Francesco Fallucca

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss

BACKGROUND AND AIMS We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic+resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA(1c) decreased in Groups B-D. VO(2max), HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO(2max) and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. CONCLUSION Physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Effect of an Intensive Exercise Intervention Strategy on Modifiable Cardiovascular Risk Factors in Subjects With Type 2 Diabetes Mellitus A Randomized Controlled Trial: The Italian Diabetes and Exercise Study (IDES)

BACKGROUND This study aimed to assess the efficacy of an intensive exercise intervention strategy in promoting physical activity (PA) and improving hemoglobin A(1c)(HbA(1c)) level and other modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS Of 691 eligible sedentary patients with T2DM and the metabolic syndrome, 606 were enrolled in 22 outpatient diabetes clinics across Italy and randomized by center, age, and diabetes treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group) vs counseling alone (control group) for 12 months. End points included HbA(1c) level (primary) and other cardiovascular risk factors and coronary heart disease risk scores (secondary). RESULTS The mean (SD) volume of PA (metabolic equivalent hours per week) was significantly higher (P < .001) in the exercise (total PA [nonsupervised conditioning PA + supervised PA], 20.0 [0.9], and nonsupervised, 12.4 [7.4]) vs control (10.0 [8.7]) group. Compared with the control group, supervised exercise produced significant improvements (mean difference [95% confidence interval]) in physical fitness; HbA(1c) level (-0.30% [-0.49% to -0.10%]; P < .001); systolic (-4.2 mm Hg [-6.9 to -1.6 mm Hg]; P = .002) and diastolic (-1.7 mm Hg [-3.3 to -1.1 mm Hg]; P = .03) blood pressure; high-density lipoprotein (3.7 mg/dL [2.2 to 5.3 mg/dL]; P < .001) and low-density lipoprotein (-9.6 mg/dL [-15.9 to -3.3 mg/dL]; P = .003) cholesterol level; waist circumference (-3.6 cm [-4.4 to -2.9 cm]; P < .001); body mass index; insulin resistance; inflammation; and risk scores. These parameters improved only marginally in controls. CONCLUSIONS This exercise intervention strategy was effective in promoting PA and improving HbA(1c) and cardiovascular risk profile. Conversely, counseling alone, though successful in achieving the currently recommended amount of activity, was of limited efficacy on cardiovascular risk factors, suggesting the need for a larger volume of PA in these high-risk subjects. Trial Registration isrctn.org Identifier: ISRCTN04252749.

Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet

The gut microbiota exerts a role in type 2 diabetes (T2D), and deviations from a mutualistic ecosystem layout are considered a key environmental factor contributing to the disease. Thus, the possibility of improving metabolic control in T2D by correcting gut microbiome dysbioses through diet has been evaluated. Here, we explore the potential of two different energy-restricted dietary approaches – the fibre-rich macrobiotic Ma-Pi 2 diet or a control diet recommended by Italian professional societies for T2D treatment – to correct gut microbiota dysbioses in T2D patients. In a previous 21-d open-label MADIAB trial, fifty-six overweight T2D patients were randomised to the Ma-Pi 2 or the control diet. For the present study, stools were collected before and after intervention from a subset of forty MADIAB participants, allowing us to characterise the gut microbiota by 16S rRNA sequencing and imputed metagenomics. To highlight microbiota dysbioses in T2D, the gut microbiota of thirteen normal-weight healthy controls were characterised. According to our findings, both diets were effective in modulating gut microbiome dysbioses in T2D, resulting in an increase of the ecosystem diversity and supporting the recovery of a balanced community of health-promoting SCFA producers, such as Faecalibacterium, Roseburia, Lachnospira, Bacteroides and Akkermansia. The Ma-Pi 2 diet, but not the control diet, was also effective in counteracting the increase of possible pro-inflammatory groups, such as Collinsella and Streptococcus, in the gut ecosystem, showing the potential to reverse pro-inflammatory dysbioses in T2D, and possibly explaining the greater efficacy in improving the metabolic control.

Influence of diet on gut microbiota, inflammation and type 2 diabetes mellitus. First experience with macrobiotic Ma-Pi 2 diet

Type 2 diabetes mellitus (T2DM) is a complex disorder influenced by both genetic and environmental factors. Recent studies have suggested that an imbalance of the intestinal microbiota may be involved in the development of several human diseases, including obesity and T2DM. The main regulators of the intestinal microbiota are age, ethnicity, the immune system and diet. A high‐fat diet may induce dysbiosis, which can result in a low‐grade inflammatory state, obesity and other metabolic disorders. Adding prebiotics to the diet may reduce inflammation, endotoxaemia and cytokine levels as well as improving insulin resistance and glucose tolerance. The administration of prebiotics such as fermentable dietary fibres, promotes glucagon‐like peptide 1 and peptide YY (anorexigenic) and decreases ghrelin (orexigenic). In a recent 21‐day, intervention study in patients with T2DM, the effect of using the macrobiotic Ma‐Pi 2 diet was investigated. Results suggested that it could induce a significant improvement in fasting blood glucose, plasma lipid fractions, plasma insulin and homeostasis. It is therefore possible that a diet rich in prebiotics and probiotics can play a role in T2DM management, probably due to positive intestinal microbiota modulation. However, this must be demonstrated by larger studies including randomized controlled trials that measure indicators of inflammation. Copyright

