in Mexican people (mainly at younger ages).…”

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confidence: 97%

Genetic polymorphisms associated with pediatric‐onset type 2 diabetes: A family‐based transmission disequilibrium test and case‐control study

et al. 2019

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Background and Objective Genetics play a very strong role in the development of pediatric‐onset type 2 diabetes (T2D); however, little information exists about specific common single nucleotide polymorphisms (SNPs) associated with T2D in this age group. The aim of the study was to analyze the association and parental transmission of 64 obesity‐related SNPs with pediatric‐onset T2D in Mexican families. Methods A total of 57 pedigrees containing 171 probands with pediatric‐onset T2D and 119 unrelated controls older than 18 years were included. The participants were genotyped for 64 polymorphisms. Association of each variant with pediatric‐onset T2D was analyzed through a parent‐offspring transmission disequilibrium test (TDT) and in a case‐control comparison by χ2 analysis. Results Five SNPs exhibited associations with pediatric‐onset T2D in the combined case‐parent trio and case‐control analysis: LINGO/rs10968576 (odds ratio [OR] 1.82, P = 0.003), POC5/rs2112347 (OR 1.96, P = 2.4E‐5), RPS10‐NUDT3/rs206936 (OR 1.40, P = 0.023), GLIS3/rs7034200 (OR 2.34, P = 1.2E‐6), and VEGFA/rs6905288 (OR 1.58, P = 0.015). The first three were also associated with obesity status. The SNPs POC5/rs2112347 and RPS10‐NUDT3/rs206936 were significantly associated through the maternal allele and GLIS3/rs7034200 through the paternal allele (P < 0.05). Conclusions These findings suggest that certain SNPs associated with obesity and other metabolic traits may also be involved in risk of pediatric‐onset T2D in Mexican families. We also identified preferential transmission of parental alleles in some variants.

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Studying progression from glucose intolerance to type 2 diabetes in obese children

Cited by 9 publications

References 46 publications

PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

Is the Mouse a Good Model of Human PPARγ-Related Metabolic Diseases?

Genetic polymorphisms associated with pediatric‐onset type 2 diabetes: A family‐based transmission disequilibrium test and case‐control study

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