Carbohydrates are one of the most argued-about topics in nutrition. It turns out the question isn’t whether you should eat carbs, but rather which carbs, in what amounts, and how your body handles them.
It comes down partly to genetics, including a well-studied gene called TCF7L2 that shapes how efficiently some people process both carbs and fat.
Why carbs got a bad reputation
Many foods linked to obesity are high in refined carbs and added sugar. Pastries, white bread, chips, and other processed snacks are easy to overeat, digest quickly, and offer little fibre or nutritional value.
Low-carb diets also produce quick, early weight loss. Cutting carbs lowers glycogen stores, and glycogen holds water, so people often drop a few pounds in the first week. Many also feel less hungry and eat less overall.
And because eating carbs raises blood sugar, and high blood sugar is linked to type 2 diabetes, people assumed carbs were the problem.
The real issue is highly processed carbs.
Carbs matter
Whole-food carbs provide diverse benefits. Vegetables, fruit, beans, oats, potatoes, quinoa, and whole grains provide fibre for gut health, vitamins like folate and vitamin C, minerals like potassium and magnesium, plant compounds like polyphenols and antioxidants, and resistant starch that feeds beneficial gut bacteria.
Carbs are also the body’s preferred fuel source for many tissues. Under normal conditions, the brain runs on glucose, red blood cells depend on it entirely, and muscles draw heavily on glycogen, stored carbohydrate, during hard exercise. The brain can adapt to ketones when carbs are scarce, but that’s the exception, not the default.
Can you survive without carbs?
Unlike certain fats and amino acids, there’s no strict daily requirement for carbohydrates. If carb intake drops very low, the liver makes its own glucose through gluconeogenesis, building it from amino acids, lactate, and glycerol. The liver also produces more ketones from fat, and after a few days or weeks, the brain becomes better at using them for fuel.
This flexibility helped humans survive food shortages throughout history. Surviving and thriving however, are different things.
Some people feel great on a ketogenic diet. Others experience fatigue, disrupted sleep, constipation, reduced exercise performance, or persistent cravings.
Why do some people do well on low-carb diets and others don’t?
Insulin sensitivity, muscle mass, activity level, liver function, gut bacteria, stress, sleep, hormones, and genetics all affect how someone handles fewer carbs.
A very insulin-sensitive endurance athlete might eat several hundred grams of carbs a day and maintain excellent blood sugar control. Someone with insulin resistance may feel much better when they cut carbs. Neither response is wrong. Metabolism exists on a spectrum, and genetics influence where each person lands.
Meet TCF7L2: one of the most studied genes for blood sugar
One of the strongest and most researched genes linked to blood sugar control is the common variant TCF7L2, a gene that is found in over 50% of the population.
Genetic panels often report two variants: rs12255372 and rs7903146. These sit close together on the gene and are often inherited together, so some panels report only one.
The two variants aren’t identical. Research on rs12255372 focuses on insulin release and blood sugar control, while research on rs7903146 covers similar ground but also examines how the gene interacts with dietary fat.
People who carry the rs12255372 GT or TT version tend to have a weaker early insulin response after eating.
Did you know? Your DNA comes in pairs. At every relevant location in your genes, you inherit one letter from each parent, and the combination you end up with, GT, TT, or GG, can shift how your body functions. For rs12255372, carrying a T in that pair connects to a slower insulin response after eating, which shapes how well your body manages blood sugar.
Carbohydrates
When you eat carbohydrates, blood sugar rises quickly. The pancreas is supposed to respond immediately, releasing a burst of insulin it already has on hand. In people with the TCF7L2 risk variant, that first burst is often weaker or slower, so blood sugar climbs higher before the body catches up. The variant also blunts the body’s response to GLP-1, a gut hormone that normally prompts the pancreas to release insulin after eating.
Liver
There’s also evidence that TCF7L2 affects how much glucose the liver releases into the bloodstream. Normally, insulin signals the liver to slow glucose production after a meal. In people with the GT or TT variant, that signal may be less effective, so the liver keeps contributing glucose even after eating.
Inflammation
Inflammation compounds this further. Inflammatory signals from excess belly fat, poor sleep, chronic stress, or an out-of-balance gut microbiome can interfere with how insulin communicates with muscle, liver, and fat cells. This can make those cells less responsive even when insulin is present. For someone whose pancreas and liver already have less room to manage blood sugar, added inflammation can shrink that room further, and the two factors tend to compound rather than act independently.
Fat
The same variant also affects how the body handles dietary fat, and the mechanism is related: TCF7L2 blunts how well the pancreas responds to GLP-1, a gut hormone that normally boosts insulin release after eating.
After you eat, your gut releases a hormone called GLP-1, which signals the pancreas to release insulin. In people with TCF7L2 risk variants, the hormone still shows up as it should. The problem is that the pancreas doesn’t respond to the signal as strongly as it should. The message arrives, but the response is weaker than expected. Researchers call this incretin resistance.
The exact reason higher-fat diets produce worse outcomes for these individuals isn’t fully understood, but the pattern holds across several studies. In a 10-week reduced-calorie trial, people with the rs7903146 TT variant lost more weight on a lower-fat diet than on a higher-fat one. A two-year weight-loss study found that people with the rs12255372 TT variant showed a strong link between fat intake and changes in weight and body fat at the six-month mark.
Why a no-carb diet may backfire
Cutting carbs can work well for some people. For people with a TCF7L2 risk variant, it’s more complicated.
TCF7L2 risk variants affect how the body handles fat, carbohydrates, and glucose in ways that can compound one another. Lower fat intake tends to produce better outcomes for people with these variants. Very low carbohydrate diets create a separate problem: when carb intake stays very low for a long time, the liver becomes efficient at manufacturing its own glucose. For someone whose genes already push the liver toward higher glucose output, that adaptation works against them, not for them.
People with this variant are poorly suited to long-term ketogenic diets, particularly if they notice rising fasting blood sugar, worsening LDL or ApoB cholesterol, poorer sleep, declining exercise performance, or difficulty reintroducing carbs without large blood sugar spikes.
The smart-carb approach
Eating modest amounts of healthy carbohydrates regularly tends to produce better results. This gives the pancreas regular practice maintaining its normal insulin release pattern and avoids the higher fat intake that also produces worse outcomes for people with this variant.
That generally means leaning on high-fibre vegetables, beans and legumes, berries, whole fruit, reasonable portions of potatoes or sweet potatoes, and oats or minimally processed whole grains if tolerated well.
Eating carbs alongside protein, healthy fats, and fibre slows digestion, softens blood sugar spikes, and reduces pressure on that first-phase insulin response.
Staying active, especially through strength training and walking after meals, also helps muscles pull glucose from the blood more efficiently.
Carbs aren’t villains, and they aren’t magic either. Humans can survive without them because our metabolism is remarkably adaptable. But surviving isn’t the same as thriving.
To understand how your genetics shape your metabolic health, talk to your Harrison team about genetic testing.
