INDIVIDUAL ARTICLE: Sugar Sag: What Is Skin Glycation and How Do You Combat It?

Skin aging is influenced by various exogenous and endogenous factors, ranging from ultraviolet (UV) light exposure and environmental toxins to biological sources, such as those that arise from normal metabolic processes (eg, free radicals). Glycation is the normal process by which glucose and other reducing sugars react with proteins to form an array of heterogeneous biomolecular structures known as advanced glycation end-products (AGEs) over time. However, AGEs are toxic to human cells and are implicated in the acceleration of inflammatory and oxidative processes, with their accumulation in the skin being associated with increased skin dulling and yellowing, fine lines, wrinkles, and skin laxity. Clinicians should become cognizant of how AGEs develop, what their biological consequences are, and familiarize themselves with available strategies to mitigate their formation. J Drugs Dermatol.  2024;23:4(Suppl 1):s5-10.

A new onset drug induced diabetes mellitus presenting with diabetic ketoacidosis in a child undergoing treatment for B cell acute lymphoblastic leukemia. A case report and review of literature.

OBJECTIVES: Hyperglycemia is a known side effect of anticancer chemotherapeutic drugs. This entity known as drug-induced diabetes mellitus usually does not present with the development of diabetic ketoacidosis (DKA). We hereby report a case of drug induced diabetes mellitus in a child with acute leukemia presenting with DKA. CASE PRESENTATION: We report a case of a teenage boy diagnosed with B cell acute lymphoblastic leukemia and was started on induction phase chemotherapy as per the Indian Collaborative Childhood Leukemia group (ICICLe) acute lymphoblastic leukemia-14 protocol. On day 12 of the induction phase, he developed hyperglycemia and presented to us with severe diabetic ketoacidosis (DKA). Serum anti glutamic acid decarboxylase 65 antibody levels were negative with low serum C peptide levels. Initially, the possibility of drug-induced acute pancreatitis was kept which was ruled out. Keeping the possibility of drug-induced hyperglycemia, the child was started on subcutaneous regular insulin which was titrated as per sugar records. Continuation of remaining chemotherapy was done by PEGylated L-asparaginase with titration of insulin as per home-based sugar records. Insulin requirement increased from 0.3 unit/kg/day to a maximum of 1 unit/kg/day during consolidation phase 1 with PEGylated L-asparaginase suggesting drug-induced hyperglycemia but subsequently insulin requirement decreased and insulin was stopped. CONCLUSIONS: Drug induced diabetes mellitus can present as DKA during induction phase of acute lymphoblastic leukemia (ALL) chemotherapy. A high index of suspicion and close monitoring are required. The insulin requirements in these patients can be very fluctuant and may become nil during the course of treatment.

Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study.

Epidemiological studies of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) with Alzheimer's disease (AD) have provided controversial findings. Furthermore, little is known about the association between pure fruit/vegetable juices and AD. The present study aims to estimate the associations of SSBs, ASBs, and pure fruit/vegetable juices with AD, and to evaluate the theoretical effects of replacing SSBs and ASBs with the different consumption of pure fruit/vegetable juices on the risk of AD. This prospective cohort study of the UK Biobank included 206,606 participants aged 39-72 years free of dementia at baseline between 2006 and 2010. Dietary intake of SSBs, ASBs, and pure fruit/vegetable juices (naturally sweet juices) were collected using a 24-h dietary recall questionnaire completed between 2009 and 2012. Incident AD was identified by medical and mortality records. Cox proportional hazard models and substitution models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 699 cases of AD were identified over a median follow-up of 9.5 years. The consumption of SSBs and ASBs (> 2 units/d) were associated with a higher risk of AD. However, participants who drank > 1-2 units/d of pure fruit/vegetable juices were associated with a lower risk of AD. In substitution models, replacing SSBs with an equivalent consumption of pure fruit/vegetable juices could be associated with a risk reduction of AD.

A scoping study on the social determinants of health and sugar consumption in the context of policy approaches for improving population health.

