Diabetes mellitus

DEPT. OF PRACTICE OF
MEDICINE
GHMCT
DIABETES MELLITUS
DR. SREELEKSHMI S.R
IST YEAR MD

DIABETES MELLITUS
Diabetes mellitus (DM) refers to
a group of common metabolic
disorders that share the
phenotype of hyperglycemia,
due to defect in insulin secretion,
insulin action or both

1552 BC
– Egyptian physician Hesy-Ra of the 3rd
Dynasty makes the first known mention of
diabetes – found on the Ebers Papyrus – and
lists remedies to combat the ‘passing of too
much urine
• 120 CE
– Greek physician Aretaeus of Cappodocia
gives the first complete medical description of
diabetes, which he likens to ‘the melting down
of flesh and limbs into urine.
H
IS
T
O
R
Y

“As Per The Who, Diabetes Mellitus (Dm) Is
Defined As A Hetrogeneous Metabolic
Disorder Characterised By Common Feature
Of Chronic Hyperglycaemia With Disturbance
Of Carbohydrate, Fat And Protein
Metabolism.”

EPIDEMOLOGY
Global estimate is 415 million individuals with diabetes
in 2017. Regional estimates of the number of individuals with
diabetes (20–79 years of age) are shown (2017).
159 M
26 M
46 M
58 M
39 M
16 M
82 M
(Adapted from the IDF Diabetes Atlas, the International Diabetes Federation, 2017.)

EPIDEMOLOGY
(Adapted from the IDF Diabetes Atlas, the International Diabetes Federation, 2019.)
ACCORDING TO THE IDF DIABETES ATLAS NINTH EDITION 2019
IN 2019, APPROXIMATELY 463 MILLION ADULTS (20-79 YEARS) WERE LIVING WITH
DIABETES ; BY 2045 THIS WILL RISE TO 700 MILLION
Over four million people aged 20–79 years are estimated to die from diabetes-related
causes in 2019. In 2019, over one million children and adolescents have type 1 diabetes.
An estimated 136 million people over 65 years old have diabetes, and the prevalence of
diabetes in this age group varies significantly between IDF Regions

CLASSIFICATION
PRIMARY DIABETES MELLITUS SECONDARY DIABETES MELLI
TYPE 1 DM /
INSULIN DEPENDENT DM/
JUVENILE DIABETES MELLITUS
TYPE 2 DM /
NON INSULIN DEPENDENT DM/
ADULT ONSET DIABETES MELLITUS

TYPE 1 DIABETES MELLITUS
TYPE 1 DM IS CAUSED BY AUTOIMMUNE DESTRUCTION OF
INSULIN PRODUCING BETA CELLS IN THE PANCREAS
RESULTING IN ABSOLUTE INSULIN DEFICIENCY
TYPE 2 DM IS CAUSED BY RESISTANCE TO THE ACTION OF
INSULIN AND AN INABILITY TO PRODUCE SUFFICIENT
INSULIN TO OVERCOME THIS ‘INSULIN RESISTANCE’.

ETIOLOGIC
CLASSIFICATION
OF DIABETES
MELLITUS AS
PER ADA

CRITERIA FOR DIAGNOSIS OF
DIABETES MELLITUS
• Fasting is defined as no caloric intake for at
least 8 hours.
• The 2-hour postprandial glucose test
should be performed using a glucose load
containing the equivalent of 75g anhydrous
glucose dissolved in water

NORMAL GLUCOSE TOLERANCE
FASTING PLASMA GLUCOSE :
< 5.6 mmol/l
<100mg/dl
2 HOUR PLASMA GLUCOSE :
< 7.8 mmol/l
<140 mg/dl
HbA1C:
< 5.6 %

PRE - DIABETES
< 5.6 – 6.9 mmol/l
<100 – 125 mg/dl
< 7.8 – 11.0 mmol/l
<140 – 199 mg/dl
HbA1C:
< 5.7 – 6.4 %
IMPAIRED FASTING GLUCOSE/
IMPAIRED GLUCOSE TOLERANCE

> 7.0 mmol/l
>126 mg/dl
>11.0 mmol/l
>200 mg/dl
HbA1C:
> 6.5 %
DIABETES MELLITUS

Note: The American Diabetes Association (ADA) recommends
diagnosing
‘pre diabetes’ with HbA1c values between 39 and 47 mmol/mol (5.7–6.4%)
and
impaired fasting glucose when the fasting plasma glucose is between 5.6
and 6.9mmol/L (100–125mg/dL).

