Heavy Cannabis Use Tied to Less Diabetes in Women

Marlene Busko 

February 09, 2022

Women who used marijuana (cannabis) at least four times in the previous month (heavy users) were less likely to have type 2 diabetes than women who were light users or nonusers, in a nationally representative US observational study.

In contrast, there were no differences in the prevalence of type 2 diabetes in men who were light or heavy cannabis users versus nonusers.

These findings are based on data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), whereby participants self-reported their cannabis use.

The study by Ayobami S. Ogunsola, MD, MPH, a graduate student at Texas A&M University School of Public Health, in College Station, and colleagues was recently published in Cannabis and Cannabinoid Research. 

What Do the Findings Mean?

Although overall findings linking cannabis use and diabetes have been inconsistent, the gender differences in the current study are consistent with animal studies and some clinical studies, senior author Ibraheem M. Karaye, MD, MPH, told Medscape Medical News.

However, these gender differences need to be confirmed, and "we strongly recommend that more biological or biochemical studies be conducted that could actually tell us the mechanisms," said Karaye, an assistant professor in the Department of Population Health, Hofstra University, Hempstead, New York.

"It's indisputable that medical marijuana has some medical benefits," he added. "Women [who use cannabis] have been shown to lose more weight than men, for example."

"If women [cannabis users] are less likely to develop diabetes or more likely to express improvement of symptoms of diabetes," he noted, "this means that hyperglycemic medications that are being prescribed should be watched scrupulously. Otherwise, there is a risk that [women] may overrespond."  

That is, Karaye continued, women "may be at risk of developing hypoglycemia because the cannabis is acting synergistically with the regular drug that is being used to treat the diabetes." 

US clinicians, especially in states with legalized medical marijuana, need to be aware of the potential synergy.

"One would have to consider the patient as a whole," he stressed. "For example, a woman that uses medical marijuana may actually respond differently to hyperglycemic medication."

Conflicting Reports Explained by Sex Differences?

Evidence on whether cannabis use is linked with type 2 diabetes is limited and conflicting, the researchers write. They hypothesized that these conflicting findings might be explained by sex differences.

To "help inform current diabetes prevention and mitigation efforts," they investigated sex differences in cannabis use and prevalence of type 2 diabetes in 15,602 men and women in the 2013-2014, 2015-2016, and 2017-2018 NHANES surveys.

Participants were classified as having type 2 diabetes if they had a physician's diagnosis; a 2-hour plasma glucose ≥ 200 mg/dL (in a glucose tolerance test); fasting blood glucose ≥ 126 mg/dL; or A1c ≥ 6.5%.

About half of respondents were women (52%) and close to half (44%) were age 18-39.

More than a third (38%) had a body mass index (BMI) of at least 30 kg/m2, indicating obesity.

Roughly 1 in 10 had a diagnosis of type 2 diabetes (13.5%) or A1c ≥ 6.5% (9.8%).

Close to a fifth smoked cigarettes (16%). Similarly, 14.5% used cannabis at least four times a week, 3.3% used it less often, and the rest did not use it. Half of participants were not physically active (49%).

Just over half had at least a college education (55%).

Heavy cannabis users were more likely to be younger than age 40 (57% of men, 57% of women), college graduates (54% of men, 63% of women), cigarette smokers (79% of men, 83% of women), and physically inactive (39% of men, 49% of women).

Among women, heavy cannabis users were 49% less likely to have type 2 diabetes than nonusers, after adjusting for age, sex, race/ethnicity, educational level, physical activity, tobacco use, alcohol use, marital status, difficulty walking, employment status, income, and BMI (adjusted odds ratio, 0.51; 95% CI, 0.31 - 0.84).

There were no significant differences between light cannabis users versus nonusers and diabetes prevalence in women, or between light or heavy cannabis users versus nonusers and diabetes prevalence in men.

Limitations, Yet Biologically Plausible

The researchers acknowledge several study limitations.

They do not know how long participants had used marijuana. The men and women may have underreported their cannabis use, especially in states where medical marijuana was not legal, and the NHANES data did not specify whether the cannabis was recreational or medicinal.

The study may have been underpowered to detect a smaller difference in men who used versus did not use marijuana.

And importantly, this was an observational study (a snapshot at one point in time), so it cannot say whether the heavy cannabis use in women caused a decreased likelihood of diabetes.

Nevertheless, the inverse association between cannabis use and presence of type 2 diabetes is biologically plausible, Ogunsola and colleagues write.

The two major cannabis compounds, cannabidiol and delta-9-tetrahydrocannabinol, stimulate CBD1 and CBD2 receptors in the central and peripheral nervous systems, respectively. And "activation of the CBD1 receptor increases insulin secretion, glucagon, and somatostatin, and activates metabolic processes in fat and skeletal muscles — mechanisms that improve glucose disposal," they explain.

The researchers speculate that the sex differences they found for this association may be due to differences in sex hormones, or the endocannabinoid system, or fat deposits.

Therefore, "additional studies are needed to investigate the sex-based heterogeneity reported in this study and to elucidate potential mechanisms for the observation," they conclude.

The study did not receive any funding and the researchers have no relevant financial disclosures.

Cannabis Cannabinoid Res. Published online January 4, 2022. Abstract

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