OBJECTIVES: To conduct a scoping review of existing research on the social determinants of health, sugar consumption and public health policy responses to address or improve health outcomes. METHODS: A total of 13 categories were developed to reflect the authors' interest in the overall focus on the social determinants of health, sugar as an independent risk factor, upstream policy action ('whole populations'), downstream policy action ('targeted') and two contemporary policy strategies (namely 'Vulnerable populations' and 'Proportionate Universalism'). The search strategy was then performed on MEDLINE (via Ovid) and Web of Science, and was limited to the English language. No time limits prior to when the database search was conducted in 2022 were set to explore the full extent of the literature in this field. RESULTS: Five hundred and sixty articles were retrieved, of which 181 met the criteria for review. When all categories were applied, the findings showed that 76% of papers focusing on sugar consumption as a risk factor for non-communicable diseases (NCDs) mentioned the social determinants of health. The majority of studies (60%) recommended downstream interventions, with 40% recommending 'upstream' interventions. A limited proportion (12%) of research work was published in dental journals. Research had been done using predominantly quantitative methods (66% of articles), with 24% of studies adopting a mixed methods approach, and 8% being exclusively qualitative. Research on contemporary strategies for sugar reduction were focused on the 'Global North' and 98% of papers used individual level data focused on targeted approaches, highlighting that there is little direct evidence for contemporary strategies aimed at reducing sugar consumption. CONCLUSIONS: Whilst the majority of public and dental health research argues that there is a need to address the social determinants of health, the findings from this study highlight that very few empirical studies have been designed to directly inform contemporary strategies for sugar reduction. More research is therefore needed that can directly assess the evidence for contemporary strategies in public health policy.

Association between brown sugar intake and decreased risk of cancer in the Amami islands region, Japan.

BACKGROUND AND OBJECTIVES: Although excess white sugar intake imposes various health burdens, brown sugar is high in minerals, polyphenols, and polycosanol. However, few epidemiological studies have assessed brown sugar intake for health benefit. People in the Amami islands region, with a relatively high proportion of individuals with longevity, consume brown sugar as a type of refreshment. This cohort study was conducted in Amami to clarify the association of brown sugar intake with mortality risk and cancer incidence. METHODS AND STUDY DESIGN: Participants were recruited from the general population of Amami as part of the Japan Multi-Institutional Collaborative Cohort Study. The number of eligible participants was 5004 (2057 men and 2947 women). During the median follow-up period of 13.4 years, 274 deaths and 338 cases of cancer were observed. HRs and 95% CIs were estimated using the Cox proportional hazard model, after adjusting for sugar-related and other variables. RESULTS: After adjusting for their related confounding factors, brown sugar intake was associated with decreased HRs and a decreasing trend for all-site and stomach cancer incidence (p = 0.001 and 0.017, respectively) in women and men, and for breast cancer incidence (p = 0.034) in women. Additionally, a decreasing trend in the HRs for lung cancer incidence was observed among never and ex-smokers (p = 0.039). Decreased HRs for overall death, cancer, and cardiovascular disease were not apparent. CONCLUSIONS: Brown sugar intake was associated with decreased risk of all-site, stomach, and breast cancer incidences in the Amami population.

Master statistical analysis plan: attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

This manuscript is a master statistical analysis plan for each of three-cluster randomized controlled trials to evaluate the efficacy of attractive targeted sugar baits (ATSB) described in an already published protocol. The master SAP contains an overarching plan for all three trials, which can be adapted to trial-specific circumstances. The primary objective of the trials is to evaluate the efficacy of ATSB in the presence of universal vector control coverage with insecticide-treated nets (ITN) or indoor residual spraying (IRS) after two transmission seasons on clinical malaria incidence as compared with universal vector control coverage with ITN or IRS alone. The primary outcome measure is the incidence rate of clinical malaria, assessed in cohorts aged 12 months to less than 15 years (≥ 5 years to 15 years in Mali) during monthly follow-up visits. The primary unadjusted analysis will be conducted on the intention-to-treat analysis population without adjustment for any anticipated confounding variables. The primary outcome will be analyzed using a multi-level model constructed on a generalized linear model framework with a Poisson likelihood and a log link function. Random intercepts will be included for each study cluster and a fixed effect for study-arm. The analyst will be blinded to study arm assignment. Several secondary outcomes will be analyzed, as well as a pooled analysis (individual patient data meta-analysis) across the three trial sites. Additionally, a standard meta-analysis is expected to be conducted using combined data from all sites.

Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA-induced dopaminergic neurodegeneration.

