Intervertebral disc degeneration: A focus on obesity and type 2 diabetes.

Obesity (OB) and type 2 diabetes (T2D) are among the most prevalent metabolic diseases. They currently affect a substantial part of the world population and are characterized by several systemic co-morbidities, including cardiovascular diseases, stroke, cancer, liver steatosis, and musculoskeletal disorders, by increasing the risk of developing osteoarthritis and intervertebral disc degeneration (IVDD). IVDD is a chronic, progressive process whose main features are disc dehydration, loss of disc height, and changes of load distribution across the spine, resulting in disc structure disruption and leading to low back pain onset. Given the high prevalence of these metabolic disorders and their association with IVDD, several studies have been conducted in order to investigate the causative role of biological and biomechanical characteristics proper to these conditions in the development of IVDD. This review aims to analyse the role of OB and T2D on IVDD, in order to clarify the pathophysiological drivers of the degenerative process and to delineate possible targets to which appropriate treatments may be addressed in the near future.

Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial.

BACKGROUND AND AIMS: Nutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH. MATERIALS AND METHODS: Twelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00-22:30h [subdivided into 'daytime without snacks' and 'daytime with snacks']) and night-time (22:31-07:59h). The effects of the two diets on the number of RH events (blood glucose <70mg/dL [3.9mmol/L]) and the percentage distribution of glucose readings within each of 16 glycemic intervals from <40mg/dL (2.2mmol/L) to >180mg/dL (4.4mmol/L) were determined. RESULTS: There were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (-2.5 events; 95% CI: -7.5, 0.0; P=0.022) and daytime with snacks (-4.25 events; 95% CI: -7.5; -2.0; P=0.013) but no difference at night. The percentage of glucose readings in the interval 71-80mg/dL (3.9-4.4mmol/L) was significantly higher on the control diet during daytime with and without snacks (P=0.03 for both), while the percentage of glucose readings in the interval 91-100mg/dL (5.1-5.6mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P=0.02). CONCLUSIONS: The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH.

Increased sclerostin and bone turnover after diet-induced weight loss in type 2 diabetes: a post hoc analysis of the MADIAB trial.

BACKGROUND: Sclerostin has been directly related to bone turnover increase in dietary-induced weight loss in non-diabetics. This has not been studied in type 2 diabetes, a condition characterized by increased circulating sclerostin and impaired bone turnover. PURPOSE: To study the effect of dietary weight loss and quality of the dietary intervention on changes of sclerostin and bone turnover markers in type 2 diabetes. METHODS: This was a post-hoc analysis of the MADIAB trial, a 21-day randomized controlled trial on overweight/obese type 2 diabetes patients. Patients were randomly assigned 1:1 to the Ma-Pi2 macrobiotic diet or a control diet based on dietary guidelines for type 2 diabetes. Serum sclerostin and circulating markers of bone resorption and formation (P1NP) were measured by enzyme linked immunosorbent assay in 40 subjects (1:1) at baseline and after 21 days treatment. RESULTS: Both Ma-Pi2 and the control diet groups had significant decreases in body weight (6.0 ± 0.2 vs. 3.2 ± 0.1 %, p < 0.001). Sclerostin increased significantly in the two groups (all p < 0.001) but Ma-Pi2 diet group experienced a greater increase in sclerostin (34.5 vs. 15 %; p = 0.024). Serum circulating markers of bone resorption increased in the two groups (all p < 0.001); circulating markers of bone resorption at the end of the treatment tended to be higher in Ma-Pi2 diet than the control diet group (p = 0.06). P1NP did not change significantly in the two group compared to baseline. Sclerostin changes were related to body mass index reduction (r = -0.37; p = 0.02). CONCLUSIONS: Diet-induced weight loss may induce significant and rapid changes in bone turnover and sclerostin levels. These changes may further impair bone health in subjects with type 2 diabetes.

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.

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 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.

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.

Physical exercise as therapy for type 2 diabetes mellitus.

Many studies have highlighted the importance of physical activity (PA) for health, and recent evidence now points to the positive improvements associated with exercise in type 2 diabetes mellitus (T2DM). However, few physicians are willing to prescribe exercise as a therapy for diabetic patients. In addition, there is a lack of information on how to implement exercise therapy especially in long-term exercise regimens. The purpose of this manuscript is to summarize standards of exercise therapy for patients with T2DM, both in terms of prescribing and monitoring, according to the American College of Sports Medicine and the American Diabetes Association guidelines. We present details of the exercise therapies used in long-term studies, describing how the parameters for exercise prescription were applied in clinical practice. These parameters are described in terms of frequency, intensity, duration, mode and rate of progression in long-term therapeutic prescriptions. Individual responses to exercise dose are discussed, and critical issues to be considered in patients with underlying disease and in T2DM patients are highlighted.

Supervised exercise training counterbalances the adverse effects of insulin therapy in overweight/obese subjects with type 2 diabetes.

OBJECTIVE: To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). RESEARCH DESIGN AND METHODS: The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory parameters were assessed at baseline and at the end of the study. RESULTS: The volume of physical activity was significantly higher in the EXE versus the CON group. Values for hemoglobin A(1c), BMI, waist circumference, high-sensitivity C-reactive protein, blood pressure, LDL cholesterol, and the coronary heart disease risk score were significantly reduced only in the EXE group. No major adverse events were observed. CONCLUSIONS: In insulin-treated subjects with type 2 diabetes, supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation, thus counterbalancing the adverse effects of insulin on these parameters.

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.

Menarche in type 1 diabetes is still delayed despite good metabolic control.

OBJECTIVE: To analyze the age at menarche of girls with type 1 diabetes (T1D) who were diagnosed with the disease before puberty and compare it with that of an age-matched group of normal girls. Previous studies on the appearance of menarche showed that the mean age of onset of menarche is delayed in girls affected by T1D compared with normal girls. DESIGN: Case-control study. SETTING: Patients and controls in an academic research environment. PATIENT(S): We studied, retrospectively, the charts of 162 consecutive girls with T1D born in a geographically defined region between 1984 and 1994 with a mean disease duration of 3-5 years, all of whom were on intensive insulin therapy since diagnosis of T1D. The control group consisted of 214 normal girls born between 1984 and 1994, who agreed to fill in an anonymous questionnaire regarding age at menarche and other clinical information. INTERVENTION(S): There was no intervention per se in the study. Age at menarche appears as a dependent variable of body mass index (BMI), HbA1c, and so on. MAIN OUTCOME MEASURE(S): BMI, HbA1c, and duration of T1D at menarche were considered among the potential factors affecting the age of menarche. RESULT(S): Age at menarche in girls with T1D was significantly delayed compared with control girls (12.6 +/- 1.5 years vs. 12.25 +/- 1.4 years, respectively). HbA1c levels and BMI did not influence the age at menarche. CONCLUSION(S): Despite intensive insulin therapy and good metabolic control since diagnosis of T1D, the age at menarche is still delayed in girls who develop T1D before puberty.