DIABETES MELLITUS

INTRODUCTION

Diabetes is a lifelong (chronic) disease and is a group of

metabolic disorder characterized by high levels of sugar in
blood (hyperglycemia) [1]. It is caused due to deficiency of
insulin or resistance to insulin or both. Insulin is secreted by β-
cells of pancreas to control blood sugar levels. Blurry visions,
excess thirst, fatigue, frequent urination, hunger, weight loss
are some of the symptoms commonly seen in diabetic patient.If
left untreated,diabetes can cause many complication.Acute
complications can include cardiovascular disease,stroke,foot
ulcers etc.[2]
 SIGN AND SYMPTOMS OF DIABETES
MELLITUS
• Increased Thirst
• Frequent Urination
• Unexpected Weight Loss
• Increased Fatigue
• Blurred Vision
• Numbness And Tingling In Your Feet And Hands
• Slow Healing Sores
• Red , Swollen ,Tender Gums
• Skin Itchy
• Irritability
SIGN AND SYMPTOMS
 EPIDEMIOLOGY
• With a diabetes prevalence of 10.3% among
adults,people with diabetes in India are likely to more
than double in the next decade from current 70 million,a
study by the country's apex research organization has
estimated.
• The prevalence of diabetes-also known as"Impaired
glucose tolerance" -is 1.4 times higher than the diabetes
of 7.3%, according to the Indian council of medical
research-IndiaB study of 57,117 adult 20years for 14
states and the union territory.
EPIDEMIOLOGY- India
 EPIDEMIOLOGY-WORLD
• IN 2017-
• Approximately 425 million adults (20-79 years) were living with diabetes; by
2045 this will rise to 629 million
• The proportion of people with type 2 diabetes is increasing in most countries
• 79% of adults with diabetes were living in low- and middle-income countries
• The greatest number of people with diabetes were between 40 and 59 years
of age
• 1 in 2 (212 million) people with diabetes were undiagnosed
• Diabetes caused 4 million deaths
• Diabetes caused at least USD 727 billion dollars in health expenditure in
2017 – 12% of total spending on adults
• More than 1,106,500 children were living with type 1 diabetes
• More than 21 million live births (1 in 7 births) were affected by diabetes
during pregnancy
• 352 million people were at risk of developing type 2 diabetes
EPIDEMIOLOGY-WORLD
 TYPES OF DIABETES
MELLITUS
DIABETES MELLITUS

TYPE 1 (IDDM) TYPE 2 (NIDDM) GESTATIONAL DM OTHER TYPES

NEONATAL DM MODY
 TYPE 1 DIABETES MELLITUS
(IDDM)
• Type 1 Diabetes is a disease in which the body doesn't
make enough insulin to control blood sugar level. T1D,
also called as the insulin-dependent diabetes mellitus
(IDDM), manifests due to the autoimmune damage of the
β-cells which then leads to the suppression or cessation
of insulin production. T1D is also called the “juvenile
diabetes’’ [5] In al type 1 cases circulating insulin level
are low or very low,and patients are more prone to
Methodist.Most patients with Diabetes Type 1 developed
the condition before the age of 40. Approximately 15% of
all people with diabetes have Type 1.
 Risk Factors For Type 1 DM
• The presence of damaging immune system cells that
make auto antibodies:-Sometimes family members of people with type
1 diabetes are tested for the presence of diabetes auto antibodies.[6] If you have
these auto antibodies, you have an increased risk of developing type 1 diabetes.
But, not everyone who has these auto antibodies develops type 1.

• Dietary factors:- A number of dietary factors have been linked to an

increased risk of type 1 diabetes, such as low vitamin D consumption; early
exposure to cow's milk or cow's milk formula; or exposure to cereals before 4
months of age. However, none of these factors has been shown to cause type 1
diabetes.

• Race:-.Type 1 diabetes is more common in whites than in other races

• Geography:- Certain countries, such as Finland and Sweden, have higher
rates of type 1 diabetes.
 TYPE 2 DIABETES MELLITUS
(NIDDM)

• Non insulin dependent diabetes mellitus (NIDDM)/

maturity onset diabetes mellitus
There is no loss or moderate reduction in beta cell mass(30-40%); insulin in
circulation is low , normal or even high. Over 90% cases are types 2 DM.
The majority of people with Type 2 have developed the condition because they are
overweight. Type 2 generally appears later on in life, compared to Type 1. Type 2 is
the most common form of diabetes. In the case of insulin resistance, the body is
producing the insulin, but insulin sensitivity is reduced and it does not do the job as
well as it should do.[7] The glucose is not entering the body's cells properly, causing
two problems:

• A build-up of glucose in the blood.

