DM by DR BELAY

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Diabetes Mellitus
BY BELAY DEMISIE(MD, MPH)

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Diabetes Mellitus
•Definition: Diabetes mellitus (DM) refers to a group of
common metabolic disorders that share the phenotype
of hyperglycemia.
•Several distinct types of DM are caused by a complex
interaction of genetics and environmental factors.

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Pancreas – Endo and Exocrine parts

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Islets of Langerhans – the composition
•A/α cells = Glucagon
•B/ β cells = Insulin – 60% of Islets cells
•D/ delta cells = Somatostatin
•F cells = Pancreatic polypeptide

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Regulation of Glucose Homeostasis
Insulin is most important regulator of hepatic glucose
production & peripheral glucose uptake & utilization.
Fasting state: Low insulin levels
•Hepatic gluconeogenesis & glycogenolysis by
glucagon and increases glucose production:
•Reduce glucose uptake in insulin sensitive tissues
•Mobilization of stored precursors: AA & FFAs

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Regulation of Glucose Homeostasis…….
•Postprandial state: rise in insulin
•Illicit fall in glucagon.
• Insulin promotes storage of carbohydrate and fat &
protein synthesis
•Major postprandial glucose is used by skeletal muscles

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Insulin Secretion
•Insulin secretion is regulated through 2 pathways :
•Direct regulation:
• Hyperglycemia sensed by β cells – the major one and
•Indirect
•Physiological stimuli : smell, sight and taste of food
•Diet containing CHOs (glucose) , proteins (AA ).
•Hormones: GH; Prolactin, Catecholamines
•Enteric hormones: Gastrin and Cholicystokinin

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Epidemiology
Prevalence of type 2 DM increasing due to
•Increasing Obesity & decreased activity
•80% 0f diabetics live in low & middle income countries
•DM increases with age

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Classification
• Based on pathogenic process that lead to hyperglycemia
• Two broad categories
• Type 1 DM :
• Complete or near- total insulin deficiency
• Type 2 DM:
a) variable degree of insulin resistance
b) Impaired insulin secretion
c)Increased glucose production

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•LADA-late onset auto immune diabetes of adults
(type 1)
•Age >30yrs, more likely to be <50yrs
•Immune markers for type 1 present, islet cell auto
antibodies (ICA), Glutamic Acid
Decarboxylate(GAD) autoantibodies
•personal or family history of other autoimmune
disease.
•Respond to oral agents early phase, more likely to
require insulin treatment within 5 years
•Complete B-cell destruction over 2-3yrs
•Usually lean body wt(normal BMI)

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Classification Cont…
• Maturity-onset diabetes of the young (MODY)
• are subtypes of DM characterized by autosomal
dominant inheritance
• early onset of hyperglycemia (usually <25 years;
sometimes in neonatal period)
• and impaired insulin secretion

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Gestational DM
•Glucose intolerance developing during pregnancy
•Most women revert to normal glucose tolerance
postpartum
•Risk of DM in the next 10-20years : 35-60%
•If diagnosed in early prenatal visit: “Overt” DM

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Spectrum of glucose homeostasis & DM

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Pathophysiology…Type 1 DM
• Interaction of Genetic, Environmental, & auto-immune
factors
• Several factors characterize type 1 DM as auto-immune
condition
• Association with genes of MHC/HLA
• Presence of Islet cell specific auto antibodies
• Frequent occurrence of other auto immune diseases
• 85% of patients have circulating islet cell auto
antibodies( ICA), Anti Insulin( AI), Anti Glutamic Acid
Decarboxylate ( Anti-GAD).
• Excessive secretion of Glucagon

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Pathogenesis of type 2 DM
• Insulin Resistance
•Increased hepatic Glucose production
•Decreased Insulin mediated Glucose
transport
•Impaired beta cell function

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Screening
• Widespread use screening test for type 2 DM is recommended
because
(1) a large number of individuals who meet the current criteria
for DM are asymptomatic and unaware that they have the
disorder,
(2) epidemiologic studies suggest that type 2 DM may be
present for up to a decade before diagnosis,
(3) some individuals with type 2 DM have one or more
diabetes-specific complications at the time of their diagnosis,
(4) treatment of type 2 DM may favorably alter the natural
history of DM.

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Approach TO DM patient
•Hx
•Family hx of DM & its cx
•Wt change
•Risk factors for CVD
•Exercise, alcohol use, smoking, nutritional hx
• Symptoms of hyperglycemia
• polyuria, polydipsia, weight loss, fatigue,
weakness, blurry vision
•Frequent superficial skin infections (vaginitis,
fungal skin infections),
•Delayed wound healing after minor trauma

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•If known DM
•type of Rx
•Level of gycemic control-Hgb A1c,FBS
•frequency of hypoglycemia
•Diabetic cx
•pt’s knowledge about DM, exercise, and
nutrition
•DM-related comorbidities -
HTN,CVD,dyslipidemia

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•P/E- complete+ special attention on
•BMI.
•> 140/90 mmHg is considered HTN in DM.
•Oral hygiene, teeth and gums, periodontal
disease is more frequent
•Peripheral pulses
•Extremities
•Callus, nail disease
•Fungal superficial infections, ulcer, fissures
•deformity ( hammer or claw toes and Charcot
foot)

