Carotid atherosclerosis and its relationship to coronary heart disease and stroke risk in patients with type 2 diabetes mellitus.

Carotid atherosclerosis (CA) and carotid plaque (CP) are highly correlated with cardiovascular disease. We aimed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM).We studied 1584 T2DM patients aged 20 years and older. CA and CP were detected using ultrasonography. Ten-year stroke and CHD risk were determined using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine.The prevalence of CA and CP increased gradually with age. Men had a higher prevalence of CA than women (CA: 58.18% vs 51.54%, P < .01). The 10-year CHD risk (27.9% vs 15.4%, P < .001) and stroke risk (15.2% vs 5.70%, P < .001) were higher in patients with CA than that of those without CA. Compared with patients without CA, the odds ratios (ORs) of CHD in CA and CP group were 4.47 and 10.78 for men, and 4.19 and 5.20 for women, respectively; in the case of stroke, the OR in CA and CP group were 8.83 and 12.07 for men, and 4.35 and 4.90 for women, respectively (P < .001 for all). Multivariate binary logistic regression analysis showed that CA was an independent risk factor for CHD [OR = 2.66, 95% confidence interval (95% CI), 2.05-3.46, P < .001] and stroke (OR = 3.11, 95% CI, 2.38-4.07, P < .001).CA and CP were prevalent in patients with T2DM and positively correlated with 10-year CHD and stroke risk. CA was an independent risk factor for 10-year CHD risk.

Association of Chronic Kidney Disease with Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus: An Observational Cross-sectional Study in Hangzhou, China.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). However, the association between CKD and CVD risk in patients with type 2 diabetes mellitus (T2DM) in China has not yet been well investigated. This study aimed to determine the association of CKD with the risks of coronary heart disease (CHD) and stroke in a Chinese population with T2DM. METHODS: A total of 1401 inpatients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study. The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD. The UK Prospective Diabetes Study risk engine was used to estimate the risks of CHD and stroke. RESULTS: CHD risk was significantly increased with CKD stage (20.1%, 24.8%, and 34.3% in T2DM patients with no CKD, CKD Stage 1-2, and Stage 3-5, respectively; P < 0.001 for all). The stroke risk was also increased with CKD stage (8.6%, 12.7%, and 25.4% in T2DM patients with no CKD, CKD Stage 1-2, and Stage 3-5, respectively; P < 0.001 for all). Compared with no-CKD group, the odds ratios (OR s) for high CHD risk were 1.7 (P < 0.001) in the CKD Stage 1-2 group and 3.5 (P < 0.001) in the CKD Stage 3-5 group. The corresponding OR s for high stroke risk were 1.9 (P < 0.001) and 8.2 (P < 0.001), respectively. CONCLUSION: In patients with T2DM, advanced CKD stage was associated with the increased risks of CHD and stroke.

Pseudohypoparathyroidism with Hashimoto's thyroiditis and Turner syndrome: a case report.

OBJECTIVE: To report the case of an individual with PHP, Turner syndrome and Hashimoto's thyroiditis. CASE: A 16-year-old girl was referred to our hospital with chief complaint of short stature. She presented with round chubby facies, short neck, obesity and short stature. Radiography indicated short metatarsals and metacarpals, which mainly affected the second, third and fourth digits. Biochemistry revealed hyperphosphatemia, increased serum concentrations of parathyroid hormone and thyroid stimulating hormone, elevated levels of follicular-stimulating hormone and prolactin, and increased thyroid peroxidase antibody and thyroglobulin antibody. Radiographic examination revealed delayed bone age and pelvic ultrasonography demonstrated an immature uterus. Karyotype analysis showed 46,X,i(Xq10), while molecular analysis revealed a same sense mutation in exon 5 of GNAS (ATC → ATT, Ile).The specific diagnosis was made of Turner syndrome in the presence of Hashimoto's thyroiditis and PHP. She was treated with calcium supplementation, calcitriol and thyroxine. CONCLUSIONS: This is the first case report to describe a combination of Turner syndrome with these other clinical entities, and their co-existence should be considered and further investigated.

Inflammatory cytokines, adiponectin, insulin resistance and metabolic control after periodontal intervention in patients with type 2 diabetes and chronic periodontitis.

