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Type 2 Diabetes Genetic Predispositions

Whites and blacks with a genetic predisposition to type 2 diabetes have an increased risk of mortality.

The epidemic of type 2 diabetes is quickly escalating in the United States. This rapid growth is projected to be disproportionately higher in certain ethnic minorities. Studies have shown that type 2 diabetes is partly determined through genetics. The predisposition on attaining certain type 2 diabetes genes could potentially increase mortality rates or its complications. As the prevalence of obesity increases in the United States, so does the type 2 diabetes epidemic. This co-epidemic is due to the social-behavioral influences. For example: the use of technology, efficient transportations, increased sedentary work and lifestyle, and electronic transactions, as well as the consumption of readily available foods rich in calories. Although these social-behavioral influences are modifiable risk factors for type 2 diabetes, the presence of these risk factors could amplify the genetic effects. Studies have shown that individuals with higher type 2 diabetes genetic predispositions may be more susceptible to the health consequences of obesity. This study was conducted to test the hypothesis that carrying higher aggregate genetic burden of type 2 diabetes risk predicted all-cause mortality, independent of BMI. It was also conducted to determine whether type 2 diabetes genetic-mortality was associated with different BMI categories or ethnicities.

The study included 6,501 participants (81.1% non-Hispanic white, 12.7% non-Hispanic  black, and 6.2% Mexican-American). 38 type 2 diabetes-related single nucleotide polymorphisms (SNPs) were genotyped. Association between aggregate genetic risk for type 2 diabetes and all-cause mortality was investigated.

After adjusting for age, sex, BMI, smoking, alcohol, and hypertension, increased mortality risk was observed for every type 2 diabetes allele an individual had, independent of BMI (OR 1.04, 95% CI 1.00 – 1.07, P = 0.05). These findings were consistent with non-Hispanic whites and non-Hispanic blacks, but not with Mexican Americans. Mexican Americans showed a negative trend even after adjustments. The analysis was repeated with Cox regression that showed generally similar results. Association of increased risk of mortality was evaluated by ethnicity, which yielded similar results for non-Hispanic whites, and non-Hispanic blacks, but not for Mexican Americans (OR 0.95, 95% CI 0.89 – 1.01, P = 0.01).

When BMI was accounted for, the mortality risk per allele was higher among obese non-Hispanic whites as compared to normal-weight non-Hispanic whites. There was a negative trend observed in normal-weight Mexican Americans (BMI <25 kg/m2, OR 0.91, 95% CI 0.82 – 1.00).

This negative trend of mortality associated with type 2 diabetes genes in normal-weight Mexican Americans warrants another study with a larger population of individuals of Mexican descent. The authors added, “Future genetic-environment interaction studies may clarify the mechanisms underlying the heterogeneous effects of T2D-related genetic variants on mortality by ethnicity and BMI, and inform lifestyle intervention strategies directed at those with stronger genetic susceptibility to T2D-related mortality.”

In addition, when asked if the genetic risk impacted mortality risk in individuals who did not develop type 2 diabetes, co-author Aaron Leong, MD, of Harvard Medical School in Boston replied, “We unfortunately couldn’t determine whether the excess mortality risk associated with a higher T2D genetic predisposition occurred only among those who did develop T2D within their lifetime, as we do not have data on new cases of T2D during follow-up. So it is possible that the higher genetic risk for T2D impacts mortality risk even if a person does not develop diabetes; however, we could not test this specific hypothesis.”

The study concluded that carriers of type 2 diabetes risk-alleles have an increased mortality risk when compared to individuals who do not carry the gene. The increased risk with the genetic burden ties in non-genetic factors such as ethnicity and body weight that lead to the increase in risk of mortality. With the increase in obesity and type 2 diabetes, individuals should maintain a normal body weight, especially individuals with a high predisposition of the generic risk factor.

Practice Pearls:

  • Individuals with diabetes carrying type 2 diabetes alleles have an increased risk of mortality.
  • High BMI (> 25 kg/mm3) is associated with increased risk of mortality in individuals with high genetic predisposition to type 2 diabetes.
  • Individuals with diabetes should maintain a normal-body weight to reduce the risk of mortality, especially the ones genetically predisposed to type 2 diabetes.

Researched and prepared by Sabair Pradhan, Doctor of Pharmacy Candidate USF College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

 

Leong A, Porneala B, Dupuis J, Florez JC, Meigs JB. Type 2 Diabetes Genetic Predisposition, Obesity, and All-Cause Mortality Risk in the U.S.: A Multiethnic Analysis. Diabetes Care. 2016

Higher Genetic T2D Risk Tied to Increased Mortality. Mega Page Today. http://www.medpagetoday.com/Endocrinology/Diabetes/56224?xid=NL_breakingnews_2016-02-17&eun=g40055d0r. Updated February 17, 2016. Accessed March 2, 2016.