A secondary analysis of indices of hepatic and beta cell function following 12 weeks of carbohydrate and energy restriction vs. free-living control in adults with type 2 diabetes.

BACKGROUND: Substantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes. METHODS: We conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR: <50 g carbohydrates; ~850-1100 kcal/day; n = 20) versus treatment-as-usual (TAU; n = 16). Participants were people with T2D, using ≥ 1 glucose-lowering medication, and a body mass index of ≥ 30 kg/m2. Main outcomes were C-peptide to proinsulin ratio, circulating microRNA 375 (miR375), homeostatic model assessment (HOMA) beta-cell function (B), fatty liver index (FLI), hepatic steatosis index (HSI), HOMA insulin resistance (IR), and circulating fetuin-A and fibroblast growth factor 21 (FGF21). Data were analysed using linear regression with baseline as a covariate. RESULTS: There was no observed change in miR375 (p = 0.42), C-peptide to proinsulin ratio (p = 0.17) or HOMA B (p = 0.15). FLI and HSI were reduced by -25.1 (p < 0.0001) and - 4.9 (p < 0.0001), respectively. HOMA IR was reduced by -46.5% (p = 0.011). FGF21 was reduced by -161.2pg/mL (p = 0.035) with a similar tendency found for fetuin-A (mean difference: -16.7ng/mL; p = 0.11). These improvements in markers of hepatic function were accompanied by reductions in circulating metabolites linked to hepatic insulin resistance (e.g., diacylglycerols, ceramides) in the Pharm TCR group. CONCLUSIONS: The Pharm-TCR intervention did not improve fasting indices of beta-cell stress; however, markers of liver fat accumulation and and liver function were improved, suggesting that a LCER diet can improve some aspects of the underlying pathophysiology of T2D. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03181165).

Life cycle assessment and techno-economic analysis of nitrogen recovery by ammonia air-stripping from wastewater treatment.

Wastewater treatment plants (WWTPs) with anaerobic digestion of biosolids produce an ammonia-rich sidestream out of which nitrogen can be recovered through air stripping. Recovered ammonia can be used to produce ammonium sulfate (AS) for agricultural use, enabling the circular return of nitrogen as fertilizer to the food system. We investigate the cost and life cycle environmental impact of recovering ammonia from the sidestream of WWTPs for conversion to AS and compare it to AS production from the Haber Bosch process. We perform life cycle assessment (LCA) to investigate the environmental impact of AS fertilizer production by air-stripping ammonia from WWTP sidestreams at varying sidestream nitrogen concentrations. Techno-economic analysis (TEA) is performed to assess the break-even selling price of sidestream AS production at a WWTP in the City of Philadelphia. Greenhouse gas emissions for air-stripping technology range between 0.2 and 0.5 kg CO2e/kg AS, about six times lower than the hydrocarbon-based Haber-Bosch process, estimated at 2.5 kg CO2e/kg AS. Further reduction of greenhouse gas emissions is feasible by replacing fossil-based energy use in air-stripping process (82-98 % of net energy demand) with renewable sources. Also, a significant reduction in mineral depletion and improvement in human and ecosystem health are observed for the air-stripping approach. Furthermore, the break-even selling price for installing sidestream-based AS production at the Philadelphia's WWTP, considering capital and operating costs, is estimated at $0.046/kg AS (100 %), which is 92 % lower than the 2014 estimate of AS's average selling price at farms in the United States. We conclude that even with varying ammonia concentrations and high sidestream volume, air-stripping technology offers an environmentally and economically favorable option for implementing nitrogen recovery and simultaneous production of AS at WWTPs.

A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes.

Type 2 diabetes can be treated, and sometimes reversed, with dietary interventions; however, strategies to implement these interventions while addressing medication changes are lacking. We conducted a 12-week pragmatic, community-based parallel-group randomized controlled trial (ClinicalTrials.gov: NCT03181165) evaluating the effect of a low-carbohydrate (<50 g), energy-restricted diet (~850-1100 kcal/day; Pharm-TCR; n = 98) compared to treatment-as-usual (TAU; n = 90), delivered by community pharmacists, on glucose-lowering medication use, cardiometabolic health, and health-related quality of life. The Pharm-TCR intervention was effective in reducing the need for glucose-lowering medications through complete discontinuation of medications (35.7%; n = 35 vs. 0%; n = 0 in TAU; p < 0.0001) and reduced medication effect score compared to TAU. These reductions occurred concurrently with clinically meaningful improvements in hemoglobin A1C, anthropometrics, blood pressure, and triglycerides (all p < 0.0001). These data indicate community pharmacists are a viable and innovative option for implementing short-term nutritional interventions for people with type 2 diabetes, particularly when medication management is a safety concern.

Pharmacist-led therapeutic carbohydrate restriction as a treatment strategy for type 2 diabetes: the Pharm-TCR randomized controlled trial protocol.

BACKGROUND: The current treatment paradigm for type 2 diabetes mellitus (T2D) typically involves use of multiple medications to lower glucose levels in hope of reducing long-term complications. However, such treatment does not necessarily address the underlying pathophysiology of the disease and very few patients achieve partial, complete, or prolonged remission of T2D after diagnosis. The therapeutic potential of nutrition has been highlighted recently based on results of clinical trials reporting remission of T2D with targeted dietary approaches. During the initial phase of such interventions that restrict carbohydrates and/or induce rapid weight loss, hypoglycemia presents a notable risk to patients. We therefore hypothesized that delivering very low-carbohydrate, low-calorie therapeutic nutrition through community pharmacies would be an innovative strategy to facilitate lowering of glycated hemoglobin (A1C) while safely reducing the use of glucose-lowering medications in T2D. METHODS: A community-based randomized controlled trial that is pragmatic in nature, following a parallel-group design will be conducted (N = 200). Participants will have an equal chance of being randomized to either a pharmacist-led, therapeutic carbohydrate restricted (Pharm-TCR) diet or guideline-based treatment as usual (TAU). Pharm-TCR involves a 12-week very low carbohydrate, calorie-restricted commercial diet plan led by pharmacists and lifestyle coaches with pharmacists responsible for managing medications in collaboration with the participants' family physicians. Main inclusion criteria are diagnosis of T2D, currently treated with glucose-lowering medications, age 30-75 years, and body mass index ≥ 30. The primary outcome is a binary measure of use of glucose-lowering medication. Secondary outcomes include A1C, anthropometrics and clinical blood markers. DISCUSSION: There are inherent risks involved if patients with T2D who take glucose-lowering medications follow very low carbohydrate diets. This randomized controlled trial aims to determine whether engaging community pharmacists is a safe and effective way to deliver therapeutic carbohydrate restriction and reduce/eliminate the need for glucose-lowering medications in people with T2D. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03181165. Registered on 8 June 2017.