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Approach TO DM patient……
•Injection sites
•retinal examination
•peripheral neuropathy
•ankle reflexes
• Vibratory sensation, touch with a
monofilament, pinprick sensation

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• Laboratory Assessment
• To meets Dx of DM- FBS,RBS,OGT
• level of glycemic control HgA1C.
• U/A-protein
• Lipid profile---dyslipidemia,
• TFT---------thyroid dysfunction
• Cardic test—if CVD risk.
• LFT
• Serum electrolyte

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Complications of DM
• 1) ACUTE - Diabetic ketoacidosis (DKA) and hyperglycemic
hyperosmolar state (HHS)
• 2) CHRONIC-
. Chronic complications divided into vascular and nonvascular
complications.

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Chronic comp……
• The vascular complications of DM are further subdivided
into:
• microvascular
• retinopathy,(proliferative, non proliferative)
• neuropathy,(mono/polyneuropathy)
• nephropathy
• macro vascular
• coronary heart disease (CHD),
• peripheral arterial disease (PAD),
• cerebrovascular disease

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Chronic compl……
• Nonvascular complications include:
• gastroparesis, (AGE, constpations)
• Infections,(Pneumonia, urinary tract infections)
• skin changes
• hearing loss and impaired mental function
• Cataracts
• Glaucoma
• Periodontal disease

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Acute complications
• Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic
state (HHS, also called nonketotic hyperglycemia) are two of
the most serious acute complications of diabetes

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HHS Vs DKA
•DKA
•Young pt with type 1 DM
•Serum glucose (250-600)
•Plasma ketones (++++)
•Plasma osmolality (300-
320)
HHS
•Elderly with type 2 DM
•Serum glucose >600
•Plasma ketones (+/-)
•Plasma osmolality (330-
380)
• Profound dehydration
and change in mentation
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Diabetic Ketoacidosis
an acute, life threatening metabolic
acidosis complicating type 1DM and some
cases of type 2 DM.
usually coupled with an increase in glucagon
concentration with two metabolic
consequences:
 1) Maximal gluconeogenesis with impaired
peripheral utilization of glucose
 2) activation of the ketogenic process and
development of metabolic acidosis.

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DKA…..
DKA is characterized by the triad of
hyperglycemia, metabolic acidosis, and
ketonemia. Metabolic acidosis is often the
major finding.
 The serum glucose concentration is usually
greater than 250mg/dL and less than 600
mg/dL
 However, serum glucose concentrations
may exceed 900 mg/dL (50 mmol/L) in
patients with DKA who are comatose

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DKA …….
Mortality in DKA is primarily due to the
underlying precipitating illness and only
rarely to the metabolic complications of
hyperglycemia or ketoacidosis
 The prognosis of DKA is substantially
worse at the extremes of age and in the
presence of coma and hypotension

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PATHOGENESIS
DKA results from relative or absolute insulin
deficiency combined with counterregulatory
hormone excess( glucagon, catecholamines,
cortisol, and growth hormone)
promotes gluconeogenesis, glycogenolysis, and
ketone body formation in the liver, as well as
increases in substrate delivery from fat and
muscle (free fatty acids, amino acids) to the
liver.→ hyperglycemia
Insulin deficiency also reduces levels of the GLUT4
glucose transporter
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Ketogenesis
KETOGENESIS occurs as a results of high
glucagon/insulin ratio:
 1) increased liberation of free fatty acids due to the loss
of the inhibitory action of insulin on the hormone
sensitive lipase.
 2) activation of the transport system.
Normally, these free fatty acids are converted to
triglycerides or VLDL in the liver.
 However, in DKA, hyperglucagonemia alters
hepatic metabolism to favor ketone body
formation.
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As a result of the hyperglycemia resultant osmotic
diuresis produces polyuria, urinary losses of
electrolytes, dehydration, and compensatory
polydipsia
Ketosis results in high levels of acetone,
acetoacetate and -hydroxybutyrate )→
metabolic acidosis
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Precipitating factors
Inadequate insulin treatment or
noncompliance
New onset diabetes (20-25 percent)
Acute illness
 Infection (30-40 percent)
Pneumonia, AGE, UTI, sepsis
 Cerebral vascular accident
 Myocardial infarction
 Acute pancreatitis

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Precipitating factors…..
Electrolyte derangements
 Metabolic acidosis and osmotic diuresis lead to total
body hypokalemia
 The measured serum sodium is reduced as a
consequence of the hyperglycemia
 Total-body stores of chloride, phosphorous, and
magnesium are also reduced in DKA.
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Precipitating factors…..
Drugs
 Clozapine or olanzapine
 Cocaine
 Lithium
 Terbutaline
Pregnancy
No obvious cause (5%)

