DIABETES MELLITUS

JUNAID O.A
DEPARTMENT OF INTERNAL MEDICINE
DIVISON OF ENDOCRINE MEDICINE
UNIMED, ONDO, ONDO STATE, NIGERIA
Objectives
• At the end of the lecture, students should understand the definition
pathogenesis and risk factors of diabetes mellitus
• Students should be able to discuss the diagnostic criteria and
investigations in diabetes mellitus
• Students should be able to understand the clinical approach to a
patient with diabetes mellitus in terms of history taking, physical
examination and management
• Students should be able to work out a follow up plan for diabetic
patients
Table of content
• Introduction
• Hormone regulation and glucose transport
• Classification
• Pathogenesis
• Diagnosis
• Clinical presentation
• Complications
Introduction
• Diabetes mellitus (DM) is a syndrome of chronic hyperglycaemia due to
relative insulin deficiency, resistance or both.
• Diabetes mellitus is a group of metabolic diseases characterised by
hyperglycaemia resulting from defects in insulin secretion, insulin action or
both.
• DM refers to a group of common metabolic disorders that share the
phenotype of hyperglycemia. Several distinct types of DM are caused by a
complex interaction of genetics and environmental factors.
• Diabetes is usually irreversible and, although patients can live a reasonably
normal lifestyle, its late complications result in reduced life expectancy and
major health costs.
• Depending on the etiology of the DM, factors contributing to hyperglycemia
include reduced insulin secretion, decreased glucose utilization, and increased
glucose production.
• The metabolic dysregulation associated with DM causes secondary
pathophysiologic changes in multiple organ systems that impose a tremendous
burden on the individual with diabetes and on the health care system.
• In the United States, DM is the leading cause of end-stage renal disease
(ESRD), nontraumatic lower extremity amputations, and adult blindness.
• It also predisposes to cardiovascular diseases. With an increasing incidence
worldwide, DM will be likely a leading cause of morbidity and mortality in the
future.
Hormone regulation and glucose transport
• Insulin is a major regulator of intermediary metabolism. Its actions in
the fasting and postprandial states differ.
• In the fasting state, its main action is to regulate glucose release by the
liver, and in the postprandial state, it additionally promotes glucose
uptake by fat and muscle.
• The effect of counter-regulatory hormones (glucagon, epinephrine
(adrenaline), cortisol and growth hormone) is to cause greater
production of glucose from the liver and less utilization of glucose in
fat and muscle for a given level of insulin.
Glucose transport
Cell membranes are not inherently permeable to glucose. A family of specialized
glucose-transporter (GLUT) proteins carry glucose through the membrane into
cells.
• GLUT-1 – enables basal non-insulin-stimulated glucose uptake into many cells.
• GLUT-2 – transports glucose into the beta cell, a prerequisite for glucose
sensing, and is also present in the renal tubules and hepatocytes.
• GLUT-3 – enables non-insulin-mediated glucose uptake into brain neurones
and placenta.
• GLUT-4 – enables much of the peripheral action of insulin. It is the channel
through which glucose is taken up into muscle and adipose tissue cells
following stimulation of the insulin receptor (
Classification
• DM can be primary or secondary
• There are two broad categories of DM, designated type 1 and type 2.
• However, there is increasing recognition of other forms of diabetes in
which the pathogenesis is better understood.
• Classification of DM is based on etiology, according to the American
Diabetes Association (2014)
• Other specific types (Secondary Diabetes)
A. Genetic defects in ß-cell function
B. Maturity-onset Diabetes of Youth (MODY 1-9)
C. Genetic defects in insulin action
D. Exocrine pancreatic diseases. Eg (pancreatitis, pancreatectomy)
E. Other endocrinopathies eg (Cushing’s, acromegaly, pheochromocytoma,
glucagonoma, thyrotoxicosis, others
F. Drug/chemical-induced eg steroids, diazoxide, thiazides, L-asparaginase,
G. Infections eg. congenital rubella, CMV, others
 Uncommon forms of immune-mediated diabetes (“Stiff-man” syndrome, anti-insulin
receptor antibodies, others)
 Other genetic syndromes. Down, Klinefelter’s, Turner’s, Prader-Willi, Laurence-Moon-
Biedl, Friedreich’s ataxia, Huntington’s chorea, myotonic dystrophy, porphyria, others

 Gestational Diabetes Mellitus (GDM)

