Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03814694. FUNDING: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.

Effects of carbohydrate restriction on postprandial glucose metabolism, ß-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes.

Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and ß-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed-meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), ß-cell sensitivity to glucose (Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% (P < 0.001), 24 h glucose by 13% (P < 0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, P < 0.05), and postprandial ISR (24%, P = 0.015), while IGI and Bup improved by 31% and 45% (both P < 0.001). The CRHP diet increased postprandial glucagon net AUC by 235% (P < 0.001), subjective satiety by 18% (P = 0.03), delayed gastric emptying by 15 min (P < 0.001), decreased gastric inhibitory polypeptide net AUC by 29% (P < 0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY, and cholecystokinin responses. A CRHP diet reduced glucose excursions and improved ß-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

Body weight and metabolic risk factors in patients with type 2 diabetes on a self-selected high-protein low-carbohydrate diet.

PURPOSE: We previously reported beneficial glucoregulatory effects of a fully provided carbohydrate-reduced, high-protein (CRHP) diet in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, in which patients maintained their body weight. Here, we investigated physiological changes during an additional 6-month period on a self-selected and self-prepared CRHP diet. METHODS: Twenty-eight patients with T2DM were instructed to consume a CRHP diet (30% of energy from carbohydrate and 30% from protein) for 24 weeks, after an initial 2 × 6-week trial when all food was prepared and provided to them. Patients received dietary advice every 2 weeks. At weeks 0, 6, 12 and 36, they underwent a 3-h intravenous glucose tolerance test, a 4-h mixed meal test, and a 48-h continuous glucose monitoring. Liver, muscle, pancreas, and visceral fat contents were measured by magnetic resonance imaging. RESULTS: During the 24-week self-selected diet period (weeks 12-36), body weight, visceral fat, liver fat, and glycated haemoglobin were maintained at the same levels achieved at the end of the fully provided diet period, and were still lower than at baseline (P < 0.05). Postprandial insulinaemia and insulin secretion were significantly greater (P < 0.05). At week 36, fasting insulin and C-peptide levels increased (P < 0.01) and daily glycaemia decreased further (P < 0.05) when compared with the end of the fully provided diet period. CONCLUSION: Substituting dietary carbohydrate for protein and fat has metabolic benefits in patients with T2DM. These beneficial effects are maintained or augmented over the next 6 months when patients self-select and self-prepare this diet in a dietitian-supported setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02764021.

An invasive foundation species enhances multifunctionality in a coastal ecosystem.

While invasive species often threaten biodiversity and human well-being, their potential to enhance functioning by offsetting the loss of native habitat has rarely been considered. We manipulated the abundance of the nonnative, habitat-forming seaweed Gracilaria vermiculophylla in large plots (25 m2) on southeastern US intertidal landscapes to assess impacts on multiple ecosystem functions underlying coastal ecosystem services. We document that in the absence of native habitat formers, this invasion has an overall positive, density-dependent impact across a diverse set of ecosystem processes (e.g., abundance and richness of nursery taxa, flow attenuation). Manipulation of invader abundance revealed both thresholds and saturations in the provisioning of ecosystem functions. Taken together, these findings call into question the focus of traditional invasion research and management that assumes negative effects of nonnatives, and emphasize the need to consider context-dependence and integrative measurements when assessing the impact of an invader, including density dependence, multifunctionality, and the status of native habitat formers. This work supports discussion of the idea that where native foundation species have been lost, invasive habitat formers may be considered as sources of valuable ecosystem functions.

