Andreea Soare

Caloric restriction may reverse age‐related autonomic decline in humans

Caloric restriction (CR) retards aging in laboratory rodents. No information is available on the effects of long‐term CR on physiologic markers of aging and longevity in humans. Heart rate variability (HRV) is a marker for cardiac autonomic functioning. The progressive decline in HRV with aging and the association of higher HRV with better health outcomes are well established. Heart rate variability assessment is a reliable tool by which the effects of CR on autonomic function can be assessed. Time‐ and frequency‐domain analyses compared 24‐h HRV in 22 CR individuals aged 35–82 years and 20 age‐matched controls eating Western diets (WD). The CR group was significantly leaner than the WD group. Heart rate was significantly lower, and virtually, all HRV values were significantly higher in the CR group than in the WD group (P < 0.002). Heart rate variability in the CR individuals was comparable with published norms for healthy individuals 20 years younger. In addition, when differences in heart rate (HR) and HRV between CR and WD were compared with previously published changes in HRV induced in healthy adults given atenolol, percent differences in each measure were generally similar in direction and magnitude and suggested declines in sympathetic and increases in parasympathetic modulation of HR and increased circadian variability associated with CR. These findings provide evidence that CR has direct systemic effects that counter the expected age‐associated changes in autonomic function so that HRV indexes in CR individuals are similar to those of individuals 20 years younger eating WDs.

Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk

In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age‐related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease. Copyright

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.

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.

WRIST CIRCUMFERENCE: AN INDEPENDENT PREDICTOR OF BOTH INSULIN RESISTANCE AND CHRONIC KIDNEY DISEASE IN AN ELDERLY POPULATION

Abstract Background and aim: It was recently reported that wrist circumference is associated with insulin resistance (IR) both in children and adults. We aimed to evaluate whether wrist circumference is a useful anthropometrical parameter for the evaluation of IR in an elderly population. Material and method: We performed a study on 40 subjects, 20 with type 2 diabetes (T2D) and 20 control subjects. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). We measured the following anthropometrical parameters: weight, height, waist circumference (WC), hip circumference, wrist circumference, waist to hip ratio (WHR), waist to height ratio (WHtR), body mass index (BMI) and body adiposity index (BAI). Results: We found statistically significant differences between the subjects with T2D and the control group for all the analyzed parameters. Statistically significant correlations between all the anthropometrical parameters and HOMA-IR were observed. However, only WC was an independent predictor of IR. Wrist circumference was the only parameter negatively correlated with the estimated glomerular filtration rate (eGFR). Furthermore, this measurement was an independent predictor of chronic kidney disease (CKD) in the studied subjects. Conclusion: Wrist circumference can be used in the general practice as a surrogate marker of IR in the elderly, being both easily determined and a cost-free method

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

BackgroundSclerostin 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.PurposeTo 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.MethodsThis 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.ResultsBoth 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).ConclusionsDiet-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.

A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes

Background:In the MADIAB trial (a 21-day randomized, controlled trial in patients with type 2 diabetes (T2D)), intervention with the Ma-Pi 2 macrobiotic diet resulted in significantly greater improvements in metabolic control compared with a standard recommended diet for patients with T2D. We report on a 6-month follow-up study, which investigated, whether these benefits extended beyond the 21-day intensive dietary intervention, in real-world conditions.Subjects:At the end of the MADIAB trial (baseline of this follow-up study), all participants continued their assigned diet (Ma-Pi or control) for 6 months. The Ma-Pi 2 group followed the Ma-Pi 4 diet during this follow-up study. Forty of the original 51 subjects (78.4%) participated in the follow-up (body mass index, 27–45 kg m−2; age, 40–75 years). Primary outcome was percentage change from baseline in HbA1c; secondary outcomes were anthropometric data and lipid panel.Results:A significantly greater median percentage reduction was observed for HbA1c in the Ma-Pi group (−11.27% (95% confidence interval (CI): −10.17; −12.36)) compared with the control group (−5.88% (95% CI: −3.79; −7.98)) (P < 0.001). Total and low-density lipoprotein (LDL) cholesterol increased in both groups with no differences between groups (P=0.331 and P=0.082, respectively). After correcting for age and gender, the Ma-Pi diet was associated with a higher percentage reduction in HbA1c (95% CI: 2.56; 7.61) and body weight (95% CI: 0.40; 3.99), and a higher percentage increase in LDL cholesterol (95% CI: −1.52; −33.16). However, all participants’ total and LDL cholesterol levels remained within recommended ranges (<200 mg dl−1 and <100 mg dl−1, respectively). The Ma-Pi diet group achieved the target median HbA1c value (<5.7% (39 mmol mol−1)) at 6 months.Conclusions:Both the Ma-Pi and control diets maintained their benefits beyond the 21-day intensive monitored intervention over a 6-month follow-up in real-world conditions. The Ma-Pi diet resulted in greater improvement in glycemic control.

Searching the Missing Link Between Alzheimer’s Disease and Diabetes

Abstract Recent studies strongly suggest a significant association between diabetes mellitus and Alzheimer Disease (AD) justifying the term “type 3 diabetes”. Studies show that impairment of glucose metabolism occurs very early in the course of AD, leading to a broad range of consequences, among which the accumulation of amyloid beta (Aβ), which per se induces insulin resistance. Furthermore, adipocytokines, recognised markers of insulin resistance, seem to play a role in the development of AD. As for insulin resistance, when AD is considered, the most studied ones are leptin and adiponectin, but also a recently described adipokine - progranulin. It is our belief that both prospective and transversal studies on subjects with both AD and type 2 diabetes (T2D) may prove the role of adipokines not only in AD, but also in this most somber association.

Buccal spray insulin in subjects with impaired glucose tolerance: Improvement in HbA1c is lost after 6 months washout therapy

With the increasing global epidemic of diabetes, especially type 2 diabetes, all major pharmaceutical companies are focusing on new molecules for the treatment of diabetes and obesity. With the better management of diabetes (improved HbA1c values), the microvascular complications have significantly reduced over the past two decades. This has been achieved without increasing hypoglycemia especially with newer technological advances (discussed at length in chapters 12 and 13 in this yearbook). We review here the abstracts related to the newer molecules that are being investigated in the management of diabetes. We searched more than 400 articles on newer agents published from July 2012 to June 2013, of which the best 19 abstracts are discussed. Also, we briefly mention newer insulin analogs and alternate insulin delivery methods, as this topic is discussed at length by colleagues in chapter 5 of this yearbook.