Article Type : Research Article
Authors : Raj A, Sharma A
Keywords : Diabetes; Hyperglycemia; Hypoglycemia; Diabetes mellitus
Diabetes is a life-long disease that affects the way your body handles
glucose, a kind of sugar, in your blood. It is often referred as Diabetes
Mellitus (DM) by doctors which describes a group of metabolic diseases
resulting in high blood glucose, either due to inadequate production of insulin
or because the body’s cells do not respond well to insulin or both. Normally,
the pancreas releases insulin to help your body store and use the sugar and fat
from the food you eat. Diabetes can occur when the pancreas produces very
little or no insulin, or when the body does not respond appropriately to
insulin. In 2014 it was estimated that over 422 million people throughout the
world had diabetes. The most common diabetes symptoms include frequent
urination, intense thirst and hunger, weight gain, unusual weight loss,
fatigue, cuts and bruises that do not heal, male sexual dysfunction, numbness
and tingling in hands and feet. According to health day reporter, Steve
Reinberg in September 2018, 30 million Americans now have diabetes. 1 in 7
Americans has diabetes, and many don’t even know they have high blood glucose
disease. According to the U.S. centers for disease control and prevention, 14%
of U.S adults have diabetes of which 10% know it and over 4% are undiagnosed.
According to the American Diabetes Association, 95% of the diabetes cases are
type 2, which is often tied to overweight or obesity. About 5 % of diabetes
cases are type 1, which can arise early in life and is not linked with
lifestyle factors. According to the report, nearly 16% of men and 12% of women
have diabetes and the risk of developing both diagnosed and undiagnosed
diabetes increases with age. In terms of population, diabetes is more common
among Hispanics (20%), and blacks (18%), than whites (12%). The research found
that overweight and obese are more likely to develop diabetes. Only 6% of
underweight or normal weight adults had the disease, while 12% of overweight
adults and 21% of obese adults had diabetes. Diabetes cannot be cured but
treatment modalities include lifestyle modifications, treatment of obesity, and
oral hypoglycemic agents like iguanids, sulfonylurea, thiazolidinedione’s,
alpha glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors and insulin.
Diabetes Mellitus (DM) is an endocrinological disorder which is a group of metabolic or heterogeneous affliction resulting from an irregularity in insulin secretions and insulin actions or both. It is one of the oldest diseases known to man. It was first reported in Egyptian manuscript about 3000 years ago. It is also referred as black-death from the 14th century. Patients with diabetes have been classified into two main categories: type-1 diabetes mellitus (T1DM), characterized by a near-absolute deficiency of insulin secretion and type-2 diabetes mellitus (T2DM) where the cause is a combination of insulin resistance and an insulin secretory defect. In 1936, the distinction between type 1 and type 2 diabetes mellitus was clearly made. Type 2 diabetes mellitus was first described as a component of metabolic syndrome in 1988. The presence of DM shows increased risk of many complications such as cardiovascular diseases, peripheral vascular diseases, stroke, neuropathy, renal failure, retinopathy, blindness, amputations, etc. People living with type 2 DM are more vulnerable to various forms of both short and long term complications, which often lead to their premature death. Drugs are used primarily to save life and alleviate symptoms. Secondary aims are to prevent long-term diabetic complications and, by eliminating various risk factors, to increase longevity.
Figure 1: Illustration of an artery with normal blood glucose level and an artery with high blood glucose levels. (Image source: foodnurish.com.
Figure 2: (Image source: babygest.com).
Figure 3: (Image source: thermofisher.com).
Figure
4: (Image source:
danii.org.au).
Globally,
the number of people with diabetes mellitus has quadrupled in the past three
decades, and diabetes mellitus is the ninth major cause of death. Most patients
with T2DM have at least one complication, and cardiovascular complications are
the leading cause of morbidity and mortality in these patients. The number of
people (20-79 years) living with diabetes in 2017 was estimated to be 424.9
million. This value is further estimated to be 628.6 million by 2045. The
largest number of people (20-79 years) with diabetes are in China, India and
United States in 2017. Diabetes in people older than 65 years was estimated to
be 122.8 million in 2017, which is further estimated to be 253.4 million in
2045. It was estimated that globally as many as 212.4 million people or half
(50.0%) of all people 20-79 years with diabetes were unaware of their disease
in 2017. In low income countries like Africa, the proportion of undiagnosed
diabetes is 69.2% while in high income countries, this value contributes to
37.3%. Asia is a major area of the rapidly emerging T2DMglobal epidemic, with
China and India the top two epicenters.