OBJECTIVE: To evaluate the effects of periodontal intervention on inflammatory cytokines, adiponectin, insulin resistance (IR), and metabolic control and to investigate the relationship between type 2 diabetes mellitus (T2DM) and moderately poor glycemic control and chronic periodontitis. METHODS AND PATIENTS: A total of 190 moderately poorly controlled (HbA1c between 7.5% and 9.5%) T2DM patients with periodontitis were randomly divided into two groups according to whether they underwent periodontal intervention: T2DM-NT and T2DM-T group. The levels of serum adiponectin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), lipid profile, glucose, insulin, homeostasis model of assessment-insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were measured at baseline and after 3 months. RESULTS: The levels of clinical periodontal variables, the probing depth, attachment loss, bleeding index, and plaque index were improved significantly in T2DM-T group after 3 months compared to T2DM-NT group (all p<0.01). After 3 months, the serum levels of hsCRP, TNF-α, IL-6, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and HOMA-IR index decreased, and adiponectin was significantly increased in T2DM-T group compared to those in the T2DM-NT group (p<0.05 or p<0.01). CONCLUSION: Periodontal intervention can improve glycemic control, lipid profile and IR, reduce serum inflammatory cytokine levels and increase serum adiponectin levels in moderately poorly controlled T2DM patients.

Intermittent high glucose enhances apoptosis in INS-1 cells.

To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducing ß-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5 mmol/L), SHG (33.3 mmol/L), and IHG (5.5 mmol/L and 33.3 mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious to ß-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.

Changes of adiponectin and inflammatory cytokines after periodontal intervention in type 2 diabetes patients with periodontitis.

OBJECTIVE: To determine serum adiponectin, C-reactive protein (CRP), TNF-α and IL-6 levels in impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) patients with periodontitis before and after periodontal intervention, and to investigate the relationship between T2DM and periodontitis. METHODS: A total of 50 IGT and 106 T2DM patients with periodontitis were enrolled. The T2DM patients were divided into two groups: T2DM without macrovascular disease (DM1) group and T2DM with macrovascular disease (DM2) group. Each group was randomly divided into two subgroups according to whether they performed periodontal intervention. The normal control group (NC group) consisted of 30 healthy adults. The serum adiponectin, CRP, TNF-α and IL-6 levels were measured at baseline and 3 months after periodontal intervention. RESULTS: The serum adiponectin levels at baseline had decreased tendency with significant difference between each two groups, while CRP, TNF-α, and IL-6 levels had increased tendency with significant difference between each two groups among NC, IGT, DM1 and DM2 groups (all P<0.01). At 3 months after periodontal intervention, the serum adiponectin levels were increased than those without periodontal intervention (all P<0.01), while CRP, IL-6 and TNF-α significantly decreased (all P<0.05) in both IGT and DM1 groups. In DM2 group, only CRP levels at 3 months after periodontal intervention were significantly decreased (P<0.05). Moreover, the HbAlc levels in T2DM patients were improved at 3 months after periodontal invention (P<0.01). CONCLUSION: Periodontal intervention is helpful for glucose control, which may be associated with increased serum adiponectin levels and decreased inflammatory cytokine levels.

[Features of insulin secretion and insulin resistance in newly diagnosed type 2 diabetes of different body mass indices].

OBJECTIVE: To investigate insulin secretion function and insulin resistance in Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2 diabetes and 40 normal controls were recruited. Height, weight were measured, insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose tolerance test were examined. The patients with fasting glucose level greater than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After normalization of the plasma glucose levels for more than 2 weeks, and withdraw this medication for 48 hours, then OGTT were repeated to assess IR and IS. RESULTS: The patients were divided into four groups based on fasting plasma glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3 mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin sensitivity and insulin secretion function compared between subgroups. (1) True insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI > or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24 groups', but their insulin secretion function were better at the same FPG level. (3) After intervention, the change of insulin sensitivity in BMI < 24 group was better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24 group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin sensitivity and insulin secretion function were decreased with the increase of FPG, but they were different between obese and non-obese group. (2) Insulin secretion function was recovered better in obese group when eliminated glucose toxicity.

[Molecular cloning of a novel retroviral NP9 gene of human endogenous retrovirus and its viral protein expression].

