Epidemiological studies have shown that increased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2 diabetes (T2D). This may result from altered energy metabolism or dietary habits. We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity. This randomized, placebo-controlled, double-blinded, crossover trial examined well-controlled T2D patients receiving isocaloric diets (protein: 1 g/kg body weight) for 4 wk. Protein requirements were covered by commercially available food supplemented ≤60% by an AA mixture either containing all AAs or lacking BCAAs. The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake. The patients underwent the mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), and skeletal muscle and white adipose tissue biopsies to assess insulin signaling. After the BCAA- diet, BCAAs were reduced by 17% during fasting (P < 0.001), by 13% during HEC (P < 0.01), and by 62% during the MMT (P < 0.001). Under clamp conditions, whole-body and hepatic insulin sensitivity did not differ between diets. After the BCAA- diet, however, the oral glucose sensitivity index was 24% (P < 0.01) and circulating fibroblast-growth factor 21 was 21% higher (P < 0.05), whereas meal-derived insulin secretion was 28% lower (P < 0.05). Adipose tissue expression of the mechanistic target of rapamycin was 13% lower, whereas the mitochondrial respiratory control ratio was 1.7-fold higher (both P < 0.05). The fecal microbiome was enriched in Bacteroidetes but depleted of Firmicutes. Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and improves white adipose tissue metabolism and gut microbiome composition. Longer-term studies will be needed to evaluate the safety and metabolic efficacy in diabetes patients.This trial was registered at clinicaltrials.gov as NCT03261362.

The aim of this study was to test the effect of a plant-based dietary intervention on beta-cell function in overweight adults with no history of diabetes. Participants (n = 75) were randomized to follow a low-fat plant-based diet (n = 38) or to make no diet changes (n = 37) for 16 weeks. At baseline and 16 weeks, beta-cell function was quantified with a mathematical model. Using a standard meal test, insulin secretory rate was calculated by C-peptide deconvolution. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance while fasting. A marked increase in meal-stimulated insulin secretion was observed in the intervention group compared with controls (interaction between group and time, Gxt, p < 0.001). HOMA-IR index fell significantly (p < 0.001) in the intervention group (treatment effect −1.0 (95% CI, −1.2 to −0.8); Gxt, p = 0.004). Changes in HOMA-IR correlated positively with changes in body mass index (BMI) and visceral fat volume (r = 0.34; p = 0.009 and r = 0.42; p = 0.001, respectively). The latter remained significant after adjustment for changes in BMI (r = 0.41; p = 0.002). Changes in glucose-induced insulin secretion correlated negatively with BMI changes (r = −0.25; p = 0.04), but not with changes in visceral fat. Beta-cell function and insulin sensitivity were significantly improved through a low-fat plant-based diet in overweight adults.

Diet modulates gut microbiota and plays an important role in human health. The aim of this study was to test the effect of a low-fat vegan diet on gut microbiota and its association with weight, body composition, and insulin resistance in overweight men and women. We enrolled 168 participants and randomly assigned them to a vegan (n = 84) or a control group (n = 84) for 16 weeks. Of these, 115 returned all gut microbiome samples. Gut microbiota composition was assessed using uBiome Explorer™ kits. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was quantified with the predicted clamp-derived insulin sensitivity index from a standard meal test. Repeated measure ANOVA was used for statistical analysis. Body weight decreased in the vegan group (treatment effect −5.9 kg [95% CI, −7.0 to −4.9 kg]; p < 0.001), mainly due to a reduction in fat mass (−3.9 kg [95% CI, −4.6 to −3.1 kg]; p < 0.001) and in visceral fat (−240 cm³ [95% CI, −345 to −135 kg]; p < 0.001). PREDIcted M, insulin sensitivity index (PREDIM) increased in the vegan group (treatment effect +0.83 [95% CI, +0.48 to +1.2]; p < 0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (+5.1% [95% CI, +2.4 to +7.9%]; p < 0.001) and correlated negatively with changes in weight (r = −0.24; p = 0.01), fat mass (r = −0.22; p = 0.02), and visceral fat (r = −0.20; p = 0.03). The relative abundance of Bacteroides fragilis decreased in both groups, but less in the vegan group, making the treatment effect positive (+18.9% [95% CI, +14.2 to +23.7%]; p < 0.001), which correlated negatively with changes in weight (r = −0.44; p < 0.001), fat mass (r = −0.43; p < 0.001), and visceral fat (r = −0.28; p = 0.003) and positively with PREDIM (r = 0.36; p < 0.001), so a smaller reduction in Bacteroides fragilis was associated with a greater loss of body weight, fat mass, visceral fat, and a greater increase in insulin sensitivity. A low-fat vegan diet induced significant changes in gut microbiota, which were related to changes in weight, body composition, and insulin sensitivity in overweight adults, suggesting a potential use in clinical practice.

