Diabetes Mellitus - Dr Rohit Bhaskar

©2021 Dr Rohit Bhaskar PT https://www.pt-pedia.com/
DIABETES MELLITUS
©2020 Rohit Bhaskar PT
Whatsapp - +919026742838
https://www.pt-pedia.com/
PRESENTED BY
DR ROHIT BHASKAR
PHYSICAL THERAPIST

 Diabetes mellitus is the 3rd leading cause of
death in many developed countries.
 Diabetes is a major cause of blindness, renal
failure, amputation, heart attacks and
stroke.
 Diabetes mellitus is a characterized
by increased blood glucose level
(hyperglycemia) due to insufficient or
inefficient (incompetent) insulin.

 Insulin isa polypeptide hormone produced by
the β-cells of islets of Langerhans of pancreas.
 It influences the metabolism of
carbohydrate, fat & protein.
 It isan anabolic hormone, promotes the
synthesis of glycogen, triacylglycerols &
proteins.
INSULIN

 Human insulin (mol. wt. 5,7341)contains 51amino acids,
arranged in 2polypeptide chains.
 A chain – 21amino acids & B chain – 30amino acids.
 Both are held together by 2interchain disulfide
bridges, connecting A7to B7&A20 to B19.
 There isan intrachain disulfide link in chain A
between the amino acids 6& 11.

 The gene for insulin synthesis is located on
chromosome 11.
 The synthesis of insulin involves two
precursors, namely preproinsulin with 108
amino acids (mol. wt. 11,500)&proinsulin with
86amino acids (mol. wt. 9,000).

 They are sequentially degraded to form
the active hormone insulin &a connecting
peptide (C-peptide).
 Insulin &C-peptide are produced
in equimolar concentration.
 C-peptide is biologically inactive.
 Its estimation is useful index for the
endogenous production of insulin.

 In the β-cells, insulin (also proinsulin)
combines with zinc to form
complexes.
 In this complex form, insulin is stored in the
granules of the cytosol which is released in
response to various stimuli by exocytosis.

 Factors stimulating insulin secretion:
 Glucose &amino acids
 Gastrointestinal hormones – secretin, gastrin,
pancreozymin increase the secretion.
 Factors inhibiting insulin secretion:
 Epinephrine from adrenal medulla is most
potent inhibitor of insulin secretion.

 Insulin has a half-life of 4-5minutes.
 About 40-50units of insulin is secreted daily
human pancreas.
 The normal range of insulin: 20-30μU/ml.
 A protease enzyme – insulinase
degrades insulin.
 Insulinase is mainly present in liver & kidney.

 Effects on carbohydrate metabolism:
 Insulin lowers blood glucose level by
promoting its utilization &storage &by
inhibiting its production.
 Effect on glucose uptake by tissues:
 Insulin isrequired for uptake of glucose by muscle
(skeletal, cardiac &smooth), adipose tissue,
leukocytes &mammary glands.

 About 80%of glucose uptake in the body
is not dependent on insulin.
 Effect on glucose utilization:
 Insulin increases glycolysis in muscle &liver.
 Insulin activates key enzymes of glycolysis –
glucokinase, PFK&pyruvate kinase.
 Glycogen production is increased, due to
increased activity of glycogen synthase
by insulin.

 Effect on glucose production:
 Insulin decreases gluconeogenesis by
suppressing the enzymes pyruvate
carboxylase, phosphoenol pyruvate
carboxykinase &glucose 6-phosphatase.
 Insulin also inhibits glycogenolysis by
inactivating the enzyme glycogen
phosphorylase.

 Effects on lipid metabolism:
 The net effect of insulin on lipid metabolism
is to reduce the release of fatty acids from
the stored fat &decrease the production
of ketone bodies.
 Adipose tissue is the most sensitive to the
action of insulin.

