Canadian Real-World Outcomes of Omnipod Initiation in People with Type 1 Diabetes (COPPER study): Evidence from the LMC Diabetes Registry.

AIMS: To investigate real-world clinical outcomes in adults with type 1 diabetes who initiated the Omnipod Insulin Management System (Insulet Corp., Acton, MA, USA) compared to a matched cohort who maintained multiple daily injection therapy. METHODS: This retrospective observational study used data from the Canadian LMC Diabetes Registry. Adults with type 1 diabetes who switched from multiple daily injections to the Omnipod system as usual standard of care between January 2011 and April 2019 were matched to a cohort of adults with type 1 diabetes who maintained multiple daily injection therapy, using propensity-score matching. The primary outcome was change in HbA1c at 3- to 6-month follow-up. RESULTS: Propensity-score matching resulted in a final analytical cohort of 286 individuals (143/cohort). HbA1c in the Omnipod cohort was reduced by a mean ± sd of -3 ± 10 mmol/mol (-0.2 ± 1.0%; P = 0.005) with no change in the MDI cohort [0 ± 10 mmol/mol (0.0 ± 1.0%); P = 0.74]. HbA1c change was seen only in persons with baseline HbA1c ≥75 mmol/mol (≥9.0%) [Omnipod cohort: -15 ± 12 mmol/mol (-1.4 ± 1.1%); P < 0.001] with a between-treatment difference [mean (95% CI)] of -12 (-18, -6) mmol/mol [-1.1 (-1.6, -0.5) %, P < 0.001]. The median total daily dose of insulin was lower following Omnipod initiation (baseline 0.63 U/kg vs follow-up 0.53 U/kg; P < 0.001), with no change in the MDI cohort (baseline 0.68 U/kg vs follow-up 0.67 U/kg; P = 0.23). CONCLUSIONS: Adults with type 1 diabetes who initiated use of the Omnipod system in a real-world clinical setting had lower HbA1c and total daily dose of insulin at 3- to 6-month follow-up compared to a matched cohort of adults who maintained multiple daily injection therapy. A treatment difference in HbA1c change was seen only in people with baseline HbA1c ≥ 75 mmol/mol (9.0%). (Clinical trials registration: NCT04226378).

SGLT2 inhibitors and incretin agents: Associations with alanine aminotransferase activity in type 2 diabetes.

AIM: The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group. METHODS: We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups. RESULTS: A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups. CONCLUSION: SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.

Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERß) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERß signaling in mediating DOL effects in male mice to further decipher sex differences. METHODS: Male 21 day-old WT and ERßKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. RESULTS: ERßKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. CONCLUSIONS: The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.

Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study.

AIMS: To determine the global extent of hypoglycaemia experienced by patients with diabetes using insulin, as there is a lack of data on the prevalence of hypoglycaemia in developed and developing countries. METHODS: This non-interventional, multicentre, 6-month retrospective and 4-week prospective study using self-assessment questionnaire and patient diaries included 27 585 patients, aged ≥18 years, with type 1 diabetes (T1D; n = 8022) or type 2 diabetes (T2D; n = 19 563) treated with insulin for >12 months, at 2004 sites in 24 countries worldwide. The primary endpoint was the proportion of patients experiencing at least one hypoglycaemic event during the observational period. RESULTS: During the prospective period, 83.0% of patients with T1D and 46.5% of patients with T2D reported hypoglycaemia. Rates of any, nocturnal and severe hypoglycaemia were 73.3 [95% confidence interval (CI) 72.6-74.0], 11.3 (95% CI 11.0-11.6) and 4.9 (95% CI 4.7-5.1) events/patient-year for T1D and 19.3 (95% CI 19.1-19.6), 3.7 (95% CI 3.6-3.8) and 2.5 events/patient-year (95% CI 2.4-2.5) for T2D, respectively. The highest rates of any hypoglycaemia were observed in Latin America for T1D and Russia for T2D. Glycated haemoglobin level was not a significant predictor of hypoglycaemia. CONCLUSIONS: We report hypoglycaemia rates in a global population, including those in countries without previous data. Overall hypoglycaemia rates were high, with large variations between geographical regions. Further investigation into these differences may help to optimize therapy and reduce the risk of hypoglycaemia.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial.

