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Did you know DNA affects your ability to store sugar?

Changes in glycogen storage can affect your risk of diabetes

Three days left until your next marathon. On top of the many months of hard training, you’ve stocked up on whole grains, sweet potatoes and tart cherries. You’re giving your body one final boost with carbohydrate loading, a technique used to maximize endurance by increasing the amount of fuel (glycogen) stored in your muscles. When executed properly, carb-loading could shave minutes off your race time. Yet, the outcome of carb-loading is not as universal as we would like it to be. This is because our response to carbohydrates is influenced by a variety of factors, including training environment, body weight and genetics. Genes in particular, have a substantial effect on many aspects of carbohydrate biology, from absorption, to breakdown and storage.

Our muscles use both fats and glucose for energy. Although fats generate twice as much energy as glucose, our primary energy source during intense exercise is the easily-accessible glucose. This glucose is stored as glycogen within our body, and training and carb-loading can optimize this storage supply. Bread, pasta and rice are typical foods in a  pre-marathon carb-loading diet. The high carbohydrate content of these foods helps increase glycogen stores and blood glucose levels. Elevated blood glucose also stimulates the release of insulin to promote glycogen storage.

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In addition to diet, genetic variation also plays a role in the accumulation of glycogen in our muscles. The glucokinase (GCK) enzyme controls the first step required to convert glucose to glycogen. When blood glucose levels are low, the glucokinase regulatory protein (GCKR), turns of the GCK enzyme. This GCK-GCKR complex is then stored in a separate compartment of the cell. When glucose becomes available, GCK is released so it can facilitate the conversion of glucose to glycogen. However, people with a genetic variant of GCKR, called rs1260326, are unable to inactivate GCK. They store glycogen even when blood glucose levels are low, resulting in persistently low blood glucose levels. These people might have an advantage when it comes to carb-loading because they will be able to fill their glycogen stores to the brim.

Lower blood sugar levels associated with rs1260326 also come with another added benefit – protection against type II diabetes. Diabetes is characterized by persistently high glucose levels in the blood, so it’s easy to see how a genetic change that enhances the storage of glucose will reduce the risk of diabetes. These findings suggest that blocking GCKR (which will increase GCK levels and lower blood glucose levels) is a potential therapeutic option for treating diabetes. Two such anti-diabetic compounds have been identified in mice, and future experiments will show their effectiveness in people.

Our relationship with carbohydrates is anything but simple. In the wake of ever-increasing rates of diabetes, sugar is often blamed for hyperactivity in kids, weight gain and even cancer. But our bodies do need some sugar, and carb-loading is a prime example of the benefits. However, it’s an excessive consumption of sugar that increases our risk of conditions that affect our health such as diabetes, obesity and cardiovascular disease. Yet there are some of us with small genetic changes that may actually be somewhat protected from the detrimental affects of excess sugar – a reassuring fact since limiting our sugar consumption is no simple task.

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