Here are potential responses to the questions: 1. Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Complications of diabetes include: - Acute complications like diabetic ketoacidosis and hyperosmolar hyperglycemic state. - Microvascular complications like diabetic retinopathy (leading to blindness), nephropathy (leading to renal failure) and neuropathy (causing pain and impaired healing). - Macrovascular complications like atherosclerosis leading to cardiovascular disease (heart attacks and strokes), peripheral vascular disease (leg pain and poor wound healing). 2. Diabetes is classified into Type 1 (caused by auto

1. DIABETES

2. • A chronic condition, characterized by hyperglycaemia and
due to impaired insulin secretion, with or without insulin
resistance.
• As per the WHO, diabetes mellitus (DM) is defined as a
heterogeneous metabolic disorder characterized by common
feature of chronic hyperglycemia with disturbance of
carbohydrate, fat and protein metabolism.

3. • DM is expected to continue as a major health problem
owing to its serious complications, especially end-stage
renal disease, IHD, gangrene of the lower extremities,
and blindness in the adults.

4. Classification and Etiology
• TYPE 1 DIABETES MELLITUS (10%)
[Insulin-dependent, or juvenile-onset diabetes]
➢ TYPE 1A: Immune-Mediated
➢ Type 1B: Idiopathic
• Type 2 DIABETES MELLITUS (80%)
[Non-insulin dependent, maturity-onset diabetes]

5. • OTHER SPECIFIC TYPES OF DIABETES (10%)
A. Genetic defect of Beta cell function
B. Genetic defect in insulin action
C. Disease of exocrine pancreas
D. Endocrinopathies
E. Drug or chemical induced
F. Infections
G. Uncommon forms of immune-mediated DM
H. Other genetic syndromes
• GESTATIONAL DIABETES MELLITUS

6. TYPE- I DM
• It constitutes about 10% cases of DM.
• It was previously termed as juvenile-onset diabetes (JOD) due to
its occurrence in younger age, and was called
insulin- dependent DM (IDDM) because it was known that these
patients have absolute requirement for insulin replacement as
treatment.

7. Type 1 DM
• Type 1 DM is further divided into 2 subtypes:
• Subtype 1A (immune-mediated) DM characterized by autoimmune
destruction of β-cells which usually leads to insulin deficiency.
• Subtype 1B (idiopathic) DM characterized by insulin deficiency with
tendency to develop ketosis but these patients are negative for
autoimmune markers.
• Type 1 DM occurs commonly in patients under 30 years of age.
• In fact, 5-10% patients who develop DM above 30 years of age are of
type 1A DM and hence the term JOD has become obsolete.

8. TYPE- II DM
• It was previously called maturity-onset diabetes (MOD), or non-insulin
dependent diabetes mellitus (NIDDM) of obese and non-obese type.
• Although type 2 DM predominantly affects older individuals, it is now
known that it also occurs in obese adolescent children; hence the term
MOD for it is inappropriate.
• Moreover, many type 2 DM patients also require insulin therapy to control
hyperglycaemia or to prevent ketosis and thus are not truly non-insulin
dependent.

10. OTHER SPECIFIC ETIOLOGIC TYPES OF DM
• 10% cases of DM have a known specific etiologic defect.
• One important subtype in this group is maturity-onset diabetes of
the young (MODY) which has autosomal dominant inheritance,
early onset of hyperglycaemia and impaired insulin secretion.

11. GESTATIONAL DM
• About 4% pregnant women develop DM due to metabolic
changes during pregnancy.
• Although they revert back to normal glycaemia after delivery,
these women are prone to develop DM later in their life.

12. DIFFERENCE
BETWEEN
TYPE I & TYPE II

14. PATHOPHYSIOLOGY
• Depending upon etiology of DM, hyperglycaemia may result
from the following:
• Reduced insulin secretion
• Decreased glucose use by the body
• Increased glucose production.

15. ➢ OCCURRENCE OF DISEASE
• Insulin is the major hormone that regulates the uptake of glucose from the
blood into most cells of the body, especially the liver, muscle and adipose
tissue.
• Glucose obtained from 3 places:
1. The intestinal absorption of food, the breakdown of glycogen;
2. The storage form of glucose found in the liver, and gluconeogenesis,
3 The generation of glucose from non-carbohydrate substrates in the body.

