Tag: Insulin Resistance

Antioxidant-rich diets linked to lower type 2 diabetes risk, supplements less effective
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Scientists at the Karolinska Institute in Sweden have conducted a systematic review and meta-analysis to determine the relationship between dietary antioxidant intake and type 2 diabetes risk.

The study is published in the journal Advances in Nutrition.

Review: Vitamins C, E, and beta-carotene and risk of type 2 diabetes: a systematic review and meta-analysis. Image Credit: alicja neumiler / Shutterstock

Background

Type 2 diabetes is a serious metabolic disease characterized by reduced secretion or impaired functioning of insulin and subsequent increase in blood glucose level (hyperglycemia). Insulin resistance and pancreatic beta-cell dysfunction are two major hallmarks of the disease.

More than 10% of the global population is currently affected by type 2 diabetes. Its prevalence is sharply increasing worldwide mainly because of an increasing inclination towards unhealthy food habits and sedentary lifestyles.

Diet plays an important role in regulating the body’s metabolism, among various lifestyle factors. Evidence indicates that an increased adherence to healthy diets, such as the Mediterranean or DASH (Dietary Approach to Stop Hypertension), can significantly reduce the risk of type 2 diabetes. The fundamental characteristic of these diets is a higher intake of plant-based foods rich in antioxidants, including vitamins C, E, and beta-carotene.

In this systematic review and meta-analysis, scientists have assessed whether consumption of dietary vitamins C, E and beta-carotene can reduce the risk of type 2 diabetes.

Study design

The scientists searched various electronic databases to identify studies investigating the association between dietary intakes, circulating levels, or supplementation of vitamin C, E, and beta-carotene and type 2 diabetes incidence or insulin resistance/sensitivity and beta cell function in non-diabetic individuals.

The final screening led to the identification of 25 prospective observational studies and 15 randomized controlled trials. Moderate and serious risks of bias were observed in 21 and 4 observational studies, respectively. Among randomized controlled trials, 13 had a low risk of bias, and 2 had some concerns.

Important observations

The study found that moderate intakes of vitamins C, E, and beta-carotene can reduce the risk of type 2 diabetes.

Vitamin C

The meta-analysis of observational studies revealed that a vitamin C intake of up to 70 mg per day can reduce type 2 diabetes risk by 24%. However, no further risk reduction was observed for an intake higher than this level.

An inverse association was observed between dietary intake of vitamin C and insulin resistance. Vitamin C intake also showed a positive impact on beta cell function.

Vitamin E

The meta-analysis of observational studies revealed that the vitamin E intake of up to 12 mg per day can reduce the risk of type 2 diabetes by 28%. Similar to vitamin C, no further risk reduction was observed for an intake higher than this level.

The meta-analysis of randomized clinical trials revealed that vitamin E supplementation does not have any protective effect against type 2 diabetes development. However, vitamin E supplementation showed a positive impact on insulin sensitivity.

Beta-carotene

The meta-analysis of observational studies revealed that the beta-carotene intake of up to 4 mg per day can reduce the risk of type 2 diabetes by 22%. No further risk reduction was observed above this level.

The meta-analysis of randomized controlled trials revealed that beta-carotene supplementation cannot reduce the risk of type 2 diabetes. It was also observed that circulating beta-carotene can reduce insulin resistance and increase insulin sensitivity.

Study significance

This systematic review and meta-analysis found an inverse association between dietary and circulating vitamins C, E, and beta-carotene and the risk of type 2 diabetes. However, no protective efficacy of supplementation with these antioxidants has been observed against type 2 diabetes.

The robust antioxidant properties of these vitamins are mainly responsible for their anti-diabetic effects. Vitamin C is a water-soluble vitamin commonly found in fruits and vegetables. It can remove free radicals in the body’s hydrophilic compartments and regenerate vitamin E from its oxidized form.

Vitamin E is a fat-soluble vitamin commonly found in nuts, seeds, and vegetable oils. It can prevent lipid peroxidation and protect lipid parts of the body, such as cell membranes. Beta-carotene is a fat-soluble provitamin A carotenoid commonly found in fruits and vegetables. Similar to vitamin E, beta-carotene can protect lipid parts of the body from free radical-mediated damage.
Article Revisions

Mar 27 2024 – Addition of Graphical abstract illustration.
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March 26, 2024
Regular intake of sugary drinks, fruit juices tied to higher Type 2 diabetes risk in boys
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A small, long-term study of almost 500 children in Massachusetts has found that regularly drinking sugary drinks and 100% fruit juices during childhood and adolescence may be linked to a higher risk of developing Type 2 diabetes among boys than girls, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention│Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago. The meeting offers the latest science on population-based health and wellness and implications for lifestyle.

While these findings are preliminary, they support the existing evidence about the potential relationship between beverages with added sugar and long-term risk of Type 2 diabetes in children. Pediatricians and other health care professionals should caution young patients and their parents about sugary drinks and fruit juices when discussing healthy eating habits.”