• BLOOD GLUCOSE
LEVEL
ABOVE NORMAL
• C PEPTIDE : LOW
• +VE AUTO ANTIBODIES
TYPE 1
DIABETES
MELLITUS
• BLOOD GLUCOSE LEVEL
ABOVE NORMAL
• C PEPTIDE : NORMAL/HIGH
• -VE AUTO ANTIBODIES
• INSULIN RESISTANCE
TYPE 2
DIABETES
MELLITUS
• BLOOD GLUCOSE LEVEL
ABOVE NORMAL
• C PEPTIDE : NORMAL
• -VE AUTO ANTIBODIES
• +VE FAMILY HISTORY
MODY

Factors Contributing To Hyperglycemia
HYPERGLYCEMIA
REDUCED INSULIN SECRETION
DECREASED GLUCOSE UTILIZATION
INCREASED GLUCOSE PRODUCTION

TYPE 1
DIABETES MELLITUS
Autoimmunity against the
insulin-producing beta
cells
1
Complete
or
near-total insulin
deficiency

TYPE 2
DIABETES MELLITUS
INSULIN RESISTANCE
IMPAIRED INSULIN
SECRETION
INCREASED HEPATIC
GLUCOSE PRODUCTION

01
02
03
GENETIC DEFECTS OF BETA CELL
DEVELOPMENT OR FUNCTION
CHARACTERISED BY MUTATIONS IN
1. HEPATOCYTE NUCLEAR
TRANSCRIPTION FACTOR (HNF) 4α
(MODY 1)
2. GLUCOKINASE (MODY 2)
3. HNF-1α (MODY 3)
TRANSIENT
NEONATAL DIABETES
DISEASES OF
EXOCRINE PANCREAS
PANCREATITIS
CYSTIC FIBROSIS
HAEMOCHROMATOSIS
GENETIC DEFECTS IN
INSULIN ACTION
OTHER TYPES OF
DIABETES MELLITUS
04

05
06
07
ENDOCRINOPATHIES
1. ACROMEGALY
2. CUSHING’S SYNDROME
3. GLUCAGONOMA
4. PHEOCHROMOCYTOMA
5. HYPERTHYROIDISM
DRUG OR CHEMICAL
INDUCED
GLUCOCORTICOIDS
INFECTIONS
CONGENITAL RUBELLA
CYTOMEGALOVIRUS
COXSACKIEVIRUS
OTHER GENETIC
SYNDROMES
WOLFRAM’S SYNDROME
DOWN’S SYNDROME
KLINEFELTER’S
SYNDROME TURNER’S
SYNDROME
FRIEDREICH’S ATAXIA
OTHER TYPES OF
DIABETES MELLITUS
08

GESTATIONAL DIABETES MELLITUS
Glucose intolerance developing during the second or
third trimester of pregnancy is classified as
gestational diabetes mellitus (GDM)
INCREASED
INSULIN
DEMANDS
IMPAIRED GLUCOSE
TOLERANCE /
DIABETES
• The American Diabetes Association (ADA) recommends
that diabetes diagnosed within the first trimester be
classified as preexisting pregestational diabetes rather
than GDM

GESTATIONAL DIABETES MELLITUS
 Most women with GDM revert to normal glucose
tolerance postpartum but have a substantial risk
(35–60%) of developing DM in the next 10–20
years.
 Children born to a mother with GDM also have an
increased risk of developing metabolic syndrome
and type 2 DM later in life.

FUNCTIONAL ANATOMY AND
PHYIOLOGY

A. The normal adult pancreas contains
about 1 million islets, which are
scattered throughout the exocrine
parenchyma.
B. The core of each islet consists of β
cells that produce insulin, and is
surrounded by a cortex of endocrine
cells that produce other hormones,
including glucagon (α cells),
somatostatin (δ cells) and pancreatic
polypeptide (PP cells).
PANCREATIC STRUCTURE AND ENDOCRINE
FUNCTION.

SCHEMATIC REPRESENTATION OF THE PANCREATIC β CELL

INSULIN SECRETION
GLUCOSE
LEVEL
>
70mg/dL
GLUCOSE
• GLUCOSE IS THE KEY
REGULATOR OF INSULIN
SECRETION BY BETA CELLS OF
PANCREAS
• GLUCOSE LEVELS >3.9 mmol/L
(70 mg/dL) STIMULATES
INSULIN SYNTHESIS

PROCESSING OF PRO-INSULIN INTO
INSULIN AND C-PEPTIDE
Pro-insulin in the pancreatic β cell is cleaved
to release insulin and equi molar amounts
of inert C-peptide (connecting peptide).
Measurement of C-peptide can be used to
assess endogenous insulin secretory
capacity

01
02
03
INSULIN BIOSYNTHESIS
FROM BETA CELLS OF ISLETS OF PANCREAS
PRE PRO INSULIN
PRO INSULIN
LEVELS OF PRO INSULIN
ELEVATED IN BOTH TYPE 1 AND
DUE TO BETA CELL
DYSFUNCTION
INSULIN & C- PEPTIDE
THE MATURED INSULIN
MOLECULE & C- PEPTIDE ARE
STORED TOGETHER AND CO-
SECRETED FROM THE
SECRETORY GRANULES IN BETA
CELLS.
C- PEPTIDE
• IT IS A USEFUL MARKER OF
ENDOGENOUS INSULIN
SECRETION
• BECAUSE IT IS CLEARED
MORE SLOWLY THAN
INSULIN
• IT ALLOWS THE
DISCRIMINATION OF
ENDOGENOUS AND
EXOGENOUS SOURCES OF
INSULIN IN EVALUATION OF
HYPOGLYCEMIA
PRE PRO INSULIN
PRO INSULIN
INSULIN & C - PEPTIDE

