Diabetes Mellitus

PART I

Definition ,pathogenesis,
classification, manifestations and
management of DM

Endocrine Lecture, Clinical- I, Medical Students

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
 Complications of diabetes
 What is diabetes
mellitus?
Diabetes Mellitus

Definition
 Group of common metabolic disorders that share the
phenotype of hyperglycemia resulting from defects in
insulin secretion, insulin action, or both.

 The chronic hyperglycemia of diabetes is associated

with long-term damage, dysfunction, and failure of
different organs, especially
 the eyes
 kidneys
 nerves
 heart, and blood vessels
Etiologic Classification of DM
Classification cont.

 Current classification of Dm Diverge from previous

classification in two ways
 The First : The term Insulin Dependent Diabetes
Mellitus (IDDM) and Non Insulin Dependent Diabetes
Mellitus (NIDDM) are Obsolete

 Since many individuals with Type 2 DM eventually

require insulin treatment for control of glycaemia
 the use of NIDDM generated considerable confusion.
Classification cont.

 The Second: difference is that the age is not a criterion

in the classification system.

 Although T1DM most commonly develops before the

age of 30, an autoimmune B cell destruction process
can develop at any age.

 Although T2DM more typically develops with

increasing age. It is now being diagnosed more
frequently in children and young adult.
Criteria for the diagnosis of
Diabetes
1.A1C > 6.5%. The test should be performed in a
laboratory using a method that is NGSP certified and
standardized to the DCCT assay.*
OR
2. FPG >126 mg/dL (7.0 mmol/L). Fasting is defined as no
caloric intake for at least 8 h.*
OR
3. 2-h PG >200 mg/dL (11.1 mmol/L) after 75 gm , OGTT.

 The test should be performed as described by the WHO, using a glucose

load containing the equivalent of 75 g anhydrous glucose dissolved in
water.*

OR
Criteria of Dx cont.

4. In a patient with classic symptoms of hyperglycemia or

hyperglycemic crisis, a random plasma glucose >200
mg/dl (11.1 mmol/L).

*In the absence of unequivocal hyperglycemia, results

should be confirmed by repeat testing.
Categories of increased risk for
diabetes (Prediabetes)*
 FPG ->100 mg/dL (5.6mmol/L) to 125 mg/d(6.9 mmol/L) (IFG)
OR
 2-h PG in the 75-g OGTT ->140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0
mmol/L) (IGT)
OR
 A1C-> 5.7–6.4%

 *For all three tests, risk is continuous, extending below

the lower limit of the range and becoming
disproportionately greater at higher ends of the range.
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, Plasma Glucose Level < 140 mg/dl, after 75 gm. OGTT

 HbA1c - < 5.7 %

RISK FACTORS FOR TYPE 2 DIABETES
MELLITUS
Spectrum of Glucose Homeostasis
and Diabetes Mellitus
 Epidemiology
 Theworld prevalence diabetes has risen dramatically
over the past two decades.

 The prevalence of both type 1 and type 2 DM is

increasing world wide, the prevalence of type 2 DM is
rising much more rapidly.

 Presumably because of:

 Increasing obesity
 Reduced physical activity, sedentary life
 The aging of the population
 Economic development
 Increasing urbanization
 less healthy diets
Prevalence of DM in Africa, Ethiopia

WHO STEPS SURVEY, 2015, Ethiopia,

The prevalence of DM was found to be 3.2%
 3.5% males and
 3.0% in females
The prevalence of impaired fasting blood glucose level
was 9.1% with the ADA criteria and 3.8% with the WHO
criteria
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

 T1DM- results from autoimmune beta cell destruction

 Most individuals have evidence of islet directed

autoimmunity
Pathogenesis of T1DM cont.
 Some individuals lack markers indicative of
autoimmune process and involving the beta cells and
the genetic markers.
“Idiopathic type 1 dm”
 They develop insulin deficiency by unknown mechanism

 They are ketosis prone

 These individuals are mainly African Americans, and

Asian heritage
Genetic susceptibility

 Individuals with genetic susceptibility have normal beta cells

at birth

 Begin to lose the beta cells secondary to auto immune

destruction that occurs over months to years

 The autoimmune process triggered

 by infectious or
 environmental stimulus and to be sustained by a beta
cell specific molecules.

 Immunologic markers appears after the triggering events but

before diabetes becomes clinically overt.
Genetic susceptibility cont.

