Chapter1:-

Introduction
INTRODUCTION

According to WHO, Diabetes Mellitus is defined as heterogeneous metabolic disorder

characterized by common feature of chronic hyperglycemia with disturbance of
carbohydrate, fat and protein metabolism.

Diabetes mellitus (DM) is commonest endocrine disorder that affects more than 100
million people worldwide (11.4% population). It is caused by deficiency or ineffective
production of insulin by pancreas which results in increase or decrease in
concentrations of glucose in the blood. It is found to damage many of body systems
particularly blood vessels, eyes, kidney, heart and nerves.

Diabetes mellitus has been classified into two types:

(1) Insulin dependent diabetes mellitus (IDDM, Type I) (10%)

(2) Non-insulin dependent diabetes mellitus (NIDDM, Type II) (80%)

Type I diabetes is an autoimmune disease characterized by a local inflammatory

reaction in and around islets that is followed by selective destruction of insulin
secreting cells whereas Type II diabetes is characterized by peripheral insulin resistance
and impaired insulin secretion 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. Drugs are used
primarily to save life and alleviate symptoms. Secondary aims are to prevent long-term

complications such as cardiovascular diseases, peripheral vascular diseases, stroke,

Nuropathy, renal failure, Retinopathy, blindness, amputations etc. 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.

Insulin replacement therapy is the mainstay for patients with type 1 DM while diet and

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lifestyle modifications are considered the cornerstone for the treatment and
management of type2 DM. Various types of hypoglycemic agents such as biguanides
and sulfonamides are also available for treatment of diabetes. The main disadvantage of
currently available drugs is that they have to be given throughout the life and produce
side effects. Medicinal plants and their bio-active constituents can be used for treatment
of DM throughout the world especially in countries where access to the conventional
anti-DM agents is inadequate Various experimental models are also available to screen
anti diabetic activity of plant. The present review therefore is an attempt to know more
precisely about diabetes mellifluous, its clinical presentation, epidemiological data,
complications and current available treatment of diabetes.

Fig 1. Shows Normal blood and Diabetic blood

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 CHAPTER 2:
LITERATURE REVIEW
2.1 EPIDEMIOLOGY
The epidemiology of diabetes focuses on the distribution, determinants, and health
outcomes of diabetes in populations. Diabetes is a metabolic disorder characterized by
hyperglycaemia, and it is classified primarily into type 1, type 2, and gestational
diabetes.

2.1.1 Global Prevalence:-

1.Type 1 Diabetes:

*Incidence: Type1 diabetes accounts for about 5-10% of all diabetes cases. It often
develops in childhood or adolescence but can occur at any age.

*Geographic Variation: Its Higher incidence in Northern European countries,

such as Sweden and Finland, and lower in Asian and African countries.

2. Type 2 Diabetes:

* Incidence: Type2 diabetes accounts for about 90-95% of all diabetes cases.
Its prevalence is rising globally, with significant increases in both developed and

developing countries.

* Geographic Variation: Higher prevalence in countries with westernized

lifestyles, including the USA, India, and China. Urbanization and lifestyle changes are

major contributing factors.

3. Gestational Diabetes:

*Prevalence: Gestational diabetes varies widely, affecting approximately 1-14% of

pregnancies globally. Higher rates are observed in women with higher BMI, advanced
maternal age, and certain ethnic backgrounds, such as South Asian, Middle Eastern.

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 2.1.2 Risk Factors:-
1.Type 1 Diabetes:
In this, there is an autoimmune mediated destruction of pancreatic beta cells. This leads
to reduced production of insulin and insulin deficiency in the body. The cause of
autoimmune mediated destruction of beta cells is not completely understood and is
believed to be due to multiple factors including genetic susceptibility, genetic etc.

*Genetic: Strong genetic predisposition with associations to specific HLA genotype.

*Environmental: Possible triggers include viral infections and early exposure to

cow’s milk.

2.Type 2 Diabetes:
Type 2 diabetes is usually associated with obesity, age, High blood pressure, lifestyle,
High cholesterol level, physical inactivity, high cholesterol levels, PCOS etc.

*Genetic: Family history and genetic susceptibility play significant roles.

*Lifestyle: Obesity, physical inactivity, and poor diet are major modifiable risk
factors.