INSULIN ACTION
GLUCOSE
Once insulin is secreted into the portal venous system, ~50% is
removed and degraded by the liver. Unextracted insulin enters the
systemic circulation where it binds to receptors in target sites.
Insulin binding to its receptor stimulates intrinsic tyrosine
kinase activity, leading to receptor auto phosphorylation and
the recruitment of intracellular signaling molecules, such as
insulin receptor substrates (IRS).
IRS and other adaptor proteins initiate a complex cascade
of phosphorylation and dephosphorylation reactions,
resulting in the widespread metabolic and mitogenic
effects of insulin.
50% is removed and degraded
Remaining insulin enters
the systemic circulation
binds to receptors in target
sites
stimulates intrinsic Tyrosine kinase activity
Insulin Receptor Substrates (IRS)

• GLUCOSE HOMOEOSTASIS IS ACHIEVED THROUGH THE COORDINATED
ACTIONS OF MULTIPLE ORGANS ,BUT MAINLY REFLECTS
A BALANCE BETWEEN THE
 ENTRY OF GLUCOSE INTO CIRCULATION FROM THE LIVER,
SUPPLEMENTED BY INTESTINAL ABSORPTION OF GLUCOSE
AFTER MEALS
 UPTAKE OF GLUCOSE BY PERIPHERAL TISSUES PARTICULARLY BRAIN
AND MUSCLES

REGULATION OF GLUCOSE
HOMOEOSTASIS
02
HEPATIC GLUCOSE
PRODUCTION
(GLUCONEOGENESIS)
PERIPHERAL TISSUE
GLUCOSE UPTAKE AND
UTILIZATION
ENERGY INTAKE
FROM INGESTED
FOOD
GLUCOSE
HOMOEOSTASIS
INSULIN
MOST IMPORTANT REGULATOR
NEURAL INPUT
METABOLIC SIGNALS
OTHER HORMONES
EG. : GLUCAGON

ACTIONS OF INSULIN
Major metabolic pathways of fuel
metabolism and the actions of
insulin. ⊕ indicates stimulation and
⊖ indicates suppression by insulin.
In response to a rise in blood
glucose, e.g. after a meal, insulin is
released, suppressing
gluconeogenesis and promoting
glycogen synthesis and storage.
Insulin promotes the peripheral
uptake of glucose, particularly in
skeletal muscle, and encourages
storage (as muscle glycogen).
It also promotes protein
synthesis and lipogenesis, and
suppresses lipolysis.

01
02
03
Glucagon is secreted by pancreatic alpha cells normally only, when blood
glucose or insulin levels are low or during exercise, is increased in DM and
stimulates glycogenolysis and gluconeogenesis by the liver and to a small
degree by the renal medulla
Postprandially, the glucose load elicits a rise in insulin and fall in glucagon, leading to a
reversal of these processes. Insulin, an anabolic hormone, promotes the storage of
carbohydrate and fat and protein synthesis.The major portion of postprandial glucose is used
by skeletal muscle, an effect of insulin-stimulated glucose uptake. Other tissues, most notably
the brain, use glucose in an insulin-independent fashion.
In the fasting state, low insulin levels, together with modest increases in
glucagon, increase glucose production by promoting hepatic
gluconeogenesis and glycogen breakdown (glycogenolysis) and reducing
glucose uptake in insulin sensitive tissues (skeletal muscle and fat),
thereby promoting mobilization of stored precursors such as amino acids
and free fatty acids (lipolysis)
Glucose Homoeostasis

01
02
03
FAT METABOLISM
Insulin is the major regulator of fatty acid metabolism.
Low insulin level during
fasting permits lipolysis &
release of fatty acids and
glycerol into circulation
High insulin levels after
meals promote
triglyceride accumulation.
partial oxidation of fatty acids in the liver provides energy
to drive gluconeogenesis and also produces ketone bodies
When the rate of production by the liver exceeds their
removal, hyperketonaemia results
This occurs physiologically during starvation, when low
insulin levels and high catecholamine levels

AETIOLOGY AND
PATHOGENESIS OF
DIABETES

TYPE 1
DIABETES MELLITUS
TYPE 1 DM IS A T CELL-
MEDIATED AUTO IMMUNE
DISEASE INVOLVING
IMMUNE MEDIATED
DESTRUCTION OF INSULIN
SECRETING BETA CELLS IN
THE PANCREATIC ISLETS

TYPE 1 DM IS THE RESULT
OF INTERACTIONS OF
GENETIC, ENVIRONMENTAL
& IMMUNOLOGIC FACTORS
ULTIMATELY LEADING TO
IMMUNE MEDIATED
DESTRUCTION OF
PANCREATIC BETA CELLS
AND INSULIN DEFICIENCY
TYPE 1
DIABETES MELLITUS

TYPE 1
DIABETES MELLITUS
AGE
TYPE 1 DM CAN
DEVELOP AT ANY AGE,
BUT MORE COMMONLY
DEVELOPS BEFORE 20
YEARS OF AGE
Marked hyperglycaemia, accompanied by the classical
symptoms of diabetes, occurs only when 80–90% of the
functional capacity of β cells has been lost.

