Learn more about Dr. Coy and the creation of his sugar solutions.
Dr Johannes Coy is a world-renowned scientist whose research focuses on the health benefits of sugar awareness. Dr Coy has made a number of important genetic discoveries which change our understanding of cancer and nutrition and make him the leading expert on sugars.
Book: Fit with Sugar, by Dr Johannes Coy
Dr Coy has written several books about cancer nutrition. His latest book, Fit with Sugar, is now available. In this book, you’ll discover the evolutionary role of sugar in the human body. Consuming too much conventional sugar isn’t good for our health, but with the right sugars, we can stop cell ageing, keep the brain fit, protect against diseases and switch on fat burning. Find out how you can maintain physical and mental performance using natural low- glycaemic sugars and sugar substitutes. The book includes many delicious recipes for cakes, snacks and desserts, so you can implement a sugar-conscious diet easily and intelligently, without giving up sweet treats.
Buy the book: Cancer-Fighting Diet: Diet and Nutrition Strategies to Help Weaken Cancer Cells and Improve Treatment, by Dr Johannes Coy.
Research & Resources
All sugars are not alike: Isomaltulose better than table sugar for type 2 diabetes patients
Like sucrose (table sugar), the natural disaccharide isomaltulose (PalatinoseTM) consists of glucose and fructose, but it is apparently more suitable for people with type 2 diabetes with regard to regulating blood glucose levels. The favorable metabolic effect of isomaltulose is due to the almost opposing release profiles of the gut hormones GLP-1 and GIP, a new study shows.
Novel findings on the metabolic effects of the low glycaemic carbohydrate isomaltulose (Palatinose)
This study included three human intervention trials to investigate the physiological characteristics of isomaltulose (iso). The results showed that iso is effectively absorbed from the small intestine, regardless of the food matrix, and provides a prolonged delivery of blood glucose. It was found to have lower postprandial blood glucose and insulin responses compared to sucrose. Regular consumption of iso within a Western-type diet was well tolerated and did not affect blood lipids in individuals with hyperlipidemia. Although no significant differences were observed compared to sucrose after the 4-week intervention, iso shows promise as a carbohydrate option for individuals at risk of vascular diseases.
The genes and enzymes for the catabolism of galactitol, D-tagatose, and related carbohydrates in Klebsiella oxytoca M5a1 and other enteric bacteria display convergent evolution
Enteric bacteria (Enteriobacteriaceae) carry on their single chromosome about 4000 genes that all strains have in common (referred to here as “obligatory genes”), and up to 1300 “facultative” genes that vary from strain to strain and from species to species. In closely related species, obligatory and facultative genes are orthologous genes that are found at similar loci. We have analyzed a set of facultative genes involved in the degradation of the carbohydrates galactitol, D-tagatose, D-galactosamine and N-acetyl-galactosamine in various pathogenic and non-pathogenic strains of these bacteria. The four carbohydrates are transported into the cell by phosphotransferase (PTS) uptake systems, and are metabolized by closely related or even identical catabolic enzymes via pathways that share several intermediates. In about 60% of Escherichia coli strains the genes for galactitol degradation map to a gat operon at 46.8 min. In strains of Salmonella enterica, Klebsiella pneumoniae and K. oxytoca, the corresponding gat genes, although orthologous to their E. coli counterparts, are found at 70.7 min, clustered in a regulon together with three tag genes for the degradation of D-tagatose, an isomer of D-fructose. In contrast, in all the E. coli strains tested, this chromosomal site was found to be occupied by an aga/kba gene cluster for the degradation of D-galactosamine and N-acetyl-galactosamine. The aga/kba and the tag genes were paralogous either to the gat cluster or to the fru genes for degradation of D-fructose. Finally, in more then 90% of strains of both Klebsiella species, and in about 5% of the E. coli strains, two operons were found at 46.8 min that comprise paralogous genes for catabolism of the isomers D-arabinitol (genes atl or dal) and ribitol (genes rtl or rbt). In these strains gat genes were invariably absent from this location, and they were totally absent in S. enterica. These results strongly indicate that these various gene clusters and metabolic pathways have been subject to convergent evolution among the Enterobacteriaceae. This apparently involved recent horizontal gene transfer and recombination events, as indicated by major chromosomal rearrangements found in their immediate vicinity.
Effects of D-Tagatose on the Growth of Intestinal Microflora and the Fermentation of Yogurt
To investigate the effect of tagatose on the growth of intestinal bacteria, various species were cultivated individually on m-PYF medium containing tagatose as a carbon source. The tagatose inhibited the growth of intestinal harmful microorganisms such as Staphylococcus aureus subsp. aureus, Listeria monocytogenes, Vibrio parahaemolyticus, Salmonella Typhimurium, and Pseudomonas fluorescens. In the case of beneficial microorganisms found in the intestine, Lactobacillus casei grew effectively on m-PYF medium containing tagatose, while Lactobacillus plantarum, Lactobacillus brevis, Leuconostoc citreum, and Lactobacillus acidophilus did not. To examine the effect of tagatose on fermentation by Lactobacillus casei, yogurt was prepared with tagatose as a carbon source. The resulting acid production stimulated a remarkable growth of lactic acid bacteria in the yogurt. After fermentation for 24 hours, the viable cell count and viscosity of yogurt were above 8.49 log CFU/mL and 1,266 cps, respectively. Moreover, sensory evaluations showed that the yogurt supplemented with tagatose was as acceptable as control yogurt prepared with glucose as a carbon source. The changes in pH, titratable acidity and lactic acid bacteria in yogurt prepared with tagatose did not show any significant changes during storage for 15 days at 4°C.
