Diabetes Mellitus
How Body maintain Blood Glucose Level
Diabetes Mellitus
A disease in which the body’s ability to produce or
respond to the hormone insulin is impaired, resulting in
abnormal metabolism of carbohydrates and elevated
levels of glucose in the blood.
A multisystem disease related to:
Abnormal insulin production, or
Impaired insulin utilization, or
Impaired carbohydrate, protein metabolism.
Leading cause of heart disease, stroke, adult blindness,
and non-traumatic lower limb amputations
Normal Insulin Metabolism
Insulin
Produced by the cells in the islets of Langherans of
the pancreas
Facilitates normal glucose range of 3.9 – 6.7 mmol/L
Promotes glucose transport from the bloodstream across
the cell membrane to the cytoplasm of the cell.
Analogous to a “key” that unlocks the cell door to allow
glucose inside the cell.
Insulin Stimulation Mechanism
Insulin after a meal:
Stimulates storage of glucose as glycogen
Inhibits gluconeogenesis
Enhances fat deposition in adipose tissue
Increases protein synthesis
Fasting state
Counter-regulatory hormones (especially glucagon) stimulate
glycogen → glucose
When glucose unavailable during fasting state
Lipolysis (fat breakdown)
Proteolysis (amino acid breakdown)
Pathophysiology
Insulin is the principal hormone that regulates uptake of glucose
from the blood into most cells (primarily muscle and fat cells, but
not central nervous system cells). Therefore deficiency of insulin
or the insensitivity of its receptors plays a central role in all forms
of diabetes mellitus. Most of the carbohydrates in food are
converted within a few hours to the monosaccharide glucose, the
principal carbohydrate found in blood and used by the body as
fuel. Insulin is released into the blood by beta cells (β-cells),
found in the Islets of Langerhans in the pancreas, in response to
rising levels of blood glucose, typically after eating. Insulin is
used by about two-thirds of the body's cells to absorb glucose
from the blood for use as fuel, for conversion to other needed
molecules, or for storage.
Conti..
Insulin is also the principal control signal for conversion
of glucose to glycogen for internal storage in liver and
muscle cells. Lowered glucose levels result both in the
reduced release of insulin from the beta cells. If the
amount of insulin available is insufficient, if cells
respond poorly to the effects of insulin (insulin
insensitivity or resistance), there can be persistent high
levels of blood glucose, poor protein synthesis, and
other metabolic derangements, such as acidosis.
ALTERED CHO METABOLISM
Insulin
Glucose Utilization
+
Glycogenolysis
Hyperglycemia
Glucosuria
(osmotic diuresis)
Polyuria*
(and electrolyte imbalance)
Polydipsia*
* Hallmark symptoms of diabetes
ALTERED PROTEIN METABOLISM
Insulin
Protein Catabolism
Gluconeogenesis
(amino acids → glucose)
Hyperglycemia
Weight Loss and Fatigue
ALTERED FAT METABOLISM
Insulin
Lipolysis
Free fatty acids + ketones
Acidosis + Weight Loss
Type 1 Diabetes Mellitus
Type 1 diabetes has universally replaced several former terms,
including childhood-onset diabetes, juvenile diabetes, and
insulin-dependent diabetes mellitus (IDDM).
Causes or Risk Factors:
Genetic predisposition
Exposure to a virus
Most often occurs in people under 30 years of age
Peak onset between ages 11 and 13years of age.
Progressive destruction of pancreatic cells.
Auto antibodies cause a reduction of 80% to 90% of normal
cell function and manifestations develop when the pancreas can
no longer produce insulin.
DM Type 1
Clinical Manifestations
Weight loss
Polydipsia (excessive thirst)
Polyuria (frequent urination)
Polyphagia (excessive hunger)
Weakness and fatigue
Diabetic ketoacidosis (DKA)
Life-threatening complication of Type 1 DM
Occurs in the absence of insulin.
Results in metabolic acidosis.
Type 2 Diabetes Mellitus
Type 2 diabetes has replaced several former terms, including adult-
onset diabetes, obesity-related diabetes, and non-insulin-
dependent diabetes mellitus (NIDDM).
