Can Diabetes be Controlled by Lifestyle Activities?-Juniper Publishers
Authored by Hemachandra Reddy P
Abstract
Diabetes is a complex disease that affects millions
of people worldwide. Diabetes is a metabolic disease, in which increased
blood glucose levels ultimately lead to heart disease, stroke, kidney
failure, foot ulcers, and damage to the eyes. Current prevalence rates
of diabetes are extremely high in countries throughout the world.
Multiple forms of diabetes have been identified, including type 1, type
2, type 3, neonatal and gestational. The purpose of this article is to
discuss recent developments in diabetes research, including prevalence,
morbidity and mortality rates, and lifestyle factors that are associated
with diabetes onset and progression. This article also discusses how
lifestyle factors delay and or prevent diabetes.
Introduction
Diabetes is a chronic disease that affects millions
of people worldwide. Diabetes is mostly polygenic condition, accounts
for about 95% of total diabetes cases and it is mostly late- onset.
Genetic mutations in single gene cause diabetes, referred monogenic.
Monogenic forms of diabetes accounts for about 1-5% of all cases
diabetes and monogenic diabetes occur in young people [1].
Genetic mutations in monogenic form of diabetes reduce the production
of hormone insulin in the beta cells of pancreas, which is responsible
for the maintenance of blood glucose level. Diabetes is a collection of
multiple metabolic diseases, in which high levels of blood glucose are
present over an extended period of time. Most persons with diabetes
remain undiagnosed early in the disease process [2].
In most cases, blood glucose levels in persons with diabetes increase
with age, leading to heart disease, stroke, chronic kidney failure, foot
ulcers, and damage to the eyes. Such high glucose levels are associated
with frequent urination and increased thirst and hunger.
The purpose of this mini-review is to explain recent research findings in investigations of diabetes, including:
a. Prevalence,
b. Morbidity and mortality rates,
c. Types of diabetes,
d. Factors that affect diabetes and
e. Current research findings about diabetes therapeutics.
Prevalence of diabetes
The worldwide prevalence of diabetes was 2.8% in
2000, and it is expected to increase to 4.4% by 2030. The total number
of persons with diabetes worldwide is estimated to increase from 171
million in 2000 to 366 million in 2030 [3].
The most important demographic change regulating to diabetes prevalence
across the world is that it is increasing in people older than 65 years
[3].
According to the Center for Disease Control and Prevention, in the
United States the number of persons with diabetes older than 65 years of
age rose nearly 300% between 1980 and 2014, from 5.5 million in 1980 to
22 million in 2014. The percentage of Americans age 65years of age or
older remains high at 25.9%, with 1.4 million Americans diagnosed with
diabetes each year [4].
Morbidity and mortality rates of persons with diabetes
Acute complications from diabetes include diabetic
ketoacidosis, a life-threatening condition that develops especially in
persons with type1 diabetes, when cells in the body are unable to get
the glucose they need for energy due to insulin insufficiency. When
glucose cannot get into the cells, it stays in the blood. The kidneys
filter some of the sugar from the blood and remove it through urine. But
when cells cannot receive sugar for energy, the body begins breaking
down fat and muscle for energy. When this occurs, fatty acids are
produced and enter the bloodstream, causing a life-threatening chemical
imbalance called diabetic ketoacidosis.
Another acute complication from diabetes is
nonketotic hyperosmolar coma, which is when blood sugar levels rise, and
the body tries to get rid of the excess sugar by passing it into the
urine, initially resulting in increased urination. However, at later
stages, urination decreases and thirst increases. Without sufficient
liquids, dehydration can result, leading to seizures, a coma, and
eventually death. This process may take days or even weeks to develop.
Persons with type 1 and type 2 diabetes may succumb to this
complication.
Current morbidity and mortality rates of persons with
diabetes are very high in the United States (Statistics about diabetes,
American Diabetes Association. According to the American Diabetes
Association, from 2009 to 2012, of the adults aged 18 years or older who
were with diagnosed diabetes, 71% had increased blood pressure and 65%
had LDL cholesterol levels greater than normal (Statistics about
diabetes, American Diabetes Association. Based on statistics from 2003
to 2006, cardiovascular disease death rates were about 1.7 times higher
among adults with diagnosed diabetes who were aged 18 years or older
compared to adults who did not receive a diabetes diagnosis, after
adjusting for age differences in these population groups. In 2010,
hospitalization rates due to heart attack were 1.8 times higher among
adults diagnosed with diabetes who were aged 20 years or older [4,5].