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Clinical features
Symptoms:
Intense thirst
Polyuria
Nausea,vomiting
Abdominal pain (more common in children)
Shortness of breathe
Weight loss
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Signs:
.dry tongue, inelastic skin, sunken eye
.kussmauls respiration(rapid and deep breathing)
.Abdominal tenderness(may resemble acute
abdomen)
.hypotension
.Rapid weak pulse
.hypothermia
.Fruity breath odor of acetone
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History
• Asymptomatic
• Poly symptoms
• Abdominal pain
nausea,
vomiting
• Lethargy,obtund
ation,coma
P/E
• Signs of volume
depletion
• Kussmaul
respiration
• Neurologic
findings
• Signs of
precipitating
illness
Lab findings
• Hyperglycemia
• Serum and urine
ketones
• Serum
osmolalityꜛ
• Wide anion gap
• CBC,serum
electrolytes ,EC
G,arterial blood
gas analysis…
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Diagnostic criteria for DKA
– hyperglycemia (>250 mg/dl)
– ketosis (ketonemia or ketonuria)
– acidosis (pH<7.3, HCO3<15mEq/L)
• supporting features are volume depletion and
Kussmaul’s breathing.
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DKA
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
(mEq/L)
15-18 10 to <15 <10 >18
Urine ketones* Positive Positive Positive Small
Serum
ketones*
Positive Positive Positive Small
Effective
serum
osmolality
(mOsm/kg)•
Variable Variable Variable >320
Anion gapΔ >10 >12 >12 Variable
Alteration in
sensoria or
mental
obtundation
Alert Alert/drowsy Stupor/coma Stupor/coma

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Differential diagnosis
Starvation ketosis
Alcoholic ketoacidosis(bicarbonate>15 meq/l)
Hyperemesis gravidarum
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MANAGEMENT AND
COMPLICATIONS OF DKA

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Principles of mgt
Fluid replacement
Insulin therapy
Electrolyte replacement
Identification and Rx of ppt factors
Close monitoring

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Fluid Replacement
Objectives:
 Restoration of circulating volume.
Replacement of sodium and the ECF and intracellular fluid
deficit of water.
•Fluid loss averages 5L, hence replace 5-6L of fluid in the
first 24 hrs
Replace fluids: 2–3 L of 0.9% saline over first 1–3 h (10–20
mL/kg per hour
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insulin therapy is essential:-
•Normalize blood glucose concentration.
•Suppress lipolysis and ketogenesis and
•Correct acidosis.
•increases peripheral ketone body use
Insulin therapy
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Insulin
Administer short-acting insulin: 0.1 units/kg per hour
by continuous IV infusion
 Increase two- to threefold if no response by 2–4 h.
 If the initial serum potassium is <3.3 mmol/L (3.3
meq/L), do not administer insulin until the potassium
is corrected.
The insulin decreases glucose by 50-70mg/dl per hr.
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Insulin……
 However, if the serum glucose doesn’t fall by 50-
70mg/dl in first hour, double insulin infusion rate every
hour until steady decline is achieved.
Maintain the serum glucose between 150-250mg/dl
Give initial bolus of 10IU IV and 10 IU IM of regular
insulin
Then give 5 IU IV every one hour until blood sugar
falls below 200 and urine ketone is twice negative
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cont…
In Patients with known diabetes who were previously
treated with insulin may be given insulin at the dose
they were receiving before the onset of DKA
In insulin-naive patients, insulin regimen should be
started at a dose of 0.5 to 0.8 U/kg per day
Administer long-acting insulin overlapping with
insulin infusion and SC insulin injection for a 2–4
hour
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Modified sliding scale
• 180-199 2 IU
• 200 - 249 3IU
• 250 - 299 4IU
greater than 300 5IU

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Follow up
Clinical
• Vital signs(Q 1-4 hrs)
• Input/output
• Mental status
Lab
• RBS(Q 1-2 hrs)
• Urine ketone(Q 2-4
hrs)
• Serum K+(Q 4hrs for
the 1st
24 hrs)
• RFT
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Complications of DKA
Hypoglycemia (common)
Hypokalemia
Cerebral edema,
 High mortality
 Treat with mannitol, oxygen
ARDS
Fluid overload,

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HHS treatment
Similar principles of management with DKA
Calculated fluid deficit averages 9-10 L, should be
reversed over the next 1 to 2 days
Patient should be discharged on insulin ( some may
switch to oral agents later.
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Management of DM
 Pt education
prevention - diet, exercise
Mx during acutes illnesses
Mx of hypoglycemia
foot & skin care
modify risk factors

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•Exercise
• ↓CVS risk ,↓BP,↓body fat,↓blood glucose
• Maintain muscle mass
• Increase insulin sensitivity
• Can lead to hyper/hypoglycemia based on
• Pre exercise glycemic level
• Pre exercise insulin level
• Extent of exercise

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Exercise…..
• Monitor RBS before, during & after ex.
• Delay if RBS <100mg/dl or >250
• Eat meal 1-3hr before ex. Or take supplemental CHO
atleast every 30min.
• ↓insulin doses
• Avoid injection of insulin to the exercising limb

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Pharmacologic Treatment

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Treatment of type 1 DM
Insulin is the main stay of treatment

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Quiz
1) Write five precipitants of DKA
2) Write diagnostic criteria of DM and DKA
3) What are complications of DM
4) Write management principles of DKA
5) What are components of Islets of langrhans

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THANK YOU