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The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview.

ABSTRACT: Type 2 diabetes (T2D) is one of the scourges of modern times, with many millions of people affected by the disease. Diabetes occurs most frequently in those who are overweight or obese. However, not all overweight and obese persons develop diabetes, and there are those who develop the disease who are lean and physically active. Certain ethnicities, especially indigenous populations, are at considerably higher risk of obesity and diabetes than those of white European ancestry. The patterns and distributions of diabetes have led some to speculate that the disease is caused by interactions between genetic and obesogenic lifestyle factors. Whilst to many this is a plausible explanation, remarkably little reliable evidence exists to support it. In this review, an overview of published literature relating to genetic and lifestyle risk factors for T2D is provided. The review also describes the concepts and rationale that have motivated the view that gene-lifestyle interactions cause diabetes and overviews the empirical evidence published to date to support this hypothesis.

SUBMITTER: Franks PW

PROVIDER: S-EPMC3820646 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview.

Franks Paul W PW

Scientifica 20121008

Type 2 diabetes (T2D) is one of the scourges of modern times, with many millions of people affected by the disease. Diabetes occurs most frequently in those who are overweight or obese. However, not all overweight and obese persons develop diabetes, and there are those who develop the disease who are lean and physically active. Certain ethnicities, especially indigenous populations, are at considerably higher risk of obesity and diabetes than those of white European ancestry. The patterns and di ...[more]

PMID: 24278702

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Project description:This comprehensive review of the literature aimed to investigate the interplay between the oral microbiome, oral cavity conditions, and host immune response in Diabetes mellitus (DM). Moreover, this review also aimed to investigate how DM related risk factors, such as advanced age, hyperglycemia, hyperlipidemia, obesity, hypertension and polycystic ovary syndrome (PCOS), act in promoting or modifying specific mechanisms that could potentially perpetuate both altered systemic and oral conditions. We found that poorly controlled glycemic index may exert a negative effect on the immune system of affected individuals, leading to a deficient immune response or to an exacerbation of the inflammatory response exacerbating DM-related complications. Hyperglycemia induces alterations in the oral microbiome since poor glycemic control is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of individuals with DM. A bidirectional relationship between periodontal diseases and DM has been suggested: DM patients may have an exaggerated inflammatory response, poor repair and bone resorption that aggravates periodontal disease whereas the increased levels of systemic pro-inflammatory mediators found in individuals affected with periodontal disease exacerbates insulin resistance. SARS-CoV-2 infection may represent an aggravating factor for individuals with DM. Individuals with DM tend to have low salivary flow and a high prevalence of xerostomia, but the association between prevalence/experience of dental caries and DM is still unclear. DM has also been associated to the development of lesions in the oral mucosa, especially potentially malignant ones and those associated with fungal infections. Obesity plays an important role in the induction and progression of DM. Co-affected obese and DM individuals tend to present worse oral health conditions. A decrease in HDL and, an increase in triglycerides bloodstream levels seem to be associated with an increase on the load of periodontopathogens on oral cavity. Moreover, DM may increase the likelihood of halitosis. Prevalence of impaired taste perception and impaired smell recognition tend to be greater in DM patients. An important interplay among oral cavity microbiome, DM, obesity and hypertension has been proposed as the reduction of nitrate into nitrite, in addition to contribute to lowering of blood pressure, reduces oxidative stress and increases insulin secretion, being these effects desirable for the control of obesity and DM. Women with PCOS tend to present a distinct oral microbial composition and an elevated systemic response to selective members of this microbial community, but the association between oral microbiome, PCOS are DM is still unknown. The results of the studies presented in this review suggest the interplay among the oral microbiome, oral cavity conditions, host immune response and DM and some of the DM associated risk factors exist. DM individuals need to be encouraged and motivated for an adequate oral health care. In addition, these results show the importance of adopting multidisciplinary management of DM and of strengthening physicians-dentists relationship focusing on both systemic and on oral cavity conditions of DM patients.

Project description:Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.

Dataset Information

The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview.

Publications

The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview.

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