INTRODUCTION AND CAUSES OF DIABETES MELLITUS TYPE 1

1. DIABETES MELLITUS Type 1
AMITY INSTITUTE OF PHYSIOTHERAPY
AMITY UNIVERSITY UTTAR PRADESH
IRAM ANWAR

2. TABLE OF CONTENTS
DECLARATION………………………………………………………………
FACULTY GUIDED APPROVAL……………………………………………
ACKNOWLEDGEMENT……………………………………………………..
LIST OF FIGURES……………………………………………………………
INTRODUCTION……………………………………………………………..
CAUSE ………………………………………………………………………..
SIGN AND SYMPTOM……………………………………………………….
TYPES…………………………………………………………………………
PATHOGENESIS……………………………………………………………...
DIAGNOSIS…………………………………………………………………...
PREVENTION…………………………………………………………………
MANAGEMENT………………………………………………………………
COMPLICATION……………………………………………………………..
REFERENCES………………………………………………………………...

3. DIABETES MELLITUS Type 1

4. INTRODUCTION
DIABETES MELLITUS TYPE 1
 Diabetes mellitus (DM), commonly referred to as diabetes, is a group of
metabolic diseases in which there are high blood sugar levels over a prolonged
period. Symptoms of high blood sugar include frequent urination, increased
thirst, and increased hunger. If left untreated, diabetes can cause many
complications. Acute complications include diabetic ketoacidosis and
nonketotic hyperosmolar coma. Serious long-term complications include
cardiovascular disease, stroke, chronic kidney failure, foot ulcers, and damage
to the eyes.
 Diabetes is due to either the pancreas not producing enough insulin or the
cells of the body not responding properly to the insulin produced. There are
three main types of diabetes mellitus:
 Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia due to
absolute or relative deficiency of insulin, or both (i.e. defects in insulin
secretion, insulin action or both).
 Diabetic ketoacidosis is a major medical emergency and remains a serious cause
of morbidity, principally in people with type1 Diabetes.
 A significant number of newly diagnosed diabetes a common course of events
is that patients develop an intercurrent infection, lose their appetite, and either
stop or that under these circumstances less insulin is required.
 Treatment with insulin is typically required for survival. Insulin therapy is usually
given by injection just under the skin but can also be delivered by an insulin pump.

 A diabetic diet and exercise are an important part of management. Untreated, diabetes
can cause many complications. Complications of relatively rapid onset
include diabetic ketoacidosis and nonketotic hyperosmolar coma. Long-term
complications include heart disease, stroke, kidney failure, foot ulcers and damage to
the eyes. Furthermore, complications may arise from low blood sugar caused by
excessive dosing of insulin

6. CAUSES
1.Genetics
Type 1 diabetes is a disease that involves many genes.
The risk of a child developing type 1 diabetes is about 5% if the father has it, about 8% if a
sibling has it, and about 3% if the mother has it.
If one identical twin is affected there is about a 50% chance the other will also be
affected. Some studies of heritability has estimated it at 80 to 86%.
More than 50 genes are associated with type 1 diabetes
2.Environmental
Environmental factors can influence expression of type 1.
For identical twins, when one twin has type 1 diabetes, the other twin only has it 30%-50% of
the time.
Thus for 50%-70% of identical twins where one has the disease, the other will not, despite
having exactly the same genome; this suggests that environmental factors, in addition to
genetic factors, can influence the disease's prevalence
3.Chemicals and drugs
Some chemicals and drugs selectively destroy pancreatic cells.
Pyrinuron (Vacor), a rodenticide introduced in the United States in 1976, selectively destroys
pancreatic beta cells, resulting in type 1 diabetes after accidental poisoning.
Pyrinuron was withdrawn from the U.S. market in 1979 and it is not approved by
the Environmental Protection Agency for use in the U.S.
Streptozotocin (Zanosar), an antineoplastic agent, is selectively toxic to the beta cells of
the pancreatic islets. It is used in research for inducing type 1 diabetes on rodents[31] and for
treating metastatic cancer of the pancreatic islet cells in patients whose cancer cannot be
removed by surgery.[32] Other pancreatic problems, including trauma, pancreatitis, or tumors
(either malignant or benign) can also lead to loss of insulin production.

