tóm tắt luận án hiệu quả kiểm soát glucose máu, cải thiện một số chỉ tiêu hóa sinh của thực phẩm chức năng chiết xuất từ lá vối - ổi - sen (voscap) trên bệnh nhân đtđ type 2 tại hà nội

THE NATIONAL INSTITUTE OF NUTRITION PHAM THI LAN ANH EFFECTS OF VOSCAP, A FUNCTIONAL FOOD EXTRACTED FROM CLEITOCALYX OPERCULATUS, GUAVA AND LOTUS LEAVES ON CONTROL OF BLOOD GLUCOSEAND SO

THE NATIONAL INSTITUTE OF NUTRITION

PHAM THI LAN ANH

EFFECTS OF VOSCAP, A FUNCTIONAL FOOD EXTRACTED FROM CLEITOCALYX OPERCULATUS, GUAVA AND LOTUS LEAVES ON CONTROL OF BLOOD GLUCOSEAND SOME BIOCHEMICAL INDICATORSIN PATIENTS WITH

DIABETES TYPE 2 IN HANOI

NUTRITION PHD THESIS SUMMARY

HA NOI, 2013

NATIONAL INSTITUTE OF NUTRITION

=============

Scientific Advisors:

1 Pham Van Hoan Assc Prof., MD., PhD

2 Truong Tuyet Mai MD., PhD

Rapportor I:

Rapportor II:

Rapportor III:

The thesis to be defended at the National Institute

of Nutrition Training Council

The National Institute of Nutrition Ha Noi

ABBREVIATIONS LIST

ADA: American Diabetes Association

ALT: Alanine transaminase

AST: Aspartate transaminase

BMI: Body Mass Index

NGSP: National Glyco-hemoglobin Standardization Progam

JNC VII: Joint National Committee 7

THA: Hypertension

TP.HCM: Ho Chi Minh City

VOSCAP: Cleitocalyx operculatus, Guava, Lotus capsule

WHO: World Health Organization

INTRODUCTION

Diabetes mellitus type 2 is a non-communicable chronicdisease related to nutrition and lifestyle, growing very fast in manycountries around the world Diabetes is a group of metabolic diseasescharacterized by chronic hyperglycaemia as a result of the lack orreduced activity of insulin or a combination of both

In 2010, it was estimated that the world has about 285million adults with diabetes aged 20-79, the number continued togrow 154% from 2010 to 2012 In 2013 study of EndocrinologyHospital showed the prevalence of diabetes was 5.7% (7.2% in theSouth West, lowest was in the Central Highlands 3.8%) The rate ofglucose intolerance also increased quickly from 7.7% in 2002 tonearly 12.8% in 2012

Postprandial blood glucose control in patients with diabetestype 2, in addition to weight loss, exercise and diet changes, there is aneed to coordinate with diabetes medications, including inhibitors ofα-glucosidase α-glucosidase inhibitors slow the digestion of doubletrack glucose absorption, lead to reduced revenues, thereby slowingthe rise of blood glucose after eating Polyphenols composition ofplant have been scientifically demonstrated the ability to inhibit α-glucosidase in the intestinal epithelial cells, helping to limitpostprandial hyperglycaemia Polyphenols also work to improve theactivity and insulin secretion, reduce blood fat VOSCAP

combination product is extracted from the leaves of robusta, guavaand lotus has only been tested effectively control blood glucose inhealthy and diabetic rats This is the next step, VOSCAP product hasbeen tested on both healthy people and people with diabetes type 2.

STUDYOBJECTIVES:

1 To identify the control of postprandial blood glucose of

VOSCAP product on healthy and in patients with diabetes type 2.

2 To assess the effects of VOSCAP product on blood glucose control, HbA1c, Insulin Resistance in patients with diabetes type

2 after 12 weeks - trial and the changes in blood glucose 6 weeks after discontinuation of the trial.

3 To assess the changes of some other indicators related

biochemical (blood fat and uric acid) and other index (blood pressure, the use of pharmacy diabetes treatment) in patients with diabetes type 2 after 12 weeks - trail of VOSCAP product and the changes in these indicators 6 weeks after discontinuation of the trial.