A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet. METHODS: The primary outcome of the study was change in HbA1c. Secondary outcomes reported in the present paper include glycaemic variables, ectopic fat content and 24 h blood pressure. Eligibility criteria were: men and women with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), age >18 years, haemoglobin >6/>7 mmol/l (women/men) and eGFR >30 ml min-1 (1.73 m)-2. Participants were randomised by drawing blinded ballots to 6 + 6 weeks of an iso-energetic CRHP vs CD diet in an open label, crossover design aiming at body weight stability. The CRHP/CD diets contained carbohydrate 30/50 energy per cent (E%), protein 30/17E% and fat 40/33E%, respectively. Participants underwent a meal test at the end of each diet period and glycaemic variables, lipid profiles, 24 h blood pressure and ectopic fat including liver and pancreatic fat content were assessed at baseline and at the end of each diet period. Data were collected at Copenhagen University Hospital, Bispebjerg and Copenhagen University Hospital, Herlev. RESULTS: Twenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbA1c (mean ± SEM: -6.2 ± 0.8 mmol/mol (-0.6 ± 0.1%) vs -0.75 ± 1.0 mmol/mol (-0.1 ± 0.1%); p < 0.001). Nine (out of 37) pre-specified secondary outcomes are reported in the present paper, of which five were significantly different between the diets, (p < 0.05); compared with a CD diet, a CRHP diet reduced the secondary outcomes (mean ± SEM or medians [interquartile range]) of fasting plasma glucose (-0.71 ± 0.20 mmol/l vs 0.03 ± 0.23 mmol/l; p < 0.05), postprandial plasma glucose AUC (9.58 ± 0.29 mmol/l × 240 min vs 11.89 ± 0.43 mmol/l × 240 min; p < 0.001) and net AUC (1.25 ± 0.20 mmol/l × 240 min vs 3.10 ± 0.25 mmol/l × 240 min; p < 0.001), hepatic fat content (-2.4% [-7.8% to -1.0%] vs 0.2% [-2.3% to 0.9%]; p < 0.01) and pancreatic fat content (-1.7% [-3.5% to 0.6%] vs 0.5% [-1.0% to 2.0%]; p < 0.05). Changes in other secondary outcomes, i.e. 24 h blood pressure and muscle-, visceral- or subcutaneous adipose tissue, did not differ between diets. CONCLUSIONS/INTERPRETATION: A moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbA1c and hepatic fat content in weight stable individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02764021. FUNDING: The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg.

Impacts of Climate Change on Marine Foundation Species.

Marine foundation species are the biotic basis for many of the world's coastal ecosystems, providing structural habitat, food, and protection for myriad plants and animals as well as many ecosystem services. However, climate change poses a significant threat to foundation species and the ecosystems they support. We review the impacts of climate change on common marine foundation species, including corals, kelps, seagrasses, salt marsh plants, mangroves, and bivalves. It is evident that marine foundation species have already been severely impacted by several climate change drivers, often through interactive effects with other human stressors, such as pollution, overfishing, and coastal development. Despite considerable variation in geographical, environmental, and ecological contexts, direct and indirect effects of gradual warming and subsequent heatwaves have emerged as the most pervasive drivers of observed impact and potent threat across all marine foundation species, but effects from sea level rise, ocean acidification, and increased storminess are expected to increase. Documented impacts include changes in the genetic structures, physiology, abundance, and distribution of the foundation species themselves and changes to their interactions with other species, with flow-on effects to associated communities, biodiversity, and ecosystem functioning. We discuss strategies to support marine foundation species into the Anthropocene, in order to increase their resilience and ensure the persistence of the ecosystem services they provide.

Global impacts of marine heatwaves on coastal foundation species.

With increasingly intense marine heatwaves affecting nearshore regions, foundation species are coming under increasing stress. To better understand their impacts, we examine responses of critical, habitat-forming foundation species (macroalgae, seagrass, corals) to marine heatwaves in 1322 shallow coastal areas located across 85 marine ecoregions. We find compelling evidence that intense, summer marine heatwaves play a significant role in the decline of foundation species globally. Critically, detrimental effects increase towards species warm-range edges and over time. We also identify several ecoregions where foundation species don't respond to marine heatwaves, suggestive of some resilience to warming events. Cumulative marine heatwave intensity, absolute temperature, and location within a species' range are key factors mediating impacts. Our results suggest many coastal ecosystems are losing foundation species, potentially impacting associated biodiversity, ecological function, and ecosystem services provision. Understanding relationships between marine heatwaves and foundation species offers the potential to predict impacts that are critical for developing management and adaptation approaches.