*Socioeconomic Factors: Lower socioeconomic status is associated with higher

risk due to limited access to healthy foods and healthcare.

*Obesity: Excess body weight, particularly abdominal obesity, increases the risk of

developing type 2 diabetes.

*Physical inactivity: Sedentary lifestyles contribute to insulin resistance and

weight

gain, increasing the risk of type 2 diabetes.

*Age: The risk of type 2 diabetes increases with age, especially after 45 years old.

*High blood pressure: Hypertension is often associated with insulin resistance,

contributing to the development of type 2 diabetes.

*High cholesterol levels: Elevated levels of LDL cholesterol and triglycerides and

low levels of HDL cholesterol are associated with an increased risk of type 2

diabetes.

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*PCOS:- Women with PCOS have a higher risk of developing insulin resistance and
type 2 diabetes.

2.1.3 Complications:-
*Micro vascular: Retinoopathy (eye problem), nephropathy (kidney problem), and
neuropathy (nerve damage).

*Macro vascular: Cardiovascular diseases, including heart attack and stroke.

*Others: Increased risk of infections, foot ulcers, and amputations.

2.2 Pathophysiology:-

The psychopathology of diabetes is knotty connected to insulin levels and our body’s

ability to utilize this insulin hormone. In type 1 diabetes, there is an absolute

deficiency of insulin due to autoimmune destruction of the pancreatic beta cells. In

contrast, type2 diabetes is characterized by insulin resistance in peripheral tissues,

along with an eventual decline in beta-cell function.

Under normal circumstances, pancreatic beta cells release insulin in response to

elevated blood glucose levels. This insulin facilitates the uptake of glucose by tissues,

thereby lowering blood glucose concentrations. The brain, which relies on a continuous

supply of glucose for normal functioning, can be significantly affected by fluctuations

in blood glucose levels.

Hypoglcemia, defined as abnormally low plasma glucose levels, is a common

complication of diabetes treatment, particularly with the use of insulin and oral

Anti hyperglycemia agents. The body’s response to hypoglycaemia involves a complex

interplay between the central nervous system and metabolic regulation. The central

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nervous system, upon detecting low glucose levels, mobilizes energy reserves to

maintain cerebral blood flow and tissue integrity. This response is influenced by several

factors, including arterial plasma glucose levels, the rate of decline in plasma glucose,

and the availability of other metabolic.

Low plasma glucose triggers an increase in autonomic activity, which includes a series

of physiological responses aimed at restoring normal glucose levels. These responses

encompass decreased insulin secretion, increased release of counter-regulatory

hormones such as glucagon and epinephrine, and a heightened sympathetically

response. The clinical manifestations of hypoglycaemia range from mild symptoms like

sweating and palpitations to severe outcomes such as cognitive dysfunction, seizures,

and coma. Diagnosis of hypoglycaemia necessitates confirmation of low plasma

glucose

levels and the presence of corresponding symptoms. The immediate treatment for

hypoglycaemia is the administration of glucose, which quickly raises blood sugar levels

and alleviates symptoms.

Fig 2. Shows Pathophysiology of diabetes mellitus

2.3 Symptoms Of Diabetes:-

 Increased thirst (Polydipsia)
 Frequent urination (Poly urea)
 Extreme Hunger (Polyphagia)
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  Unintended Weight loss (Fatigue)
 Fatigue
 Blurred Vision
 Slow Healing of Wounds
 Frequent Infections
 Numbness inn Hands and feet.

Specific Symptoms of Type1 Diabetes:

 Keto acidosis
 Rapid Onset of Symptoms

Specific Symptoms Of Type2 Diabetes:

 Gradual Onset of Symptoms
 Darkened Skin

Other Symptoms:-
Presence of Ketones in Urine.
Increased irritability.

Fig 3. shows Symptoms of Diabetes Mellitus

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 CHAPTER 3:
Objectives Of Diabetes
Treatment

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The aim of managing diabetes mellifluous is primarily to maintain blood glucose levels within a

target range to prevent complications and promote overall health and well-being.

This include:-

1.Blood Glucose Control: Keeping blood glucose levels as close to normal as possible

through monitoring, medication (such as insulin or oral hypoglycaemic agents), and lifestyle

modifications (diet, exercise).

