OBJECTIVEThe aim of this study is to determine whether the SUMO4 M55V polymorphism is associated with susceptibility to type 2 diabetes mellitus (T2DM).

METHODSA meta-analysis was performed to detect the potential association of the SUMO4 M55V polymorphism and susceptibility to T2DM under dominant, recessive, co-dominant (homogeneous and heterogeneous), and additive models.

RESULTSA total of eight articles including 10 case-control studies, with a total of 2932 cases and 2679 controls, were included in this meta-analysis. The significant association between the SUMO4 M55V polymorphism and susceptibility to T2DM was observed in the dominant model (GG + GA versus AA: OR = 1.21, 95% CI = 1.05-1.40, P = 0.009), recessive model (GG versus GA + AA: OR = 1.29, 95% CI = 1.07-1.356, P = 0.010), homozygous model (GG versus AA: OR = 1.41, 95% CI = 1.06-1.56, P = 0.001), and additive model (G versus A: OR = 1.18, 95% CI = 1.08-1.29, P = 0.001), and marginally significant in the heterozygous model (GA versus AA: OR = 1.16, 95% CI = 0.98-1.36, P = 0.080). In subgroup analyses, significant associations were observed in the Chinese population under four genetic models excluding the heterozygous model, whereas no statistically significant associations were observed in the Japanese population under each of the five genetic models.

CONCLUSIONThe meta-analysis demonstrated that the G allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM, mainly in the Chinese population, while the association in other ethnic population needs to be further validated in studies with relatively large samples.

Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Genetic Predisposition to Disease ; epidemiology ; genetics ; Humans ; Small Ubiquitin-Related Modifier Proteins ; genetics ; metabolism

BACKGROUND: Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China. METHODS: A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed. RESULTS: In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P  < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further. CONCLUSIONS The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.
Adult ; Blood Glucose/metabolism* ; China/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Diabetes, Gestational ; Female ; Fetal Macrosomia ; Glucose Intolerance ; Humans ; Male ; Pregnancy ; Retrospective Studies

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

OBJECTIVETo explore the impact of the waist circumference change on new onset diabetes (NOD) in the impaired fasting glucose (IFG) population.

METHODSA total of 12 657 subjects who took part in the health examination from 2006 to 2007 and from 2010 to 2011 from the employees of Kailuan Group and met the inclusion criteria were selected as the observation cohort.Of the 12 657 subjects, 10 697 were male, 1960 were female, with age of (49.9 ± 11.3) years old. According to the baseline waist circumference (WC) measurements and its quartile in the health examinations during 2006 to 2007, the observation population was divided into four groups (first, second, third and the fourth quartile groups) . Multiple logistic regression analysis was used to test the relation between the increasing of WC and NOD.

RESULTSThe incidences in the IFG population of NOD were 4.27% (1884/12 657) in the total population;4.25% (1581/10 697) in male and 4.44% (303/1960) in females, respectively (P < 0.05) . Along with increasing WC in the 4 quartile groups, the incidences of NOD was progressively increased, which were 2.19% (235/3083) , 3.07% (333/3114) , 4.47% (473/3037) and 7.08% (843/3423) , respectively;2.34% (213/2626) , 3.06% (282/2645) , 4.37% (393/2582), 7.00% (693/2844) in males and 1.38% (22/457) , 3.12% (51/469) , 5.05% (80/455) , 7.45% (150/579) in female (P < 0.05) . Multiple logistic regression analysis showed that compared with the first quartile group, the second, third and fourth quartile group had increased risk of NOD after adjusting for age, gender and other risk factors, the OR (95%CI) values were 1.38(1.13-1.68), 1.79 (1.47-2.09) and 3.10 (2.57-3.75), respectively.

CONCLUSIONThe incidence of NOD in the IFG population increased as the WC increased.

Adult ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; epidemiology ; Female ; Glucose Intolerance ; epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Waist Circumference

OBJECTIVES: To investigate whether smoking and the smoking status are predictors of the incident impaired fasting glucose (IFG) or type 2 diabetes in Korean men. METHODS: A cohort of 1,717 Korean men without IFG or diabetes, who underwent annual periodic health examinations for 4 years (2002-2006), were retrospectively investigated. IFG and diabetes were defined as a serum fasting glucose concentration of 100-125 mg/dL and more than 126 mg/dL, respectively. Cox's proportional hazards model was used to evaluate the association between smoking and development of IFG or type 2 diabetes. RESULTS: A total of 558 cases (32.5%) of incident IFG and 50 cases (2.9%) of diabetes occurred. After controlling for the potential predictors of diabetes, the relative risk for IFG, compared with the never smokers, was 1.02 (95% CI=0.88 to 1.19) for the ever-smokers, 0.96 (95% CI=0.79-1.16) for those who smoked 1-9 cigarettes/d, 1.15 (95% CI=1.01 to 1.30) for those who smoked 10-19 cigarettes/d, and 1.31 (95% CI=1.10 to 1.57) for those who smoked 20 or more cigarettes/d (the P value for the current smokers was only p<0.002). The respective multivariate adjusted relative risks for type 2 diabetes, compared with the neversmokers, were 1.07 (95% CI=0.64 to 1.92), 1.47 (95% CI=0.71 to 3.04), 1.84 (95% CI=0.92-3.04), and 1.87 (95% CI=1.13-3.67), respectively (the P value for the current smokers was only p=0.004). CONCLUSIONS: The smoking status and the number of cigarettes smoked daily are associated with an increased risk for developing IFG or type 2 diabetes in Korean men.
Adult ; Blood Glucose/*analysis ; Body Mass Index ; Diabetes Mellitus, Type 2/*metabolism ; Health Behavior ; Health Status ; Humans ; Korea/epidemiology ; Male ; Retrospective Studies ; Risk Factors ; Smoking/*adverse effects