 Effect on lipogenesis:
 Insulin favours the synthesis of
triacylglycerols from glucose by providing
more glycerol 3-phosphate & NADPH.
 Insulin increases the activity of acetyl CoA
carboxylase, a key enzyme in fatty acid
synthesis.
©2021 Dr Rohit Bhaskar PT https://www.pt-
pedia.com/

 Effect on lipolysis:
 Insulin decreases the activity of hormone-
sensitive lipase &reduces the release of fatty
acids from stored fat.
 The mobilization of fatty acids from liver is
also decreased by insulin.
 Effect on ketogenesis:
 Insulin reduces ketogenesis by decreasing
the activity of HMG CoA synthetase.

 Effects on protein metabolism:
 It stimulates the entry of amino acids into the
cells, increases protein synthesis &reduces
protein degradation.
 Insulin promotes cell growth & replication.
 Thisis mediated through certain factors such
as epidermal growth factor (EGF),platelet
derived growth factor & prostaglandins.

 Insulin receptor mediated signal
transduction:
 Insulin receptor:
 It is a tetramer consisting of 4subunits – α2β2.
 The subunits are in the glycosylated form.
 They are held together by disulfide linkages.
 α – subunit (mol. wt. 135,000)is extracellular &
it contains insulin binding site.

 β – subunit (mw. 95,000)isa transmembrane
protein which isactivated by insulin.
 The cytoplasmic domain of β – subunit has
tyrosine kinase activity.
 The insulin receptor is synthesized as a single
polypeptide & cleaved to α & β subunits which are
then assembled.
 Insulin receptor has a half-life of 6-12hours.
 About 20,000receptors/cell in mammals.

 Signal transduction:
 Insulin binds to the receptor, a
conformational change is induced in the α-
subunits of insulin receptor.
 Thisresults in the generation of signals which
are transduced to β-subunits.
 The net effect is that insulin binding activates
tyrosine kinase activity of intracellular β-
subunit of insulin receptor.

 Thiscauses the autophosphorylation of
tyrosine residues on β-subunit.
 Receptor tyrosine kinase also phosphorylates
insulin receptor substrate (IRS).
 The phosphorylated IRS, in turn, promotes
activation of other protein kinases &
phosphatases, finally leading to
biological
action.

 Insulin-mediated glucose transport:
 The binding of insulin to insulin receptor signals the
translocation of vesicles containing glucose
transporters from intracellular pool to the plasma
membrane.
 The vesicles fuse with the membrane recruiting the
glucose transporters.
 The glucose transporters are responsible for the
insulin-mediated uptake of glucose by the cells.

 As the insulin level falls, the glucose
transporters move away from the
membrane to the intracellular pool for
storage & recycle.
 Insulin mediated enzyme synthesis:
 Insulin promotes the synthesis of enzymes
suchas glucokinase, PFK&pyruvate kinase.
 Thisis brought about by increased
transcription & translation.

 Glucagon, secreted by α-cells of the pancreas.
 It isa polypeptide hormone composed of 29
amino acids (mol. wt. 3,500)in a single chain.
 It issynthesized as proglucagon, on sequential
degradation releases active glucagon.
 Its amino acid sequence isthe same in all
mammalian species &half-life. i.e. about 5
minutes.

 The secretion of glucagon is stimulated by
low blood glucose concentration, amino
acids derived from dietary protein &low
levels of epinephrine.
 Increased blood glucose level
markedly inhibits glucagon secretion.

 Glucagon enhances the blood glucose
level (hyperglycemic).
 Primarily, glucagon acts on liver to cause
increased synthesis of glucose &enhanced
degradation of glycogen.

 Effects on lipid metabolism:
 Glucagon promotes fatty acid
oxidation resulting in energy
production & ketone body synthesis.
 Effects on protein metabolism:
 Glucagon increases the amino acid
uptake by liver & promotes
gluconeogenesis.

 The maintenance of glucose level in
blood within narrow limits is a very finely
& efficiently regulated system.
 It is essential to have continuous supply of
glucose to the brain.

 Following a meal, glucose isabsorbed from the
intestine and enters the blood.
 The rise in blood glucose level stimulates the
secretion of insulin.
 The uptake of glucose by most extrahepatic tissues,
except brain isdependent on insulin.
 Insulin helps in the storage of glucose as
glycogen or its conversion to fat.

