Genetic architecture of type 2 diabetes

Hara, Kazuo; Shojima, Nobuhiro; Hosoe, Jun; Kadowaki, Takashi

doi:10.1016/j.bbrc.2014.08.012

Cited by 49 publications

(35 citation statements)

References 102 publications

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“…In non-Sikh, south Asians, the study detected six associations, including SNPs of RBM38/HMGB1P1, PLXNA4, SCAP, and chr5p11 [45]. Further evaluation in east Asians, Europeans and a joint meta-analysis of 27 multiethnic studies did not identify any additional loci, nor found any evidence of the new variant [46]. Moreover, a recent review of the evidence in African-American populations highlighted that the risk loci identified in European populations did not overlap.…”

Section: Ethnic Differences In T2dm Riskmentioning

confidence: 82%

The Impact of Personalized Medicine of Type 2 Diabetes Mellitus in the Global Health Context

et al. 2016

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Advances in the fields of genomic sciences have given rise to personalized medicine. This new paradigm draws upon a patient's genetic and metabolic makeup in order to tailor diagnostics and treatment. Personalized medicine holds remarkable promises to improve prevention and management of chronic diseases of global relevance, such as Type 2 diabetes mellitus (T2DM). This review article aims at summarizing the evidence from genome-based sciences on T2DM risk and management in different populations and in the Global Health context. Opinions from leading experts in the field were also included. Based on these findings, strengths and weaknesses of personalized approach to T2DM in a global context are delineated. Implications for future research and implementation on that subject are discussed.

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Section: Ethnic Differences In T2dm Riskmentioning

confidence: 82%

The Impact of Personalized Medicine of Type 2 Diabetes Mellitus in the Global Health Context

et al. 2016

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“…For instance, in the human brain that is 2% of the bodyweight but accounts for 20% of the whole body metabolism [14,15], neurons can no longer replicate in normal adults but manifest evident IR in T2D patients. Indeed, currently no IR-causing mutation has been identified, although certain genetic backgrounds may predispose the individuals to IR [16][17][18].…”

Section: Type 2 Diabetes (T2d) Is Irreversible But Sans An Irreversimentioning

confidence: 99%

Is Type 2 Diabetes One of Such Aging Phenomena That Lack an Irreversible Structural Change?

Jia¹,

Chen²,

Jia³

et al. 2015

J Diabetes Metab

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All biological functions should have a structural basis. Any functional change should be due to an alteration in the related structure. If a functional change is irreversible, it should be due to the irreversibility of the structural alteration. For instance, cancer is irreversible because cancer cells have irreversible genetic mutations. However, Type 2 Diabetes (T2D) with Insulin-Resistance (IR) as a central mechanism is irreversible but seems to lack a corresponding irreversible structural change. IR and T2D exhibit many abnormalities that are attributable to altered mitochondria or altered cellular RNAs, proteins, lipids, etc. without genetic mutations involved. These alterations are reversible, because mitochondrial biogenesis can be induced by such as exercise whereas RNAs, proteins and lipids will degrade after some time. Aging is irreversible but many aging manifestations also lack corresponding permanent structural changes, and IR may be one such manifestation. IR affects mainly striated muscles, adipose tissue, brain and liver that are collectively defined herein as the "catabolic cell type" for their low proliferation rates but high metabolism of glucose via oxidation-phosphorylation in mitochondria. In contrast, fast-proliferating cells are defined as the "anabolic cell type" because they are the main cancer origins and often metabolize glucose via glycolysis. Dichotomizing T2D-and cancer-targeted cells and pointing out that the irreversible IR as an aging phenomenon lacks a corresponding irreversible structural change may help understand the differences between, and the mechanisms of, T2D and cancer, although these concepts challenge the "structural-functional relationship" dogma in not only biology but also philosophy. We have been Taught that a Function is Based on a StructureWe as biologists or medical researchers are well educated on structures of various organisms, including the human one. Here, a structure can be something fairly large, such as the anatomy at the macroscopic and microscopic levels, but can also be something very small at the molecular level, such as the sequences and conformations of the DNAs, RNAs, proteins, lipids, starches, etc. Out of this educational background, a concept of structural-functional relationship has been firmly entrenched in our mind. This concept says that a function is based on one sort of architecture or makeup, and any change in a function ultimately can be causally linked to an alteration in the related structure. If the structural alteration is reversed, the function will return to normal as well. For example, based on this rationale, cardiac surgery is performed to fix congenital heart malformation of children. Conversely, irreversible change in a function should be due to an irreversible alteration of a structure.At the molecular level, for a long time it had been thought that proteins were the only executors of cellular functions and all genes had to be expressed ultimately as proteins to be functional, but we now know that many RNAs can al...

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“…Type 2 diabetes (T2D) is a heterogeneous and multi-factorial metabolic disease (genetic and environmental factors), characterized by increase in peripheral blood glucose (hyperglycemia) due to insulin resistance (decreased action of insulin at targeted tissues) and/or pancreatic beta-cell dysfunction (1). T2D is known as non-insulin dependent diabetes, accounting for 90% of diabetic patients who possess several pathogenic factors such as lifestyle, overeating, and genetic elements, implying a 2.4 fold increased risk for T2D in individuals with positive family history (2).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Transcription Factor 7 like 2 polymorphisms and haplotypes in risk of Type 2 Diabetes

Saravani

Irani

Galavi

2016

Revista Romana De Medicina De Laborator

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Genetic architecture of type 2 diabetes

Cited by 49 publications

References 102 publications

The Impact of Personalized Medicine of Type 2 Diabetes Mellitus in the Global Health Context

The Impact of Personalized Medicine of Type 2 Diabetes Mellitus in the Global Health Context

Is Type 2 Diabetes One of Such Aging Phenomena That Lack an Irreversible Structural Change?

Evaluation of Transcription Factor 7 like 2 polymorphisms and haplotypes in risk of Type 2 Diabetes

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