 Impaired Glucose Tolerance (IGT)
 Impaired Fasting Glucose (IFG)
Epidemiology
• The worldwide prevalence of DM has risen dramatically over the past
two decades, from an estimated 30 million cases in 1985 to 382
million in 2013.
• Based on current trends, the International Diabetes Federation projects
that 592 million individuals will have diabetes by the year 2035.
• Although the prevalence of both type 1 and type 2 DM is increasing
worldwide, the prevalence of type 2 DM is rising much more rapidly,
presumably because of increasing obesity, reduced activity levels as
countries become more industrialized, and the aging of the population.
Epidemiology
• The countries with the greatest number of individuals with diabetes in
2013 are China, india, USA, brazil, Russia.
• Worldwide, most individuals with diabetes are between the ages of
40 and 59 years.
• There is considerable geographic variation in the incidence of both
type 1 and type 2 DM.
• Scandinavia has the highest incidence of type 1 DM; the lowest
incidence is in the Pacific Rim where it is 20- to 30-fold lower.
• Diabetes is a major cause of mortality, but several studies indicate that
diabetes is likely underreported as a cause of death. In the United
States, diabetes was listed as the seventh leading cause of death in
2010.
• A recent estimate suggested that diabetes was responsible for almost
5.1 million deaths or 8% of deaths worldwide in 2013.
• In 2013, it was estimated that $548 billion or 11% of health care
expenditures worldwide were spent on individuals with diabetes.
Pathogenesis: Type 1 DM
• Type 1 DM is the result of interactions of genetic, environmental, and immunologic factors that
ultimately lead to the destruction of the pancreatic beta cells and insulin deficiency. Type 1 DM,
which can develop at any age, develops most commonly before 20 years of age.
• Type 1 DM results from autoimmune beta cell destruction, and most, but not all, individuals have
evidence of islet-directed autoimmunity.
• The major susceptibility gene (MHC) for type 1 DM is located in the HLA region on chromosome
6.
• Individuals with a genetic susceptibility are thought to have normal beta cell mass at birth but
begin to lose beta cells secondary to autoimmune destruction that occurs over months to years.
• This autoimmune process is thought to be triggered by an infectious or environmental stimulus
and to be sustained by a beta cell–specific molecule.
• Features of diabetes do not become evident until a majority of beta cells are
destroyed (70–80%).
• After the initial clinical presentation of type 1 DM, a “honeymoon” phase may
ensue during which time glycemic control is achieved with modest doses of
insulin or, rarely, insulin is not needed.
• Many individuals with long-standing type 1 DM produce a small amount of insulin
(as reflected by C-peptide production), and some individuals with more than 50
years of type 1 DM have insulin-positive cells in the pancreas at autopsy.
Temporal model for development of type 1
DM
• A cleaner environment with less early stimulation of the immune system in
childhood may increase susceptibility for type 1 diabetes, as for atopic/allergic
conditions (the hygiene hypothesis) and more rapid weight gain in childhood and
adolescence leading to increased insulin resistance might accelerate clinical
onset (the accelerator hypothesis).
• Children who test positive for two or more autoantibodies have a >80% risk of
progression to diabetes, and the risk approaches 100% in those who additionally
lose their first phase insulin response to intravenous glucose and/or develop
glucose intolerance.
• The ability to predict type 1 diabetes with this degree of precision has opened
the way to trials of disease prevention, but intervention before clinical onset of
diabetes has so far proved unsuccessful.
Pathogenesis; Type 2 DM
• Type 2 diabetes is a common condition in all populations enjoying an
affluent lifestyle, and has increased in parallel with the adoption of a
western lifestyle and increasing obesity.
• Insulin resistance and abnormal insulin secretion are central to the
development of type 2 DM.
• The four major determinants are increasing age, obesity, ethnicity and
family history.
• In poor countries, diabetes is a disease of the rich, but in rich
countries, it is a disease of the poor; obesity being the common
factor.
• Obesity increases the risk of type 2 diabetes 80–100 fold. On average,
the inhabitants of affluent countries gain almost 1g daily between the
ages of 25 and 55 years.
• Further, our sedentary lifestyle means that the proportion of obese
young adults is rising rapidly, and epidemic obesity will create a huge
public health problem for the future.
Genetics
• Type 2 DM has a strong genetic component. The concordance of type
2 DM in identical twins is between 70 and 90%.
• Individuals with a parent with type 2 DM have an increased risk of
diabetes; if both parents have type 2 DM, the risk approaches 40%.
• Insulin resistance, as demonstrated by reduced glucose utilization in
skeletal muscle, is present in many non-diabetic, first-degree relatives
of individuals with type 2 DM.
• Type 2 DM is characterized by impaired insulin secretion, insulin
resistance, excessive hepatic glucose production, and abnormal fat
metabolism.
• In the early stages of the disorder, glucose tolerance remains near-
normal, despite insulin resistance, because 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.
• IGT, characterized by elevations in postprandial glucose, then
develops.
• A further decline in insulin secretion and an increase in hepatic
glucose production lead to overt diabetes with fasting hyperglycemia.
• Ultimately, beta cell failure ensues.
• Although both insulin resistance and impaired insulin secretion
contribute to the pathogenesis of type 2 DM, the relative contribution
of each varies from individual to individual.
• The Diabetes Prevention Program (DPP) demonstrated that intensive
changes in lifestyle (diet and exercise for 30 min/d five times/week) in
individuals with IGT prevented or delayed the development of type 2
DM by 58% compared to placebo.
GESTATIONAL DIABETES MELLITUS