THE NEW CONTRIBUTIONS OF THE THESIS

1 This is a study of Vietnam's first test using VOSCAP productderived from plant extracts of cleitocalyx operculatus, lotus leaves toassess the effect of blood glucose control in both healthy volunteersand patients with diabetes type 2

2 This is a long-term clinical trials, not just taking VOSCAP productduring 12 weeks to evaluate the effectiveness of blood glucosecontrol in healthy volunteers and patients with diabetes type 2, but

also continue to monitor for another 6 weeks later the end of the test

to assess the ability to maintain the efficiency of the product

CHAPTER 1: OVERVIEW

1.1 The situation of diabetes in the world and Vietnam: 1.1.1 The situation of diabetes in the world:

In recent years, disease patterns have changed, the infections tend to

a reduction, in contrast to non-communicable diseases such ascardiovascular, psychiatric, cancer especially diabetes andmetabolic disorders are increasing In the late 20th century and early21st century, the WHO experts had predicted, "The 21st century will

be the century of the Endocrine diseases and metabolic disorders,especially diabetes a non-communicable disease would be the fastestgrowing one”

The number of people with diabetes worldwide increasedfrom 171 million in 2000 to 194 million in 2003, jumped to 246million in 2006 and forecasted to increase to 380-399 million in

2025 Of which, in the developed countries, the disease rate increased42% and that in the developing countries increased 170% Amongpeople with diabetes, the diabetes type 2 mainly accounts for about85-95% Diabetes is ranking the 4th in cause of death in the world,causing reduced 5 to 10 years of life expectancy, the leading cause ofblindness and end-stage renal failure as well as the leading cause ofamputation not due to injury Every 10 seconds, there is a person diesdue to diabetes and its complications, every 30 seconds there is acomplication of diabetes foot amputation The cost of treatment ofdiabetes worldwide in 2007 was estimated U.S $ 232 trillion,projected to grow to 302 trillion in 2025

Diabetes increases fastest in countries with economic rapidgrowth like India, China The rate of diabetes in the Southeast Asiacountries is also relatively high In the Philippines, in 2008 thediabetes rate was 7.2%, impaired glucose tolerance was 6.5% andfasting blood glucose disorders 2.1%; Diabetes rate in urban areaswas 8.3% and rural areas was 5.8% In 2008, the diabetes rate inIndonesia was 5.7%, the rate of reduced glucose tolerance was 10.2%

in the age group above 15 years old

According to Wilds et al., the rate of diabetes of all agesaround the world in 2000 increased to 2.8% and in 2030 increase to4.4% (171 million in 2000 and 366 million in 2030) A researchconducted by Shaw JE et al showed the diabetes rates worldwideamong adults 20-79 was 6.4% (285 million) and will increase to7.7% (439 million people) by the year 2030 There are 69% of adultswith diabetes in developing countries and 20% in developedcountries A study of David R et al 2011 showed that: In 2011, therewere 366 million people with diabetes aged 20-79, this figureexpected to rise to 552 million by 2030

1.1.1 Diabetes situation in Vietnam:

In Vietnam, diabetes has tended to increase over time and thelevel of economic development and urbanization In 1991, Mai TheTrach et al investigated in 4912 people in Hanoi, by the standards ofthe World Health organization (WHO 1985), the prevalence ofdiabetes in subjects over 15 years old was 1.2%, of which 1.44% inthe urban and 0.63% in the suburbs; The percentage of blood glucose

intolerance was 1.6% In 1993, Mai The Trach et al surveyed on5,416 people over age 15 or older in the HCM city, the resultsshowed diabetes rate was 2.52%.

In 2001, the epidemiological investigation on diabetesapplied new international standard with the help of leading expertsfrom WHO, conducted in 4 cities: Hanoi, Hai Phong, Da Nang and

Ho Chi Minh City Result of this investigation is really alarm bellsabout the situation of non-communicable diseases in general anddiabetes in particular in Vietnam, the prevalence of diabetes in 4 bigcities of Hanoi, Ho Chi Minh City, Hai Phong and Da Nang insubjects aged 30-64 was 4.9%, glucose intolerance rate was 5.9%,the rate of fasting blood glucose disorder was 2.8%, the rate ofsubjects with risk factors for diabetes was 38.5%; It is so worried that44% of the people with diabetes has not been diagnosed and givenany preventive and treatment guidelines

In 2002, Endocrinology Hospital conducted a national survey

of diabetes risk factors on over 9,122 people in 90 wards, ò which

1833 subjects in the Central Highlands, 2722 in the delta region,2,759 in the cities, 45% of male and 55% of female The resultsshowed people with diabetes type 2 nearly tripled over the last 10years; The rate of diabetes type 2 aged 30-69 was about 5.7%; Andthe rate in the urban and industrial zones was higher, 7,0% - 10%

In 2013, the study of Endocrinology Hospital showed that theprevalence of diabetes was 5.7% (the highest was in the South West

at 7.2%, the lowest was 3.8% in the Highland) The rate of glucose

intolerance also increased quickly from 7.7% in 2002 to 12.8% in

2012 According to this study, people over age 45 are at risk fordiabetes type 24 times higher than those under 45 years of age.People with high blood pressure are at diabetes risk for more than 3times the other People with large waist are at diabetes risk for 2.6times higher

1.1.3 The consequences of diabetes mellitus type 2:

Diabetes is a serious disease threat to life and cause manycomplications According to the International Diabetes Association,diabetes is the leading cause of death ranking the 4th or 5th in thedeveloped countries and is being considered epidemic in developingcountries Approximately 50% of diabetic patients withcomplications such as coronary heart disease, heart attack, stroke,neuropathy, cuts amputation, kidney failure, blindness caused bydiabetes These complications result in disability and reduced lifeexpectancy Diabetes leads to serious consequences for the healthand economy of the entire society

1.2 Diagnosis of diabetes type 2.

According to the ADA, the diagnostic criterias for diabetessince 2010 are:

- HbA1c ≥ 6.5%

- Fasting blood glucose level ≥ 7.0 mmol / l (≥ 126mg/dl)

- Blood glucose level ≥ 11.1 mmol / l (200mg/dl) at the time of 2hours after glucose tolerance test orally

- There are symptoms of diabetes (clinical) blood glucose level at anypoint ≥ 11.1 mmol / l (200mg/dl).

1.3 Treatment of diabetes type 2:

The goal of diabetes treatment is to reduce or loss the clinicalsymptoms of hyperglycaemia, to maintain blood glucose values asclose to normal as possible, but do not cause hypoglycaemia andprevent acute and chronic complications, maintain your ideal weightand improve the quality of life for patients To achieve this goal,diabetes treatments will include methods of taking and not takingmedications/ drugs Not taking medications is a method that adjuststhe lifestyle, including reasonable diet and physical activity

Besides the use of pharmaceutical medications/ drugs, manyherbs have been recommended to use for patients with diabetes, withthe purpose of supporting or alternative treatment Some polyphenols

of plant have the ability to temporarily inhibit activity of metabolicenzyme of glucose which reduces the postprandial hyperglycaemia.Currently, in addition to single-use plants, studies in India, China,South Korea and some other countries have demonstrated the role ofcombinations of herbs (Polyherbal Formulation) to increase theeffectiveness of diabetes type 2 treatments in laboratory, diabeticmice and in patients with diabetes Some herbs products proved tohave the advantage of combined different active extracted groups,reducing blood glucose with a synergistic mechanism, providingbetter therapeutic efficacy with an excellent safety profile

Robusta, guava and lotus leaves have been known to be thefamiliar plants, long used in Vietnam with more experience in folkremedies and no toxicity Results of initial studies of VOS mixtureextracted from leaves of robusta, guava, lotus leaves which containmainly polyphenol components have proven their safety with theability to control blood glucose in diabetic rats.

CHAPTER 2: SUBJECTS AND METHODS

- Conducted in two different days: the first day subjects drink whitewater and a formulated meal (control day), in the second day (trialday - 7 days after) the subjects have been taken VOSCAP tablets andeat a formulated meal as in the first day

2.2.1 Phase 2: Assessing the effectiveness of blood glucose control

in patients with long-term type 2 diabetes

This is a clinical trial in subjects with diabetes patients

- Tested effective intervention after 12 weeks

- Assessing the maintained effectiveness of VOSCAP 6 weeks afterintervention

2.2 Object, location, time studies:

Object selection criterias:

• For patients with diabetes type 2:

- Voluntary to participate in the study.