Susceptibility to T1DM involves multiple genes

The major susceptibility gene is located in the

 HLA region on chromosome 6,

 Class II major Histocomaptibilty complex (MHC)
molecules are involved,
 present the antigen to T helper cells and thus are
involved in initiating the immune response
Genetic susceptibility cont.

 Beta cell mass then begins to decrease- and insulin

secretion progressively declines

 Features of diabetes don't become evident until a

majority of beta cells destroyed (70-80%)

 After the initial clinical presentation of T1DM

“ Honey moon” phase may occur, requires modest
insulin dose or insulin not needed

 Autoimmune process destroys remaining beta cells,

individual become insulin deficient
Immunologic Markers

 Islet Cell auto antibodies(ICAs)- are composite of

several different antibodies directed at pancreatic islets
molecules such as
GAD

Insulin ( IAA)
IA-2

ZnT8

 Are markers of autoimmune process

Environmental factors

 Numerous environmental events have been proposed

to trigger the autoimmune process in genetically
susceptible individuals

 E.g viruses coxsasackie, Rubella, enteroviruse

 Bovine milk protein
 Nitrosourea compounds
 Microbiome

 None have been conclusively linked to diabetes

The temporal development
of T1DM
 Pathogenesis of Type 2
diabetes mellitus (T2DM)
 Type2 DM is characterized by impaired insulin
secretion, insulin resistance, excessive hepatic glucose
production, and abnormal fat metabolism

 Moststudies support that the insulin resistance

precedes an insulin secretary defect

 But
diabetes develops only when insulin secretion
become inadequate
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 inactivity modulate the disease process.
Genetic considerations cont.

 The genes that predispose to T2DM are incompletely

identified

 A recent genome study identified a large number of

more than 20 genes, convey a relative small risk for
T2DM

 The mechanism by which the genetic loci increase the

susceptibility to type 2dm are not clear
Pathophysiology

Mechanisms of Pathogenesis of Type 2 Dm

 Impaired Insulin secretion

 Insulin resistance
 Increased hepatic glucose production
 Abnormal fat metabolism
 Impaired insulin secretion

 In type 2 Dm, insulin secretion initially increases in

response to insulin resistance to maintain normal
glucose tolerance

 The insulin secretory defect is mild and selectively

involves glucose stimulated insulin secretion, with
increased c-peptide

 Eventually the insulin secretory defect progress to a

state of inadequate insulin secretion,
Impaired insulin secretion cont.

 The reason for decline is unclear,

 but genetic defects are incriminated as the cause

 Iselet amyloid pepetide or amyline is co secreted by

beta cells and forms amyloid fibrillar deposit in islets
cells
Impaired insulin secretion cont.

 Metabolic environment of dm , i.e chronic

hyperglycaemia paradoxically impairs iselet function

 “Glucose Toxicity”and leads to worsening of

hyperglycaemia

 In addition elevation of free fatty acid level

 “lipotoxicity” and dietary fat may also worsen the islet
function.
 Insulin resistance
 Insulin resistance the decreased ability of insulin to act
effectively on target tissues
(especially muscle, liver, and fat)

 is a prominent feature of type 2 DM and results from a

combination of genetic susceptibility and obesity.

 Insulin resistance impairs glucose utilization by insulin-

sensitive tissues and increases hepatic glucose output; both
effects contribute to the hyperglycemia
 IR . cont.

 Increased hepatic glucose output predominantly

accounts for increased FPG levels,

 whereas decreased peripheral glucose usage results in

postprandial hyperglycemia.

 In skeletal muscle, there is a greater impairment in

nonoxidative glucose usage (glycogen formation) than
in oxidative glucose metabolism through glycolysis.
Increased Hepatic Glucose production

 Insulin resistance in the liver reflects the failure of

hyperinsulinemia to supress gluconeogenesis

 Which results in fasting hyperglycemia and decreased

glycogen storage by the liver in the postprandial state

 Increased hepatic glucose production occurs early in

the course of diabetes
Increased Hepatic Glucose production
cont.
 The result of Insulin resistance in adipose tissue

 →lipolysis and free fatty acid flux from adipocytes are

increased →

 leading to increased lipid (VLDL and

Triglyceride)synthesis in hepatocytes
Increased Hepatic Glucose production
cont.
 The lipid storage or steatosis in the liver

 may lead to non alcoholic fatty liver disease and

abnormal liver function test

 This is also responsible for dyslipaedema found in type

2 DM
↑ Triglyceride
↓ High density lipoprotien(HDL)
↑and small density lipoprotien particles (LDL)
Insulin Resistance Syndromes