Effect of L-glucose and D-tagatose on bacterial growth in media and a cooked cured ham product
Cured meats such as ham can undergo premature spoilage on account of the proliferation of lactic acid bacteria. This spoilage is generally evident from a milkiness in the purge of vacuum-packaged sliced ham. Although cured, most hams are at more risk of spoilage than other types of processed meat products because they contain considerably higher concentrations of carbohydrates, approximately 2 to 7%, usually in the form of dextrose and corn syrup solids. Unfortunately, the meat industry is restricted with respect to the choice of preservatives and bactericidal agents. An alternative approach from these chemical compounds would be to use novel carbohydrate sources that are unrecognizable to spoilage bacteria. L-Glucose and D-tagatose are two such potential sugars, and in a series of tests in vitro, the ability of bacteria to utilize each as an energy source was compared to that of D-glucose. Results showed that both L-glucose and D-tagatose are not easily catabolized by a variety of lactic bacteria and not at all by pathogenic bacteria such as Escherichia coli O157:H7, Salmonella Typhimurium, Staphylococcus aureus, Bacillus cereus, and Yersinia enterocolitica. In a separate study, D-glucose, L-glucose, and D-tagatose were added to a chopped and formed ham formulation and the rate of bacterial growth was monitored. Analysis of data by a general linear model revealed that the growth rates of total aerobic and lactic acid bacteria were significantly (P < 0.05) slower for the formulation containing D-tagatose than those containing L- or D-glucose. Levels of Enterobacteriaceae were initially low and these bacteria did not significantly (P < 0.20) change in the presence of any of the sugars used in the meat formulations. Compared to the control sample containing D-glucose, the shelf life of the chopped and formed ham containing D-tagatose at 10 degrees C was extended by 7 to 10 days. These results indicate that D-tagatose could deter the growth of microorganisms and inhibit the rate of spoilage in a meat product containing carbohydrates.
Naturally occurring rare sugars are free radical scavengers and can ameliorate endoplasmic reticulum stress
Because of potential use of naturally occurring rare sugars as sweeteners, their effect on superoxide (SO), hydroxyl and peroxyl radicals and endoplasmic reticulum (ER) stress was examined in human coronary artery endothelial cells. SO generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence. Phycoerythrin fluorescence based assay was used to monitor scavenging activity of sugars in the presence of hydroxyl or peroxyl radical generators [CuSO4 and azobis (2 amidinopropane) hydrochloride respectively]. Measurements were made in relative light units (RLU). ER stress was measured with an ER stress-sensitive secreted alkaline phosphatase (SAP) assay and by Western blot analysis of the expression and phosphorylation of key proteins in the unfolded protein response, namely CHOP47, eIF2α and JNK1. D-Glucose (27.5 mM) increased SO generation (5536 ± 283 vs. 2963 ± 205 RLU in controls; p < 0.0007) and decreased SAP secretion (73411 ± 3971 vs. 101749 ± 7652 RLU in controls; p < 0.005) indicating ER stress. Treatment of cells with 5.5 or 27.5 mM of D-allulose, D-allose, D-sorbose and D-tagatose reduced SO generation (all p < 0.05). This could not be attributed to inhibition of cellular uptake of dextrose by the rare sugars tested. In a cell free system, all four rare sugars had significantly more SO, hydroxyl and peroxyl radical scavenging activity compared to dextrose (all p < 0.01). Treatment of cells with rare sugars reduced ER stress. However, unlike other three rare sugars, D-sorbose did not inhibit tunicamycin-induced eIF2α phosphorylation. Naturally occurring rare sugars are free radical scavengers and can reduce ER stress.
Antioxidant and cytoprotective properties of D-tagatose in cultured murine hepatocytes
D-Tagatose is a zero-energy producing ketohexose that is a powerful cytoprotective agent against chemically induced cell injury. To further explore the underlying mechanisms of cytoprotection, we investigated the effects of D-tagatose on both the generation of superoxide anion radicals and the consequences of oxidative stress driven by prooxidant compounds in intact cells. Primary cultures of hepatocytes derived from male C57BL/6 mice were exposed to the redox cycling drug nitrofurantoin (NFT). Lethal cell injury induced by 300 microM NFT was completely prevented by high concentrations (20 mM) of D-tagatose, whereas equimolar concentrations of glucose, mannitol, or xylose were ineffective. The extent of NFT-induced intracellular superoxide anion radical formation was not altered by D-tagatose, indicating that the ketohexose did not inhibit the reductive bioactivation of NFT. However, the NFT-induced decline of the intracellular GSH content was largely prevented by D-tagatose. The sugar also afforded complete protection against NFT toxicity in hepatocytes that had been chemically depleted of GSH. Furthermore, the ketohexose fully protected from increases in both membrane lipid peroxidation and protein carbonyl formation. In addition, D-tagatose completely prevented oxidative cell injury inflicted by toxic iron overload with ferric nitrilotriacetate (100 microM). In contrast, D-tagatose did not protect against lethal cell injury induced by tert-butyl hydroperoxide, a prooxidant which acts by hydroxyl radical-independent mechanisms and which is partitioned in the lipid bilayer. These results indicate that D-tagatose, which is a weak iron chelator, can antagonize the iron-dependent toxic consequences of intracellular oxidative stress in hepatocytes. The antioxidant properties of D-tagatose may result from sequestering the redox-active iron, thereby protecting more critical targets from the damaging potential of hydroxyl radical.
90-Day oral toxicity study of D-tagatose in rats
D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose’s safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet.