Any degree of glucose intolerance with onset or first

recognition during pregnancy.
Diabetic women who became pregnant are not
included.
At risk of developing DM subsequently
Definition applies regardless of mode of therapy or
whether it persists after pregnancy.
DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS (ADA)

1. Symptoms of diabetes plus casual plasma glucose

concentration> 200mg/dl (11.1mmol/L)

Casual is defined as anytime of day without regard to time

since last meal.
OR
2. FPG > 126mg/dl (7.0mmol/L).
Fasting is defined as no caloric intake for at least 8hr
 OR
3. 2-h. PG > 200mg/dl (11.1mmol/L) during an OGTT (using
75g anhydrous glucose dissolved
300ml of water)

* In the absence of unequivocal hyperglycemia, with acute

metabolic decompensation, the criteria should be confirmed
by repeat testing on a different day.
 Impaired Fasting Glucose (IFG) and Impaired glucose
tolerance(IGT) refer to a metabolic stage intermediate between
normal glucose homeostasis and diabetes = prediabetes
Impaired FPG >110mg/dl / (6.1) mmol/L - <126 mg/dl (7.0
mmol/L)
Upper limit of normal fasting plasma glucose =109mg/dl
(6.1mmol/L)
IGT= FPG < 140mg/dl (7.8 mmol/l)
2h PG(Post load) >140(7.8 mmol/L) and <200mg/dl (11.1
mmo/L)
Clinical presentation
• It can be acute, subacute, or asymptomatic.
Acute presentation
• Young people often present with a 2 – 6 week history and report the
classic triad of symptoms:
•
Polyuria – due to the osmotic diuresis that results when blood glucose


levels exceed the renal threshold

•
Thirst (Polydipsia) – due to the resulting loss of fluid and electrolytes


•
Weight loss – due to fluid depletion and the accelerated breakdown of


fat and muscle secondary to insulin deficiency.

Ketonuria is often present in young people and may progress to
ketoacidosis if these early symptoms are not recognized and treated.
Subacute presentation

• The clinical onset may be over several months or years, particularly in

older patients.
• Thirst, polyuria and weight loss are typically present but patients may
complain of such symptoms as lack of energy, visual blurring (owing
to glucose-induced changes in refraction) or pruritus vulvae or
balanitis that is due to Candida infection.
Asymptomatic
• Glycosuria or a raised blood glucose may be detected on routine
examination (e.g. for insurance purposes) in individuals who have no
symptoms of ill-health.
• Glycosuria is not diagnostic of diabetes but indicates the need for
further investigations.
• About 1% of the population have renal glycosuria.
• This is an inherited low renal threshold for glucose, transmitted either
as a mendelian dominant or recessive trait.
Metabolic Disturbance
• Hyperglycaemia and glycosuria
• Increased urine specific gravity
• Increased serum and urine osmolality
• ketonemia and ketonuria
• Decreased blood and urine pH (acidosis)
• Electrolyte imbalance
COMPLICATIONS
 ACUTE
Diabetic ketoacidosis (DKA)
Hyperosmolar Hyperglycemic State (HHS)
Hypoglycaemia
 CHRONIC (MICRO- AND MACROVASCULAR)
Diabetic Neuropathy
Diabetic Nephropathy
Diabetic Retinopathy
ACUTE COMPLICATIONS
HYPOGLYCAEMIA