The metabolic syndrome, the insulin resistance

syndrome, and syndrome X are terms used to describe
a constellation of metabolic derangements that includes

 Insulin resistance
 Hypertension,

 Dyslipidemia (decreased HDL and elevated

triglycerides),
 Central or visceral obesity,
 Type 2 DM or IGT/IFG, and
 Accelerated cardiovascular disease
Pathophysiology of Type 2
DM
Specify the clinical
manifestations of diabetes
mellitus
Type 1 diabetes

 Affects people of any age, but onset usually occurs in

children or young adults

 Patient present suddenly with acute clinical

symptoms of hyperglycemia

 Or present in state of diabetic ketoacidosis

TIDM cont.

 Requires insulin for life to control the levels of glucose

in their blood

 Associated with other Endocrine disease. e.g

 Addison’s disease,
 Auto immune hypothyroidism, pernicious
anemia, vitiligo etc
Clinical Presentations
 Type 1 diabetes often develops suddenly and can produce
symptoms:
Type 2 Diabetes
 Type 2 diabetes is the most common type of diabetes.

 Majority are overweight/obese.

 Itusually occurs in adults, but is increasingly seen in

children and adolescents.

•Frequent urination
•Excessive thirst
•Weight loss
•Blurred vision
 About 50 % of the pt. are asymptomatic
 They can present with complications of DM
 Or with other metabolic syndrome
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
 and assessment of the patient’s knowledge about diabetes,
exercise, and nutrition.
Management of diabetes mellitus cont.
 Physical examination
 Complete physical examination
 BMI
 Examine : the B/P, the eyes , Peripheral nerves ,
cardiovascular system, peripheral arterial disease, foot
examination

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

 Laboratory evaluation
 Determine the FBS,RBS,HbA1C,LFT,RFT,LIPIDS, ECG,
 Measurement of Islet cell antibodies
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

 Diabetes management requires a multidisciplinary

team
Treatment Goals for Adults with
Diabetes

CGM targets
Patient education, Nutrition , Exercise

 Diabetes education : by educators

 Patient education allows the individual to improve

compliance and to assume greater responsibility for
their care,

 Education about Diabetes mellitus, diet, exercise,

insulin injection, oral anti diabetic agents, blood
glucose monitoring skills, foot exam, urine sugar and
ketone determination, acute and chronic complications,
risk factors prevention. etc
Patient education, Nutrition , Exercise
cont.
 Nutrition

 Coordinate and match daily calorie intake with the

amount of daily insulin injection/and, or antidiabetic
agents

 Dietary management is similar to type 1 and type 2

dm

 Modify for pt. with CKD, restrict daily

 protein intake to 0.8 g/kg/day
 restrict salt , to 2-3 gm/day
 Nutritional recommendation for adults with
diabetes
Exercise

 Has a multiple positive benefits

 Cardiovascular risk reduction

 Reduced blood pressure, maintenance of muscle mass

 Reduction in body fat and weight loss

 Lower plasma glucose level

 Recommendation- 30-45 minutes /day , 5 days

/week
Monitoring of self blood glucose
control

 Optimal monitoring of glycemic control involves:

o Glucose measurement by the patient.

i.e. Self Blood Glucose monitoring (SMBG), CGM
o Plasma Glucose determination , laboratory
o Assessment of long term control by determination of HbA1C
(Non glycated hemoglobin for 2-3 months)
Management of type 1 dm

 Intensified insulin therapy improves microvasular

and macrovscular complications of DM

 Conventional insulin therapy

 Multiple daily insulin injection
 Insulin infusion devices (CSII)
 Management of type 1 DM
cont.

 Current Insulin preparation are generated by

Recombinant DNA technology, consists of amino acid
sequences of human Insulin

 Most insulin is formulated as U-100 units/ml

 Insulin syringe ,U-100, novo fine needles

 New preparations on short acting insulin
U-300, U-500
Insulin preparation
Insulin

 Insulin initiation dose to type 1 dm is 0.4-0.5 unit/kg Sc, 2/3 am,

1/3 pm (1/3 to 1/2 of the total dose should be regular insulin)
 Increase 2-4 units every week
 Insulin formulations are available as “pens”, Vials
 Insulin regimens
 Conventional: BID
 Multiple
daily Insulin Injection: A combination of Basal insulin
and Bolus insulin
 Continuous Subcutaneous Insulin Infusion (CSII) : Basal insulin
infusion and bolus insulin infusion

NEW: Closed loop system : data from continuous glucose

measurement regulate the insulin infusion rate.
Type 2 DM

Essential elements in comprehensive care of type 2 diabetes

Type 2 DM drugs
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 FBS >250
mg/dl ,
RBS consistently >300 mg/dl, or ketonuria
 In patients in whom it is difficult to distinguish type 1 from
type 2 DM
Summary

 How do you define diabetes mellitus?