AIMS: To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. METHODS: After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. RESULTS: The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 ± 1.2% vs -0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. CONCLUSIONS: Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes.

In situ observations of a possible skate nursery off the western Antarctic Peninsula.

A dense aggregation of skate egg cases was imaged during a photographic survey of the sea floor along the western Antarctic Peninsula in November 2013. Egg cases were noted in a narrow band between 394 and 443 m depth. Although some skate species in other oceans are known to utilize restricted areas to deposit eggs in great numbers, such nurseries have not been described in the Southern Ocean.

Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials.

AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. METHODS: Six randomized, placebo-controlled studies of lixisenatide 20 µg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. RESULTS: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9 mmol/l, p < 0.001) and glucose excursion (LS mean difference vs. placebo: -4.5 mmol/l, p < 0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0 ng/l, p < 0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p < 0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. CONCLUSIONS: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion.

Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P).

AIMS: To compare the efficacy and safety of once-daily prandial lixisenatide with placebo in type 2 diabetes mellitus (T2DM) insufficiently controlled by pioglitazone ± metformin. METHODS: This randomized, double-blind study included a 24-week main treatment period and a ≥52-week variable extension period. Patients were randomized 2 : 1 to receive lixisenatide 20 µg once daily or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) at week 24. RESULTS: In total, 484 patients were randomized: 323 to lixisenatide; 161 to placebo. After 24 weeks, lixisenatide once daily significantly improved HbA1c (-0.56% vs. placebo; p < 0.0001) and increased the proportion of patients achieving HbA1c <7% compared with placebo (52.3% vs. 26.4%, respectively; p < 0.0001) and significantly improved fasting plasma glucose (-0.84 mmol/l vs. placebo; p < 0.0001). There was a small decrease in body weight with lixisenatide once daily and a small increase with placebo, with no statistically significant difference between the two groups. Overall, lixisenatide once daily was well tolerated, with a similar proportion of treatment-emergent adverse events (TEAEs) and serious TEAEs between groups (lixisenatide: 72.4% and 2.5%; placebo: 72.7% and 1.9%). Symptomatic hypoglycaemia rates were also relatively low in both groups (lixisenatide 3.4% and placebo 1.2%), with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable extension period. CONCLUSIONS: Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia, and was well tolerated over 24 weeks and during the long-term, double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin.

One hundred questions of importance to the conservation of global biological diversity.

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.

Achieving a "Broad view of health": findings from the California Healthy Cities and Communities Evaluation

Promoting a "broad view of health" is an important objective of the healthy cities movement, including recognition of the powerful role that social relations and living conditions play in the health of community members. This article presents a quantitative approach to assessing consensus and change in ideas about health determinants among local coalition members. A ranking of five determinants of health in the form of paired comparisons was included in a survey of coalition members of 20 local healthy communities projects in California. Findings revealed conflicting views among members in the planning year, with some respondents emphasizing the role of social factors and living conditions and others emphasizing the role of health care and lifestyle decisions. Data collected at the end of the funded intervention showed movement toward a broader view of health, with greater consensus on this view in select communities. (AU)

Perceptions of parenting: individual differences and the effect of community.

Neighborhood norms are an important determinant of beliefs and attitudes about parenting, and measuring changes in community norms is an important component of evaluating community-based programs for improving child outcomes. The purpose of this study was to determine whether or not a survey of community residents' perceptions of parenting could be used to measure community parenting norms and whether these perceptions differed by individual or community characteristics. Two community surveys with 870 and 914 respondents, respectively, were conducted in 3 low-income neighborhoods. Results indicated that perceptions of parenting could be measured reliably at the community level although it is important to consider the presence of multiple norms when using such measures. Furthermore, differences in perceptions of parenting associated with individual characteristics were markedly decreased when neighborhood characteristics were considered, suggesting that the association of individual characteristics with perceptions of parenting is confounded by neighborhood characteristics.

Newborn screening in Wisconsin: program overview and test addition.

