Genetic and Environmental Factors Associated with Type 2 Diabetes and Diabetic Vascular Complications

Overview

Journal Rev Diabet Stud

Specialty Endocrinology

Date 2012 Sep 14

PMID 22972441

Citations 144

Authors

Mariana Murea

Lijun Ma

Barry I Freedman

Affiliations

Soon will be listed here.

Abstract

Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene- and exposure-related underpinnings of T2D will soon result.

Citing Articles

Pancreatic Volume in Thalassemia: Determinants and Association with Alterations of Glucose Metabolism.

Meloni A, Restaino G, Positano V, Pistoia L, Keilberg P, Santodirocco M Diagnostics (Basel). 2025; 15(5).

PMID: 40075815 PMC: 11899254. DOI: 10.3390/diagnostics15050568.

Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design.

Li X, Zhou Z, Ma Y, Ding K, Xiao H, Wu T Biomedicines. 2025; 13(1).

PMID: 39857704 PMC: 11761613. DOI: 10.3390/biomedicines13010120.

Corporate genome screening India (CoGsI) identified genetic variants association with T2D in young Indian professionals.

Husami S, Kaur T, Gupta L, Rastogi G, Singh L, Meena P Sci Rep. 2025; 15(1):506.

PMID: 39747296 PMC: 11697386. DOI: 10.1038/s41598-024-84160-2.

Integrative analysis of PANoptosis-related genes in diabetic retinopathy: machine learning identification and experimental validation.

Chen H, Chen E, Cao T, Feng F, Lin M, Wang X Front Immunol. 2024; 15:1486251.

PMID: 39697326 PMC: 11652367. DOI: 10.3389/fimmu.2024.1486251.

Comprehensive review of opportunities and challenges of ethnomedicinal plants for managing type 2 diabetes.

Mahmoud V, Shayesteh R, Foong Yun Loh T, Chan S, Sethi G, Burgess K Heliyon. 2024; 10(23):e39699.

PMID: 39687111 PMC: 11648782. DOI: 10.1016/j.heliyon.2024.e39699.

References

Altshuler D, Hirschhorn J, Klannemark M, Lindgren C, Vohl M, Nemesh J . The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000; 26(1):76-80. DOI: 10.1038/79216. View

Imamura M, Maeda S . Genetics of type 2 diabetes: the GWAS era and future perspectives [Review]. Endocr J. 2011; 58(9):723-39. DOI: 10.1507/endocrj.ej11-0113. View

Lazar M . How obesity causes diabetes: not a tall tale. Science. 2005; 307(5708):373-5. DOI: 10.1126/science.1104342. View

Yuan D, Yuan D, Liu Q . Association of the receptor for advanced glycation end products gene polymorphisms with diabetic retinopathy in type 2 diabetes: a meta-analysis. Ophthalmologica. 2012; 227(4):223-32. DOI: 10.1159/000335628. View

Wilson P, Meigs J, Sullivan L, Fox C, Nathan D, DAgostino Sr R . Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med. 2007; 167(10):1068-74. DOI: 10.1001/archinte.167.10.1068. View

Xiang K, Wang Y, Zheng T, Jia W, Li J, Chen L . Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes. 2003; 53(1):228-34. DOI: 10.2337/diabetes.53.1.228. View

Ramracheya R, Muller D, Squires P, Brereton H, Sugden D, Huang G . Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res. 2008; 44(3):273-9. DOI: 10.1111/j.1600-079X.2007.00523.x. View

Craddock N, Hurles M, Cardin N, Pearson R, Plagnol V, Robson S . Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010; 464(7289):713-20. PMC: 2892339. DOI: 10.1038/nature08979. View

Gerstein H, Miller M, Genuth S, Ismail-Beigi F, Buse J, Goff Jr D . Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011; 364(9):818-28. PMC: 4083508. DOI: 10.1056/NEJMoa1006524. View

10.

Mussig K, Staiger H, Machicao F, Haring H, Fritsche A . Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia. 2010; 53(11):2289-97. DOI: 10.1007/s00125-010-1876-8. View

11.

Eichler E, Flint J, Gibson G, Kong A, Leal S, Moore J . Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11(6):446-50. PMC: 2942068. DOI: 10.1038/nrg2809. View

12.

Stein G, Zaidi S, Stein J, Lian J, van Wijnen A, Montecino M . Transcription-factor-mediated epigenetic control of cell fate and lineage commitment. Biochem Cell Biol. 2009; 87(1):1-6. PMC: 2708786. DOI: 10.1139/O08-094. View

13.

Salonen J, Nyyssonen K, Tuomainen T, Maenpaa P, Korpela H, Kaplan G . Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men. BMJ. 1995; 311(7013):1124-7. PMC: 2551054. DOI: 10.1136/bmj.311.7013.1124. View

14.

Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N . Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011; 364(9):829-841. PMC: 4109980. DOI: 10.1056/NEJMoa1008862. View

15.

Coogan P, White L, Jerrett M, Brook R, Su J, Seto E . Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation. 2012; 125(6):767-72. PMC: 3326581. DOI: 10.1161/CIRCULATIONAHA.111.052753. View

16.

Cilensek I, Mankoc S, Petrovic M, Petrovic D . The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients (Caucasians) with type 2 diabetes mellitus. Mol Biol Rep. 2012; 39(6):7061-7. DOI: 10.1007/s11033-012-1537-8. View

17.

Meigs J, Cupples L, Wilson P . Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes. 2000; 49(12):2201-7. DOI: 10.2337/diabetes.49.12.2201. View

18.

Chen S, Feng B, George B, Chakrabarti R, Chen M, Chakrabarti S . Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells. Am J Physiol Endocrinol Metab. 2009; 298(1):E127-37. DOI: 10.1152/ajpendo.00432.2009. View

19.

Zhou K, Bellenguez C, Spencer C, Bennett A, Coleman R, Tavendale R . Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2010; 43(2):117-20. PMC: 3030919. DOI: 10.1038/ng.735. View

20.

Allison M, Budoff M, Nasir K, Wong N, Detrano R, Kronmal R . Ethnic-specific risks for atherosclerotic calcification of the thoracic and abdominal aorta (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2009; 104(6):812-7. PMC: 2755558. DOI: 10.1016/j.amjcard.2009.05.004. View