- Fasting blood glucose an average of ≥ 7 to <8 mmol / L, and HbA1c <8.0%

- Aged 40-70

- BMI from 18.5 to 25.0

Exclusion criterias:

- Diabetes mellitus type 1

- Kidney or liver disease, chronic /acute digestive diseases

- Deaf, dumb, psychosis, confusion

- Subjects must use insulin, α-glucosidase inhibitors during the study period

Location and time study:

Location: National Institute of Nutrition

Time: June 6/2011 to March 3/2012

2.4 Sample size and sampling method

2.4.1 Sample sizes and sampling methods diabetes patients:

Sample sizes and sampling methods for diabetic patients:

Applying the formula:

2 1

])(

Calculated n = 30, the estimated dropout rate is 20%, so the totalnumber of participants is 36.

For the two groups: 36 x 2 = 72 subjects

Selection of subjects with diabetes type 2:

- Make a list and preliminary screening diabetic members in the club.Choose the 72 subjects eligible for selection Make a list of 72subjects eligible and agreed to participate in taking VOS tablets for

12 weeks and continue to be monitored for 6 weeks after intervention(phase 2) Among 72 selected diabetic patients, 50 patients had beenrandomly selected to participate in postprandial blood glucose testing(Phase 1)

Sampling healthy subjects:

Sampling: selected 50 healthy voluntary students by convenient method

2.5 Research steps

2.5.1 Phase 1: Testing blood glucose change after eating.

2.5.1.1 Preparation of formulated meals with a total energy of 250 kcal:

The composition of the diet included:

- 01 bowls of scream rice: 55 gams of rice (160 kcal)

- 01 table spoons 35 gams minced lean meat + 4 gams fat + 1 gam meat soup (90 kcal)

2.5.1.2 Conducting trial 1 and 2 to assess postprandial blood glucose control of VOSCAP product

Each trial was conducted on 50 patients in 2 different days:

in the first day the subjects just drinking plain water (control day), inthe second day, 7 day later, they took VOSCAP (intervention day).The participants were asked to fast for at least 8 hours before thefinger blood sample was taken (T0), then drunk water or VOSCAPand ate 1 formulated meal within 8-10 minutes The finger bloodsamples then were taken after 15, 30, 60, 90 and 120 minutes aftereating Blood glucose level was measured by Accucheck – aJapanese machine

2.5.2 Phase 2: Evaluation of VOSCAP product on blood glucose control and some other biochemical and health indicators in patients with diabetes type 2

Divided the subjects into 2 groups: control and intervention one.Subjects of interventions group were taken 2 VOSCAP capsulestwice a day, 10-15 minutes before eating Those in the control group,due to no placebo used, they were continuously takenmedication/drugs for diabetes treatment and to be closely monitored.Both groups had received advisory diet and exercise regime at homebased on each patient actual diet All selected indicators of the 2groups’ subjects were evaluated at time point T0, T6, T12, and T18

2.6 Methods of data collection and evaluation criteria 2.6.1 Data collection in phase 1

- General information were gathered by direct interviewing subjects,

including age, gender, occupation, weight, height, blood pressure,

- Blood glucose concentration in mmol / L at different points weredetermined before eating, 15, 30, 60, 90 and 120 minutes after eating

- The area under the curve of increased blood glucose wasdetermined

2.6.2 Data collection Phase 2

General information: Direct interviews by the doctors with designed questionnaire to collect general information, information related to living habits, diet, current health status, disease history,

pre-Food consumption and food frequency.

Anthropometric indicators: height, weight.

Biochemical indicators: blood glucose, HbA1c, cholesterol, triglycerides, c-HCL, Creatinine, AST / ALT, uric acid, insulin 2.7 The error and bias control measures

Anthropometric data were collected by two investigators

(interviewer) of the National Institute of Nutrition, who are very technically proficiency and skill The blood samples were taken

in the morning by technicians who were experienced to minimize vein broken and erythrocyte rupture.

2.8 Analysis and data processing

The survey data are cleaned, then double entered using EPI DATA Data analysis using SPSS software 16.0 The data on the area under the curve increased (IAUC) analysis by Frank Schoonjans MedCalc software Data on diet were checked and double entered and