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2.  Epidemiology
 Introduction to diabetes mellitus .
 Plasma sugar level
 Symptoms
 Classification
 Type 1 diabetes
 Type 2 diabetes
 Normal functioning of insulin
 Pathogenesis of T1D.
 Pathogenesis of T2D.
 Gestational diabetes mellitus
 Secondary diabetes mellitus
 Pre diabetes
 Values for diagnosis of DM
 Investigations.
 Management of DM
 Complications
INDEX

3. EPIDEMIOLOGY

4.  Diabetes mellitus (DM) is a group of diseases characterized by
HIGH LEVELS OF BLOOD GLUCOSE resulting from defects in
insulin production, insulin action, or both.
 Clinical syndrome characterised by hyperglycaemia due to
ABSOLUTE or RELATIVE DEFICIENCY OF INSULIN and by long
term complication involving eyes,kidneys,nerves and blood
vessels.
 The term diabetes mellitus describes a metabolic disorder of
multiple aetiology characterized by CHRONIC
HYPERGLYCAEMIA with disturbances of carbohydrate, fat and
protein metabolism resulting from defects in insulin secretion,
insulin action, or both.
INTRODUCTION TO DIABETES MELLITUS

5.  Hyperglycemia
 Glycosuria
 Hyperlipidemia
 Neg.N2 balance (excreation >consumption)
 Peripheral vascular insufficiency
 Ketonuria
 Ketonemia
 Increase in Vessel wall matrix
 Nephropathy
 Retinopathy
 Sclerosis of glomerulus
Characteristic Features:-

6. ▪ Values as per WHO
Plasma sugar level :-
Euglycemic Prediabetic Diabetic
Fasting
glucose level (
8 hrs after
meal)
< 100 mg/dl 100-126 mg/dl > 126 mg/dl
Oral glucose
tolerance test
(2 hrs later)
< 140 mg/dl 140-200 mg/dl > 200 mg/dl

7.  thirst
 polyuria
 blurring of vision
 weight loss
 Loosening of skin
 Burning feet
Symptoms:-
In its more severe forms-
 ketoacidosis
 Non – ketotic hyperosmolar
coma and lactic acidosis
 stupor
 coma
 death
Diabetes Long-term Effects :-
 progressive development of the specific complications of
retinopathy with potential blindness.
 nephropathy that may lead to renal failure.
 neuropathy with risk of foot ulcers, amputation, Charcot joints,
and features of autonomic dysfunction, including sexual
dysfunction.
 increased risk of cardiovascular, peripheral vascular and
cerebrovascular disease.

8. Diabetes Mellitus
Type 1
Insulin dependent diabetes
mellitus
[IDDM]
Type 2
Non insulin dependent
diabetes mellitus
[NIDDM]

9.  Was previously called insulin-dependent diabetes mellitus (IDDM)
or juvenile-onset diabetes.
 Type 1 diabetes develops when the body’s immune system
destroys pancreatic beta cells, the only cells in the body that make
the hormone insulin that regulates blood glucose.
 usually strikes children and young adults, although disease onset
can occur at any age.
 account for 5% to 10% of all diagnosed cases of diabetes.
 Risk factor for T1D :-
 Autoimmune - Antibody against beta cell
 Genetic - Presence of HLA gene ,Gene polymorphism
 Environmental factors - Viral infection , Beta cell mimicry by
antigens.

10.  Was previously called non-insulin-dependent diabetes mellitus
(NIDDM) or adult-onset diabetes.
 account for about 90% to 95% of all diagnosed cases of diabetes.
 It usually begins as insulin resistance, a disorder in which the
cells do not use insulin properly.
 As the need for insulin rises, the pancreas gradually loses its ability
to produce insulin and finally leads to insulin deficiency.
 Risk factors of T2D :-
 older age,
 obesity,
 family history of diabetes
 history of gestational
diabetes
 impaired glucose
metabolism
 physical inactivity
 race/ethnicity. (African
Americans, Hispanic/Latino
Americans, American Indians).
 Type 2 diabetes is increasingly
being diagnosed in children and
adolescents.

11. Normal functioning of insulin:-

12. Pathogenesis of T1D :-

14.  T1D is an chronic autoimmune disease in which antibody destroy
endogenous beta cell antigens leading to absolute deficiency of
insulin.
 Exogenous insulin is needed for survival.
 Insulin unavailable-
 Diabetic ketoacidosis
 Diabetic coma
 Involve both genetic susceptibility and environmental factors.
 Genetic susceptibility-
 Gene polymorphism
 HLA gene
 Environmental factors-
 Infections
 Mimicry of beta cells by antigen (foreign body)
 Intestinal dysbiosis (decrease in intestinal flora)Involve both
genetic susceptibility and environmental factors.
 Viral attack on beta cell leading destruction of beta cells along
with virus.