Earlier
Diabetes was classified mainly into two types as Type 1 or Insulin-Dependent
Diabetes Mellitus (IDDM) and Type 2 or Non-Insulin-Dependent Diabetes Mellitus
(NIDDM) which were proposed by WHO in 1980 and 1985. In recent years, the
traditional way of classifying DM has been replaced by new classification which
includes mainly four types of DM.
?.
Type 1 Diabetes Mellitus
A. Autoimmune
B. Idiopathic
?.
Type 2 Diabetes Mellitus
It
ranges from relative insulin deficiency to disorders of insulin secretion and
insulin resistance.
III.
Gestational Diabetes Mellitus (Occurs in Pregnant woman)
IV.
Other specific types of Diabetes Mellitus
A. Genetic
defects in ?-cell function
1. Chromosome
12, HNF-1? (MODY 3)
2. Chromosome
7, glycosidase (MODY 2)
3. Chromosome
20, HNF-4? (MODY 1)
4. Mitochondrial
DNA
5. Monogenic
Diabetes
B. Genetic
defects in insulin action
1. Type
A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall
syndrome
4. Lipotrophic
diabetes
C. Disease
of the exocrine pancreas
1. Pancreatitis
2. Pancreatectomy/trauma
3. Neoplasia
4. Cystic
fibrosis
5. Hemochromatosis
6. Fibrocalcificpancreatopathy
D. Endocrinopathies
1. Acromegaly
2. Cushing’s
syndrome
3. Glucagonoma
4. Pheochromocytoma
5. Hyperthyroidism
6. Somatostatinoma
7. Aldosteronoma
E. Pharmacologically or chemically induced
1. Vacor
2. Pentamidine
3. Nicotinic
acid
4. Glucocorticoids
5. Thyroid
hormones
6. Diazoxide
7. ?-adrenergic
agonists
8. Thiazides
9. Dilantin
(phenytoin)
10. ?-interferon
F. Others
1. Infections
1. Congenital
rubella
2. Cytomegalovirus
3. Others
2. Infrequent
forms of autoimmune diabetes
1. Stiff-man
syndrome
2. Antibodies
against insulin receptors
3. Others
3. Other
syndromes occasionally associated with diabetes
1. Down’s
syndrome
2. Klinefelter’s
syndrome
3. Turner’s
syndrome
4. Wolfram’s
syndrome
5. Friedreich’s
ataxia
6. Huntington’s
chorea
7. Lawrence-Moon-Biedel
syndrome
8. Myotonic
dystrophy
9. Porphyria
10. Prader-Willi
syndrome
G. Post-Transplant
Type 1 Diabetes Mellitus
It
is also known as insulin-dependent diabetes or juvenile-onset diabetes (because
it often begins in childhood). It is an autoimmune condition characterized by
beta cell destruction. Thus, the damaged pancreas doesn’t make insulin. It may
also be caused by a genetic predisposition.
Patients
with type 1 diabetes are associated with a number of medical risks such as:
1. Diabetic Retinopathy (damage to the
tiny blood vessels in eyes)
2. Diabetic Neuropathy (damage to the
nerves) and
3. Diabetic Nephropathy (damage to the
kidneys)
Serious
conditions like risk of heart disease and stroke may also arise in such
patients. All type 1 diabetic patients require insulin therapy to maintain
normal blood glucose level. Insulin can be injected through the skin into the
fatty tissue below by the following methods:
·
Syringes
·
Insulin pens that use pre-filled
cartridges and a fine needle
·
Jet injectors that use high pressure air
to send a spray of insulin through the skin
·
Insulin pumps that dispense insulin
through flexible tubing to a catheter under the skin of the abdomen
A
doctor generally prescribes for A1C blood test which estimates the blood sugar
levels over the previous three months. This test provides information about how
well the blood sugar level is controlled and doctors can easily identify the
risk of complications.
Following
activities are advised in case of type 1 diabetes.
·
Proper diet plan (Dietician or doctors can
advise about meal plan)
·
Regular exercise
·
Frequent testing of blood sugar levels
·
Taking insulin and other medications as
per doctor’s advise
Type 2 diabetes mellitus
It
is also known as non-insulin dependent or adult onset diabetes. However, over
the past 20 years, this has become common in children and teens because of
overweight and obesity. Type 2 diabetes is more common than type 1 and accounts
for 90% of the total diabetes cases throughout the world. This type of diabetes
effects the use of glucose for energy by the body. It stops the body from using
insulin properly, which results in high blood sugar level if not treated on
time.
