Diabetes Mellitus

Definition ,pathogenesis, classification,

manifestations and management of DM
Outline of presentation

• Objectives
• Definition of Diabetes mellitus
• Etiological classification
• Diagnostic criteria
• Pathogenesis of type 1 DM
• Pathogenesis of type 2 DM
• Clinical presentations
• Management of diabetes mellitus
Objectives
Main objective

After completing the session , students will be able to

determine the classification and Diagnosis, describe the
pathogenesis, identify the clinical presentation, be able to
manage diabetes mellitus.
Specific objectives
 Determine the definition of DM
Determine the etiological classification of dm
Determine the diagnostic criteria of dm
Describe the Pathogenesis of type 1 DM
Describe the Pathogenesis of type 2 DM
 Identify the clinical presentations
 Management of diabetes mellitus
What is diabetes mellitus?
Definition

Diabetes is a group of metabolic diseases

characterized by hyperglycemia resulting from
defects in insulin secretion, insulin action, or
both.
Etiologic Classification of DM
Diabetes can be classified into the following four categories:
1. Type 1 diabetes ( due to β cell destruction, usually
leading
to absolute insulin deficiency)
A. Immune Mediated
B. Idiopathic
2. Type 2 diabetes (due to a progressive insulin secretary
defect on the background of insulin resistance)
3. Specific types of diabetes due to other causes, e.g.,
 monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset
diabetes of the young [MODY]),
 diseases of the exocrine pancreas (such as cystic fibrosis),
 and drug- or chemical-induced diabetes (such as in the treatment of HIV/AIDS or after
organ transplantation)…prednisolone, NNRTI, PI
 Endocrinopathies: acromegaly , cushing syndrome, pheochromocytoma

4. Gestational diabetes mellitus (GDM)

 Criteria for the diagnosis of Diabetes
1. A1C - > 6.5%.

2. FPG >126 mg/dL (7.0 mmol/L) OR

3. 2-h PG >200 mg/dL (11.1 mmol/L) after 75 gm , OGTT

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random

plasma glucose >200 mg/dl (11.1 mmol/L).

Pre diabetes

• FPG 100 mg/dL - 125 mg/d (IFG)

OR

• 2-h PG in the 75-g OGTT 140 mg/dL - 199 mg/dL (IGT)

OR

• A1C 5.7–6.4
When do you say that an individual has
“Normal Blood Glucose” value ?
 Normal Blood Glucose values

• FBG- < 100 mg/dl (< 5.6mmol/L)

• 2 hr, 75 gm. OGTT, Plasma Glucose Level < 140 mg/dl

• HbA1c - < 5.7 %

 Pathogenesis of Type 1 diabetes
mellitus (T1DM)
• Is the result of interaction of
genetic , environment and immunologic factors

• Ultimately leads to destruction of pancreatic beta cells and insulin deficiency

 Immunologic Markers

• Islet Cell auto antibodies(ICAs)-

1. GAD: glutamic acid decarboxylase

2. Insulin AUTOANTIBODY ( IAA)
3. IA-2

Are markers of autoimmune process

Pathogenesis of Type 2 diabetes mellitus (T2DM)

• Decreased Insulin secretion and Insulin resistance are central to the

development of T2DM

1. Impaired Insulin secretion

2. Insulin resistance
Genetic considerations
T2DM has a strong genetic component

The concordance of T2DM in identical twin is between 70-90%

If both parents have Type 2 Dm, the risk approaches 40%
The disease is polygenic and multifactorial

In addition to genetic susceptibility, environmental factors such as

 obesity,
nutrition and
 physical activity modulate the disease process
Clinical Features of Diabetes Mellitus
• Polydypsia, polyphagia and Polyuria

• Unexplained weight loss and weakness

• Other features of DM

• blurred vision,

• recurrent skin infections, recurrent itching of the vulva,

• abnormal sensory/ motor neurologic findings on extremities, &

• foot abnormalities (various deformities,ulcers, and ischemia) could be a presenting

signs
CLASSIFICATION OF DM
Individuals with type 1 DM likely have

1. lean body habitus;

2. requirement of insulin as initial therapy;

3. propensity to develop ketoacidosis;

4) Affects people of any age, but onset usually occurs in children or young
adults
5) Patient present suddenly with acute clinical symptoms of hyperglycemia

