Gut microbiome response to short-term dietary interventions in reactive hypoglycemia subjects.

BACKGROUND: Reactive hypoglycemia is a metabolic disorder that provokes severe hypoglycemic episodes after meals. Over recent years, the gut microbiota has been recognized as potential target for the control of metabolic diseases, and the possibility to correct gut microbiota dysbioses through diet, favouring the recovery of metabolic homeostasis, has been considered. METHODS: We investigate the impact of 2 short-term (3-day) nutritional interventions, based on the macrobiotic Ma-Pi 2 diet and a control Mediterranean diet, on the structure and functionality of the gut microbiota in 12 patients affected by reactive hypoglycemia. The gut microbiota composition was characterized by next-generation sequencing of the V3 to V4 region of the 16S rRNA gene, and the ecosystem functionality was addressed by measuring the faecal concentration of short-chain fatty acids (SCFAs). In order to measure the short-term physiological gut microbiota fluctuation, the microbiomes of 7 healthy people were characterized before and after 3 days of constant diet. RESULTS: While no convergence of the gut microbiota compositional profiles was observed, a significant increase in SCFA faecal levels was induced only in the Ma-Pi 2 diet group, suggesting the potential of this diet to support a short-term functional convergence of the gut microbiota, regardless of the individual compositional layout. CONCLUSIONS: The Ma-Pi 2 diet, with its high fibre load, was effective in increasing the production of SCFAs by the gut microbiota. Because these metabolites are known for their ability to counterbalance the metabolic deregulation in persons with glucose impairment disorders, their increased bioavailability could be of some relevance in reactive hypoglycemia.

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.

Diet and diabetes: a cornerstone for therapy.

An appropriate diet represents the cornerstone for diabetes therapy. Diets that differ in their carbohydrate, lipid and protein content are used but the evidence of their effects on the long term is missing. Several confounding factors and compliance to diet render difficult the evaluation of the 'best diet' for diabetes. On a short run, however, useful indications can be obtained regarding the effective diets capable to optimize metabolic control in type 2 diabetes.

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.

The Italian Diabetes and Exercise Study (IDES): design and methods for a prospective Italian multicentre trial of intensive lifestyle intervention in people with type 2 diabetes and the metabolic syndrome.

BACKGROUND AND AIMS: The IDES is a prospective Italian multicentre randomized controlled trial to evaluate the efficacy of an intensive lifestyle intervention on modifiable cardiovascular disease (CVD) risk factors in a large cohort of people with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS: We recruited 606 subjects with type 2 diabetes and waist circumference >94 cm (M) and >80 cm (F), plus >1 other metabolic syndrome trait (IDF criteria) for both sexes, aged 40-75 years, BMI 27-40 kg/m(2), diabetes duration >1 year with a sedentary lifestyle of >6 months. Patients were randomized into two groups: a control group, receiving conventional care including exercise counselling and an intervention group, treated with a mixed (aerobic and resistance) exercise programme (150 min/week) prescribed and supervised for 12 months. Primary outcome is HbA1c reduction. Secondary outcomes include other traditional and non-traditional risk factors and their relationship to exercise volume/intensity and fitness; dosage of glucose, lipid and blood pressure-lowering drugs; global CVD 10-year risk; patient well-being; and costs. CONCLUSION: This trial verifies whether a prescribed and supervised exercise programme, including both aerobic and resistance training, is more effective than conventional exercise counselling in reducing modifiable CVD risk factors in type 2 diabetic subjects with the metabolic syndrome.

The loss of entropy circadian rhythm in sinusal R-R intervals of type 1 diabetic pregnant women suggests an indeterministic chaos in cardiac pacing (minimum delirium cordis syndrome). A newly identifiable type of silent cardiac dysautonomia?

OBJECTIVE: The scope of this study is to detect whether or not the entropy (E) circadian rhythm (CR) is maintained preserved in sinusal R-R intervals (SRRI), its loss being the expression of a transition to an indeterministic chaos in heart rate variability (HRV). METHODS: The E of SRRI was estimated in 14 type I diabetic pregnant women (DPW) in the first trimester of an apparently uncomplicated gestation (7 patients - mean age = 30.3 +/- 4.1 y - without clinical and laboratory evidence of cardiac autonomic neuropathy, and 7 patients - mean age = 30.7 +/- 3.6 y - with positive tests for a cardiac dysautonomia). The E CR was studied via the single cosinor method, and summarized via the population-mean cosinor method. RESULTS: The E CR was found not to be preserved in both the investigated type I DPW, despite the occurrence of the SRRI CR. CONCLUSIONS: The loss of the E CR confirms that in type I DPW there is a transition to an indeterministic disorder in HRV due to the lack of an autocorrelated periodic chaos in cardiac pacing. Such an unphysiological neurovegetative regulation suggests a new silent cardiac dysautonomic syndrome, that we intend to call "minimum delirium cordis syndrome" (MDCS). Can the MDCS be regarded as a condition of cardiovascular risk? To answer this question, it seems justified to suggest that the study of the E CR should be added to the routine tests that are presently applied to clinical analysis of the Holter ECG, being the classic tests of linear analysis not methodologically suitable for detecting the indeterministic chaos of the MDCS.

Exercise training can modify the natural history of diabetic peripheral neuropathy.

