BACKGROUNDWe investigated whether and to what extent the ratio between circulating fibrinogen (Fg) and its degradation products (FDP) reflects the severity of coronary artery disease (CAD) in type 2 diabetic patients.

METHODSPlasma levels of Fg and FDP were determined, and Fg/FDP ratio was calculated in 344 consecutive patients with type 2 diabetes and chest pain on exertion undergoing coronary angiography. The severity of CAD was evaluated by the number of significant CAD (>50% luminal diameter narrowing) and Gensini score.

RESULTSPlasma Fg was higher, but Fg/FDP ratio was lower in patients with significant CAD (n = 255) compared with those without (n = 89), due to a disproportionate increase in FDP. Fg and FDP correlated positively, while Fg/FDP ratio negatively, with the number of diseased coronary arteries and the tertile of Gensini score (all P values for trend < 0.01). After adjusting for age, sex, risk factors for CAD, lipid profiles, glycosylated hemoglobin A1c, creatinine, leukocyte count, and high-sensitivity C-reactive protein, Fg/FDP ratio remained an independent determinant for multivessel coronary disease (MVD) (odds ratio [OR], 0.869; 95% confidence interval [CI], 0.788-0.958, P = 0.005) and high tertile of Gensini score (OR, 0.797, 95% CI, 0.682-0.930, P = 0.004). The area under the curve of Fg/FDP ratio was larger than that of Fg for predicting the presence of MVD (0.647 vs. 0.563, P = 0.048) and Gensini score ≥ 30 (0.656 vs. 0.538, P = 0.026).

CONCLUSIONSElevated plasma Fg and FDP level and reduced Fg/FDP ratio are associated with presence of CAD, and Fg/FDP ratio is superior to Fg in reflecting severe coronary atherosclerosis for patients with type 2 diabetes.

Aged ; Coronary Angiography ; Coronary Artery Disease ; blood ; diagnosis ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Fibrin ; metabolism ; Fibrinogen ; metabolism ; Humans ; Male ; Middle Aged

While long-standing diabetes is a risk factor of pancreatic cancer, new-onset diabetes could be a consequence of underlying pancreatic malignancy. About 30% to 50% of pancreatic cancer patients have new-onset diabetes. Because diabetes develops in preclinical or early stages of pancreatic cancer, it could serve as an excellent clue for early detection of pancreatic cancer. Insulin resistance associated with hyperglycemia and hyperinsulinemia by diabetogenic factors secreted from cancer cells have been suggested to be a possible mechanism of pancreatic cancer-induced diabetes. It is difficult to differentiate pancreatic cancer-induced diabetes from the more common type 2 diabetes. Although several clinical features and potential biomarkers have been investigated, optimal strategies and modalities to screen pancreatic cancer among the new-onset diabetes have not yet been fully determined.
Adiponectin/metabolism ; Age Factors ; Body Mass Index ; Cytokines/metabolism ; Diabetes Mellitus, Type 2/*complications/*diagnosis/pathology ; Humans ; Pancreatic Neoplasms/*complications/*diagnosis/pathology ; Tomography, X-Ray Computed

Biomarkers ; blood ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; diagnosis ; genetics ; metabolism ; Humans ; MicroRNAs ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Precision Medicine ; methods