• The cells are not getting the glucose they need for
energy and growth.
 RISK FACTORS FOR TYPE 2
DM
• Obesity:- The number one risk factor for type 2 diabetes is obesity. Greater weight
means a higher risk of insulin resistance because fat interferes with the body's ability
to use insulin. The number of children being diagnosed with type 2 diabetes has also
risen.[8]
• Sedentary lifestyle:- A sedentary lifestyle is damaging to health and bears
responsibility for the growing obesity problems." Inactivity and being overweight go
hand in hand towards a diagnosis of type 2.[9] Muscle cells have more insulin
receptors than fat cells, so a person can decrease insulin resistance by exercising.
Being more active also lowers blood sugar levels by helping insulin to be more
effective.
• Unhealthy eating habit:- People who have been diagnosed with type 2 diabetes are
overweight. Unhealthy eating contributes largely to obesity. Too much fat, not
enough fiber and too many simple carbohydrates all contribute to a diagnosis of
diabetes.[10] Eating right is can turn the diagnosis around and reverse or prevent Type
2.
• Family history and genetics:- If you have a relative who has/had diabetes your risk
might be greater. The risk increases if the relative is a close one - if your father or
mother has/had diabetes your risk might be greater than if your uncle has/had it
 GESTATIONAL DIABETES MELLITUS
• Gestational diabetes only happens during pregnancy. It
means you have high blood sugar levels, but those levels
were normal before you were pregnant. If you have it,
you can still have a healthy baby with help from your
doctor and by doing simple things to manage your blood
sugar also called blood glucose. After your baby is born,
gestational diabetes usually goes away. Gestational
diabetes makes you more likely to develop type 2
diabetes, but it won’t definitely happen.[11]
 CAUSES OF GESTATIONAL
DM
• During pregnancy, the placenta (responsible for supplying oxygen and nutrients from
mother to the developing baby) makes hormones that can lead to a buildup of glucose
in your blood.
Usually, your pancreas can make enough insulin to handle that. If not, your blood
sugar levels will rise and can cause gestational diabetes.[12]

• Risk factors for gestational diabetes mellitus

• Age:- Women older than age 25 are at increased risk.

• Family or Personal History:- Your risk increases if you have prediabetes -a
precursor to type 2 diabetes — or if a close family member, such as a parent or
sibling, has type 2 diabetes. You're also at greater risk if you had gestational diabetes
during a previous pregnancy, if you delivered a very large baby or if you had an
unexplained stillbirth.
• Weight: -Being overweight before pregnancy increases your risk.
• Race:- For reasons that aren't clear, women who are black, Hispanic, American Indian
or Asian are more likely to develop gestational diabetes.
 OTHER TYPES OF DM
• Maturity onset diabetes of the young (MODY) :- MODY is a rare form
of diabetes which is different from both Type 1 and Type 2 diabetes, and runs strongly
in families. MODY is caused by a mutation (or change) in a single gene. If a parent
has this gene mutation, any child they have, has a 50 per cent chance of inheriting it
from them.[13] If a child does inherit the mutation they will generally go on to develop
MODY before they’re 25, whatever their weight, lifestyle, ethnic group etc.

• Neonatal diabetes:- Neonatal diabetes is a form of diabetes that is diagnosed

under the age of nine months.[14] It’s a different type of diabetes than the more
common Type 1 diabetes as it’s not an autoimmune condition (where the body has
destroyed its insulin producing cells).
 DIAGNOSE TEST FOR DIABETES
MELLITUS
• Tests for type 1 and type 2 diabetes

• Glycated hemoglobin (A1C) test

This blood test, which doesn't require fasting, indicates your average blood sugar
level for the past two to three months. It measures the percentage of blood sugar
attached to hemoglobin, the oxygen-carrying protein in red blood cells.
The higher your blood sugar levels, the more hemoglobin you'll have with sugar
attached. An A1C level of 6.5 percent or higher on two separate tests indicates that
you have diabetes.[15] An A1C between 5.7 and 6.4 percent indicates prediabetes (A
condition in which blood sugar is high but not high enough to be type 2 diabetes)
Below 5.7 is considered normal.
 If the A1C test results aren't consistent, the test isn't available, or you have certain
conditions that can make the A1C test inaccurate — such as if you're pregnant or have an
uncommon form of hemoglobin (known as a hemoglobin variant) — your doctor may use
the following tests to diagnose diabetes:

• Random blood sugar test.

