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Genetic variations that control KLF14 have little impact on overall weight but have high impact on where in the body excess fat is stored. In women, versions of the gene that result in fat being preferentially deposited around the hips, rather than around the abdomen, provide protection against diabetes. The different variations of KLF14 have an impact on the development of fat cells.
In women carrying the version of the KLF14 gene that is associated with increased risk of diabetes, the individual fat cells are much larger and full of fat. This is likely to happen because there are fewer of such cells in the first place, such that each cell ends up needing to take up more fat, resulting in inefficient, unhealthy fat cells that are more likely to contribute to diabetes.
The effects of these gene variations were specific to females, women who inherited the risk version of the gene from their mothers, the impact is to increase diabetes risk about 30%. Abnormalities in fat tissue, fat in the liver and in the insulin-producing cells of the pancreas can contribute.
Being over-weight increases the risk of type 2 diabetes, but where any excess fat is stored in the body has a big impact on disease risk. Excess fat stored around the hips tends to be free of metabolic consequences while fat around the waist may increase diabetes risk.
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