Soren Harnois-Leblanc, Ph.D., lead investigator, registered dietitian and postdoctoral researcher in the department of population medicine at Harvard Pilgrim Health Care Institute and Harvard Medical School

According to a 2022 American Heart Association fact sheet about sugary drinks, nearly two-thirds of children and adolescents in the U.S. consume at least one sugary drink, such as soda, lemonade or an energy drink, each day. It also notes that in addition to weight gain, eating too many foods with added sugars, especially from sugary drinks, raises the risk of developing heart disease, high blood pressure, Type 2 diabetes and tooth decay.

Using data from Project Viva, an ongoing long-term study of women and their children in eastern Massachusetts that began in 1999, researchers explored whether drinking sugary drinks, 100% fruit juices and eating fresh fruits were associated with markers for developing Type 2 diabetes. Researchers calculated the average consumption of sugary drinks, 100% fruit juices, and fresh fruits over childhood and adolescence based on dietary records and assessed their potential associations to three markers of Type 2 diabetes: insulin resistance, fasting blood glucose level and HbA1c levels. These markers were measured by a single blood test while fasting in late adolescence (approximately age 17).

The analysis found:
- Each daily serving of sugary drinks (approx. 8 ounces) during childhood and adolescence among boys was associated with a 34% increase in insulin resistance; a 5.6 milligrams per deciliter (mg/dl) increase in fasting glucose levels; and a 0.12% increase in HbA1c levels in late adolescence.
- Drinking 100% fruit juice throughout childhood and adolescence was linked to a 0.07% increase in HbA1c levels in late adolescence per daily serving of 100% fruit juice among the boys in the study, with only a slight increase in girls of 0.02%.
- Eating fresh fruit during childhood and adolescence did not appear to have a positive or negative effect on the risk of developing Type 2 diabetes among the boys or girls in the study, according to Harnois-Leblanc.
The associations between regularly drinking sugar-sweetened beverage and insulin resistance, fasting blood glucose levels and elevated HbA1c levels among boys persisted when other health, family and social factors were considered. These factors included socioeconomic status; child’s and mother’s body mass index; mother’s age at time of child’s birth; maternal and paternal history of Type 1 or Type 2 diabetes; overall diet quality and other lifestyle behaviors.

“Although several aspects of biology and behaviors differ between boys and girls, I would have expected to also find an association between sugar-sweetened beverages and fruit juice intake and the increases in insulin resistance, glycemia and HbA1c levels in late-adolescent girls. I was also surprised that eating whole fruits did not reduce the levels of these markers of Type 2 diabetes,” Harnois-Leblanc said.

“The next steps are to use more advanced statistical tools to enable us to better understand the potential causal role of sugary drinks and fruit juices, and to examine whether the relationships may also differ among children by race and/or ethnicity.”

Study background and details:
- Researchers analyzed data of children of the 2,128 pregnant women who had children while enrolled in Project Viva. 972 of the children met criteria for inclusion in this study (parent-completed questionnaires at the child’s age-3 examination and no personal or parental history of Type 1 or Type 2 diabetes, assessed separately from parental history of Type 2 diabetes). Of the 972 children, 455 had a fasting blood sample collected at a research visit in late adolescence, Harnois-Leblanc noted.
- 240 of the children in the study were girls and 215 were boys.
- Project Viva is a long-term study of women and their children in eastern Massachusetts that began enrollment in 1999. The study is focused on improving maternal and child health by examining the potential impact of various life and health factors during and after pregnancy on the mother’s health and their children’s health, including a review of diet and nutrition. Children were followed from birth to late adolescence, up to age 20 at most recent follow-up.
- Researchers evaluated the frequency of drinking sugary drinks, fruit juices and eating fresh fruit (based on standard serving sizes) from questionnaires completed by the parent at the child’s age of approximately 3, 8 and 13 years old; and measured fasting blood glucose, insulin and HbA1c levels in late adolescence (average age of 17.4 years).
The study had several limitations. Although it found an association between regularly drinking sugary drinks and fruit juices and the development of markers for Type 2 diabetes, it could not prove that the drinks caused Type 2 diabetes. Additionally, the relatively small number of study participants may have affected the strength of the association found between sugary drinks and fruit juices and the increased risk of developing Type 2 diabetes.

“Diet and cardiometabolic health are complex, with many factors varying over time and interacting in different ways, and this study represents one small piece of this puzzle,” Harnois-Leblanc said.

American Heart Association nutrition committee member Penny M. Kris-Etherton, Ph.D., R.D., FAHA, said, “This study has shown that greater sugar sweetened beverage intake, including fruit juice, throughout childhood and adolescents is associated with higher markers of diabetes risk in late adolescents in boys but not girls. It is striking that many measures of Type 2 diabetes risk were increased in boys at such an early age.”

Kris-Etherton, an emeritus professor of nutritional sciences at Penn State University, was also a co-author of the Association’s 2018 science advisory on low-calorie sweetened beverages and cardiometabolic health.

“Importantly, although fruit intake did not appear to be protective, it nonetheless was not associated with increased Type 2 diabetes risk,” she said. “These findings support the current dietary recommendations of the Association, and many organizations, to limit or eliminate drinking sugar sweetened beverages and instead consume whole fruits, which are high in so many nutrients especially the shortfall nutrients in the average American diet.” (Shortfall nutrients are the vitamins and nutrients that people are missing each day from the foods they eat; long-term deficiencies in some vitamins and nutrients have been linked to adverse health outcomes.)