6) a family or personal history of other autoimmune disorders such as

• autoimmune thyroid disease,
• adrenal insufficiency,
• pernicious anemia,
• celiac disease,
• Vitiligo
TYPE2 DM
• individuals with type 2 DM often exhibit
• (1) obesity; 80% are obese,elderly individuals may be lean;
• (2) may not require insulin therapy initially;
• (3) may have associated conditions such as
• insulin resistance,
• hypertension,
• cardiovascular disease,
• dyslipidemia,
• polycystic ovarian syndrome
• In type 2 DM, insulin resistance is often associated with
• abdominal obesity
• hypertriglyceridemia
• most individuals diagnosed with type 2 DM are older,
About half of type 2 diabetes patient remained asymptomatic or

might have non -specific symptoms

Some of type 2 DM could present with chronic complications of

diabetes mellitus
Management of DM
• Approach to the management of diabetes mellitus
History
 details related to DM and its complications
Prior diabetes therapy, follow up
 Weight , family history
Risk factors
 Symptoms of hyperglycemia and hypoglycemia
 History of chronic complications of Dm
Symptoms of infection
Physical examination
Complete physical examination
BMI
Examine : the B/P, the eyes , Peripheral nerves , cardiovascular system,
peripheral arterial disease

Classify the patient as type 1 dm , type 2 dm

 Laboratory evaluation
determine the FBS,RBS,HbA1C,LFT,RFT,LIPIDS
ECG, measurement of Iselet cell antibodies
Insulin
Insulin initiation dose to type 1 dm is 0.4-0.5 unit/kg Sc, 2/3 am, 1/3
pm
(If available, 1/3 of the total dose should be regular insulin

Increase 2-4 units every week

ORAL Glucose lowering agents
Indication for Insulin therapy for Type 2 DM

• Failure to control blood glucose with oral drugs

• Temporary use for major stress, e.g. surgery, medical illness.

• Advanced kidney or liver failure

• Pregnancy

• Initial therapy for patients presenting with fasting blood glucose >250 mg/dl ,
random glucose consistently >300 mg/dl, or ketonuria

• In patients in whom it is difficult to distinguish type 1 from type 2 DM

Patient education

• Education about Diabetes mellitus,

• diet,
• exercise,
• insulin injection,
• oral antidiabetic agents,
• blood glucose monitoring skills,
• foot exam,
• urine sugar and ketone determination,
• acute and chronic complications,
•
Monitoring of self blood glucose
control
• Optimal monitoring of glycaemic control involves

• Glucose measurement by the patient.i.e Self Blood Glose

Monitoring (SMBG)

• Plasma Glucose determination , laboratory

• Assessment of long term control by determination of

HbA1C (Non glycated hemoglobin for 2-3 months)
Exercise
 Has a multiple positive benefits

• Including cardiovascular risk reduction

• Reduced blood pressure, maintenance of muscle mass

• Reduction in body fat and weight loss

• Lower plasma glucose level

Recommendation- 30 mints /day , 5 days /week

Goal of therapy of DM

• To eliminate symptoms related to hyperglycemia

• Reduce or eliminate the long term microvascular and

macrovascular complications of DM

• To allow the patient to achieve as normal life style as

possible
Treatment Goals for Adults with Diabetes
Treatment Goals for Adults with Diabetes
Acute and Chronic complications of DM

38
Outline of presentation
• Objectives

• Acute complications (DKA,HHS, Hypoglycemia)

• Chronic complications (microvascular ,macrovasular and

other complications of DM

• Summary

39
Objectives
After completing the session :

• Students will be able to determine the classification and

Diagnosis of complications of DM , describe the
pathogenesis, identify the clinical presentations, be able to
manage the acute and chronic complications of diabetes
mellitus.

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Case 1. Discuss the case in group of 4 members

A 32 yrs, old Diabetes patient for 3 yrs. who has been taking
Insulated insulin 22 U, am and 12 U,pm, SC.
He developed cough , chest pain and fever of four days
duration, these symptoms were accompanied with
polyurea , polydypsia , vomiting and abdominal pain of two
days duration.
On Physical Examination: Young patient with deep breathing,
confused, B/P, : 70/50mmHg, pulse 120/minute, Temp. 38,6
0
c., sunken eyes , Bronchial breathing sound in Left lower
posterior lung field.
Questions
What are the Diagnosis of the patient? 41
Case 1. Answers.

• 1. Type 1 DM, DKA, Pneumonia

• 2. FBS/RBS, Urine analysis ,Urine ketone/sugar, CXR,
electrolytes

N.B. Patient results were: RBS 450 mg/dl,

• Urine sugar :4+,
• Urine ketones 3+,
• CXR: Homogenous opacification in the left lower lung field

42
Acute complication of DM

• Dabetic Ketoacidosis (DKA)

• Hyperglycaemic Hyperosmolar state (HSS)

• Hypoglycaemia

43
Diabetic Ketoacidosis (DKA)

• A collection of severe and potentially life-threatening metabolic

disturbances:

• which is characterized by the triad of

1. hyperglycemia,

2. anion gap metabolic acidosis, and

3. ketonemia.
• Metabolic acidosis is often the major finding.