The acute effect of D-tagatose on food intake in human subjects
A double-blind randomized crossover study was performed with nineteen normal-weight men to investigate the effect on subsequent ad libitum food intake of replacing 29 g sucrose with 29 g D-tagatose as sweetener to a breakfast meal. D-Tagatose is a malabsorbed stereoisomer of fructose with potential application as a bulk sweetener. Food intake was measured at lunch offered 4 h after the breakfast meal, during the afternoon with access to abundant snacks, and finally at a supper buffet 9 h after the breakfast. Energy intake at lunch and during the snacking period was similar after ingesting the two sugars, while it was 15% lower after ingesting D-tagatose than with sucrose at supper (P < 0.05). Gastrointestinal factors such as the osmotic effects of unabsorbed D-tagatose causing distension of the gut might have mediated the acute appetite-suppressing effect. The present paper also refers to data from a preceding study in which we observed an increased self-reported energy intake after ingestion of D-tagatose compared with sucrose which, in fact, suggests a relative hyperphagic effect of D-tagatose. However, self-reported food intake may be biased by selective under-reporting and this subsequent study with a more controlled assessment of food intake was therefore conducted. This present study did not support any hyperphagic effect of D-tagatose, but rather suggests that D-tagatose may contribute to a reduced energy intake.
DDDAS Design of Drug Interventions for the Treatment of Dyslipidemia in ApoE-/- Mice
Computational models of complex systems, such as signaling networks and biological systems, can be used to explain the behavior of such systems under various conditions. The large number of integrated processes and variables, and the nonlinearities inherent in the fundamental processes, make it difficult for scientists unassisted by computer simulations to effectively predict the consequences of a particular intervention. For this reason, computer simulation has become an important tool for generating hypotheses about the behavior of these systems that can then be tested in the laboratory and clinic. A dynamic data-driven application simulation (DDDAS) was designed by Biospherics to model complex metabolic disease pathways by testing potential binary therapies in simulations at various combinations of two points in the pathways. Since DDDAS chooses the most effective pair-wise combinations, this data-driven system allows for the implementation of real-time data to model or predict a measurement or event. By incorporating data dynamically rather than statically, the predictions and measurements become more reliable. Dyslipidemia, a common precursor to atherosclerosis, can be manifested by high triglycerides, increased apolipoprotein (Apo) B, high levels of LDL, and low levels of HDL. SPX106 and D-tagatose is a combination drug therapy composed of a carbohydrate (D-tagatose) and SPX106. D-tagatose has been studied for the treatment of diabetes for several years, and has the ability to lower blood insulin levels and to decrease glycogen formation. SPX106 is a natural substance that accelerates lipid catabolism and inhibits dyslipidemia. In apolipoprotein E knockout mice (ApoE-/-), this drug combination has been shown to significantly lower both the amount of atherosclerosis and blood cholesterol levels. This study used 26 male ApoE-/- mice (n=13 in each group, control and treated). The control group received the normal “Western” diet (Harlan TD88137) and the treatment group received a modified version in which the sucrose was replaced with D-tagatose and 1g of SPX106 was added for every kilogram of chow. Mice were fed the diet for 8 weeks and then sacrificed via cardiac puncture. Blood serum was analyzed for cholesterol concentration. A significant difference was observed between the control and treated groups for total cholesterol levels. FPLC separations were done on fractions from both control and treated groups. A significant difference between VLDL and HDL levels was found between the treated and control mice (p<0.05 for both). Aortas were also taken and preserved in formalin to be quantified for atherosclerosis. Aortic sinuses were frozen in OCT and sectioned using a cryostat and then quantified for atherosclerosis. Treated mice showed statistically significant reduction in atherosclerosis in the aortic arch (p<0.01), the thoracic aorta (p<0.05), and the aortic sinus (p<0.05) as well as a reduction of cholesterol (p<0.05).
BSN723T Prevents Atherosclerosis and Weight Gain in ApoE Knockout Mice Fed a Western Diet
This study tests the hypothesis that BSN723T can prevent the development of hyperlipidemia and atherosclerosis in ApoE-/- knockout mice fed a Western (high fat, high cholesterol, and high sucrose) diet. BSN723T is a combination drug therapy consisting of D-tagatose and dihydromyricetin (BSN723). D-tagatose has an antihyperglycemic effect in animal and human studies and shows promise as a treatment for type 2 diabetes and obesity. Many claims regarding BSN723’s pharmacological activities have been made including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory, and anti-atherosclerotic effects. To our knowledge this is the first study that combines D-tagatose and BSN723 for the treatment of hyperlipidemia and the prevention of atherosclerosis.ApoE-deficient mice were randomized into five groups with equivalent mean body weights. The mice were given the following diets for 8 weeks: Group 1 – Standard diet; Group 2 – Western diet; Group 3 – Western diet formulated with D-tagatose; Group 4 – Western diet formulated with BSN723; Group 5 – Western diet formulated with BSN723T. Mice were measured for weight gain, tissue and organ weights, total serum cholesterol and triglycerides and formation of atherosclerosis.The addition of D-tagatose, either alone or in combination with BSN723, prevented the increase in adipose tissue and weight gain brought on by the Western diet. Both D-tagatose and BSN723 alone reduced total cholesterol and the formation of atherosclerosis in the aorta compared to mice on the Western diet. Addition of BSN723 to D-tagatose (BSN723T) did not increase efficacy in prevention of increases in cholesterol or atherosclerosis compared to D-tagatose alone. Addition of either D-tagatose or BSN723 alone to a Western diet prevented weight gain, increases in total serum cholesterol and triglycerides, and the formation of atherosclerosis. However, there was no additive or synergistic effect on the measured parameters with the combination BSN723T treatment.