15. ▪ Hyperglycemia & ketosis occur when > 90 % of Beta cells have
been destroyed.
▪ Loss of ability to differentiate b/w self and non self in T-cells
therefore antibody against B- cells produced.
▪ Through cytokines - INF-γ and TNF.
▪ T-killer direct attach on beta cells.
▪ Multifactorial complex disease
▪ Genetic
▪ Environmental
▪ Inflammation
Mechanism of Beta cell destruction:-

16. Pathogenesis of T2D :-

18. ● Two defect characterize T2D-
■ Decreased ability of peripheral tissue to respond to insulin.
(Insulin resistance)
■ β- cell dysfunction leads to irregular insulin level.
● Both these process lead to relative deficiency of insulin.
● Insulin looses contact with its receptors to due to high amount of FFA in
blood.
● High FFA leads to less insulin sensitivity.

19. ▪ It is decreased/failure of target cells to insulin action.
▪ Its main cause is obesity
▪ Obesity :-
▪ Amount of fat - Increased BMI lead to high chances of T2D.
▪ Distribution pattern of body fat - Abd. Fat > peripheral fat
( central obesity)
▪ Free fatty acid - FFA increase in blood leads to decreased
sensitivity of tissues towards insulin.
▪ Adipokines – Adipose cytokines
▪ Release of Prohyperglycemic adipokines leads to
hyperglycemia.
▪ Release of Antihyperglycemic adipokines leads to
hypoglycemia.
▪ Inflammation- FFA & high glucose level causes release of
proinflammatory cytokine which leads to insulin resistance and β-
cell dysfunction simultaneously.
Insulin Resistance :-

20. β-Cell dysfunction:-
Obesity
High amount of FFA
Insulin resistance
Beta cell hyperplasia
[ for years ]
Beta cell failure
EARLY STAGE
Cell exhaust so low production and leads to +ve GTT
LATE STAGE
Less insulin so hyperglycemia leads to NIDDM

21. Criteria T1D T2D
Onset age < 20 yr > 40 yr
Type of onset Sudden + severe Gradual
Frequency 10-20% 80-90%
Weight Normal Obese
HLA Association (+)nt Association (-)nt
Family history < 20% About 60%
Genetic locus Uncommon Chromosome-6
Pathogenesis Auto immune- beta cell def. Normal
Islet cells Ab (+)nt 80% Ab(-)nt
Blood insulin Severe deficiency High/ normal/relative def.
Amyline No amyline deposition (+)nt around beta cells
Complication Develop ketoacidosis HHS
other autoimmune disease Yes Uncommon
Management Insulin + diet Diet + insulin + oral DM drugs

22.  A form of glucose intolerance that is diagnosed in some women
during pregnancy.
 Gestational diabetes occurs more frequently among African
Americans, Hispanic/Latino Americans, and American Indians.
 It is also more common among obese women and women with
a family history of diabetes.
 During pregnancy, gestational diabetes requires treatment to
normalize maternal blood glucose levels to avoid complications
in the infant.
 After pregnancy, 5% to 10% of women with gestational diabetes
are found to have type 2 diabetes.
 Women who have had gestational diabetes have a 20% to 50%
chance of developing diabetes in the next 5-10 years.
Gestational diabetes :-

23. Secondary DM :-
▪ Acromegaly, Cushing syndrome, Thyrotoxicosis,
▪ Pheochromocytoma
▪ Chronic pancreatitis,
▪ Cancer
▪ Drug induced hyperglycemia:
▪ Atypical Antipsychotics - Alter receptor binding characteristics, leading to
increased insulin resistance.
▪ Beta-blockers - Inhibit insulin secretion.
▪ Calcium Channel Blockers - Inhibits secretion of insulin by interfering with
cytosolic calcium release.
▪ Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.
▪ Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive
potassium channels.
▪ Niacin - They cause increased insulin resistance due to increased free
fatty acid mobilization.
▪ Phenothiazines - Inhibit insulin secretion.
▪ Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
▪ Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also
cause increased insulin resistance due to increased free fatty acid
mobilization.

24. Diagnosis for Diabetes
mellitus:-

25. Prediabetes: Impaired glucose tolerance
and impaired fasting glucose :-
▪ Prediabetes is a term used to distinguish people who are at
increased risk of developing diabetes. People with prediabetes
have impaired fasting glucose (IFG) or impaired glucose tolerance
(IGT). Some people may have both IFG and IGT.
▪ IFG is a condition in which the fasting blood sugar level is elevated
(100 to 125 milligrams per decilitre or mg/dL) after an overnight fast
but is not high enough to be classified as diabetes.
▪ IGT is a condition in which the blood sugar level is elevated (140 to
199 mg/dL after a 2-hour oral glucose tolerance test), but is not high
enough to be classified as diabetes.
▪ Progression to diabetes among those with prediabetes is not
inevitable.
▪ People with prediabetes are already at increased risk for other
adverse health outcomes such as heart disease and stroke.

