Background: Insulin therapy has been the mainstay in managing women with gestational diabetes mellitus (GDM), but some disadvantages of insulin have led to the use of glyburide, which is inexpensive in some countries,...Background: Insulin therapy has been the mainstay in managing women with gestational diabetes mellitus (GDM), but some disadvantages of insulin have led to the use of glyburide, which is inexpensive in some countries, to manage GDM. However, there has been debate over its effectiveness, efficacy and safety when compared to insulin for maternal glycaemic control, and some adverse neonatal outcomes in GDM. Method: A systematic review of eight randomised controlled trial (RCT) studies was undertaken to compare glyburide and insulin. Studies involving 849 participants were included in the quantitative analysis. Results: There was no significant difference between glyburide and insulin in maternal fasting (P = 0.09;SMD: 0.13;95% CI: ﹣0.02 to 0.28) and postprandial (P = 0.45;SMD: 0.05;95% CI: ﹣0.09 to 0.19) glycaemic control and glycosylated hae-moglobin (P = 0.35;SMD: 0.08;95% CI: ﹣0.08 to 0.24). When compared with insulin, glyburide had an increase risk ratio (RR) for neonatal hypoglycaemia (P = 0.0002;RR: 2.27;95% CI: 1.47 to 3.51) and large for gestational age babies (P = 0.03;RR: 1.60;95% CI: 1.06 to 2.41). Estimation of standard mean difference shows that neonatal birth weight was significantly higher in subjects receiving glyburide than in the insulin group (P = 0.002;SMD: 0.21;95% CI: 0.08 to 0.35). Conclusions: Glyburide was seen to be clinically effective and a safer alternative to insulin for maternal glycaemic control in GDM women. It is affordable, convenient and requires no comprehensive educative training at the time of initiation of therapy. However, its adverse outcomes—neonatal hypogly-caemia, high neonatal birth weight and large for gestational age babies—call for careful monitoring of GDM patients for any need for supplemental insulin.展开更多
BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can oc...BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can occur later in life.Mutations in the ABCC8 gene,which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells,are associated with TNDM and permanent neonatal diabetes.This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulfonylurea therapy.CASE SUMMARY We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed,treated,or referred for follow-up between September 2017 and September 2023.The patients were tested for mutations using targeted next-generation sequencing.Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before.Both children had an onset of post-infectious diabetic ketoacidosis,which is worth noting.At a follow-up visit after discontinuing insulin injection,oral glyburide was found to be effective with no adverse reactions.CONCLUSION Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.展开更多
OBJECTIVE: To determine the role of membrane potential and intracellular calcium kinetic changes in producing vascular hyporeactivity during severe hemorrhagic shock. METHODS: Rats were subjected to hemorrhagic shock ...OBJECTIVE: To determine the role of membrane potential and intracellular calcium kinetic changes in producing vascular hyporeactivity during severe hemorrhagic shock. METHODS: Rats were subjected to hemorrhagic shock (HS) for 2 hours. The spinotrapezius muscle was prepared for microscopy and the responses of arterioles in the muscle to norepinephrine (NE) were tested. The resting membrane potentials of isolated arterial strips were measured with a microelectrode. Membrane potential and intracellular Ca2+ ([Ca2+]i) changes in isolated arteriolar smooth muscle cells (ASMCs) were determined with fluorescent probes and a confocal microscopy. RESULTS: The arteriolar resting membrane potential was decreased from -36.7 +/- 6.3 mV in control to -29.2 +/- 5.3 mV concurrent with the increase of vasoreactivity to NE at 20 minutes after HS. At 120 minutes post-HS, the resting potential hyperpolarized to -51.9 +/- 9.1 mV, and NE stimulated [Ca2+]i increase was reduced to 50% of the control values during the appearance of arteriolar hyporeactivity, i.e. the NE threshold of the arteriolar response increased 15 fold 2 hours after the onset of hemorrhage as compared with normal animals. The state of vasoreactivity was closely related to the resting potential of vascular smooth muscle in hemorrhagic shock, with a correlation coefficient of 0.96. Treatment with glybenclamide, a selective blocker of ATP-sensitive K+ (KATP) channels, decreased the resting potential, increased NE-stimulated [Ca2+]i increase, and partially restored vasoreactivity in severe hemorrhagic shock. CONCLUSION: The results suggested that membrane hyperpolarization and the reduction of NE-stimulated [Ca2+]i increase in smooth muscle cells appeared to contribute to the vascular hyporeactivity in hemorrhagic shock. The mechanism is likely to involve in KATP channels.展开更多
