Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03230123 |
| Other study ID # |
BIO-123 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
July 24, 2017 |
| Last updated |
July 24, 2017 |
| Start date |
May 2016 |
| Est. completion date |
June 2018 |
Study information
| Verified date |
July 2017 |
| Source |
Federal University of São Paulo |
| Contact |
Maria C Izar, M.D., Ph.D. |
| Phone |
55-11-55764961 |
| Email |
mcoizar[@]terra.com.br |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Costa ES, Izar MC, Fonseca FAH, França C, Tria H. The benefits of green banana biomass
consumption in patients with diabetes mellitus. Federal University of São Paulo, São Paulo,
2015.
According to the Guidelines of the Brazilian Society of Diabetes, Diabetes Mellitus (DM) is a
heterogeneous group of metabolic disorders associated with microvascular complications,
hyperglycemia, resulting in a higher risk of developing cardiovascular disease. Currently, it
is estimated that the world population with diabetes is 382 million people and it is expected
to reach 471 million in 2035. About 80% of individuals with diabetes live in developing
countries where the epidemic has greater intensity. In the Diabetes Control and Complications
Trial and UK Prospective Diabetes Study demonstrated that intensive glycemic control (HbA1c ~
7.0%) reduces chronic microvascular complications. The resistant starch (RS) is defined as
starch and products of its hydrolysis are not absorbed in the small intestine. The green
banana presents significant levels of RS, and it is considered a source for the intake of
this substance. These foods have physiological functions in the intestinal regulation in
glycemic control and delayed gastric emptying. To our knowledge, there are no long-term
studies with DM to prove the benefits of resistant starch use. The objective of this study is
to assess the benefits of green banana biomass consumption by patients with Pre DM and DM.
Considering the possibility of improving glucose, lipid profile, increasing the secretion of
glucagon-like peptide-1 (GLP-1), insulin, adiponectin, and reduction in inflammatory markers
IL-6, PCR.
Description:
INTRODUCTION Cardiovascular Disease and Diabetes In Brazil, chronic non-communicable diseases
(NCDs) were the cause of 72% of deaths and reached 63% in the world in 2008, with large
numbers of premature deaths. Cardiovascular disease (31.3%), Diabetes Mellitus (DM) (5.2%),
cancer (16.3%) and respiratory disease (5.8%) are the main causes of NCDs, leading to loss of
quality of life, causing economic impacts that lead to increased poverty. These factors can
be reversed through broad interventions and cost-effective health promotion. (Schmidt et al,
2011;. Malta et.al., 2011).
Currently, it is estimated that the world population with diabetes is 382 million people and
it is expected to reach 471 million in 2035. About 80% of individuals with diabetes live in
developing countries, where the epidemic has greater intensity, with increasing proportion of
people affected in younger age groups, coexisting with the problem that infectious diseases
still represent. (International Diabetes Federation, 2013; Brazilian Diabetes Society, 2015).
Brazilian data show in 2011 that DM mortality rates (per 100,000 inhabitants) is 30.1 for the
general population, 27.2 in men and 32.9 in women, increasing significantly with advancing
age, which varies from 0.50 for the age group among 0-29 years to 223.8 for individuals aged
from 60 or more, ie an increase of 448 times. (Ministry of Health (USA), 2014; Brazilian
Diabetes Society, 2015).
According to the Brazilian Society of Diabetes (2015), DM is a heterogeneous group of
metabolic disorders associated to microvascular complications, hyperglycemia, resulting in a
higher risk of developing cardiovascular disease (CVD), resulting from defects in insulin
action, in insulin secretion or both.
The reference values for diagnosis of DM are glycated hemoglobin (HbA1c)> 6.5% being
confirmed in another collecting and dispensable in case of symptoms or glucose> 200 mg and
prediabetes HbA1c between 5.7% and 6 4% (Brazilian Society of Diabetes, 2015).