Effect of a 6-Week Carbohydrate-Reduced High-Protein Diet on Levels of FGF21 and GDF15 in People With Type 2 Diabetes.

Context: Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are increased in type 2 diabetes and are potential regulators of metabolism. The effect of changes in caloric intake and macronutrient composition on their circulating levels in patients with type 2 diabetes are unknown. Objective: To explore the effects of a carbohydrate-reduced high-protein diet with and without a clinically significant weight loss on circulating levels of FGF21 and GDF15 in patients with type 2 diabetes. Methods: We measured circulating FGF21 and GDF15 in patients with type 2 diabetes who completed 2 previously published diet interventions. Study 1 randomized 28 subjects to an isocaloric diet in a 6 + 6-week crossover trial consisting of, in random order, a carbohydrate-reduced high-protein (CRHP) or a conventional diabetes (CD) diet. Study 2 randomized 72 subjects to a 6-week hypocaloric diet aiming at a ∼6% weight loss induced by either a CRHP or a CD diet. Fasting plasma FGF21 and GDF15 were measured before and after the interventions in a subset of samples (n = 24 in study 1, n = 66 in study 2). Results: Plasma levels of FGF21 were reduced by 54% in the isocaloric study (P < .05) and 18% in the hypocaloric study (P < .05) in CRHP-treated individuals only. Circulating GDF15 levels increased by 18% (P < .05) following weight loss in combination with a CRHP diet but only in those treated with metformin. Conclusion: The CRHP diet significantly reduced FGF21 in people with type 2 diabetes independent of weight loss, supporting the role of FGF21 as a "nutrient sensor." Combining metformin treatment with carbohydrate restriction and weight loss may provide additional metabolic improvements due to the rise in circulating GDF15.

Long-term community shifts driven by local extinction of an iconic foundation species following an extreme marine heatwave.

Gradual ocean warming combined with stronger marine heatwaves (MHWs) can reduce abundances of foundation species that control community structures, biodiversity, and ecosystem functioning. However, few studies have documented long-term succession trajectories following the more extreme events that cause localized extinctions of foundation species. Here, we documented long-term successional changes to marine benthic communities in Pile Bay, New Zealand, following the Tasman 2017/18 MHW, which caused localized extinctions of dominant southern bull kelp (Durvillaea sp.). Six years on, multiscale annual and seasonal surveys show no sign of Durvillaea recolonization. Instead, the invasive annual kelp (Undaria pinnatifida), rapidly colonized areas previously dominated by Durvillaea, followed by large changes to the understory community, as Durvillaea holdfasts and encrusting coralline algae were replaced by coralline turf. Between 3 and 6 years after the total loss of Durvillaea, smaller native fucoids colonized in high densities. Although Undaria initially colonized plots throughout Durvillaea's tidal range, later in the succession Undaria only retained dominance in the lower intertidal zone and only in spring. Ultimately, the tidal zone was slowly replaced by alternative foundation species, composed of different canopy-forming brown seaweeds that dominated different intertidal elevations, resulting in a net increase in canopy and understory diversity. This study is a rare example of long-term effects following an extreme MHW that caused extinctions of a locally dominant canopy-former, but these events and their associated dramatic changes to community structures and biodiversity are expected to become increasingly common as MHWs continue to increase in strength, frequency, and duration.

Facilitation of animals is stronger during summer marine heatwaves and around morphologically complex foundation species.