7. SIGNS AND SYMPTOMS
 Thirst, dry mouth
 Polyuria
 Nocturia
 Tiredness, fatigue
 Recent change in weight
 Blurring of vision
 Pruritus vulvae, balanitis (genital candidiasis)
 Nausea: headache
 Hyperphagia; predilection for sweet foods
 Dry skin
 Rapid deep breathing,
 Drowsiness
 Increased thirst,
 Frequent urination,
 Abdominal pain,
 Vomiting
 Irritability
 Difficulty in concentrating
GENERAL CHARACTERISTICS
Features Type 1 DM
1. Age on onset <40 years
2. Duration of symptoms Days or weeks
3. Body habitus normal to wasted
4. Plasma insulin low to absent
5. Plasma glucagon high, suppressible
6. Acute complication ketoacidosis
7. Insulin therapy Responsive
8. Sulphonylurea therapy unresponsive
9. Autoantibodies yes
10. Other autoimmune disease yes

9. TYPES OF DIABETES MELLITUS TYPE 1
AETIOLOGICAL CLASSIFICATION
TYPE 1 DIABETES
❖Type 1A (Immune- mediated)
❖Type 2B (Idiopathic)
Type 1 DM
❖Usually begins before the age of 40.
❖Body habitus is normal to wasted.
❖Two broad categories of DM are designated type 1 and type 2
 In type 1 DM there is absolute insulin deficiency. Type 1 is subdivided into two
groups : type 1A due to autoimmune destruction of beta –cells and type 1B where
beta-cells destruction nearly 10% of patients above the age of 30 years have this type
of DM.
 The terms insulin-dependent diabetes mellitus (IDDM) and non-insulin – dependent
diabetes mellitus (NIDDM) are no longer used because several patients with NIDDM
eventually would require insulin.
 Maturity onset of diabetes in the young (MODY) is characterised by autosomal
dominant inheritance , early onset of diabetes and impairment of insulin secretion..
Potential diabetics
❖Potential diabetics are persons with a normal glucose tolerance test who have an increased
risk of developing diabetes for genetics reasons. Examples are :
Children of two diabetic parents.
sibling of a diabetic.
Non-diabetic member of a pair of monozygotic twins where the other is a diabetic.
Latent Diabetics
❖ Latent diabetics are persons in whom the glucose tolerance test is normal but who are
known to have given an abnormal result under conditions imposing a burden on the

10. pancreatic cells –e.g. during pregnancy , infection , severe stress (physical or mental ), during
treatment with corticosteroids, thiazide diuretics or other diabetogenic drugs , or when
overweight.

11. PATHOGENESISOF Type 1 DIABETES MELLITUS
❖Type 1 diabetes appears when more than 90% of beta-cells of pancreas are destroyed by an
autoimmune process. The pathogenetic sequence is given blow.
❖First, genetic susceptibility to the disease must be present. about 95% of patients with type
1 DM have either HLADR3 and DR4. most individuals with type 1 DM do not have first
degree relative with diabetes.
❖Second, an environmental event (commonly viral infection) initiates the process in
genetically susceptible individuals.
❖Third step in the sequence is an inflammatory response in the pancreas called “insulitis”.
There is infiltration of the islets with activated T lymphocytes.
❖Fourth step is the activation of autoimmunity. There is an alteration of the surface of the
beta-cell such that it no longer recognised as “self” but is seen by the immune system as a
foreign cell or “non-self”.
❖Fifth step is the development of an immune response. Though islet cell antibodies (ICA)
are present in most patients, they are not involved in destructive process. Instead,
activated T lymphocytes present in the islet release cytokines (tumour necrosis factor
alpha, interferon gamma and interleukin 1) that destroy beta-cells. CD8+cell –induced
cytoxicity and apoptopsis are also invoived. This results in an immune attack on beta-
cells, with resultant destructive of beta-cells. When more than 90% of betacells are
destroyed, diabetes appears. Alpha-cells remain intact.
❖The events that trigger the transition from glucose intolerance to frank diabetes are often
associated with increased insulin requirements that might occur during stress, infection or
puberty. Thus, following initial development of frank DM, many patients become
Euglycaemic without need of insulin for sometimes. This is called “honeymoon phase”.
This generally lasts for a few months after which the patient develops frank DM again.
❖Markers of immune destruction of the beta-cells include islet cell autoantibodies,
autoantibodies to insulin, autoantibodies to glutamic acid decarboxylase (GAD65), and
autoantibodies to the tyrosine phosphatase IA-2 and IA-2beta .one and usually more of
these autoantibodies are present are in 85-90% of individuals when fasting
hyperglycaemia is initially detected.
❖The disease also has strong HLA associations with linkage to the DQA and DQB genes,
and it is influenced by the DRB genes. These alleles can be either predisposing or
protective.

12. ❖ These patients are also prone to other autoimmune disorders such as Graves’ disease,
Hashimoto’s thyroiditis, Addison’s disease, vitiligo, coeliac sprue, autoimmune hepatitis,
myasthenia gravis and pernicious anaemia.
 A clear understanding of the biochemical basis and pathophysiology of this problem is
essential for its efficient treatment.
 The hyperglycaemia causes a profound osmotic diuresis leading to dehydration and
electrolyte loss, particularly of sodium and potassium.
 Ketosis results from insulin deficiency, exacerbated by elevated catecholmines and
other stress hormones, resulting in unrestrained lipolysis and supply of free fatty acids
for hepatic ketogenesis.

