Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus.

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RT(G) was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors.

Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report.

BACKGROUND: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). METHODS: Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily). RESULTS: Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels. CONCLUSIONS: Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

[Research on the effect of statins on insulin secretion from pancreatic islet in rats and its mechanisms].

OBJECTIVE: To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. METHODS: According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group (incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group (incubated with 100 µmol/L atorvastatin), the fluvastatin group (incubated with 100 µmol/L fluvastatin) and the pravastatin group (incubated with 100 µmol/L pravastatin). Stimulated by 2.8, 5.5, 11.1, 16.7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 µmol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37°C bath incubation method and ATP content was measured by chemiluminescence method. RESULTS: Incubated with 100 µmol/L atorvastatin for 30 minutes, in the presence of 16.7 mmol/L glucose, the ATP content [(9.54 ± 1.64) pmol/islet vs (12.33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0.21 vs 2.39 ± 0.30) were significantly reduced in comparison with the control group (P < 0.05). Cultured with 100 µmol/L fluvastatin for 24 hours, the ATP content [(10.24 ± 2.01) pmol/islet vs (12.31 ± 2.16) pmol/islet] and GSIS (3.12 ± 0.32 vs 4.17 ± 0.37) were all significantly decreased at the higher glucose concentration of 16.7 mmol/L (P < 0.05). CONCLUSION: Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.

Relationship between circadian blood pressure variability and function of islet α and ß cell in type 2 diabetes with dyssomnia.

AIMS: To investigate the relationship between circadian blood pressure (BP) variability and function of islet α and ß cell in type 2 diabetes (T2D) with dyssomnia. METHODS: Patients with T2D were divided into dyssomnia group and non-dyssomnia group by PSQI. OGTT, insulin and glucagon-releasing test were tested, and ambulatory BP was monitored for 24 hours to compare two groups with α and ß cell, circadian BP variability and fasting and post-meal BP variability. The correlation and regression analysis were made between PSQI and other indicators. RESULTS: In dyssomnia group, ① Glucagon, glucagon/insulin ratio and AUCG were significantly higher (P < 0.05). ② Fasting insulin (13.32 ± 4.54 mIU/L), AUCI (8.51 ± 0.54) and HOMA-IR (4.62 ± 1.11) were high (P < 0.05). But ISI (-4.27 ± 0.77) was low (P < 0.05). ③ Mean 24-hour and nighttime SBP and DBP, as well as their standard deviations and coefficients of variation, were all higher in the dyssomnia group (P < 0.05). Multiple stepwise regression analysis showed that PSQI score was positively related to AUCG, HOMA-IR, nighttime SBP, and negatively related to ISI and nocturnal BP fall (P < 0.05). CONCLUSION: Dyssomnia may cause abnormal circadian BP variability through various mechanisms. Improving dyssomnia can help to better function the islet α and ß cell and restore normal circadian BP variability.

Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus: A meta-analysis.

Many studies have accessed the association between eNOS-4b/a polymorphism and the risk of diabetic nephropathy (DN) among type 2 diabetic subjects. However, the results are conflicting and inconclusive. The aim of current meta-analysis was to more precisely estimate the relationship. Pubmed, Embase, the China National Knowledge Infrastructure and the Wanfang Database were searched for articles published up to May 26th, 2013 that addressed eNOS-4b/a polymorphism and the risk of DN among type 2 diabetic subjects. 18 studies were included in this meta-analysis. eNOS-4b/a polymorphisms were associated with an overall significantly increased risk of DN (allele model: OR = 1.44, 95% CI = 1.14-1.82; additive model: OR = 2.03, 95% CI = 1.14-3.62; dominant model: OR = 1.34, 95% CI = 1.07-1.68; recessive model: OR = 2.01, 95% CI = 1.12-3.61). Subgroup analysis revealed a significant association between the eNOS-4b/a polymorphism and DN in Asian population, especially in Chinese population, but not in non Asian populations. Our meta-analysis supported an association between the 4b/a polymorphism of eNOS gene and increased risk of DN in type 2 diabetes among Asians, especially in Chinese population.

Association between eNOS 4b/a polymorphism and the risk of diabetic retinopathy in type 2 diabetes mellitus: a meta-analysis.

Many studies have assessed the association between eNOS-4b/a polymorphism and the risk of diabetic retinopathy (DR) among type 2 diabetic subjects. However, the results are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and 3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The main analysis indicated no significant association between eNOS-4b/a polymorphism and the risk of DR in overall population [allelic model: OR = 0.94 (0.79-1.11); additive model: OR = 0.91 (0.73-1.14); recessive model: OR = 1.01 (0.81-1.25); dominant model: OR = 0.91 (0.75-1.09)]. Subgroup analysis by ethnicity also indicated no significant association. In conclusion, the current meta-analysis did not observe any association between the polymorphism of eNOS 4b/a and the risk of DR among type 2 diabetic subjects. However, larger well-designed studies are required to confirm this finding.