Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. PURPOSE: To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. STUDY SELECTION: 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4). DATA EXTRACTION: 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. DATA SYNTHESIS: In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. LIMITATION: Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. CONCLUSION: Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Does prolonged ß-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials.

BACKGROUND: The emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of ß-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged ß-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent ß-lactam infusion. METHODS: Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models. RESULTS: Fourteen randomized controlled trials (RCTs) were included. Prolonged infusion ß-lactams were not associated with decreased mortality (n=982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n=1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for ß-lactam subclasses and equivalent total daily ß-lactam doses yielded similar results. Most studies had notable methodological flaws. CONCLUSIONS: No clinical advantage was observed for prolonged infusion ß-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of ß-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed.

A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14.

The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns.

Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P=0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P=0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.