Background: The aim of this study was to evaluate a method based on a single accelerometer for the assessment of gait symmetry and regularity in subjects wearing lower limb prostheses.Methods: Ten transfemoral amputees and ten healthy control subjects were studied. For the purpose of this study, subjects wore a triaxial accelerometer on their thorax, and foot insoles. Subjects were asked to walk straight ahead for 70 m at their natural speed, and at a lower and faster speed. Indices of step and stride regularity (Ad1 and Ad2, respectively) were obtained by the autocorrelation coefficients computed from the three acceleration components. Step and stride durations were calculated from the plantar pressure data and were used to compute two reference indices (SI1 and SI2) for step and stride regularity.Results: Regression analysis showed that both Ad1 well correlates with SI1 (R²up to 0.74), and Ad2 well correlates with SI2 (R²up to 0.52). A ROC analysis showed that Ad1 and Ad2 has generally a good sensitivity and specificity in classifying amputee's walking trial, as having a normal or a pathologic step or stride regularity as defined by means of the reference indices SI1 and SI2. In particular, the antero-posterior component of Ad1 and the vertical component of Ad2 had a sensitivity of 90.6% and 87.2%, and a specificity of 92.3% and 81.8%, respectively.Conclusions: The use of a simple accelerometer, whose components can be analyzed by the autocorrelation function method, is adequate for the assessment of gait symmetry and regularity in transfemoral amputees.

We aimed to analyze the shape of the glucose, insulin, and C-peptide curves during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. Five-hundred ninety-two OGTT curves were analyzed, mainly from women with former gestational diabetes, with glycemic concentrations characterized by normal glucose tolerance ( n = 411), impaired glucose metabolism ( n = 134), and Type 2 diabetes ( n = 47). Glucose curves were classified according to their shape (monophasic, biphasic, triphasic, and 4/5-phases), and the metabolic condition of the subjects, divided according to the glucose shape stratification, was analyzed. Indices of shape based on the discrete second-order derivative of the curve patterns were also defined. We found that the majority of the glucose curves were monophasic ( n = 262). Complex shapes were less frequent but not rare ( n = 37 for the 4/5-phases shape, i.e., three peaks). There was a tendency toward the amelioration of the metabolic condition for increasing complexity of the shape, as indicated by lower glucose concentrations, improved insulin sensitivity and β-cell function. The shape index computed on C-peptide, WHOSH_CP (WHole-Ogtt-SHape-index–C-peptide), showed a progressive increase [monophasic: 0.93 ± 0.04 (dimensionless); 4/5-phases: 1.35 ± 0.14], and it showed properties typical of β-cell function indices. We also found that the type of glucose shape is often associated to similar insulin and C-peptide shape. In conclusion, OGTT curves can be characterized by high variability, and complex OGTT shape is associated with better glucose tolerance. WHOSH_CP (WHole-Ogtt-SHape-index) may be a powerful index of β-cell function much simpler than model-based indices.