585 research outputs found
C-peptide, Na+,K+-ATPase, and Diabetes
Na+,K+-ATPase is an ubiquitous membrane enzyme
that allows the extrusion of three sodium ions from the cell
and two potassium ions from the extracellular fluid. Its activity
is decreased in many tissues of streptozotocin-induced
diabetic animals. This impairment could be at least partly
responsible for the development of diabetic complications.
Na+,K+-ATPase activity is decreased in the red blood cell
membranes of type 1 diabetic individuals, irrespective of the
degree of diabetic control. It is less impaired or even normal
in those of type 2 diabetic patients. The authors have
shown that in the red blood cells of type 2 diabetic patients,
Na+,K+-ATPase activity was strongly related to blood C-peptide
levels in non–insulin-treated patients (in whom C-peptide
concentration reflects that of insulin) as well as in
insulin-treated patients. Furthermore, a gene-environment
relationship has been observed. The alpha-1 isoform of the
enzyme predominant in red blood cells and nerve tissue is
encoded by the ATP1A1 gene.Apolymorphism in the intron
1 of this gene is associated with lower enzyme activity in patients
with C-peptide deficiency either with type 1 or type
2 diabetes, but not in normal individuals. There are several
lines of evidence for a low C-peptide level being responsible
for low Na+,K+-ATPase activity in the red blood cells.
Short-term C-peptide infusion to type 1 diabetic patients
restores normal Na+,K+-ATPase activity. Islet transplantation,
which restores endogenous C-peptide secretion, enhances
Na+,K+-ATPase activity proportionally to the rise
in C-peptide. This C-peptide effect is not indirect. In fact,
incubation of diabetic red blood cells with C-peptide at
physiological concentration leads to an increase of Na+,K+-ATPase activity. In isolated proximal tubules of rats or
in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K+-ATPase activity. This impairment in Na+,K+-ATPase activity,
mainly secondary to the lack of C-peptide, plays probably
a role in the development of diabetic complications.
Arguments have been developed showing that the diabetesinduced
decrease in Na+,K+-ATPase activity compromises
microvascular blood flow by two mechanisms: by affecting
microvascular regulation and by decreasing red blood cell
deformability, which leads to an increase in blood viscosity.
C-peptide infusion restores red blood cell deformability
and microvascular blood flow concomitantly with Na+,K+-ATPase activity. The defect in ATPase is strongly related to
diabetic neuropathy. Patients with neuropathy have lower
ATPase activity than those without. The diabetes-induced
impairment in Na+,K+-ATPase activity is identical in red
blood cells and neural tissue. Red blood cell ATPase activity
is related to nerve conduction velocity in the peroneal
and the tibial nerve of diabetic patients. C-peptide infusion
to diabetic rats increases endoneural ATPase activity in rat.
Because the defect in Na+,K+-ATPase activity is also probably
involved in the development of diabetic nephropathy and
cardiomyopathy, physiological C-peptide infusion could be
beneficial for the prevention of diabetic complications
Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes
Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response
Analysis of Insulin Doses of Chinese Type 2 Diabetic Patients with Intensive Insulin Treatment
BACKGROUND: To investigate the daily insulin doses and the ratio of basal insulin to total daily insulin in Chinese type 2 diabetic patients who received basal bolus insulin therapy. METHODOLOGY/PRINCIPAL FINDINGS: Totally 2480 patients prescribed with pre-meal bolus insulin and bedtime basal insulin were included. The mean daily insulin doses was 38.22 ± 14.92 IU/day, the mean daily insulin doses per weight was 0.58 ± 0.22 IU/kg, the mean bolus insulin dose was 0.44 ± 0.17 IU/kg and the mean basal insulin dose was 0.13 ± 0.08 IU/kg. The mean basal/total daily insulin ratio (BD/TDD) was 0.23 ± 0.08. In most patients (47.94%), the BD/TDD was between 0.20 and 0.30. Diabetic duration, BMI, HbA1c, fasting and postprandial blood glucose level were positively associated with daily insulin dose, while age was negatively associated with daily insulin dose. Diabetic duration, BMI, HbA1c, fasting blood glucose level, and using metformin were positively associated with BD/TDD ratio, while age, postprandial C peptide, postprandial blood glucose level and CRE level were negatively associated with BD/TDD ratio. CONCLUSIONS/SIGNIFICANCE: The daily insulin doses of intensive treatment in Chinese type 2 diabetic patients was 38.22 IU/day, the mean daily insulin doses per weight was 0.58 IU/kg, mean BD/TDD ratio was 0.23
Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.
One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort
Insulin Detemir in the Treatment of Type 1 and Type 2 Diabetes
Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients
Insulin detemir in a twice daily insulin regimen versus a three times daily insulin regimen in the treatment of type 1 diabetes in children: A pilot randomized controlled trial
Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund
Plasminogen Activator Inhibitor-1 4G/5G Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis
Background: The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. Objective and Methods: The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95 % confidence interval (CI) was assessed by the random effect model. Results: The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95 % CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P,0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02)
Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)
Using a sample of 122 million Upsilon(3S) events recorded with the BaBar
detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for
the spin-singlet partner of the P-wave chi_{bJ}(1P) states in the
sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We
observe an excess of events above background in the distribution of the recoil
mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width
of the observed signal is consistent with experimental resolution, and its
significance is 3.1sigma, including systematic uncertainties. We obtain the
value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching
fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
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