Also in 2010, after adjusting for age differences, hospitalization
rates for victims of stroke were 1.5 times higher among adults diagnosed
with diabetes [5].
In 2005 to 2008, of the adults with diabetes aged 40
years or older, 4.2 million (28.5%) had diabetic retinopathy, that is,
damage to the small blood vessels in the retina, which can ultimately
result in loss of vision [4,5]. In 2011, diabetes was listed as the primary cause of kidney failure in 44% of all new cases of kidney failure.
And in this same year, a total of 228,924 people of
all ages who were diagnosed with kidney failure were living on chronic
dialysis except for those who had a kidney transplant [4,5].
A recent 2017 study reported that health problems associated with
diabetes had been significantly underreported in the United States, and
that Americans with diabetes have about a 90% higher death rate than
those without diabetes [6]. These rates of illnesses, morbidity, and mortality figures underscore diabetes as a major and increasing health concern.
Cost of diabetes
In 2012, the costs of treating illnesses associated
with diabetes, such as blindness, heart attack, and stroke, rose to $245
billion in the United States, with direct medical costs of about $176
billion. After adjusting for age and sex differences in persons
diagnosed with diabetes, their average medical expenditures were found
to be 2.3 times higher than for persons without diabetes [4,5].
Types of diabetes
The levels of glucose in the blood determine the
severity of diabetes, but the age of diabetes onset usually determines
its type. Multiple forms of diabetes have been identified, including
type 1, type 2, type 3, neonatal and, gestational [2,7,8].
Type 1 diabetes: Type 1 diabetes is
early-onset, usually when the patient is 30 years of age or younger.
Five percent of the total number of diabetic patients has type 1. Type 1
diabetes occurs after first 6 months of life. Early-onset, type 1is
typically associated with inherited gene mutations [2].
Type 1 diabetes is also called an insulin-dependent diabetes because
persons with type 1 diabetes need to manage their blood glucose levels
through insulin shots.
Type 2 diabetes: Type diabetes is a late-onset
disease, in that its symptoms first appear in persons older than 30
years of age. Type 2 diabetes covers over 90% of the total diabetic
population. Type 2 diabetes encompasses persons with higher- than-normal
blood sugar levels, which may lead to increased insulin resistance and
insulin deficiency [2,10]. Type 2 diabetes is associated with some non-modifiable and some modifiable risk factors.
Type 3 diabetes: Type 3 diabetes has been identified as a possible form of Alzheimer's disease [2,8].
Persons with type 3 diabetes exhibit cognitive impairment and oxidative
stress that affect glucose metabolism symptoms that also characterize
persons with AD, in terms of insulin resistance, and mitochondrial
dysfunction. Several recent studies have also shown underlying,
mechanistic links across metabolic changes and carbohydrates, lipids,
proteins, and brain dysfunction in persons with AD and in persons with
type 3 diabetes [8].
Neonatal diabetes: Neonatal diabetes occurs in
the first six months of life and it is monogenic. It is a condition
occurs one in 100,000 to 500,000 live births. Infants with neonatal
diabetes do not produce sufficient insulin and this condition often
confused with type 1 diabetes.
Gestational diabetes: Gestational diabetes is
the onset of diabetes in mothers during pregnancy, typically
accompanying carbohydrate intolerance. Gestational diabetes is usually
diagnosed at later stages of pregnancy.
The following conditions are associated with gestational diabetes in pregnant mothers:
a. Age 25 or older,
b. Over weight mother, particularly body mass index is 30
or higher,
c. Mothers have polycystic ovarian syndrome,
d. Have a medical condition that makes diabetes more likely, such as glucose intolerance,
e. Mothers, who take medications like glucocorticoids for asthma or an autoimmune disease,
f. Mothers who take beta-blockers for high blood pressure, or antipsychotic drugs and
Mechanistic action in diabetes: Hypoglycemic
hormone, insulin is produced by the pancreas. In turn, insulin regulates
glucose metabolism which also in turn regulates plasma glucose. Genetic
abnormalities of insulin gene lead to insufficient and/ or defective
production of insulin, typically leading to type 1 diabetes [2].