BACKGROUND: Diabetes is the most important cause of peripheral neuropathy (DPN). No definitive treatment for DPN has been established, and very few data on the role of exercise training on DPN have been reported. AIM OF THE STUDY: We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients. PARTICIPANTS AND METHODS: Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled, randomized, and subdivided in two groups: 31 diabetic participants [15 f, 16 m; 49+/-15.5 years old; body mass index (BMI)=27.9+/-4.7], who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50% to 85% of the heart rate reserve (exercise group: EXE), and a control group of 47 diabetic participants (CON; 24 f, 23 m; 52.9+/-13.4 years old; BMI=30.9+/-8.4). Vibration perception threshold (VPT), nerve distal latency (DL), nerve conduction velocity (NCV), and nerve action potential amplitude (NAPA) in the lower limbs were measured. RESULTS: We found significant differences on Delta (delta) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period (P<.001, for both). The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group (17% vs. 0.0%, P<.05, and 29.8% vs. 6.45%, P<.05, respectively). In addition, the percentage of diabetic patients who developed increased VPT (25 V) during the study was significantly higher in the CON than the EXE group (21.3% vs. 12.9%, P<.05). Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups (P<.05); no significant change in Malleolus VPT between the two groups occurred. CONCLUSIONS: This study suggests, for the first time, that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN.

Gut microbiota and Ma-Pi 2 macrobiotic diet in the treatment of type 2 diabetes.

In the past 10 years the prevalence of type 2 diabetes mellitus (T2DM) has increased hugely worldwide, driven by a rise in the numbers of overweight and obese individuals. A number of diets have been shown to be effective for the management of T2DM: the Mediterranean diet, the vegetarian diet and the low-calorie diet. Results of studies clearly indicate, however, that the efficacy of these diets is not solely related to the biochemical structure of the individual nutrients they contain. This review discusses this point with reference to the potential role of the intestinal microbiota in diabetes. The macrobiotic Ma-Pi 2 diet is rich in carbohydrates, whole grains and vegetables, with no animal fat or protein or added sugar. In short- and medium-term trials conducted in patients with T2DM, the Ma-Pi 2 diet has been found to significantly improve indicators of metabolic control, including fasting blood glucose, glycosylated hemoglobin, the serum lipid profile, body mass index, body weight and blood pressure. The diet may also alter the gut microbiota composition, which could additionally affect glycemic control. As a result, the Ma-Pi 2 diet could be considered a valid additional short- to medium-term treatment for T2DM.

The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with type 2 diabetes: a post hoc analysis of the MADIAB trial.

INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D) emphasize diet as essential therapy. However, the effect of diet on systemic inflammation remains unclear. We investigated the effects of consuming a macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on markers of inflammation in patients with T2D. METHODS: This was a post hoc analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in 51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for T2D. Biological antioxidant potential of plasma and circulating levels of high-sensitivity C reactive protein, interleukin-6, tumor necrosis factor-α, and insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2 or control diet, markers of inflammation were reduced in both groups. The antioxidant potential of plasma improved significantly in the Ma-Pi group. A significant reduction in insulin growth factor-1 was observed in the Ma-Pi group versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of the markers of insulin resistance and inflammation, compared with baseline values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the control diet in reducing insulin growth factor-1 and may be beneficial for patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN10467793.

Twenty-four-hour blood pressure monitoring in normoalbuminuric normotensive type 1 diabetic women during pregnancy.

UNLABELLED: We monitored blood pressure (BP) for a 24-h period in type 1 diabetic women at each trimester of pregnancy (10-13, 20-22, and 30-33 weeks of gestation) to identify early alterations of BP profile in pregnancies complicated by hypertension. PATIENTS AND METHODS: We prospectively studied 71 type 1 diabetic pregnant women and 48 nondiabetic pregnant women (homogeneous by age and pre-pregnancy BMI) consecutively recruited at 10+/-2 weeks of pregnancy in the space of 2 years (1999-2000). They were all normotensive (<130/80 mm Hg) and normoalbuminuric (AER<20 microg/min) at entry to the study. STATISTICS: Analysis of variance (ANOVA) and simple regression and chi(2) were applied as appropriate by an Apple software program (Stat View). RESULTS: In diabetic women, we recorded higher levels of diastolic BP (even if within a normal range) at each time point; diabetic vs. nondiabetic women: first trim daytime diastolic BP: 71.35+/-8.75 vs. 67.7+/-9.7, P=.01; second trim nighttime diastolic BP: 62.15+/-6.45 vs. 58.05+/-6.7, P=.05; third trim nighttime diastolic BP: 66.03+/-8.72 vs. 60.7+/-6.5, P=.01. Among diabetics, those who later developed pregnancy-induced hypertension (36.6%) showed significantly higher values of BP at the first and third trimester compared to those who remained normotensive. In the two groups, there were no differences in age and pre-pregnancy BMI by contrast of diabetes duration (hypertensive vs. normotensive, 19.18+/-7.3 vs. 14.35+/-9.1 years, P=.03) and age of diagnosis (hypertensive vs. normotensive, 9.6+/-5.5 vs. 14.7+/-8.6 years, P=.01). Positive correlation was found between fasting blood glucose and diastolic BP at each trimester of pregnancy.

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.

BACKGROUND: Diet 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. METHODS: A 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. RESULTS: After 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. CONCLUSIONS: Intervention 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 REGISTRATION: Current Controlled Trials ISRCTN10467793.

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.