OBJECTIVE: To investigate the relationship between retroviruses and autoimmune diseases, to clone the novel retroviral NP9 gene from human endogenous retrovirus (HERV), and to construct its expression vector. METHODS: The viral NP9 gene was amplified and cloned by RT-PCR and T-A clone techniques, and its sequence was determined with Perkin-Elmer 377 DNA Sequencer. The amplified viral NP9 gene was subcloned into the prokaryotic express vector pQE30. The recombinant plasmids were identified by restriction endonuclease digestion and sequencing. The recombinant pQE30-NP9 protein was expressed in M15 host cells under the IPTG induction and showed with SDS-PAGE,and the corresponding NP9 viral protein was identified with Western blot analysis. RESULT: A specific band of 250 bp was amplified using RT-PCR from total RNA of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and confirmed as the NP9 gene via T-A clone and DNA sequencing analyses. SDS-PAGE profile showed a clear protein band with a relative molecular weight 9 kD in the IPTG-induced samples, which was confirmed as viral NP9 protein by Western blot analysis. CONCLUSION: The NP9 gene has been successfully isolated and cloned from PBMCs of SLE patients and the corresponding NP9 viral protein expressed in prokaryotic expression vector.

[Preliminary clinical observation on effect of soduim ferulate in treating diabetic nephropathy].

OBJECTIVE: To investigate the effect of sodium ferulate (SF) on diabetic nephropathy (DN). METHODS: Forty-eight DN patients of early stage and 54 DN patients of clinical stage were randomly divided into two groups, the conventional treatment group and the SF treatment group. Indexes, including urinary albumin excretion rate (UAER), serum endothelin (ET), blood urea nitrogen (BUN), serum creatinine (Scr) and fasting blood glucose (FBG) were observed. RESULTS: The levels of UAER, BUN and ET were decreased in all DN patients, either early stage or clinical stage, after treated with SF for 4 weeks (P < 0.05, P < 0.01), but changed insignificantly in those treated with conventional treatment. CONCLUSION: SF can decrease the levels of UAER and BUN in DN patients, the mechanism may relate with the decreasing of ET production and antagonizing to the binding of ET with its receptors.

Expression of a novel human retroviral NP9 gene and potential roles of its protein in systemic lupus erythematosus patients.

OBJECTIVE: To investigate the expression of a novel retroviral (NP9) gene transcripts and the possible role of its protein in systemic lupus erythematosus (SLE) patients. METHODS: The retroviral NP9 gene in SLE patients was isolated and cloned using RT-PCR and TA cloning techniques, and it was analyzed by sequencing. The expression of the NP9 genes in 40 patients with SLE and 48 normal controls using RT-PCR was detected. NCBI BLAST and DNASIS 3.1 software were used to analyze the features of protein of NP9 gene. RESULTS: The positive ratio (77.5%) of the mRNA expression of the retroviral NP9 gene in SLE patients is significantly higher than that (8.3%) in normal subjects (P<0.01). The recombinant NP9 protein comprises 74 AA with pI 9.59. Amino acid sequence analysis indicates that the retroviral NP9 protein shares higher homologies with several human proteins with important biological functions. CONCLUSION: SLE patients possess specific novel retroviral NP9 transcripts. The expression of the retroviral NP9 gene may involve in the genesis or development of SLE.

[Study of functional L1 retrotransposon in human type 2 diabetes susceptibility loci].

OBJECTIVE: To investigate the susceptibility gene of type 2 diabetes mellitus (T2DM) through a novel strategy. METHODS: Firstly, the common feature of the putative susceptibility genes in the reported susceptibility loci was searched by using NCBI BLAST, and a functional L1 retrotransposon in the loci was found. Secondly, the mRNA expression level of the functional L1 retrotransposon in 25 Han T2DM patients and 22 normal controls was investigated by reverse transcription-polymerase chain reaction, and statistical analysis was implemented in statistical package SPSS10.0. Thirdly, L1 retrotransponson genome mutation screening was performed via sequencing. RESULTS: Screening the human genome for the retrotransposon genome via alignment with the L1 genome using NCBI BLAST showed the functional L1 retrotransposons distribute on most chromosomes except for chromosomes 19, 21 and Y on which rare type 2 diabetes susceptibility loci were reported to reside, and their distribution sites are consistent with the locations of the reported candidate type 2 diabetes susceptibility loci. The mRNA expression level of the functional L1 retrotransposon in the T2DM patients was significantly lower than that in normal subjects (P<0.001). Nonsense mutations including deletion and/or point mutations were observed in all of the 6 T2DM patients tested, but no mutation was observed in all of the 4 normal controls tested. CONCLUSION: The functional L1 retrotransposon may be a candidate susceptibility gene of type 2 diabetes or a key regulator of the susceptibility genes, and it may be an ideal candidate biomarker for screening type 2 diabetes.