Combined effects of replacement of sucrose with d-tagatose and addition of different probiotic strains on quality characteristics of chocolate milk
Nowadays, tendency to improve human nutrition and consume new healthful foods such as low-calorie and functional ones has been increased. In this study, effects of ratios of sucrose/d-tagatose (100:0, 0:100, or 50:50) as well as type of commercial probiotic strains (Lactobacillus acidophilus LAFTI L10, Lactobacillus casei LAFTI L26, Lactobacillus rhamnosus HN001, and Bifidobacterium animalis subsp. lactis LAFTI B94) on biochemical and microbiological characteristics, percent of residual sugar, color, and sensory attributes of synbiotic chocolate milk were investigated during 21 days of refrigerated storage (5 °C). The treatments inoculated with L. acidophilus, L. casei, L. rhamnosus, and B. lactis showed significantly higher biochemical and color changes compared to non-probiotic ones. The greatest viability at the end of storage was related to the treatment of d-tagatose with L. rhamnosus (T-R) as well as d-tagatose with L. casei (T-C). Although L. acidophilus, L. casei, and L. rhamnosus mostly tended to ferment d-tagatose, B. lactis did not substantially consume the mentioned sugar. In general, the treatments T-R, ST-R (sucrose and d-tagatose with L. rhamnosus), T-B (d-tagatose with B. lactis), and ST-B (sucrose and d-tagatose with B. lactis) were realized as the best ones in terms of probiotic viability, functional property of d-tagatose, and sensory attributes. In conclusion, d-tagatose could be successfully used as a natural sugar substitute with functional properties for probiotic chocolate milks enhancing their health benefits, but the proper selection of ratio of sucrose/d-tagatose and type of probiotic strain is recommended.
Synbiotic impact of tagatose on viability of Lactobacillus rhamnosus strain GG mediated by the phosphotransferase system (PTS)
Synbiotics, the combination of prebiotics and probiotics, has been shown to produce synergistic effects that promote gastrointestinal well-being of host. Tagatose is a low calorie food ingredient with putative health-promoting benefits. Herein, we investigated its synbiotic impact on the viability of Lactobacillus casei 01 and Lactobacillus rhamnosus strain GG and the potential mechanism involved. Tagatose, as a synbiotic substrate, enhanced the growth of L. casei 01 and L. rhamnosus strain GG compared to other prebiotics. Other gut-indigenous such as Clostridium spp. readily utilized fructooligosaccharide (FOS), the most widely used functional prebiotics, but not tagatose. Additionally, tagatose enhanced probiotic functions of L. casei 01 and L. rhamnosus strain GG by reinforcing their attachment on HT-29 intestine epithelial cells and enhancing their cholesterol-lowering activities. Whole transcriptome study and quantitative real-time polymerase chain reaction (qRT-PCR) test showed that the presence of tagatose in L. rhamnosus strain GG caused induction of a large number of genes associated with carbohydrate metabolism including the phosphotransferase system (PTS). Collectively, these results indicate the tagatose enhanced the growth of L. casei 01 and L. rhamnosus strain GG and their probiotic activities by activating tagatose-associated PTS networks. Importantly, this study highlights the potential application of tagatose and L. casei 01 and/or L. rhamnosus strain GG as a synbiotic partner in functional dairy foods (i.e. yogurt and cheese) and therapeutic dietary supplements.
Disposition of D-[U-14C]tagatose in the rat
The purpose of this experiment was to determine the disposition of D-tagatose, under development as a low-calorie sweetener, in conventional and germ-free male rats. One group of conventional rats was fed a diet containing D-tagatose (100 g/kg) mixed with the nonpurified diet (900 g/kg) for 28 days. Then, [U-14C]-labeled D-tagatose was administered as a single dose (approximately 220-380 kBq) to 4 of these adapted rats, as well as to 15 conventional and germ-free rats with no prior exposure (i.e., unadapted) to D-tagatose. Eleven of the 19 dosed animals (4 adapted conventional, 3 unadapted conventional and 2 unadapted germ-free, all dosed orally, plus 2 unadapted conventional dosed intravenously) were placed in metabolism chambers and samples of CO2, urine, and feces taken at regular intervals. At termination, a complete material balance was obtained based on the recovery of 14C. Over the 6-h digestive period, D-tagatose was metabolized to release 39.9 and 13.9% of the oral dose as CO2 in the adapted conventional rats and in the unadapted germ-free rats, respectively. Total releases approximated 68 and 22%, respectively. The difference in CO2 evolution is ascribed to microbial fermentation of D-tagatose in the gut of the conventional rats. The role of adaptation was confirmed by finding 93% less D-tagatose in the feces of the adapted conventional rat than in the feces of the unadapted conventional rat. The intestinal absorption of D-tagatose in the rat is estimated to be 20%. The results demonstrate that D-tagatose is metabolized primarily by microorganisms in the gut of the rat, with an upper limit between 15 and 20% of oral dose metabolized by the host.
Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study
The ketohexose D-tagatose is a new sweetener with a low energy content. This low energy content may be due to either low absorption of the D-tagatose or decreased absorption of other nutrients.The aims of this study were to measure the excretion of D-tagatose from the human small bowel, to calculate the apparent absorption of D-tagatose, and to study the effects of D-tagatose on the small-bowel excretion of other carbohydrates.A controlled diet was served for 2 periods of 2 d during 3 consecutive weeks to 6 ileostomy subjects. In one of the periods, 15 g D-tagatose was added to the diet daily. Duplicate portions of the diet and ileostomy effluents were freeze-dried and analyzed to calculate the apparent net absorption of D-tagatose and carbohydrates.Median D-tagatose excretion was 19% (range: 12-31%), which corresponded to a calculated apparent absorption of 81% (69-88%). Of the total amount of D-tagatose excreted [2.8 g (1.7-4.4 g)], 60% (8-88%) was excreted within 3 h. Between 3 and 5 h, 32% (11-82%) was excreted. Excretion of wet matter increased by 41% (24-52%) with D-tagatose ingestion. Sucrose and D-glucose excretion increased to a small extent, whereas no significant changes were found in the excretion of dry matter, energy, starch, or D-fructose.The apparent absorption of 15 g D-tagatose/d was 81%. D-Tagatose had only a minor influence on the apparent absorption of other nutrients.