The health care resource called Know Diabetes by Heart, developed by the American Heart Association and the American Diabetes Association, provides information about preventing heart disease and stroke while living with Type 2 diabetes. The initiative aims to raise awareness and understanding of the link between Type 2 diabetes and cardiovascular disease, provide resources and support to help people better manage their risk for heart disease and stroke, support health care professionals by sharing the latest clinical guidelines and science and engage health systems to improve quality of care for people with Type 2 diabetes.

Source:

American Heart Association
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March 20, 2024
Mouse models shed light on the effects of metformin use during pregnancy on offspring

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With the rise in gestational diabetes and metabolic disorders during pregnancy, metformin is also being prescribed more frequently. Although it is known that the oral antidiabetic agent can cross the placental barrier, the impacts on the brain development of the child are largely unknown. An interdisciplinary research team from the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) have now been able to demonstrate in a mouse model that although metformin has positive effects in pregnant animals, it does not in the offspring. The results were published in the specialist journal Molecular Metabolism.

Current figures show that around one in six pregnant women worldwide are affected by a special form of diabetes known as gestational diabetes. According to the Robert Koch Institute, 63,000 women in Germany were affected by the disease in 2021, and the trend is increasing.

These numbers are alarming because excessively high blood sugar levels during pregnancy are associated with negative consequences for mother and child. This increases the risk of affected women developing type 2 diabetes later on and their children have a higher risk of developing metabolic disorders and being overweight.

Long-term effect of metformin on offspring is unclear

For several years, the placenta-crossing oral antidiabetic agent metformin has been increasingly gaining importance as an alternative to insulin administration when lifestyle changes show no success during the treatment of gestational diabetes. However, there are currently only a few studies on the long-term effects of metformin on the health of offspring. It is known that metformin has an impact on the AMPK signaling pathway, which regulates the networking of nerve cells during brain development.

The interdisciplinary team of DIfE researchers led by Junior Research Group Leader Dr. Rachel Lippert therefore grappled with two central questions: Is metformin treatment only beneficial for the mother or also the child? And does metformin treatment lead to long-term negative physiological changes in the offspring, especially in connection with the development of neuronal circuits in the hypothalamus, a critical region in the regulation of energy homeostasis?

Mouse models shed some light

To answer the key questions, the researchers used two mouse models to represent the main causes of gestational diabetes: severe obesity of the mother before pregnancy and excessive weight gain during pregnancy. These metabolic states were achieved by means of different feeding patterns, with the mice receiving either a high-fat or control diet. The antidiabetic treatment of female mice and their offspring took place during the lactation period as this corresponds to the third trimester of a human pregnancy in terms of brain development.

Treatment involved insulin, metformin, or a placebo, whereby the dosage was based on standard human treatments. The research team collected data on the body weight of the mice, analyzed various metabolic parameters and hormones, and examined molecular signaling pathways in the hypothalamus.

Maternal metabolic state is crucial

“As a result of antidiabetic treatment in the early postnatal period, we were able to identify alterations in the weight gain and hormonal status of the offspring, which were critically dependent on the metabolic state of the mother,” explains Lippert. Furthermore, sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure were also observed. Together with the metformin-induced shift in the examined hormone levels, the results indicate that the maternal metabolic state must be taken into account before starting the treatment of gestational diabetes.

Focusing on prevention

According to Rachel Lippert, treatment of gestational diabetes in future could entail developing a medication that is available for all and does not cross the placenta.

Given the increasing prevalence, education about gestational diabetes and preventive measures are of vital importance. If we can find a way to manage lifestyle and diet more proactively, we are in a better position to exploit the potential of gestational diabetes treatment.”

Dr. Rachel Lippert, Junior Research Group Leader

Source:

Deutsches Zentrum fuer Diabetesforschung DZD

Journal reference:

Cantacorps, L., et al. (2024). Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice. Molecular Metabolism. doi.org/10.1016/j.molmet.2023.101860.

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March 18, 2024
Early type 2 diabetes risk skyrockets with low birthweight and overweight at age 20
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New research being presented at this year’s European Congress on Obesity (ECO) in Venice, Italy (12-15 May), and published in Diabetologia (the journal of th European Association for The Study of Diabetes [EASD]) suggests that having a low birthweight together with being overweight in young adulthood (but not childhood) contributes to the development of type 2 diabetes at an early age (59 years or younger) in men.

Notably, the study involving over 34,000 Swedish men, found that those born with a low birthweight (<2.5 kg/5 lbs 8oz) who were also overweight at aged 20 years (BMI >25kg/m²) were 10 times more likely to develop early type 2 diabetes than those with a birthweight in the normal range (2.5-4.5 kg) who were normal weight as young adults (BMI <25 kg/m²).

Importantly, the researchers from the University of Gothenburg and Sahlgrenska University Hospital also found that babies with a low birthweight who were overweight at age 20 years had a 27% absolute risk of developing early type 2 diabetes, compared with an absolute risk of 6% for those with a birthweight in the normal range who were also normal weight at aged 20 years. This suggests that preventing excess weight gain during young adulthood in boys born with low birthweight could reduce the absolute risk of early type 2 diabetes by 21%.