Foundation species create biogenic habitats, modify environmental conditions, augment biodiversity, and control animal community structures. In recent decades, marine heatwaves (MHWs) have affected the ecology of foundation species worldwide, and perhaps also their associated animal communities. However, no realistic field experiment has tested how MHWs affect animals that live in and around these foundation species. We therefore tested, in a four-factorial field experiment, if colonisation by small mobile marine animals (epifauna) onto plates with attached single versus co-occurring foundation species of different morphological complexities, were affected by 3-5°C heating (that mirrored a recent extreme MHW in the study area) and if the heating effect on the epifauna varied within and between seasons. For this experiment mimics of turf seaweed represented the single foundation species and holdfasts of seven common canopy-forming seaweed represented the co-occurring foundation species with different morphological complexities. We found that the taxonomic richness and total abundance of epifauna, dominated by copepods, generally were higher on heated plates with complex seaweed holdfasts in warmer summer trials. Furthermore, several interactions between test-factors were significant, e.g., epifaunal abundances, were, across taxonomic groups, generally higher in warmer than colder summer trials. These results suggest that, in temperate ecosystems, small, mobile, short-lived, and fast-growing marine epifauna can be facilitated by warmer oceans and morphologically complex foundation species, implying that future MHWs may increase secondary production and trophic transfers between primary producers and fish. Future studies should test whether these results can be scaled to other ecological species-interactions, across latitudes and biogeographical regions, and if similar results are found after longer MHWs or within live foundation species under real MHW conditions.

Spatiotemporal stressors, not secondary structures or small temperature increases, control rapid facilitation of intertidal epifauna.

Small animals (epifauna) are ubiquitous in marine systems. Epifauna have high secondary production and provide trophic linkages between primary producers and higher-order consumers, like fish. Despite their importance, little is known about how these animals respond to warming or how their communities vary across spatiotemporal gradients. Here we use mimics of turf seaweed and invasive kelp holdfast to test, in a 5-factorial field experiment, whether intertidal epifauna are facilitated by different habitat structures, temperature conditions, and along cooccurring spatiotemporal gradients. We found that facilitation of epifauna by intertidal turf seaweed peaked in summer, at low elevation, in older habitats and at a less wave-exposed site. However, epifauna were not affected by the presence of a secondary structure like kelp holdfast mimics or small temperature increases from passive solar heating of black and white mimics. There were many significant two-way, but few higher order interactions, showing stronger facilitation under specific environmental conditions, like at low elevation in summer, or low elevation in old habitats. These results highlight that turf-associated epifauna are controlled by vertical elevation, season, hydrodynamics, and habitat age, and appear to be resilient to small temperature increases. Findings are important to better understand linkages between primary producers and higher order consumers and system-wide productivity, and because fast growing turf, facilitated by global warming and eutrophication, are increasingly outcompeting slower growing large perennial canopy forming seaweeds, like kelp and rockweeds.

Biological Impacts of Marine Heatwaves.

Climatic extremes are becoming increasingly common against a background trend of global warming. In the oceans, marine heatwaves (MHWs)-discrete periods of anomalously warm water-have intensified and become more frequent over the past century, impacting the integrity of marine ecosystems globally. We review and synthesize current understanding of MHW impacts at the individual, population, and community levels. We then examine how these impacts affect broader ecosystem services and discuss the current state of research on biological impacts of MHWs. Finally, we explore current and emergent approaches to predicting the occurrence andimpacts of future events, along with adaptation and management approaches. With further increases in intensity and frequency projected for coming decades, MHWs are emerging as pervasive stressors to marine ecosystems globally. A deeper mechanistic understanding of their biological impacts is needed to better predict and adapt to increased MHW activity in the Anthropocene.

Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes.

Context: Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown. Objective: This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes. Methods: A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions. Results: By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition. Conclusion: Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes.

Herbivory limits success of vegetation restoration globally.