Varies from RPG <70mg/dl depending on previous long

clinical symptom and cognitive ability

Causes: Errors from care providers

Altered pharmacokinetics of drugs
Change in drug sensitivity
Inadequate carbohydrate
DIABETIC KETOACIDOSIS
Usually precipitated by infection or vomiting
Insulin deficiency leads to:
 Switch from hepatic glycolysis to gluconeogenesis
and glycogenolysis with consequent hyperglycaemia
Unrestrained lipolysis  NEFA to liver
Switch from NEFA re-esterification to oxidation  Ketone
bodies (3 hydoxybutyrate + acetoacetate & acetone
Kussmaul kien (deep) respiration
laboratory findings
Hyperglycaemia
Metabolic acidosis with  anion gap
Ketones
Electrolyte changes:
 Total body deficit of water (5-8litres);
 K+(300-1000mmol), Na (400-700mmol)
 Hypomagnesaemia, Hypophosphataemia
Hyperkalaemia 20 to acidosis
Low plasma Bicarbonate
Lactic acidosis if hypotensive,

Electrolyte changes:
 Total body deficit of water, K+, Na
 5-8litres; 300-1000mmol; 400-700mmol
 Hypomagnesaemia, hypophosphataemia
HYPEROSMOLAR HYPERGLEMIC STATE (HHS)

Opposite ends of a spectrum with DKA

Insulin is relative and not absolute
Hyperglycaemia is more severe than DKA
Patient is older
Infection is major ppt. Cause
Pathophysiology:

Marked hyperglycaemia / hyperosmolality

Minor ketosis and acidosis

Why absent significant ketosis in HHS?

Dehydration and hyperosmolality inhibit lipolysis and

ketogenesis
CHRONIC COMPLICATIONS

DIABETIC NEPHROPATHY
Macroscopic features
Enlarged kidney - tubular hypertrophy and hyperplasia.
Interstitial expansion

End stage renal disease - small kidney

Pyelonephritis - Renal scarring
Papillary necrosis – common in infection.
Clinical nephropathy
Urinary albumin concentration (UAC) >300mg/l(30mg/dl)
Urinary albumin excretion rate (UAER) >300mg/24 hr
Urinary albumin excretion >500mg/24 hr
Microalbuminuria(Paucialbuminuria)
UAC 20-300 mg/l
UAER 20-200µg/min (timed overnight collection)
30-300 mg/mmol - male
Albumin: Creatinine ratio (ACR) 2.5-25 mg/mmol - male
30-300 mg/g-male
3.5-25 mg/mmol- female
40-300mg/g - female
DIABETIC RETINOPATHY

Microaneurysm, excessive vascular permeability, vaso-

obliteration, proliferation of new vessels and fibrous
tissue.
Contraction of vitreous and fibrous vascular proliferations
Risk Factors ↑ prolonged hyperglycaemia
PERIPHERAL NEUROPATHY

Diabetic Neuropathy: is a clinical state of nerve damage

in a patient in which a patient complains of symptoms
(pains, paraesthesia) or is shown to have neurological
deficit.

Likely to lead to problems (anaesthetic foot)

DIABETIC FOOT

It is infection, ulceration and/or destruction of deep

tissues associated with neurological abnormalities and
various degrees of peripheral vascular disease in lower
limb
40 - 60% of non traumatic lower limb diabetic
amputations
85% of diabetic lower limb amputations arise from foot
ulcers
4-10% prevalence in diabetic population
METABOLIC SYNDROME