Type 2 diabetes is being diagnosed at progressively younger ages, suggesting that significant risk may begin to accumulate during the developmental period. The association between low birthweight and overweight in childhood and/or young adulthood and type 2 diabetes in adults is already known, but it has been unclear how much influence the combination of these two factors exerts.

To find out more, researchers analyzed data from 34,231 men born between 1945 and 1961 involved in the BMI Epidemiology Study (BEST) Gothenburg-;a population-based cohort examining the associations between growth and BMI development in early life and the risk of disease in later life.

The researchers analyzed birthweight and BMI of participants from school health care records (at the age of 8 years) and from medical examinations on enrolment in the military (at age 20), which was mandatory until 2010.

Participants were followed from 30 years of age until type 2 diabetes diagnosis, death, or emigration, or until 31^st December 2019. Information on type 2 diabetes diagnoses was retrieved from Swedish national registers to estimate the risk of early (<59.4 years) and late (>59.4 years) type 2 diabetes. They also examined whether these associations were independent of, or modified by, socioeconomic factors such as level of education.

During an average 34 years follow up (after 30 years of age), a total of 2,733 cases of type 2 diabetes were diagnosed (1,367 cases of early diabetes and 1,366 cases of late diabetes). The analyses found that birthweight below the average (median; <3.6 kg/7lbs 9oz) and overweight at age 20 years (BMI >25 kg/m²), but not overweight at age 8 years (BMI >17.9 kg/m²), were associated with an increased risk of both early and late type 2 diabetes.

Furthermore, low birthweight and overweight in young adulthood were found to have an additive effect on the risk of type 2 diabetes. For example, having a below average birthweight (<3.6 kg/7lbs 9oz), followed by overweight at 20 years of age was associated with a six times greater risk of developing early type 2 diabetes. Whereas a lower birthweight (<2.5 kg/5 lbs 8oz) combined with later overweight at 20 years was linked with a 10 fold greater risk of developing early type 2 diabetes.

Adjusting for education, a known risk factor for type 2 diabetes, did little to change the results.

Our findings establish low birthweight and overweight in young adulthood as the main developmental determinants, whereas overweight in childhood is of lesser importance for type 2 diabetes in adult men. The combination of low birthweight followed by overweight at age 20 years is associated with a massive excess risk for early type 2 diabetes, which is substantially higher than the risk associated with low birthweight or being overweight as a young adult separately.”

Dr Jimmy Celind, lead author, researcher at Sahlgrenska Academy’s Institute of Medicine, University of Gothenburg

Co-author Dr Jenny Kindblom from Sahlgrenska University Hospital adds, “It’s possible that the metabolic consequences of fetal growth restriction, which promotes resilience against starvation through fat storage and insulin resistance, when combined with a detrimental BMI trajectory during puberty when the insulin resistance is at a lifetime peak due to the surge of growth and sex hormones, result in an additive excess risk for later type 2 diabetes. Public health initiatives should target boys born with low birthweight to work on prevention of overweight as young adults, to reduce this huge excess risk for early type 2 diabetes.”

The authors acknowledge that the findings are associations only and that the study wasn’t designed to measure direct cause and effect, and point to several limitations, including that the participants were mainly white men which may limit the generalisability of the findings to other ethnicities and women. In addition, the analyses were unable to account for the influence of other known risk factors for type 2 diabetes such as smoking, dietary habits, and physical activity which could have influenced the results.
Sources:

Diabetologia

European Congress on Obesity
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March 5, 2024
Increased adherence to DASH diet related to decreased probabilities of metabolic disease conditions among adolescents, particularly overweight girls

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In a recent study published in Scientific Reports, researchers evaluated the relationship between Dietary Approaches to Stop Hypertension (DASH) and metabolic health status among Iranian overweight and obese adolescents.

Study: Association of priori-defined DASH dietary pattern with metabolic health status among Iranian adolescents with overweight and obesity. Image Credit: monticello/Shutterstock.com

Background

Adolescent overweight and obesity are global health concerns associated with metabolic conditions such as hypertension, blood lipid abnormalities, impaired glucose metabolism, and insulin resistance. These diseases increase the risk of cardiovascular disease, type 2 diabetes, and early death—lifestyle variables such as food and physical exercise influence metabolic health.

Recent studies report favorable relationships between high vegetable and fruit intake and low sugary beverages and fats, implying a link between healthy diets and metabolically healthy overweight or obesity. The DASH diet, which contains more vegetables, fruits, whole grains, legumes, seeds, and low-fat-type dairy foods, has been researched in adolescents, but disputed findings call for more research.

About the study

In the present cross-sectional study, researchers explored the metabolic impact of DASH diets among overweight and obese adolescents.

The team surveyed 203 adolescents aged 12 to 18 years with overweight or obesity status, as determined by body mass index (BMI) values using the Quetelet formula. Eligible students did not follow weight-loss diets, had no endocrinal or genetic disease, and did not use vitamin or mineral supplements or medications that could alter their metabolic profiles.

The researchers obtained dietary intake data using standardized food frequency questionnaires (FFQs). They also collected data on anthropometric parameters such as circulating insulin, blood pressure, lipid profile, and fasting blood sugar. The team characterized DASH scores based on eight components, i.e., higher intake of low-fat dairy foods, whole grains, seeds, nuts, vegetables, fruits, and legumes, and lower consumption of sodium, sweetened beverages, and processed and red meats.