 What are the diagnostic criteria to diagnosis diabetes
mellitus?
 How do you describe the pathogenesis of Type 1 and type
type 2 dm?
 Specify the pharmacologic management of type 1 dm and
type 2 dm.
 Describe the management plan of diabetic patient at
clinic level.
Diabetes Mellitus

PART II

Acute and Chronic

complications of diabetes
mellitus
Case 1.
 A 32 yrs, old Diabetes patient for 3 yrs. who has been taking
Insulatared 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?
How do you confirm the diagnosis?
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
Acute complications of DM

 Dabetic Ketoacidosis (DKA)

 Hyperglycaemic Hyperosmolar state (HSS)

 Hypoglycaemia
Dabetic Ketoacidosis (DKA)

 DKA and HHS are associated

 with absolute or relative insulin deficiency,

 volume depletion
 and acid base abnormalities

 Causes a serious complications or death if not promptly

diagnosed and treated
Pathogenesis

 DKA results from absolute or relative insulin deficiency

combined with counter regulatory hormone excess
(glucagon, catecholamine, cortisol and growth hormone

 The decrease ratio of insulin to glucagon

 promotes gluconeogenesis
 glycogenolysis

 and ketone body formation in the liver

 increase in substrate deliver from fat and muscle (free
fatty acid and amino acids ) to the liver
Pathogenesis cont.

 The combination of insulin deficiency and hyperglycaemia

 reduces the hepatic level of Fructose 2,6 biphosphate

 Which alters the activity of phosphofruktokinase and fructose

1,6 bisphosphatase

 Glucagon excess decreases the activity of pyruvate kinase

 whereas insulin deficiency increases the activity of

phosphoenol pyruvate carboxykinase.
Pathogenesis cont.

 This changes shift the handling of pyruvate toward

glucose synthesis and away from glycolysis

 The increased level of glucagon and catecholamine in

the
face of low insulin levels promote glycogenolysis

 Insulin deficiency also reduces levels of the GLUT 4

glucose transporter
Pathogenesis cont.

 Ketosis results from marked

 Increase in free fatty acid release from adipocytes,

resulting ketone body formation in the liver

 Reduced insulin level in combination with elevations in

catecholamine's and growth hormone

Increase lipolysis and release of free fatty acids and

increase triglyceride and VLDL production
Pathogenesis cont

 Normally this free acids are converted in the liver to

triglyceride and VLDL.

 However in DKA hyperglucagonemia alters hepatic

metabolism
to sever ketone body formation through activation of the
enzyme carntine palmitoiltranferase I.

• This enzyme is crucial for regulating fatty acid transport into

• mitochondria where beta oxidation and conversion to ketone
• bodies occur
 What are the precipitating factors of
DKA?
Clinical manifestations and
precipitating events of DKA
Laboratory values in DKA and HHS
Management of DKA

Principles of management

 Fluid replacement
 Insulin therapy (short acting)
 Potassium replacement
 Management of precipitating factors
Management of DKA cont.
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

 Management is the same as Mg. of DKA, except increase

fluid administration up to 8-10 lt.
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.
Clinical presentation and diagnosis of
hypoglycaemia
 Adrenergic manifestations are
 palpitation
 sweating
 hunger pain
 weakness.
 Neuroglucopenic manifestations include
 headache
 drowsiness
 lethargy and coma

 Diagnosis
of hypoglycemia is based on clinical
manifestation and/or blood sugar values ≤ 70 mg/dl.
Treatment of Hypoglycemia

 Oral treatment with glucose containing food, sweetened

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

 1 tablespoonful of sugar or honey (equivalent to 15 gm-

20 gm of glucose)

 If no response, intravenous 50% glucose 40ml iv stat,

repeat the same in 15 minutes if there is no response
Treatment of Hypoglycemia cont.