 Normally, 2to 2½hours after a meal,
blood glucose level falls to near fasting
levels.
 It may go down further; but this is
prevented by processes that contribute
glucose to the blood.
 For another 3hours, hepatic glycogenolysis
will take care of the blood glucose level.

 Thereafter gluconeogenesis will take charge of
the situation.
 Liver isthe major organ that supplies the glucose
for maintaining blood glucose level.
 Glucagon, epinephrine, glucocorticoids, growth
hormone, ACTH&thyroxine will keep the blood
glucose level from falling.
 They are referred to as antiinsulin hormones or
hyperglycemic hormones.

 Random blood sugar
 Fasting blood sugar
 Post-prandial blood sugar
 Hyperglycemia
 Hypogycemia
 Glucose is estimated by GOD/POD
or hexokinase method.

 Insulin:
 It is produced in response to hyperglycemia.
 Some amino acids, free fatty acids, ketone
bodies, drugs suchas tolbutamide also cause
the secretion of insulin.
 It is hypoglycemic hormone that lowers in
blood glucose level.

 Glucagon:
 Hypoglycemia stimulates its production.
 It increases blood glucose concentration.
 It enhances gluconeogenesis & glycogenolysis.
 Epinephrine:
 It is secreted by adrenal medulla.
 It acts on muscle &liver to bring about
glycogenolysis by increasing phosphorylase
activity.

 Thyroxine:
 It isa hormone of thyroid gland.
 It elevates blood glucose level by stimulating hepatic
glycogenolysis & gluconeogenesis.
 Glucocorticoids:
 Glucocorticoids increases gluconeogenesis.
 Theglucose utilization by extrahepatic tissuesis inhibited by
glucocorticoids.
 Theoverall effect of glucocorticoids isto elevate
blood glucose concentration.
 GH &ACTHalso increases blood glucose.

 A fall in plasma glucose less than 50mg/dl is
called as hypoglycemia.
 Hypoglycemia is life-threatening.
 The manifestations include headache,
anxiety, confusion, sweating, slurred speech,
seizures &coma, and, if not corrected,
death.

 Post-prandial hypoglycemia:
 This is also called reactive hypoglycemia & is
observed in subjects with an elevated insulin
secretion following a meal.
 Thiscauses transient hypoglycemia &is
associated with mild symptoms.
 The patient is advised to eat frequently
rather than the 3usual meals.

 Fasting hypoglycemia:
 Fasting hypoglycemia isnot very common.
 It isobserved in patients with pancreatic β- cell
tumor &hepatocellular damage.
 Hypoglycemia due to alcohol intake:
 Alcohol consumption causes hypoglycemia
 Thisisdue to the accumulation of NADH, which
diverts pyruvate &oxaloacetate to form
lactate & malate.

 Finally gluconeogenesis is reduced due to
alcohol consumption.
 Hypoglycemia due to insulin overdose:
 The most common complication of insulin
therapy in diabetic patients is
hypoglycemia.
 Thisis particularly observed in patients who
are on intensive treatment.

 Diabetes mellitus (DM) is a metabolic
disease due to absolute or relative insulin
deficiency.
 DM is a common clinical condition.
 It is a major cause for morbidity & mortality.
 Mainly two types.
 Type 1diabetes mellitus (T1DM).
 Type 2diabetes mellitus (T2DM).

 Also known as IDDM or (less frequently)
juvenile onset diabetes, mainly occurs in
childhood (between 12-15years age).
 IDDM accounts for about 10 to 20% of
the known diabetics.
 Characterized by almost total deficiency
of
insulin due to destruction of β-cells.

 The β-cell destruction may be caused by
drugs, viruses or autoimmunity.
 Due to certain genetic variation, the β-cells
are destroyed by immune mediated injury.
 Symptoms of diabetes appear when 80-90%
of the - β cells have been destroyed.
 The pancreas ultimately fails to secrete insulin
 The patients of IDDM require insulin therapy.