A blood sample will be taken at a random time. Regardless of when you last ate, a
random blood sugar level of 200 milligrams per deciliter (mg/dL) — 11.1 millimeters per liter
(mmol/L) — or higher suggests diabetes.[16]

• Fasting blood sugar test.

A blood sample will be taken after an overnight fast. A fasting blood sugar level less than
100 mg/dL (5.6 mmol/L) is normal. A fasting blood sugar level from 100 to 125 mg/dL (5.6 to
6.9 mmol/L) is considered prediabetes. If it's 126 mg/dL (7 mmol/L) or higher on two
separate tests, you have diabetes.

• Oral glucose tolerance test.

For this test, you fast overnight, and the fasting blood sugar level is measured. Then you
drink a sugary liquid, and blood sugar levels are tested periodically for the next two hours.

A blood sugar level less than 140 mg/dL (7.8 mmol/L) is normal. A reading of more than
200 mg/dL (11.1 mmol/L) after two hours indicates diabetes. A reading between 140 and
199 mg/dL (7.8 mmol/L and 11.0 mmol/L) indicates prediabetes.[17]
 TESTS FOR GESTATIONAL
DIABETES MELLITUS
Your doctor will likely evaluate your risk factors for gestational diabetes early in your
pregnancy:

• Initial glucose challenge test :- You'll begin the glucose challenge test by drinking a
syrupy glucose solution. One hour later, you'll have a blood test to measure your blood
sugar level. A blood sugar level below 140 mg/dL (7.8 mmol/L) is usually considered normal
on a glucose challenge test, although this may vary at specific clinics or labs.
If your blood sugar level is higher than normal, it only means you have a higher risk of
gestational diabetes. [18]

• Follow-up glucose tolerance testing:- For the follow-up test, you'll be asked to fast
overnight and then have your fasting blood sugar level measured. Then you'll drink another
sweet solution — this one containing a higher concentration of glucose — and your blood
sugar level will be checked every hour for a period of three hours.
If at least two of the blood sugar readings are higher than the normal values established
for each of the three hours of the test, you'll be diagnosed with gestational diabetes .[19]
 TREATMENT FOR ALL TYPES OF
DIABETES
• Healthy eating:Contrary to popular perception,there is no
specific diet plan.You'll need to center your diet on more
fruits,vegetables,lean proteins and whole grains-food that are high in
nutrition and fibre and calories of low fat, and cut down on saturated
fats refined carbohydrates and sweets.[20] In fact it's the best eating
plan for the entire family.Sugary foods are OK IN a while as long as
they are counted as a part of your meal plan.
• Physical activity: Everyone needs regular aerobic
exercise, and one of the three hours of test, one can be diagnosed
with gestational diabetes.[21] People who have diabetes have no
exception.Exercise lowers body sugar level by moving sugar into
cells, where it is used for energy.Exercise also increase sensitivity to
insulin, which means body need less insulin top transport sugar to
cells.
 TREATMENTS FOR TYPE 1 DIABEES
MELLITUS
• Insulin :- People with type 1 diabetes need insulin therapy to survive. Many people with type 2
diabetes or gestational diabetes also need insulin therapy.
Insulin is usually given subcutaneously either by injections or by an insulin pump Research of other
routes of administration is underway. In acute-care settings, insulin may also be given intravenously. In
general, there are three types of insulin, characterized by the rate which they are metabolized by the
body. They are rapid acting insulin's, intermediate acting insulin's and long acting insulin's.[22]
TYPES OF INSULIN USED IN THE TREATMENT OF THE TYPE 1 DM