Glycogen synthase activation by sugars in isolated hepatocytes
We have investigated the activation by sugars of glycogen synthase in relation to (i) phosphorylase a activity and (ii) changes in the intracellular concentration of glucose 6-phosphate and adenine nucleotides. All the sugars tested in this work present the common denominator of activating glycogen synthase. On the other hand, phosphorylase a activity is decreased by mannose and glucose, unchanged by galactose and xylitol, and increased by tagatose, glyceraldehyde, and fructose. Dihydroxyacetone exerts a biphasic effect on phosphorylase. These findings provide additional evidence proving that glycogen synthase can be activated regardless of the levels of phosphorylase a, clearly establishing that a nonsequential mechanism for the activation of glycogen synthase occurs in liver cells. The glycogen synthase activation state is related to the concentrations of glucose 6-phosphate and adenine nucleotides. In this respect, tagatose, glyceraldehyde, and fructose deplete ATP and increase AMP contents, whereas glucose, mannose, galactose, xylitol, and dihydroxyacetone do not alter the concentration of these nucleotides. In addition, all these sugars, except glyceraldehyde, increase the intracellular content of glucose 6-phosphate. The activation of glycogen synthase by sugars is reflected in decreases on both kinetic constants of the enzyme, M0.5 (for glucose 6-phosphate) and S0.5 (for UDP-glucose). We propose that hepatocyte glycogen synthase is activated by monosaccharides by a mechanism triggered by changes in glucose 6-phosphate and adenine nucleotide concentrations which have been described to modify glycogen synthase phosphatase activity. This mechanism represents a metabolite control of the sugar-induced activation of hepatocyte glycogen synthase.
Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice
Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr(-/-)) mice. LDLr(-/-) male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.
Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans
Macronutrient “preloads” can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia.
Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study
The present study determined the effect of tagatose supplementation on postprandial hyperglycemia in normal (n = 54) and hyperglycemic subjects [n = 40, impaired fasting glucose (IFG) and newly diagnosed type 2 diabetes]. In a double-blind crossover designed study, study subjects were randomly assigned to consume a sucralose-erythritol drink (the placebo) or a tagatose-containing drink (the test) with a seven-day interval. Finally, 85 subjects completed the study (normal, n = 52; hyperglycemic, n = 33). Blood samples were collected at 0, 30, 60 and 120 min after ingestion and analyzed for fasting and postprandial levels of glucose, insulin and C-peptide. Basic anthropometric parameters and lipid files were also measured. Hyperglycemic subjects were basically older and heavier, and showed higher levels of triglyceride, total- and LDL-cholesterols and apolipoprotein AI and B compared with normal subjects. After consuming the tagatose (5 g)-containing drink, hyperglycemic subjects had a significant reduction in serum levels of glucose at 120 min (p = 0.019) and glucose area under the curve (AUC) (p = 0.017), however these were not observed in normal subjects. When ages were matched between the two groups, the glucose response patterns were shown to be similar. Additionally, normal subjects who received a high-dose of tagatose-containing drinks (10 g) showed significantly lower levels of insulin at 30 min (p = 0.004) and 60 min (p = 0.011), insulin AUC (p = 0.009), and C-peptide at 30 min (p = 0.004), 60 min (p = 0.011) and C-peptide AUC (p = 0.023). In conclusion, a single dietary supplement in the form of a tagatose-containing drink may be beneficial for controlling postprandial glycemic response in Koreans.
D-tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes
D-Tagatose (D-tag), a hexose bulk sweetener, does not affect plasma glucose levels when orally administered to rodents. Additionally, D-tag attenuates the rise in plasma glucose after mice are administered oral sucrose. The current study was undertaken to investigate the acute glycaemic effects of oral D-tag alone or in combination with oral glucose in human subjects with and without type 2 diabetes mellitus. Glycaemic responses to D-tag also were investigated in subjects after oral sucrose to examine whether the glucose-lowering effects of D-tag in rodents may result from a direct inhibition of intestinal disaccharidases.
Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans
D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics.
Reduced Susceptibility to Sugar-Induced Metabolic Derangements and Impairments of Myocardial Redox Signalling in Mice Chronically Fed with D-Tagatose when Compared to Fructose
D-tagatose is an isomer of fructose and is ~90% as sweet as sucrose with less caloric value. Nowadays, D-tagatose is used as a nutritive or low-calorie sweetener. Despite clinical findings suggesting that D-tagatose could be beneficial in subjects with type 2 diabetes, there are no experimental data comparing D-tagatose with fructose, in terms of metabolic derangements and related molecular mechanisms evoked by chronic exposure to these two monosaccharides.C57Bl/6j mice were fed with a control diet plus water (CD), a control diet plus 30% fructose syrup (L-Fr), a 30% fructose solid diet plus water (S-Fr), a control diet plus 30% D-tagatose syrup (L-Tg), or a 30% D-tagatose solid diet plus water (S-Tg), during 24 weeks.Both solid and liquid fructose feeding led to increased body weight, abnormal systemic glucose homeostasis, and an altered lipid profile. These effects were associated with vigorous increase in oxidative markers. None of these metabolic abnormalities were detected when mice were fed with both the solid and liquid D-tagatose diets, either at the systemic or at the local level. Interestingly, both fructose formulations led to significant Advanced Glycation End Products (AGEs) accumulation in mouse hearts, as well as a robust increase in both myocardial AGE receptor (RAGE) expression and NF-κB activation. In contrast, no toxicological effects were shown in hearts of mice chronically exposed to liquid or solid D-tagatose.Our results clearly suggest that chronic overconsumption of D-tagatose in both formulations, liquid or solid, does not exert the same deleterious metabolic derangements evoked by fructose administration, due to differences in carbohydrate interference with selective proinflammatory and oxidative stress cascades.
D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration
D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.