Insulin resistance and the dysmetabolic syndrome are

closely associated
95% are insulin resistant
It is the genesis of macrovascular disease
complications
Insulin resistance,  hyperinsulinism 
hyperglycaemia of Type 2 DM deleterious vascular
changes  artherosclerosis progression  myocardial
infarction and stroke
MANAGEMENT
Outline
• Problems of a diabetic
• Management of blood glucose
• Classification of anti- diabetic agents
• Oral anti- diabetic agents
• Injectables
• Considerations in management plan
• Treatment targets in diabetes care
• Benefits of treatment
• Assessment of long term glycaemic control.
Problems of a diabetic
• Hyperglycaemia
• Hypertension
• Dyslipidaemia
• Other co-morbid conditions- cardiovascular disease, renal disease,
liver disease etc
• Diabetes complications
• Management of DM is a multi-disciplinary approach.
• When the complications of DM arise, subspecialists (including
neurologists, nephrologists, vascular surgeons, cardiologists,
ophthalmologists, and podiatrists) with experience in DM-related
complications are essential.
Goals of therapy
• Eliminate symptoms related to hyperglycaemia
• Reduce/ Eliminate long term micro/ Macro vascular complications
• Achievement of a normal lifestyle as much as possible
Guidelines for On-going Medical care for
diabetics (IDF)
Optimal and individualized glycemic control
• Self-monitoring of blood glucose (individualized frequency)
• HbA1c testing (2–4 times/year)
• Patient education in diabetes management (annual); diabetes-self
management education and support
• Medical nutrition therapy and education (annual)
• Eye examination (annual or biannual)
• Foot examination (1–2 times/year by physician; daily by patient)
• Screening for diabetic nephropathy (annual)
• Blood pressure measurement (quarterly)
• Lipid profile and serum creatinine (estimate GFR) (annual)
• Influenza/pneumococcal/hepatitis B immunizations
• Consider antiplatelet therapy
Management of blood glucose
• Education, Nutrition and Exercise
• Oral anti- diabetic agents
• Injectables
Education on diabetes
• A continuous effort
• Education on Nutrition and exercise
• Care during illness
• Education on medications and side effects
• The ADA refers to education about the individualized management plan
for the patient as diabetes self-management education (DSME) and
diabetes self-management support (DSMS).
• More frequent contact between the patient and the diabetes
management team (e.g., electronic, telephone) improves glycemic
control.
Components of DM Education
• Self monitoring of blood glucose (SMBG)
• Urine ketone monitoring (type 1 DM)
• Insulin administration
• Diabetes during illness
• Prevention and Treatment of hypoglycaemia
• Foot care and skin care
• Diabetes management before, during and after exercise.
NUTRITION (Diet)
Medical nutrition therapy (MNT)
• Optimal coordination of caloric intake with other aspects of diabetes
therapy( insulin, exercise, weight loss)
• Divided into Primary, Secondary and Tertiary
• Primary- targeted for DM prevention
• Secondary- to prevent complications in DM
• Tertiary- to prevent worsening of DM complications
Nutrition (Diet)
• General principles- diet that contains fruits, vegetables, fibre
containing food and low fat milk
• Food with low glycaemic index ( Glycaemic index of a food is the
estimate of the post prandial rise in blood glucose after taking such
food)
• In T2DM- caloric reduction and reduced fat intake,
Nutritional Recommendations for individuals
with DM or Pre-DM
Component of MNT
CHO
• 45-65% of total caloric intake
FAT-
• 20- 35% of total calorie
• Mainly unsaturated fats
• Saturated fat < 7% of total calorie
• <200mg/day of dietary cholesterol
Protein
• 10- 35% of total calorie
• Others
• Fibre containing food
• Non- nutritive sweetners
Exercise
• Exercise has multiple positive benefits including cardiovascular risk
reduction, reduced blood pressure, maintenance of muscle mass,
reduction in body fat, and weight loss.
• For individuals with type 1 or type 2 DM, exercise is also useful for
lowering plasma glucose (during and following exercise) and
increasing insulin sensitivity.
• 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.
• Despite its benefits, exercise presents challenges for individuals with DM because
they lack the normal glucoregulatory mechanisms (normally, insulin falls and
glucagon rises during exercise).
• Individuals with type 1 DM are prone to either hyperglycemia or hypoglycemia
during exercise, depending on the preexercise plasma glucose, the circulating
insulin level, and the level of exercise-induced catecholamines.
• If the insulin level is too low, the rise in catecholamines may increase the plasma
glucose excessively, promote ketone body formation, and possibly lead to
ketoacidosis.
• Conversely, if the circulating insulin level is excessive, this relative hyperinsulinemia
may reduce hepatic glucose production and increase glucose entry into muscle,
leading to hypoglycemia.
To avoid exercise-related hyper- or hypoglycemia, individuals with type 1 DM should
• (1) monitor blood glucose before, during, and after exercise;
• (2) delay exercise if blood glucose is >14 mmol/L (250 mg/dL) and ketones are present;
• (3) if the blood glucose is <5.6 mmol/L (100 mg/dL), ingest carbohydrate before exercising;
• (4) monitor glucose during exercise and ingest carbohydrate to prevent hypoglycemia;
• (5) decrease insulin doses (based on previous experience) before exercise and inject insulin into
a non exercising area; and
• (6) learn individual glucose responses to different types of exercise and increase food intake for
up to 24 h after exercise, depending on intensity and duration of exercise.

