Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.

AIM: To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide. METHODS: In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs. RESULTS: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period. CONCLUSIONS: An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission.

Multi-decadal geochemical evolution of drainage from underground coal mines in the Appalachian basin, USA.

Coal mine drainage (CMD) in Appalachia is a widespread source of dissolved metals, SO4, and acidity that can degrade aquatic habitats and water supplies for decades following mine closure and flooding. In the bituminous coalfield of Pennsylvania, the Irwin Coal Basin (ICB) contains a series of partly to completely flooded, abandoned underground mines separated by leaky barriers within the Pittsburgh coal seam. CMD originated throughout the basin from minepool aquifers that formed after mine closures dating from 1910 to 1957. Historical and recent water quality data for eight CMD sites across the ICB, plus mineralogy and cation-exchange capacity of overburden lithologies, were analyzed to quantify important reactants and evaluate spatial and temporal water-quality trends. As overburden thickness and residence time increase along a ~ 50-km flowpath northeast to southwest in the basin, CMD becomes more alkaline, and Na concentrations increase. Since the 1970s, all eight ICB discharges have become less acidic, with exponential decreases in acidity, SO4, and Fe concentrations; only two CMD remain net-acidic (acidic pH at equilibrium). Exponential decay models that include a steady-state asymptote consistent with background groundwater chemistry and siderite equilibrium describe the early-stage, rapid contaminant concentration decay immediately after the "first flush" (initial flooding) and the progressive evolution toward late-stage background conditions. A geochemical evolution PHREEQC model indicates that spatial and temporal trends in pH, net-acidity, SO4, Fe, and major cations could be explained by the continuous dilution of first flush water by ambient groundwater combined with sustained water-mineral reactions involving pyrite and carbonates (calcite, dolomite, siderite) plus cation-exchange by clays (illite, chlorite, mixed-layer illite/smectite). These data and model results indicate that 1) cation-exchange reactions enhance calcite dissolution and alkalinity production, resulting in the evolution of CMD to Na-SO4-HCO3 type waters, and 2) siderite equilibrium could maintain dissolved Fe >16 mg/L over the next 40 years.

Omega-3 Polyunsaturated Fatty Acids with Adipose Tissue Inflammation: Longitudinal Analysis in the PROMISE Cohort.

OBJECTIVES: Although pre-clinical studies have shown a beneficial impact of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on adipose (AT) inflammation, the current literature from human studies is limited. Therefore, we aimed to evaluate the longitudinal associations of circulating levels of n-3 PUFAs with biomarkers of AT inflammation. METHODS: Longitudinal data from participants in the PROMISE cohort (n = 474) were used. AT inflammation was measured using circulating biomarkers at baseline and up to 2 follow-up visits. n-3 PUFAs were measured at baseline in four serum lipid fractions. Generalized estimating equations (GEE) analyses evaluated longitudinal associations between n-3 PUFAs and AT inflammation, adjusting for covariates. RESULTS: Fully adjusted GEE models indicated that higher baseline proportions of eicosapentaenoic acid (EPA), n-3 docosapentaenoic acid (n-3 DPA), and docosahexaenoic acid (DHA) in total serum were significantly inversely associated with longitudinal change in soluble CD163 (sCD163) (all p < 0.05). A significant positive association of n-3 DPA and DHA with longitudinal change in adiponectin (p < 0.05) was also observed. Generally consistent associations were observed between n-3 PUFAs and sCD163 and adiponectin in the four lipid fractions. CONCLUSIONS: These findings will add to the limited evidence on the potential role n-3 PUFAs have in the prevention and management of AT inflammation in humans and may help inform future interventions targeting chronic inflammation at the level of AT.

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Context: Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined. Objective: Our objective was to assess the association of uVDBP with longitudinal changes in kidney function. Methods: Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates. Results: Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 µg/mmol, 2.63 µg/mmol, and 2.48 µg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (ß = 30.67 and ß = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Assessing Meaningful Improvement: Focus on the Tinnitus Functional Index.

Many studies have attempted to determine methodology for interpreting change on outcome instruments that result from an intervention. The objective of these studies has been to devise methods to identify the minimal level of change that would be consistent with actual benefit perceived by the patient, and not just statistically significant change. With respect to intervention for bothersome tinnitus, the authors of the original study to develop and validate the Tinnitus Functional Index (TFI) suggested that a minimum 13-point reduction in the TFI score was likely to reflect a change perceived as meaningful to an individual. The 13-point estimation of meaningful change for an individual is appropriate for use with any adult seeking care for tinnitus. However, it cannot be relied upon in isolation to determine if an individual believes that there has been a noticeable, or meaningful improvement in their quality of life. It is important to use subjective impressions elicited from the patient to assist in interpreting the meaning of TFI data for an individual. For clinicians engaging in care for tinnitus, we recommend using the TFI and pairing it with the patient's belief/impression as to whether they are doing better than they were before care for tinnitus was provided. Ideally, the outcome assessment would be conducted by someone other than the clinician who provided the intervention.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study.