The prevention of congenital anomalies and their sequelae is an important public health objective. One strategy for preventing morbidity and mortality due to congenital disorders is Wisconsin's Newborn Screening Program. Wisconsin has been a national leader in newborn screening since its inception with phenylketonuria screening in 1966. Wisconsin's program is a collaborative effort of the State Maternal and Child Health Program, housed within the Division of Public Health of the Department of Health and Family Services; the State Laboratory of Hygiene; physicians and other health professionals; and families. After in-depth consideration, the Department recently approved the addition of 14 fatty acid oxidation disorders and organic acidemias. This paper provides an overview of the Newborn Screening Program and introduces the disorders that Wisconsin added to the newborn screening panel in April 2000. Technologic advances have provided Wisconsin with yet another tool to improve the health of its citizens and prevent significant morbidity and mortality.

Racial disparities in African American and white infant mortality United States and Wisconsin, 1980 to 1998.

Infant mortality is a powerful indicator for assessing the health of a population, and the extent to which society invests in its children. This paper examines infant mortality trends in the United States and Wisconsin among the African American and white populations from 1980 to 1998. Data from the National Center for Health Statistics and Wisconsin Birth and Infant Death Reports were used to examine overall infant mortality trends from 1980 to 1998 for African American and white infants. The overall infant mortality rate in Wisconsin decreased steadily from 10.3 infant deaths per 1000 live births in 1980 to 7.2 in 1998. White infant mortality followed this trend, declining from 9.6 in 1980 to 5.6 in 1998. African American infant mortality has remained about the same since 1980 at 18 infant deaths per 1000 live births, even though the overall percentage of African American live births in Wisconsin increased from 6% in 1980 to 10% in 1998. The ratio of African American to white infant mortality rates in Wisconsin increased from 2 to 1 in 1980 to 3.2 to 1 in 1998. While the Wisconsin African American infant mortality rate remained even since 1980, the US rate declined from 22.2 in 1980 to 14.1 in 1998. The Wisconsin African American rate in 1998, 17.9, surpassed the national rate. The use of 5-year running averages to smooth out year-to-year fluctuations showed statistically significant declines in Wisconsin white infant mortality rates and no change in Wisconsin African American infant mortality rates. These trends show the importance for Wisconsin to sustain its current efforts to reduce black infant mortality. At the same time, Wisconsin-based research efforts to determine strategies and factors that work should continue and influence the future design of systems, programs, and policies to eliminate the disparity.

Photon diffusion coefficient in an absorbing medium.

A number of investigators have recently claimed, based on both analysis from transport theory and transport-theory-based Monte Carlo calculations, that the diffusion coefficient for photon migration should be taken to be independent of absorption. We show that these analyses are flawed and that the correct way of extracting diffusion theory from transport theory gives an absorption-dependent diffusion coefficient. Experiments by two different sets of investigators give conflicting results concerning whether the diffusion coefficient depends on absorption. The discrepancy between theory and the earlier set of experiments poses an interesting challenge.

Nonlinear effects of localized absorption perturbations on the light distribution in a turbid medium.

A theoretical model of photon propagation in a scattering medium is presented, from which algebraic formulas for the detector-reading perturbations (delta R) produced by one or two localized perturbations in the macroscopic absorption cross section (delta mu a) are derived. Examination of these shows that when delta mu a is titrated from very small to large magnitudes in one voxel, the curve traced by the corresponding delta R values is a rectangular hyperbola. Furthermore, while delta Rinfinity identical to lim delta mu a-->infinity delta R is dependent on the location of the detector with respect to the source and the voxel, the ratio delta R/ delta Rinfinity is independent of the detector location. We also find that when delta mu a is varied in two voxels simultaneously, the quantity delta R (delta mu a,1 [symbol: see text] delta mu a,2) is a bilinear rational function of the delta mu aS. These results apply not only in the case of steady-state illumination and detection but to time-harmonic measurements as well. The validity of the theoretical formulas is demonstrated by applying them to the results of selected numerical diffusion computations. Potential applications of the derived expressions to image-reconstruction problems are discussed.