2.Preventing Complications: Diabetes can lead to various complications over time,

including cardiovascular disease, retinopathy, neuropathy, and nephropathy. Managing blood

glucose levels, blood pressure, and cholesterol, as well as regular medical check-ups, can help

prevent or delay the onset of these complications.

3.Lifestyle Modifications: Adopting a healthy lifestyle, including a balanced diet, regular

physical activity, maintaining a healthy weight, avoiding tobacco use, and moderating alcohol

consumption, can significantly impact diabetes management and overall health.

4.Education and Self-Management: For empowering diabetic patients to manage their

conditions successfully, education and support are essentials to provide. This includes

understanding the disease, monitoring blood glucose levels, administering medication (if

required), and making informed lifestyle choices.

5.Psychological Support: Diabetes management can be challenging both physically

and Providing psychological support and addressing mental health needs can improve
health,

CHAPTER 4:-
Work undertaken the Practice School
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 The diabetes and its treatment project may include research methodologies,
management of patients with diabetes mellifluous, lifestyle interventions, drug used ,
and educational initiatives aimed at managing diabetes effectively.

It could involve clinical trials, data analysis, patient education programs and
collaborations with healthcare providers to improve outcomes for individuals living
with diabetes.

4.1Research Methodologies

Researchers have discovered an innovative way to deliver insulin orally, potentially

transforming diabetes management. This new medication has been successfully tested
on baboons, demonstrating its ability to lower blood sugar level without causing
hypoglycaemia, a common risk with traditional insulin injections. The insulin is
designed to be released in response to high blood sugar levels, mimicking the natural
functions of pancreas more closely to current methods. Human clinical trials for this
oral insulin are set to begin in 2025.

To treat diabetes mellifluous in a safer and more efficient manner, clinical trials for novel
insulin therapy are essential. The purpose of these multiphase studies is to evaluate many
elements of the novel insulin formulation, such as safety, effectiveness, dose, and side effects.
Here is a summary of what new insulin clinical trials normally entail:

1.Pre clinical Studies:-

* Laboratory Research: In vitro studies on cell lines to understand the insulin’s molecular

properties and mechanisms of action.

*Animal Testing: Testing on animal models to evaluate the pharmacology kinetics (how the

drug is absorbed, distributed, metabolized, and excreted) and pharmacology dynamics (the

effects of the drug and its mechanism of action) of the new insulin.

2. Phase 1 Clinical Trials:-

*Goal: Evaluate dose and safety.

*Participants: A small sample of people with diabetes or healthy volunteers (20–100).

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* Focus: Understanding the pharmacology kinetics and pharmacology dynamics of insulin in

well as determining the ideal dosage range and any possible adverse effects.

3. Phase 2 Clinical Trials:-

*Goal: Assess effectiveness and adverse effects.

*Participants: A larger group of people with diabetes (between 100 and 300).

*Focus: Evaluating the new insulin's ability to regulate blood glucose levels, comprehensive

how it affects the body, and keeping an eye on safety and adverse effects.

4 .Phase 3 Clinical Trials:-

*Goal: Verify efficacy and track negative responses.

*Participants: A sizable cohort of 300–3,000 diabetics, frequently drawn from several

clinical settings.

*Focus: Assessing long-term consequences and quality of life implications, comparing the

novel insulin to currently recommended conventional therapies, and obtaining more thorough

data on safety and efficacy.

3. Regulatory Review and Approval:-

*Submission: Information from every stage is gathered and sent for examination to regulatory

bodies (like the FDA in the US or the EMA in Europe).

* Evaluation: To make sure the new insulin is safe and effective for use by the general public,

regulatory agencies evaluate the data.

* Approval: The novel insulin may be sold and administered if it is accepted.

4. Phase 4 (Post-Marketing Surveillance):-

* Goal: Keep an eye on long-term efficacy and safety.

* Participants: A wide range of users in actual environments.

Priorities include identifying any infrequent or persistent side effects, verifying the insulin's
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 continued efficacy, and guaranteeing its general safety over a wider range of patient demographics.

4.2 Management of patients with Diabetes Mellitus

Managing patients with diabetes mellitus involves a comprehensive approach to control blood sugar

levels, prevent complications, and improve overall health and quality of life. Here's an overview of

key aspects:

1. Medical Management:

Blood Glucose Monitoring: Regularly checking blood glucose levels helps in managing diabetes

effectively. Patients may need to monitor their levels multiple times a day, depending on their

treatment plan.