Birth Weight: Genetic and Intrauterine Environment in Normal Pregnancy

Recent meta-analysis (1) and systematic review (2) show that high and low birth weight are related in a U-shaped manner to later risk of type 2 diabetes. It is also interesting to denote the positive birth weight/type 2 diabetes associations within the normal weight range. It is now widely accepted that both genetic and environmental factors are engaged in intrauterine growth, glucose tolerance, and development of type 2 diabetes in later life. The polymorphisms of the insulin receptor substrate (IRS)-1 (3) and β3-adrenergic receptor (β3-AR) genes (4) are genetic risk factors that are associated with insulin resistance and predisposition to type 2 diabetes. …

The effect of the macrobiotic Ma-Pi 2 diet vs. the recommended diet in the management of type 2 diabetes: the randomized controlled MADIAB trial

BackgroundDiet is an important component of type 2 diabetes therapy. Low adherence to current therapeutic diets points out to the need for alternative dietary approaches. This study evaluated the effect of a different dietary approach, the macrobiotic Ma-Pi 2 diet, and compared it with standard diets recommended for patients with type 2 diabetes.MethodsA randomized, controlled, open-label, 21-day trial was undertaken in patients with type 2 diabetes comparing the Ma-Pi 2 diet with standard (control) diet recommended by professional societies for treatment of type 2 diabetes. Changes in fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) were primary outcomes. HbA1c, insulin resistance (IR), lipid panel and anthropometrics were secondary outcomes.ResultsAfter correcting for age, gender, BMI at baseline, and physical activity, there was a significantly greater reduction in the primary outcomes FBG (95% CI: 1.79; 13.46) and PPBG (95% CI: 5.39; 31.44) in those patients receiving the Ma-Pi 2 diet compared with those receiving the control diet. Statistically significantly greater reductions in the secondary outcomes, HbA1c (95% CI: 1.28; 5.46), insulin resistance, total cholesterol, LDL cholesterol and LDL/HDL ratio, BMI, body weight, waist and hip circumference were also found in the Ma-Pi 2 diet group compared with the control diet group. The latter group had a significantly greater reduction of triglycerides compared with the Ma-Pi 2 diet group.ConclusionsIntervention with a short-term Ma-Pi 2 diet resulted in significantly greater improvements in metabolic control in patients with type 2 diabetes compared with intervention with standard diets recommended for these patients.Trial registrationCurrent Controlled Trials ISRCTN10467793.

Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients: a meta-analysis: response to Snowling and Hopkins

We read with great interest the results of the meta-analysis by Snowling and Hopkins (1) on the effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients. This most recent meta-analysis of post-2000 randomized controlled trials is perhaps most important because of the size of the cohort (over 1,000 type 2 diabetic patients) and for the study of characteristics and magnitude of effects in more detail than in the previous Boule meta-analyses (2). Snowling and Hopkins determined that an A1C reduction of 0.8 ± 0.3% is “small” and affirmed in their conclusion that “there are sufficient studies to allow us to conclude that aerobic, resistance, and combined exercise have …

Glucagon and growth hormone secretion in insulin-treated diabetics: Effects of added sulfonylureas

Eleven insulin-dependent ketosis-prone diabetics were given glibenclamide (5 mg/day) in addition to their usual insulin treatment for a period of 1 or 6 mo. There was significant reduction in arginine-induced IRG and hGH secretion and no change in blood glucose levels after either 1 or 6 mo of treatment. During that time no change in weight or insulin requirement was observed. The importance of the duration of treatment and the fact that in this type of patient the effects on IRG and hGH secretion could not be mediated by the influence on insulin secretion are stressed.

Ma-Pi 2 macrobiotic diet and type 2 diabetes mellitus: pooled analysis of short-term intervention studies.

The macrobiotic, Ma‐Pi 2 diet (12% protein, 18% fat and 70% carbohydrate), has shown benefit in adults with type 2 diabetes mellitus (T2DM). This pooled analysis aims to confirm results from four, 21‐day intervention studies with the Ma‐Pi 2 diet, carried out in Cuba, China, Ghana and Italy. Baseline and end of study biochemical, body composition and blood pressure data, were compared using multivariate statistical methods and assessment of the Cohen effect size (d). Results showed that all measured indicators demonstrated significant changes (p < 0.001); most of them with a very high (d ≥ 1.30), or high (d = 0.80–1.29) effect size. The global effect size of the diet was Italy (1.96), China (1.79), Cuba (1.38) and Ghana (0.98). The magnitude of the individual effect on each variable by country, and the global effect by country, was independent of the sample size (p > 0.05). Similarly, glycemia and glycemic profiles in all four studies were independent of the sample size (p = 0.237). The Ma‐Pi diet 2 significantly reduced glycemia, serum lipids, uremia and cardiovascular risk in adults with T2DM. These results suggest that the Ma‐Pi 2 diet could be a valid alternative treatment for patients with T2DM and point to the need for further clinical studies. Mechanisms related to its benefits as a functional diet are discussed.

Physical activity/exercise training in type 2 diabetes. The role of the Italian Diabetes and Exercise Study.

Cardiorespiratory fitness is inversely related to the development of type 2 diabetes and cardiovascular morbidity and mortality. Trials in individuals with impaired glucose tolerance have highlighted the role of physical activity/exercise in the prevention of type 2 diabetes. Moreover, physical activity and exercise training have been recognized as treatment options for patients with type 2 diabetes. Both aerobic and resistance training were shown to produce beneficial effects by reducing HbA1c, inducing weight loss and improving fat distribution, lipid profile and blood pressure in patients with type 2 diabetes. Mixed aerobic and resistance training was recently shown to be more effective than either one alone in ameliorating HbA1c. However, further research is needed to establish the volume, intensity and type of exercise that are required to reduce cardiovascular burden and particularly to define the best strategy for promoting long‐term compliance and durable lifestyle changes in individuals with type 2 diabetes.