Insulin resistance (IR), overweight/obesity, and fatty liver commonly occur together but are independently associated with an increased risk of developing type 2 diabetes mellitus, according to results from a Korean study published onlineFebruary 14 and in the April print issue of Diabetes Care.
Investigators led by Ki-Chul Sung, MD, PhD, from the Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, found that 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 from a South Korean occupational cohort 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.
"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," the authors write.
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 (ie, >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.
The study was partially supported by a grant from Samsung Biomedical Research, as well as in part by the Southampton National Institute for Health Research Biomedical Research Unit in Nutrition, Lifestyle and Obesity. The authors have disclosed no relevant conflicts of interest.
Diabetes Care. Published online February 14, 2012. Abstract