BACKGROUND: The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories. METHODS: We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes. RESULTS: WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34). CONCLUSIONS: This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Acupuncture Reduces Severity of Hot Flashes in Breast Cancer: A Randomized Single-Blind Trial.

This study evaluated the effectiveness of traditional Chinese medicine-based therapeutic acupuncture (TA) in reducing the severity of hot flashes (HFs) in breast cancer patients and compared the effectiveness of TA to "sham" placebo acupuncture (SA). Subjects experiencing more than 10 episodes of HF/week were randomly assigned to TA or SA. The response was assessed by the Menopause-specific Quality of Life (MenQoL) scale, scoring the subject's perception of the severity of HFs. HFs were scored at baseline, after treatment, and 1-month follow-up. A total of 54 subjects enrolled (28 TA and 26 SA). Seven women withdrew from the study. A hot flash diary documented the number of HFs a subject experienced. Analysis included 47 subjects (27 TA and 20 SA). A statistically significant response in HF scores was noted in the TA group compared with the SA group (P = .0064.) On average HF scores dropped by 1.89 with TA, and only 0.16 with SA. At follow-up, TA subjects had a sustained response. TA is effective in reducing the intensity and severity of HF. With SA, no relative response/change in HF scores was noted. Larger studies and longer follow-up to assess durability of response to TA are needed.

Severe (level 3) hypoglycaemia occurrence in a real-world cohort of adults with type 1 or 2 diabetes mellitus (iNPHORM, United States).

AIMS: Among adults with insulin- and/or secretagogue-treated diabetes in the United States, very little is known about the real-world descriptive epidemiology of iatrogenic severe (level 3) hypoglycaemia. Addressing this gap, we collected primary, longitudinal data to quantify the absolute frequency of events as well as incidence rates and proportions. MATERIALS AND METHODS: iNPHORM is a US-wide, 12-month ambidirectional panel survey (2020-2021). Adults with type 1 diabetes mellitus (T1DM) or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T2DM) were recruited from a probability-based internet panel. Participants completing ≥1 follow-up questionnaire(s) were analysed. RESULTS: Among 978 respondents [T1DM 17%; mean age 51 (SD 14.3) years; male: 49.6%], 63% of level 3 events were treated outside the health care system (e.g. by family/friend/colleague), and <5% required hospitalization. Following the 12-month prospective period, one-third of individuals reported ≥1 event(s) [T1DM 44.2% (95% CI 36.8%-51.8%); T2DM 30.8% (95% CI 28.7%-35.1%), p = .0404, α = 0.0007]; and the incidence rate was 5.01 (95% CI 4.15-6.05) events per person-year (EPPY) [T1DM 3.57 (95% CI 2.49-5.11) EPPY; T2DM 5.29 (95% CI 4.26-6.57) EPPY, p = .1352, α = 0.0007]. Level 3 hypoglycaemia requiring non-transport emergency medical services was more common in T2DM than T1DM (p < .0001, α = 0.0016). In total, >90% of events were experienced by <15% of participants. CONCLUSIONS: iNPHORM is one of the first long-term, prospective US-based investigations on level 3 hypoglycaemia epidemiology. Our results underscore the importance of participant-reported data to ascertain its burden. Events were alarmingly frequent, irrespective of diabetes type, and concentrated in a small subsample.

Patient and physician perspectives and experiences of basal insulin titration in type 2 diabetes in the United States: Cross-sectional surveys.

AIM: Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education. MATERIALS AND METHODS: In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months. RESULTS: In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%). CONCLUSIONS: There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.

Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and ß-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

A unique group of circulating very-long-chain saturated fatty acids (VLCSFAs), including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have been associated with a lower risk of type 2 diabetes, although associations with early metabolic risk phenotypes preceding type 2 diabetes have received limited study. We aimed to examine the associations of VLCSFAs with longitudinal changes in insulin sensitivity and ß-cell function in a cohort at risk for type 2 diabetes. VLCSFAs in the four main serum pools (phospholipid, triacylglycerol, cholesteryl ester, and nonesterified fatty acid) were extracted from fasting baseline samples (n = 467). Generalized estimating equations were used to determine the associations between VLCSFAs and changes over 9 years in validated indices of insulin sensitivity (HOMA2-%S [insulin sensitivity as percentage of normal population and ISI) and ß-cell function (insulinogenic index [IGI], IGI divided by HOMA-insulin resistance [IGI/IR], and insulin secretion sensitivity index 2 [ISSI-2]). Associations of VLCSFAs with outcomes were strongest in the triacylglycerol lipid pool: 20:0 was positively associated with both insulin sensitivity and ß-cell function (5.01% increase in HOMA2-%S and 4.01-6.28% increase in IGI/IR and ISSI-2 per SD increase in 20:0); 22:0 was positively associated with insulin sensitivity, with a 6.55% increase in HOMA2-%S and a 5.80% increase in ISI per SD increase in 22:0. Lastly, 24:0 was positively associated with insulin sensitivity and ß-cell function (7.94-8.45% increase in HOMA2-%S and ISI, and a 4.61-6.93% increase in IGI/IR and ISSI-2 per SD increase in 24:0). Fewer significant associations were observed in the cholesteryl ester and nonesterified pools. Overall, our results indicate positive longitudinal associations of VLCSFAs with insulin sensitivity and ß-cell function, especially within the triacylglycerol pool.

Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

A drug-incorporated-microparticle-eggshell-membrane-scaffold (DIMES) dressing: A novel biomaterial for localised wound regeneration.

Chronic wounds affect millions of people annually and have emotional and financial implications in addition to health issues. The current treatment for chronic wounds involves the repeated use of bandages and drugs such as antibiotics over an extended period. A cost-effective and convenient solution for wound healing is the development of drug-incorporated bandages. This study aimed to develop a biocompatible bandage made of drug-incorporated poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) and eggshell membrane (ESM) for cornea wound healing. ESM has desirable properties for wound healing and can be isolated from eggshells using acetic acid or ethylenediaminetetraacetic acid (EDTA) protocols. Fluorescein isothiocyanate-labelled Bovine Serum Albumin (FITC-BSA) was used as a model drug, and the PLGA MPs were fabricated using a solvent extraction method. The MPs were successfully attached to the fibrous layer of the ESM using NaOH. The surface features of the ESM samples containing MPs were studied using a field emission scanning electron microscope (FESEM) and compared with blank ESM images. The findings indicated that the MPs were attached to the ESM fibres and had similar shapes and sizes as the control MPs. The fibre diameters of the MPs samples were assessed using Fiji-ImageJ software, and no significant changes were observed compared to the blank ESM. The surface roughness, Ra values, of the MPs incorporated ESM samples were evaluated and compared to the blank ESM, and no significant changes were found. Fourier transform infrared (FTIR) spectroscopy was used to analyse the chemical Composition of the bandage, and the spectra showed that the FBM were effectively incorporated into the ESM. The FTIR spectra identified the major peaks of the natural ESM and the PLGA polymer in the bandage. The bandage was transparent but had a reduced visibility in the waterproof test card method. The bandage achieved sustained drug release up to 10 days and was found to be biocompatible and non-toxic in a chorioallantoic membrane (CAM) assay. Overall, the drug-incorporated PLGA MPs-ESM bandage has great potential for treating chronic wounds.

Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes.

In early type 2 diabetes, the strategy of "induction" with short-term intensive insulin therapy followed by "maintenance" with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this secondary analysis of ClinicalTrials.Gov NCT02192424, adults with ≤5-years diabetes duration were randomized to 3-weeks induction insulin therapy (glargine/lispro) followed by metformin maintenance either with or without intermittent 2-week courses of insulin every 3-months for 2-years. Sustained stabilization (higher beta-cell function at 2-years than at baseline) was achieved in 55 of 99 participants. Independent predictors of sustained stabilization were the change in beta-cell function during induction and changes in hepatic insulin resistance and alanine aminotransferase during maintenance. Thus, initial reversibility of beta-cell dysfunction during induction and subsequent preservation of hepatic insulin sensitivity during maintenance are associated with sustained stabilization of beta-cell function following short-term insulin and metformin.ClinicalTrials.Gov NCT02192424.

Development and validation of a real-world model to predict 1-year Level 3 (severe) hypoglycaemia risk in adults with diabetes (the iNPHORM study, United States).

