Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D.
Alzheimer Disease ; Amyloid ; Blood Vessels ; Cerebrovascular Disorders ; Dementia ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Humans ; Islet Amyloid Polypeptide ; Models, Animal ; Neurologic Manifestations ; Pathology ; Prediabetic State ; Rodentia

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.
Adult ; Biomarkers/blood ; Body Mass Index ; C-Reactive Protein/analysis ; Chemokines/*blood ; Creatinine/blood/urine ; Diabetes Mellitus, Type 2/*blood/diagnosis ; Female ; Humans ; Insulin/blood ; Intercellular Signaling Peptides and Proteins/*blood ; Intra-Abdominal Fat/*pathology ; Linear Models ; Lipocalins/blood ; Male ; Middle Aged ; Obesity/complications ; Triglycerides/blood

The aim of this study was to evaluate the association of plasma fibroblast growth factor (FGF)-21 with angiographically significant coronary artery disease (CAD) in patients with type 2 diabetes mellitus. Serum FGF-21 was measured in 120 patients undergoing coronary angiography. Patients were divided into 4 groups based on the presence/absence of type 2 diabetes mellitus and of significant CAD. The atherosclerotic burden was obtained by two angiographic scores: Gensini score (GS) and Extent score (ES). FGF-21 levels were higher in type 2 diabetes mellitus than in non-diabetic patients (P = 0.014). FGF-21 levels were significantly correlated with GS (r = 0.358, P < 0.001) and ES (r = 0.324, P < 0.001) in univariate analysis with all patients. After adjusting for several confounding factors, both GS and ES were associated with FGF-21 in all patients (r = 0.271, P = 0.014; r = 0.217, P = 0.041, respectively). However, FGF-21 lost significant correlation with both GS and ES with type 2 diabetes mellitus in the final model. The patients with type 2 diabetes mellitus and CAD feature had elevated FGF-21 levels. Despite of a limited role in diabetic patients, FGF-21 levels are independently associated with angiographic severity and extent of CAD.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Artery Disease/complications/*diagnosis/pathology ; Diabetes Mellitus, Type 2/complications/*diagnosis ; Female ; Fibroblast Growth Factors/*blood ; Humans ; Male ; Middle Aged ; Regression Analysis ; Severity of Illness Index ; Young Adult

In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.
Blood Platelets/metabolism ; Cell- and Tissue-Based Therapy ; Diabetes Mellitus, Type 2/complications/pathology ; Fibroblasts/cytology/transplantation ; Humans ; Keratinocytes/cytology/transplantation ; Stromal Cells/cytology/transplantation ; Tissue Engineering ; Ulcer/etiology/therapy ; *Wound Healing

Aged ; Diabetes Mellitus, Type 2 ; complications ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; etiology ; pathology ; Retrospective Studies

OBJECTIVEObesity is a major risk factor for type 2 diabetes, many indexes can be used to describes obesity and predict diabetes. This research attempts to identify the best indicator of obesity to screening diabetes in Chinese population.

METHODSA cross-sectional data of 8121 subjects aged 35-60 years were included in this research belongs to the Diabetes Appropriate Technology Intervention Study. Anthropometric indicators including body weight, height, waist circumferences (WC), body fat index (BFI) and visceral fat index (VFI) and blood biochemical indicators after an overnight fast [fasting blood glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triacylglycerol] were measured. BMI (body mass index) and Weight to Height Ratio was calculated.

RESULTSSubjects with obesity had a higher risk of physician diagnosed diabetes (OR=2.50, 95% CI 1.83-3.43), new diagnosed diabetes (OR=4.23, 95% CI 2.91-6.15) and pre-diabetes (OR=1.75, 95% CI 1.31-2.34) compared to those with normal Body mass index (BMI). There was a significant trend of increased risk of all diabetes status with increased waist circumference (WC). The waist-to-height ratio (WHtR) yielded the most significant association with new diagnosed diabetes and physician diagnosed diabetes than other indices.