TYPE 1
DIABETES MELLITUS
TRIGGER
IN SUSCEPTIBLE
INDIVIDUALS, THE
AUTOIMMUNE PROCESS IS
THOUGHT TO BE TRIGGERED
BY AN INFECTIOUS OR
ENVIRONMENTAL STIMULUS
THE TRIGGERING EVENTS
ARE OFTEN ASSOCIATED
WITH INCREASED INSULIN
REQUIREMENTS, AS MIGHT
OCCUR DURING INFECTIONS
OR AT PUBERTY

TYPE 1
DIABETES MELLITUS
GENETIC
CONSIDERARIONS
THE MAJOR SUSCEPTIBILITY GENE FOR
TYPE 1 DM IS LOCATED IN THE HLA REGION
ON CHROMOSOME 6.
Most individuals with type 1 DM have
the HLA DR3 and/or DR4 halotype
Although the risk of developing type 1
DM is increased tenfold in relatives of
individuals with the disease, the risk is
relatively low: 3–4% if the parent has
type 1 DM and 5–15% in a sibling
 The concordance of type 1 DM in identical
twins ranges between 40 and 60%

The pathology in the pre-diabetic
pancreas is characterised by an
inflammatory lesion within islets,
‘insulitis’
With infiltration of the islets by
mononuclear cells containing
activated macrophages, helper
cytotoxic and suppressor T
lymphocytes, natural killer cells
and B lymphocytes.

PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
INFILTRATION OF
LYMPHOCYTES IN
PANCREATIC ISLETS /
INSULITIS
DESTRUCTION OF BETA
CELLS AND ISLET
ATROPHIES

PROINSULIN
INSULIN
GLUTAMIC ACID
DECARBOXYLASE (GAD;
the biosynthetic enzyme for
the neurotransmitter GABA),
ICA-512/IA-
2(homology
with tyrosine
phosphatases),
beta cell–
specific zinc
transporter
(ZnT-8).
PANCREATIC ISLET MOLECULES TARGETED BY THE AUTOIMMUNE PROCESS INCLUDE :
GAD
Insulin
IA-2/ICA-512
ZnT-8
serve as a marker of the autoimmune process of type 1 DM
Islet cell antibodies can be present long before the clinical presentation
of type 1 diabetes, and their detection can be useful in confirming a
diagnosis of type 1 diabetes

1.
• Viruses (coxsackie, rubella, enteroviruses most prominently)
2.
• Bovine milk proteins
3.
• Nitrosourea compounds
4.
• Vitamin D deficiency
5.
• Other environmental toxins
Putative environmental triggers include :

INSUFFICIENT INSULIN
fatigue, polyuria, nocturia,
thirst and polydipsia,
susceptibility to urinary and
genital tract infections, and
later tachycardia and
hypotension.
Weight loss
Metabolic disturbances in Type 1 DM

SLOW ONSET TYPE 1 DM / LATENT AUTOIMMUNE DIABETES OF ADULTHOOD
LADA is defined as the presence of islet autoantibodies in high titre ,
without rapid progression to insulin therapy (which would usually signify
type 1 diabetes).
Patients with LADA can often present and be managed similarly to those
with type 2 diabetes, but they do progress more rapidly to requiring insulin
treatment for glucose control
While type 1 diabetes is classically thought of as a disease of children
and young adults (most commonly presenting between 5 and 7 years
of age and at or near puberty), it can manifest at any age, with as much
as half of cases thought to develop in adults.
It is also possible for patients who have a more insidious onset of
diabetes to have an autoimmune aetiology

200
INSULIN RESISTANCE
ABNORMAL INSULIN SECRETION
TYPE 2
DIABETES MELLITUS
Type 2 DM likely encompasses a range
of disorders with the common phenotype of hyperglycemia

In general, Latinos have greater insulin
resistance
&
East Asians and South Asians have more
beta cell dysfunction, but both defects
are present in both populations.
East and South Asians appear to develop type 2
DM at a younger age and a lower BMI
*According to HARRISON Principle Of Internal Medicine

RISK
FACTORS
OBESITY
PHYSICAL
INACTIVITY
RACE/
ETHINICITY
PREVIOUS
IFG /
IGT
HISTORY OF
GDM
HTN
140/90mmhg
ABNORMAL
LIPID
PROFILE
TGL
>250 MG/DL
PCOS /
ACANTHOSIS
FAMILY
HISTORY

TYPE 2
DIABETES MELLITUS
METABOLIC
ABNORMALITIES

 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.
TYPE 2
DIABETES MELLITUS

TYPE 2
DIABETES MELLITUS
Insulin resistance impairs
glucose utilization by insulin
sensitive tissues
and
increases hepatic glucose
output
both effects contribute to the
hyperglycemia

GENETIC
CONSIDERATIONS
IDENTICAL
TWINS
RISK
• THE CONCORDANCE OF
TYPE 2 DM IN IDENTICAL TWINS IS
BETWEEN 70 AND 90%.
• IF BOTH PARENTS HAVE TYPE 2
DM, THE RISK APPROACHES
40%.
IDENTICAL
TWINS
BOTH
PARENTS
SINGLE
PARENT
70% - 90%
90%
70%
40%
* THE DISEASE IS POLYGENIC AND MULTIFACTORIAL,
BECAUSE IN ADDITION TO GENETIC SUSCEPTIBILITY,
ENVIRONMENTAL FACTORS (SUCH AS OBESITY, POOR
NUTRITION, AND PHYSICAL INACTIVITY) MODULATE THE
PHENOTYPE.

