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PDA103T - 10 Diabetes Mellitus
PDA103T - 10 Diabetes Mellitus
Diabetes mellitus
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Biochemical Aspects of
Diabetes Mellitus
2
Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Overview
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Comparison between type 1 & type 2 DM
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Type 1 Diabetes Mellitus
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Type 1 Diabetes Mellitus
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Onset of type 1 DM
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes of type 1 DM
1- Hyperglycemia
2- Diabetic Ketoacidosis (DKA)
3- Hypertriacylglyceridemia & hypercholestrolemia
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes of type 1 DM (cont.)
Proteolysis
Lipolysis
Uptake of AA by liver
in Adipose Tissue
In Sk. Ms. & Adipose In Liver
Glucose Uptake Glycogenlysis
Gluconeogenesis Fatty Acids
in liver
Gluconeogenesis
Plasma Hyperglycemia
Osmolality
ketone Bodies Coma Prerenal Uremia
Glycosuria (KETOGENESIS)
Metabolic Low
Osmotic diuresis Ketonemia Acidosis Renal H+
With Loss of water & Na+ Excretion
Low
& Hypovolemia Nausea Acetone Increased Blood
& Ketonuria Smelt Respiration Bicarbonate
on Breath
Polyuria, Vomiting
Low pCO2
Thirst &
Dehydration Low GFR
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes of type 1 DM (cont.)
Metabolic & Clinical Abnormalities in DKA
Diagnosis of DKA
1- History (for a cause of DKA)
2- Clinical Examination
3- Lab Investigations:
Investigations (to confirm the diagnosis & follow up of treatment)
- Urine by dipstick: Glucose & Ketones +++ (RAPID TEST)
- Blood Chemistry Analysis:
* Blood Glucose:
Glucose High
* Blood Urea:
Urea High (due to dehydration)
* Electrolytes: Low (or normal) sodium
High (or normal) potassium
* Assessment of acid-base status:
status (metabolic acidosis)
- Blood Bicarbonate: Low (usually below 5 mmol/L)
- pCO2: Low (compensatory)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes of type 1 DM (cont.)
Metabolic & Clinical Abnormalities in DKA
4- Potassium is given with insulin treatment as insulin induces K+ entry into cells
5- IV GLUCOSE SHOULD BE STARTED IN CASE GLUCOSE IN BLOOD FALLS BELOW 10 mmol/L (AVOID
HYPOGLYCEMIA INDUCED BY INSULIN)
Chylomicrons (from diet fat) accumulates (due to low lipoprotein lipase activity as a
result of low or absent insulin)
Chylomicrons contain Triacyglycerols (mainly) & Cholesterol
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes of type 1 DM
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Diagnosis of type 1 DM
• Clinically:
Age: during childhood or puberty (< 20 years of age)
With Abrupt (Sudden) appearance of :
Polyuria, Polydepsia, Polyphagia, Fatigue, Weight loss
Complication as ketoacidosis (common, may be the cause of
diagnosis)
• Laboratory diagnosis:
Fasting blood glucose: > or equal 126 mg/dl
100 – 125 mg/dl is called impaired fasting blood glucose
HBA1c: High (more than 6% of normal hemoglobin)
Insulin level in blood: low
Circulating islet-cell antibodies detection
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Biochemical Aspects
for Treatment & Control of Type 1 DM
AIM
Exogenous insulin by subcutaneous injection is given to:
Strategies of Treatment
1- Standard Treatment
2- Intensive Treatment (Tight Control)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Biochemical Aspects
for Treatment & Control of Type 1 DM (cont.)
1- Standard Treatment:
By one or two injections of insulin/day
AIM: Mean blood glucose level 225-275 mg/dl (normal: 110 mg/dl)
HbA1c level: 8-9 % of total Hb (normal: 6% of total hemoglobin)
HbA1c:
is proportional to average blood concentration over the previous several
months
So, it provides a measure of how proper treatment normalized blood
glucose in diabetic over
several months
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Treatment of type 1 DM (cont.)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Biochemical Aspects
for Treatment & Control of Type 1 DM (cont.)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Type 2 Diabetes Mellitus
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Type 2 DM
• 90% of diabetics (in USA)
• Develops gradually
• may be without obvious symptoms
• may be detected by routine screening tests
• BUT: many type 2 diabetics have symptoms of polyuria & polydepsia
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Causes of Type 2 DM
Insulin Resistance & Dysfunctional-cell
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Causes of type 2 DM (cont.)
Insulin Resistance & Dysfunctional-cell
2- In late cases, -cell dysfunction with low insulin secretion occurs due to
increased amounts of free fatty acids & other factors secreted by fat cells (as
leptin & resistin) may end in development of type 2 DM (hyperglycemia).
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Causes of type 2 DM (cont.)
Insulin resistance & dysfunctional-cell
In Type 2 DM
Initially (In early stages : with Insulin resistance)
the pancreas retains -cell capacity
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes in Type 2 DM
Metabolic abnormalities of type 2 DM are the results of insulin resistance (in liver,
muscle & adipose tissue)
1- Hyperglycemia
2- Hypertriacylglyceridemia
3- Nonketotic hyperglycemic coma
In cases with severe hyperglycemia especially in older age diabetics type 2
Hyperglycemia induces osmotic diuresis with loss of ECF
The osmotic diuresis causes loss of water in excess of sodium
leading to very high plasma osmolality (with hypernatremia)
& marked dehydration
No ketgenesis due to presence of sufficient insulin to prevent DKA
(or sometimes there is minimal ketogenesis with minimal metabolic
acidosis i.e. Bicarbonate is not much lowered as in DKA)
Treatment:
Fluid replacement + Insulin IV infusion + follow up (Emergency Case!!)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Metabolic changes in Type 2 DM
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Chronic Effects of DM
Cataract
Diabetic Retinopathy
Diabetic Nephropathy
Diabetic Neuropathy
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Treatment of Type 2 DM
• AIM:
1- To maintain blood glucose concentrations within normal limits
2- To prevent the development of long-term complications occurring due
to prolonged hyperglycemia
• Lines of treatment:
1- Weight reduction (to control insulin resistance)
2- Exercise
3- Dietary modification
4- Hypoglycemic agents
5- Insulin (required in some cases)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Case Study
Parents of a 15 years old boy was reported by his school that he was found drowsy & they have
got to take him to hospital according to the advice of his school doctor.
In the hospital, his mother told the doctor that her son seemed unusually thirsty for the last 3
months & she thought that he had lost weight. She admitted also that on the morning
before leaving for school, he was complaining of abdominal pain & discomfort.
On examination:
Semiconscious
Deep & rapid respiration
Pulse rate 120 beats/minute
BP: 90/50
Cold extremities
Urine Analysis:
• Urine Dipstick Test:
- Glucose +++
- Ketone +++
- Albumin ++
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Summary
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences