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20th May 2022
Higher arterial stiffness (AS) rather than the presence of hypertension is a better predictor for the development of diabetes according to the findings of a prospective study by a team of Chinese researchers.
The World Health Organization estimates that there are approximately 422 million people worldwide that have diabetes. The most common form of diabetes is type 2 and in 2017, it was estimated that approximately 462 million individuals were affected by the condition, corresponding to 6.28% of the world’s population. Hypertension is common in those with type 2 diabetes and reportedly affects over two-thirds of patients and a Chinese study has suggested that a higher blood pressure is a risk factor for type 2 diabetes in both middle-aged and elderly patients.
Furthermore, the presence of arterial stiffness, especially in the aorta, has been shown to be an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension. In addition, other work has suggested that the presence of arterial stiffness is associated with an increased incidence of diabetes, independent of other risk factors and may represent an early risk marker for developing diabetes. However, whether arterial stiffness among hypertensive patients is a useful prognostic marker for the development of diabetes compared with hypertension alone is unclear.
For the present study, the Chinese researchers looked at data obtained from the Kailuan study, which is an ongoing prospective study following patients initially free of hypertension and examines factors associated with development of the condition. In a subgroup of patients, brachial-ankle pulse wave velocity measurements, which is a widely used technique to assess arterial stiffness, were taken. The researchers set the primary outcome as the development of diabetes during the follow-up period. Participants blood pressure and arterial stiffness was categorised as ideal vascular function (IVF) and normotensive, normotensive with AS, hypertensive and with normal AS and hypertensive and with elevated AS (HTAS).
Arterial stiffness and the development of type 2 diabetes
A total of 11,166 participants were enrolled in the study and followed for 6.16 years during which time 768 (6.88%) of incident cases of type 2 diabetes were identified.
After adjustment for covariates (e.g., age, gender, co-morbidities), compared to the IVF group, individuals in the HTAS group had the highest risk developing type 2 diabetes (hazard ratio, HR = 2.42, 95% CI 1.93 – 3.03). This was followed by the normotensive, elevated AS group (HR = 2.11, 95% CI 1.64 – 2.61). Interestingly, the lowest risk was associated with those who were hypertensive and with normal AS (HR = 1.48). These results did not change when further adjusted for mean arterial or diastolic pressure.
The researchers then examined whether an elevated AS or hypertension, or both, increased the predictive power of a conventional model, i.e., with age, sex, BMI, smoking status etc, for the development of diabetes The results showed that the C statistic increased from 0.690 to 0.707 (p = 0.0003), i.e., had more predictive power, after addition of AS. However, the predictive power increased to 0.709 when both hypertension and AS were added, in other words, there was little additional benefit to the model by adding hypertension alone.
The authors concluded that an elevated AS performed better than hypertension for the prediction of type 2 diabetes and suggested that future strategies for the prevention of type 2 diabetes should focus on both hypertension and AS.
Tian X et al. Hypertension, Arterial Stiffness, and Diabetes: a Prospective Cohort Study Hypertension 2022
12th May 2022
A higher level of dairy consumption in Chinese adults has been found to be linked to an increased overall risk of developing cancer and in particular, liver and female breast cancers. This was the key finding of a prospective study by researchers from the UK and China.
Across the globe in 2020, it has been estimated that cancer was responsible for an estimated 19.3 million new cases and almost 10.0 million cancer deaths. Several dietary factors are linked with a reduced risk of developing cancer, including for example, a higher intake of fruit and vegetables, which is associated with a 17% lower cancer mortality. Another food linked with cancer is dairy products and a higher dairy consumption lowers the risk of developing colorectal cancer. However, intake of egg, fish and dairy consumption has remained at a low level among Chinese people with other work finding that dairy consumption was seriously inadequate in Chinese elderly and appears to be reducing. As a result, for the present study, researchers were interested in determining if, despite low levels of intake among the Chinese (compared to Westernised countries), dairy intake was associated with the incidence of cancer.
Turning to data held within the China Kadoorie Biobank, which represents a population-based prospective analysis with over 0.5 million adults across China, the researchers obtained information on the frequency of dairy consumption and which was categorised as daily, 4 – 6 day/week, 1 – 3 days/week, monthly or never/ready and which served as a baseline. The information on dairy intake was re-collected at two follow-up surveys and used to estimate mean intake of dairy foods. Cox regression analysis was used to link incident cancers with dairy consumption and adjusted for several covariates including a family history of cancer, alcohol intake and levels of smoking.