 Also called as non-insulin dependent
diabetes mellitus (NIDDM).
 Accounting for 80to 90%of diabetic population.
 NIDDM occurs in adults (above 35years) &is
less severe than IDDM.
 The causative factors of NIDDM include
genetic & environmental.
 NIDDM commonly occurs in obese individuals.

 Gestational diabetes mellitus (GDM):
 Thisterm is used when carbohydrate intolerance is
noticed, for the first time, during a pregnancy.
 A known diabetic patient, who becomes
pregnant, is not included in this category.
 Glucose challenge test (GCT) is done between 22 &
24 weeks of pregnancy by giving an oral glucose
load of 50g of glucose regardless of the time.
 If the 2-hour post-glucose value is >140 mg/dl, the test
is positive.

 Impaired glucose tolerance (IGT):
 Also called as Impaired Glucose Regulation (IGR).
 Plasma glucose values are above the normal level,
but below the diabetic levels.
 In IGT, the FBSvalue is 110&126mg/dl &PPBSvalue is
between 140&200mg/dl.
 Requires careful follow-up because IGT progresses to
frank diabetes at the rate of 2%patients peryear.

 Impaired fasting glycemia (IFG):
 In this condition, fasting plasma glucose is
above normal (between 110&126mg/dl);
but the 2hour post-glucose value is within
normal limits (less than 140mg/dl).
 These persons need no immediate
treatment; but are to be kept under
constant check up.

 Secondary to other known causes:
 Endocrinopathies (Cushing's disease,
thyrotoxicosis, acromegaly)
 Drug induced (steroids, beta blockers, etc.)
 Pancreatic diseases (chronic pancreatitis,
fibrocalculus pancreatitis, hemochromatosis,
cystic fibrosis).

 The diagnosis of diabetes can be made on
the basis of individual's response to the oral
glucose load, commonly referred to as oral
glucose tolerance test (OGTT).
 Preparation of the subject:
 Carbohydrate-rich diet for at least 3
days prior to the test.

 All drugs known to influence carbohydrate
metabolism should be discontinued (2 days).
 The subject should avoid strenuous exercise on the
previous day of the test.
 Person should be in an overnight fasting state.
 During the course of GTT,the person should
be comfortably seated &should refrain from
smoking & exercise.

 Glucose tolerance test should be conducted
preferably in the morning (ideal 9to 11AM).
 A fasting blood sample is drawn and urine
collected.
 The subject is given 75g glucose orally,
dissolved in about 300ml of water, to be
drunk in about 5minutes.

 Blood &urine samples are collected at
30minute intervals for at least 2hours.
 All blood samples are subjected to
glucose estimation while urine samples
are qualitatively tested for glucose.
©2021 Dr Rohit Bhaskar PT https://www.pt-
pedia.com/

 The fasting plasma glucose level is 75-110mg/dl
in normal persons.
 On oral glucose load, concentration
increases &peak value (140mg/dl) is
reached in less than an hour which returns to
normal by 2hours.
 Glucose is not detected in any of the
urine samples

 In individuals with impaired glucose
tolerance, the fasting (110-126mg/dl) as well
as 2hour (140-200mg/dl) plasma glucose
levels are elevated.
 These subjects slowly develop frank diabetes.
 Dietary restriction &exercise are
advocated for the treatment of impaired
glucose tolerance.

Condition Plasma glucose concentration as mmol/l (mg/dl)
Normal IGT Diabetes
Fasting
<6.1
(<110)
<7.0
(<126)
>7.0
(>126)
2hours
after
glucose
<7.8
(<140)
<11.1
(<200)
>11.1
(>200)

 For conducting GTTin children, oral glucose is
given on the basis of weight (1.5to 1.75g/kg).
 In case of pregnant women, 100g
oral glucose is recommended.
 Mini GTTcarried out in some laboratories,
fasting and 2hrs. sample (instead of 1/2 hr.
intervals) of blood &urine are collected.