BACKGROUND: Diets high in saturated fat and sugar, termed "Western diets," have been associated with several negative health outcomes, including increased risk for neurodegenerative disease. Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and is characterized by the progressive death of dopaminergic neurons in the brain. We build upon previous work characterizing the impact of high-sugar diets in Caenorhabditis elegans to mechanistically evaluate the relationship between high-sugar diets and dopaminergic neurodegeneration. RESULTS: Adult high-glucose and high-fructose diets, or exposure from day 1 to 5 of adulthood, led to increased lipid content, shorter lifespan, and decreased reproduction. However, in contrast to previous reports, we found that adult chronic high-glucose and high-fructose diets did not induce dopaminergic neurodegeneration alone and were protective from 6-hydroxydopamine (6-OHDA) induced degeneration. Neither sugar altered baseline electron transport chain function and both increased vulnerability to organism-wide ATP depletion when the electron transport chain was inhibited, arguing against energetic rescue as a basis for neuroprotection. The induction of oxidative stress by 6-OHDA is hypothesized to contribute to its pathology, and high-sugar diets prevented this increase in the soma of the dopaminergic neurons. However, we did not find increased expression of antioxidant enzymes or glutathione levels. Instead, we found evidence suggesting downregulation of the dopamine reuptake transporter dat-1 that could result in decreased 6-OHDA uptake. CONCLUSIONS: Our work uncovers a neuroprotective role for high-sugar diets, despite concomitant decreases in lifespan and reproduction. Our results support the broader finding that ATP depletion alone is insufficient to induce dopaminergic neurodegeneration, whereas increased neuronal oxidative stress may drive degeneration. Finally, our work highlights the importance of evaluating lifestyle by toxicant interactions.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Total sugar, added sugar, fructose, and sucrose intake and all-cause, cardiovascular, and cancer mortality: A systematic review and dose-response meta-analysis of prospective cohort studies.

OBJECTIVES: We performed a systematic review and dose-response meta-analysis to assess the association of total sugars, added sugars, fructose, and sucrose with all-cause, cardiovascular disease (CVD), and cancer mortality. METHODS: We searched PubMed, Embase, and Web of Science for prospective cohort studies up to May 10, 2022. Pooled relative risks and 95% CIs were calculated by random effect models, and the linear and non-linear dose-response associations were explored by restricted cubic splines. RESULTS: Comparing the highest with the lowest categories of total sugars, the summary RR was 1.09 (95% CI, 1.02-1.15; I2 = 71.9%) for all-cause mortality, 1.10 (1.02-1.18; I2 = 12.7%) for CVD mortality, and 1.00 (0.94-1.05; I2 = 0) for cancer mortality. For fructose, the summary relative risk was 1.09 (1.03-1.16; I2 = 58.4%) for all-cause mortality, 1.11 (1.03-1.20; I2 = 37.4%) for CVD mortality, and 1.00 (0.95-1.06; I2 = 0) for cancer mortality. Restricted cubic splines found non-linear associations of total sugars and fructose with all-cause and CVD mortality (P for non-linearity < 0.001). A significant increment in risk of all-cause and CVD mortality was observed with >10% energy intake to 20% energy intake for total sugars and fructose. No association was found for the added sugars and sucrose with all-cause, CVD, and cancer mortality. CONCLUSIONS: Increased intake of total sugars and fructose is associated with all-cause and CVD mortality but not associated with cancer mortality, which could have implications for guideline recommendations regarding the risk of mortality related to sugar intake.

Sugar intake and colorectal cancer risk: A prospective Japanese cohort study.

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle-aged adults in a Japanese large-scale population-based cohort study. The participants (42,405 men and 48,600 women) who were 45-74 years old and answered the questionnaire in 1995-1999 in the Japan Public Health Center-based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147-item food frequency questionnaire and divided into quintiles (Q1-Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow-up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07-2.87] for Q1 vs. Q5; p linear trend  = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle-aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.

Population Impact of Sugar-Sweetened Beverages on Dental Caries and Overweight/Obesity in Australian Children.

KNOWLEDGE TRANSFER STATEMENT: The reported findings greatly consolidated evidence of detrimental effects of sugars intake on child oral health and overweight and obesity, some of the most prevalent chronic conditions in children. Evidence on population impact of sugars intake is directly informative to policy makers and the public about the potential impact of population-based programs targeting sugars intake to prevent dental caries and overweight and obesity.

Sugar Consumption Pattern among Cardiometabolic Risk Individuals: A Scoping Review.

BACKGROUND: The global prevalence of noncommunicable diseases has risen rapidly over the past decade. Research has focused on dietary management, particularly dietary sugar, to prevent and treat noncommunicable diseases. OBJECTIVE: This study undertakes a scoping review of research on the impacts of dietary sugar on cardiometabolic related health outcomes. METHODS: Ovid Medline, Scopus and Web of Science Core collection databases were used to identify papers published from January 1, 2010 onwards. The included studies had to be cross-sectional or cohort studies, peered review, published in English and in adults, aged 18 years old and above. Articles had to determine the impacts of sugar intake on cardiometabolic related health outcomes. Study quality was measured using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. In addition, a narrative synthesis of extracted information was conducted. RESULTS: Thirty-one articles were included in this review. All studies had a large sample size, and the exposure measure was clearly defined, valid and applied consistently across all study participants. Exposure was measured using validated questionnaires. All data were statistically analysed and adjusted for critical potential confounding variables. Results showed that dietary sugar intake was significantly associated with metabolic syndrome, blood pressure, blood glucose, blood lipids, and body weight. CONCLUSION: Dietary sugar intake significantly increased cardiometabolic risks through mechanisms dependent and independent of weight gain. It is essential to create public awareness on the topics of cardiometabolic risk management and dietary sugars intake.