Dairy consumption and incident cancer
Among a population of 510,146 individuals with a mean age of 52 years (59% women), 20.4% reported intake of dairy foods at least once a week (subsequently referred to as ‘regular dairy consumers’) and which was largely for milk. Participants were followed for a mean of 10.8 years, during which time there were 29,277 incident cancer cases recorded. In the fully adjusted models, each 50g/day increase in dairy consumption was associated with a 7% increased risk of total cancer (hazard ratio, HR = 1.07, 95% CI 1.04 – 1.11) when compared to those who never consumed dairy foods. Furthermore, among regular dairy consumers, there was a significant increased risk of liver cancer (HR = 1.12, 95% CI 1.02 – 1.22) and for female breast cancer (HR = 1.17, 95% CI 1.07 – 1.29). There was no significant association for any other form of cancer including colorectal cancer.
The authors concluded that higher dairy consumption was associated with a greater risk of cancer among Chinese individuals even though levels of dairy intake are low compared to Westernised countries.
Kakkoura MG et al. Dairy consumption and risks of total and site-specific cancers in Chinese adults: an 11-year prospective study of 0.5 million people. BMC Med 2022
A higher body fat level in men is associated with an elevated risk of prostate cancer death according to a meta-analysis of prospective studies by researchers from the Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide and in 2020 there were more than 1.4 million new cases of prostate cancer. Prior evidence indicates that there is a positive association between height and the risk of prostate cancer, with taller men being at a greater risk but also that those with greater adiposity, have an elevated risk of high-grade prostate cancer and prostate cancer death. Moreover, other work suggests that a higher body fat level, based on central adiposity is a more relevant factor and that a higher waist circumference was an important risk factor for prostate cancer.
For the present study, the Oxford team use data from the UK Biobank and focused on men who had originally undergone anthropometric measurements (e.g., height, weight, waist and hip circumference). A subgroup of these men also underwent abdominal MRI and a dual-energy X-ray absorptiometry (DXA) scan and for whom body mass index (BMI), waist and hip circumferences were re-assessed. The primary outcome of interest was prostate cancer as the underlying cause of death. In addition, the researchers combined their Biobank data with other published prospective studies to undertake a dose response meta-analysis.
Higher body fat levels and prostate cancer death
Among a cohort of 21,8237 men with a mean age at recruitment of 56.5 years, over a follow-up period of 11.6 years, 661 men (mean age = 63.1 years), died of prostate cancer.
In a multivariable-adjusted model, there was no statistically significant association of BMI, body fat percentage and waist circumference and prostate cancer mortality. However, for the waist to hip ratio (WHR), this association was significant per 0.05 unit increase (hazard ratio, HR = 1.07, 95% CI 1.01 – 1.14, P for trend = 0.028) when comparing the highest to lowest WHR quartiles.
In the meta-analysis, the hazard ratio was 1.10 (95% CI 1.07 – 1.12) for every 5kg/m2 increase in BMI, 1.03 for every 5% increase in body fat percentage, and 1.06 for every 0.05 increase in WHR.
Using the estimate for the effect of BMI from the meta-analysis, the authors estimated that as approximately 11,900 men died from prostate cancer each year (averaged between 2016 – 2018) and if their estimate was accurate, a reduction in mean BMI of 5kg/m2 would potentially lead to 1309 fewer prostate cancer deaths every year in the UK.
They concluded that men with higher body fat (both total and central) were at a higher risk of death from prostate cancer and that these findings provided a reason for men to maintain a healthy weight.
Perez‐Cornago A et al. Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies BMC Med 2022
7th April 2022
Metformin use by fathers with diabetes, three months before conception, is linked to an increased risk of birth defects among their offspring. This was the main finding of a study by Danish researchers from the Department of Epidemiology, Biostatistics and Bio-demography, and Interdisciplinary Center on Population Dynamics, University of Southern Denmark, Denmark.
It is already known that diabetic men have a significantly higher percentage of sperm with nuclear DNA damage and which is a factor associated with compromised fertility and increased miscarriage rates. Furthermore, other research suggests that there is a relationship between male and female diabetes and fecundity (i.e., their ability to produce live offspring) and that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive. However, as well as men, data also shows that among pregnant women with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects in their offspring.