18. • Insulin is released into the blood by β-cells in the pancreas, in response to
rising levels of blood glucose, typically after eating. Lower glucose levels
result in decreased insulin release from the β-cells and in the breakdown
of glycogen to glucose.
• This process is mainly controlled by the hormone glucagon, which acts in
the opposite manner to insulin.
• If the amount of insulin available is insufficient, if cells respond poorly to
the effects of insulin (insulin sensitivity or insulin resistance) or if the
insulin itself is defective, then glucose will not be absorbed properly by
the body cells that require it, and it will not be stored appropriately in the
liver and muscles.
• The net effect is persistently high levels of blood glucose, poor protein
synthesis, and other metabolic derangements, such as acidosis.

19. PATHOGENESIS OF TYPE 1 DM.
• Pathogenesis of type 1A DM occurs based on 3 mutually interlinked
mechanisms: genetic susceptibility, autoimmune factors, and certain
environmental factors.
• At birth, individuals with genetic susceptibility to this disorder have
normal β-cell mass.
• β-cells act as autoantigens and activate CD4+ T lymphocytes, bringing
about immune destruction of pancreatic β-cells by autoimmune
phenomena and taking months to years. The trigger for autoimmune
process appears to be some infectious or environmental factor that
specifically targets β cells.

22. PATHOGENESIS OF TYPE 2 DM
•In essence, hyperglycaemia in type 2 DM is not due to the destruction of β- cells but is
instead a failure of β- cells to meet the requirement of insulin in the body. Its pathogenesis
can be summed up by interlinking the above factors as under:
•Type 2 DM is a more complex multifactorial disease.
•There is a greater role for the genetic defect and heredity.
•Two main mechanisms for hyperglycaemia in type 2 DM—insulin resistance and
Impaired insulin secretion, is interlinked.
•While obesity plays a role in the pathogenesis of insulin resistance, impaired insulin
secretion may be from many constitutional factors.
•Increased hepatic synthesis of glucose in the initial period of disease contributes to
hyperglycaemia.

25. CLINICAL MANIFESTATIONS

26. CLINICAL MANIFESTATIONS
•The symptoms of both type 1 and type 2 diabetes are similar, but they usually vary in
intensity.
•Common symptoms include polyuria(increased urine production, particularly
noticeable at night) and polydipsia (increased thirst).
•Symptoms are frequently accompanied by fatigue due to an inability to utilize
glucose and marked weight loss because of the breakdown of body protein and fat
as an alternative energy source to glucose.
•Patients may also experience a higher infection rate, especially Candida, and urinary
tract infections due to increased urinary glucose levels.

27. Type 1 diabetes
• In a significant proportion, the presenting symptoms are those of diabetic
ketoacidosis, nausea, vomiting, dehydration, shortness of breath and, in
extreme cases, coma.
• Many patients with type 2 diabetes have hyperglycaemia, with few or no
classic symptoms.
• Recurring infections, for example, urinary tract, chest, and soft tissue
are common because sustained hyperglycaemia can result in severe
impairment of phagocyte function, and Raised glucose levels provide a
growth medium for bacteria.

28. Generalized pruritus and symptoms of vaginitis, which may be due to
candidal infection, are frequently the initial complaints of women with
type 2 diabetes.
• Retinopathy may be detected on routine ophthalmological examination.
• Alternatively, a combination of neuropathy, peripheral vascular disease
(PVD) and infection may manifest as foot ulceration
• In some cases, patients present with the hyperosmolar hyperglycaemic
state (HHS) where glucose levels in excess of 35 mmol /L and excessive
dehydration have occurred.