GENETIC
CONSIDERATIONS
RISK
• MOST PROMINENT AMONG GENES THAT PREDISPOSE
TO TYPE 2 DM IS THE TRANSCRIPTION FACTOR 7–LIKE 2
GENE
• INSULIN RESISTANCE, AS DEMONSTRATED BY REDUCED
GLUCOSE UTILIZATION IN SKELETAL MUSCLE, IS
PRESENT IN MANY NONDIABETIC, FIRST-DEGREE
RELATIVES OF INDIVIDUALS WITH TYPE 2 DM.

THE IN UTERO
ENVIRONMENT ALSO
CONTRIBUTES,
AND
EITHER INCREASED OR
REDUCED BIRTH WEIGHT
INCREASES THE RISK OF
TYPE 2 DM IN ADULT LIFE.

Children of
pregnancies
complicated by
gestational
hyperglycemia also
exhibit an increased
risk of type 2 DM.

01
02
03
IMPAIRED INSULIN
SECRETION
INSULIN
RESISTANCE
EXCESSIVE HEPATIC
GLUCOSE
PRODUCTION
TYPE 2
DIABETES MELLITUS
IS CHARACTERIZED BY :
04
05
ABNORMAL FAT
METABOLISM
SYSTEMIC
LOWGRADE
INFLAMMATION
• Obesity, particularly visceral or central (as evidenced by
the hip-waist ratio), is very common in type 2 DM (≥80%
of patients are obese).

Natural history of type 2 diabetes
1. In the early stage of the
disorder, the response to
progressive insulin
resistance is an increase in
insulin secretion by the
pancreatic cells, causing
hyperinsulinaemia.
2. Eventually, the β cells are
unable to compensate
adequately and blood
glucose rises, producing
hyperglycaemia.
3. With further β-cell failure,
glycaemic control
deteriorates and treatment
requirements escalate.

PATHOPHYSIOLOGY - TYPE 2 DIABETES MELLITUS
GLUCOSE TOLERANCE REMAINS
NEAR-NORMAL
IMPAIRED GLUCOSE
TOLERANCE
OVERT
DIABETES
In the early stages of
the disorder
Despite insulin resistance, the
pancreatic beta cells compensate
by increasing insulin output
As insulin resistance and
compensatory hyperinsulinemia
progress, the pancreatic islets in
certain individuals are unable to
sustain the hyperinsulinemic state.
Elevations in postprandial glucose
A further decline in insulin
secretion and an increase in
hepatic glucose production lead to
Fasting hyperglycemia

Insulin Resistance And The Metabolic Syndrome
More common in individuals who are obese
HYPERTENSION
DYSLIPIDAEMIA
NON ALCOHOLIC FATTY LIVER
DISEASE
PCOS

Induces insulin resistance
Release large amounts of free fatty acids
Intra-abdominal ‘central’ adipose tissue
• Adipokines released by adipose tissues also influence insulin
sensitivity of other tissues

Induces insulin resistance
accumulation of free fatty acids in skeletal muscles
Down regulation of insulin sensitive kinases
PHYSICAL INACTIVITY

TYPE 2
DIABETES MELLITUS
INCREASED HEPATIC GLUCOSE
OUTPUT PREDOMINANTLY
ACCOUNTS FOR INCREASED FPG
LEVELS
DECREASED PERIPHERAL GLUCOSE
UTILIZATION RESULTS IN
POSTPRANDIAL HYPERGLYCEMIA.

IMPAIRED INSULIN SECRETION
Beta cell mass is decreased by ~50% in individuals with long-standing type 2 DM.
overall beta cell function is reduced by as much as 50% at the onset of type 2 DM.
In type 2 DM, insulin secretion initially increases in response to insulin resistance to
maintain normal glucose tolerance.
Islet amyloid polypeptide or amylin, co-secreted by
the beta cell, forms amyloid fibrillar deposits found in
the islets of individuals with long-standing type 2 DM.

The history and physical examination
should assess for symptoms or signs
of acute hyperglycemia
and
screen for chronic microvascular and
macrovascular complications and
conditions associated with DM

1.Current weight
2.Recent changes in weight
3.Family history of DM and its complications,
4.Sleep history
5.Risk factors for cardiovascular disease
6.Exercise
7.Smoking status
8.History of pancreatic disease
9.Ethanol use.
A complete medical history should be obtained with
special emphasis on DM-relevant aspects such as

1.
• ) Patients of type 1 DM usually manifest at early age,generally
below the age of 35.
2.
• The onset of symptoms is often abrupt
3.
• At presentation, these patients have polyuria, polydipsia and
polyphagia.
4
• The patients are not obese but have generally progressive loss
of weight
5
• These patients are prone to develop metabolic complications
such as ketoacidosis and hypoglycaemic episodes.

1.
•.This form of diabetes generally manifests in middle life or beyond,
usually above the age of 40.
2.
•The onset of symptoms in type 2 DM is slow and insidious.
3.
• Generally, the patient is asymptomatic when the diagnosis is made on the basis of
glucosuria or hyperglycaemia during physical examination, or may present with polyuria
and polydipsia
4
• The patients are frequently obese and have unexplained weakness and loss of
weight.
5
• Metabolic complications such as ketoacidosis are infrequent

Contrasting Features of Type 1 and Type 2 Diabetes Mellitus.

