Future Directions

Halki Diabetes Remedy

How To Treat Diabetes Naturally

Get Instant Access

The next step forward will be the discovery of more susceptibility loci that are currently undetected and to explore the physiological mechanisms and pathways that underlie the observed association using various approaches.

One approach is to initiate a fourth wave of genome-wide association studies to further increase the sample size of the initial discovery stage. This will further improve the power to uncover common variants with even smaller effect sizes (Li and Loos, 2008). The power to reveal novel loci might vary across populations because of differences in effect sizes and allele frequencies; hence, the study of ethnicities other than white Europeans might also provide new gene-discovery opportunities. For example, a study in Asian Indians required only a small discovery sample to identify the near-MC4R because the frequency of the risk-allele was substantially higher than in Europeans (Chambers et al, 2008; Loos et al, 2008). Similarly, a relatively small study in Japanese individuals (Unoki et al, 2008) was sufficient to discover KCNQ1 variants to be associated with type 2 diabetes.

Most of the studies, so far, have used BMI as a simple and inexpensive proxy measure of adiposity, which is easy to collect in large samples. More accurate measures of adiposity might further improve power, yet these are often more expensive and harder to collect. Genome-wide association studies for body fat percentage, waist circumference, extreme obesity risk and for mediating traits that underlie obesity, such as food intake and energy expenditure, may reveal new obesity susceptibility loci that are currently hidden in studies that use BMI as the main outcome. Similarly for type 2 diabetes, genome-wide association studies for fasting glucose, fasting insulin levels, HbA1C and other intermediary phenotypes for type 2 diabetes such as insulin resistance and impaired glucose tolerance might identify novel diabetes susceptibility loci.

Another strategy would be to examine the contribution of other sources of genetic variations such as copy number variants and rare variants to the predisposition to obesity and diabetes, which have so far been unexplored. Further advances in technology will be required before the analyses of copy number variants can be implemented at a larger scale. Yet, the observation that the NEGR1 locus might represent a copy number variant indicates the potential importance of this source of variation (Willer et al., 2009).

Finally, follow-up of the established loci in molecular and physiological studies will be important to determine the mechanisms through which the loci confer disease susceptibility. A prime challenge before these loci can be passed on to physiologists is pinpointing the causal variant or gene. This will require high-throughput sequencing of the region of interest in extreme cases and controls from different ethnicities. It is only when the causal locus is identified and its modes of action are completely understood that this information can be translated into mainstream health care and clinical practice.

Genome-wide association studies have led to an era of gene discovery for common diseases such as obesity and type 2 diabetes. Although candidate gene studies have identified a few genetic variants convincingly associated with obesity and diabetes traits, genome-wide association studies have identified at least 15 loci in less than 3 years of time. This recent progress has also provided valuable insights into pathophysiological mechanisms and pathways that underlie the disease development. This offers great hopes for genetic risk profiling and therapeutic intervention; however, implementation of such strategies in health care remains in the future, as we need first to learn more about the causal variants and their functional implications in relation to obesity and type 2 diabetes.

Was this article helpful?

0 0
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment