Stress induced hyperglycemia is the body's protect response against strong (patho-physiological and/or psychological) stress, sometimes the blood glucose level is too high due to out of the body's adjustment. Renal glucose threshold (about 9 mmol/L) is a window of glucose leak from capillary to interstitial tissue. It is important to keep blood glucose level < 9 mmol/L, for reducing vascular sclerosis as well as organs hypoperfusion, meanwhile pay attention to preventing more dangerous hypoglycemia. Glucose, as the main energy substrate, should be daily supply and its metabolism should be monitored. We used to talk "nutritional support". Support is conform the physiological ability of host, but therapy is to coordinate and change pathophysiology. So, nutritional support is not equal to nutritional therapy. For critical ill patients, we need to emphasize "nutritional therapy", i.e, do not give nutritional treatment without metabolic monitoring, make up for deficiencies and avoid metabolites overloading, rational adjustment to protect and coordinate organs function.
Humans ; Blood Glucose/metabolism* ; Critical Illness/therapy* ; Hyperglycemia/therapy* ; Nutritional Support ; Glucose

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.
Humans ; PPAR gamma/metabolism* ; Curcumin/therapeutic use* ; Phosphatidylinositol 3-Kinases ; Diabetes Mellitus/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Hyperglycemia/drug therapy* ; Glucose

Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
Cardiovascular Diseases ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies/etiology* ; Humans ; Hyperglycemia/metabolism* ; Multicenter Studies as Topic

OBJECTIVE: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis. METHODS: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT_2A receptor (5-HT_2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe. RESULTS: There were up-regulated expressions of 5-HT_2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H₂O₂) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor β1 (TGF-β1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT_2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-β1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT_2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2. CONCLUSION Hyperglycemia-induced myofibroblastization and TGF-β1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT_2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT_2AR is involved in the regulation of 5-HT synthases and MAO-A expression.
Male ; Mice ; Humans ; Animals ; Hepatic Stellate Cells/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Serotonin/metabolism* ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/complications* ; Hydrogen Peroxide/metabolism* ; Mice, Inbred C57BL ; Liver Cirrhosis/etiology* ; Hyperglycemia/pathology* ; Monoamine Oxidase/metabolism* ; Inflammation ; Glucose/metabolism* ; Cytidine Diphosphate/pharmacology*

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
Animals ; Bacteria ; classification ; genetics ; isolation & purification ; metabolism ; Butyrates ; metabolism ; Fatty Liver ; drug therapy ; Fungal Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; genetics ; Hyperglycemia ; drug therapy ; Hyperlipidemias ; drug therapy ; Intestines ; drug effects ; microbiology ; Male ; Metabolic Syndrome ; drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia ; chemistry

High-fat diets affect male reproduction and sexual function. Therefore, we evaluated the effects of prolonged resveratrol administration on the metabolic, sperm, and testicular parameters of rats fed a cafeteria diet. Male Wistar rats were divided at weaning into control (C, n = 20) and cafeteria (CAF, n = 16) groups. At 3 months, half of them were given daily supplementations of resveratrol (C-R, n = 10; CAF-R, n = 8) at a dosage of 30 mg kg^-1 body mass for 2 months. Animals were killed at 5 months of age, and blood, spermatozoa, and testes were collected for further analysis. Data were analyzed by one-way ANOVA, and P < 0.05 was considered statistically significant. The CAF diet promoted hyperglycemia (P < 0.0001), and treatment with resveratrol reversed this condition (P < 0.0001). The CAF diet reduced sperm viability and motility, while resveratrol improved these parameters (P < 0.05). Regarding testicular morphology, the height of the seminiferous epithelium was reduced in the CAF group compared with that of the C group (P = 0.0007). Spermatogenic cell proliferation was also reduced in the CAF group compared with that of the C group. However, the CAF-R showed an increase in cell proliferation rate compared with that of the untreated CAF group (P = 0.0024). Although it did not modify body mass, the consumption of a CAF diet promoted hyperglycemia, adverse testicular morphology remodeling, and abnormal sperm, which were attenuated by treatment with resveratrol, thus suggesting a protective effect of this antioxidant on spermatogenesis.
Animals ; Antioxidants/therapeutic use* ; Blood Glucose ; Cell Proliferation/drug effects* ; Diet, High-Fat ; Hyperglycemia/metabolism* ; Lipids/blood* ; Male ; Rats ; Rats, Wistar ; Resveratrol/therapeutic use* ; Sperm Motility/drug effects* ; Spermatozoa/metabolism* ; Testis/metabolism*

Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms.
Animals ; Bile Acids and Salts ; blood ; metabolism ; Blood Glucose ; drug effects ; metabolism ; Circadian Rhythm ; Diabetes Mellitus ; blood ; drug therapy ; metabolism ; Energy Metabolism ; Homeostasis ; Humans ; Hyperglycemia ; metabolism ; physiopathology ; Hypoglycemic Agents ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; drug effects ; Lipid Metabolism ; Liver ; drug effects ; metabolism ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction

PURPOSE: Metabolic syndrome (MS) is characterized by a collection of interdependent disorders, including abdominal obesity, dyslipidemia, hyperglycemia, hypertension, and diabetes. The current study aimed to estimate the prevalence of MS in Qom, Iran. MATERIALS AND METHODS: A population-based screening program was conducted in the city of Qom, in 845 urban adult men over 25 years old in 2014. Abdominal obesity, fasting blood glucose (FBG), blood pressure, and the serum lipid profile were measured in subjects after fasting for at least 8 hours. MS was defined according to the Adult Treatment Panel III criteria. Data were analyzed using the chi-square test, t-test, and multiple logistic regression. RESULTS: The overall prevalence of MS was 23.0%, and the most common prevalent metabolic abnormalities associated with MS were low high-density lipoprotein cholesterol (< 40 mg/dL) in 34.3% of subjects, a waist circumference >102 cm in 33.9%, blood pressure ≥130/85 mmHg in 27.6%, fasting triglycerides (TG) ≥150 mg/dL in 25%, and FBG ≥110 mg/dL in 20.6%. A FBG level ≥110 mg/dL (odds ratio [OR]=4.85; 95% confidence interval [CI], 2.14~8.24), dyslipidemia (OR=3.51; 95% CI, 2.10~5.89), and a fasting TG ≥150 mg/dL were the most important factors contributing to MS. CONCLUSIONS: The prevalence of MS in men in Qom was higher than has been reported in other countries, but it was lower than the mean values that have been reported elsewhere in Iran. FBG was the most important factor contributing to MS, and all elements of the lipid profile showed important associations with MS.
Adult ; Blood Glucose ; Blood Pressure ; Cholesterol ; Dyslipidemias ; Fasting ; Humans ; Hyperglycemia ; Hyperlipidemias ; Hypertension ; Iran ; Lipid Metabolism Disorders ; Lipoproteins ; Logistic Models ; Male ; Mass Screening ; Obesity, Abdominal ; Prevalence ; Triglycerides ; Waist Circumference

BACKGROUND: Insulin resistance is a major pathogenic hallmark of impaired glucose metabolism. We assessed the accuracy of insulin resistance and cut-off values using homeostasis model assessment of insulin resistance (HOMA-IR) to classify type 2 diabetes mellitus (T2DM) and dysglycemia according to age and sex. METHODS: In this cross-sectional study, we analyzed 4,291 anti-diabetic drug-naïve adults (≥20 years) from the 6th Korea National Health and Nutrition Examination Survey in 2015. Metabolic syndrome (MetS) was defined by the modified National Cholesterol Education Program III guideline. Diagnosis of dysglycemia and T2DM were based on fasting glucose and glycosylated hemoglobin levels. The receiver operating characteristic curve and optimal cut-off values of HOMA-IR were assessed to identify T2DM/dysglycemia according to sex and were further analyzed by age. RESULTS: Sex differences were found in the association of MetS and the different MetS components with T2DM/dysglycemia. The overall optimal cut-off value of HOMA-IR for identifying dysglycemia was 1.6 in both sex. The cut-off values for T2DM were 2.87 in men and 2.36 in women. However, there are differences in diagnostic range of HOMA-IR to distinguish T2DM according to sex and age, and the accuracy of HOMA-IR in identifying T2DM gradually decreased with age especially in women. CONCLUSION: Insulin resistance is closely associated with the risk for T2DM/dysglycemia. The accuracy of HOMA-IR levels is characterized by sex- and age-specific differences in identifying T2DM. In addition to insulin resistance index, insulin secretory function, and different MetS components should be considered in the detection of early T2DM, especially in elderly.
Adult* ; Aged ; Cholesterol ; Cross-Sectional Studies ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diagnosis ; Education ; Fasting ; Female ; Glucose ; Hemoglobin A, Glycosylated ; Homeostasis ; Humans ; Hyperglycemia ; Insulin Resistance* ; Insulin* ; Korea ; Male ; Metabolism ; Nutrition Surveys ; ROC Curve ; Sex Characteristics

BACKGROUND: Bone fractures are high in elderly patients with type 2 diabetes mellitus (T2DM). Hyperglycemia and chronic kidney disease may increase the risk of fracture prevalence via altered bone metabolism, but whether glycemic control and kidney function are associated with the risk of fracture prevalence remains unclear. This study evaluated the relationship between glycemic control and baseline estimated glomerular filtration rate (eGFR) and risk of fracture prevalence in older and middle-aged patients with T2DM. METHODS: Patients who underwent a general medical check-up between 2009 and 2013 were selected from the Korean National Health Insurance Sharing Service records. Chi-square test and multiple logistic regression analysis were used to assess the relationship between glycemic control and eGFR and risk of fracture prevalence. RESULTS: Cumulative fracture prevalence were higher in patients with T2DM, irrespective of whether they had tight or less stringent glycemic control (fasting blood glucose [FBG] ≥ 110 mg/dL). After adjustment for baseline age and FBG, tight and less stringent glycemic control was significantly associated with increased adjusted risk of fracture prevalence in middle-aged patients with T2DM (OR=1.13, 95% CI, 1.05–1.21, p=0.0005 vs OR=1.13, 95% CI, 1.06–1.20, p=0.0001), but not in older patients. Baseline eGFR was not significantly related to fracture prevalence in either older or middle-aged patients. CONCLUSION: Less stringent glycemic control significantly increased the adjusted risk of fracture prevalence in middle-aged patients with T2DM. Further studies are needed to confirm the effect of tight glycemic control on fracture prevalence.
Aged ; Blood Glucose ; Cohort Studies* ; Diabetes Mellitus, Type 2 ; Fractures, Bone ; Glomerular Filtration Rate ; Humans ; Hyperglycemia ; Kidney ; Logistic Models ; Metabolism ; National Health Programs* ; Prevalence* ; Renal Insufficiency, Chronic ; Retrospective Studies*