The classic triad of symptoms
associated with diabetes mellitus
consists of:
• ! thirst
• ! polyuria (often nocturia)
• ! weight loss

PRESENTING PROBLEMS IN DIABETES MELLITUS
HYPERGLYCEMIA

HYPERGLYCEMIA
DIAGNOSIS :
• THE DIAGNOSIS OF DIABETES IS SIMPLE: IT IS BASED ON
CONFIRMATION OF HYPERGLYCAEMIA USING
EITHER
FASTING GLUCOSE
RANDOM GLUCOSE
AN OGTT
HBA1C

Symptoms of hyperglycemia include :
POLYUREA
POLYDIPSIA
POLYPHAGIA
3P’S

WEIGHTLOSS
BLURRY VISION
FATIGUE

SLOW HEALING OF
SKIN LESIONS AFTER
MINOR TRAUMA
FREQUENT SUPERFICIAL
INFECTIONS
(VAGINITIS,BALANITIS,
FUNGAL INFECTION)

Metabolic derrangements :
CATABOLIC STATE OF
PATIENT due to :
• URINARY LOSS OF GLUCOSE
AND CALORIES
• MUSCLE BREAKDOWN DUE TO
PROTEIN DEGRADATION
• DECREASED PROTEIN
SYNTHESIS
HYPERGLYCEMIA
(OSMOTIC DIURESIS)

BLURRED VISION RESULTS FROM :
CHANGES IN THE WATER CONTENT OF THE LENS
AND
RESOLVES AS HYPERGLYCEMIA IS CONTROLLED.

HYPERGLYCEMIA
Physical signs in patients with type 2 diabetes at diagnosis depend on the mode
of presentation.
• More Than 80% Are Overweight And The Obesity Is
Often Central ( Truncal Or Abdominal).
• Hypertension Is Present In At Least 50% Of
Patients With Type 2 Diabetes
• Dyslipidaemia Is also Common
• Acanthosis nigricans in insulin resistance

ACANTHOSIS NIGRICANS
Acanthosis nigricans has a predilection for the axillae, groins and other body folds. In
this condition, there is hyperpigmentation with diffuse velvety thickening of the
Skin.

COMPLICATIONS OF DIABETES MELLITUS

DIABETIC
KETOACIDOSIS
HYPEROSMOLAR
NON KETOTIC COMA
HYPOGLYCAEMIA.
ACUTE METABOLIC
COMPLICATIONS

DIABETIC KETOACIDOSIS
HYPERGLYCAEMIC HYPEROSMOLAR STATE
HYPOGLYCAEMIA

Diabetic ketoacidosis
DKA is characteristic of type 1 diabetes and is often the presenting problem in newly
diagnosed patients.
• HYPERKETONAEMIA (≥ 3.0 mmol/L)
or ketonuria (more than 2+ on standard
urine sticks)
• HYPERGLYCAEMIA (blood glucose ≥
11 mmol/L (approximately 200 mg/dL))
• METABOLIC ACIDOSIS (venous
bicarbonate < 15 mmol/L and/or venous
pH < 7.3 (H+ > 50 nmol/L)).
The Cardinal Features are :

Hyperosmolar hyperglycaemic
nonketotic coma
• It is caused by severe dehydration resulting from sustained
hyperglycaemic diuresis.
•
• The loss of glucose in urine is so intense that the patient is unable
to drink sufficient water to maintain urinary fluid loss.
• The usual clinical features of ketoacidosis are absent but
prominent central nervous signs are present.

HYPOGLYCEMIA
• Hypoglycaemic episode may develop in patients of type 1 DM.
• It may result from excessive administration of insulin, missing a
meal, or due to stress.

DIABETIC RETINOPATHY
Diabetes mellitus is by far the commonest disease that can affect any part of
the eye and produces vascular changes in the fundi of most patients within a
few years of diagnosis.
• Venous dilatation is the earliest change (4.51), which may persist while
microaneurysms (dots) and retinal haemorrhages (blots) develop.
These changes of dot and blot haemorrhages are collectively called
background retinopathy, which does not cause any visual
impairment unless a haemorrhage involves the macula.

VENOUS DILATATION IS THE
EARLIEST CHANGE

MICRO ANEURYSMS

DOT AND BLOT HEMORRHAGES

Soft exudates are seen as fluffy, white spots with indistinct margins (4.57, 4.58) reflecting
infarcted areas caused by the occlusion of arteriolar precapillaries. These occur early in the
course of the disease, particularly if the patient also has hypertension. Patients with soft
exudates should be examined more frequently than once a year.
Diabetes mellitus:
soft exudates
(micro infarcts)
with
indistinct margins

Hard (serous) exudates are small, white or yellowishwhite dots with well-defined
margins scattered singly, in clusters (4.59), or in circinate rings
Diabetes mellitus:
hard exudates. Note
the circinate ring at
the upper temporal
pole

Neovascularization is a common and dangerous manifestation of diabetic
retinopathy and usually occurs after the reactive stage when there are hard and soft
exudates, haemorrhages and venous dilatation
Venous dilatation
with beading (note
a-v nipping), soft
and hard exudates
and haemorrhages
(preproliferative
retinopathy}

DIABETIC NEPHROPATHY
• Diabetic nephropathy is a leading cause of chronic renal failure.
• It is characterized by thickening of the glomerular basement
membrane, mesangial expansion, and glomerular sclerosis.
• These changes cause glomerular hypertension and progressive
decline in GFR.
• Systemic hypertension may accelerate progression.
Diagnosis is by detection of urinary albumin.
–Albumin concentration 30 to 300 mg/24 h signifies
microalbuminuria and early diabetic nephropathy.