D-Tagatose, a stereoisomer of D-fructose, increases hydrogen production in humans without affecting 24-hour energy expenditure or respiratory exchange ratio
In growth studies on rats, the ketohexose D-tagatose has been shown to contribute no net metabolizable energy, and a pronounced thermic effect of the sugar has been suggested to account for the absence of energy. In a double-blind and balanced cross-over design, we measured 24-h energy expenditure in eight normal weight humans in a respiration chamber during the consumption of 30 g D-tagatose or 30 g sucrose/d. Metabolic measurements were performed before and after a 2-wk adaptation period with a 30-g daily intake of the test sugar. Total 24-h energy expenditure and hour-by-hour profile were unaffected by the test sugar. The nonprotein respiratory exchange ratio (RERnp) was similar during consumption of D-tagatose and sucrose. However, the effect on RERnp due to CO2 produced by fermentation of D-tagatose could not be quantified in this study. A significant increase in 24-h H2 production (35%) during D-tagatose administration suggests a substantial malabsorption of the sugar. We found no effects of the 2-wk adaptation period on the measured gas exchange variables. Significantly lower fasting plasma insulin and triglyceride concentrations were observed during D-tagatose administration compared with the sucrose period. No effects of D-tagatose on body weight and composition were seen, but the perception of fullness 2.5 h after the sugar load was greater with D-tagatose. In conclusion, this study does not suggest a pronounced thermic effect of D-tagatose, and other mechanisms seem to be required to explain its lack of net energy.
Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers
Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3×15 g daily) and placebo (sucrose, 3×15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid.
The Role of the Pentose Phosphate Pathway in Diabetes and Cancer
T2DM is a chronic metabolic disease featured by persistently abnormal hyperglycemia, which can cause serious chronic damage to kidneys, eyes, and nerves. Deregulated insulin secretion and progressive insulin resistance are two main characteristics of T2DM (6). Over the past few decades, studies on the pathogenesis of T2DM have revealed a close relationship between the PPP, obesity-related insulin resistance and T2DM. In this part, we will mainly focus on the role of the PPP in obesity-related insulin resistance, insulin secretion and chronic diabetic complications.
Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes
In people with T2DM, exogenous insulin therapy was associated with an increased risk of diabetes-related complications, cancer, and all-cause mortality. Differences in baseline characteristics between treatment groups should be considered when interpreting these results.
Insulin use and increased risk of mortality in type 2 diabetes: a cohort study
We observed a significant and graded association between mortality risk and insulin exposure level in an inception cohort of patients with type 2 diabetes that persisted despite multivariable adjustment.
Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity
Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis, and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function and provides a novel therapeutic strategy for MAFLD prevention and treatment.
Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults
This study investigated metabolomic markers associated with the development of central adiposity in young adults. Participants with incident central adiposity gain had higher levels of blood erythritol compared to those with stable adiposity. Participants with higher baseline hemoglobin A1c (HbA1c) levels also had significantly higher blood erythritol. Erythritol was found to be synthesized from glucose through the pentose-phosphate pathway, suggesting its potential role in the association between erythritol and obesity in young adults.
Letter Regarding Article, “Metabolomic Pattern Predicts Incident Coronary Heart Disease”
This article discusses the use of erythritol, a metabolite, as a predictive marker for coronary heart disease. Erythritol is a naturally occurring noncaloric sweetener and not an artificial sweetener. The presence of erythritol in blood samples cannot be explained by its consumption as a sugar replacement. Studies have shown an association between erythritol levels and impaired glycemic control and central adiposity. The conversion of glucose to erythritol via the pentose-phosphate pathway may play a role in reflecting impaired glycemic control and its related complications. Further research is needed to fully understand the connection between erythritol concentrations and these health conditions.
Diabetes UK
Sucrose Intake Elevates Erythritol in Plasma and Urine in Male Mice
This study investigated the impact of diet and genetic factors on erythritol levels in mice, a biomarker linked to diabetes and cardiovascular issues. Researchers fed mice different diets (low-fat or high-fat) and provided them with either plain water or sucrose water. They measured erythritol concentrations in blood, urine, and tissues. The study found that dietary sucrose significantly increased erythritol levels, regardless of the mice’s diet. The presence or absence of certain enzymes (SORD and ADH1) did not significantly influence plasma erythritol levels, but mice lacking the SORD enzyme had lower kidney erythritol content when fed sucrose.
Effect of chronic exposure to ketohexoses on pancreatic β-cell function in INS-1 rat insulinoma cells
This study examines the impact of various rare sugars on pancreatic β-cells, specifically in the context of type 2 diabetes, where chronic high blood sugar can harm these cells. The research focused on whether long-term exposure to ketohexoses—such as d-allulose, d-fructose, d-tagatose, l-allulose, l-sorbose, and l-fructose—causes damage, suppresses insulin gene expression, or induces apoptosis in INS-1 rat pancreatic insulinoma cells. The findings showed that d-fructose, d-tagatose, l-allulose, and l-sorbose reduced insulin gene expression, while d-allulose, d-sorbose, l-fructose, and l-tagatose did not. None of the sugars caused cell apoptosis or altered glucose metabolism, indicating that long-term use of d-allulose, d-sorbose, l-fructose, and l-tagatose is unlikely to negatively impact pancreatic β-cell function.
A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control
This study explores the benefits of three natural, low-glycemic sugars—isomaltulose, D-tagatose, and trehalose—in managing diabetes. These sugars, which are not produced by the human body but are commonly used in food products, help regulate blood sugar levels and improve insulin response, aiding in better control of hyperglycemia in diabetic patients. The review compares these sugars with other sweeteners and emphasizes their potential in both pharmaceutical and food industries for improving the health of people with diabetes.
Mammalian metabolism of erythritol: a predictive biomarker of metabolic dysfunction
This study investigated the impact of diet and genetic factors on erythritol levels in mice, a biomarker linked to diabetes and cardiovascular issues. Researchers fed mice different diets (low-fat or high-fat) and provided them with either plain water or sucrose water. They measured erythritol concentrations in blood, urine, and tissues. The study found that dietary sucrose significantly increased erythritol levels, regardless of the mice’s diet. The presence or absence of certain enzymes (SORD and ADH1) did not significantly influence plasma erythritol levels, but mice lacking the SORD enzyme had lower kidney erythritol content when fed sucrose.