Restoring vegetation in degraded ecosystems is an increasingly common practice for promoting biodiversity and ecological function, but successful implementation is hampered by an incomplete understanding of the processes that limit restoration success. By synthesizing terrestrial and aquatic studies globally (2594 experimental tests from 610 articles), we reveal substantial herbivore control of vegetation under restoration. Herbivores at restoration sites reduced vegetation abundance more strongly (by 89%, on average) than those at relatively undegraded sites and suppressed, rather than fostered, plant diversity. These effects were particularly pronounced in regions with higher temperatures and lower precipitation. Excluding targeted herbivores temporarily or introducing their predators improved restoration by magnitudes similar to or greater than those achieved by managing plant competition or facilitation. Thus, managing herbivory is a promising strategy for enhancing vegetation restoration efforts.

Unravelling seasonal trends in coastal marine heatwave metrics across global biogeographical realms.

Marine heatwaves (MHWs) can cause dramatic changes to ecologically, culturally, and economically important coastal ecosystems. To date, MHW studies have focused on geographically isolated regions or broad-scale global oceanic analyses, without considering coastal biogeographical regions and seasons. However, to understand impacts from MHWs on diverse coastal communities, a combined biogeographical-seasonal approach is necessary, because (1) bioregions reflect community-wide temperature tolerances and (2) summer or winter heatwaves likely affect communities differently. We therefore carried out season-specific Theil-Sen robust linear regressions and Pettitt change point analyses from 1982 to 2021 on the number of events, number of MHW days, mean intensity, maximum intensity, and cumulative intensity of MHWs, for each of the world's 12 major coastal biogeographical realms. We found that 70% of 240 trend analyses increased significantly, 5% decreased and 25% were unaffected. There were clear differences between trends in metrics within biogeographical regions, and among seasons. For the significant increases, most change points occurred between 1998 and 2006. Regression slopes were generally positive across MHW metrics, seasons, and biogeographical realms as well as being highest after change point detection. Trends were highest for the Arctic, Northern Pacific, and Northern Atlantic realms in summer, and lowest for the Southern Ocean and several equatorial realms in other seasons. Our analysis highlights that future case studies should incorporate break point changes and seasonality in MHW analysis, to increase our understanding of how future, more frequent, and stronger MHWs will affect coastal ecosystems.

Weight loss improves ß-cell function independently of dietary carbohydrate restriction in people with type 2 diabetes: A 6-week randomized controlled trial.

Background: Carbohydrate restriction may benefit ß-cell function and glucose metabolism in type 2 diabetes (T2D) but also leads to weight loss which in itself is beneficial. Methods: In order to determine the additional effect of carbohydrate restriction in addition to a fixed body weight loss, we randomly assigned 72 adults with T2D and obesity (mean ± SD HbA1c 7.4 ± 0.7%, BMI 33 ± 5 kg/m2) to a carbohydrate-reduced high-protein diet (CRHP; energy percent from carbohydrate/protein/fat: 30/30/40) or an isocaloric conventional diabetes diet (CD; 50/17/33) for 6 weeks. All foods were provided free of charge and total energy intake was tailored individually, so both groups lost 6% of baseline body weight. Results: Despite significantly greater reductions in HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol) after 6 weeks, the CRHP diet neither improved glucose tolerance, ß-cell response to glucose, insulin sensitivity, during a 4-h oral glucose tolerance test, nor basal proinsulin secretion when compared to the CD diet, but increased C-peptide concentration and insulin secretion rate (area under the curve [AUC] and peak) significantly more (~10%, P ≤ 0.03 for all). Furthermore, compared with the CD diet, the CRHP diet borderline increased basal glucagon concentration (16 [-0.1, 34]%, P = 0.05), but decreased glucagon net AUC (-2.0 [-3.4, -0.6] mmol/L ×240 min, P < 0.01), decreased basal triglyceride and total AUC (~20%, P < 0.01 for both), and increased gastric inhibitory polypeptide total AUC (14%, P = 0.01). Conclusion: A moderately carbohydrate-restricted diet for 6 weeks decreased HbA1c but did not improve ß-cell function or glucose tolerance beyond the effects of weight loss when compared with a conventional diabetes diet in people with T2D. Clinical trials registration: www.Clinicaltrials.gov, Identifier: NCT02472951.