26. Values of Diagnosis of Diabetes Mellitus :-
Normal value Diabetic value
Fasting <100 mg/dl
<5.6mMol/L
> 125 mg/dl
>6.7mMol/L
2 hrs after glucose load
Post-parendial (PP)
<125 mg/dl
<6.7 mMol/L
> 150 mg/dl
>10 mMol/L
Normal fasting plasma
glucose (FPG)
<100 md/dl
<5.6 mMol/L
>100 mg/dl
>5.6 mMol/L
FPG 100-125 mg/dl
5.6-6.7 mg/dl
Impaired fasting
FPG >126 mg/dl
7.0 mMol/L
Provisional ∆ of DM but
must be confirmed by tests.
2 hrs after glucose load <140 mg/dl
7.8 mMol/L
Normal glucose tolerance
2 hrs after glucose load 140-199 mg/dl
7.8-11.1 mMol/L
Impaired glucose
tolerance(IGT)
2 hrs after glucose load >200 mg/dl
11.2mMol/L
Provisional ∆ of DM but
must be confirmed by tests.

27.  Oral glucose tolerance test (OGTT) :-
 In asymptomatic cases if FBS lies b/w 100-126 mg/dl then go for
OGTT.
 OGTT will be performed in morning after patient has fasted
overnight (atleast 8 hrs) and patient should be relaxed for ½ hr
before test.
 Glycosylated Haemoglobin(HbA1C) :-
 Long term assesment (for last 90-120 days) of degree of glycemic
control is assesed by measurement of HbA1C.
 Advantage:-
 No dietry preparation for patient is required.
 It has direct relation with poor control and development of
complication.
 It is also a good measure of prediction of microvascular
complication.
Investigations :-

28.  Urine examination
 Glucosuria
 Ketonuria
 Single plasma glucose estimation
 Blood glucose level
 Post prandial plasma glucose
 After meal
 Not useful for diagnosis
 Useful for prognosis.
Management of diabetes :-
Life style modification
 diet
 moderate-intensity physical activity (such as walking for 2 1/2
hours each week).
Medication
 Treatment with metformin was most effective among younger,
heavier people (those 25-40 years of age who were 50 to 80
pounds overweight) and less effective among older people and
people who were not as overweight.
 Similarly, in the STOP-NIDDM Trial, treatment of people with IGT
with the drug acarbose reduced the risk of developing diabetes by
25% over 3 years.

29.  Diet is a basic part of management in every case. Treatment cannot
be effective unless adequate attention is given to ensuring
appropriate nutrition.
 Dietary treatment should aim at:
 ensuring weight control
 providing nutritional requirements
 allowing good glycaemic control with blood glucose levels as
close to normal as possible
 correcting any associated blood lipid abnormalities
 DIETARY GUIDELINES
 Dietary fat – unsaturated [ 25 -30 % ], saturated [10 % ].
 Cholesterol – less than 300 mg/day .
 Protein – 10-15 %
 Complex carbohydrate with high fibre – 50-60 %
 Avoid excessive salt .

30.  Physical activity promotes weight reduction and improves insulin
sensitivity, thus lowering blood glucose levels.
 Together with dietary treatment, a programme of regular physical
activity and exercise should be considered for each person. Such a
programme must be tailored to the individual’s health status and
fitness.
 People should, however, be educated about the potential risk of
hypoglycaemia and how to avoid it.

31.  There are currently four classes of oral anti-diabetic agents:
 Biguanides
 Insulin Secretagogues – Sulphonylureas
 Insulin Secretagogues – Non-sulphonyl ureas
 α-glucosidase inhibitors
 Thiazolidinediones (TZDs)

32.  If glycaemic control is not achieved (HbA1c > 6.5% and/or; FPG >
7.0 mmol/L or; RPG >11.0mmol/L) with lifestyle modification within 1
–3 months, ORAL ANTI-DIABETIC AGENT should be initiated.
 In the presence of marked hyperglycaemia in newly diagnosed
symptomatic type 2 diabetes (HbA1c > 8%, FPG > 11.1 mmol/L, or
RPG > 14 mmol/L), oral anti-diabetic agents can be considered at
the outset together with lifestyle modification.
Oral Agent Monotherapy :-
 As first line therapy:
 Obese type 2 patients, consider use of metformin, acarbose or TZD.
 Non-obese type 2 patients, consider the use of metformin or insulin
secretagogues
 Metformin is the drug of choice in overweight/obese patients. TZDs and
acarbose are acceptable alternatives in those who are intolerant to
metformin.
 If monotherapy fails, a combination of TZDs, acarbose and metformin is
recommended. If targets are still not achieved, insulin secretagogues
may be added.

