Three Independent Factors Increase Diabetes Risk

Insulin resistance, overweight/obesity, and fatty liver commonly occur together but are independently associated with an increased risk of developing type 2 diabetes….

Ki-Chul Sung, MD, PhD, who led investigators from the Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, found that insulin resistance (IR) was linked to an almost quadrupled risk for diabetes (odds ratio [OR], 3.92; 95% confidence interval [CI], 2.86 – 5.37; P < .0001) during a 5-year period, whereas fatty liver and overweight/obesity increased the risk by factors of 2.42 (95% CI, 1.74 - 3.36; P < .0001) and 1.62 (95% CI, 1.17 - 2.24; P < .004), respectively.

Among those with 2 risk factors, the combination of overweight/obesity and fatty liver was associated with the lowest risk for diabetes (OR, 3.23; 95% CI, 1.78 – 5.89; P < .001), and IR/fatty liver with the highest risk (OR, 6.73; 95% CI, 3.49 - 12.73; P < .001).

A cluster of all 3 factors was linked to more than a 14-fold increased risk for diabetes during the 5-year period (OR, 14.13; 95% CI, 8.99 – 22.21; P < .001).

When evaluating the association of each of these risk factors with type 2 diabetes, adjustments were made for age, sex, educational status, smoking status, alcohol consumption, and exercise frequency as well as triglycerides and alanine aminotransferase levels.

Although IR, overweight/obesity, and fatty liver are strongly correlated, the dissociation between these risk factors suggests that different pathogenetic mechanisms may be in play.

“The clustering of IR, overweight/obesity, and fatty liver is common and markedly increases the odds of developing type 2 diabetes, but these factors also have effects independently of each other and confounding factors,” the authors write, adding that treatment for each factor may be warranted.

For the study, investigators recruited 12,853 nondiabetic individuals in 2003. At a 5-year follow-up in 2008, 223 cases of incident cases of diabetes were identified: 26 of those diagnosed (12%) had none of the 3 risk factors, 37 (17%) had 1 risk factor, 56 (25%) had 2 risk factors, and 104 (47%) had all 3 risk factors.

The authors wrote, “Fatty liver is emerging as an independent risk factor for diabetes, and our data suggest that its association with incident diabetes may be stronger than that of overweight/obesity and weaker than that of IR.”

Because of the striking and marked increase in odds of diabetes with the occurrence of all 3 risk factors, the authors suggest that targeted specific approaches to ameliorating the effects of each factor may have great effect on reducing the risk of developing diabetes.

Study limitations include a preponderance of men in an occupational cohort derived from 1 ethnic group, and use of ultrasound to identify fatty liver, which picks up moderate fatty liver disease (i.e., more than 30% liver fat infiltration) but not minor amounts of fatty liver infiltration. In addition, no data were available on family history of diabetes, use of drugs, and other key information that may increase one’s risk of diabetes.

“Further research is needed to understand the separate pathogenetic mechanisms by which IR, overweight/obesity, and fatty liver contribute individually to the development of type 2 diabetes,” the authors write, noting that the efficacy of lifestyle and pharmaceutical interventions may vary for different combinations of risk factors.

Diabetes Care. Published online February 14, 2012.