In men, the entire spermatogenic process is thought to require approximately 74 days and for the present study, the Danish team looked at fathers who had a prescription for any diabetic medication, including insulin, metformin and sulfonylureas, during the three months before conception, which they termed the sperm development period (sDev). Since diabetes is known to affect sperm, their primary interest was to examine if the use of diabetic medicines might prevent damage to paternal sperm. They used a national patient registry to extract individual-level data and excluded mothers who were diabetic and using diabetic medication at any time prior to birth. The primary outcome of interest was the diagnosis of 1 or more major birth defects in the first year of life. The authors calculated odds ratios and adjusted for several factors birth year, paternal age, income, education, maternal age and smoking status.
Metformin use and birth defects
A total of 1,116,779 offspring were included in the analysis, of whom, 3.3% had one or more birth defects. A total of 7,029 offspring were exposed to paternal diabetic medication including insulins (5,298), metformin (1,451) and sulfonylureas (647). The main birth defects observed among metformin-exposed offspring were genital defects, all of which occurred in boys.
In regression analysis, the adjusted odds ratio (aOR) for birth defects during the sDev period for insulins was 0.98 (95% CI 0.85 – 1.14), 1.40 (95% CI 1.08 – 1.82, p = 0.012) for metformin and 1.34 (95% CI 0.94 – 1.92) for sulfonylureas.
Interestingly, the frequency of birth defects varied among paternal metformin users at different time points in comparison to the sDev period. For example, longer than 1 year before the sDev, the frequency was 4% but this increased to 4.4% one year before sDev before peaking at 5.2% during sDev. Moreover, the frequency declined thereafter to 3.3% more than one year after sDev. However, the birth defect frequency was non-significant and no higher than non-metformin users, at all time points other than during sDev.
The authors concluded that preconception use of metformin is associated with major birth defects, particularly genital birth defects in boys, although added that further work was required to confirm these findings.
Wensink MJ et al. Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring. A Nationwide Cohort Study Ann Intern Med 2022
30th March 2022
The consumption of foods and beverages which contain artificial sweeteners has been found to be associated with a slight increased risk of cancer according to the results of a large, French cohort study by researchers from the Sorbonne Paris Nord University, University of Paris, France.
The World Health Organization recommends that both adults and children should reduce their intake of free sugars to less than 10% of total energy intake. Consequently, manufacturers developed alternatives to sugar and artificial sweeteners were developed, one of which is aspartame, that has been used since 1981 and is present in more than 6,000 products. Although aspartame contains the same number of calories as sugar, it is around 200 times sweeter than sugar. The potential carcinogenicity of artificial sweeteners like aspartame has always been controversial and one review in 2014 suggested that the studies performed in the 1970s did not provide adequate scientific support for the safety of aspartame and that more recent life-span carcinogenicity data undertaken with rodents provide consistent evidence of aspartame’s carcinogenic potential. Moreover, a 2021 review of aspartame and cancer concluded that new findings confirm that aspartame is a chemical carcinogen in rodents. Nevertheless, it has been unclear from studies in humans whether artificial sweeteners are associated with an increased risk of cancer. For example, one 2012 prospective study that evaluated whether the consumption of aspartame- and sugar-containing soda is associated with risk of haematopoietic cancers, concluded that the apparent cancer risk in individuals who consume regular soda do not permit the ruling out of chance as an explanation. In contrast, a second study concluded that higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer.
With some uncertainty over the association between cancer and intake of artificial sweeteners, for the present study, the French team prospectively followed participants in the NutriNet-Sante study. This prospective trial was designed to determine, among adults, any associations between nutrition and health. Nutritional intake information is collected at baseline and every year on various factors such as health status, physical activity, smoking status and diet using 24-hour dietary recall questionnaires through which the intake of artificial sweeteners can be assessed.
Artificial sweeteners and cancer risk
A total of 102,865 participants with a baseline mean age of 42.2 years (78.5% female) were followed for a median of 7.8 years and consumption of artificial sweeteners was recorded for 36.9% of participants.
A total of 3,358 incident cancers developed during the follow-up period. Compared those who did not consume artificial sweeteners, among high consumers, there was an increased risk of cancer development (hazard ratio, HR = 1.13, 95% CI 1.03 – 1.25, p-trend = 0.002). Two sweeteners in particular, aspartame (HR = 1.15, p = 0.002) and acesulfame-K (HR = 1.13, p = 0.007) were associated with higher cancer risks. In addition, aspartame was associated with an increased risk of breast cancer (HR = 1.22, 95% CI 1.01 – 1.48, p = 0.036).
Based on these findings, the authors concluded that while the study could not establish causal links, their findings did not support the use of artificial sweeteners as a safe alternative to sugar in food and beverages.
Debras C et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study PLoS Med 2022