11 research outputs found
Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment
Aim: To investigate the impact of renal function on the safety and efficacy of insulin glargine
300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100).
Materials and Methods: A meta-analysis was performed using pooled 6-month data from the
EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of
type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300
or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m2
.
Results: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of
individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100
groups, for both renal function subgroups. There was a reduced risk of nocturnal
(12:00-5:59 AM) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in
both renal function subgroups (eGFR <60 mL/min/1.73 m2
: relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m2
: RR 0.75 [95% CI 0.67-0.85]). For
confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours)
the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI
0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups.
Conclusions: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced
overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups
Efficiency of Purine Utilization by Helicobacter pylori: Roles for Adenosine Deaminase and a NupC Homolog
The ability to synthesize and salvage purines is crucial for colonization by a variety of human bacterial pathogens. Helicobacter pylori colonizes the gastric epithelium of humans, yet its specific purine requirements are poorly understood, and the transport mechanisms underlying purine uptake remain unknown. Using a fully defined synthetic growth medium, we determined that H. pylori 26695 possesses a complete salvage pathway that allows for growth on any biological purine nucleobase or nucleoside with the exception of xanthosine. Doubling times in this medium varied between 7 and 14 hours depending on the purine source, with hypoxanthine, inosine and adenosine representing the purines utilized most efficiently for growth. The ability to grow on adenine or adenosine was studied using enzyme assays, revealing deamination of adenosine but not adenine by H. pylori 26695 cell lysates. Using mutant analysis we show that a strain lacking the gene encoding a NupC homolog (HP1180) was growth-retarded in a defined medium supplemented with certain purines. This strain was attenuated for uptake of radiolabeled adenosine, guanosine, and inosine, showing a role for this transporter in uptake of purine nucleosides. Deletion of the GMP biosynthesis gene guaA had no discernible effect on mouse stomach colonization, in contrast to findings in numerous bacterial pathogens. In this study we define a more comprehensive model for purine acquisition and salvage in H. pylori that includes purine uptake by a NupC homolog and catabolism of adenosine via adenosine deaminase
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Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment
Aim: To investigate the impact of renal function on the safety and efficacy of insulin glargine
300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100).
Materials and Methods: A meta-analysis was performed using pooled 6-month data from the
EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of
type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300
or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m2
.
Results: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of
individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100
groups, for both renal function subgroups. There was a reduced risk of nocturnal
(12:00-5:59 AM) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in
both renal function subgroups (eGFR <60 mL/min/1.73 m2
: relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m2
: RR 0.75 [95% CI 0.67-0.85]). For
confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours)
the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI
0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups.
Conclusions: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced
overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups