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  • George Wang, MD, PhD

What is the root cause of type 2 diabetes?

Glucometer next to fruits and vegetables

Many people have come to know that refined carbohydrates, including sugar, are detrimental to health, because these food products increase the risk for obesity, cardiovascular disease, and diabetes, among other diseases. However, what most people are not aware of, even in 2023, is that patients with these chronic diseases can often successfully achieve remission through therapeutic dietary and lifestyle interventions, such that they will no longer be dependent on the chronic use of medications. Let’s focus here on a crucial and potentially lifechanging topic, achieving remission from type 2 diabetes.

In this first blog of a two-blog series, we discuss how type 2 diabetes comes about. In the next blog, we will discuss how type 2 diabetes remission can be achieved.

This is an important topic to address because diabetes is well-known to be associated with such long-term complications as cardiovascular disease (including heart attacks and strokes), chronic kidney disease, peripheral neuropathy (resulting in tingling, numbness, and/or pain in the extremities), blindness, and increased susceptibility to infections.

How does type 2 diabetes occur in the first place?

Type 2 diabetes results from the body’s ineffective use of insulin (the hormone that the pancreas secretes in response to a rise in the blood sugar level after a meal), as well as insufficient insulin release. Normally, as blood sugar (glucose) level rises, the beta cells of the pancreas secrete insulin into the bloodstream. When healthy cells “see” insulin and binds to it, blood glucose is taken into the cells, and the blood sugar level decreases and becomes normal. What happens in type 2 diabetes is that the cells of the body, such as the muscle and fat cells, have become resistant or numb, so to speak, to the insulin that circulates in the blood. This is a phenomenon called insulin resistance, which is essentially an impairment in the body’s ability to respond normally to insulin and thereby optimize blood sugar levels. When insulin resistance is present in the body but blood glucose levels are not yet in the diabetic range, this condition is called prediabetes.

What happens next is that, because of insulin resistance, the beta cells of the pancreas output higher and higher amounts of insulin in order to maintain normal blood glucose, until eventually the function of the beta cells deteriorates and the blood sugar level can no longer be kept normal, resulting in type 2 diabetes. This understanding overthrows the previous notion that, in type 2 diabetes, an inability of the pancreas to produce insulin only happens at a late stage of the disease. Rather, both insulin resistance and inadequate beta-cell function of the pancreas (“beta-cell dysfunction”) occur together at the onset of type 2 diabetes (1).

Different classes of diabetes medications lower blood glucose levels through different mechanisms (such as increasing insulin production or reducing insulin resistance while the medications are taken daily or regularly), but they do not address the root cause of the problem, which is excess caloric intake more than what the body needs, resulting in insulin resistance. For diabetics who are not motivated to make dietary changes or are unable to make dietary changes (for example, lack of adequate access to healthful foods), these medications do help diabetics control their blood sugar levels. However, for people who have access to healthful foods and are motivated to make dietary changes to address the root cause of the disease, achieving type 2 diabetes remission without the need to take diabetes medications is a realistic goal for many. (We will discuss caveats in the next blog.)

A randomized, controlled trial that was done more than 20 years ago already showed us that lifestyle intervention is more effective than metformin, a commonly used diabetes medication, in preventing the new onset of type 2 diabetes (2). Among more than 3000 study participants who were randomly assigned to receive lifestyle intervention, metformin, or placebo, lifestyle intervention reduced the incidence of diabetes by 58 percent, while metformin reduced the incidence by only 31 percent, compared with placebo. High-quality evidence from research has also shown that higher consumptions of both red meat and processed meat are associated with an increased risk of developing type 2 diabetes (3).

At the root cause, insulin resistance results from increased caloric intake that is in excess of energy expenditure. When we overfeed ourselves beyond our body’s daily energy needs, a positive energy balance and weight gain result. The fat (adipose) tissue in obesity fosters a chronic, low-grade inflammation that is a major and well-known cause of insulin resistance (4). For example, eating unhealthful foods that are high in calories and saturated fats but low in nutrient content, typical of the standard American diet, coupled with reduced physical activity or a sedentary lifestyle, can lead to insulin resistance.