The team obtained blood samples from all participants for biochemical analysis. They measured insulin levels by enzyme-linked immunosorbent assays (ELISA) and ascertained metabolic health status based on insulin resistance, determined using the International Diabetes Federation (IDF) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) criteria.

The researchers assessed physical activity levels using the Physical Activity Questionnaire for Adolescents (PAQ-A) and total calorie intake using the United States Department of Agriculture (USDA) food composition database. They used multivariate logistic regression to calculate the odds ratios (ORs) for the association between DASH diets and metabolic health, adjusting for age, gender, physical activity, socioeconomic status, and total calorie intake.

Results

The mean values for age and BMI of the study participants were 14 years and 27 kg/m2, respectively. Among participants, 79 (42 girls and 37 boys, 39%) suffered from metabolically unhealthy overweight or obesity (MUO) by the IDF definition, and 62 (32 girls and 35 boys, 33%) were MUO following the IDF and HOMA-IR guidelines. Using the IDF definition, MUO prevalence in the DASH diet’s highest tertile was lower compared to the lowest statistical tertile (10 vs. 67%). Using HOMA-IR guidelines yielded similar findings (10 vs. 61%).

Individuals in the uppermost tertile of the DASH diet were more physically active, with higher HDL-c levels and lower blood pressure, fasting blood sugar, insulin, triglyceride, and HOMA-IR levels, compared to those in the lowest tertile. Confounder adjustment showed that individuals in the highest vs. lowest DASH tertile had 91% and 92% lower MUO odds using the IDF/IR (OR, 0.09) and IDF definition (OR, 0.08), respectively.

The highest vs. lowest DASH adherence was associated with decreased odds of hyperglycemia, hypertriglyceridemia, insulin resistance, and low HDL cholesterolemia, with odds ratios of 0.1, 0.3, 0.1, and 0.3, respectively. Subgroup analysis by BMI and sex indicated that the association was more robust among females (OR, 0.02) than males (OR, 0.09). The DASH diet likely improves metabolic health by lowering inflammation because of its high fiber, antioxidants, potassium, magnesium, and low salt content.

Conclusions

Overall, the study findings showed that increased adherence to the DASH diet was related to decreased probabilities of metabolic disease conditions among Iranian adolescents, particularly overweight girls. The study also found that adhering to the DASH diet reduced the risk of hypertriglyceridemia, hyperglycemia, insulin resistance, and low HDL cholesterol. Further research, including prospective surveys, could validate the study findings.

The inverse association observed between the DASH dietary pattern and the MUO category in the current study indicates that adolescents must increase the intake of health-associated DASH components, including fruits, vegetables, legumes, low-fat-type dairy foods, whole grains, seeds, and nuts while limiting the consumption of unhealthy foods such as processed and red meats, sweetened beverages, and salt to improve dietary quality and decrease the metabolic disease burden.

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March 4, 2024
Resistant starch diet proves a game changer for weight loss and diabetes control
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In a recent study published in the journal Nature Metabolism, a team of scientists investigated whether modulation of the gut microbiome using dietary fiber supplementation in the form of resistant starch could help with insulin resistance and weight loss and offer a potential treatment avenue for metabolic disorders.

Study: Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota. Image Credit: Sokor Space / Shutterstock

Background

Obesity has been classified as a global epidemic, with substantial research being conducted on strategies to reduce weight and prevent obesity. It contributes significantly to the global mortality rates by increasing the risk of metabolic diseases such as diabetes, as well as cardiovascular disease risk. Weight management and effective weight loss can lower the risk of these diseases.

Increasing evidence indicates that the gut microbiome plays a pivotal role in the regulation of human physiology and development of various diseases. Gut microbiome composition and diversity are intricately linked to the metabolism of glucose and fat and inflammation.

Furthermore, while fecal microbiome transplantation has been used to establish healthy gut microbiome communities, the procedure has not yielded effective or long-term results. However, diet can be used to modulate the gut microbiome, and dietary interventions, either alone or in conjunction with fecal microbiome transplantation, could potentially improve the clinical outcomes.

About the study

In the present study, the team conducted a randomized, crossover clinical trial involving overweight individuals to determine whether dietary supplementation with resistant starch positively impacted obesity and metabolic phenotypes. They also conducted metagenomic and metabolomic analyses to understand how the resistant starch affected the composition of the gut microbiome and its function.

Furthermore, they studied antibiotic-treated mice that had received gut microbiomes from human donors that had already been modified through resistant starch supplementation to understand how gut microbiomes modified through supplementation with resistant starch influence glucose metabolism and adiposity. The metabolomic advantages offered by the gut microbiome modified through resistant starch supplements were also explored.

Resistant starch cannot be broken down by the amylase enzymes produced in humans, functioning as a dietary fiber. During digestion, resistant starch does not get broken down in the stomach or small intestine but moves into the large intestine or colon, where the gut microbiome ferments this dietary fiber. Rodent model studies have shown a decrease in body fat and better metabolic outcomes when the carbohydrate portion of their diet consists mainly of resistant starch.