D-Tagatose Is a Promising Sweetener to Control Glycaemia: A New Functional Food
Studies have shown that tagatose has low glycemic index, a potent hypoglycemic effect, and eventually could be associated with important benefits for the treatment of obesity. The authors concluded that D-tag is promising as a sweetener without major adverse effects observed in these clinical studies.”
Tagatose: from a sweetener to a new diabetic medication?
This study tested the dietary effect of the consumption of tagatose in type 2 diabetes and its ability to be a functional food for diabetics.
Effect of Oral Nutritional Supplements with Sucromalt and Isomaltulose versus Standard Formula on Glycaemic Index, Entero-Insular Axis Peptides and Subjective Appetite in Patients with Type 2 Diabetes: A Randomised Cross-Over Study
This study looked at how special oral nutritional supplements for people with type 2 diabetes (ONS-D) affect their blood sugar levels, insulin levels, hormones related to digestion (GIP and GLP-1), and subjective appetite. The ONS-D supplements had a lower impact on blood sugar levels compared to a standard formula, and they also resulted in lower insulin and GIP levels. However, the ONS-D supplements increased the levels of GLP-1, which is beneficial for diabetes management. People who consumed the ONS-D felt less hungry compared to those who had the standard formula. These findings suggest that the ONS-D supplements can help control blood sugar levels and appetite in individuals with type 2 diabetes.
Short-term replacement of starch with isomaltulose enhances both insulin-dependent and -independent glucose uptake in rat skeletal muscle
This study investigated the impact of replacing high-glycemic index carbohydrates with a low-glycemic index disaccharide called isomaltulose on insulin action in skeletal muscle. Male rats were fed isomaltulose for 12 hours, and the results showed that isomaltulose increased insulin-induced glucose uptake in muscle tissue compared to starch. This effect was not influenced by changes in visceral fat mass. Additionally, isomaltulose treatment enhanced glucose uptake in response to exercise and increased AMP-activated protein kinase phosphorylation. These findings suggest that temporarily replacing starch with isomaltulose, along with exercise, may be a promising approach for managing insulin resistance.
Low Glycemic Index Prototype Isomaltulose-Update of Clinical Trials
Low glycemic index diets are considered beneficial for blood glucose control in diabetes and overall metabolic health. Isomaltulose, a natural disaccharide derived from sucrose, is a prototype of low-glycemic index carbohydrates. It is widely used in various food applications and clinical nutrition feeds. This overview examines clinical trials on isomaltulose, including its impact on glycemia, fat oxidation, weight-loss maintenance, and pregnancy. The findings suggest potential advantages of isomaltulose compared to high glycemic index sugars and carbohydrates in these contexts.
Prevalence of auto-antibodies against D-ribose-glycated-hemoglobin in diabetes mellitus
High blood sugar levels lead to the formation of advanced glycation end products (AGEs), which contribute to the progression of diabetes. In a study, structural changes in hemoglobin (Hb) caused by D-ribose were observed, potentially triggering an autoimmune response in diabetic patients. Autoantibodies against D-ribose glycated-Hb were found to be prevalent in diabetic patients’ blood, indicating their potential as biomarkers for diabetes progression.
Ramadan and Diabetes: A Narrative Review and Practice Update
This review explores the impact of fasting during the Islamic month of Ramadan on patients with diabetes mellitus. It provides recommendations for managing diabetes during Ramadan, emphasizing the importance of pre-Ramadan assessments to ensure a safe fasting experience. The review acknowledges the personal choice to fast but advises against fasting for patients assessed to be at high or very high risk, especially considering the additional risk posed by the COVID-19 pandemic. Advanced insulin delivery and glucose monitoring technologies are highlighted as helpful tools for supporting high-risk patients. While formal trial data is limited, there is sufficient evidence on the safety and efficacy of various hypoglycemic agents to guide treatment decisions. Overall, Ramadan presents an opportunity for patient engagement and improved diabetes management.
Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels
Diabetes mellitus is a prevalent metabolic disorder, and flavonoids, natural compounds found in fruits and vegetables, have shown potential in managing diabetes. This review summarizes the current understanding of how dietary flavonoids affect glucose metabolism, hepatic enzymes, and lipid profiles, offering insights into their anti-diabetic effects. Further research is needed to clarify the mechanisms of action and potential side effects of flavonoids for diabetes treatment.
Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose
This study investigated the association between glycated hemoglobin (HbA1c) and carotid atherosclerosis in an elderly Korean population with normal fasting glucose. The analysis of 1,133 participants revealed that higher HbA1c levels were independently associated with increased carotid intima-media thickness (IMT), indicating carotid atherosclerosis. This association remained significant after adjusting for various factors. However, fasting insulin and glucose levels did not show a significant association with carotid IMT. These findings suggest that HbA1c may serve as an informative marker for carotid atherosclerosis in elderly individuals with normoglycemia.
Effects of Three Low-Doses of D-Tagatose on Glycemic Control Over Six Months in Subjects with Mild Type 2 Diabetes Mellitus Under Control with Diet and Exercise
This study examined the safety and effectiveness of D-tagatose in individuals with type 2 diabetes. Participants received different doses of D-tagatose for six months. The 7.5 g dose showed the greatest success in reducing HbA1c levels, while the 5.0 g dose was the minimum effective dose. D-tagatose was well tolerated, and higher doses resulted in greater improvements in various measures.
Safety and Efficacy of D-Tagatose in Glycemic Control in Subjects with Type 2 Diabetes
This study aimed to assess the effects of D-tagatose on glycemic control and safety in individuals with type 2 diabetes. Participants received either D-tagatose or a placebo. D-tagatose significantly reduced HbA1c levels compared to placebo and also showed positive effects on fasting blood glucose, LDL cholesterol, total cholesterol, and the proportion of subjects achieving HbA1c targets. However, D-tagatose did not affect triglyceride levels or HDL cholesterol. Overall, D-tagatose was effective in treating various therapy targets of type 2 diabetes.