The excess-calorie dietary habit also leads to a phenomenon called “lipotoxicity,” which occurs when higher levels of fatty acids circulate in the blood and more lipids accumulate in the cells of the body, particularly in the muscle and liver. The circulating fatty acids interfere with the action of insulin, and the accumulation of lipid products inside cells causes insulin resistance (4). In other words, lipotoxicity compromises the normal response of cells to insulin, and it does so by affecting glucose transporters, which are “channels” that move to the surface of cells to allow glucose to enter cells, such as muscle cells and fat cells. These channels are regulated by insulin (5). When these channels are affected, insulin resistance results, requiring higher amounts of insulin in order to “push” glucose into cells (6). Exercise moves these glucose transporters to the surface of cells and, therefore, can improve insulin resistance in people with type 2 diabetes (5). (However, exercise alone, without any dietary changes, is unlikely to result in type 2 diabetes remission.)

We can see the real-life implications of the above concepts by looking at a 2015 research study in which healthy men were fed a high-calorie version of the common U.S. diet (7). These men rapidly gained weight over a week, and insulin resistance quickly developed after just 2 to 3 days of starting the high-calorie diet. In this early stage of the excess calorie intake, insulin resistance was associated with increased oxidative stress. The oxidative stress, in turn, was associated with changes to the glucose transport channels mentioned above. These research results are particularly interesting because they suggest that an unhealthy dietary pattern with excess calories may quickly cause oxidative stress and insulin resistance even before appreciable weight gain is established.

In addition to insulin resistance, people with type 2 diabetes also have what is called beta-cell dysfunction of the pancreas, as mentioned above, which is associated with inadequate insulin production. Part of this defect is due to a loss in the number of beta cells in the pancreas that produce insulin. Lipotoxicity, as explained above, results in beta-cell loss (1).

Genetic influences are important as well, because certain genes play important roles in the development of insulin resistance, beta-cell dysfunction, and, therefore, type 2 diabetes (1). Because the prevalence of type 2 diabetes has increased rapidly in recent decades, faster than what can be accounted for by genetic changes in the population, discussions by experts have also focused on the role that environmental changes (such as environmental chemicals) may play in the diabetes epidemic.

(While type 1 diabetes is not the topic of this discussion, it should be noted that insulin resistance also contributes to the morbidity associated with type 1 diabetes. Therefore, a lifestyle medicine approach to the treatment of type 1 diabetes is also important to minimize an escalating need for insulin injections and improve outcomes in this disease.)

The above summary is a somewhat simplified view of the origins of insulin resistance and beta-cell dysfunction (though it may not exactly be a breeze to read through this subject). We have not, for example, touched on the role of the gut microbiota in the development of insulin resistance (4). But for the purposes of this discussion, this summary serves to pinpoint the primary drivers of insulin resistance and type 2 diabetes. With this understanding, we can move on to consider how to treat type 2 diabetes at the root cause.

Please continue reading our next blog, “Achieving Type 2 Diabetes Remission.”

(If you have diabetes or other medical conditions, consult your physician before making dietary changes or any changes to your medical treatment.)


1. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014 Mar 22;383(9922):1068-83.

2. Knowler WC, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403.

3. Neuenschwander M, et al. Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies. BMJ. 2019 Jul 3;366:l2368.

4. Johnson AM, Olefsky JM. The origins and drivers of insulin resistance. Cell. 2013 Feb 14;152(4):673-84.

5. Shepherd PR, Kahn BB. Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. N Engl J Med. 1999 Jul 22;341(4):248-57.

6. Kelly J, Karlsen M, Steinke G. Type 2 Diabetes Remission and Lifestyle Medicine: A Position Statement From the American College of Lifestyle Medicine. Am J Lifestyle Med. 2020 Jun 8;14(4):406-419.

7. Boden G, et al. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Sci Transl Med. 2015 Sep 9;7(304):304re7.


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