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*

The prevalence of diabetes mellitus (DM) and associated diseases such as cancers are substantially increasing worldwide. About 80% of the patients with pancreatic cancer have glucose metabolism alterations. This suggests an association between type 2 DM and pancreatic cancer risk and progression. There are hypotheses that show metabolic links between the diseases, due to insulin resistance, hyperglycemia, hyperinsulinemia, low grade chronic inflammation, and alteration in the insulin-insulin-like growth factor axis. The use of diabetes medications can influence the extent of carcinogenesis of the pancreas. This study briefly reviews recent literature on investigation of metabolic link of type 2 DM, risk of carcinogenesis of the pancreas and their association, as well as the current understanding of metabolic pathways implicated in metabolism and cellular growth. The main finding of this review, although there are discrepancies, is that according to most research long-term DM does not raise the risk of pancreatic cancer. The longest duration of DM may reflect hypoinsulinemia due to treatment for hyperglycemia, but recent onset diabetes was associated with increased risk for pancreatic cancer due to hyperinsulinemia and hyperglycemia. In conclusion, the review demonstrates that type 2 DM and the duration of diabetes pose a risk for pancreatic carcinogenesis, and that there is biological link between the diseases.
Diabetes Mellitus, Type 2/complications/epidemiology/metabolism/*pathology ; Humans ; Hyperglycemia/pathology ; Insulin/metabolism ; Insulin Resistance ; Insulin-Like Growth Factor I/metabolism ; Pancreatic Neoplasms/epidemiology/*etiology ; Risk Factors

A 68-year-old woman with poorly controlled diabetes mellitus presented to the emergency department with choreoathetoid movements affecting the upper and lower left limbs. Computed tomography of the brain did not show any intracranial abnormalities. However, subsequent magnetic resonance (MR) imaging of the brain revealed an increased T1 signal in the right basal ganglia, raising the suspicion of nonketotic hyperglycaemic chorea-hemiballismus. Management consisted of adjusting her insulin dose to achieve good glycaemic control. The patient subsequently recovered and was discharged after eight days. There are many causes of basal ganglia T1 hyperintensity, including hyperglycaemia in patients with poorly controlled diabetes mellitus. This case emphasises the importance of MR imaging in the early diagnosis of hyperglycaemia as a cause of chorea-hemiballismus, to enable early treatment and a better clinical outcome.
Aged ; Brain ; diagnostic imaging ; Chorea ; diagnosis ; etiology ; Diagnosis, Differential ; Dyskinesias ; diagnosis ; etiology ; Female ; Humans ; Hyperglycemia ; complications ; diagnosis ; Magnetic Resonance Imaging ; methods ; Tomography, X-Ray Computed ; methods

Central pontine myelinolysis (CPM) is classically described as a demyelinating condition that results from the rapid correction of hyponatraemia. CPM has also been reported to arise from hyperglycaemia in association with concomitant acidosis, hypernatraemia and hyperosmolar syndrome. Herein, we report a rare presentation of CPM, which was purely secondary to hyperosmolar hyperglycaemia. The patient presented with ataxia and pseudobulbar affect, which evolved subacutely over a duration of two weeks. It is important to note that, in addition to acute changes in osmolality, a subacute shift secondary to hyperglycaemia may also lead to CPM.
Diagnosis, Differential ; Female ; Humans ; Hyperglycemia ; complications ; Magnetic Resonance Imaging ; Middle Aged ; Myelinolysis, Central Pontine ; diagnosis ; etiology ; Tomography, X-Ray Computed

Hyperglycemia significantly increases the risk of cardiovascular disease (CVD) in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called "harmless hyperglycemia" Furthermore, these cardiovascular benefits go beyond lowering blood glucose levels. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.
Blood Glucose ; analysis ; Cardiovascular Diseases ; prevention & control ; Diabetes Mellitus ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hyperglycemia ; complications ; etiology

OBJECTIVETo investigate the impact of hyperglycemia on the hydrogen sulfide (H2S) signaling pathway in rat penile tissue and its relationship with erectile function.

METHODSTwenty healthy male Sprague Dawley (SD) rats aged 8 weeks were randomly divided into groups A (4-week healthy control), B (4-week diabetes mellitus model), C (6-week healthy control) and D (6-week diabetes mellitus model). The rats in groups B and D were injected intraperitoneally with streptozotocin at 50 mg/kg to induce diabetes mellitus, while those in groups A and C with the same volume of normal saline. The animals were killed at 4 (groups A and B) and 6 weeks (groups C and D) after treatment for measurement of the maximal intracavernous pressure/mean arterial blood pressure (ICP(max)/MAP) by electrostimulation, determination of the H2S concentration in the plasma and penile tissue, and detection of the expressions of cystathionine-beta-synthetase (CBS) and cystathionine-gamma-lyase (CSE) in the penile corpus cavernosum by immunohisto- chemistry and Western blot.