In individuals with type 2 DM, exercise-related hypoglycemia is less common but can occur in
individuals taking either insulin or insulin secretagogues.
Oral Anti-diabetic agents
Classification
1. Insulin sensitizers- biguanide, thiazolidinediones
2. Insulin secretagogues- Sulphonylureas, meglitinides
3. Others- DPP 4 inhibitors, α- glucosidase inhibitors
BIGUANIDE
• Metformin- only biguanide in use
• Phenformin- withdrawn years ago due to side effects of lactic acidosis
• Foremost anti- diabetic agent
• Usually first line in Type 2 DM, especially obese patients
Mechanism of Action and side effects
• Acts on the liver by inhibiting hepatic gluconeogenesis and
increasing insulin sensitivity
• Its is readily available and low cost
• Does not cause hypoglycaemia and weight gain
• Side effects include GI disturbance-(diarrhoea, abdominal
cramps), lactic acidosis
• Contraindicated in renal and hepatic failure
Thiazolodinediones
• a.k.a Glitazones, examples Pioglitazone, Rosiglitazone
• Activates PPAR- gamma- peroxisome proliferator activated
receptor
• Increases insulin sensitivity
• Does not cause hypoglycaemia
• S/E- fluid retention, increased risk of heart failure, fractures.
Sulphonylureas
• Acts on beta cell to increase insulin secretion
• 1st generation- tolbutamide, chlorpropramide
• 2nd generation- glibenclamide, gliclazide
• 3rd generation- glimeperide
• Available and affordable
• Good reduction in HbA1c
• S/E- hypoglycaemia, weight gain
Meglitinides
• Acts by increasing insulin secretion
• E.g Nateglinide, Repaglinide
• S/E hypoglycaemia
DPP - 4 inhibitors
• Sitagliptin , Vildagliptin
• Inhibits DPP-4 activity, increasing GLP-1 concentration
• Effects include glucose dependent increase in insulin
secretion and reduction in glucagon production
Alpha glucosidase inhibitors
• Reduces glucose absorption in GIT, by inhibiting enzymes
that cleaves oligosaccharides to simple sugars
• S/E flatulence, diarrhoea, abdominal distension.
Injectable Anti-diabetics
• Insulin
• GLP-1 agonist (aka incretin analogues/ mimetics)- exanatide,
liraglutide
• Amylin agonist eg pramlintide
Insulin
Classification
• Animal vs Human vs Analogue
• Rapid vs Short vs Intermediate Vs Long acting
• Single vs Mixed preparation
• Inhaled
Brief history
• In 1921 the Canadian scientists Fredrick G. Banting, Charles
H. Best, J.J.R. Macleod and James B. Collip discovered
insulin.

• They extracted insulin from the islets of animal pancreases.

Up to that time type 1 diabetes was a virtual death sentence
for patients suffering from it.
Action
1. Increases glucose uptake, particularly in muscle, liver and
adipose tissue
2. Suppresses glucose output from the liver
3. Increases formation of fat
4. Inhibits breakdown of fats
5. Promotes amino-acid uptake and prevents protein
breakdown
• Due to their short duration, rapid- or short-acting insulins are usually
used to replicate the surge or bolus of insulin seen in a person
without diabetes following ingestion of food.

• Due to their longer duration, intermediate or long-acting insulins are

used to provide background or basal insulin coverage.
Injection sites
• The abdomen
• Deltoid area
• Thighs
• Buttock
– I.M injection is not recommended for routine injection
– Rotation of the injection site is important to prevent lipodystrophy
– Rotating within one area is recommended
– Exercise increases the rate of absorption from injection sites
Indication for insulin use
Type 1 diabetes

Type 2 diabetes with OHA failure

Type 2 diabetes with nephropathy

Hyperglycaemic emergency

Sepsis, DM foot ulcer

Surgery

GDM
• People with type 1 diabetes require insulin for survival – they cannot be managed on oral
agents.
• There is some limited evidence suggesting that the use of metformin within the first
trimester of pregnancy is safe.
• However, there is no evidence for other oral glucose-lowering agents. Therefore the use
of oral agents is not recommended during pregnancy. Ideally, women with type 2
diabetes on oral glucose-lowering medicines should be transferred to insulin therapy
prior to conception.
• Oral glucose-lowering medicines should not be recommenced until after the birth and
the woman is no longer breast feeding.
• People with type 2 diabetes may require short-term insulin therapy during periods
where their blood glucose levels remain high – such as around a surgical event or illness.
Insulin Delivery
• Many people who are on insulin to manage their diabetes inject the
insulin with a needle and syringe (just under the skin).