INSULIN PREPARATION

SHORT ACTING INTERMEDIATE ACTING LONG ACTING

INSULIN ZINC SUSPENSION

INSULIN GLARGIN
REGULAR INSULIN
INSULIN DETEMIR
ISOPANE INSULIN
 ACTIONS OF INSULIN
• Insulin helps control blood glucose level by
signaling the liver and muscle and fat cells
to take in glucose from the blood.Insulin
therefore helps cells to take in glucose to
be used for energy.if the body has
sufficient energy, insulin signals the liver to
take up glucose and store it as glycogen.
MECHANISM OF ACTION OF INSULIN
(IDDM)
TREATMENT FOR TYPE 2 DM (NIDDM)
Oral diabetes medications are used in the treatment of type 2 diabetes Medicines within this
category fall within one of several classes, including;[23]
A) Enhance insulin secretion
1) sulfonylureas (KATP channel blocker)
First generation- Tolbutamide
Second generation- Glibenclamide,Glipizide
2) Meglitinide/Phenylalanine analogues
Repaglinide,Nateglinide
3) Glucagon like pepetide -1 (GLP1) Receptor Agonist (Injectable Drugs)
Excenatide, Liraglutide
4) Dipeptidyl Peptidase -4 (DPP4) Inhibitors
Sitagliptin , vildagliptin
B) Overcome insulin resistance
1) Biguanide (Ampk Activator)
Metformin
2)Thiazolidinediones (PPARalpha Activator
Pioglitazine
C) Miscellaneous Antidiabetic Drugs
1) Alpha glucosidase inhibitors
Acarbose , Miglitol
2) Amylin Analogue
Pramlintide
3 )Dopamine D2 Receptor Agonist
Bromocriptine
4) Sodium Glucose Cotransport 2 Inhibitors
Dopagliflozin
 MECHANISM OF ACTION
1)Sulphonyl urease:- Sus SU Drugs

SU receptor
Closure of ATP dependant Potassium channel

cause depolarisation

increase calcium inside the cell

stimulate release of insulin

2) Meglitinide Analogues:- Su s Meglitinide drugs

SU receptor
Closure of ATP dependant Potassium channel

cause depolarisation

increase calcium inside the cell

stimulate release of insulin
• GLP1 Receptor Agonist:- Food in GIT Glucose GLP1 liraglutide

Act on beta cell

Increase the insulin release

• DPP4 Inhibitors :- sitagliptin

GLP1 Inactivate peptide (Degrade)

 PATHOPHYSIOLOGY
• Insulin secretion from the beta-cell in the
pancreas normally reduce glucose output
by the liver and increase glucose uptake by
skeletal muscles and adipose tissue .
• Once beta-cell dysfunction in the pancreas
and or insulin resistance in liver skeleton
muscle occur,hyperglycemia develops
leading to an excessive amount of blood
glucose.
 HERBAL DRUG TREATMENT FOR
DIABETES
• Acacia arabica
• Achyranthes aspera
• Allium sativum (garlic)
• Allium cepa: (onion)
• Azadirachta indica
• Tinospora cordifolia: (Guduchi)
• Commando
• Bitter Melon
• Fenugreek
• Gymnema
PATHOPHYSIOLOGY
 NEW ANTI DIABETIC DRUGS
• New Drug Treatments for Type 1 and Type 2 Diabetes

• NN1250/Insulin Degludec/Tresiba
NN1250/Insulin Degludec is being developed by Novo Nordisk and has reached
phase 3 clinical trials. This is a completely neutral, soluble, and subcutaneous ultra-
long-acting new-generation insulin that lasts for over 24 hours. This insulin is designed
for basal insulin treatment of both type 1 and type 2 diabetes mellitus.[25]
• LY2405319
LY2405319 is a new drug being developed by Eli Lilly. The drug is in a new class of
treatments known as FGF21 analogues. FGF21 stands for fibroblast growth factor 21,
which is a hormone in the body that stimulates glucose uptake of adipose cells (fat
cells). In initial phase 1 human studies, the drug has shown beneficial effects on blood
lipid levels, blood glucose levels and reduction in body weight. [26]
 LIFESTYLE FOR TYPE 1 AND TYPE 2
DM
• Identify yourself:- Wear a tag or bracelet that says you have diabetes. Keep a
glucagon kit nearby in case of a low blood sugar emergency — and make sure your
friends and loved ones know how to use it.[27]
• Pay attention to your feet:-Wash your feet daily in lukewarm water. Dry them
gently, especially between the toes. Moisturize with lotion, but not between the toes.
Check your feet every day for blisters, cuts, sores, redness or swelling. Consult your
doctor if you have a sore or other foot problem that doesn't start to heal on its own.[28]
• Keep your blood pressure and cholesterol under control:- Eating healthy
foods and exercising regularly can go a long way toward controlling high blood
pressure and cholesterol. Medication may be needed, too.
• Take care of your teeth:- Diabetes may leave you prone to gum infections. Brush
and floss your teeth at least twice a day. And if you have type 1 or type 2 diabetes,
schedule dental exams at least once a year. Consult your dentist right away if your
gums bleed or look red or swollen.
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