The present clinical trial included participants with excess body weight who did not have any chronic disorders, were not using any probiotics or antibiotics, and were not undergoing any treatments that would impact their glucose metabolism. The participants were randomly assigned to the treatment or control group, with the treatment group receiving resistant starch in the form of high-amylose maize and the control group receiving amylopectin with no resistant starch.

The starch was provided in sachets in powdered form, and all the participants in the treatment and control groups consumed one packet of the appropriate starch twice a day before a balanced, isoenergetic meal that was provided thrice a day. Since this was a crossover clinical trial, all the participants underwent two eight-week-long interventions, one for the resistant starch treatment and the other for the control treatment.

Results

The results showed that supplementation with resistant starch helped achieve a mean weight loss of about 2.8 kg and improved insulin resistance in overweight participants. The study also found that the beneficial effects of resistant starch supplementation were associated largely with gut microbiome composition changes.

The bacterium Bifidobacterium adolescentis was found to be associated with resistant starch supplementation in humans, and the monocolonization of mice with this bacterium protected them from diet-induced obesity. Resistance starch impacted lipid and fat metabolism by reducing inflammation, restoring the intestinal barrier, and altering the bile acid profile.

The gut microbiota impacts the host physiology through signaling metabolites, of which bile acids play a significant role. Secondary bile acids, such as glycodesoxycholic acid, deoxycholic acid, glycocholic acid, and taurodeoxycholic acid, are important in improving insulin sensitivity and ameliorating hepatic steatosis. The enzyme bile salt hydrolase carries out the deconjugation of secondary bile acids.

The study found that resistant starch supplementation decreased the production of bile salt hydrolase and increased the levels of secondary bile acids. The results were reciprocated in the mice after they were monocolonized with B. adolescentis from humans who underwent resistant starch supplementation.

Resistant starch (RS, 40 g d^-1) accompanied with isoenergetic and balanced diets led to an obvious reduction in body weight and improvement of insulin sensitivity, as well as alteration in metagenomics and metabolomics. Faecal microbiota transplantation (FMT) showed benefits of RS were associated with the reshaped gut microbiota composition. Monocolonization of mice with B. adolescentis, which was closely correlated with the benefits of RS in human protected mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota influenced metabolites of gut microbiome, reduced chronic low-grade inflammation by improving intestinal integrity, inhibited lipid absorption by modulating angiopoietin-like 4 (ANGPTL4), and improved the sensitivity of fibroblast growth factor 21 (FGF21) in adipose tissue. SPF, specific-pathogen-free; LPS, lipopolysaccharide; BCAAs, branched-chain amino acids; Erk1/2, extracellular signal-regulated kinase 1/2; FGFR1, fibroblast growth factor receptor 1. Created with BioRender.com.

Conclusions

To summarize, the study found that supplementation with resistant starch can facilitate weight loss by increasing the abundance of B. adolescentis in the gut microbiome. It can also help improve insulin sensitivity through gut microbiome-induced changes in the levels of secondary bile acids and lowering of inflammation.
Journal reference:

Li, H., Zhang, L., Li, J., Wu, Q., Qian, L., He, J., Ni, Y., KovatchevaDatchary, P., Yuan, R., Liu, S., Shen, L., Zhang, M., Sheng, B., Li, P., Kang, K., Wu, L., Fang, Q., Long, X., Wang, X., & Li, Y. (2024). Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota. Nature Metabolism. DOI: 10.1038/s4225502400988y, https://www.nature.com/articles/s42255-024-00988-y
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February 28, 2024
Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat

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A recent Nature Communications study performed analyses of blood samples obtained from a randomized clinical trial. It showed that three cycles of fasting-mimicking diet (FMD) in adults were associated with lower pre-diabetes markers, lower hepatic fat, and a higher lymphoid-to-myeloid ratio, which is an indicator of the aging of the immune system.

Study: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Image Credit: Kmpzzz/Shutterstock.com

Background

Metabolic syndromes are characterized by the co-occurrence of three symptoms from within: abdominal obesity, dyslipidemia, insulin resistance, and elevated CRP levels. Research has shown that obesity accelerates liver aging and acts on other molecular hallmarks of aging. Another feature of aging is immunosenescence, which is the altered function and composition of the immune system.

Dysfunction in different types of cells stemming from aging is at the center of many diseases, including cancer, cardiovascular disease, and so on. This suggests that intervening in the aging process could lead to the prevention or amelioration of human diseases. This has indeed been noted in animal models where slowing down cellular deterioration led to new or functional intra-cellular components.

Everyday nutrition has been seen to play a crucial role in speeding up the aging process in rodents, and this could possibly be true in humans as well. Besides the nutrient content, the number of hours for which meals are consumed influences lifespan and health. In this regard, time-restricted eating (TRE), periodic water-only fasting (PF), and intermittent fasting (IF) have gained popularity recently.

About the study

A fasting-mimicking diet (FMD) is a low-calorie, plant-based, and low-protein dietary intervention that lasts for 5-days. FMD followed by a normal diet has been seen to have positive effects on both cellular healthspan and function. The hypothesis tested here was that FMD cycles reduce biological age by improving the levels of various markers of aging.

For this study, blood samples were obtained from a randomized control trial, followed by recording cellular and metabolic measurements. Insights were also provided on lymphoid/myeloid ratios, blood markers, and visceral and hepatic fat, which are secondary outcome measures and biomarkers associated with age-related diseases and aging generally.

