- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Ketoacidosis is a metabolic state associated with pathologically high serum and urine concentrations of ketone bodies, namely acetone, acetoacetate and beta-hydroxybutyrate. During catabolic states, ...
Ketoacidosis is a metabolic state associated with pathologically high serum and urine concentrations of ketone bodies, namely acetone, acetoacetate and beta-hydroxybutyrate. During catabolic states, fatty acids are metabolized to ketone bodies, which can be readily utilized for fuel by individual cells in the body. Of the three major ketone bodies, acetoacetic acid is the only true ketoacid chemically, while beta-hydroxybutyric acid is a hydroxy acid, and acetone is a true ketone. Figure 1 shows the schematic of ketogenesis where the fatty acids generated after lipolysis in the adipose tissues enter the hepatocytes via the bloodstream and undergo beta-oxidation to form the various ketone bodies. This biochemical cascade is stimulated by the combination of low insulin levels and high glucagon levels (i.e., a low insulin/glucagon ratio). Low insulin levels, most often secondary to absolute or relative hypoglycemia as with fasting, activate hormone-sensitive lipase, which is responsible for the breakdown of triglycerides to free fatty acid and glycerol. The clinically relevant ketoacidoses to be discussed include diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA) and starvation ketoacidosis. DKA is a potentially life-threatening complication of uncontrolled diabetes mellitus if not recognized and treated early. It typically occurs in the setting of hyperglycemia with relative or absolute insulin deficiency. The paucity of insulin causes unopposed lipolysis and oxidation of free fatty acids, resulting in ketone body production and subsequent increased anion gap metabolic acidosis. Alcoholic ketoacidosis occurs in patients with chronic alcohol abuse, liver disease, and acute alcohol ingestion. Starvation ketoacidosis occurs after the body is deprived of glucose as the primary source of energy for a prolonged time and fatty acids replace glucose as the major metabolic fuel.
- High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome. [Journal Article]
- CPCell Physiol Biochem 2018 Dec 06; 51(5):2041-2051
- CONCLUSIONS: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.
- Inhibitory effects of polysaccharide from Diaphragma juglandis fructus on α-amylase and α-d-glucosidase activity, streptozotocin-induced hyperglycemia model, advanced glycation end-products formation, and H2O2-induced oxidative damage. [Journal Article]
- IJInt J Biol Macromol 2018 Dec 03
- In present study, the in vitro and in vivo hemolysis inhibitory, protective effect against reactive oxygen species (ROS) induced oxidative damage in L02 cells, hypoglycemic, and antiglycation activit...
In present study, the in vitro and in vivo hemolysis inhibitory, protective effect against reactive oxygen species (ROS) induced oxidative damage in L02 cells, hypoglycemic, and antiglycation activities of DJP-2, a pure polysaccharide fraction from Diaphragma juglandis fructus, were investigated. Results demonstrated that DJP-2 showed remarkable hemolysis inhibitory activity. Pretreatment with DJP-2 markedly weakened the oxidative damage induced by H2O2 in hepatic L02 cells via strengthening the cell viability. DJP-2 also showed clear in vivo and in vitro hypoglycemic activities. Besides, DJP-2 with the concentration of 3 mg/mL exerted more significant antiglycation activities than aminoguanidine during 30 days of incubation. The results obtained in this study would be beneficial for the application of DJP-2 to treat various diseases related to oxidative stress and AGEs. The elucidation of the potential bioactivities of DJP-2 will facilitate its further study and application in the functional food industry and pharmaceuticals industry.
- Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists. [Journal Article]
- EElife 2018 Dec 06; 7
- Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a ver...
Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a vertebrate 'insulin-free' model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.
- The comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and no weight gain in patients uncontrolled with metformin therapy: results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial. [Journal Article]
- DODiabetes Obes Metab 2018 Dec 05
- CONCLUSIONS: This study provides evidence that compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and no weight gain in T2D patients inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively shorter diabetes duration. This article is protected by copyright. All rights reserved.
- Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs). [Journal Article]
- IJInt J Cancer 2018 Dec 05
- The mTOR inhibitor everolimus is effective against advanced pancreatic neuroendocrine tumors (pNETs). However, it can cause metabolic adverse events, such as hyperglycemia, hypertriglyceridemia and h...