In a meta-analysis carried out with prospective studies it was suggested a significant
association of high levels of IL-6 and CRP, with increased risk of diabetes type 2. These
results support the hypothesis that chronic inflammation is a predictor of the development of
diabetes type 2. IL-6 is a pleiotropic pro-inflammatory cytokine, is produced by a variety of
cells including activated leukocytes, endothelial cells and adipocytes. CRP is an acute phase
protein plasma and synthesized in the liver. CRP was shown to be a sensitive marker of
systemic inflammation (Wang et al., 2013).
The Diabetes Control and Complications Trial (DCCT, 1993) and UK Prospective Diabetes Study
(UKPDS, 1998) demonstrated that intensive glycemic control (HbA1c ~ 7.0%) reduces chronic
microvascular complications, and can also reduce the occurrence of acute myocardial nonfatal
infarction in long term (Ali et al, 2013; American Diabetes Association, 2014; DCCT, 1993;
UKPDS, 1998).
In the UKPDS (1998), newly diagnosed type 2 diabetic participants were followed for 10 years
and intensive control (mean HbA1c 7.0%) which resulted in reducing the rate of microvascular
complications by 25% compared to the conventional treatment (mean HbA1c 7.9%).
The meta-analysis that included three large clinical trials in patients with type 2 diabetes
(ADVANCE, ACCORD and VADT) suggests a significant benefit of intensive glycemic control for
CVD in participants with newly diagnosed DM, lower HbA1c at baseline and / or in the absence
of known CVD (Fonseca et al, 2013;. Skyler, 2009).
The conclusion of the follow-up study of DCCT, that intensive glycemic control started in
relatively young individuals, free of CVD risk factors, was associated with a 57% reduction
in major CVD, supports the above hypothesis. The DCCT-Epidemiology of Diabetes Interventions
and Complications (EDIC) demanded nine years of follow-up after the end of the DCCT, to
finally become statistically significant (American Diabetes Association, 2014; DCCT, DTIS,
2008) and demonstrate the effectiveness and benefits in reduce long-term complications of CVD
and improve the prospects for a healthy life (DCCT, DTIS, 2014).
Green banana biomass The resistant starch (RS) is defined as starch and products of its
hydrolysis are not absorbed in the small intestine. The green banana presents significant
levels of RS, and is considered a source for ingestion of this substance (Braga, 2011). These
foods have physiological functions in the intestinal regulation, glycemic control, beneficial
effects on fatty acid metabolism and delayed gastric emptying. To our knowledge, there are no
long-term studies with DM to prove the benefits of resistant starch use (Evert et al., 2014).
The use of RS may reduce the risk of cardiovascular diseases and contributes to weight loss,
beyond to promote satiety for a longer period of time (Rahman et al., 2007). The effect of RS
on serum lipids in humans are conflicting, however, both studies showed a decrease in total
cholesterol and serum triglycerides (Behall, Howe, 1995; Shah, 2012).
The process of digestion and absorption of food takes place primarily in the mammalian
intestine, which also releases a group of hormones called incretins. These hormones play an
important role in modulating the response of pancreatic islet cells, capable of enhancing
insulin secretion, and consequently lead to a decrease of glucagon, thus collaborating to
decrease in glucose levels in the blood, especially after meals, when they tend to increase
these levels (Doyle, Egan, 2007; Nelson, Cox, 2006).
When the food reaches the intestine, the L and K cells produce GLP-1 and glucose-dependent
insulinotropic peptide (GIP), which act in various tissues. In the hypothalamus, they reduce
the appetite, sending cholinergic and peptidergic signals to the vagus, inhibiting the antral
motility and stimulating the pyloric, thus contributing to the inhibition of gastric
emptying. GLP-1 and GIP stimulate the secretion of amylin and insulin and inhibit glucagon
release. Insulin has satiating effect on the central nervous system, while amylin slows
gastric emptying by vagal action (Tambascia et al., 2014).