RESULTSWith electrostimulation of the pelvic ganglia at 5V and 7 V, ICP(max)/MAP was significantly reduced in groups B (0.19 +/- 0.03 and 0.29 +/- 0.04) and D (0.14 +/- 0.04 and 0.25 +/- 0.04) as compared with A (0.46 +/- 0.07 and 0.68 +/- 0.09) and C (0.43 +/- 0.07 and 0.65 +/- 0.16) (P < 0.05). No statistically significant differences were found in the level of serum testosterone either between groups A and B ([469.19 +/- 126.46] ng/dl vs [359.08 +/- 60.06] ng/dl, P > 0.05) or between C and D ([470.44 +/- 209.28] ng/dl vs [297.01 +/- 96.58] ng/dl, P > 0.05). Groups B and D showed remarkable reduction in the H2S concentration (P < 0.05) and the expressions of CBS and CSE (P < 0.05) in comparison with A and C, and the CBS and CSE expressions were even more significantly decreased in D than in B (P < 0.05).

CONCLUSIONThe reduced concentration of H2S and decreased expressions of CBS and CSE in the penile corpus cavernosum of the diabetic rats suggested that the H2S signaling pathway might be involved in hyperglycemia-induced erectile dysfunction.

Animals ; Blood Pressure ; physiology ; Cystathionine gamma-Lyase ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; Electric Stimulation ; methods ; Erectile Dysfunction ; etiology ; Humans ; Hydrogen Sulfide ; metabolism ; Hyperglycemia ; metabolism ; Lyases ; metabolism ; Male ; Penis ; enzymology ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Testosterone ; metabolism

The data of 1,265 in-patients with diabetic ketosis or ketoacidosis treated in West China Hospital from October 2005 to October 2011 were analyzed retrospectively, and 8 of whom met fulminant type 1 diabetes (F1D) diagnostic criteria. The clinical features of the 8 F1D patients were investigated and compared with other 16 newly diagnosed autoimmune type 1 diabetes (T1D) patients, gender- and age-matched and with acute onset of ketoacidosis. During the six years between 2005 and 2011, the incidence of FID was 6.3 per thousand (8/T265) among all patients with diabetic ketosis or ketoacidosis admitted to the West China Hospital. The averaged age of the patients at onset of F1D was (30. 1 +/- 9. 7) years old, and the duration of diabetes was (4. 0 +/- 2. 4) days. Five of the 8 F1D patients had flu-like symptoms, and 7 had gastrointestinal symptoms. Blood glucose of F1D patients on admission was significantly higher than that of autoimmune T1D patients (P<0. 01), while the glycated hemoglobin (HbAlc) was lower than that of autoimmune T1D patients (P<0. 01). Additionally, fasting and postprandial C-peptide was significantly lower in F1D patients, with more severe acidosis, electrolytes and acid-base disturbances. The data suggest, that, compared with the autoimmune T1D patients, F1D patients have more complicated and more severe clinical manifestation with more severe hyperglycemia, more significant insulin deficiency and more obvious fluid electrolytes and acid-base disturbances. However, the sensitivity and the specificity of the diagnostic criteria of F1D are still needed to be improved for the Chinese people, so more multi-center and large-scale clinical trials should be conducted in the future.
Adult ; Autoantibodies ; blood ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; classification ; diagnosis ; epidemiology ; Diabetic Ketoacidosis ; etiology ; Humans ; Hyperglycemia ; epidemiology ; immunology ; Incidence ; Retrospective Studies ; Young Adult

Animal gastrointestinal tract contains a complex community of microbes, whose composition ultimately reflects the co-evolution of microorganisms with their animal host. The gut microbial community of humans and animals has received significant attention from researchers because of its association with health and disease. The application of metagenomics technology enables researchers to study not only the microbial composition but also the function of microbes in the gastrointestinal tract. In this paper, combined with our own findings, we summarized advances in studying gastrointestinal tract microorganism with metagenomics and the bioinformatics technology.
Animals ; Gastrointestinal Tract ; microbiology ; Humans ; Hyperglycemia ; etiology ; Inflammatory Bowel Diseases ; etiology ; Metagenome ; physiology ; Metagenomics ; methods ; Obesity ; etiology

Acute Disease ; Alcoholism ; complications ; Gastrointestinal Hemorrhage ; etiology ; Humans ; Hyperglycemia ; etiology ; Infant ; Male