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Grit your teeth for a lesser-known complication of diabetes
Type 2 diabetes was associated with a 20% increased risk of tooth loss after adjusting for multiple other risk factors in a meta-analysis of 22 recent observational studies from around the world.
The risk of tooth loss with type 2 diabetes (versus no diabetes) ranged from 15% higher in cross-sectional studies to 29% higher in cohort studies to five times higher in case-control studies.
“For diabetes, there are various known complications that are considered in [patient] treatment and management, including neuropathy, nephropathy, cardiovascular [disease] and hypertension, and kidney disease,” senior author Abdolhalim Rajabi, PhD, told this news organization in an email.
“However, a chronic complication of this disease, which may be less noticeable and less tangible, is missing teeth, which can also exacerbate other complications in patients with diabetes,” Dr. Rajabi, a biostatistician at Golestan University of Medical Sciences, Gorgan, Iran, continued.
The meta-analysis showed that “physicians should pay attention to [dental health] in the management and control of diabetic patients,” he summarized.
The analysis by Amir Reza Ahmadian, DDS, dean of the Faculty of Dentistry, Golestan University of Medical Sciences, and colleagues was recently published in BMC Endocrine Disorders.
“Our study is the first comprehensive meta-analysis about the association between [type 2 diabetes] and tooth loss,” Dr. Ahmadian and colleagues write. It summarizes articles in dentistry and medicine about “an important question:” the relationship between type 2 diabetes and tooth loss.
Nevertheless, “large-scale prospective studies are needed to validate the current results in the future,” they conclude.
Oral complications of diabetes
Diabetes increases the risk of oral disease directly by a gingival inflammatory response and indirectly by decreased saliva production due to antidiabetic medications.
Oral complications arising from this include dry mouth, tooth decay, and periodontal disease (gum disease). The latter ranges from gingivitis (gum inflammation) to severe periodontal disease (periodontitis) that can lead to tooth loss, the authors explain.
About a third of people with diabetes have severe periodontal disease, and the American Diabetes Association estimates that one in five cases of tooth loss in adults is related to diabetes.
Tooth loss has decreased over the past decades but is still a major health problem and is associated with poorer quality of life as well as risk of cardiovascular disease, hypertension, stroke, and cancer.
Previous studies and meta-analyses of the relationship between type 2 diabetes and tooth loss have reported inconsistent findings, and they did not include several more recent studies.
Therefore, Dr. Ahmadian and colleagues performed a meta-analysis of 13 cross-sectional, six cohort, and three case-control studies that investigated the link between type 2 diabetes and tooth loss published from 2007 to 2021.
Eleven studies were from North and South America: Brazil (2), Columbia (1), Mexico (2), and the United States (6). Seven studies were from Europe: Belgium (1), Finland (2), France (1), Germany (2), and Portugal (1). Four studies were from the Middle East and Asia: Saudi Arabia (1), South Korea (1), Thailand (1), and Yemen (1).
Diabetes was diagnosed based on glucose or A1c levels in half the studies and based on self-report in the other studies. Most studies investigated any tooth loss (16 studies) and the rest only considered loss of five or more teeth.
The meta-analysis included 677,532 patients, ranging from 60 to 379,021 patients per study. Most studies (77%) were judged to be of moderate or high quality.
The studies adjusted for confounders, including age, sex, place of residence, education, lifestyle factors (smoking, alcohol consumption, physical activity), use of medications and vitamin supplements, and health insurance.
Overall, after adjusting for confounders, participants with type 2 diabetes had a significantly (20%) greater risk of tooth loss than participants without diabetes (adjusted odds ratio, 1.20; P < 0.001).
The association persisted in the different study types. The risk of tooth loss was highest in the case-control studies (OR, 5.10), but was also significantly higher in the cohort (OR, 1.29) and cross-sectional studies (OR, 1.15).
The association “was also present in other subgroups, including ... method of diagnosing type 2 diabetes, continent, study quality, and number of tooth loss,” the researchers write.
“This event seems to be in line with what has been reported in other epidemiologic studies, as several cases have supported the link between diabetes, periodontal disease, and tooth decay,” which “are two common reasons for the endpoint of the tooth loss parameter,” they note.