Medications: Depending on the type and severity of diabetes, patients may require oral medications,

insulin injections, or both to control blood sugar levels.

Dietary Management: A well-balanced diet, rich in whole grains, fruits, vegetables, proteins,

and healthy fats, is essential.

Physical Activity: Regular exercise helps improve insulin sensitivity and lower blood sugar levels.

1.Education and Self-Management:

Diabetes Education: Providing patients with education about their condition, including the

importance of medication adherence, dietary habits, exercise, and blood sugar monitoring, empowers

them to manage their diabetes effectively.

Self-Monitoring: Encourage patients to monitor their blood sugar levels regularly and keep track of

their diet, physical activity, and medications.

Regular Medical Follow-Up: Patients should have regular follow-up visits with healthcare

providers, including physicians, endocrinologists, and diabetes educators, to monitor their blood sugar

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 levels, assess the effectiveness of treatment, and adjust medications or lifestyle interventions as

needed.

4.3 Prevention Strategies:-

*Primary Prevention: Lifestyle interventions such as maintaining a healthy weight, regular physical

activity, and a balanced diet can prevent or delay the onset of type 2 diabetes.

*Secondary Prevention: Early detection through screening, especially for high-risk populations, and

effective management to prevent complications.

*Tertiary Prevention: Comprehensive management of diabetes and its complications to improve

quality of life and reduce mortality.

*Economic Burden: Diabetes imposes substantial economic costs on individuals and healthcare

systems due to the need for ongoing medical care, monitoring, and treatment of complications.

*Policy and Programs: National and international public health initiatives aim to reduce the burden

of diabetes through education, policy changes, and improved healthcare access.

*Dietary Changes: Balanced Diet

Carbohydrate management

Portion control.

*Weight Management:-
 Achieving and Maintaining a Healthy Weight: For individuals who are
overweight or obese, losing even a small amount of weight can significantly
improve blood sugar levels and reduce the risk of diabetes-related complications.
A combination of diet, exercise, and behavioral strategies is often used to achieve
sustainable weight loss.

*Behavioral Changes:- Stress Management

Sleep hygiene.

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 4.4 Management Of Diabetic Acidosis ( Diabetic Coma):-

Diabetic acidosis is a medical emergency and requires prompt management.

It is more common in patients with diabetes 1 mellitus and rare in patients with diabetics 2
mellitus.

The key measures in the management of diabetic acidosis are mentioned in Table1.

Table1 Diabetic acidosis

1. Regular insulin:-

Intravenous bolus followed by infusion.

2. Fluid replacement:-

Intravenous fluids-initially normal saline is infused followed by 5% glucose in

½ N saline.

3. Potassium:-

Hypoglycemia can occur during insulin therapy and acidosis correction. ECG
monitoring and serum potassium measurements should be performed.

4. Sodium bicarbonate (if required)

5. Phosphate (if required)

6. Antibiotics ( to treat any infections, if present)

7. Supportive management of airway, breathing, circulation, fluid and electrolyte

balance.

4.5 Management Of Hyper molar (Non Ketotic Hyperglycemia) Coma:-

A medical emergency, hyperbola hyperglycemia coma needs to be treated right away. Patients

with type 2 diabetes mellifluous experience it. The patient exhibits heterosexuality, dehydration, and

hyperglycaemia. Ketosis does not exist. The management strategies are comparable to those for

diabetic acidosis. But the patient needs more fluid replacement more quickly, and alkali therapy

is usually not required.

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4.6 Pharmacological Agents

Pharmacological treatment of type 1 diabetes:-

The basis of atreatment for type 1 diabetes is insulin therapy. Although, thanks to research, non-insulin

supplement treatment is now used in laboratories and clinical trials to find new treatment options for

diabetes. Metformin, a biguanide, is the most common drug used to manage diabetes. It is sometimes

supplemented with amylin analogues, GLP-1 receptors, and sodium-glucose co-transporter 2 (SGLT2)

inhibitors. These medications grant good outcomes and management in type 1 diabetes mellitus

patients .

Pharmacological treatment of type 2 diabetes mellitus

The various drugs administered to treat type 2 diabetes mellitus patients have different mechanisms to

reverse the effects of hyperglycaemia by reducing blood sugar levels.