文摘Background: Insulin therapy has been the mainstay in managing women with gestational diabetes mellitus (GDM), but some disadvantages of insulin have led to the use of glyburide, which is inexpensive in some countries, to manage GDM. However, there has been debate over its effectiveness, efficacy and safety when compared to insulin for maternal glycaemic control, and some adverse neonatal outcomes in GDM. Method: A systematic review of eight randomised controlled trial (RCT) studies was undertaken to compare glyburide and insulin. Studies involving 849 participants were included in the quantitative analysis. Results: There was no significant difference between glyburide and insulin in maternal fasting (P = 0.09;SMD: 0.13;95% CI: ﹣0.02 to 0.28) and postprandial (P = 0.45;SMD: 0.05;95% CI: ﹣0.09 to 0.19) glycaemic control and glycosylated hae-moglobin (P = 0.35;SMD: 0.08;95% CI: ﹣0.08 to 0.24). When compared with insulin, glyburide had an increase risk ratio (RR) for neonatal hypoglycaemia (P = 0.0002;RR: 2.27;95% CI: 1.47 to 3.51) and large for gestational age babies (P = 0.03;RR: 1.60;95% CI: 1.06 to 2.41). Estimation of standard mean difference shows that neonatal birth weight was significantly higher in subjects receiving glyburide than in the insulin group (P = 0.002;SMD: 0.21;95% CI: 0.08 to 0.35). Conclusions: Glyburide was seen to be clinically effective and a safer alternative to insulin for maternal glycaemic control in GDM women. It is affordable, convenient and requires no comprehensive educative training at the time of initiation of therapy. However, its adverse outcomes—neonatal hypogly-caemia, high neonatal birth weight and large for gestational age babies—call for careful monitoring of GDM patients for any need for supplemental insulin.
基金Supported by the Department of Science and Technology of Henan Province,China,No.222102310461。
文摘BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can occur later in life.Mutations in the ABCC8 gene,which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells,are associated with TNDM and permanent neonatal diabetes.This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulfonylurea therapy.CASE SUMMARY We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed,treated,or referred for follow-up between September 2017 and September 2023.The patients were tested for mutations using targeted next-generation sequencing.Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before.Both children had an onset of post-infectious diabetic ketoacidosis,which is worth noting.At a follow-up visit after discontinuing insulin injection,oral glyburide was found to be effective with no adverse reactions.CONCLUSION Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.
文摘OBJECTIVE: To determine the role of membrane potential and intracellular calcium kinetic changes in producing vascular hyporeactivity during severe hemorrhagic shock. METHODS: Rats were subjected to hemorrhagic shock (HS) for 2 hours. The spinotrapezius muscle was prepared for microscopy and the responses of arterioles in the muscle to norepinephrine (NE) were tested. The resting membrane potentials of isolated arterial strips were measured with a microelectrode. Membrane potential and intracellular Ca2+ ([Ca2+]i) changes in isolated arteriolar smooth muscle cells (ASMCs) were determined with fluorescent probes and a confocal microscopy. RESULTS: The arteriolar resting membrane potential was decreased from -36.7 +/- 6.3 mV in control to -29.2 +/- 5.3 mV concurrent with the increase of vasoreactivity to NE at 20 minutes after HS. At 120 minutes post-HS, the resting potential hyperpolarized to -51.9 +/- 9.1 mV, and NE stimulated [Ca2+]i increase was reduced to 50% of the control values during the appearance of arteriolar hyporeactivity, i.e. the NE threshold of the arteriolar response increased 15 fold 2 hours after the onset of hemorrhage as compared with normal animals. The state of vasoreactivity was closely related to the resting potential of vascular smooth muscle in hemorrhagic shock, with a correlation coefficient of 0.96. Treatment with glybenclamide, a selective blocker of ATP-sensitive K+ (KATP) channels, decreased the resting potential, increased NE-stimulated [Ca2+]i increase, and partially restored vasoreactivity in severe hemorrhagic shock. CONCLUSION: The results suggested that membrane hyperpolarization and the reduction of NE-stimulated [Ca2+]i increase in smooth muscle cells appeared to contribute to the vascular hyporeactivity in hemorrhagic shock. The mechanism is likely to involve in KATP channels.
