Sclerosteosis caused by a novel nonsense mutation of SOST in a consanguineous family.

Sclerosteosis, characterized by the hyperostosis of cranial and tubular bones, is a rare autosomal recessive hereditary disorder caused by mutation of SOST gene. Four nonsense mutations of SOST have been identified worldwide. Here, we report two affected siblings who carried a novel nonsense mutation of SOST in a consanguineous family from China. The proband manifested typical symptoms of sclerosteosis, whereas the symptoms were absent in another affected sibling. Two nucleotide substitutions in exon 2 of SOST were identified, c.444_445TC>AA, resulting in a premature stop codon, p.Cys148→Stop. This truncated mutation loses 66 amino acid residues which contain 3 cysteine residues of the cysteine-knot motif, leading to loss of function of SOST. The symptoms of sclerosteosis may be clinically heterogeneous in some patients, even with the same mutation. Our results support the notion that founder effects from the ancestors contribute to the disease onset.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance of type 2 diabetes.

AIM: To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS: According to the body mass index (BMI), 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI<25Kg/M(2) (30 cases) and the other group was obese diabetes patients with BMI>25Kg/M(2) (30 cases). There were 28 healthy persons in the control group. ELISA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment (HOMO). RESULTS: The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group (non-obese: 8.58+/-0.86, obese: 6.22+/-1.34 vs 10.53+/-1.47 P<0.05); moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group (6.22+/-1.34 vs 8.58+/-0.86, P<0.05). The levels of plasma resistin were increased significantly in diabetes group compared to that in control group (obese: 18.64+/-4.65, non-obese: 24.05+/-9.07 vs 14.16+/-5.25, P<0.05, P<0.05); furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group (P<0.05). Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride (respectively, r=-0.55, P<0.01; r=-0.51, P<0.05; r=-0.52, P<0.05ûr=-0.39, P<0.05), while it was positively correlated with insulin sensitive index (r=0.45, P<0.05). Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index (respectively, r=0.40, P<0.05; r=0.52, P<0.05; r=0.46, P<0.01; r=0.27, P<0.05), and negatively correlated with insulin sensitive index (r=-0.32, P<0.05). CONCLUSION: Plasma adiponectin and resistin are associated with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.

Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China.

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.

[Analysis of correlative factors affecting IIEF-5 scores of type 2 diabetic patients].

OBJECTIVE: To investigate the correlative factors affecting the IIEF-5 scores of the patient with type 2 diabetic mellitus (T2DM). METHODS: A total of 149 T2DM patients were investigated for the relationships between their IIEF-5 score and such factors as age, body mass index (BMI), fasting plasma glucose (FPG), 2hPG, insulin (INS), GHbA1c, C-peptide, nitric oxide (NO), testosterone (T), estradiol (E2), the ratio of testosterone to estradiol (T/E), erythrocyte aldose reductase (AR), drinking, smoking, concomitant diseases, complications and medication. RESULTS: The scores of the groups of smoking, complication, medication and concomitant disease were significantly lower than those of the controls. There was significant negative correlation between IIEF-5 scores and age, BMI, FPG, 2hPG, INS, GHbA1c and AR (P < 0.05), and significant positive correlation between IIEF-5 scores and NO (P < 0.05). But there was no correlation between drinking, T, E2 and T/E2 (P > 0.05). CONCLUSION: Many factors may affect the IIEF-5 scores of T2DM patients.

The Starling mechanism of the urinary bladder contractile function and the influence of hyperglycemia on diabetic rats.

UNLABELLED: Diabetic cystopathy is one of the common complications of diabetes. Bladder dysfunction in diabetes is attributable to diabetic neuropathy that induces sensory and autonomic nerve dysfunction. MATERIALS AND METHODS: In the present study, the contractile mechanism of the bladder was evaluated both with and without electrical stimulation in normal rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats with insulin treatment. RESULTS: Both the normal and diabetic rats had optimal capacity of bladder and optimal length of detrusor muscle strips. The peak values of the volume-pressure curves of the bladder and length-tension curves of detrusor muscle strips as well as the enhanced values after electrical stimulation in 6- and 10-week diabetic groups were lower than in the 6- and 10-week normal groups and insulin-treated groups. However, there was no significant difference in peak and enhanced values between normal rats and diabetic rats treated with insulin, indicating that voiding function was improved after insulin treatment. CONCLUSIONS: The contractile function of rat's bladder including normal rats, diabetic rats, and diabetic rats treated with insulin is similar to the 'Starling mechanism.' It can be impaired by hyperglycemia, and insulin treatment is helpful to restore this function.

[High glucose lowers insulin receptor substrate 2 expression and induces apoptosis in mouse islet cells in vitro].

OBJECTIVE: To investigate the role of insulin receptor substrate 2 (IRS2) and Bax on mouse islet cell apoptosis in the presence of high glucose in vitro. METHODS: The pancreatic islet cells were isolated from Kunming mice and divided into 6 groups (G1-G6 groups) for a 72-h culture in the media containing different concentrations of glucose (5.6, 7.8, 11.1, 16.7, 22.2, and 27.6 mmol/L, respectively). Insulin secretion by the cells was evaluated by radioimmunoassay, and the expressions of IRS2 and Bax were detected using immunocytochemistry and immunofluorescence assay, respectively. Hoechst33342 staining was employed to observe the cell apoptosis. RESULTS: Exposure to 5.6-11.1 mmol/L glucose resulted in increased insulin secretion and progressive elevation of IRS2 and Bax expression, whereas the cell apoptosis underwent no obvious changes. In the presence of glucose above 16.7 mmol/L, the percentages of apoptotic islet cells increased with glucose concentration, but insulin secretion and IRS2 expression decreased; Bax expression significantly increased in the presence of high-concentration glucose. CONCLUSION: Prolonged exposure of mouse islet cells to high glucose induces apoptosis and impairs insulin secretion of the cells. Decreased IRS2 expression and increased Bax expression may play an important role in the glucotoxicity in mouse islet cells.