 Toevaluate the glucose handling of the
body under physiological conditions, fasting
blood sample is drawn, the subject is
allowed to take heavy breakfast, blood
samples are collected at 1hour &2hrs (post-
prandial- meaning after food).
 Urine samples are also collected.
 Thistype of test is commonly employed in
established diabetic patients for
monitoring the control.

 For individuals with suspected malabsorption,
intravenous GTTis carried out.
 Corticosteroid stressed GTTis employed to detect
latent diabetes.
 Glycosuria:
 The commonest cause of glucose excretion in urine
(glycosuria) is diabetes mellitus.
 Glycosuria is the first line screening test for diabetes.
 Normally, glucose does not appear in urine until
the plasma glucose concentration exceeds renal
threshold (180 mg/dl).

 Renal glycosuria:
 Renal glycosuria is a benign condition due
to a reduced renal threshold for glucose.
 It is unrelated to diabetes &should not
be mistaken as diabetes.
 Further, it is not accompanied by the
classical symptoms of diabetes.

 Alimentary glycosuria:
 In certain individuals, blood glucose level rises
rapidly after meals resulting in its spill over
into urine.
 Thiscondition is referred to as alimentary
glycosuria.
 It is observed in some normal people & in
patients of hepatic diseases, hyperthyroidism
&peptic ulcer.

Hyperglycemia:
 Elevation of blood glucose concentration is
the hallmark of uncontrolled diabetes.
 Hyperglycemia is primarily due to reduced
glucose uptake by tissues &its increased
production via gluconeogenesis &
glycogenolys.
 Glucose is excreted into urine (glycosuria).

Ketoacidosis:
 Increased mobilization of fatty acids results
in overproduction of ketone bodies which
often leads to ketoacidosis.
 Hypertriglyceridemia:
 Conversion of fatty acids to TAGs&secretion
of VLDL&chylomicrons is higher indiabetics.
 Plasma levels of VLDL, chylomicrans, TAGs&
cholesterol are increased.

 Glycosuria – glucose excretion in urine.
 Due to osmotic effect, more water
accompanies the glucose (polyuria).
 Tocompensate for this loss of water, thirst
center isactivated &more water istaken
(polydypsia).
 Tocompensate the loss of glucose &protein,
patient will take more food (polyphagia).

 Diabetic keto acidosis (DKA):
 DKA more common in T1DM.
 Normally the blood level of ketone bodies is
<1mg/dl &only traces are excreted inurine.
 Increased synthesis causes the accumulation of
ketone bodies in blood.
 It causes ketonemia, ketonuria &smell of
acetone in breath.
 Together constitute ketosis.

 Detected by Rothera's test.
 Supportive evidence may be derived
from estimation of serum electrolytes,
acid–base parameters &glucose
estimation.

 The urine of a patient with diabetic keto
acidosis will give positive Benedict's test as
well as Rothera's test.
 But in starvation ketosis, Benedict's test is
negative, but Rothera's test will be positive.

 Diabetes Mellitus:
 The combination of hyperglycemia,
glucosuria, ketonuria &ketonemia is
called diabetic ketoacidosis (DKA).
 Untreated diabetes mellitus is the most
common cause for ketosis.
 Deficiency of insulin causes accelerated
lipolysis &more fatty acids are released into
circulation.

 Oxidation of these fatty acids increases
the acetyl CoA pool.
 Enhanced gluconeogenesis restricts the
oxidation of acetyl CoA by TCAcycle,
since availability of oxaloacetate is less.

 In starvation, dietary supply of glucose is
decreased.
 Available oxaloacetate is channelled to
gluconeogenesis.
 The increased rate of lipolysis provides
excess acetyl CoA which is channeled to
ketone bodies.
 The high glucagon favors ketogenesis.

 Hyperemesis (vomiting) in early pregnancy may
also lead to starvation-like condition &may lead
to ketosis.
 In both diabetes mellitus &starvation, the
oxaloacetate is channelled to
gluconeogenesis.
 Acetyl CoA cannot be fully oxidized in TCA cycle.
 Thisexcess acetyl CoA is channelled into ketogenic
pathway.

