The Cost-Effectiveness of Personalized Genetic Medicine

Greeley, Siri Atma W.; John, Priya M.; Winn, Aaron N.; Ornelas, Joseph; Lipton, Rebecca B.; Philipson, Louis H.; Bell, Graeme I.; Huang, Elbert S.

doi:10.2337/dc10-1616

Cited by 80 publications

(72 citation statements)

References 25 publications

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“…[8] So several population-based studies in individuals of pre-diabetes were performed. [9,10,11,12,13,14] The normal range of blood glucose exists between (80-120) mg/dl. An individual is said to be diabetic if the blood glucose level after 12 hours of fasting exceeds 120mg/dl and postprandial blood glucose exceeds 180 mg/dl.…”

Section: World Journal Of Pharmaceutical Researchmentioning

confidence: 99%

Current Antidiabetic Drugs and Strategies for the Treatment of Type 2 Diabetes Mellitus

Joshi¹

2017

WJPR

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A constant increase in the features of metabolic syndrome leading to serious complications including neuropathy, retinopathy and nephropathy has resulted in worldwide epidemic of Type 2 diabetes mellitus or insulin resistance. Most of the available antidiabetic drugs were developed in the absence of defined molecular targets or a clear understanding of disease pathogenesis. Moreover, the available drugs suffer from one or the other side effects. Emerging knowledge of key physiologic mechanisms related to probable causes of hepatic and muscle insulin resistance on glucose metabolism has led to a number of new emerging molecular drug targets. Type 2 diabetes mellitus is a major contributor of deaths in India and worldwide, there is a urgent need to develop new drugs that will be helpful to diminish the overall diabetic load of world population. The present review provides the description of existing antidiabetic drugs and their respective molecular targets. There is a information regarding the antidiabetic targets that include receptors and enzymes that enhance glucose-stimulated insulin secretion, suppress hepatic glucose production, increase skeletal muscle glucose transport and utilization, increase insulin sensitivity and intracellular insulin signaling with reduction in circulating and intracellular lipids. It also emphasizes on the need for developing novel antidiabetic drugs having lower side effects and more efficacy.

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Section: World Journal Of Pharmaceutical Researchmentioning

confidence: 99%

Current Antidiabetic Drugs and Strategies for the Treatment of Type 2 Diabetes Mellitus

Joshi¹

2017

WJPR

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“…Patients and consumers report their motivation for utilizing genetic testing is to increase their certainty of disease risk (Esplen et al 2007) or to motivate behavior change (Bradfield et al 2012, Committee On 2013 including individuals at high-risk for T2D (Boerschmann et al 2010, Grant et al 2009, McCarthy et al 2013, Cheng et al 2008, Eriksson 2007, Flegal et al 2010, Esplen et al 2007, Markowitz et al 2011). Parent's intention for genetic testing is to make health-related decisions for both themselves and for their children (Bradfield et al 2012, Haga et al 2012, Bollinger et al 2012, Tercyak et al 2011, Hay et al 2012, even when they understand the limitations and risks, including the benefit of knowing genetic risk to make positive lifestyle changes in their children.…”

Section: Call For Research Into the Clinical Utility Of Genetic Testimentioning

confidence: 99%

Genetic Testing for Type 2 Diabetes in High-Risk Children: the Case for Primordial Prevention