Dietary supplementation with d-tagatose in subjects with type 2 diabetes leads to weight loss and raises high-density lipoprotein cholesterol
This pilot study investigated the effects of oral d-tagatose on individuals with type 2 diabetes. Participants took 15 g of d-tagatose three times daily for 1 year. No serious adverse effects were observed, although some experienced mild and transient gastrointestinal side effects. After excluding subjects who had changes in diabetes medications, body weight decreased significantly, and there was a non-significant reduction in glycated hemoglobin levels. Among participants not on lipid-modifying medications, high-density lipoprotein cholesterol levels increased significantly. These findings suggest that d-tagatose may have potential as an adjunct in the management of type 2 diabetes.
Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers
Researchers conducted a study to see if consuming 3.3 g of trehalose daily improves glucose tolerance in healthy Japanese individuals. They compared it to a group consuming sucrose. After 12 weeks, the trehalose group had lower fasting and post-meal blood glucose levels compared to the sucrose group. This suggests that even a small amount of trehalose could help lower post-meal blood sugar in healthy individuals.
Childhood neurodevelopmental disorders and maternal diabetes: A population-based cohort study
A retrospective cohort study in Taiwan examined the risk of neurodevelopmental disorders (NDDs) in children born to mothers with different types of diabetes. The study found that offspring of mothers with type 1 diabetes had the highest risk of NDDs, followed by type 2 diabetes and gestational diabetes. Specific disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, developmental delay, intellectual disability, cerebral palsy, and epilepsy/infantile spasms were associated with maternal diabetes. This study highlights the importance of understanding the potential risks of different types of diabetes on neurodevelopment in offspring.
Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies
This umbrella review analyzed the available evidence from meta-analyses of prospective observational studies to evaluate the associations between prediabetes and the incidence of diabetes-related complications in adults. The review found that prediabetes was associated with an increased risk of all-cause mortality, cardiovascular outcomes, coronary heart disease, stroke, chronic kidney disease, certain cancers, and dementia. However, no associations were observed with incident depressive symptoms and cognitive impairment. The certainty of evidence varied across the outcomes. The review highlights the need for further high-quality studies, especially focusing on HbA1c-defined prediabetes and other relevant health outcomes, to strengthen the evidence in this area.
Ketogenic diet – a literature review
The ketogenic diet has gained attention for its potential benefits in various health conditions. It has been found to aid in weight reduction, improve lipid profile, and potentially reduce the need for antidiabetic drugs and insulin therapy in type 2 diabetes. Animal studies suggest positive effects in cancer treatment, although human studies are limited. Additionally, there are reports of the ketogenic diet delaying the onset of dementia symptoms. However, the long-term impact on cardiovascular risk is still unknown, emphasizing the need for careful consideration before adopting the diet.
Significant Systemic Insulin Resistance is Associated With Unique Glioblastoma Multiforme Phenotype
This study investigated the relationship between insulin resistance and a specific type of brain cancer called glioblastoma multiforme (GBM), which is characterized by the presence of gemistocytes (GCs). These GCs are typically associated with reactive astrocytes, a type of brain cell. The study aimed to find a connection between insulin resistance and the presence of GCs in newly diagnosed GBM patients.
The researchers looked at medical records of 220 patients with newly diagnosed GBM. Among these patients, 26.3% had a history of type 2 diabetes at the time of diagnosis. They found that in the group of GBM patients with GCs, poorly-controlled diabetes was more common compared to the group without GCs. Specifically, there was a higher prevalence of poorly-controlled diabetes in the GC-GBM group (18.75%) compared to the non-GC GBM group (9.5%). In the subset of diabetic patients, those with GC-GBM were more likely to exhibit characteristics of insulin resistance, such as being male, morbidly obese, and not using synthetic insulin before diagnosis.
In conclusion, this study suggests that systemic metabolic factors related to insulin resistance, including type 2 diabetes, morbid obesity, and male gender, are associated with a distinct histological subtype of GBM characterized by the presence of GCs. This association is particularly significant in poorly-controlled type 2 diabetes GBM patients who do not use synthetic insulin. The findings highlight the potential relevance of glucose metabolism in astrocytes and its connection to high-grade brain tumors. Further research is needed to explore how patients’ metabolic status, tumor characteristics, molecular changes, and use of anti-diabetic drugs impact survival in GBM patients.
Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
This study explores the link between pancreatic cancer, obesity, type 2 diabetes, and high levels of insulin in the blood (hyperinsulinemia). It is known that high insulin production is an independent risk factor for cancer, including pancreatic cancer. Previous research showed that reducing insulin production could suppress the development of pre-cancerous pancreatic lesions (PanIN) in mice with a specific genetic mutation (Kras). However, the precise mechanisms behind this connection and whether hyperinsulinemia directly affects PanIN precursor cells were unclear.
The study found that insulin receptors (Insr) in pancreatic acinar cells expressing the KrasG12D mutation were not essential for regulating glucose levels but were crucial for the formation of PanIN lesions in the presence of diet-induced hyperinsulinemia and obesity. The mechanism behind this involved an increase in the translation of digestive enzyme proteins, which led to local inflammation and the development of PanIN lesions in vivo. In laboratory experiments, insulin was shown to promote the transformation of acinar cells into ductal cells (acinar-to-ductal metaplasia) in a manner dependent on trypsin and insulin receptors.
In summary, this study sheds light on how obesity-driven hyperinsulinemia is connected to the development of pancreatic cancer. It shows that insulin receptors in pancreatic cells are not required for regulating blood sugar but play a crucial role in the formation of pre-cancerous pancreatic lesions under conditions of obesity and high insulin levels. The study provides insights into the mechanisms underlying the link between hyperinsulinemia and the development of pancreatic cancer.
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