Sugar-Sweetened and Artificially Sweetened Beverages Consumption and Risk of Cardiovascular Health.

INTRODUCTION: Sugar-sweetened and artificially sweetened beverages are routinely consumed worldwide. Given their popularity, there has been much debate about the effect that these beverages have on cardiovascular health. We sought to determine the exact relationship between sugar-sweetened and artificially sweetened beverages consumption on cardiovascular health. METHODS: All studies that reported an association between sugar-sweetened/artificially sweetened beverages consumption and cardiovascular health were extracted from database inception to September 2022 using keywords from several databases. We used the DerSimonian & Laird random-effects method for the analysis. RESULTS: Of the total 16 prospective studies, 1,405,375 individuals were followed for a median follow-up of 14.8 years. Compared with low sugar-sweetened and artificially sweetened beverage consumption, a higher consumption of sugar-sweetened and artificially sweetened beverages was associated with greater cardiovascular outcomes (hazard ratio [HR] of 1.27, 95% confidence interval [CI] of 1.16-1.40 and risk ratios of 1.16, 95% CI of 1.02-1.33). Similarly, compared with low artificially sweetened beverages consumption, a higher consumption of artificially sweetened beverages was associated with greater cardiovascular outcomes (HR of 1.32, 95% CI of 1.12-1.57). Likewise, compared with low sugar-sweetened beverages consumption, a higher consumption of sugar-sweetened beverages was associated with greater cardiovascular outcomes (HR of 1.21, 95% CI of 1.07-1.37 and risk ratios of 1.22, 95% CI of 1.09-1.35). CONCLUSIONS: Increasing consumption of sugar-sweetened and artificially sweetened beverages may be correlated with an increased risk of developing cardiovascular/vascular complications and mortality, albeit without causality of cardiovascular/vascular morbidity.

The Impact of Free and Added Sugars on Cognitive Function: A Systematic Review and Meta-Analysis.

A relationship between excessive sugar consumption and cognitive function has been described in animal models, but the specific effects of sugars in humans remains unclear. This systematic review and meta-analysis aimed to evaluate the current knowledge, research characteristics, and quality of evidence of studies investigating the impacts of free and added sugars on human cognition in healthy participants. The review identified 77 studies (65 experimental trials, n = 3831; 9 cross-sectional studies, n = 11,456; and 3 cohort studies, n = 2059). All cohort studies and eight of the nine cross-sectional studies found significant positive correlations between added sugar consumption and risk of cognitive impairment. Four studies identified reduced risk of cognitive impairment associated with natural fructose-containing foods. The majority of randomised control trials assessed short-term glucose facilitation effects on cognitive outcomes. The results from these studies suggest the need for a tightly regulated blood glucose level, dependent on individualised physiological factors, for optimal cognitive function. A meta-analysis of a subset of studies that assessed the impact of glucose on recall found improvements in immediate free recall compared to controls (p = 0.002). The findings highlight the potentially detrimental effect of excessive, long-term, or prenatal added sugar consumption on cognitive function. Further research is needed to examine the specific effects of free and added sugars on cognitive function.

Prenatal Caffeine Exposure Is Linked to Elevated Sugar Intake and BMI, Altered Reward Sensitivity, and Aberrant Insular Thickness in Adolescents: An ABCD Investigation.

Prenatal caffeine exposure (PCE) has been positively associated with elevated body mass index (BMI) in children. Why this association occurs is unclear, but it is possible that PCE alters the in utero development of brain structures associated with food preference, leading to more total sugar intake (TSI, grams) later in childhood. To test this hypothesis, we investigated if PCE (daily/weekly/ 0.01) of excessive PCE (vs. no exposure) with elevated BMI (daily/weekly/daily limit; consistent in boys and girls), increased TSI (daily) and insular thickness (daily/weekly), as well as low middle frontal cortex (MFC) activation (daily). Our sub-analysis revealed an association of daily/weekly PCE (vs. no exposure) with increased gram sugar intake from soft drinks. We also identified a positive relationship of excessive PCE with elevated TSI and increased insular thickness (a key gustatory region), while in a Sobel test, reward sensitivity (reduced brain reactivity to reward anticipation in MFC; tracks reward outcomes) mediated (Test statistic = 2.23; p = 0.02) the PCE-linked BMI changes in adolescents. Our findings suggest that excessive PCE might be detrimental to frontal lobe development and altered reward sensitivity to food, thereby increasing risk for elevated TSI and obesity. Our results support recommendations to limit caffeine intake during pregnancy.