Background: Low carbohydrate high fat (LCHF) diets are increasing in popularity amongst patients with type 2 diabetes (T2D), however it is unclear what constitutes a sustainable LCHF diet in a real-world setting. Methods: This descriptive multi-method study characterized the diets, T2D status, and personal experiences of individuals with T2D who claimed to have followed an LCHF diet for at least 6 months. Participants completed a medications history, mixed-method dietary assessment, provided a blood sample, and were interviewed in-depth about their experiences with the diet (First-Assessment). Past medical records were obtained corresponding to T2D diagnosis and prior to starting their LCHF diets. Additionally, participants were followed up 15 months later to assess T2D remission (Follow-Up). Results: Twenty-eight participants completed First-Assessment and 24 completed Follow-Up. Habitual carbohydrate intake was 20 to 50 g/d for 10 participants and 50 to 115 g/d for 17 participants. Commonly reported foods were full-fat dairy, non-starchy vegetables, coconut oil, eggs, nuts, olives and avocados, olive oil, and red meat and poultry with fat. Median (interquartile range) for HbA1c was 7.5 (6.5-9.5) % prior to starting their diets, 5.8 (5.4-6.2) % at First-Assessment and 5.9 (5.3-6.6) % at Follow-Up. Reported body weight and glucose-lowering medication requirements were considerably lower at both assessments than when starting the diet. At Follow-Up, 24 participants had been following their LCHF diets for 35 (26-53) months, the majority of which were in full or partial T2D remission. Participants perceived reduced hunger and cravings as one of the most important aspects of their diets. Of concern, many participants felt unsupported by their doctors. Conclusion: This study described the foods and characteristics of an LCHF "lifestyle" that was sustainable and effective for certain T2D patients in a real-world setting. Plain Language SummaryUntil recently, low carbohydrate high fat (LCHF) diets were not supported by most T2D dietary guidelines, and the high fat component of these diets is still controversial due to concerns over long-term health outcomes. Despite this, there are a growing number of individuals following their own version of an LCHF diet to manage their T2D. The aim of this study was to characterize the diets, health, and personal experiences of individuals with T2D who claimed to have followed an LCHF diet for at least the previous 6 months.A total of 28 participants completed the study and 24 of these participants were assessed for a second time after 15 months. We found that:

Very little is known about how long-term (>6 months) adaptation to a low-carbohydrate, high-fat (LCHF) diet affects insulin signaling in healthy, well-trained individuals. This study compared glucose tolerance; skeletal muscle glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) content; and muscle enzyme activities representative of the main energy pathways (3-hydroxyacetyl-CoA dehydrogenase, creatine kinase, citrate synthase, lactate dehydrogenase, phosphofructokinase, phosphorylase) in trained cyclists who followed either a long-term LCHF or a mixed-macronutrient (Mixed) diet. On separate days, a 2-hr oral glucose tolerance test was conducted, and muscle samples were obtained from the vastus lateralis of fasted participants. The LCHF group had reduced glucose tolerance compared with the Mixed group, as plasma glucose concentrations were significantly higher throughout the oral glucose tolerance test and serum insulin concentrations peaked later (LCHF, 60 min; Mixed, 30 min). Whole-body insulin sensitivity was not statistically significantly different between groups (Matsuda index: LCHF, 8.7 ± 3.4 vs. Mixed, 12.9 ± 4.6; p = .08). GLUT4 (LCHF: 1.13 ± 0.24; Mixed: 1.44 ± 0.16; p = .026) and IRS1 (LCHF: 0.25 ± 0.13; Mixed: 0.46 ± 0.09; p = .016) protein content was lower in LCHF muscle, but enzyme activities were not different. We conclude that well-trained cyclists habituated to an LCHF diet had reduced glucose tolerance compared with matched controls on a mixed diet. Lower skeletal muscle GLUT4 and IRS1 contents may partially explain this finding. This could possibly reflect an adaptation to reduced habitual glucose availability rather than the development of a pathological insulin resistance.

Scientific evidence suggests that low-carbohydrate high-fat (LCHF) diets may be effective for managing non-communicable diseases (NCDs). Eat Better South Africa (EBSA) is an organization that runs LCHF nutrition education programs for women from low-income communities. Three focus group discussions (FGDs) were held with 18 women who had taken part in an EBSA program between 2015 and 2017, to explore their perceptions and to identify the facilitators and barriers they faced in implementing and sustaining dietary changes. Thematic analysis of the focus groups was conducted using NVivo 12 software. Women reported that they decided to enroll in the program because they suffered from NCDs. Most women said that the EBSA diet made them feel less hungry, more energetic and they felt that their health had improved. Most women spoke of socioeconomic challenges which made it difficult for them to follow EBSA’s recommendations, such as employment status, safety issues in the community, and lack of support from relatives and doctors. Hence, women felt they needed more support from EBSA after the program. The social determinants that affected these women’s ability to change their health behavior are also NCD risk factors, and these should be assessed to improve the program for other communities.

Angiotensin‐1‐converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N‐domain in complex with Aβ fragments. For the physiological Aβ(1–16) peptide, a novel ACE cleavage site was found at His14‐Gln15. Furthermore, Aβ(1–16) was preferentially cleaved by the individual N‐domain; however, the presence of an inactive C‐domain in full‐length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4–10)Q and Aβ(4–10)Y, underwent endoproteolytic cleavage at the Asp7‐Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4–10)Y. Surprisingly, in contrast to Aβ(1–16) and Aβ(4–10)Q, sACE showed positive domain cooperativity and the double C‐domain (CC‐sACE) construct no cooperativity towards Aβ(4–10)Y. The structures of the Aβ peptide–ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C‐terminal P2′ position to the S2′ pocket and recognizes the main chain of the P1′ peptide. It is likely that N‐domain selectivity for the amyloid peptide is conferred through the N‐domain specific S2′ residue Thr358. Additionally, the N‐domain can accommodate larger substrates through movement of the N‐terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full‐length forms.DatabaseThe atomic coordinates and structure factors for N‐domain ACE with Aβ peptides 4–10 (5AM8), 10–16 (5AM9), 1–16 (5AMA), 35–42 (5AMB) and (4–10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/).

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