Low glycemic index diets are supposed to achieve a more beneficial effect on blood glucose control in people with diabetes mellitus and may also provide metabolic benefits for the general population. A prototype of a low-glycemic index carbohydrate is the natural occurring disaccharide isomaltulose that can be commercially produced from sucrose (beet sugar) to industrial scale. It is currently used in various food and drink applications as well as special and clinical nutrition feeds and formula diet as a food ingredient and alternative sugar. Here we provide an overview on clinical trials with isomaltulose including an analysis of its effects on glycemia and fat oxidation as compared to high glycemic index sugars and carbohydrates. In addition, we discuss recent reports on beneficial effects in weight-loss maintenance and pregnancy.

Lipotoxicity is a major contributor to type 2 diabetes mainly promoting mitochondrial dysfunction. Lipotoxic stress is mediated by elevated levels of free fatty acids through various mechanisms and pathways. Impaired peroxisome proliferator-activated receptor (PPAR) signaling, enhanced oxidative stress levels, and uncoupling of the respiratory chain result in ATP deficiency, while β-cell viability can be severely impaired by lipotoxic modulation of PI3K/Akt and mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) pathways. However, fatty acids are physiologically required for an unimpaired β-cell function. Thus, preparation, concentration, and treatment duration determine whether the outcome is beneficial or detrimental when fatty acids are employed in experimental setups. Further, ageing is a crucial contributor to β-cell decay. Cellular senescence is connected to loss of function in β-cells and can further be promoted by lipotoxicity. The potential benefit of nutrients has been broadly investigated, and particularly polyphenols were shown to be protective against both lipotoxicity and cellular senescence, maintaining the physiology of β-cells. Positive effects on blood glucose regulation, mitigation of oxidative stress by radical scavenging properties or regulation of antioxidative enzymes, and modulation of apoptotic factors were reported. This review summarizes the significance of lipotoxicity and cellular senescence for mitochondrial dysfunction in the pancreatic β-cell and outlines potential beneficial effects of plant-based nutrients by the example of polyphenols.

Free fatty acids are essentially involved in the pathogenesis of chronic diseases such as diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease. They promote mitochondrial dysfunction, oxidative stress, respiratory chain uncoupling, and endoplasmic reticulum stress and modulate stress-sensitive pathways. These detrimental biological effects summarized as lipotoxicity mainly depend on fatty acid carbon chain length, degree of unsaturation, concentration, and treatment time. Preparation of fatty acid solutions involves dissolving and complexing. Solvent toxicity and concentration, amount of bovine serum albumin (BSA), and ratio of albumin to fatty acids can vary significantly between equal concentrations, mediating considerable harmful effects and/or interference with certain assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Herein, we studied the impact of commonly used solvents ethanol and dimethyl sulfoxide and varying concentrations of BSA directly and in solution with oleic acid on MTT to formazan conversion, adenosine triphosphate level, and insulin content and secretion of murine β-cell line MIN6 employing different treatment duration. Our data show that experimental outcomes and assay readouts can be significantly affected by mere preparation of fatty acid solutions and should thus be carefully considered and described in detail to ensure comparability and distinct evaluation of data.

The failure of insulin-producing β-cells is the underlying cause of hyperglycemia in diabetes mellitus. β-cell decay has been linked to hypoxia, chronic inflammation, and oxidative stress. Thioredoxin (Trx) proteins are major actors in redox signaling and essential for signal transduction and the cellular stress response. We have analyzed the cytosolic, mitochondrial, and extracellular Trx system proteins in hypoxic and cytokine-induced stress using β-cell culture, isolated pancreatic islets, and pancreatic islet transplantation modelling low oxygen supply. Protein levels of cytosolic Trx1 and Trx reductase (TrxR) 1 significantly decreased, while mitochondrial Trx2 and TrxR2 increased upon hypoxia and reoxygenation. Interestingly, Trx1 was secreted by β-cells during hypoxia. Moreover, murine and human pancreatic islet grafts released Trx1 upon glucose stimulation. Survival of transplanted islets was substantially impaired by the TrxR inhibitor auranofin. Since a release was prominent upon hypoxia, putative paracrine effects of Trx1 on β-cells were examined. In fact, exogenously added recombinant hTrx1 mitigated apoptosis and preserved glucose sensitivity in pancreatic islets subjected to hypoxia and inflammatory stimuli, dependent on its redox activity. Human subjects were studied, demonstrating a transient increase in extracellular Trx1 in serum after glucose challenge. This increase correlated with better pancreatic islet function. Moreover, hTrx1 inhibited the migration of primary murine macrophages. In conclusion, our study offers evidence for paracrine functions of extracellular Trx1 that improve the survival and function of pancreatic β-cells.

Background: Diabetes technology is a fundamental part of modern diabetes therapy. Its widespread usage is associated with an increasing amount of “diabetes technology waste.” The aim of this study was to quantify this waste in a real-world situation in a specialized diabetes practice in Germany. Methods: Eighty patients with diabetes and insulin treatment participated and collected all of their therapy-associated waste for three months. Their attitude toward sustainability of antidiabetic therapy, waste generation, and their own waste reduction/separation behavior was surveyed. Results: In total, 23 707 pieces of therapy-associated waste were collected. They comprised 5362 test strips, 630 glucose sensors, 14 619 needles, 519 insulin cartridges, 599 pens, and 1463 pieces of aids for insulin pump therapy. Type and quantity of the collected waste depended on the type of diabetes and the respective therapy, ie, multiple daily injections, usage of glucose sensors, or pump therapy. Most participants (92%) were surprised by the amounts of waste and reported an increased awareness toward the resource consumption of their therapy (87%). The survey indicated an enhanced interest in waste separation (94%) and a demand for the reduction and recycling of devices/aids (93%). Conclusions: Our data revealed the amount and complexity of the waste generated by modern diabetes therapy. Extrapolating these data, it can be estimated that around 1.2 billion pieces of diabetes technology waste are generated in Germany per year. The major concern of the study participants was the limited number of recycling options. A clear demand for improved sustainability of the medical products was expressed.

Histomorphological and functional alterations in pancreatic islet composition directly correlate with hyperglycemia severity. Progressive deterioration of metabolic control in subjects suffering from type 2 diabetes is predominantly caused by impaired beta-cell functionality. The glutaredoxin system is supposed to wield protective properties for beta-cells. Therefore, we sought to identify a correlation between the structural changes observed in diabetic pancreatic islets with altered glutaredoxin 5 expression, in order to determine an underlying mechanism of beta-cell impairment. Islets of db/db mice presenting with uncontrolled diabetes were assessed in terms of morphological structure and insulin, glucagon, and glutaredoxin 5 expression. MIN6 cell function and glutaredoxin 5 expression were analyzed after exposure to oleic acid and hypoxia. Islets of diabese mice were marked by typical remodeling and distinct reduction of, and shifts, in localization of glutaredoxin 5-positive cells. These islets featured decreased glutaredoxin 5 as well as insulin and glucagon content. In beta-cell culture, glutaredoxin 5 protein and mRNA expression were decreased by hypoxia and oleic acid but not by leptin treatment. Our study demonstrates that glutaredoxin 5 expression patterns are distinctively altered in islets of rodents presenting with uncontrolled diabesity. In vitro, reduction of islet-cell glutaredoxin 5 expression was mediated by hypoxia and oleic acid. Thus, glutaredoxin 5-deficiency in islets during diabetes may be caused by lipotoxicity and hypoxia.