OBJECTIVES: The beta3 adrenergic receptor(beta3 -AR) may play an important role in the regulation of energy expenditure and lipolysis. A mutation of the beta3 - AR gene(Trp64Arg) has been reported to be associated with early onset of non-insulin dependent diabetes mellitus(NIDDM), obesity and syndrome X which are related with insulin resistance. It is well known that Korean NIDDM patients, in contrast to Caucasians, are mainly non-obese and have experienced severe weight loss during the course of disease. We studied the frequency of the mutation in Korean NIDDM patients and non-diabetics control and evaluated the clinical characteristics of Korean obese NIDDM patients. We investigated the frequency of the mutation in NIDDM patients and clinical characteristics of the patients with the mutation in order to elucidate the significance of the mutation in the pathogenesis of NIDDM in Koreans. METHODS: We studied 401 NIDDM patients and 99 controls. The NIDDM patients were divided into two groups, non-obese group and obese group, according to their body mass index at diagnosis of the disease. The Trp64Arg mutation was detected by the PCR/RFLP method using restriction enzyme Mva I. RESULTS: The Trp64Arg allele frequency(16M) of NIDDM did not differ from that(16%) of controls. Although the mutant allele frequency was not different between non-obese and obese group both in NIDDM patients and controls, the frequency of patient with the mutant allele was significantly higher in obese NIDDM patients than in non-obese NIDDM patients(38.5% vs. 26.9%, P=0.04). However, no significant differences were found in clinical and laboratory findings between the NIDDM patients with the mutant allele and those without the mutant allele. CONCLUSION: These data suggest that beta3 -AR mutation might be associated with Korean obese NIDDM, and other factors might also be associated with the development of obesity and insulin resistance in NIDDM patients.
Alleles ; Body Mass Index ; Diabetes Mellitus, Type 2* ; Diagnosis ; Energy Metabolism ; Gene Frequency ; Humans ; Insulin Resistance ; Lipolysis ; Obesity ; Receptors, Adrenergic* ; Weight Loss

OBJECTIVETo investigate the significance of high sensitivity C-reactive protein (hsCRP) levels in serum for detecting type 2 diabetes mellitus (T2DM) patients at risk of developing nonalcoholic fatty liver (NAFLD).

METHODSIndividuals with T2DM (n = 9489) were recruited from the Kailuan Company between 2006 and 2007 for the first phase of this community-based prospective cohort study. For the second phase of the study, the original cohort was recruited for follow-up (at two years from each subject's original enrollment date (baseline)). The total followed-up subjects (n = 2802; 2344 males, 458 females, 22-88 years old) were categorized into quartiles according to baseline measurements of serum hsCRP levels (less than or equal to 0.30, > 0.30-0.60, > 0.60-1.92 and > 1.92 mg/L) and used to determine the relationship between change in incidence rates of NAFLD and predictive value of baseline serum hsCRP levels by logistic regression analysis.

RESULTSTwenty-nine percent (n = 813) of the followed-up subjects developed NAFLD. The incidence (%) of NAFLD at the two-year follow-up had increased in conjunction with the level of serum hsCRP detected at baseline (quartile 1: 22.5%, 2: 27.3%, 3: 32.1%, and 4: 34.3%; all, P less than 0.01). It was found that the subjects in the highest quartile had an increased risk of NAFLD (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.42-2.28, P less than 0.01), as compared with those in the lowest quartile. Moreover, when the regression model was adjusted for baseline factors of age, sex, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum glucose, and body mass index, the risk of NAFLD remained significantly higher for the highest quartile (vs. the lowest quartile; OR = 1.49, 95% CI: 1.16-1.91, P less than 0.01).

CONCLUSIONSerum hsCRP levels may be predictive of development of NAFLD in individuals with type 2 diabetes mellitus. The risk of NAFLD increases in parallel with increasing levels of serum hsCRP.

C-Reactive Protein ; metabolism ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Humans ; Non-alcoholic Fatty Liver Disease ; diagnosis ; Prospective Studies ; Risk Factors

Coronary Angiography ; Coronary Artery Disease ; complications ; diagnosis ; diagnostic imaging ; Diabetes Mellitus, Type 2 ; blood ; complications ; Glycated Hemoglobin A ; metabolism ; Humans ; Mass Screening