The biological age of participants was studied before and after they completed 3FMD cycles.

It is also important to note that the biological age and the chronological age may differ because aging is a heterogeneous process. Biological age is based on many multisystem biomarkers, which helps us understand the rate and level of organismal aging.

Study findings

A calorie reduction of 15–20% below the normal levels was seen to have significant effects on the risk factors for multiple diseases. Preliminary findings showed that alternate-day fasting and caloric restriction (CR) are effective at reducing the risks related to aging. However, chronic CR is quite a severe intervention that could, in principle, reverse the benefits by reducing lean body mass and weight.

The cohort comprised individuals who were healthier than the average American person. In this cohort, 3 FMD cycles were followed by a reduction in median biological age of 2.5 years. Furthermore, reductions in 20-year risk for cause-specific and all-cause mortality were noted.

The findings assume that the associations between mortality and biological age mirror the effect of change in biological age, but this fact is yet to be proven. Nevertheless, the results documented here offer early evidence of the potential health benefits of FMD, even in a cohort of relatively healthier individuals.

The benefits of FMD were most noted in individuals who were relatively more unhealthy at baseline. In terms of mechanisms, FMD lowered the hepatic fat fraction and visceral fat in study participants with non-alcoholic fatty liver disease and obesity. In this way, FMD cycles act to prevent diabetes and metabolic syndrome. Another explanation could be the importance of shared mechanisms, e.g., general rejuvenating effects in organs and cells, which lower systemic inflammation.

Conclusions

In sum, it was suggested that sustained FMD or similar dietary interventions may lead to improvements in population health by extending life expectancy, slowing the rate of aging, and reducing the risks of disease-specific mortality. More specifically, 3 FMD cycles each year could lead to a less than one year gain in biological age for every year increase in chronological age.

A key limitation of the study centers around the small sample size and lack of heterogeneity in health status at baseline. Characteristics that study participants did not capture could change the impact of FMD on biological age, thereby making the current estimates inaccurate. Furthermore, extrapolation of the 3–6 months effects of the FMD to lifelong intervention should be interpreted with caution. This is because the effects may cease to persist if participants return to their pre-intervention lifestyles.

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February 21, 2024
Fasting-mimicking diet reduces biological age and disease risks, study shows
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Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study.

The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).

The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.

This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age.”

Valter Longo, Professor, USC Leonard Davis School

Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can:
- Promote stem cell regeneration
- Lessen chemotherapy side effects
- Reduce the signs of dementia in mice
In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.

The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.

Lower disease risks & more youthful cells

The study analyzed the diet’s effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.

The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.

An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio – an indicator of a more youthful immune system.

Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age – a measure of how well one’s cells and tissues are functioning, as opposed to chronological age – by 2.5 years on average.

“This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function,” Longo said.

The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD’s potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.

“Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age,” Longo said.

Source:

University of Southern California

Journal reference:

Brandhorst, S., et al. (2024). Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications. doi.org/10.1038/s41467-024-45260-9.
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February 20, 2024
Melatonin treatment does not affect insulin resistance of night shift workers

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Melatonin treatment does not affect the insulin resistance or the glucose tolerance of night shift workers, according to a new study from the University of Surrey and the University Medical Centre Hamburg. Melatonin treatment does, however, significantly improve the sleep quality of those working shifts.

In this study, scientists explored how oral melatonin affects insulin resistance and blood pressure in night shift workers, who face a higher risk of Type 2 diabetes. Insulin resistance is when cells struggle to absorb glucose from the blood. Previous research suggests melatonin could help these workers’ glucose tolerance and heart health. This led scientists to investigate melatonin’s broader effects on the body.

Night shift work is necessary for our emergency and health services and to keep our economy moving. However, working night shifts disrupt our circadian rhythms, which are driven by light/dark cycles and are associated with sleep disturbances, cardiometabolic diseases and increased risk of diabetes.

We need to find ways to limit the adverse health implications for night shift workers so they can continue in their roles whilst protecting their long-term health.”

Debra Skene, Professor of Neuroendocrinology, University of Surrey

To investigate the impact of melatonin, 24 night shift workers and 12 healthy non-shift workers were recruited and underwent glucose tolerance testing and blood pressure monitoring for 24 hours. Night shift workers were then randomised to receive oral melatonin (2 mg) or a placebo at night time or in the morning, depending on their shift schedule, for 12 weeks.

The authors identified that night shift workers were significantly more insulin-resistant than non-night shift workers. After 12 weeks of taking the hormone melatonin, no significant effect was observed in serum glucose or insulin concentrations, which are markers of insulin resistance. Similarly, for blood pressure, treatment with melatonin had no significant effect.

Unsurprisingly, melatonin significantly improved the sleep quality of night shift workers. During the initial assessment, only 21 per cent of night shift workers described their sleep quality as good; however, after 12 weeks of melatonin treatment, 50 per cent of this cohort indicated good sleep quality. The proportion of good versus poor sleepers remained almost unchanged in the placebo group.

Professor Skene added:

“The benefits of improved sleep for shift workers via melatonin are undeniable, and people should feel more rested and alert. However, since there is no evidence that the use of melatonin reduces insulin resistance, we need to find alternate ways to improve insulin resistance and lessen the likelihood of a person developing type 2 diabetes.”