CONCLUSIONCentral obesity is significantly correlated with diabetes. VFI was most correlated with pre-diabetes while WHtR is an efficient screening index than BMI and WC in Chinese community diabetes screening.

Adipose Tissue ; physiology ; Adult ; Aged ; Asian Continental Ancestry Group ; Blood Glucose ; Body Mass Index ; China ; epidemiology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; epidemiology ; etiology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Obesity ; complications ; Waist Circumference ; Waist-Hip Ratio

OBJECTIVETo study the clinicopathological features of diabetic microangiopathy in liver and diabetic hepatosclerosis (DHS) of elderly male with type 2 diabetes mellitus (T2DM).

METHODSOne hundred and twenty autopsy cases with T2DM (diabetic group) and contemporary 48 cases, non-diabetic and glucose tolerance abnormal, matched by gender and age (control group) were selected in the study. Cases with the cirrhosis and fibrosis of liver caused by other foregone etiological factors were excluded. The histopathological changes of microangiopathy in liver, hepatic portal areas and hepatic sinusoid were investigated by HE staining, histochemical and immunohistochemical stain methods. The clinical data of diagnostic DHS cases were analyzed.

RESULTS(1) Microangiopathy was observed in 54.2% (65/120) cases of diabetic group. Histological features: microangiopathy was found in interlobular arteries (especially in arteriole, the lumen diameter < 100 µm), which included endothelial denudation, eosinophilic material deposition in the tunica intima of artery, and eccentric intimal thickening. The smooth muscle fibers of tunica media were hyperplastic or atrophy. Fibroplasia and collagen deposition were found in the tunica adventitia of artery. Arterial lumina showed stenosis and occlusion. Microangiopathy was seen in 16.7% (8/48) cases of the control group. There was statistically significant difference between the two groups (χ(2) = 19.622, P < 0.01). (2) The fibrosis and sclerosis of portal areas were detected in 55.8% (67/120) cases of T2DM group. Hyaline collagen fiber tissues was deposited around interlobular arteries, interlobular veins and interlobular bile ducts, resulting in enlargement of the portal area and the secondary atrophy and disappearance of portal triad. The fibrosis and sclerosis of portal areas were detected in 22.9% (11/48) cases of the control group. There was a statistically significant difference between the two groups (χ(2) = 14.936, P < 0.01). (3) The pathological features of 14.2% (17/120) cases were consistent with the diagnosis of DHS. The fibrous tissue extended from fibrosis or sclerosis of portal areas, or eosinophilic material deposition in the hepatic sinusoid in non-zonal pattern. The results of histochemical staining showed collagen fiber deposition in hepatic sinusoid. Stainings for Collagen IV, SMA, CD34 were found in the hepatic sinusoid. The sclerosis of hepatic sinusoid was not detected in any case in the control group.Overall, 13/17 and 11/17 DHS cases had liver microangiopathy and portal areas sclerosis respectively. Diabetic nephropathy was seen in 10 of 17 DHS cases. Among the 17 cases, 7 cases showed ALP elevation, of which there were 3 cases with ALT and AST mild elevation.

CONCLUSIONSDiabetic microangiopathy is common in the liver of elderly men with T2DM. And DHS is associated with diabetic microangiopathy. Fibrosis and sclerosis of portal areas may be the early or concomitant changes of DHS on histological ground. DHS is one of the complications of T2DM.

Actins ; metabolism ; Aged ; Aged, 80 and over ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Antigens, CD34 ; metabolism ; Aspartate Aminotransferases ; blood ; Collagen Type IV ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Angiopathies ; blood ; etiology ; metabolism ; pathology ; Diabetic Nephropathies ; complications ; pathology ; Humans ; Liver ; blood supply ; pathology ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Sclerosis