In type 2 diabetes, the body is unable to regulate sugar levels in the
blood. Several factors are involved in sugar level regulation in type 2
diabetes, including genetic and environmental interactions and increased
calorie intake (high fat diet) and lack of exercise. All of these
factors induce insulin- related abnormalities, ultimately leading to
events that cause late-onset type 2 diabetes. Overall, the elevated
level of blood glucose is due to the failure of beta cells in the
pancreas to produce insulin or to regulate insulin resistance.
Modifiable and non-modifiable factors associated with diabetes: There are many factors associated with the onset of diabetes, some of which are modifiable and some not modifiable.
a. Modifiable factors: Persons diagnosed with
diabetes are behaviors that persons can change in order to manage their
diabetes and to lower blood glucose levels, such as altering diet,
increasing exercise, and eliminating unhealthy lifestyle activities
(e.g., smoking, excessive alcohol, insufficient sleep) [2].
Modifiable factors in persons who are pre-diabetic, regardless of their
age, are a diet high in fat and low in fresh fruits, vegetables, and
whole grains. Foods containing low levels of sugar may also prevent
and/or delays diabetes onset. In addition, the maintenance of normal
cholesterol and blood pressure levels may also reduce pre-diabetes
symptoms and diabetes onset.
b.Non-modifiable factors: Sex, age,
ethnicity, and changes in genomes are major non-modifiable factors.
People over 65 are likely to develop pre-diabetes, and most with type 1
and type 2 diabetes are unaware of their pre-diabetic conditions. People
have increased risk of developing pre-diabetes after age 40 years of
age [2]. Individuals with inherited DNA changes in the genome are susceptible to diabetes.
I.Ethnicity: Ethnicity plays a key role in
development of pre-diabetes. Some ethnic groups carry a higher risk of
developing diabetes. These ethnics groups are Africans, Alaskan Natives,
American Indians, Asians, Latinos, and individuals of Pacific Islander
descent.
II. Genetics: Changes in the genome contribute
significantly to both early-onset type 1 and late-onset type 2
diabetes. Individuals with polymorphisms in individual genes in the
genome are likely to be obese and to develop pre-diabetes and diabetes [7].
Polymorphisms in the genes HLA-DQA1, HLA- DQB1, and HLA-DRB1 in persons
with diabetes have been found to correlate with the development of type
1diabetes [7].
Genetic polymorphisms in these genes alter proteins play critical roles
in the immune system of type 1 diabetes. It is likely that interactions
between genome changes with environmental conditions and/ or diet
promote obesity, pre-diabetes, and diabetes in human populations. In
addition, epigenetic factors, including diet and lifestyle are other
major contributors to the development of obesity, pre-diabetes, and
diabetes.
III.Exercise: Exercise plays an important role
in the maintenance of body weight and blood sugar levels and in
reducing pre-diabetes symptoms. Health benefits associated with physical
activity are rapidly being identified. For example, exercise improves
blood circulation, reduces the risk of heart disease, reduces the risk
of stroke, improves self-esteem, and improves whole-body blood glucose
levels [11].
Some exercises may also improve changes in skeletal muscle since
skeletal muscle is responsible for the disposal of glucose from the
blood. In addition, white adipose tissue shows beneficial effects with
physical activity and exercise [11].
IV.Diet: Diet plays a significant role in the
maintenance of blood sugar levels in in persons who are obese or who
have pre-diabetes and diabetes symptoms. Mounting evidence suggests that
nutritional therapy is useful for improving glycemic control and
metabolism. Recent research into diabetes also suggests the importance
of using evidence-based, rather than anecdotal-based, nutritional
therapy that is based on a patient's level of insulin [12-14].
Nutritional education in diabetes selfmanagement programs is a critical
component of a therapeutic plan for persons with diabetes.