29. DIAGNOSIS
• URINE TESTING
• Glucosuria
• Ketonuria
• SINGLE BLOOD SUGAR ESTIMATION: Fasting plasma glucose(FPG),
Postprandial Plasma glucose(PPG), Random or Casual sugar
• ORAL GLUCOSE TOLERANCE TEST: Test done to confirm the diagnosis
in doubtful cases (i.e. cases were FPG and /or PPG are in the borderline
range). In this test, one has to drink 75 g glucose (sugar) in water on
empty stomach and blood sugar is to be tested after 2 hours.
• OTHER TESTS

32. MANAGEMENT AND TREATMENT
• The major goal in treating diabetes is to keep blood sugar (glucose) levels as close to
normal as possible, without causing abnormally low levels of blood sugar
(hypoglycemia).
• Lifestyle modifications and including a healthy diet (high protein and low
carbohydrate and fat diet), management of stress, avoidance of alcohol and tobacco
etc. are found to be effective.
• Type I diabetes is treated with insulin, exercise, and a diabetic diet.
• Type II diabetes is treated first with weight reduction, a diabetic diet, and exercise.
• Patients with type I diabetes mellitus require lifelong insulin therapy. Most require 2
or more injections of insulin daily, with doses adjusted based on self-monitoring of
blood glucose levels.
• Early initiation of pharmacologic therapy is associated with improved glycemic
control and reduced long-term complications in type II diabetes.

33. Drug classes used for the treatment of diabetes include the following:

34. INSULIN THERAPY

35. COMPLICATIONS

37. Both types of diabetes mellitus may develop complications
which are broadly divided into 2 major groups:
I. Acute metabolic complications include diabetic ketoacidosis,
hyperosmolar nonketotic coma, and hypoglycaemia.
I. Late systemic complications: These are atherosclerosis, diabetic
microangiopathy, diabetic nephropathy, diabetic neuropathy, diabetic
retinopathy and infections.

38. ACUTE METABOLIC COMPLICATIONS
Diabetic ketoacidosis (DKA)
•Ketoacidosis can develop in patients with severe insulin deficiency combined with glucagon
excess.
•Failure to take insulin and exposure to stress are the usual precipitating causes.
•Severe lack of insulin causes lipolysis in the adipose tissues, releasing free fatty acids into the
plasma. The liver takes These free fatty acids, oxidising them through acetyl coenzyme- A to
ketone bodies. Such free fatty acid oxidation to ketone bodies is accelerated in the presence of
elevated levels of glucagon.
•Once the rate of ketogenesis exceeds the rate ketonaemia and ketonuria occur.
•If urinary excretion of ketone bodies is prevented due to dehydration, systemic metabolic
ketoacidosis occurs.
•Clinically, the condition is characterised by anorexia, nausea, vomiting, deep and fast
breathing, mental confusion and coma. Most patients of ketoacidosis recover.

40. ACUTE METABOLIC COMPLICATIONS
Hyperosmolar hyperglycaemic nonketotic coma (HHS)
• A complication of type 2 DM. It is caused by severe dehydration resulting
from sustained hyperglycaemic diuresis.
• The loss of glucose in the urine is so intense that the patient is unable to
drink sufficient water to maintain the urinary fluid loss.
• The usual clinical features of ketoacidosis are absent but prominent
Central nervous signs are present.
• Blood sugar is extremely high and plasma osmolality is high. Thrombotic
And bleeding complications are frequent due to the high viscosity of blood.
• The mortality rate in a hyperosmolar nonketotic coma is high.

41. ACUTE METABOLIC COMPLICATIONS
Hypoglycaemia
• May develop in patients with type 1 DM. It may result from excessive
administration of insulin, missing a meal, or due to stress.
• Hypoglycaemic episodes produce permanent brain damage or may result
in worsening of diabetic control and rebound hyperglycaemia, the so-called
Somogyi’s effect.

42. LONG TERM
COMPLICATIONS

43. • Visual impairment and blindness due to diabetic retinopathy
• Renal failure and hypertension due to diabetic nephropathy
• Pain, paraesthesia, muscle weakness and autonomic dysfunction due to
diabetic neuropathy
• Cardiac disease, peripheral vascular disease and stroke due to
macrovascular disease

44. MICROVASCULAR COMPLICATIONS OF DIABETES
• It includes retinopathy, nephropathy & neuropathy.
MACROVASCULAR COMPLICATIONS OF DIABETES
• The central pathological mechanism in macrovascular disease is the process
of atherosclerosis, which leads to the narrowing of arterial walls throughout
the body.
MACRO- AND MICROVASCULAR DISEASE COMBINED
• Diabetic foot problems

45. MICROVASCULAR COMPLICATIONS OF DIABETES
Diabetic retinopathy
• Diabetic retinopathy may be the most common microvascular complication
of diabetes.
• Aldose reductase may participate in the development of diabetes
complications.
• Polyol pathway involves the conversion of glucose into sorbitol.
• High glucose levels increase the flux of sugar molecules through the polyol
pathway, which causes sorbitol accumulation in cells.
• Osmotic stress from sorbitol accumulation has been postulated as an
underlying mechanism in the development of diabetic microvascular
complications, including diabetic retinopathy.