Bodinham et al. (2012) examined the effects of the resistant starch consumption on insulin
secretion in 12 overweight individuals. The subjects consumed 40 g RS or 27 g of rapidly
digestible starch per day for four weeks, separated by a four week washout. The results
showed a significant increase in plasma insulin concentrations and C-peptide after four weeks
of supplementation with RS compared to placebo. The mechanism of action is unclear, but may
be associated with increased secretion of incretins such as GLP-1. On the other hand,
Freeland et al. (2010) showed that for occurring increased secretion of GLP-1, the RS intake
must be greater than one year. (Bodinham et al., 2014).
One study evaluated 90 subjects with impaired fasting glucose, impaired glucose tolerance or
newly diagnosed type 2 diabetes. The intervention group should consume rice containing 6.51 g
of RS and the control group should eat rice without supplementation for four weeks. They
evaluated the levels of fasting and postprandial glucose and insulin levels, markers of
oxidative stress, endothelial function, 24-hour food recall and food frequency questionnaire.
The aim of this study was to evaluate whether dietary treatment with rice containing RS for
four weeks reduces blood sugar and oxidative stress, as well as promoting the improvement of
endothelial function. During the study period, the intervention group showed a tendency to
decrease fasting glucose levels, reduction in serum fasting insulin compared to the control
group. In patients with impaired fasting glucose, impaired glucose tolerance or newly
diagnosed type 2 diabetes in dietary treatment for four weeks with rice containing RS was
associated with improvement in endothelial function with a reduction in post-prandial glucose
and oxidative stress compared to control group (Kwak et al., 2012).
Bodinham et al. (2014), observed the effect of RS consumption in insulin sensitivity, glucose
control and body fat in 17 subjects with type 2 diabetes. The subjects consumed 40 g of RS
(derived from corn) or 27 g of a fastly digestible starch per day, during 12 weeks, separated
by a washout period of 12 weeks. During the last week of each intervention, participants were
instructed to perform the dietary record, bowel habits and symptoms diary, to evaluate the
gastrointestinal tolerance of supplements. In the intervention group compared to the control
group, increase in triglycerides was observed, but the total cholesterol, adiponectin and
leptin showed no change, there was a decrease of TNF and there was no modification in IL-6
and adiponectin, and significantly greater increase in the postprandial GLP-1. The mechanism
of action is unclear, but may be associated with increased secretion of incretins (such as
GLP-1), which according to the author could act on the muscle for glucose uptake, since there
was no change in insulin secretion (Bodinham et al, 2014;. Guimarães et al, 2007)..
Robertson et al. (2012) evaluated 15 men and women with insulin resistance. The intervention
included 40 g / day RS derived from corn in comparison to a placebo for eight weeks and eight
weeks washout between interventions. There was an increase of glucose uptake in the forearm
muscle by analysis arterio - venous forearm muscle (increase of 65% after 15 minutes of RS
intake). The function of the adipose tissue was affected with greater suppression of fatty
acids after the treatment with RS and an increase in gene expression for the
hormone-sensitive lipase, lipoprotein lipase, lipase and fatty triglycerides in the biopsy
samples.
Garcia-Rodriguez et al. (2013) evaluated the use of enteral formula for patients with
diabetes enriched with RS and the effect on postprandial in 24 healthy or type 2 diabetes
subjects. The results showed a lower blood glucose levels in individuals with type 2 diabetes
after consumption of enriched formula RS compared to the use of commercially available
formulas (Glucerna and Novasource). This indicates that the composition of the enriched
formula may have contributed to the improvement of glycemic response after consumption and,
therefore, it may have a distinct advantage over the other two classic products. The RS
present in the formula can produce a slow, sustained release of glucose into the circulation
with a corresponding increase in insulin secretion, which may reduce the risk of
hypoglycemia.
Given the above studies of nutritional intervention cited, they were not found long-term,
with a considerable sample of individuals with pre-DM and DM and green banana biomass
consumption. Thus, it takes long term studies in patients with pre DM and DM to evaluate the
benefits of RS consumption, considering the possibility of improved glycemic control, lipid,
increase in GLP-1, insulin, adiponectin, and reduction of the inflammation markers IL-6 and
CRP.