 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 and etc
when patient is able to take food PO safely.
Chronic complications of DM

 Affects many organ systems

 Responsible for the majority of

 morbidity and mortality associated with diabetes
Classification of Chronic
complication of DM
Pathogenesis of Chronic complications

 Chronic hyperglycemia is an important etiologic factor

leading to complications of DM

 The mechanism by which such cellular and organ

dysfunction is unknown

 Four prominent theories, have been proposed how

hyperglycemia might lead to chronic complications
Pathogenetic mechanisms cont.
1. Advanced Glycosylation End Product (AGEs)

 Increased intracellular glucose leads to the

formulation of AGEs

 Whichbinds to a cell surface receptor via non

enzymatic glycosylation

 of intra and extracellular proteins, leading to cross-

linking of proteins, accelerated atherosclerosis,
AGEs cont.

 Glomerulardysfunction, endothelial
dysfunction, and altered extracellular
matrix composition.
Pathogenetic mechanisms cont.

2. Sorbitol pathway

 hyperglycemia increases glucose metabolism via the

sorbitol pathway

 Intracellular glucose is predominantly metabolized by

phosphorylation and subsequent glycolysis,

 when increased some glucose is converted to sorbitol by the

enzyme aldose reductase,
Pathogenetic mechanisms cont.

 Increase sorbitol concentration

 alters redox potential,
 increases cellular osmolality
 and generate reactive oxygen species ,

=> leads to cellular dysfunction-retinopathy,

nephropathy, neuropathy
Pathogenetic mechanisms cont.

[Link] of Protein Kinase C activity (PKC)

 Hyperglycaemia increases the formation of

diacylglycerol leading to activation of PKC

 PKC alters the transcription of genes for

 fibronectin,
 Type IV collagen,
 contractile protiens
 and extracellular matrix proteins in endothelial cells
and neurons
Pathogenetic mechanisms cont.

4. The Hexosamine Pathway

 Which generates fructose 6, phosphate, a substrate for O

linked glycosylation and proteoglycan production ,

 then alter function by glycosylation of proteins

 such as endothelial nitric oxide synthase
 or by changes in gene expression of transforming
growth factor B (TGF B0 or plasminogen activator I
(PAI -1)
 Diabetic Retinopathy
Classified in to
 Proliferative diabetic Retinopathy and
 Non proliferative Diabetic retinopathy
 Macular edema

 The leading cause of blindness in type 1 and type 2

dm.

 Blindness is mainly due to

 progressive diabetic retinopathy and
 clinically significant macular edema
Diabetic retinopathy cont.

 Mechanism of retinopathy includes

 loss of retinal pericytes,

 increased retinal vascular permeability,
 alteration in retinal blood flow,
 abnormal retinal microvasculature,

=>all leads to retinal ischemia

Treatment of diabetic retinopathy

 Regular, comprehensive eye examinations are essential

for all individuals with DM

 Intensive control of blood glucose and blood pressure

 Laser photocoagulation
 Panretinal - for proliferative retinopathy
 Focal-for macular oedema
 Anti–vascular endothelial growth factor therapy (ocular
injection).
Diabetic Nephropathy
 Is the leading cause of ESRD
 Leading cause of DM related morbidity and mortality
 Increase the risk of cardiovascular disease
 Only 20–40% of patients with diabetes develop diabetic
nephropathy
 The sequence of events of diabetic nephropathy in
type 1 dm appears also similar in type 2DM.
Five stages=>
 In the first year- increase GFR, leads to glomerular
hyperperfusion and renal hypertrophy
Diabetic Nephropathy cont.

 During the first 5 year- thickening of glomerular

basement membrane, glomerular hypertrophy,
mesangial volume expansion, GFR returns to normal

 After 5-10 yrs. Begins microabuminuria

(30-299mg/dl in 24 hrs)

 Over the next 10 yrs. - 50 % progress to

macroalbuminuria

 Steadily progress and reach to ESRD in 7-10 yrs.

Diagnostic test and treatment of
diabetic nephropathy
 An annual microalbuminuria measurement (albumin-to-
creatinine ratio in spot urine)
 Microalbuminuria
 “persistent albuminuria” (30–299 mg/24 h)” and
 “persistent albuminuria (≥300 mg/24 h)” to Creatinine
 U/A, BUN & Creatinine
 RX.
 Intensive control of blood sugar and blood pressure
 Restrict salt and protein intake
 ACE /ARB inhibitors
 Chronic Dialysis
 Renal Transplantation
Diabetic Neuropathy

 Diabetic neuropathy occurs in 50 % of DM pt.