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

Von Willebrand factor (vWF) is a glycoprotein with a crucial role in the formation of platelet thrombi, and ADAMTS13 is the main enzyme responsible for vWF cleavage. Both are important in the relationship between diabetic nephropathy, hypercoagulability, and cardiovascular disease. This study evaluated a potential relationship between vitamin D (vitD) levels, vWF, ADAMTS13 activity, and inflammation in diabetic patients on chronic hemodialysis (HD). Blood samples from 52 diabetic patients on chronic HD were obtained to determine vitD levels, vWF, and ADAMTS13 activity, and inflammatory markers. HD patients were grouped according to 25-hydroxyvitamin D [25(OH) VitD]<25 nmol/L (n=16) or >25 nmol/L (n=36). vWF antigen and vWF activity were elevated in both groups, with an average of 214.3±82.6% and 175.8±72.6%, respectively. Average ADAMTS13 activity was within the normal range in both groups. Blood samples from the vitD <25 nmol/L group showed a positive correlation between c-reactive protein (CRP) and vWF levels (P=0.023; r=0.564; 95% confidence interval=0.095-0.828), with a negative correlation between HbA1c and 25(OH) VitD (P=0.015; r=-0.337; 95% confidence interval=-0.337-0.19). Diabetic patients on chronic HD had elevated vWF levels and activity with no significant change in ADAMTS13 activity. The correlation between CRP and vWF levels in the 25(OH) VitD<25 nmol/L group suggests inflammatory-related endothelial dysfunction in these patients.
ADAMTS13 Protein/*metabolism ; Aged ; C-Reactive Protein/analysis ; Diabetes Mellitus, Type 2/complications/*diagnosis/metabolism ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Male ; Middle Aged ; Renal Dialysis ; Renal Insufficiency, Chronic/complications/*diagnosis/metabolism ; Vitamin D/*analogs & derivatives/blood ; von Willebrand Factor/*metabolism

Correlation between the intrahepatic inflammatory pathogenesis and the TCM theory of liver collateral injury by toxins in patients of type 2 diabetes mellitus (T2DM) with insulin resistance (IR) was investigated, to elucidate that removing toxins, dredging collateral and modulating Gan could be one of the effective approaches for inhibiting intrahepatic inflammation mechanism of T2DM with IR.
Chemokine CCL2 ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; physiopathology ; Diagnosis, Differential ; Humans ; Inflammation ; etiology ; metabolism ; physiopathology ; Insulin Resistance ; Liver ; metabolism ; pathology ; physiopathology ; Medicine, Chinese Traditional ; NF-kappa B ; metabolism

The angiotensin-converting enzyme (ACE) gene DD homozygote has been suggested to be a significant risk factor for the progression of diabetic nephropathy. We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years. There were no significant differences in age, sex, body mass index, HbA1c level, or lipid profiles between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of hypertension [group 1: 82.5% (85/103) vs. group 2: 50.0% (44/88), p < 0.05] and diabetic retinopathy [group 1: 103/103 (100%) vs. group 2: 28/88 (31.8%), p < 0.05] than group 2. Daily urinary albumin excretion was also higher in group 1 than in group 2 [group 1: 2873 +/- 2176 mg/day vs. 12 +/- 7 g/day, p < 0.05]. The frequencies of the DD, ID, and II genotypes of the ACE gene in group 1 and group 2 were 26.2%, 47.6%, and 26.2%, and 7.9%, 57.9%, and 34.2%, respectively. The ACE genotype frequencies between the two groups were significantly different according to a chi-square test with Bonferroni's correction (p = 0.004). The presence of the DD genotype increased the risk of ESRF 4.286-fold compared to the II genotype [odds ratio 4.286, 95% CI 1.60- 11.42, p = 0.005]. The frequency of the D-allele was higher in both male and female patients in group 1 compared to group 2, but reached statistical significance only in males [male, group 1: 50.8% vs. group 2: 35.0%, p = 0.018, female, group 1: 48.8% vs. group 2: 39.5%, p = 0.231]. This study, although limited by sample size, showed that type 2 diabetic ESRF patients more frequently expressed the DD genotype. These findings may substantiate the previously noted relationship between the ACE DD genotype and the progression of diabetic nephropathy in Korean type 2 diabetic patients.
Renal Dialysis ; *Polymorphism, Genetic ; Peptidyl-Dipeptidase A/*genetics/metabolism ; Middle Aged ; Male ; Kidney Failure, Chronic/diagnosis/*genetics ; Humans ; Homozygote ; Gene Frequency ; Female ; Diabetic Nephropathies/diagnosis/*genetics ; Diabetes Mellitus, Type 2/diagnosis/*genetics ; Aged