Accounts for 90% of patients with diabetes
Usually occurs in people over 40 years old
80-90% of patients are overweight
Insulin resistance
Body tissues do not respond to insulin
Results in hyperglycemia
Decreased (but not absent) production of insulin.
Marked hyperglycemia (27.6 – 55.1 mmol/L)
Risk Factors of DM Type 2
Family History
Obesity
Habitual physical inactivity
Previously identified impaired glucose
tolerance
(IGT) or impaired fasting glucose (IFG)
Hypertension
Hyperlipidemia
DM Type 2
Clinical Manifestations
Non-specific symptoms, Patients can be asymptomatic.
Most patients are discovered while performing urine glucose
screening.
Fatigue
Recurrent infections
Prolonged wound healing
Visual changes
Polyuria
Polydipsia
Polyphagia
Fatigue
Weight loss
Gestational Diabetes
Develops during pregnancy and detected at 24 to 28
weeks of gestation
Gestational diabetes mellitus (GDM) resembles type 2
diabetes in several respects, involving a combination of
relatively inadequate insulin secretion and
responsiveness. It occurs in about 2%–5% of all
pregnancies and may improve or disappear after
delivery.
Conti…
Gestational diabetes is fully treatable but requires careful medical
supervision throughout the pregnancy. About 20%–50% of
affected women develop type 2 diabetes later in life. Untreated
gestational diabetes can damage the health of the fetus or mother.
Risks to the baby include macrodome (high birth weight),
congenital cardiac and central nervous system anomalies, and
skeletal muscle malformations. Increased fetal insulin may inhibit
fetal surfactant production and cause respiratory distress
syndrome. Hyperbilirubinemia may result from red blood cell
destruction. In severe cases, perinatal death may occur.
Secondary Diabetes
Results from another medical condition or due to the
treatment of a medical condition that causes abnormal
blood glucose levels
Cushing syndrome (e.g. steroid administration)
Hyperthyroidism
Parenteral nutrition
Gestational Diabetes Management
➢ Dietary control
➢ If blood glucose is not controlled by dietary control,
insulin therapy is initiated
➢ One dose of NPH or NPH + regular insulin (2:1)
given before breakfast. Adjust regimen according to
Glucose level.
➢ Sulfonylureas: Effective, but require further studies to
demonstrate safety.
Diagnostic Criteria
HbA1c
Diagnostic Criteria
Fasting plasma glucose level 7 mmol/L or >126mg/dl
Random plasma glucose level 11.1 mmol/L or >200mg/dl plus
symptoms
Impaired Glucose Tolerance Test – patient is “challenged” with
glucose load. Patient should be able to maintain normal BG.
Diabetes if BG > 11.1 mmol/L or >200mg/dl, 2 hr post challenge
Hemoglobin A1C test (glycosylated Hgb)
Reflects amount of glucose attached to Hgb over life of RBC
Indicates overall glucose control over previous 90 – 120 days
Management of DM
❖ Medications
❖ Dietary and exercise modification
❖ Regular complication monitoring
❖ Self monitoring of blood glucose
❖ Control of BP and lipid level
Diabetes Mellitus Drug Therapy: Insulin
Insulin
Cannot be taken orally
Self-administered by SQ injection
Types of insulin
Rapid-acting: Lispro
*Short-acting: Regular
*Intermediate-acting: NPH or Lente
Long-acting: Ultralente, Lantus
Diabetes Mellitus Drug Therapy: Insulin
Problems with insulin therapy
Hypoglycemia
Allergicreactions
Local inflammatory reaction
Lipodystrophy
Hypertrophy or atrophy of SQ tissue because of
frequent use of same injection on same site.
Diabetes Mellitus Drug Therapy: Oral Agents
Not insulin
Work to improve the mechanisms in which insulin
and glucose are produced and used by the body
Increase insulin production by pancreas
Reduce glucose production by liver
Enhance insulin sensitivity and glucose transport
into cell
Slow absorption of carbohydrate in intestine
Diabetes Mellitus Acute Complication : DKA
Diabetic Ketoacidosis (DKA): BG > 20 – 30 mmol/L
Usually in Type 1 diabetes; can occur in Type 2
Causes:
Infection**
Stressors(physiological, psychological)
Stopping insulin.