We aimed to explore the associations of dietary patterns with blood lipid profiles and obesity in adults with type 2 diabetes. The data were obtained from the Forth Korean National Health and Nutrition Examination Survey, 2007-2008. Adults 30 yr or older, from which had both biochemical and dietary data were obtained. Among them, 680 subjects were defined as having diabetes based on criteria of fasting glucose > or = 126 mg/dL, anti-diabetic treatment, or previously diagnosed diabetes. Dietary data from a 24-hr recall were used to derive dietary patterns by factor analysis. Four dietary patterns by factor analysis were identified: 'Bread & Meat & Alcohol', 'Noodles & Seafood', 'Rice & Vegetables', and 'Korean Healthy' patterns. Serum cholesterol levels in the highest quartile of the 'Bread & Meat & Alcohol' pattern were significantly higher compared with those in the lowest quartile. In addition, total cholesterol and triglyceride levels in the highest quartile of the 'Korean Healthy' pattern were significantly lower after adjusting for potential confounders. Dietary patterns of adults with diabetes were found to be associated with blood lipid profiles. 'Korean Healthy' pattern including whole grains, legumes, vegetables, and fruits could thus improve lipid profiles among those with type 2 diabetes.
Adult ; Aged ; Cholesterol/blood ; Demography ; Diabetes Mellitus, Type 2/*blood/complications/pathology ; *Diet ; Female ; Food Habits ; Humans ; Lipids/*blood ; Male ; Middle Aged ; Nutrition Surveys ; Obesity/complications ; Republic of Korea ; Triglycerides/blood

OBJECTIVETo investigate the possible involvement of erythr opoietin (EPO)/erythropoietin receptor (EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).

METHODSEPOR positive circulating progenitor cells (CPCs: CD34(+)) and endothelial progenitor cells (EPCs: CD34(+)KDR(+)) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients with out diabetes ( n=7),non-proliferative DR (NPDR, n=7),non-proliferative DR (PDR, n=8), and PDR complicated with diabetic nephr opathy (PDR-DN, n=7).

RESULTSThe numbers of EPOR(+) CPCs and EPOR(+) EPCs were reduced remarkably in NPDR compared with the control group (both Pü0.01), whereas rebounded in PDR and PDR-DN groups in varyingdegrees. Similar changes were observed in respect of the proportion of EPOR(+)CPCs in CPCs (NPDR vs. control, Pü0.01) and that of EPOR(+) EPCs in EPCs (NPDR vs. control, Pü0.05).

CONCLUSIONExogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR(+)EPCs associated with ischemia.

Aged ; Cell Count ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; pathology ; Endothelium, Vascular ; cytology ; Erythropoietin ; blood ; Female ; Humans ; Male ; Middle Aged ; Receptors, Erythropoietin ; analysis ; Stem Cells ; physiology

Our study was performed to determine whether cardiac autonomic neuropathy can predict deterioration of the renal function in normoalbuminuric, normotensive people with type 2 diabetes mellitus (DM). One hundred and fifty-six normoalbuminuric, normotensive people with type 2 DM were included in our retrospective longitudinal study. We categorized normal patterns, early patterns, and definite or severe patterns according to the results of the cardiac autonomic function test. Of 156 patients included, 54 had normal patterns, 75 had early patterns, 25 had definite or severe patterns, and 2 had atypical patterns. During a median follow-up of nine years, glomerular filtration rates (GFR) remained stable in the normal and early pattern groups (mean changes, 4.50% and 0.77%, respectively) but declined in those with definite or severe patterns (mean change, -10.28%; p=0.047). An abnormal heart response to the deep breathing test of the cardiac autonomic function tests was an independent predictor of GFR decline. Our data suggest that cardiac autonomic neuropathy, especially with a definite or severe pattern, might be associated with a subsequent deterioration in renal function in normoalbuminuric, normotensive people with type 2 DM.
Aged ; Blood Pressure ; Diabetes Complications ; Diabetes Mellitus, Type 2/*diagnosis/*pathology ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Heart Diseases/*complications ; Heart Rate ; Humans ; Kidney/*pathology ; Kidney Diseases/*therapy ; Male ; Middle Aged ; Nephrology/methods ; Neurodegenerative Diseases/*complications