In type 2 diabetes, insulin resistance occur because the insulin secreted by the pancreas is not enough to maintain the blood sugar level. Insulin resistance usually happens in fat, liver and muscle cells. Both fasting and post prandial plasma glucose concentration is increased. The normal glucose homeostasis cannot be maintained due to insufficient concentration of plasma insulin. Over a period of time, this results in beta cell failure which results in insulin deficiency in the body. Insulin resistance happens by several factors such as obesity, improper diet, hormonal imbalances, lack of physical activity, genetics and long term use of certain medications like HIV/AIDS medications and corticosteroids.
Table 1: Top 10 countries for
number of people with diabetes (20-79 years), 2017 and 2045.
2017 |
|
|
2045 |
|
|
Rank |
Country/Territory |
Number of people with
Diabetes (Million) |
Rank |
Country/Territory |
Number of people with
Diabetes (Million) |
1. |
China |
114.4 |
1. |
India |
134.3 |
2. |
India |
72.9 |
2. |
China |
119.8 |
3. |
United States |
30.2 |
3. |
United States |
35.6 |
4. |
Brazil |
12.5 |
4. |
Mexico |
21.8 |
5. |
Mexico |
12.0 |
5. |
Brazil |
20.3 |
6. |
Indonesia |
10.3 |
6. |
Egypt |
16.7 |
7. |
Russian Federation |
8.5 |
7. |
Indonesia |
16.7 |
8. |
Egypt |
8.2 |
8. |
Pakistan |
16.1 |
9. |
Germany |
7.5 |
9. |
Bangladesh |
13.7 |
10. |
Pakistan |
7.5 |
10. |
Turkey |
11.2 |
Table
2: People living with
diabetes (20-79 years) who are undiagnosed per region, 2017.
Rank |
International
Diabetes Federation (IDF) region |
Proportion
Undiagnosed (%) |
Number of people with
undiagnosed diabetes (million) |
1. |
Africa |
69.2 |
10.7 |
2. |
South-East Asia |
57.6 |
47.2 |
3. |
Western Pacific |
54.1 |
85.9 |
4. |
Middle East and North Africa |
49.0 |
19.0 |
5. |
South and Central America |
40.0 |
10.4 |
6. |
Europe |
37.9 |
22.0 |
7. |
North America and Caribbean |
37.6 |
17.3 |
Table 3: Test results for diagnosis of diabetes and prediabetes.
Diagnosis |
A1C |
Fasting Plasma Glucose |
Oral Glucose Tolerance Test |
Random Plasma Glucose Test |
Normal |
below 5.7% |
99 mg/ dl or below |
139 mg/ dl or below |
N/A |
Prediabetes |
5.7% to 6.4% |
100 to 125 mg/ dl |
140 to 199 mg/ dl |
N/A |
Diabetes |
6.5% or above |
126 mg/ dl or above |
200 mg/ dl or above |
200 mg/ dl or above |
(Source: American Diabetes Association) |
Table 4: Types of Oral antidiabetics.
S. No. |
Class |
Examples |
Mechanism of Action |
1. |
Alpha Glucosidase inhibitors |
Acarbose, Miglitol and
Voglibose |
They
work by slowing down the digestion of carbohydrates, which in turn prevents
blood glucose from rising too fast after meals.
|
2. |
Biguanides |
Metformin |
These drugs wok by
preventing the production of glucose in the liver and reducing the amount of
sugar absorbed by the intestines. Metformin is commonly used as first-line
treatment for type 2 diabetes. |
3. |
Bile acid sequestrants or
bile acid resins (BARs) |
Colestipol, Colesevelam and
Cholestyramine |
These drugs lower the
cholesterol level. |
4. |
Dopamine-2 agonists |
Bromocryptine |
These
drugs reset the hypothalamic circadin rhythm, which obesity can effect. This
reset helps reverse insulin resistance and causes a decrease in glucose
production in the liver.
|
5. |
DPP-4 inhibitors or gliptins |
Sitagliptin, Linagliptin,
Vildagliptin, Saxagliptin and Alogliptin |
These drugs help improve
blood sugar levels by preventing the breakdown of GLP-1 by blocking the
enzyme dipeptidyl peptidase-4. |
6. |
Meglitinides |
Repaglinide and Nateglinide |
Stimulate the pancreas to
release insulin. |
7. |
SGLT2 inhibitors (Sodium
Glucose Transport Protein 2) |
Canagliflozin, Dapagliflozin
and Empagliflozin.
|
These are the drugs which
lowers blood glucose levels by excreting the excess glucose in urine. |
8. |
Sulfonylureas |
Glimepiride, Glyburide and
Glipizide |
They stimulate pancreas to
release insulin in order to reduce the blood glucose levels.
|
9. |
Thiazolidinediones |
Rosiglitazone and
Pioglitazone |
They work by reducing the
glucose production in the liver.
|
Table 5: Types of Insulin used to treat type
2 diabetes are as below.