1. Sulfonylureas are insulin secretagogues that have been used extensively in the treatment of

patients with diabetes. They are mostly metabolized in the liver and sometimes excreted by the

kidneys. Irrespective of blood glucose levels, sulfonamides trigger insulin secretion from

the pancreas. Also, sulfonamides inhibit glucagon secretion, enhance insulin sensitivity in

peripheral tissues, and reduce hepatic insulin clearance .

2.Meglitinides are drugs that increase insulin secretion from the pancreas, and they are dependent

on glucose levels, which reduces the risk of hypoglycaemia. It has a short duration of action and

can be administered to match the postprandial increase in glucose.

3.Metformin (Glucose phage) improves hepatic insulin sensitivity and reduces hepatic glucose

production. It also reduces insulin resistance in the peripheral tissues by reducing free fatty

acids, triglycerides, and high blood glucose levels . It carries out its antihyperglycemic

action without influencing insulin secretion. Also, it elevates gut glucose utilization and

triggers GLP-1 secretion. Metformin is commonly administered as the first pharmacological

agent in the treatment of diabetes because of its affordable price, efficiency, and few side

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4.Sodium-glucose transport protein 2 (SGLT2) inhibitors They are a class of oral anti diabetic

agents administered to lower blood glucose levels in adult patients with type 2

diabetes mellitus. Its action is not affected by insulin resistance or the insulin levels in the body.

5.Glucagon-like peptide-1 (GLP-1) GLP-1 is produced and stored in the L cells of the ileum

and colon. Neural and hormonal mechanisms coupled with the presence of food in

the gastrointestinal tract trigger its release. GLP-1 enhances insulin secretion by the beta cells

and inhibits glucagon secretion by the alpha cells when blood glucose levels are elevated

above normal .

6.Pramlintide (symlin) Pramlintide is a synthetic derivative of amylin. It is soluble in

nature and administered orally. In response to nutrient stimuli, the pancreas secures Amylin

with insulin. It reduces post-prandial stimulated glucagon secretion, slows down gastric

emptying, and suppresses appetite.

7.Proscription-QR reduces insulin sensitivity and resistance, leading to a decrease in

hepatic glucose production and an increase in glucose disposal. It does not elevate insulin

levels, making it effective in patients who produce insulin but are insulin resistant.

Proscription-QR improves glycaemic levels in patients with type 2 diabetes mellifluous when

administered as a monotherapy drug or combined with other anti hyperglycemia agents .

8.Thiazolidinediones (TZDS) reduce insulin resistance while simultaneously activating the .

response to insulin. Teds improve hypoglycemic control and act to reverse certain disease

complications like polycystic ovarian syndrome, atherosclerosis, and other cardiovascular

diseases in patients with type 2 diabetes mellifluous. However, side effects like weight gain

and osteoporosis can be very serious, causing its use to be limited .

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 Fig. 4. Sites of action of the pharmacological agents.

Fig. 5. Effects of secretion of insulin hormone on pancreas.

DISCUSSION:-
Diabetes mellifluous is a chronic condition characterized by high levels of sugar in the blood. Along
with medication or insulin therapy, treatment usually entails dietary and activity modifications. To
properly manage the illness, regular blood sugar monitoring and constant collaboration with
healthcare experts are essential. There are other kinds of diabetes drugs, such as inject able insulin and
oral drugs like metformin. Furthermore, more recent drugs like as SGLT2 inhibitors and GLP-1
receptor agonists have demonstrated promise in controlling blood sugar levels and lowering the risk
of complications.

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CONCLUSION:
Effective diabetes management requires a multifaceted approach that includes lifestyle adjustments,

medication, continuous monitoring and education. Even while diabetes is still incurable, there are

measures that can greatly improve quality of life and avoid or lessen complications. Future

improvements in medical science and treatment could lead to a cure or at least more effective

therapies. However, research studies have helped in the prognosis, diagnosis, treatment, and

management of its different forms. The pathophysiology of the prognosis and diagnosis

dictates the treatment option to be administered. Although it is important to note that such

pharmacological agents have different side effects, new studies aid in the proper application

and combination of the drugs. Eating the right diet, increasing physical activity, and

monitoring and maintaining healthy glucose levels are some of the ways individuals can

prevent the risk of the disease.

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