V. Education and awareness: An awareness of
and education about obesity, pre-diabetes conditions, and diabetes are
important for persons with diabetes to consider changing their
lifestyle. Educational material is available from clinics and local
hospitals, and even from online sources. But currently, it is the
responsibility of persons with diabetes to seek out these educational
materials. Self-management classes about diabetes and lifestyle choices
may be useful in providing persons with information to help them
maintain the best quality of life possible, given their diabetes and in
providing pre-diabetic persons information to help them avoid becoming
diabetic [12,15].
The main objective of these self-management classes is teaching
persons, self-sufficiency in using problem-solving skills to lead a
healthier life. Overall, such self-management education has been an
effective tool in reducing diabetes in persons currently at risk or in
persons already diagnosed with the disease.
Research into the Molecular Mechanisms Underlying Diabetes
Research is being actively pursued to better
understand molecular mechanisms underlying both type 1 and type 2
diabetes, using cell, rodent, nonhuman primate and human models [16,17].
Increasing evidence suggests that diabetes is a polygenic condition, in
which DNA changes in multiple genes are involved in the development of
diabetes. The regulation of genes has been found to change in persons
with diabetes, and this dysregulation in turn affects the synthesis of
proteins, a problem known to occur in persons with type 1 and type 2
diabetes.
In addition, elevated inflammatory responses,
oxidative stress, and mitochondrial dysfunction are cellular events that
have been extensively reported in obese persons and persons with type 1
and type 2 diabetes [18].
In these populations, defective regulation of insulin has been found to
induce inflammation, oxidative stress, and mitochondrial dysfunction in
tissues typically affected by diabetes, including tissues of the
pancreas, liver, and brain, and skeletal muscles.
A naturally occurring mouse model for diabetes, the
TallyHo mouse model, shows diabetic characteristics similar to those of
humans with diabetes [19].
Genetic studies of TallyHo mice revealed that multiple DNA changes in
multiple genes result in diabetic features found in humans with diabetes
[19-21],
including increased body weight, increased blood sugar levels, abnormal
insulin regulation, and increased inflammation in the pancreas, liver,
brain, and skeletal muscles. These features were found to increase with
age in the TallyHo mice, just as they were found to increase with age in
humans with diabetes [21].
It is possible that the types of polygenic changes found in the TallyHo
mice also exist in humans with diabetes. Research is needed to better
understand the molecular relationships between genome changes and
diabetic characteristics in humans who have been so diagnosed.
Most recently, several researchers have newly
proposed that AD is a type 3 diabetes, based on molecular similarities
in obese persons with diabetes who exhibit insulin resistance and who
also have AD [8].
These studies revealed that insulin is involved in the activation of
the glycogen synthase kinase 3p, an enzyme that, in excess, results in
the phosphorylation of tau. Phosphorylated tau is involved in the
formation of neurofibrillary tangles, a hallmark of AD. Interestingly,
insulin also plays a crucial role in the formation and increase of
amyloid beta (AE), also a hallmark of brains from persons with AD.
Current Status of Therapeutics
Researchers in basic science, pharmaceutical
companies, and clinicians worldwide are intensely working on identifying
therapeutic targets that are capable of reducing abnormalities
associated with diabetes, including the reduction of insulin resistance
and insulin deficiency. However, no therapeutic targets have been
identified. However, recent research into treatments for diabetes has
resulted in several FDA-approved molecules that target diabetes. These
FDA-approved products include Metformin, Januvia, and drugs with
alpha-glucosidase inhibitors, such as Orlistat [2].
Since diabetes is a polygenic condition, researchers are attempting to
develop genome- based treatments, based on the particular genetic
composition of individual with diabetes rather than treatments designed
for most persons with diabetes, regardless of their genetic makeup.
Clinicians are also researching changes in lifestyle activities that
could help maintain blood pressure and healthy blood sugar levels in
persons with diabetes, with such lifestyle changes including increased
daily exercise and a well-balanced diet that has no sugars, reduced
fats, and fresh fruits and vegetables.
Since most people are undiagnosed early on in the
diabetes disease process, increased education about symptoms of diabetes
may lead persons to seek out health care providers early, rather than
late, in the diabetes disease process and to learn how changes in their
lifestyle activities can be reduce their symptoms of diabetes.
To Know More About Current Research in Diabetes & Obesity
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