Type |
Time to take effect |
Duration |
Rapid-acting |
About 15 minutes with peak
in 1 hour |
2 – 4 hours |
Short-acting (Regular) |
About 30 minutes with peak
in 2 – 3 hours |
3 – 6 hours |
Intermediate-acting |
About 2 to 4 hours with peak
in 2 – 4 hours |
12 – 18 hours |
Long-acting |
About hours after injection
with no peak |
24 hours or longer |
Following
activities are advised in case of type 2 diabetes.
·
Proper diet plan (Dietician or doctors can
advise about meal plan)
·
Regular exercise
·
Frequent testing of blood sugar levels
·
Taking oral medications as per doctor’s
advice
Common
symptoms of type 1 and type 2 diabetes
·
Feeling more thirsty than usual
·
Frequent urination
·
Weight loss without exercise
·
Blurred vision
·
Feeling tired and weak
·
Presence of ketones in urine
·
Slow healing of cuts and wound
·
Mood changes or feeling irritable
·
Getting a lot of infection, such as gum,
skin and vaginal infections
It
is also known as pregnancy induced diabetes. It is a temporary condition in
which the blood glucose levels increase during third trimester of pregnancy but
usually return to normal after delivery. According to Centers of Disease
Control and Prevention (CDC), between 2 – 10% pregnancies each year results in
gestational diabetes. Women with gestational diabetes are at an increased risk
of complications during pregnancy and at delivery. These women and their
children are possibly at an increased risk of type 2 diabetes in the future.
According to CDC report, around 50% of people with gestational diabetes will
later develop type 2 diabetes.
Complications associated with
Gestational diabetes
Uncontrolled
or untreated blood sugar levels can cause problems to babies as well as their
mother. Most women with gestational diabetes deliver healthy babies if proper
treatment is given.
Complications
in baby can be of the following types.
· Low
blood sugar: Babies may be hypoglycemic shortly after
their birth because their own insulin production is high.
· Premature
birth: Gestational diabetes increases the risk of mothers
giving premature birth.Excess growth: High glucose levels in mother can cross the
placenta which can trigger the baby’s pancreas to make extra insulin. This in
turn, can cause the baby to grow too large. As a result of this, it may require
a C-section.
· Death:
If the gestational diabetes is left untreated, it may result in the death of
the baby before delivery or shortly after delivery.
· Type
2 Diabetes later in life: Mothers with gestational diabetes
are at a higher risk of developing type 2 diabetes later in their life. The
same applies to their babies.
Following
activities are advised in case of gestational diabetes.
·
Proper diet plan (Dietician or doctors can
advise about meal plan)
·
Regular exercise
·
Staying active
·
Monitoring blood sugar levels
·
Monitoring the growth and development of
the fetus
·
Keeping weight gain under control
·
Taking oral medications or insulin as per
doctor’s advice to control blood sugar level
Diabetes
and Prediabetes can be diagnosed by several methods by a doctor or a registered
healthcare practitioner. Doctors general recommend different tests depending on
whether the patient has any symptoms or not, or if the patient is pregnant.
Diagnosis at an early stage can be accomplished through relatively inexpensive
blood glucose test. The blood test may be repeated on a second day to diagnose
diabetes on recommendation of a doctor. However, if your blood glucose level is
very high, or if you have classic symptoms of hyperglycemia in addition to one
positive test, second test may not be required by the doctor to diagnose
diabetes (Tables 1-5) (Figures 1-4).
1. Fasting Plasma Glucose Test (FPG): In this
test, the patient should not eat or drink anything except water for at least 8
hours. The patient is advised to have a normal dinner and then undergo fasting
overnight. The test is done next day in the morning before having breakfast.
2. A1C Test: In this test, the average blood
glucose for the past two to three months is measured. This test is also called
hemoglobin A1C, HbA1C, glycated hemoglobin, and glycosylated hemoglobin test.