This study was published in the journal Pharmacological Research.

Source:

Journal reference:

Hannemann, J., et al. (2024). Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study. Pharmacological Research. doi.org/10.1016/j.phrs.2023.107011.

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February 19, 2024
Risk of non-alcoholic fatty liver disease for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus

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In a recent study published in the British Medical Journal, researchers investigated the link between non-alcoholic fatty liver disease (NAFLD) in individuals with type 2 diabetes mellitus (T2DM) and all-cause death and cardiovascular disease. They found that individuals with NAFLD and T2DM show an increased risk of cardiovascular disease (CVD) and all-cause death.

Study: Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. Image Credit: Explode/Shutterstock.com

Background

The prevalence of NAFLD is on the rise globally and is often associated with metabolic disorders involving insulin resistance. It poses a significant health concern due to its potential to lead to liver complications and CVD, which is a leading cause of mortality, especially among NAFLD patients.

T2DM is a major risk factor for CVD and is closely linked to higher NAFLD prevalence and severity. The complex relationship between NAFLD and T2DM suggests a synergistic effect on cardiovascular risk, with a substantial proportion of T2DM patients also having NAFLD. However, studies examining their association with CVD have yielded mixed results. While some found no correlation, others demonstrated a doubled risk of CVD in T2DM patients with NAFLD compared to those without. Additionally, previous studies were limited by their cross-sectional designs and small sample sizes.

To address this gap, researchers in the present study aimed to assess the risk of CVD and all-cause mortality associated with NAFLD in T2DM patients using a large-scale, population-based longitudinal approach.

About the study

This nationwide cohort study utilized data from the National Health Information Database linked t the National Health Screening Program. The exclusion criteria were age ≤ 20 years, consumption of ≥30 g/day alcohol, missing data, or a history of type 1 diabetes mellitus, chronic hepatitis B, and C, liver cirrhosis, hepatocellular carcinoma, or CVD. Additionally, patients who developed CVD within one year were also excluded.

A total of 7,796,763 participants were selected, and the endpoint was the occurrence of all-cause death, CVD, or until 31 December 2018. CVD included myocardial infarction or ischemic stroke, confirmed through hospital admissions with corresponding claims for brain magnetic resonance imaging or computed tomography. The patients were followed-up for a median of 8.13 years.

Data on anthropometric measurements and laboratory parameters were collected. Blood pressure was measured in a seated position, and fasting venous blood samples were taken to assess various parameters, including glucose, liver enzymes, lipid profile, and creatinine levels. Additionally, the estimated glomerular filtration rate was determined.

Information on lifestyle factors such as smoking, alcohol consumption, regular exercise, and socioeconomic status was obtained through a standardized self-assessment questionnaire. Statistical methods included Cox proportional hazards models adjusted for various factors, Kaplan-Meier survival curves, and subgroup analyses.

Results and discussion

Among the participants, 6.49% of the participants had T2DM. Grade 1 and 2 NAFLD were found in 22.04% and 11.11% of participants, respectively. A higher proportion of T2DM patients had grade 2 NAFLD (26.73%) and grade 1 NAFLD (34.06%) compared to those without T2DM. Among participants with T2DM, 6.77% had CVD, and about 8.38% of participants died. In contrast, among those without T2DM, 2.24% had CVD, and about 2.71% of participants died.

Incidence rates for CVD, myocardial infarction, ischemic stroke, and all-cause mortality increased with the severity of NAFLD and were higher in patients with T2DM than in those without. Hazard ratios for these outcomes were also higher with grade 1 and grade 2 NAFLD compared to no NAFLD, regardless of T2DM status. Moreover, the five-year absolute risk for these outcomes increased with NAFLD severity, particularly in patients with T2DM. Risk differences for CVD, myocardial infarction, ischemic stroke, and all-cause death were higher between no NAFLD and grade 2 NAFLD than between no NAFLD and grade 1 NAFLD. Additionally, these risk differences were higher in patients with T2DM compared to those without T2DM.

NAFLD was linked to an increased risk of cardiovascular disease, myocardial infarction, ischemic stroke, and all-cause death in both T2DM and non-T2DM patients (p<0.001). Among NAFLD patients, those with grade 2 NAFLD exhibited the highest risk, followed by grade 1 NAFLD.

Further, the incidence rates of CVD, myocardial infarction, ischemic stroke, and all-cause death increased sequentially from no NAFLD to grade 1 NAFLD and to grade 2 NAFLD across all age groups, with higher rates observed in T2DM patients.

The study’s limitations include the use of the fatty liver index for NAFLD definition, lack of assessment of glycated hemoglobin variability and changes in diabetes drugs, limited generalizability to other ethnicities, and the inability to evaluate hepatic fibrosis.

Conclusion

In conclusion, patients with T2DM and even mild NAFLD have a higher risk of cardiovascular disease and all-cause death. The risk gap between no NAFLD and grade 1 or grade 2 NAFLD is more significant in T2DM patients than in those without. The findings emphasize the need for NAFLD screening and prevention in T2DM patients to reduce subsequent cardiovascular risk and mortality.

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February 16, 2024