DIABETIC NEUROPATHY
Diabetic neuropathy is the result of
– nerve ischemia from microvascular disease,
– direct effects of hyperglycemia on neurons, and
– intracellular metabolic changes that impair nerve function.
There are multiple types, including
– symmetric polyneuropathy
– autonomic neuropathy.

DIABETIC FOOT
THE MAXIM, 'LOOK AT THE DIABETIC'S FEET FIRST
THEN AT THEIR FACE'
The breakdown of the diabetic foot is caused by a
combination of dryness, neuropathy, infection,
vascular maldistribution and inadequate foot care.

DIABETIC FOOT
NEUROPATHIC ULCER also called a trophic, perforating or pressure ulcer
characteristically occurs on the plantar surface (11.8)
and at the base of the big toe (11.9).
11.8
Deep ulcer crater,
reaching the muscle,
with non healing,
callous, undermined
edge
11.9
Ulcer with well
defined,
undermined
edge penetrating to
subcutaneous tissues

CHARCOT’S ARTHROPATHY
Diabetic neuropathy causes disarticulation producing a Charcot joint
In diabetes mellitus, the mid tarsal joints are involved with gross destructive changes, new bone
formation, joint instability and deformity
clawing of toes, falling arches and drooping malleoli

DIABETES DERMOPATHY
Necrobiosis lipoidica diabeticorum is an uncommon cutaneous lesion in diabetic patients
(approximately 0.2%) but it is strongly associated with the disease.
Most of the patients are less than 40 years of age and females predominate over males (ratio
3:1).

DIABETES DERMOPATHY
Necrobiosis lipoidica is often bilateral but not necessarily symmetrical (11.23). The legs are
affected in approximately 85% of patients and in the remaining 15% the lesions may develop
on the arms, head or abdomen.

DIABETES DERMOPATHY
The initial lesion is a reddish fleshy plaque, somewhat round or oval in shape (11.24), with sharply
defined and elevated borders. It extends outwards in an annular fashion, the borders becoming
irregular but often remaining elevated and erythematous, while the centre becomes depressed from
atrophy of the epidermis, which looks transparent and takes a yellowish hue.

DIABETES DERMOPATHY
Granuloma annulare has been observed in diabetic patients.
The lesions occur characteristically on the dorsum of the hands and fingers, the extensor surfaces
of the elbows and knees, on the dorsal surface of the foot (11.28) and around the
ankles (11.29)

DIABETES DERMOPATHY
Diabetic bullae (bullosis diabeticorum), occur in longstanding diabetics with neuropathy.
They may be unilateral or bilateral and usually appear on the toes, plantar and dorsal surfaces
of the foot, and on the fingers

PRAYER SIGN
Painless limited extension of the proximal
meta carpophalangeal joints and/or inter
phalangeal joints with spontaneous flexion of
the fingers. There is decreased ability to fully
flex or fully extend the fingers. This is the so-
called “Namaste” or “Prayer” sign.
This sign gives an indication of metabolic
control of diabetes and microvascular
disease.

INVESTIGATIONS
1. URINE GLUCOSE
• Testing the urine for glucose with dipsticks is a common
screening procedure for detecting diabetes.
• If possible, testing should be performed on urine passed
1–2 hours after a meal to maximise sensitivity.
• Glycosuria always warrants further assessment by blood
testing.

INVESTIGATIONS
2. BLOOD GLUCOSE
• Laboratory glucose testing in blood relies on an
enzymatic reaction (glucose oxidase) and is cheap,
usually automated and highly reliable.

INVESTIGATIONS
3.GLYCATED HAEMOGLOBIN
• Glycated haemoglobin provides an accurate and
objective measure of glycaemic control over a period of
weeks to months.
• In diabetes, the slow non-enzymatic covalent attachment
of glucose to haemoglobin (glycation) increases the
amount in the HbA1 (HbA1c) fraction relative to non
glycated adult haemoglobin (HbA0). These fractions can
be separated by chromatography

INVESTIGATIONS
3.GLYCATED HAEMOGLOBIN
• The rate of formation of HbA1c is directly proportional to
the ambient blood glucose concentration;
• A rise of 11 mmol/mol in HbA1c corresponds to an
approximate average increase of 2 mmol/L (36 mg/dL) in
blood glucose.
• Although HbA1c concentration reflects the integrated
blood glucose control over the lifespan of erythrocytes
(120 days), HbA1c is most sensitive to changes in
glycaemic control occurring in the month before
measurement

INVESTIGATIONS
4.INTERSTITIAL GLUCOSE
• A relatively new approach to measuring glucose levels in
diabetes is through the use of interstitial continuous
glucose monitoring (CGM). CGM systems use a tiny
sensor inserted under the skin to check glucose levels in
interstitial fluid.