This test has an advantage over other tests because the patient does not have
to undergo fasting or drink glucose before test.
3. Oral Glucose Tolerance Test (OGTT): You
will have to fast for at least 8 hours before this test. Blood sample is taken
to measure the glucose level after fasting and then you are allowed to drink a
liquid which is high in sugar. After 2 hours of drinking the liquid, another
blood sample is withdrawn to check the glucose level in blood.
4 Random plasma glucose test: In this test,
blood glucose can be tested anytime of the day without fasting.
5. Glucose challenge test: This test is done
to check gestational diabetes in pregnant woman. Fasting is not required for
this test. The patient is given a sweet liquid containing glucose to drink.
Blood sample is taken after one hour of drinking sweet liquid to measure the
blood glucose content. If the blood sugar level is too high, oral glucose
tolerance test after fasting will be done to confirm gestational diabetes.
There
is a guideline developed by American Diabetes Association (ADA) which
recommends screening of following people for diabetes.
· Anyone with a BMI (Body Mass Index) higher
than 25 (23 for Asian Americans), regardless of age, if they have any
additional risk factors like sedentary lifestyle, high blood pressure, high
cholesterol level, a history of polycystic ovary syndrome, heart disease or
family history of diabetes.
· Any person older than 35 years of age
should have their blood sugar tested. If the results are normal, screening can
be done every 3 years after that.
· Women with gestational diabetes should be
screened for diabetes every 3 years.
· Anyone who has been diagnosed with
prediabetes should undergo screening every year.
· HIV positive patients are advised to go
for regular screening
Prevention
of Diabetes
Diabetes
can be prevented by certain lifestyle changes. We can easily prevent or delay
the onset of type 2 diabetes by following ways.
·
Maintain a healthy body weight as per body
mass index.
·
Regular physical exercise for 30 minutes daily.
·
Avoid junk food, sugar and saturated fat.
Eat a healthy diet.
·
Quit smoking
·
Manage stress and anxiety.
· Monitor and keep your blood pressure and
cholesterol within normal range.
·
Regular screening for diabetes.
Treatment
of Diabetes
Managing
diabetes is important to live a long and healthy life. Depending on type of
diabetes, blood sugar monitoring, insulin and oral drugs may be taken for the
treatment. Early treatment in people with prediabetes can also return their
blood glucose levels to normal range.
1. Treatment for type 1 diabetes: Patients
with type 1 diabetes are required to take insulin injections or insulin pump as
a lifelong insulin therapy. Patients are advised to self-monitor their glucose
level at home using glucose test strips. Depending on the glucose level, 2 or
more injections of insulin may be advised by the doctor. Some of the patients
may also be required to undergo pancreas transplant or islet cell transplant
depending on the severity and on the recommendation of a doctor.
2. Treatment of type 2 diabetes: Oral anti diabetic drugs or insulin or both may be required to treat type 2 diabetes mellitus along with a healthy lifestyle, regular physical exercise and proper diet plan. Some of the oral antidiabetic drugs work by increasing the release of insulin by pancreas while some of them prevent the production and release of glucose by the liver. There are many different types of oral antidiabetic drugs having their own mechanism of action to reduce the blood sugar level. For example; metformin, glimepiride, sitagliptin, voglibose, dapagliflozin, etc.
It
is advised that patients with diabetes mellitus either type 1 or type 2 should
monitor their blood glucose concentrations periodically at home using a
glucometer. Glucometer is a simple device to measure the blood sugar level at
home. Whenever the patient have the symptoms of hypoglycemia, this device is
very helpful in such conditions. The patient can prick their finger with the
needle provided with the device and a drop of blood is enough to measure the
blood sugar level using this device [1-17].
·
The number of people with diabetes
increased from 108 million in 1980 to 422 million in 2014. Prevalence has been
rising more rapidly in low and middle income countries than in high income
countries.
·
Diabetes is a major cause of blindness,
kidney failure, heart attacks, stroke and lower limb amputation.
·
Between 2000 and 2019, there was a 3%
increase in diabetes mortality rates by age.
·
In 2019, diabetes and kidney disease due
to diabetes caused an estimated 2 million deaths.
·
A healthy diet, regular physical activity,
maintaining a normal body weight and avoiding tobacco use are ways to prevent
or delay the onset of type 2 diabetes.
·
Diabetes can be treated and its
consequences avoided or delayed with diet, physical activity, medication and
regular screening and treatment for complications.