AIMS: We aimed to develop and internally validate a real-world prognostic model for Level 3 hypoglycaemia risk compatible with outpatient care in the United States. MATERIALS AND METHODS: iNPHORM is a 12-month, US-based panel survey. Adults (18-90 years old) with type 1 diabetes mellitus or insulin- and/or secretagogue-treated type 2 diabetes mellitus were recruited from a nationwide, probability-based internet panel. Among participants completing ≥ 1 follow-up questionnaire(s), we modelled 1-year Level 3 hypoglycaemia risk using Andersen and Gill's Cox survival and penalized regression with multiple imputation. Candidate variables were selected for their clinical relevance and ease of capture at point-of-care. RESULTS: In total, 986 participants [type 1 diabetes mellitus: 17%; men: 49.6%; mean age: 51 (SD: 14.3) years] were analysed. Across follow-up, 035.1 (95% CI: 32.2-38.1)% reported ≥1 Level 3 event(s), and the rate was 5.0 (95% CI: 4.1-6.0) events per person-year. Our final model showed strong discriminative validity and parsimony (optimism corrected c-statistic: 0.77). Numerous variables were selected: age; sex; body mass index; marital status; level of education; insurance coverage; race; ethnicity; food insecurity; diabetes type; glycated haemoglobin value; glycated haemoglobin variability; number, type and dose of various medications; number of SH events requiring hospital care (past year and over follow-up); type and number of comorbidities and complications; number of diabetes-related health care visits (past year); use of continuous/flash glucose monitoring; and general health status. CONCLUSIONS: iNPHORM is the first US-based primary prognostic study on Level 3 hypoglycaemia. Future model implementation could potentiate risk-tailored strategies that reduce real-world event occurrence and overall diabetes burden.

Environmental determinants of vegetation in the drawdown zones of a Columbia River Treaty reservoir: a template for ecosystem enhancement.

Water storage reservoirs alternately inundate and expose the drawdown zones, limiting riparian vegetation that provides wildlife habitats and contributes to the aquatic food-web. To characterize plant distributions and hydrogeomorphic associations, we inventoried quadrats in transects extending from the full-pool (FP) margin, downwards 12 m through the drawdown zones at sites around the Duncan Reservoir in British Columbia, Canada. Among the 69 plant species, black cottonwoods (Populus trichocarpa), willows (primarily Salix sitchensis) and other trees and shrubs occurred sparsely, rarely extending below 2 m below FP. Perennial herbaceous plants, especially horsetail (Equisetum arvense) and sedges (primarily Carex utriculata), were most common, extending down ~5 m below FP, and ruderal annual plants occurred sparsely at greater depths. Vegetation Cover and Species Richness were correlated with environmental factors, with (1) Elevation being highly influential, reflecting inundation duration and depth. (2) Position, longitudinal location, reflected greater vegetation diversity downstream of the reservoir. (3) Finer Substrate texture was favorable to retain moisture, but coarse sediments would resist erosion. (4) Shallow Slope was favorable to reduce drainage and included finer sediments. (5) Distance from the FP shoreline could reflect seed source proximity. Stepwise linear modeling with combined environmental factors accounted for ~30% of the variation in Vegetation Cover and Richness, and Canonical Correspondence Analysis revealed plant groupings relative to the environmental influences. At this and other storage reservoirs, regimes that reduce the frequency and duration of inundation could promote vegetation in locations with suitable environmental conditions in the upper drawdown zones, thus providing ecosystem enhancement.

Real-World Effects of Second-Generation Versus Earlier Intermediate/Basal Insulin Analogues on Rates of Hypoglycemia in Adults with Type 1 and 2 Diabetes (iNPHORM, US).