Wessel¹,

Marrero²

2017

RIO

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Extensive research now demonstrates that lifestyle modification can significantly lower risk of developing type 2 diabetes (T2D) in high-risk adults. In children, the evidence for lifestyle modification is not as robust, but the rapidly rising rate of obesity in children coupled with the substantial difficulty in changing behaviors later in life illuminates the need to implement prevention efforts early in the life course of children. Genetic data can now be used early in the life course to identify children at high-risk of developing T2D before traditional clinical measures can detect the presence of prediabetes; a metabolic condition associated with obesity that significantly increases risk for developing T2D. Such early detection of risk may enable the promotion of "primordial prevention" in which parents implement behavior change for their at risk children. Young children with genetic risk are a novel target population. Here we review the literature on genetic testing for prevention as it relates to chronic diseases and specifically use T2D as a model. We discuss the history of primordial prevention, the need for primordial prevention of T2D and the role genetic testing has in primordial prevention of high-risk families. (Ogden et al. 2014a). In children, the prevalence of obesity and T2D is rising dramatically (May et al. 2012). Currently 32% of U.S. children are overweight or obese (Ogden et al. 2014b). High rates of overweight/obesity begin at birth and continue to grow throughout early childhood Ogden et al. 2010. A study representing 7,738 U.S. children followed from kindergarten through 8 grade showed that part of the course of obesity is already established by age 5 and for those children who were overweight in kindergarten, 45% became obese in the early elementary years (Cunningham et al. 2014). This observation is supported by a study that reported ages 2-6 years is the most critical growth period for prediction of adult obesity (De Kroon et al. 2010). Of importance to this discussion, the effect of genetic variation on obesity begins in childhood and manifests in rapid growth leading to adult obesity (Belsky et al. 2012). KeywordsT2D is a slow progressing disease that occurs in genetically predisposed individuals preceded by behaviors (diet and physical activity) established early in life; where ~40% of the variation in T2D can be explained by genetic factors (Kaprio et al. 1992). et al. 2008). Not surprising is the genetic architecture of obesity is very similar in children and adults (Bradfield et al. 2012). Given that the effect of genetic variation on obesity begins in childhood and manifests in rapid growth leading to adult obesity (Belsky et al. 2012); the potential utility of genetic testing, particularly as it applies to children, is its ability to identify risk for diabetes before other clinical markers appear such as excessive weight gain. The Case for Genetic Testing as a Vehicle to Stimulate Primordial PreventionIn 1978 Toma Strasser, a cardiovascular epidemiologist at the Wor...

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“…Furthermore, a recent study demonstrated that personalized genetic medicine applied to patients with NDM, which is currently based on standard Sanger sequencing of KCNJ11 and ABCC8 that is performed by clinical diagnostic laboratories (at a cost of $2,815 in the U.S. [9]), leads to high financial benefits (9). However, as KCNJ11 and ABCC8 encode a total of 40 coding exons, this genetic testing is obviously time-consuming, laborintensive, and restricted to two genes only while NDM can be due to mutations in at least 11 genes (Table 1) (1,4).…”

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confidence: 99%

Highly Sensitive Diagnosis of 43 Monogenic Forms of Diabetes or Obesity Through One-Step PCR-Based Enrichment in Combination With Next-Generation Sequencing

et al. 2014

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OBJECTIVEAccurate etiological diagnosis of monogenic forms of diabetes and obesity is useful as it can lead to marked improvements in patient care and genetic counseling. Currently, molecular diagnosis based on Sanger sequencing is restricted to only a few genes, as this technology is expensive, time-consuming, and laborintensive. High-throughput next-generation sequencing (NGS) provides an opportunity to develop innovative cost-efficient methods for sensitive diabetes and obesity multigene screening. RESEARCH DESIGN AND METHODSWe assessed a new method based on PCR enrichment in microdroplets (RainDance Technologies) and NGS using the Illumina HiSeq2000 for the molecular diagnosis of 43 forms of monogenic diabetes or obesity. Forty patients carrying a known causal mutation for those subtypes according to diagnostic laboratories were blindly reanalyzed. RESULTSExcept for one variant, we reidentified all causal mutations in each patient associated with an almost-perfect sequencing of the targets (mean of 98.6%). We failed to call one highly complex indel, although we identified a dramatic drop of coverage at this locus. In three patients, we detected other mutations with a putatively deleterious effect in addition to those reported by the genetic diagnostic laboratories. CONCLUSIONSOur NGS approach provides an efficient means of highly sensitive screening for mutations in genes associated with monogenic forms of diabetes and obesity. As cost and time to deliver results have been key barriers to uncovering a molecular cause in the many undiagnosed cases likely to exist, the present methodology should be considered in patients displaying features of monogenic diabetes or obesity. A.B. and J.P. contributed equally to this work.

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The Cost-Effectiveness of Personalized Genetic Medicine

Cited by 80 publications

References 25 publications

Current Antidiabetic Drugs and Strategies for the Treatment of Type 2 Diabetes Mellitus

Current Antidiabetic Drugs and Strategies for the Treatment of Type 2 Diabetes Mellitus

Genetic Testing for Type 2 Diabetes in High-Risk Children: the Case for Primordial Prevention

Highly Sensitive Diagnosis of 43 Monogenic Forms of Diabetes or Obesity Through One-Step PCR-Based Enrichment in Combination With Next-Generation Sequencing

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