The researchers did not find any publication bias. However, most of the studies were cross-sectional, so they cannot determine a causal relationship between diabetes and tooth loss.
The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Type 2 diabetes was associated with a 20% increased risk of tooth loss after adjusting for multiple other risk factors in a meta-analysis of 22 recent observational studies from around the world.
The risk of tooth loss with type 2 diabetes (versus no diabetes) ranged from 15% higher in cross-sectional studies to 29% higher in cohort studies to five times higher in case-control studies.
“For diabetes, there are various known complications that are considered in [patient] treatment and management, including neuropathy, nephropathy, cardiovascular [disease] and hypertension, and kidney disease,” senior author Abdolhalim Rajabi, PhD, told this news organization in an email.
“However, a chronic complication of this disease, which may be less noticeable and less tangible, is missing teeth, which can also exacerbate other complications in patients with diabetes,” Dr. Rajabi, a biostatistician at Golestan University of Medical Sciences, Gorgan, Iran, continued.
The meta-analysis showed that “physicians should pay attention to [dental health] in the management and control of diabetic patients,” he summarized.
The analysis by Amir Reza Ahmadian, DDS, dean of the Faculty of Dentistry, Golestan University of Medical Sciences, and colleagues was recently published in BMC Endocrine Disorders.
“Our study is the first comprehensive meta-analysis about the association between [type 2 diabetes] and tooth loss,” Dr. Ahmadian and colleagues write. It summarizes articles in dentistry and medicine about “an important question:” the relationship between type 2 diabetes and tooth loss.
Nevertheless, “large-scale prospective studies are needed to validate the current results in the future,” they conclude.
Oral complications of diabetes
Diabetes increases the risk of oral disease directly by a gingival inflammatory response and indirectly by decreased saliva production due to antidiabetic medications.
Oral complications arising from this include dry mouth, tooth decay, and periodontal disease (gum disease). The latter ranges from gingivitis (gum inflammation) to severe periodontal disease (periodontitis) that can lead to tooth loss, the authors explain.
About a third of people with diabetes have severe periodontal disease, and the American Diabetes Association estimates that one in five cases of tooth loss in adults is related to diabetes.
Tooth loss has decreased over the past decades but is still a major health problem and is associated with poorer quality of life as well as risk of cardiovascular disease, hypertension, stroke, and cancer.
Previous studies and meta-analyses of the relationship between type 2 diabetes and tooth loss have reported inconsistent findings, and they did not include several more recent studies.
Therefore, Dr. Ahmadian and colleagues performed a meta-analysis of 13 cross-sectional, six cohort, and three case-control studies that investigated the link between type 2 diabetes and tooth loss published from 2007 to 2021.
Eleven studies were from North and South America: Brazil (2), Columbia (1), Mexico (2), and the United States (6). Seven studies were from Europe: Belgium (1), Finland (2), France (1), Germany (2), and Portugal (1). Four studies were from the Middle East and Asia: Saudi Arabia (1), South Korea (1), Thailand (1), and Yemen (1).
Diabetes was diagnosed based on glucose or A1c levels in half the studies and based on self-report in the other studies. Most studies investigated any tooth loss (16 studies) and the rest only considered loss of five or more teeth.
The meta-analysis included 677,532 patients, ranging from 60 to 379,021 patients per study. Most studies (77%) were judged to be of moderate or high quality.
The studies adjusted for confounders, including age, sex, place of residence, education, lifestyle factors (smoking, alcohol consumption, physical activity), use of medications and vitamin supplements, and health insurance.
Overall, after adjusting for confounders, participants with type 2 diabetes had a significantly (20%) greater risk of tooth loss than participants without diabetes (adjusted odds ratio, 1.20; P < 0.001).
The association persisted in the different study types. The risk of tooth loss was highest in the case-control studies (OR, 5.10), but was also significantly higher in the cohort (OR, 1.29) and cross-sectional studies (OR, 1.15).
The association “was also present in other subgroups, including ... method of diagnosing type 2 diabetes, continent, study quality, and number of tooth loss,” the researchers write.
“This event seems to be in line with what has been reported in other epidemiologic studies, as several cases have supported the link between diabetes, periodontal disease, and tooth decay,” which “are two common reasons for the endpoint of the tooth loss parameter,” they note.