INVESTIGATIONS
5.C PEPTIDE
• C-peptide is the connecting peptide that is cleaved in the
production of insulin from pro-insulin .
• It can be readily measured in blood and urine by
sensitive immunoassays.
• Serum C-peptide is a marker of endogenous insulin
secretion.

INVESTIGATIONS
6.ISLET AUTOANTIBODIES
• As type 1 diabetes is a characterised by autoimmune
destruction of the pancreatic β cells, it can be useful in
the differential diagnosis of diabetes to establish
evidence of such an autoimmune process.

INVESTIGATIONS
7. URINE AND BLOOD KETONES
• Acetoacetate can be identified in urine by the
nitroprusside reaction, using either tablets or dipsticks.
• Ketonuria may be found in normal people who have
been fasting or exercising strenuously for long periods,
vomiting repeatedly, or eating a diet high in fat and low
in carbohydrate
• Ketonuria is therefore not pathognomonic of diabetes
but, if it is associated with glycosuria, the diagnosis of
diabetes is highly likely.

DIABETES MELLITUS - MANAGEMENT
THE GOALS OF THERAPY FOR TYPE 1 AND TYPE 2 DM
ARE TO :
(1)
Eliminate
symptoms related
to hyperglycemia
(2)
Reduce or eliminate the
long-term micro vascular
and macro vascular
complications of DM
(3)
Allow the patient to
achieve as normal a
lifestyle as possible
• SYMPTOMS OF DIABETES USUALLY
RESOLVE WHEN THE PLASMA GLUCOSE
IS <11.1 MMOL/L (200 MG/DL)

TYPE 1
DIABETES MELLITUS
The American Diabetes
Association (ADA) uses the term
“Lifestyle Management” to
refer to aspects of diabetes
care, including:
(1) diabetes self-management
education (DSME)
(2) nutrition therapy; and
(3) psychosocial care.

GENERAL DIETARY GUIDELINES
• VEGETABLES
• FRUITS
• WHOLE GRAINS
• LEGUMES
• LOW FAT DAIRY PRODUCTS
• FOOD HIGHER IN FIBER
• LOWER IN GLYCEMIC CONTENT

FAT IN DIET
• MEDITERRANEAN – STYLE DIET RICH IN
MONOUNSATURATED FATTY ACIDS
• MINIMAL TRANS FAT CONCEPTION

CARBOHYDRATE IN DIET
• MONITOR CARBOHYDRATE DIET IN REGARD
TO CALORIES
• MINIMAL INTAKE OF SUCROSE CONTAINING FOODS
• FRUCTOSE IS PREFFERD OVER SUCROSE
• CONSIDER USING GLYCEMIC INDEX TO PREDICT
HOW CONSUMPTION OF A PARTICULAR FOOD MAY
AFFECT BLOOD GLUCOSE

ADULTS SHOULD LIMIT
THEIR SODIUM INTAKE TO
NO MORE THAN 6 G DAILY.
SALT INTAKE

PHYSICAL ACTIVITY
cardiovascular risk reduction, reduced
blood pressure, maintenance of
muscle mass, reduction in body fat
weight loss.
Exercise has multiple positive benefits
including
For individuals with type 1 or type 2
DM, exercise is useful for lowering
plasma glucose (during and following
exercise) and increasing
insulin sensitivity.

• Resistance exercise
• Flexibility exercise
• Balance training
• Reduced sedentary behavior throughout the day are
advised.
In patients with diabetes, the ADA recommends
150 min/week (distributed over at least 3 days) of moderate aerobic physical
activity with no gaps longer than 2 days.

RESISTANCE EXERCISE
FLEXIBILITY EXERCISE

HOMOEOPATHIC APPROACH OF
TREATMENT OF DIABETES
MELLITUS

MIASMATIC BACKGROUND
Samuel Hahnemann, stated in his ‘Chronic Disease’ that Diabetes is a
Psoric manifestations.
According to many Stalwarts, Diabetes belongs to a mixed
miasmatic state of Psora and Syphilis.
DM comprises the pseudo psoric miasm.
The pseudopsoric miasm is also known as Tubercular
miasm. It is a combination of both Psora and Syphilitic
miasm.

Chronic miasmatic states Psora, Sycosis, Syphilis and the
resultant combination of these miasm play the important role
in the development of Diabetes mellitus.
Syphilis by its destructive process cause a diminution of the
effective mass of islets of langerhans, which leads to absolute
lack of insulin resulting I.D.D.M.,
Psora leads to functional disturbances resulting diminished
effectiveness of insulin and developing N.I.D.D.M.,
Sycosis by its incoordination results in endocrinal disharmony
and dysfunctional feed back mechanism, thereby insulin
antagonist increases in circulation leading to relative decrease
in biological effectiveness of insulin.

Now the basic pathology behind all Complications is angiopathy [both micro
and macro] which comes under the domain of syphilitic miasm.

Diabetes mellitus

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