PURPOSE: Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. MATERIALS AND METHODS: One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8+/-11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. RESULTS: Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7+/-7.0 vs. 15.8+/-10.9 microg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). CONCLUSION: Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF.
Adiponectin/*blood ; Aged ; Diabetes Mellitus, Type 2/epidemiology/metabolism ; Female ; Heart Failure/*epidemiology/*metabolism/ultrasonography ; Humans ; Male ; Metabolic Syndrome X/*epidemiology/*metabolism ; Middle Aged ; Risk Factors ; Ventricular Function, Left/physiology

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (> 170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (< or =170 U/ml) (19.6%) (p < 0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients.
Aged ; Coronary Arteriosclerosis/epidemiology/*metabolism/*therapy ; Coronary Restenosis/epidemiology/*metabolism ; Diabetes Mellitus, Type 2/epidemiology/*metabolism ; Female ; Glycosylation End Products, Advanced/*blood ; Humans ; Male ; Middle Aged ; Research Support, Non-U.S. Gov't ; Risk Factors ; *Stents

BACKGROUNDStroke is now the most prevalent and debilitating disease affecting diabetic population in China. The study aimed to investigate the prevalence of stroke and metabolic disorders in the middle-aged and elderly Chinese with type 2 diabetes.

METHODSA total of 4 629 subjects with type 2 diabetes (males: 1 917; females: 2 712) aged ≥ 40 years from Shijingshan district, Beijing, China from November 2011 to August 2012 were included in the study. Data on demographic information, lifestyle, history of diabetes mellitus, stroke, coronary heart disease, hypertension, and dyslipidemia were collected. The oral glucose tolerance test or a standard meal test was performed. Non-fatal stroke was reported by the subjects. The 2-tailed test was used, and P < 0.05 was regarded as statistically significant.

RESULTSPrevalence of stroke in the subjects with type 2 diabetes was 5.5%. The prevalence of smoking, overweight or obesity, hypertension, and dyslipidemia was 41.0%, 65.8%, 67.4%, and 52.0% in males, and 2.2%, 65.5%, 69.5%, and 57.6% in females. Multivariate Logistic regression analysis showed that increased age, hypertension, diabetic duration, and overweight or obesity were positively correlated with stroke in the population with type 2 diabetes, whereas high-density lipoprotein cholesterol level was negatively correlated with stroke. After adjustment for age and gender, the odds ratio values of stroke in subjects having 1, 2 or ≥3 of 4 risk factors, including smoking, overweight or obesity, hypertension and dyslipidemia, were 2.302 (95% CI: 0.789-6.712), 4.089 (95% CI: 1.470-11.373), 6.023 (95% CI: 2.176-16.666), compared with subjects without any of the above 4 risk factors.

CONCLUSIONSThe prevalence of stroke was higher in middle-aged and elderly Chinese with type 2 diabetes than that in the general population. With the aggregation of risk factors, the prevalence of stroke increased.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 2 ; epidemiology ; metabolism ; Female ; Humans ; Male ; Metabolic Diseases ; epidemiology ; metabolism ; Middle Aged ; Risk Factors ; Stroke ; epidemiology ; metabolism

OBJECTIVE: To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
 METHODS: Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
 RESULTS: 1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
 CONCLUSION Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.
Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Cerebrum ; metabolism ; Choline ; metabolism ; Cognition ; Cognition Disorders ; epidemiology ; Creatine ; metabolism ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Nephropathies ; epidemiology ; Glomerular Filtration Rate ; Humans ; Neuropsychological Tests

PURPOSE: The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). MATERIALS AND METHODS: Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). RESULTS: Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (ρ=0.407) or fasting C-peptide (ρ=0.402) were demonstrated. CONCLUSION: Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.
Adult ; Aged ; Biomarkers/metabolism ; C-Peptide/metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2/*complications/metabolism ; Female ; Hemoglobin A, Glycosylated/metabolism ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*epidemiology/metabolism/pathology ; Odds Ratio ; Prevalence