Effects of Carbohydrate Restriction on Body Weight and Glycemic Control in Individuals with Type 2 Diabetes: A Randomized Controlled Trial of Efficacy in Real-Life Settings.

A fully provided, hypocaloric, carbohydrate-reduced high-protein (CRHP) diet compared to a hypocaloric conventional diabetes (CD) diet for 6 weeks improved glycemic control to a greater extent in face of an intended 6% weight loss in individuals with type 2 diabetes mellitus (T2DM). The present 24-week extension of that study reports on the efficacy of CRHP and CD diets in a real-life setting. Sixty-five individuals with T2DM who completed the initial 6-week fully provided diet period (% energy from carbohydrate, protein, and fat was 30/30/40 in CRHP, and 50/17/33 in CD) continued a free-living, dietician guided 24-week period of which 59 individuals completed. The CRHP compared to CD group reported a 4% lower carbohydrate intake and had higher urea excretion by 22% (both p ≤ 0.05) at week 30, suggesting less difference in carbohydrate and protein intake between groups during the 24-week extension compared to week 6. The loss of body weight during the initial 6 weeks was maintained in both groups during the 24-week extension (-5.5 ± 4.5 and -4.6 ± 4.8 kg) as well as HbA1c (-8.4 ± 6.2 and -8.4 ± 6.9 mmol/mol) with no significant differences between groups. The additional benefits on glucoregulation harnessed by carbohydrate restriction under full diet provision for 6 weeks combined with titrated weight loss could not be maintained in a real-life setting of self-prepared diet aiming on similar diets for 6 months.

Weight-loss induced by carbohydrate restriction does not negatively affect health-related quality of life and cognition in people with type 2 diabetes: A randomised controlled trial.

BACKGROUND & AIMS: We evaluated the effect of weight loss induced by dietary carbohydrate restriction on health-related quality of life (HRQoL) and cognition in type 2 diabetes (T2D). METHODS: In this randomised parallel trial, 72 adults with T2D and overweight/obesity (mean ± SD, HbA1c: 57 ± 8 mmol/mol and BMI: 33 ± 5 kg/m2) were randomly assigned to a carbohydrate-reduced high-protein diet (CRHP: C30E%-P30E%-F40E%) or conventional diabetes diet (CD: C50E%-P17E%-F33E%) for 6 weeks, targeting a 6% weight loss. HRQoL was assessed from the short form 36 (SF-36) questionnaire, including physical and mental component summary (PCS and MCS) scores; global cognition, verbal memory, attention and psychomotor speed, and executive function were assessed from a neuropsychological test battery. RESULTS: Both diet groups achieved a 5.8 kg weight loss and improved PCS (median [25th;75th percentiles], CD: 2.7 [1.1; 4.2] vs. CRHP: 2.1 [0.7; 3.7]), with no difference between diets. The CRHP diet resulted in a clinically relevant improvement of MCS, albeit non-significantly different compared with the change after the CD diet (2.0 [-0.7; 4.8], p = 0.15). Global cognition, attention, and verbal memory were unaffected by the CRHP diet, which selectively worsened the Symbol Digit Modality Test assessing psychomotor speed when compared with the CD diet (-4.1 [-7.2;-1.1], p < 0.01). CONCLUSION: Physical health improved by weight loss independently of macronutrient distribution, while mental health and cognition may be affected by the amount of carbohydrate, protein and fat in the diet. Collectively, our data suggest that weight loss through moderate carbohydrate restriction has no clinically important impact on HRQoL and global cognition in patients with T2D. Registered under ClinicalTrials.gov Identifier no. NCT03814694.