47. MICROVASCULAR COMPLICATIONS OF DIABETES
Diabetic neuropathy
• Diabetes neuropathies can lead to a wide variety of sensory, motor and
autonomic symptoms.
• Diabetic proximal motor neuropathy is rapid in onset & evolves weakness
of thigh muscles.
• Diabetic distal motor neuropathy can lead to symptoms of impaired fine
coordination of the hands or foot slapping.
• Autonomic neuropathy may affect any part of the sympathetic or
parasympathetic nervous system.
• It can cause postural hypotension, vomiting, diarrhoea, sweating
abnormalities, impaired light reflex and impotence.

48. MICROVASCULAR COMPLICATIONS OF DIABETES
Diabetic neuropathy

49. MICROVASCULAR COMPLICATIONS OF DIABETES
Diabetic nephropathy
• Diabetic nephropathy is the leading cause of renal failure.
• In diabetic renal disease, the kidneys become enlarged & the glomerular
filtration rate (GFR) initially increases.
• If the nephropathy progresses, the GFR starts to decline.
• The presence of nephropathy is indicated by the detection of
microalbuminuria (Small amounts of albumin in urine).
• Without treatment, diabetic patients with microalbuminuria typically
progress to proteinuria and overt diabetic nephropathy.
• The pathological changes to the kidney include increased glomerular
basement membrane.

51. MACROVASCULAR COMPLICATIONS OF DIABETES
Atherosclerosis
• Atherosclerosis which leads to narrowing of arterial walls throughout the
body.
• Atherosclerosis is thought to result from chronic inflammation and injury to
the arterial wall.
• In response to endothelial injury and inflammation, oxidized lipids from
LDL particles accumulate in the endothelial wall of arteries.

52. • Monocytes then infiltrate the arterial wall and differentiate into
macrophages, which accumulate oxidized lipids to form foam cells. Once
formed, foam cells stimulate macrophage proliferation and attraction of T-
lymphocytes. The net result of the process is the formation of a lipid-rich
atherosclerotic lesion with a fibrous cap. Rupture of this lesion leads to
acute vascular infarction.
• In addition to atheroma formation, there is strong evidence of increased
platelet adhesion and hypercoagulability in type 2 diabetes.

54. MACROVASCULAR COMPLICATIONS OF DIABETES
Peripheral vascular disease (PVD)
• PVD affects the blood vessels outside the heart. In people with diabetes, it
often affects the arteries of the legs.

55. MACRO- AND MICROVASCULAR DISEASE COMBINED
Diabetic foot problems
• Infected diabetic foot ulcers count for the largest number of diabetes-related
hospitals nowadays.
• Diabetic foot problems often develop as a result of a combination of specific
problems which are sensory & diabetic neuropathy, PVD and hyperglycemia.
• There are three main types of foot ulcers: neuropathic, ischaemic & neuro
ischaemic
• Neuropathic ulcers occur when peripheral neuropathy causes loss of pain
sensation. Ulcers can be deep but painless.
• Ischaemic ulcers result from PVD and poor blood supply. Ischaemic ulcers
are painful & occur on the distal ends of the toes.
• Diabetic foot ulcers are prone to infection.

57. Questions.
1. Define diabetes mellitus. Enlist complications of diabetes and describe them in detail.
2. Classify Diabetes, Explain aetiology, pathophysiology and diagnosis.
3. Write signs and symptoms and complications of Diabetes mellitus
4. Compare and contrast: Type 1 and Type 2 diabetes mellitus. Write the complications of diabetes in brief.
5. Classify diabetic mellitus. Discuss the causes, symptoms and treatment of diabetic mellitus.