13. DIAGNOSIS OF DIABETES MELLITUS
 Diabetes may present with polyuria, polydipsia, polyphagia and significant weight
loss despite polyphagia.
 Depressed immune status may result in flare –ups of pulmonary tuberculosis, non-
healing of wounds, recurrent styes, candidial vulvae, balanitis and recurrent urinary
tract infections.
 Some patients may present with end-organ involvement- e.g. retinopathy,
nephropathy or neuropathy
 In some cases risk factors may be identifiable- e.g. obesity, pregnancy and first degree
relative of known diabetics.
 Urine examination may show glycosuria with or without ketonuria.
 Glycosylated haemoglobin (HbA1 ) levels may be elevated (normal <6%).
 HLA typing may reveal the genetics predisposition in type 1 diabetes mellitus.
 In the absence of pregnancy , IFG and IGT are not clinical entities in their own right
but rather risk factors for future diabetes as well as cardiovascular disease . Both
o have been termed “pre-diabetes”
 IFG (Impaired fasting glucose ) and IGT ( impaired glucose tolerance) are associated
with the metabolic syndrome ,which include obesity (especially abdominal or visceral
o obesity ), and hypertension .
 Medical nutrition therapy aimed at producing 5 – 10% loss of body weight , exercise
and certain pharmacological agents ( acarbose , metformin) have been variably
demonstrated to prevent or delay is the development of diabetes in people with IGT .
However , no drug therapy is recommended at present.
 At the time of diagnosis , assess the patient completely , particularly blood pressure,
possible diabetes complications such as neurologic and foot examinations , lipid
profile , urine microalbumin:creatinine ratio and an ophthalmologic assessment to
evaluate for retinopathy.

14. 1.DIAGNOSTIC CRITERIA
❖ Symptoms of diabetes plus random plasma glucose >200 mg/dL (symptoms of
diabetes plus random whole blood glucose >175 mg/dL )
OR
❖Fasting plasma glucose >125 mg/dL (whole blood glucose >88 mg/dL but <110 mg/dL
)
OR
❖2-hour plasma glucose >200 mg/dL during an oral glucose tolerance test (OGTT)
(whole blood
>175 mg/dL during an oral 75 g glucose tolerance test)

15. PREVENTIONS
Type 1 diabetes is not currently preventable. Some researchers believe it might be prevented
at the latent autoimmune stage, before it starts destroying beta cells.
1. Immunosuppressive drugs
Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta
cells, but its kidney toxicity and other side effects make it highly inappropriate for long-term
use.
2.Diet
Some research has suggested breastfeeding decreases the risk in later life and early
introduction of gluten-containing cereals in the diet increases the risk of developing islet cell
autoantibodies various other nutritional risk factors are being studied, but no firm evidence
has been found.
Children with antibodies to beta cell proteins but no overt diabetes, and treated
with niacinamide (vitamin B3), had less than half the diabetes onset incidence in a seven-year
time span than did the general population.
People with type 1 diabetes and undiagnosed celiac disease have worse glycaemic control
and a higher prevalence of nephropathy and retinopathy.
MANAGEMENT
1.Lifestyle
A low-carbohydrate diet, in addition to medications, is useful in type 1 DM. There are camps
for children to teach them how and when to use or monitor their insulin without parental help.
As psychological stress may have a negative effect on diabetes, a number of measures have
been recommended including: exercising, taking up a new hobby, or joining a charity among
others.
2.Insulin
There are four main types of insulin: rapid acting insulin, short acting insulin, intermediate
acting insulin, and long acting insulin. The rapid acting insulin is used as a bolus dosage. The
action onsets in 15 minutes with peak actions in 30 to 90 minutes. Short acting insulin action
onsets within 30 minutes with the peak action around 2 to 4 hours. Intermediate acting insulin
action onsets within 1 to 2 hours with peak action of 4 to 10 hours. Long acting insulin is

16. usually given once per day. The action onset is roughly 1 to 2 hours with a sustained action of
up to 24 hours.
COMPLICATIONS
Complications of poorly managed type 1 diabetes mellitus may include cardiovascular
disease, diabetic neuropathy, and diabetic retinopathy, among others.
People with diabetes show an increased rate of urinary tract infection
Sexual dysfunction in diabetics is often a result of physical factors such as nerve damage
and/or poor circulation, and psychological factors such as stress and/or depression caused by
the demands of the disease

17. REFRENCES
1.MEDICINE Prep manual for undergraduates
K George Mathew
Praveen Aggarwal
2.Google
Wikipedia
3.Davidson's Principles and Practice of Medicine Book
4.Essentials of Medical Physiology
by Sembulingam (Author)