by Dr. Mark Gold
The 2019 Monitoring the Future survey finds that around 35 million U.S. adults use cigarettes, about 12 percent of high school seniors use vaping products on 20 or more of the previous 30 days, and over a quarter did so within the past 30 days—an increase from 11 percent in 2017. Around 2,000 Americans under the age of 18 smoke their first cigarette every day, and over 16 million Americans have smoking-related diseases, including diabetes.1 Diabetes appears at much higher rates in individuals who use tobacco products than in those who don’t. The CDC says that tobacco products elevate the likelihood of developing type 2 diabetes by 30-40 percent, and that use of tobacco products makes managing the condition much more difficult while also increasing the chances of complications, including limb damage, heart disease, and impaired blood flow.2
Yet it’s not clear to scientists exactly why individuals who use tobacco products face much higher risks of type 2 diabetes (T2DM), especially when we normally think of weight gain as the cause of the majority of T2DM cases. A recent NIDA-funded study investigated whether certain regions of the brain might play a role in this T2DM risk. It tested the theory that nicotine control causes tobacco addiction through effects on the brain, which may then influence functions of the pancreas, blood sugar, insulin, and diabetes at the same time.
What did this study find about nicotine and diabetes?
This study found that nicotine may directly cause diabetes through the manipulation of brain areas that, surprisingly, are connected to the pancreas. A region of the brain is involved in creating negative responses to nicotine, and a protein in our bodies controls the production of hormones that boost the release of insulin by the pancreas. This study found that this pancreas-related protein is expressed in this nicotine-responding brain region. Because of this link, this study tried to learn whether this protein’s role in this brain region also plays a role in the way glucose function responds to nicotine. Researchers gave groups of mice access to nicotine through a drip that the mice could control on their own. In one group of mice, researchers eliminated this pancreas-related protein and compared mice-managed nicotine intake to control groups with intact protein function.
The mice with eliminated protein function used nicotine more than the control groups. This indicates that the pancreas-related protein limits effective management of nicotine-produced blood sugar increases while also limiting the nicotine cravings. And increases in blood glucose levels can lead to type 2 diabetes. But taking more of the drug did not lead to nicotine-produced blood glucose increases. This study points to the ways in which the brain plays an important role in the course of addiction throughout the body, and not just in the brain itself. NIDA Director Dr. Nora Volkow said, “This unanticipated finding suggests a link between nicotine use and the onset of type 2 diabetes, with implications for future prevention and treatment strategies for both diseases.”
Why is this important?
Finding that addiction-related areas of the brain may also influence other health conditions and developments in the body is a surprise. We may find that substance misuse causes heart disease, stroke, or cancers through a more direct mechanism. Rather than assuming that co-occurring disorders are flukes, it may be better to remember Occam's razor: the substances themselves may be the real culprit. This study’s findings do align with famous historical standards. Aristotle said that "Nature operates in the shortest way possible,” and while these brain circuits are complicated, they’re more efficient explanations of shorter operations.
A colleague of mine from Florida and one of this study’s authors, Dr. Paul J. Kenny, explained, “Our findings are important because they describe a mechanism that controls the addictive properties of nicotine and, surprisingly, show that the same addiction-related brain circuits also contribute to smoking-related diseases previously thought to be related to the actions of tobacco outside the brain.” This could help alter our approach to conditions like diabetes by broadening our understanding of where in our bodies, and under which circumstances, tobacco use can begin to cause problems. Part of that approach may involve paying careful attention to age, as other studies note. But isolating particular areas and regions of the brain is always helpful in crafting additional research programs and providing patients with critical information about the likelihood of risks entailed by tobacco use.
In a review of this study, Bruschetta and Diano raise some concerns about its findings, including one about sex differences: “An interesting question is whether the effect of nicotine on the mHb-pancreas axis is different in males and females.”3 While more American men than women use tobacco products, gender differences for tobacco smoking and cessation are well known.4 They point, for example, to nicotine withdrawal leading to more weight gain in women than men. Bruschetta and Diano also note that addiction to tobacco in humans depends on a complex mix of social, genetic, and other factors. Another caveat is that, because stress hormones also lead to changes in blood glucose levels, it’s possible that a different area of the brain, one that manages stress hormones, is involved in the processes identified by this study.
Tobacco use leads to disease and disability and harms nearly every organ system of the body. And it’s the leading cause of preventable death. Again, as the CDC says, it does raise the risk of developing T2DM, and associated complications. These are important points to keep in mind as it’s always possible that results from animal studies won’t be confirmed in humans. But this study still offers an explanation for the puzzling finding that individuals who use tobacco products develop T2DM even if they weigh less than they would without using tobacco products. If this data is confirmed and extended to humans, we might expect to see new treatments, especially through novel brain mechanisms, for T2DM. Dr. Kenny observed that his team’s findings could lead to the development of treatments that target these brain processes, helping individuals who use tobacco to quit and also have diabetes. Patients would have reason to welcome such advances given the efficacy of current pharmacological methods for smoking cessation. This new research can help us understand important brain areas involved in cigarette smoking, T2DM, and nicotine reinforcement. At the same time, it may help us develop treatments for individuals who use tobacco products and individuals with diabetes who don’t use tobacco products.
The brain and body are connected at the neck. They are connected directly and indirectly, and the more we look, the more connections we find. The discovery of a gene-mediated connection between the brain region called the habenula and endocrine organ and the pancreas helps us to better understand tobacco, nicotine and T2DM and refocus from the pancreas to the brain.
Centers for Disease Control and Prevention (CDC). (Last reviewed November 18, 2019). Current Cigarette Smoking Among Adults in the United States. Retrieved from https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm
CDC. (Last reviewed March 22, 2018). Smoking and Diabetes. Retrieved from https://www.cdc.gov/tobacco/campaign/tips/diseases/diabetes.html
Bruschetta, G., Diano, S. (2019). Brain-to-pancreas signalling axis links nicotine and diabetes. Nature, 574(7778), 336-337. doi: 10.1038/d41586-019-02975-w
Byars, J.A., Frost-Pineda, K., Jacobs, W.S., Gold, M.S. (2005). Naltrexone augments the effects of nicotine replacement therapy in female smokers. J Addict Dis, 24(2), 49-60. doi: 10.1300/J069v24n02_05
1. Duncan et al. (2019). Habenular TCF7L2 links nicotine addiction to diabetes. Nature, 574(7778), 372-377. doi: 10.1038/s41586-019-1653-x
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.