• The serum glucose concentration is usually greater than 500 mg/dL

(27.8 mmol/L) and less than 800 mg/dL (44.4 mmol/L) [ 2,6 ].

• However, serum glucose concentrations may exceed 900 mg/dL (50

mmol/L) in patients with DKA who are comatose
• What are the precipitating factors of DKA?

46
DKA risk factors
• T1DM
• 1st presentation
• Acute-illness
• Insulin omission (inappropriate sick-day management,
noncompliance, Eating Disorders)
DKA: Precipitating Factors

Acute illness
(MI, GIB, trauma,
10-20% pancreatitis)
20-38%
New-onset DM

5-39% Insulin omission

33%
Infections
DKA: Diagnosis

• Symptoms & Signs:

• Polyuria, polydipsia, weight-loss

• Fatigue

• N/V, abdominal pain

•  ECFv, Kussmaul’s, Acetone breath, mild impairment in cognition

• Laboratory:
• pH < 7.3, serum HCO3 < 15 mEq/L, AG > 14 mM

• Raised serum ketones (and urine ketones)

• RBS >250 mg/dl

Diagnostic criteria for diabetic ketoacidosis (DKA) and
hyperosmolar hyperglycemic
DKA
state (HHS)
HHS
Mild Moderate Severe
Plasma glucose
(mg/dL) >250 >250 >250 >600

Arterial pH 7.25-7.30 7.00-7.24 <7.00 >7.30

Serum bicarbonate 15-18 10 to <15 <10 >18

(mEq/L)

Urine ketones* Positive Positive Positive Small

Serum ketones* Positive Positive Positive Small
Effective serum
osmolality Variable Variable Variable >320
(mOsm/kg)•
Anion gapΔ >10 >12 >12 Variable

Alteration in
sensoria or mental Alert Alert/drowsy Stupor/coma Stupor/coma
obtundation

50
Management of DKA

51
Management of DKA cont.

52
Management of DKA cont.

53
Hyperglycaemic Hyperosmolar State (HHS)

• Mostly occurs in elderly type 2 DM

• Clinical features are history of polyurea, polydypsia , weight loss, weakness

• Physical Examination; dehydration, hypotension, tachycardia, altered mental

status

54
Management
• Management is the same as Mg. of DKA, except increase fluid
administration upto 8-10 lt.
• HHS is often precipitated by a serious, concurrent illness such as
1. myocardial infarction
2. stroke
3. Sepsis, pneumonia, and other serious infections
4. a debilitating condition (prior stroke or dementia) or
5. social situation that compromises water intake usually contributes
to the development of the disorder
Laboratory values in DKA and HHS

57
Laboratory values in DKA and HHS cont.

58
Hypoglycaemia
• occurs in most patients with type 1 diabetes and type 2
diabetes mellitus

• Common risk factors

 fasting or missed meals
 exercise
 insufficient meals
 overdose of hypoglycemic agents or insulin
 chronic kidney disease, hepatic disease
 alcohol consumption.

59
Clinical presentation and diagnosis of
hypoglycaemia
• adrenergic manifestations are

 palpitation

 sweating

 hunger pain

 weakness.

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• Neuroglycopenic manifestations include

 headache

 drowsiness

 lethargy and coma

Hypoglycemia diagnosed by Whipple’s triad:
.

(1) symptoms consistent with hypoglycemia,

(2) a low plasma glucose concentration measured with a precise method

(not a glucose monitor), and

• (3) relief of symptoms after the plasma glucose level is raised

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Treatment of Hypoglycemia

1. Oral treatment with glucose containing food, sweetened soft drinks

100-150 ml , 3-4 candy (candies)

2. 1 tablespoonful of sugar or honey (equivalent to 15 gm-20 gm of

glucose)

3. If no response, intravenous 40 % or 50% glucose 20 to 40ml iv stat,

repeat the same in 15 minutes if there is no response

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Treatment of Hypoglycemia

• If still there is no response start 10 % glucose solution in D/W at rate

of 100 ml /hr.

• Emergency management should be followed by

carbohydrate containing food e.g-bread, fruits when patient is able to

take food PO safely.

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Case 2. Discuss the case in group of 4 members

A 52 yrs old , Director of * P.L.C, presented with history of

profound weakness fatigue, weight loss of 3 months duration.
He developed flank pain and colour change of urine of 2 days
duration. For which he visited the near by private clinic in early
morning. His physical examination showed : B/P of 150/100,
Periorbital oedema, The lab result revealed, normal CBC, FBS-
178 mg/dl. U/A- Sugar 1+, Protein 2+, WBC- many, RBC- 10-15 .

Questions
Specify the diagnoses of the patient?
How do you confirm the diagnosis?

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Case 2. Ans.