INTRODUCTION: Second-generation basal insulin analogues have been shown to reduce hypoglycemia in several trials and observational studies of select populations; however, it remains unclear whether these results persist in real-world settings. Using self-reported hypoglycemia events, we assessed whether second-generation basal insulin analogues reduce rates of hypoglycemia events (non-severe/severe; overall/daytime/nocturnal) compared to earlier intermediate/basal insulin analogues among people with insulin-treated type 1 or 2 diabetes. METHODS: We used prospectively collected data from the Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) panel survey. This US-wide, 1-year internet-based survey assessed hypoglycemia experiences and related sociodemographic and clinical characteristics of people with diabetes (February 2020-March 2021). We estimated population-average rate ratios for hypoglycemia comparing second-generation to earlier intermediate/basal insulin analogues using negative binomial regression, adjusting for confounders. Within-person variability of repeated observations was addressed with generalized estimating equations. RESULTS: Among iNPHORM participants with complete data, N = 413 used an intermediate/basal insulin analogue for ≥ 1 month during follow-up. After adjusting for baseline and time-updated confounders, average second-generation basal insulin analogue users experienced a 19% (95% CI 3-32%, p = 0.02) lower rate of overall non-severe hypoglycemia and 43% (95% CI 26-56%, p < 0.001) a lower rate of nocturnal non-severe hypoglycemia compared to earlier intermediate/basal insulin users. Overall severe hypoglycemia rates were similar among second-generation and earlier intermediate/basal insulin users (p = 0.35); however, the rate of severe nocturnal hypoglycemia was reduced by 44% (95% CI 10-65%, p = 0.02) among second-generation insulin users compared to earlier intermediate/basal insulin users. CONCLUSION: Our real-world results suggest second-generation basal insulin analogues reduce rates of hypoglycemia, especially nocturnal non-severe and severe events. Whenever possible and feasible, clinicians should prioritize prescribing these agents over first-generation basal or intermediate insulin in people with type 1 and 2 diabetes.

Exploring quality improvement for diabetes care in First Nations communities in Canada: a multiple case study.

BACKGROUND: Indigenous peoples in Canada experience higher rates of diabetes and worse outcomes than non-Indigenous populations in Canada. Strategies are needed to address underlying health inequities and improve access to quality diabetes care. As part of the national FORGE AHEAD Research Program, this study explores two primary healthcare teams' quality improvement (QI) process of developing and implementing strategies to improve the quality of diabetes care in First Nations communities in Canada. METHODS: This study utilized a community-based participatory and qualitative case study methodology. Multiple qualitative data sources were analyzed to understand: (1) how knowledge and information was used to inform the teams' QI process; (2) how the process was influenced by the context of primary care services within communities; and (3) the factors that supported or hindered their QI process. RESULTS: The findings of this study demonstrate how teams drew upon multiple sources of knowledge and information to inform their QI work, the importance of strengthening relationships and building relationships with the community, the influence of organizational support and capacity, and the key factors that facilitated QI efforts. CONCLUSIONS: This study contributes to the ongoing calls for research in understanding the process and factors affecting the implementation of QI strategies, particularly within Indigenous communities. The knowledge generated may help inform community action and the future development, implementation and scale-up of QI programs in Indigenous communities in Canada and globally.

Association of circulating branched chain fatty acids with insulin sensitivity and beta cell function in the PROMISE cohort.

Branched chain fatty acids (BCFAs) are mainly saturated fatty acids with a methyl branch on the penultimate or antepenultimate carbon atom. While BCFAs are endogenously produced via the catabolism of branched chain amino acids, the primary exogenous source of BCFAs in the human body is via the diet, including dairy products. Recently, BCFAs have been identified as having a potentially protective role in the etiology of cardiometabolic disorders although current literature is limited. We aimed to investigate the longitudinal associations of circulating BCFAs across four serum pools with insulin sensitivity, beta cell function, and glucose concentrations in the PROMISE Cohort. Estimates of insulin sensitivity were assessed using Matsuda's insulin sensitivity index (ISI) and the homeostasis model assessment of insulin sensitivity (HOMA2). Estimates of beta cell function were determined using the insulinogenic index divided by HOMA insulin resistance and the insulin secretion-sensitivity index-2 (ISSI-2). Baseline serum samples were analyzed for BCFAs using gas-chromatography flame ionization detection. Longitudinal associations were determined using generalized estimating equations. In the free fatty acid (FFA) pool, iso15:0 and anteiso15:0 were positively associated with logHOMA2 (iso15:0 logHOMA2-%S: ß = 6.86, 95% CI: [1.64, 12.36], p < 0.05, anteiso15:0 logHOMA2-%S: ß = 6.36, 95% CI: [0.63, 12.42], p < 0.05) while anteiso14:0 was inversely associated with measures of insulin sensitivity (iso14:0 logHOMA2-%S: ß = -2.35, 95% CI: [-4.26, -0.40], p < 0.05, logISI: ß = -2.30, 95% CI: [-4.32, -0.23], p < 0.05, anteiso14:0 logHOMA2-%S: ß = -4.72, 95% CI: [-7.81, -1.52], p < 0.05, logISI: ß = -6.13, 95% CI: [-9.49, -2.66], p < 0.01). Associations in other pools were less consistent. We identified the potential importance of specific BCFAs, specifically iso14:0, anteiso14:0, iso15:0, anteiso15:0, in cardiometabolic phenotypes underlying type 2 diabetes.