Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood sugar levels (hyperglycemia). Poorly managed diabetes can lead to complications affecting multiple organ systems. Antioxidants play a crucial role in reducing oxidative stress caused by reactive oxygen species (ROS), primarily triggered by uncontrolled high blood sugar levels in diabetes. Antioxidants like vitamin C, E, selenium, and alpha-lipoic acid, when used as supplements, have shown promise in reducing oxidative stress markers and improving antioxidant status in laboratory and animal studies and diabetic patients. Antioxidant supplementation may help reduce the risk of diabetic complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Additionally, antioxidants also have anti-inflammatory properties, which could be beneficial in reducing inflammation associated with diabetes. Antioxidant supplementation has been shown to enhance endothelial function, insulin sensitivity, and glucose metabolism, thereby aiding in glycemic control and overall diabetic management. Combining antioxidants with certain medications may have therapeutic benefits, such as effectively neutralizing free radicals and enhancing the regulation of antioxidant defense systems. This review presents an update on diabetes, the sources of free radical generation, the body's natural defense mechanisms, the clinical evidence regarding using antioxidants in managing diabetic complications, and the potential new therapeutic approaches. Overall, antioxidant supplementation may offer some benefits in managing diabetic complications. However, further studies are needed to understand the mechanisms of action, determine the optimal supplementation, explore potential interactions with other medications, and conduct long-term studies to establish the possible use of antioxidants for optimal benefits in diabetes care.

Inositol, or myo-inositol, and associated analog molecules, including myo-inositol hexakisphosphate, are known to possess beneficial biomedical properties and are now being widely studied. The impact of these compounds in improving diabetic indices is significant, especially in light of the high cost of treating diabetes mellitus and associated disorders globally. It is theorized that, within ten years, the global population of people with the disease will reach 578 million individuals, with the cost of care projected to be approximately 2.5 trillion dollars. Natural alternatives to pharmaceuticals are being sought, and this has led to studies involving inositol, and myo-inositol-hexakisphosphate, also referred to as IP6. It has been reported that IP6 can improve diabetic indices and regulate the activities of some metabolic enzymes involved in lipid and carbohydrate metabolism. Current research activities have been focusing on the mechanisms of action of inositol and IP6 in the amelioration of the indices of diabetes mellitus. We demonstrated that an IP6 and inositol combination supplement may regulate insulin secretion, modulate serum leptin concentrations, food intake, and associated weight gain, which may be beneficial in both prediabetic and diabetic states. The supplement attenuates vascular damage by reducing red cell distribution width. Serum HDL is increased while serum triglycerides tend to decrease with consumption of the combination supplement, perhaps due to the modulation of lipogenesis involving reduced serum lipase activity. We also noted increased fecal lipid output following combination supplement consumption. Importantly, liver function was found to be preserved. Concurrently, serum reactive oxygen species production was reduced, indicating that inositol and IP6 supplement consumption may reduce free radical damage to tissues and organs as well as serum lipids and blood glucose by preserving liver function. This review provides an overview of the findings associated with inositol and IP6 supplementation in the effective treatment of diabetes with a view to proposing the potential mechanisms of action.

In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P<0.05) increased by phytic acid supplementation. Systemic IL-1βlevel was significantly (P<0.05) elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation.

IP6 (phytic acid) is a naturally occurring compound in plant seeds and grains. It is a poly-phosphorylated inositol derivative that has been shown to exhibit many biological activities that accrue benefits in health and diseases (cancer, diabetes, renal lithiasis, cardiovascular diseases, etc.). IP6 has been shown to have several cellular and molecular activities associated with its potential role in disease prevention. These activities include anti-oxidant properties, chelation of metal ions, inhibition of inflammation, modulation of cell signaling pathways, and modulation of the activities of enzymes and hormones that are involved in carbohydrate and lipid metabolism. Studies have shown that IP6 has anti-oxidant properties and can scavenge free radicals known to cause cellular damage and contribute to the development of chronic diseases such as cancers and cardiovascular diseases, as well as diabetes mellitus. It has also been shown to possess anti-inflammatory properties that may modulate immune responses geared towards the prevention of inflammatory conditions. Moreover, IP6 exhibits anti-cancer properties through the induction of cell cycle arrest, promoting apoptosis and inhibiting cancer cell growth. Additionally, it has been shown to have anti-mutagenic properties, which reduce the risk of malignancies by preventing DNA damage and mutations. IP6 has also been reported to have a potential role in bone health. It inhibits bone resorption and promotes bone formation, which may help in the prevention of bone diseases such as osteoporosis. Overall, IP6’s cellular and molecular activities make it a promising candidate for disease prevention. As reported in many studies, its anti-inflammatory, anti-oxidant, and anti-cancer properties support its inclusion as a dietary supplement that may protect against the development of chronic diseases. However, further studies are needed to understand the mechanisms of action of this dynamic molecule and its derivatives and determine the optimal doses and appropriate delivery methods for effective therapeutic use.

With healthcare costs rising, many affected by ailments are turning to alternative medicine for treatment. More people are choosing to complement their pharmacological regimen with dietary supplements from natural products. In this study, the compound composition of Kalanchoe Pinnata (K. pinnata) and the effects of combined preparations of K. pinnata and metformin on antioxidant activity in human skeletal muscle myoblasts (HSMMs) and human diabetic skeletal muscle myoblasts (DHSMMs) were investigated. Ultraperformance liquid chromatography fusion orbitrap mass spectrometry (UPLC-OT-FTMS) identified biologically active flavanols in K. pinnata. The main compounds identified in locally grown K. pinnata were quercetin, kaempferol, apigenin, epigallocatechin gallate (EGCG), and avicularin. Antioxidant results indicated that a combinatorial preparation of K. pinnata with metformin may modulate antioxidant responses by increasing the enzymatic activity of superoxide dismutase and increasing levels of reduced glutathione. A combination of 50 μM and 150 μg/mL of metformin and K. pinnata, respectively, resulted in a significant increase in reduced glutathione levels in non-diabetic and diabetic human skeletal muscle myoblasts and H₂O_2-stress-induced human skeletal muscle myoblasts. Additionally, a K. pinnata treatment (400 µg/mL) alone significantly increased catalase (CAT) activity for non-diabetic and diabetic human skeletal muscle myoblasts and a H₂O_2-stress-induced human skeletal muscle myoblast cell line, while significantly lowering malondialdehyde (MDA) levels. However, the treatment options were more effective at promoting cell viability after 24 h versus 72 h and did not promote cell viability after 72 h in H₂O₂-stress-induced HSMM cells. These treatment options show promise for treating oxidative-stress-mediated pathophysiological complications associated with type II diabetes.