Undiagnosed diabetes.
Diabetes Mellitus Acute Complication: DKA
Pathophysiology
Continuation of effects of insulin deficiency
Severe metabolic acidosis
Severe dehydration → shock
Severe electrolyte imbalance ( ↓ Na, ↓ K, ↓ Cl, ↓ Mg, ↓ PO4)
Clinical Manifestations
S/S of dehydration ( HR; BP, poor turgor, dry MM),
Kussmauls breathing (d/t metabolic acidosis)
Fruity breath (d/t acetone)
Abdominal pain, N & V, cardiac arrhythmias.
Management of DKA
Fluid administration: Rapid fluid administration to
restore the vascular volume,
IV infusion of insulin to restore the metabolic
abnormalities. Titrate the dose according to the
blood glucose level.
Potassium and phosphate can be added to the fluid if
needed.
Follow up:
Metabolic improvement is manifested by an
increase in serum bicarbonate or Ph.
Diabetes Mellitus Chronic Complications
Diabetic Angiopathy
Macrovascular
Microvascular
Diabetic Retinopathy
Diabetic Nephropathy
Microvascular and Macrovascular
Chronic elevation of blood glucose level leads to damage of
blood vessels (angiopathy). The endothelial cells lining the blood
vessels take in more glucose than normal, since they don't depend
on insulin. They then form more surface glycoproteins than
normal, and cause the basement membrane to grow thicker and
weaker. In diabetes, the resulting problems are grouped under
micro vascular disease (due to damage to small blood vessels)
and Macro vascular disease (due to damage to the arteries).
The damage to small blood vessels leads to a microangiopathy,
which can cause one or more of the following: Diabetic
neuropathy, Diabetic nephropathy, Diabetic retinopathy, Diabetic
cardiomyopathy.
Diabetes Mellitus Chronic Complications
Neuropathy
Skin problems
Infection
Diabetes Mellitus Chronic Complications
Microvascular
Diabetic Retinopathy
Leading cause of new blindness
Vessel occlusion → aneurysms → leakage of fluid
Vessel occlusion → new vessel growth → hemorrhage,
retinal detachment
Diabetes Mellitus Chronic Complications
Microvascular
Diabetic Nephropathy
Damage to vessels supplying glomeruli
Leading cause of ESRD
Diabetes Mellitus Chronic Complications
Microvascular
Diabetic Neuropathy
Sensory Neuropathy
• Loss of sensation, abnormal sensation, pain of
hands and/or feet
• Can progress to partial or complete loss of
sensitivity to touch and temperature → high risk
of injury without pain.
Diabetes Mellitus Chronic Complications
Microvascular
Neuropathy
Autonomic neuropathy. Examples:
• Hypoglycemic unawareness
• Silent MI
• Erectile dysfunction, decreased libido
• Neurogenic bladder → urine retention
Diabetes Mellitus Chronic Complications
Diabetic Foot
Macrovascular disease → PVD (↓ supply of oxygen, WBCs,
nutrients)
Sensory neuropathy → injury
Teach prevention of ulceration/injury
Diabetes Mellitus Chronic Complications
Infection
Immune deficiencies
Delayed detection d/t sensory neuropathy
Decreased circulation – delays or prevents immune
response
References
Diagnosis and classification of diabetes mellitus. Diabetes
Care 2006; 29 Suppl 1:S43–S48.
American Diabetes Association. Standards of medical care in
diabetes - 2017. Diabetes Care. 2017;40(suppl 1):S1-S135.
Association of glycaemia with macrovascular and microvascular
complications of Type 2 diabetes: prospective observational
study. British Medical Journal 2000; 321: 405-412.
Text book of Medical Physiology 12e by Guyton and Hall.
Kim C, Berger DK, Chamany S. Recurrence of gestational
diabetes mellitus: a systematic review. Diabetes Care.
2007;30:1314-1319.