33. ▪ Combination oral agents is indicated in :-
▪ Newly diagnosed symptomatic patients with HbA1c >10
▪ Patients who are not reaching targets after 3 months on
monotherapy .
▪ If targets have not been reached after optimal dose of combination
therapy for 3 months, consider adding intermediate-acting/long-
acting insulin (BIDS).
▪ Combination of insulin+ oral anti-diabetic agents (BIDS) has been
shown to improve glycaemic control in those not achieving target
despite maximal combination oral anti-diabetic agents.
▪ Combining insulin and the following oral anti-diabetic agents has
been shown to be effective in people with type 2 diabetes:
▪ Biguanide (metformin)
▪ Insulin secretagogues (sulphonylureas)
▪ Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is
not an approved indication)
▪ α-glucosidase inhibitor (acarbose)
▪ Insulin dose can be increased until target FPG is achieved.
Combination Oral Agents :-

34.  Short-term use:
 Acute illness, surgery, stress and emergencies
 Pregnancy
 Breast-feeding
 Insulin may be used as initial therapy in type 2 diabetes
 in marked hyperglycaemia
 Severe metabolic decompensation (diabetic ketoacidosis,
hyperosmolar nonketotic coma, lactic acidosis, severe
hypertriglyceridaemia)
 Long-term use:
 If targets have not been reached after optimal dose of combination
therapy or BIDS, consider change to multi-dose insulin therapy.
When initiating this,insulin secretagogues should be stopped and
insulin sensitisers e.g. Metformin or TZDs, can be continued.
Insulin Therapy :-

36.  Prolonged hyperglycemia
 Microvascular complication
 Macrovascular complication
 Diabetic ketoacidosis
 Non-Ketotic hyperosmolar coma and lactic acidosis
Complications of Diabetes mellitus :-

38.  Formation of advanced glycation end products(AGE).
 In diabetes glucose binds to protein non enzymatically & c/a non
enzymatic glycosylation.
 Non enzymatic glycosylation
 In early stage schiff base is formed which is liable and
rapidly dissociate.
 In later stage stable AGEs are formed which bind to AGE
receptors (RAGE) as a result RAGE-AGE intermediate are
formed.
 RAGE-AGE intermediate results in -
 Release of O°
 Increase procoagulant activity on endothelial cells.
 Increase proliferation of vascular muscle therefore it leads
to plague formation and finally to atherosclerosis.
 Atherosclerosis makes prone for CVS deseases like heart
attack etc.
Prolonged hyperglycemia :-

39. AGE in DM :-

40. ▪ Found in T1D
▪ Primary causes -
▪ insulin deficiency and increase in catabolic hormones
leading to hepatic overproduction of glucose and ketone
bodies.
▪ Secondary causes -
▪ Trauma
▪ Stroke
▪ Pancreatitis
▪ stressful condition
▪ inadequate dose of insulin.
▪ Cardinal biochemical features -
▪ Hyperglycemia
▪ Hyperketonemia
▪ Metabolic acidosis

41.  Symptoms –
 Polyuria
 Thirst
 Wt.loss
 Weakness
 Nausea
 Vomiting(coffee
brown colour)
 Leg crams
 Blurred vision
 Abd.pain
 Signs –
 Dehydration- flaccid skin and
less urination.
 Hypotension- by BP
measurement
 Imperiment in conciousness
 Air hunger- kushmaul’s
breathing (due to metabolic
acidocis)
 Shock
 Hypothermia (below 90°F)
 Smell of acetone- fruity smell
 Confusion
 Drowsiness
 COMA (sensory loss)

43.  Urea and electrolyte
 CBC with ESR
 Plasma glucose level
 Urine for ketone bodies
 Blood and urine culture
 Chest X-Ray
 Atrial blood gases to access the severity of acidosis.
 Cerebral oedema.
 Thromboembolism.
 Acute respiratory distress syndrome.
 Acute circulatory failure.

44. Diabetic ketoacidosis :-

45.  Usually occurs in elderly T2D cause is idiopathic.
 Characterised by severe hyperglycemia (>900 mg/dl).
Without significant hyperketonemia or acidosis
 Severe dehydration
 Pre renal uremia mortality > 40%
 No smell of acetone
 Ketouria is nill or absent.

47.  Patients should be educated to
practice self-care. This allows the
patient to assume responsibility
and control of his / her own
diabetes management. Self-care
should include:
 Blood glucose monitoring
 Body weight monitoring
 Foot-care
 Personal hygiene
 Healthy lifestyle/diet or physical
activity
 Identify targets for control
 Stopping smoking
Self-Care :-