DIABETES MELLITUS-2

Dr Chandrika D Nayak
Professor of Biochemistry
MMMC (Manipal Campus)

Dr Chandrika D nayak, MMMC

OBJECTIVES
• Link between metabolic alterations and symptoms
and acute complications in DM
• List long term sequelae in DM
• Mention normal
• FBS
• PPBS
• RBS and their utility in diagnosis of DM

Dr Chandrika D nayak, MMMC

 Basis for hyperglycemia & symptoms in T1D
 Insulin, ↑ Glucagon (I:G ratio )

 Glucose ↑Glycogenolysis ↑ Gluconeogenesis  Glucose

uptake by in liver in liver uptake by
muscle, ↑ Protein satiety
adipose catabolism centre
tissue in muscles
Amino
Hyperglycemia No (-) of feeding centre
acids
Glucosuria
Polyphagia
Osmotic diuresis, water loss

Polyuria Dehydration ↑ Plasma osmolarity

Polydypsia
Dr Chandrika D nayak, MMMC
+ thirst centre
Biochemical findings

• Hyperglycemia
• Hyperlipidemia
• Diabetic Ketoacidosis (DKA); a type of
metabolic acidosis
• Ketotic coma

Dr Chandrika D nayak, MMMC

  Insulin: ↑ Glucagon (I:G ratio )

induction of LP Glycosylation of LDL receptor ↑ lipolysis in

lipase in adipose
adipose tissue
tissue
 LDL uptake
↑ FFA in plasma
 VLDL & chylomicron
clearance
FFA oxidized in liver

Hypertriglyceridemia ↑ Acetyl CoA in liver

hypercholesterolemia  OAA
Ketone bodies
 TCA cycle
Ketonemia
Dehydration Ketonuria
COMA
Ketoacidosis

+ Resp. centre, kussmaul breathing

Dr Chandrika D nayak, MMMC
 Treatment for T1D
• To control hyperglycemia
• Subcutaneous exogenous insulin injections is a must
• Periodic injection
• Continuous pump assisted infusion
• Insulin used today
• Is recombinant human insulin
• Earlier bovine/porcine insulin were used
• To control ketoacidosis: replacing with fluids &
electrolytes
Dr Chandrika D nayak, MMMC
 Chronic effects of DM
• Microvascular changes: retinopathy,
nephropathy,neuropathy
• Macrovascular changes: premature
atherosclerosis, cardiovascular disease, stroke
• Diabetic cataract (sorbitol production from
glucose, osmolarity changes & damage in lens)

Dr Chandrika D nayak, MMMC

• Hyperglycemia promotes non-enzymic
condensation of glucose with Hb (HbA1C) & other
cellular proteins
• These glycated proteins later form advanced
glycation end products (AGEs)
• AGEs mediate early microvascular changes &
reduce wound healing
• AGEs bind to receptors RAGEs and release
proinflammatory molecules
Dr Chandrika D nayak, MMMC
1. Genetics
2. Obesity Insulin resistance
3. Sedentary
lifestyle
4. Ageing Hyperinsulinemia
5. 3-5% of
ladies who In combinaton with
had 1. Genetics
gestational
diabetes 2. Glucose toxicity
Decline of
3. Free fatty acid
-cell toxicity
function + 4. Proinflammatory
environment

T2D

Dr Chandrika D nayak, MMMC

 Type 2 diabetes

Hyperglycemia,
Insulin present hyperosmolar plasma
though inadequate

Insulin suppresses release Glucosuria

of glucagon

Polyuria, osmotic
Restrain of ketogenesis
diuresis & Dehydration
Patient fails to
+ drink
adequate
water

Non-ketotic hyperosmolar coma

Dr Chandrika D nayak, MMMC
 Treatment of T2D
• Goal to maintain normal limits of blood glucose
• Initial intensive therapy in newly diagnosed DM decreases risk
of MI & death
• Nutrition therapy (dietary modifications)
• Weight reduction regime
• Exercise
• Aggressive control of hypertension
• Control of dyslipidemias

Dr Chandrika D nayak, MMMC

 Lab Investigations in DM
• For diagnosis
• Fasting plasma glucose levels
• Glycosylated Hb levels
• Oral glucose tolerance test (OGTT) (chiefly for confirmation
of diagnosis in gestational DM)
• For regular monitoring of patients
• Glycosylated Hb
• Fasting and post prandial plasma glucose levels
• For complications
• Microalbuminuria
Dr Chandrika D nayak, MMMC
 Plasma glucose estimation
• Fasting (after overnight fast/ no calorie intake for 8 hrs
or more)
• Post-prandial (2 hour after a meal)
• Random (any time of the day regardless of food intake)
• Normal levels
• Fasting (FBG) : less than 60-100mg/dl
• Post-prandial (PPBG) : 80-140mg/dl
• Random (RBG) : 60-140mg/dl

Dr Chandrika D nayak, MMMC

 Urine glucose estimation
• Benedict’s test is rarely done & outdated
• Glucose dipsticks (home use)
• Other causes for glucosuria
• Renal glucosuria: Defect in the renal glucose
transporter (glucose appears in urine even
though plasma glucose is normal)

Dr Chandrika D nayak, MMMC

 Diagnosis of DM

• FBG (Fasting blood glucose) 126mg/dl

(7mmol/L) or more
• RBG/PPBG(Random/post prandial blood
glucose ) 200 mg/dl (11.1mmol/L) or more
• Glycosylated Hb 6.5% of total Hb or more

Dr Chandrika D nayak, MMMC