• Several other devices for delivering insulin are available, and new
approaches are under development.
Insulin Jet Injector
Insulin Pump
Inhaled Insulin
Insulin Pen
COMPLICATIONS
• Hypoglycaemia
• Weight gain
• Lipohypertrophy
• Lipoatrophy
• Insulin oedema
• Allergic reaction( animal insulin)
GLP-1 agonist
• Amplifies glucose stimulated insulin action
• Reduces glucagon secretion and slows gastric emptying
• Also causes weight loss
• s/e- nausea, risk of hypoglycaemia when used with insulin or
secretagogues
Amylin agonist
• Reduce glucagon secretion
• Slows gastric emptying
• s/e- nausea
Consideration in management plan
• Duration of diabetes - the shorter the duration the need for more
stringent control to prevent complications
• Age- for very old individuals control is usually less stringent
• Presence of co- morbities, past severe hypoglycaemia and non
motivated patients may require less stringent control
 Targets for blood glucose

HbA1C Pre-meal 2 hours post-

meal

ADA <7% 4.4 – 7.2mmol/L <10 mmoL/L

(80-130mg/dl) (180mg/dl)

ACE <6.5% 4 - 6.0mmol/L < 7.8 mmol/L

(72 - 110mg/dl) (< 140 mg/dl)
Targets of treatment
• It is individualised for each patient
• Hypertension also controlled- < 140/90
• Treatment of dyslipidaemia with Statins
• Anti- platelets where indicated
• Treatment of proteinuria
Benefits of treatment
• Reduces onset of complications
• May reverse complications
• Total well being of patients
Assessment of long term glycaemic control
• Measurement of glycated hemoglobin (HbA ) is the standard method
1c

for assessing long-term glycaemic control.

• When plasma glucose is consistently elevated, there is an increase in
non-enzymatic glycation of hemoglobin; this alteration reflects the
glycaemic history over the previous 2–3 months, because erythrocytes
have an average life span of 120 days
In standardized assays, the HbA1c approximates the following mean
plasma glucose values:
• HbA1c of 6% = 7.0 mmol/L (126 mg/dL),
• 7% = 8.6 mmol/L(154 mg/dL),
• 8% = 10.2 mmol/L (183 mg/dL),
• 9% = 11.8 mmol/L (212 mg/dL),
• 10% = 13.4 mmol/L (240 mg/dL),
• 11% = 14.9 mmol/L (269 mg/dL), and
• 12% = 16.5 mmol/L (298 mg/dL).
• In patients achieving their glycemic goal, the ADA recommends
measurement of the HbA1c at least twice per year.
• More frequent testing (every 3 months) is warranted when glycemic
control is inadequate or when therapy has changed.
• Clinical conditions such hemoglobinopathies, anemias, reticulocytosis,
transfusions, and uremia may interfere with the HbA1c result.
• The degree of glycation of other proteins, such as albumin, can be used as
an alternative indicator of glycemic control when the HbA1c is inaccurate.
• The fructosamine assay (measuring glycated albumin) reflects the
glycemic status over the prior 2 weeks.
Conclusion
• DM is a disease that affect the body’s control of glucose. It is better
prevented than managed.
• People with family hx of DM should be evaluated early before onset
of DM symptoms.
• Obese, pre-diabetics should be started on the non-pharmacological
management so as to prevent development of DM.
• Management of patient with DM is multidisciplinary involving the
patient also as part of the team.
References
• Harrison’s principles of internal medicine, 17th edition (2015). ISBN:
978-0-07-180216-1
• Kumar and Clark’s clinical medicine, 9th edition (2016). ISBN 978-0-
7020-4499-1
THANK YOU FOR
LISTENING
QUESTIONS
• Enumerate the standard diagnostic criteria for diabetes mellitus
• What are the factors that can affect the reliablity of HbA1c
• List the features of cardiac autonomic neuropathy
• List the components of comprehensive diabetic care