The researchers did not find any publication bias. However, most of the studies were cross-sectional, so they cannot determine a causal relationship between diabetes and tooth loss.
The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Type 2 diabetes was associated with a 20% increased risk of tooth loss after adjusting for multiple other risk factors in a meta-analysis of 22 recent observational studies from around the world.
The risk of tooth loss with type 2 diabetes (versus no diabetes) ranged from 15% higher in cross-sectional studies to 29% higher in cohort studies to five times higher in case-control studies.
“For diabetes, there are various known complications that are considered in [patient] treatment and management, including neuropathy, nephropathy, cardiovascular [disease] and hypertension, and kidney disease,” senior author Abdolhalim Rajabi, PhD, told this news organization in an email.
“However, a chronic complication of this disease, which may be less noticeable and less tangible, is missing teeth, which can also exacerbate other complications in patients with diabetes,” Dr. Rajabi, a biostatistician at Golestan University of Medical Sciences, Gorgan, Iran, continued.
The meta-analysis showed that “physicians should pay attention to [dental health] in the management and control of diabetic patients,” he summarized.
The analysis by Amir Reza Ahmadian, DDS, dean of the Faculty of Dentistry, Golestan University of Medical Sciences, and colleagues was recently published in BMC Endocrine Disorders.
“Our study is the first comprehensive meta-analysis about the association between [type 2 diabetes] and tooth loss,” Dr. Ahmadian and colleagues write. It summarizes articles in dentistry and medicine about “an important question:” the relationship between type 2 diabetes and tooth loss.
Nevertheless, “large-scale prospective studies are needed to validate the current results in the future,” they conclude.
Oral complications of diabetes
Diabetes increases the risk of oral disease directly by a gingival inflammatory response and indirectly by decreased saliva production due to antidiabetic medications.
Oral complications arising from this include dry mouth, tooth decay, and periodontal disease (gum disease). The latter ranges from gingivitis (gum inflammation) to severe periodontal disease (periodontitis) that can lead to tooth loss, the authors explain.
About a third of people with diabetes have severe periodontal disease, and the American Diabetes Association estimates that one in five cases of tooth loss in adults is related to diabetes.
Tooth loss has decreased over the past decades but is still a major health problem and is associated with poorer quality of life as well as risk of cardiovascular disease, hypertension, stroke, and cancer.
Previous studies and meta-analyses of the relationship between type 2 diabetes and tooth loss have reported inconsistent findings, and they did not include several more recent studies.
Therefore, Dr. Ahmadian and colleagues performed a meta-analysis of 13 cross-sectional, six cohort, and three case-control studies that investigated the link between type 2 diabetes and tooth loss published from 2007 to 2021.
Eleven studies were from North and South America: Brazil (2), Columbia (1), Mexico (2), and the United States (6). Seven studies were from Europe: Belgium (1), Finland (2), France (1), Germany (2), and Portugal (1). Four studies were from the Middle East and Asia: Saudi Arabia (1), South Korea (1), Thailand (1), and Yemen (1).
Diabetes was diagnosed based on glucose or A1c levels in half the studies and based on self-report in the other studies. Most studies investigated any tooth loss (16 studies) and the rest only considered loss of five or more teeth.
The meta-analysis included 677,532 patients, ranging from 60 to 379,021 patients per study. Most studies (77%) were judged to be of moderate or high quality.
The studies adjusted for confounders, including age, sex, place of residence, education, lifestyle factors (smoking, alcohol consumption, physical activity), use of medications and vitamin supplements, and health insurance.
Overall, after adjusting for confounders, participants with type 2 diabetes had a significantly (20%) greater risk of tooth loss than participants without diabetes (adjusted odds ratio, 1.20; P < 0.001).
The association persisted in the different study types. The risk of tooth loss was highest in the case-control studies (OR, 5.10), but was also significantly higher in the cohort (OR, 1.29) and cross-sectional studies (OR, 1.15).
The association “was also present in other subgroups, including ... method of diagnosing type 2 diabetes, continent, study quality, and number of tooth loss,” the researchers write.
“This event seems to be in line with what has been reported in other epidemiologic studies, as several cases have supported the link between diabetes, periodontal disease, and tooth decay,” which “are two common reasons for the endpoint of the tooth loss parameter,” they note.