 Manifest as polyneuropathy, mononeuropathy , autonomic

neuropathy

 Associated with long duration of diabetes and poor

glycaemic control

 Distal symmetrical poly neuropathy is the most common

form of peripheral neuropathy

 Manifestations are paresethesia , numbness, hyperesthesia

Diabetic Neuropathy cont.

 Physical exam : reveals sensory loss, loss of ankle

reflex, loss of vibration and position sense

 Mononeuropathy, present with dysfunction of cranial or

peripheral nerves

 Autonomic neuropathy involves multiple systems

Treatment of Diabetic Neuropathy

 Improve glycaemic control

 NSAID
 Antidepressant e.g Amytryptylline
 Anticonvulsant , Gabapentine, phenytoin
carbamazepine
 Chronic, painful diabetic neuropathy is difficult to
treat but may respond to duloxetine, amitriptyline,
gabapentin, valproate, pregabalin,or opioids.
The DCCT study

 Demonstrated that improvement of glycemic control

reduced
 nonproliferative and proliferative retinopathy (47%
reduction),
 microalbuminuria (39% reduction),
 clinical nephropathy (54% reduction),
 and neuropathy (60% reduction).
 Improved glycemic control also slowed the progression
of early diabetic complications
Genitourinary and Gastrointestinal
manifestations
 Most common GI manifestation are
 Gastro paresis: delayed gastric emptying
symptoms of anorexia, nausea, vomiting, early satiety,
and abdominal bloating
 Constipation or nocturnal diarrhea due to altered large
bowel motility
 Autonomic neuropathy leads to
 Genitourinary dysfunction manifested by Cystopathy,
 Erectile dysfunction in male and
 decrease sexual desire,dysperunia, dryness of vagina
in female
 Dx- cystometry and urodynamic studies
RX.

 Improve glycaemic control

 More frequent small meals, decrease fat and fiber diet

 Dopamine antagonists e.g metoclopramide

 Antibiotic for bacterial overgrowth

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

 Coronary Heart disease is more likely to involve

CVD cont.

 Clinical presentations are:

 Retrosternal chest pain(Angina pain)
 Silent ischemia
 Intermittent claudication of the legs
 Sign and symptoms of CHF

 Investigations
 ECG

 ECHO

 Stress test
CVD cont.

 Treatment of CVD is not different in the diabetic

individuals

 Good glycemic control

 Aggressive cardiovascular risk modification e.g

Dyslipidemia , HTN, smoking etc
Hypertension

 Hypertension accelerates complications of DM

particularly cardiovascular diseases and
D. nephropathy

 Target goal <130/80 mm/Hg

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

diuretics, calcium channel blockers
Lower extremity complications

 DM is the leading cause of nontraumatic lower

extremities amputation

 The pathogenetic factors are

 Presence of peripheral neuropathy, interefer with
normal protective mechanism,leads to major and
repetitive minor trauma
 Abnormal foot biomechanics
 Peripheral arterial disease
 Lower extremity
complications cont.
Autonomic Neuropathy- anhydrosis & altered
superficial blood flow in the foot
Infection

 Dx and Mg

 Diabetic foot education

 Other complications of DM

 Infections
Pneumonia, UTI, TB etc

 Dermatologic manifestations
Summary

 Acute complications of DM are DKA,HHS &

Hypoglycemia
 DKA results from absolute or relative insulin deficiency
combined with counter regulatory hormone excess
(glucagon, catecholamine, cortisol and growth hormone

 DX, Hyperglycaemia>250 mg/dl, glycosuria and

ketonurea, HHS->Blood sugar above 600mg/dl
 Mg., IV fluid, Potassium replacement, insulin, Rx. of
PPT. factors
Summary cont.

 Diagnosis
of hypoglycemia is based on clinical
manifestation and/or blood sugar values ≤ 70 mg/dl.

 Chronic
complications: Microangiopathy,
macrovascular,others

 Pathogenticmechanisms of chronic complications

 Advanced Glycosylation End Product (AGEs)
Sorbitol path way
Activation of Protein Kinase C activity (PKC)
The Hexosamine Pathway
Summary cont.

Diabetic retinopathy is the common cause of blindeness

Diabetic Nephropathy is the common cause of end CKD

Diabetic Foot is the common cause of non traumatic

amputations.

DM increases
 CHF, Coronary Heart Disease, PAD, MI by 2-4 fold