 Metabolic acidosis:
 Acetoacetate &β-hydroxy butyrate
are accumulated, causes metabolic
acidosis.
 There will be increased anion gap.
 Reduced buffers:
 The plasma bicarbonate is used up
for buffering of these acids.

 Kussmaul's respiration:
 Patients will have typical acidotic breathing due
to compensatory hyperventilation.
 Smell of acetone in patient's breath.
 Osmotic diuresis induced by ketonuria may lead
to dehydration.
 Sodium loss:
 The ketone bodies are excreted in urine as their
sodium salt, leading to loss of cations from the body.

 High potassium:
 Due to lowered uptake of potassium by
cells in the absence of insulin.
 Dehydration:
 Sodium loss further aggravates dehydration.
 Coma:
 Hypokalemia, dehydration & acidosis
contribute to the lethal effect of ketosis.

 Parenteral administration of insulin &
glucose.
 Intravenous bicarbonate to correct
acidosis.
 Correction of water imbalance by
normal saline.
 Correction of electrolyte imbalance.

 Hyperglycemia is directly or indirectly
associated with several complications.
 These include
 Atherosclerosis
 Retinopathy
 Nephropathy
 Neuropathy.

 Dietary management:
 A diabetic patient is advised to consume
low calories (i.e. low carbohydrate &fat),
high protein &fiber richdiet.
 Diet control &exercise will help to a
large extent obese NIDDM patients.

Hypoglycemic drugs:
 The oral hypoglycemic drugs are broadly
of two categories-sulfonylureas &
biguanides.
 Sulfonylurea suchasacetohexamide,
tolbutamide &gibenclamide are
frequently used.
 They promote the secretion of endogenous
insulin &help in reducing blood glucose level.

 Management with insulin:
 Two types of insulin preparations are
commercially available – short acting &
long acting.
 The short acting insulins are unmodified &
their action lasts for about 6hours.
 The long acting insulins are modified ones &
act for several hours, which depends on
the type of preparation.

 Glycated hemoglobin:
 Refers to the glucose derived products of normal adult
hemoglobin (HbA).
 Glycation isa post-translational, non-enzymatic addition of
sugar residue to amino acids of proteins.
 Among the glycated hemoglobins, the most abundant form is
HbA1c.
 HbA1cisproduced by the condensation of glucose
with N-terminal valine of each β-chain of HbA.

 The rate of synthesis of HbA1c is directly related to
the exposure of RBCto glucose.
 The concentration of HbA1c serves as an indication
of the blood glucose concentration over a period.
 HbA1c concentration is about 3-5%.
 In diabetic patients, HbA1c is elevated (15%).
 HbA1c reflects the mean blood glucose level over 2
months period prior to its measurement.

 Other proteins in the blood are glycated.
 Glycated serum proteins (fructosamine) can also
be measured in diabetics.
 Albumin isthe most abundant plasma
protein, glycated albumin largely contributes to
plasma fructosamine measurements.
 Albumin has shorter half-life than Hb.
 Glycated albumin represents glucose status over 3
weeks prior to its determination.

 Microalbuminuria isdefined as the excretion of
30- 300mg of albumin in urine per day.
 Microalbuminuria represents an intermediary
stage between normal albumin excretion (2.5-30
mg/d) & macroalbuminuria (>300 mg/d).
 The small increase in albumin excretion predicts
impairment in renal function in diabetic
patients.
 It indicates reversible renal damage.

THANK YOU

Diabetes Mellitus - Dr Rohit Bhaskar

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Diabetes Mellitus - Dr Rohit Bhaskar

Similar to Diabetes Mellitus - Dr Rohit Bhaskar (20)

More from Dr Rohit Bhaskar, Physio

More from Dr Rohit Bhaskar, Physio (20)

Recently uploaded

Recently uploaded (20)

Diabetes Mellitus - Dr Rohit Bhaskar