Abstract

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.

Abstract

BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.

Abstract

AIMS/INTRODUCTION Very few studies assess the effectiveness of different protocols of intermittent very-low calorie diet (VLCD) in patients with diabetes. This study was designed to compare the effects of 2 days/week and 4 days/week of intermittent VLCD on glycemic control, diabetes remission, metabolic parameters and quality of life in patients with type 2 diabetes and obesity. MATERIALS AND METHODS Participants with obesity and type 2 diabetes were recruited and randomly assigned to three groups, consisting of control, 2 days/week and 4 days/week of intermittent VLCD. In the intermittent VLCD groups, participants received a 600-kcal diet per day on restricted days and ad libitum food consumption on non-restricted days. Glycemic control, rate of diabetes remission, metabolic parameters and quality of life were evaluated at baseline, weeks 2, 10 and 20. RESULTS A total of 40 participants were enrolled. The mean body mass index was 30.1 ± 5.9 kg/m2 , and the mean glycated hemoglobin was 7.4 ± 1.2%. At week 20, there was an improvement in glycemic control in both intermittent VLCD groups with significant decreases in glycated hemoglobin levels and insulin resistance index throughout the study periods. Diabetes remission without the need for medications was equally found in 29% of participants in both intermittent VLCD groups. Serum triglyceride, bodyweight, body mass index and fat mass were also significantly decreased in both VLCD groups. No serious adverse events were encountered. CONCLUSION Intermittent VLCD was highly effective in achieving optimal glycemic control. The effects of 2 days/week and 4 days/week of intermittent VLCD on diabetes remission were relatively similar.

Abstract

Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.

Abstract

BACKGROUND The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response. METHODS A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 150 obese patients who received 16 g/d native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Anthropometry, diagnostic imaging (abdominal CT-scan, fibroscan), food-behavior questionnaires, serum biology and fecal microbiome (primary outcome; 16S rDNA sequencing) were analyzed before and after the intervention. RESULTS Both placebo and prebiotic interventions lowered energy intake, BMI, systolic blood pressure, and serum γ-GT. The prebiotic induced greater weight loss and additionally decreased diastolic blood pressure, AST and insulinemia. Metformin treatment compromised most of the gut microbiota changes and metabolic improvements linked to prebiotic intervention. The prebiotic modulated specific bacteria, associated with the improvement of anthropometry (i.e. a decrease in Desulfovibrio and Clostridium sensu stricto). A large increase in Bifidobacterium appears as a signature of inulin intake rather than a driver of prebiotic-linked biological outcomes. CONCLUSIONS Inulin-enriched diet is able to promote weight loss in obese patients, the treatment efficiency being related to gut microbiota characteristics. This treatment is more efficacious in patients who did not receive metformin as anti-diabetic drugs prior the intervention, supporting that both drug treatment and microbiota might be taken into account in personalized nutrition interventions. Registered under ClinicalTrials.gov Identifier no NCT03852069.

Abstract

There is an association between the consumption of artificial sweeteners and Type 2 diabetes in cohort studies, but intervention studies do not show a clear elevation of blood glucose after the use of artificial sweeteners. The objective of this study was to examine whether two commonly used artificial sweeteners had an adverse effect on glucose control in normal-weight subjects, and in overweight and obese subjects when consumed for 2 weeks. In the study, 39 healthy subjects (body-mass index, kg/m2) (18-45) without Type 2 diabetes with an age of 18-75 years were randomly assigned to 0.6 L/day of an artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) or 0.6 L/day of mineral water for 2 weeks each in a crossover study. There was a 4 week washout period with no drinks consumed. Glucose levels were read by a continuous glucose monitor (CGM) during each 2 week period. A 75 g oral glucose-tolerance test (OGTT) was performed at the beginning and end of each intervention period. Blood samples were collected at baseline, and 1 and 2 h for glucose and insulin. A 2 week intake of artificially sweetened beverage (ASB) did not alter concentrations of fasting glucose and fasting insulin, the area under the curve (AUC) for OGTT glucose and insulin, the incremental area under the curve (iAUC) for OGTT glucose and insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and the Matsuda index compared with the baseline and with the changes after a 2 week intake of mineral water. Continuous 2 week glucose concentrations were not significantly different after a 2 week intake of ASB compared with a 2 week intake of mineral water. This study found no harmful effect of the artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) on glucose control when consumed for 2 weeks by people without Type 2 diabetes.

Abstract

Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation).

Abstract

The effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, -0.75 kg/m2; 95% CI, -1.44 to -0.06), fasting glucose level (WMD, -4.16 mg/dL; 95% CI, -6.92 to -1.40), and homeostatic model assessment of insulin resistance (WMD, -0.54; 95% CI, -1.05 to -0.03). Fat mass (WMD, -0.98 kg; 95% CI, -2.32 to 0.36) tended to decrease in the IFD group with a significant increase in adiponectin (WMD, 1008.9 ng/mL; 95% CI, 140.5 to 1877.3) and a decrease in leptin (WMD, -0.51 ng/mL; 95% CI, -0.77 to -0.24) levels. An IFD may provide a significant metabolic benefit by improving glycemic control, insulin resistance, and adipokine concentration with a reduction of BMI in adults.

Abstract

The relationship between dietary protein consumption and the risk of type 2 diabetes (T2D) has been inconsistent. The aim of this meta-analysis was to explore the relations between dietary protein consumption and the risk of T2D. We conducted systematic retrieval of prospective studies in PubMed, Embase, and Web of Science. Summary relative risks were compiled with a fixed effects model or a random effects model, and a restricted cubic spline regression model and generalized least squares analysis were used to evaluate the diet-T2D incidence relationship. T2D risk increased with increasing consumption of total protein and animal protein, red meat, processed meat, milk, and eggs, respectively, while plant protein and yogurt had an inverse relationship. A non-linear association with the risk for T2D was found for the consumption of plant protein, processed meat, milk, yogurt, and soy. This meta-analysis suggests that substitution of plant protein and yogurt for animal protein, especially red meat and processed meat, can reduce the risk for T2D.

Abstract

OBJECTIVE In China, a low-fat diet (LFD) is mainly recommended to help improve blood glucose levels in patients with type 2 diabetes mellitus (T2DM). However, a low-carbohydrate diet (LCD) has been shown to be effective in improving blood glucose levels in America and England. A few studies, primarily randomized controlled trials, have been reported in China as well. METHOD Firstly, we designed two 'six-point formula' methods, which met the requirements of LCD and LFD, respectively. Fifty-six T2DM patients were recruited and randomly allocated to the LCD group (n = 28) and the LFD group (n = 28). The LCD group received education about LCD's six-point formula, while the LFD group received education about LFD's six-point formula. The follow-up time was three months. The indicators for glycemic control and other metabolic parameters were collected and compared between the two groups. RESULTS Forty-nine patients completed the study. The proportions of calories from three macronutrients the patients consumed met the requirements of LCD and LFD. Compared to the LFD group, there was a greater decrease in HbA1c level in the LCD group (-0.63% vs. -0.31%, p < 0.05). The dosages of insulin and fasting blood glucoses (FBG) in the third month were lower than those at baseline in both groups. Compared with baseline values, body mass index (BMI) and total cholesterol (TC) in the LCD group were significantly reduced in the third month (p < 0.05); however, there were no statistically significant differences in the LFD group. CONCLUSIONS LCD can improve blood glucose more than LFD in Chinese patients with T2DM. It can also regulate blood lipid, reduce BMI, and decrease insulin dose in patients with T2DM. In addition, the six-point formula is feasible, easily operable, and a practical educational diet for Chinese patients with T2DM.