The researchers did not find any publication bias. However, most of the studies were cross-sectional, so they cannot determine a causal relationship between diabetes and tooth loss.
The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM BMJ ENDOCRINE DISORDERS
Artificial sweeteners: A modifiable cancer risk?
People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.
Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*
These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.
“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.
“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.
Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.
“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
Important analysis, interpret with caution
“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.
“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”
Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”
His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022.
“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
Conflicting results
Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.
They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.
“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.
According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.
The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.
The current cohort included 102,865 adults who enrolled in 2009-2021.
Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.
At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.
Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).
Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%).
During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.
Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.
Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables.
Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.
Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).
The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.
The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.
Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer.
A version of this article first appeared on Medscape.com.
People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.
Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*
These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.
“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.
“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.
Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.
“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
Important analysis, interpret with caution
“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.
“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”
Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”
His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022.
“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
Conflicting results
Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.
They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.
“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.
According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.
The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.
The current cohort included 102,865 adults who enrolled in 2009-2021.
Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.
At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.
Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).
Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%).
During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.
Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.
Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables.
Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.
Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).
The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.
The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.
Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer.
A version of this article first appeared on Medscape.com.
People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.
Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*
These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.
“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.
“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.
Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.
“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
Important analysis, interpret with caution
“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.
“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”
Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”
His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022.
“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
Conflicting results
Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.
They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.
“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.
According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.
The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.
The current cohort included 102,865 adults who enrolled in 2009-2021.
Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.
At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.
Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).
Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%).
During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.
Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.
Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables.
Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.
Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).
The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.
The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.
Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer.
A version of this article first appeared on Medscape.com.
FROM PLOS MEDICINE
Lights on during sleep can play havoc with metabolism
“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.
And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.
The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.
Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”
“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.
That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
How light during sleep may affect insulin, melatonin, heart rate
Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.
In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.
Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).
However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.
The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.
Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.
The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”
The dim light condition was less than 3 lux, which is dimmer than a night light.
When participants were awake, the room lighting was 240 lux.
Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m2.
The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.
They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.
Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.
Participants slept for a similar time, around 7 hours, in both conditions.
Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.
In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.
The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.
And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.
The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.
Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”
“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.
That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
How light during sleep may affect insulin, melatonin, heart rate
Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.
In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.
Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).
However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.
The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.
Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.
The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”
The dim light condition was less than 3 lux, which is dimmer than a night light.
When participants were awake, the room lighting was 240 lux.
Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m2.
The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.
They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.
Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.
Participants slept for a similar time, around 7 hours, in both conditions.
Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.
In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.
The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.
And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.
The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.
Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”
“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.
That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
How light during sleep may affect insulin, melatonin, heart rate
Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.
In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.
Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).
However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.
The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.
Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.
The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”
The dim light condition was less than 3 lux, which is dimmer than a night light.
When participants were awake, the room lighting was 240 lux.
Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m2.
The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.
They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.
Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.
Participants slept for a similar time, around 7 hours, in both conditions.
Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.
In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.
The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
Heavy cannabis use tied to less diabetes in women
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 U.S. 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, 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, said in an interview.
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 Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.
“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, Dr. 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.”
U.S. 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 wrote. 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 of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 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 of at least 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% confidence interval, 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 acknowledged 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, Dr. Ogunsola and colleagues wrote.
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 explained.
The researchers speculated that the sex differences they found for this association may be caused by 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 concluded.
The study did not receive any funding and the researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
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 U.S. 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, 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, said in an interview.
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 Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.
“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, Dr. 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.”
U.S. 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 wrote. 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 of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 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 of at least 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% confidence interval, 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 acknowledged 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, Dr. Ogunsola and colleagues wrote.
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 explained.
The researchers speculated that the sex differences they found for this association may be caused by 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 concluded.
The study did not receive any funding and the researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
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 U.S. 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, 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, said in an interview.
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 Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.
“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, Dr. 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.”
U.S. 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 wrote. 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 of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 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 of at least 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% confidence interval, 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 acknowledged 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, Dr. Ogunsola and colleagues wrote.
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 explained.
The researchers speculated that the sex differences they found for this association may be caused by 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 concluded.
The study did not receive any funding and the researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM CANNABIS AND CANNABINOID RESEARCH