1. Type 2 diabetes mellitus

• HTN
• UTI
• Diabetic Nephropathy
• R/O Acute glomerulonephritis
• 2. Repeat FBS and U/A, HbA1c, RFT, U/S

66
Chronic complications of DM
• Affects many organ systems

• Responsible for the majority of

morbidity and
mortality associated with diabetes

67
Classification of Chronic complication of
DM
• Diabetes-related complications can be divided into

1. vascular and

2. nonvascular complications

68
The vascular complications of DM are further subdivided into

1. microvascular (retinopathy, neuropathy, nephropathy) and

2. macrovascular complications (coronary heart disease [CHD],

peripheral arterial disease [PAD], cerebrovascular disease)
Nonvascular complications include

1. gastroparesis,

2. infections,

3. skin changes, and

4. hearing loss
Pathogenesis of Chronic complications

• Chronic hyperglycemia is an important etiologic factor leading to

complications of DM

71
Pathogenetic mechanisms
• Four prominent theories, have been proposed how hyperglycemia might
lead to chronic complications

1. Advanced Glycosylation End Product (AGEs)

2. Sorbitol path way

3. Activation of Protein Kinase C activity (PKC)

4. The Hexosamine Pathway

Diabetic Retinopathy
Classified in to
• Proliferative diabetic Retinopathy and
• Non proliferative Diabetic retinopathy
• Macular Oedema

• The leading cause of blindness in type 1 and type 2 dm.

• Blindness is mainly due to

• progressive diabetic retinopathy and
• clinically significant macular oedema
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Diabetic retinopathy cont.
Treatment of diabetic retinopathy

• Intensive control of blood glucose and blood pressure

• Laser photocoagulation

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Diabetic Nephropathy
• Is the leading cause of ESRD

• Leading cause of DM related morbidity and mortality

• Increase the risk of cardiovascular disease

75
Diagnostic test
 Microalbuminuria test,
 U/A,
 RFT,
 U/S

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treatment of diabetic nephropathy
 Intensive control of blood sugar and blood pressure

 Restrict salt and protein intake

 ACE /ARB inhibitors

 Chronic Dialysis

 Renal Transplantation
Diabetic Neuropathy cont.
• Physical exam : reveals sensory loss, loss of ankle reflex, loss of
vibration and position sense

• Mononeuropathy, present with dysfunction of isolated cranial or

peripheral nerves

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Autonomic neuropathy

• involves multiple systems

• In CVS cause a resting tachycardia and orthostatic hypotension.

• GI- Gastroparesis and bladder emptying abnormalities

79
• Hyperhidrosis of the upper extremities and

• anhidrosis of the lower extremities result from sympathetic nervous

system dysfunction
• reduce counterregulatory hormone release (especially
catecholamines),

• leading to an inability to sense hypoglycemia appropriately

• hypoglycemia unawareness;, thereby subjecting the patient to the risk

of severe hypoglycemia and

• complicating efforts to improve glycemic control

Treatment

1. Improve glycaemic control

2. NSAID
3. Antidepressant e.g Amytryptylline
4. Anticonvulsant , Gabapentine, phenytoin carbamazepine
Cardiovascular disease (CVD) and DM

• CVD is a Macrovascular complication of DM

• CVD is increased in individuals with type 1 and type 2 dm

• 2-4 fold increase in CHF, Coronary Heart Disease, PAD, MI

• 5 fold increase of sudden death

83
CVD cont.

• Clinical presentations are:

• Retrosternal chest pain(Angina pain)

• Silent ischemia

• Intermittent claudication of the legs

• Sign and symptoms of CHF

84
• Investigations
• ECG
• ECHO
• Stress test
Treatment of CVD

• Good glycaemic control

• Aggressive cardiovascular risk modification e.g Dyslipaedimia , HTN,

smoking etc

86
Hypertension
• Hypertension accelerates complications of DM
particularly cardiovascular diseases and
nephropathy

 Target goal <130/80 mm/Hg

 Rx- ACE inhibitors, ARBs, beta blockers, thiazide diuretics, calcium

channel blockers

87
Lower extremity complications

• DM is the leading cause of nontraumatic lower extremities

amputation

• Autonomic Neuropathy- anhydrosis & altered superficial blood flow in

the foot and Infection Cause foot ulcer

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treatment
• Glycemic control

• Diabetic foot education

Other complications of DM

• Infections –

1. Pneumonia, UTI, TB

2. rhinocerebral mucormycosis,

3. emphysematous infections of the gallbladder and urinary tract,

4. “malignant” or invasive otitis externa.

5. emphysematous pyelonephritis and emphysematous cystitis

90
Dermatologic manifestations

• pigmented pretibial papules,

• xerosis and pruritus
• Vitiligo, Acanthosis nigricans, Lipoatrophy and lipohypertrophy
• Necrobiosis lipoidica diabeticorum
THANK YOU