The mTOR inhibitor everolimus is effective against advanced pancreatic neuroendocrine tumors (pNETs). However, it can cause metabolic adverse events, such as hyperglycemia, hypertriglyceridemia and hypercholesterolemia. In this work we aimed at evaluating the impact of systemic and tumor lipid metabolism on everolimus efficacy. We carried out a monocentric, retrospective study to correlate plasma triglyceride and cholesterol levels with the progression free survival (PFS) of advanced pNET patients treated with everolimus. In formalin fixed, paraffin embedded (FFPE) tumor specimens, we also assessed by mRNA quantification and immunohistochemistry the expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), two enzymes crucially involved in fatty acid biosynthesis, and we analyzed their impact on PFS. We evaluated 58 consecutive pNET patients who started everolimus between December 2006 and January 2015. Patients with higher plasma triglycerides during the first three months of treatment had an increased risk of disease progression (aHR 3.08, 95% CIs 1.15-8.21; p = 0.025). In 23 FFPE tumor specimens amenable for IHC evaluations, we found a positive correlation between ACC1 and FASN at both mRNA (r = 0.87, p = 0.00045) and protein (r = 0.68, p = 0.0004) level. Patients with higher ACC1 protein expression in metastatic lesions had significantly lower PFS when compared to patients with lower ACC1 levels (5.5 vs 36 months; aHR 4.49, 95% CIs 1.08-18.72; p = 0.039). In conclusion, systemic and tumor lipid metabolism are associated with the PFS of everolimus-treated patients with advanced pNETs; based on these findings, dietary and pharmacological interventions targeting lipid metabolism could improve everolimus efficacy in this patient population. Pancreatic neuroendocrine tumors (pNETs) are highly heterogeneous, so to improve treatment, it's critical to learn more about how different tumor types respond to therapy. The mTOR inhibitor everolimus is a standard therapy for pNETs. Here, the authors conducted a retrospective study to evaluate how circulating triglyceride and cholesterol levels affect the efficacy of everolimus. Patients with higher plasma triglyceride levels at the start of treatment, they found, had worse outcomes. In addition, they noted a correlation between disease progression and higher intratumoral levels of ACC1, a key enzyme in fatty acid biosynthesis. This article is protected by copyright. All rights reserved.
- Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions. [Journal Article]
- BTBiol Trace Elem Res 2018 Dec 05
- The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. F...
The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.
- Associations of Insulin Levels and Insulin Resistance With Urine Glucose Excretion Independent of Blood Glucose in Chinese Adults With Prediabetes and Newly Diagnosed Diabetes. [Journal Article]
- FPFront Physiol 2018; 9:1666
- Several studies have demonstrated that renal glucose reabsorption is increased in patients with type 2 diabetes. However, the increased renal glucose reabsorption may contribute to the progression of...
Several studies have demonstrated that renal glucose reabsorption is increased in patients with type 2 diabetes. However, the increased renal glucose reabsorption may contribute to the progression of hyperglycemia. Therefore, promoting urine glucose excretion (UGE) by suppression of renal glucose reabsorption is an attractive approach for the treatment of diabetes. Insulin resistance is identified as a major characteristic in the pathogenesis of type 2 diabetes. Thus, our aim was to evaluate the association of UGE with serum insulin levels and insulin resistance in subjects with glucose abnormalities, including prediabetes and newly diagnosed diabetes (NDD). The present study included 1129 subjects, 826 individuals with prediabetes and 303 individuals with NDD. Urine samples were collected within 2 h of oral glucose loading for the measurement of glucose. Fasting serum insulin was measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was assessed. Multiple linear regression analysis and multivariate logistic regression analysis were performed to determine the association of UGE with insulin levels and HOMA-IR. A negative association between serum insulin levels and UGE was observed. The relationship remained significant after adjustment for potential confounders, including age, gender, blood pressure and glucose (β = -5.271, 95% CI: -9.775 to -0.767, p = 0.022). Furthermore, multivariable logistic regression model showed that increased insulin levels were associated with a decreased risk for high UGE after multivariable adjustment. In addition, similar correlation was also observed between HOMA-IR and UGE. HOMA-IR was negatively correlated with UGE after controlling for potential confounders. Moreover, an independent inverse relationship between HOMA-IR and the risk of high UGE was found (OR = 0.85, 95% CI: 0.78-0.93, p < 0.001). In conclusion, insulin levels and HOMA-IR were negatively correlated with UGE after adjusting for potential confounders. Subjects with increased insulin levels or IR were at a decreased risk of high UGE independent of blood glucose. The study suggests that insulin might affect UGE through other ways, in addition to the direct blood glucose-lowering effect, thereby resulting in reduced UGE.
- Diabetes and depression in Lebanon and association with glycemic control: a cross-sectional study. [Journal Article]
- DMDiabetes Metab Syndr Obes 2018; 11:717-728
- CONCLUSIONS: Depression was found to be present among 28.8% of the patients with diabetes mellitus in Lebanon; however, no association was established between depression and glycemic control.
New Search Next
- Coefficients in the CAVI Equation and the Comparison Between CAVI With and Without the Coefficients Using Clinical Data. [Journal Article]
- JAJ Atheroscler Thromb 2018 Dec 04
- CONCLUSIONS: In both the epidemiologic and clinical studies, there was no discrepancy in terms of significant differences between CAVI and haβ. These results suggest that both are valid as indices of stiffness of the arterial tree from the origin of the aorta to the ankle.