Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.
The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.
Action of insulin
Action of insulin on CHO, Fat and Protein Metabolism
Facilitates the transport of glucose into muscle and adipose cells
Facilitates the conversion of glucose to glycogen for storage in the liver and muscle.
Decreases the breakdown and release of glucose from glycogen by the liver
Stimulates protein synthesis
Inhibits protein breakdown; diminishes gluconeogenesis
Stimulates lipogenesis- the transport of triglycerides to adipose tissue
Inhibits lipolysis – prevents excessive production of ketones or ketoacidosis
Major Reason for Insulin Secretion
Elevated blood glucose levels
Increased fatty acids
Glucagon, growth hormone, cortisol
Decreased blood glucose levels
Decreased food intake (fasting)
an excessive amount of glucose circulates in the blood plasma
chronic levels exceeding 125 mg/dl can produce organ damage
What goes wrong in Diabetes ?
Multitude of mechanisms
Uptake or breakdown
Type 1 Diabetes
Low or absent endogenous insulin
Dependent on exogenous insulin for life
Onset generally < 30 years
5-10% of cases of diabetes
Symptoms: 3 P’s: polyuria, polydypsia, polyphagia
Type 1 Diabetes cell
Metabolic defects in Type 1 Diabetes
Hyperglycemia and ketoacidosis
Type 2 Diabetes
Insulin levels may be normal, elevated or depressed
Characterized by insulin resistance,
diminished tissue sensitivity to insulin,
and impaired beta cell function (delayed or inadequate insulin release)
Often occurs >40 years
Type 2 Diabetic cell
REMEMBER: the main action of the insulin receptor is to signal the cell to absorb glucose .
A decrease in insulin receptor signaling leads to type 2 diabetes mellitus.
Thus, the cells are not able to take up glucose, leading to hyperglycemia (an increase in glucose circulating in the blood), and all the resulting sequelae.
Type 2 Diabetes
Risk factors: family history, sedentary lifestyle, obesity and aging
Controlled by weight loss, oral hypoglycemic agents and or insulin
Metabolic defects in Type 2 Diabetes
Hypertriacylglycerolemia ----- low levels of insulin ---- decreased activity of lipoprotein lipase ------ raised plasma level of VLDL
Long term effects of Diabetes Mellitus
Microvascular complications :-
Macrovascular complications :-
- cardiovascular disease
Screening/Diagnosis of Diabetes
Decreased insulin production or action
-> Increased glucose accumulates in blood
-> need to dilute glucose in circulating blood
-> fluids drawn from intracellular spaces to vascular bed
-> Thirst (polydipsia)
-> increased fluid intake
-> increased fluid volume
-> kidneys need to excrete excess volume
-> Polyuria (frequent urination)
Glycosuria (excretion of glucose into urine)
Lack of glucose for energy/metabolism
-> cells starve
-> increased hunger ( Polyphagia )
-> increased food intake (weight gain)
No glucose to metabolize
-> protein metabolism (nitrogen imbalance)
-> fat metabolism: (ketone bodies (ketosis))
Polydipsia, polyuria and polyphagia can lead to a fluctuations in blood glucose levels (hyperglycemia and hypoglycemia)
-> damage to small blood vessels throughout the body
-> serious impairment, especially kidneys, eyes, and heart
In pregnancy: decreased glucose to uterus and increased glucose to fetus
-> hypoglycemia at birth
Importance of glucose regulation
The brain: normally dependent on glucose for oxidative metabolism and function
brain fuel deprivation
functional brain failure
corrected by raising plasma glucose concentrations
Osmotic water loss (cellular and systemic)
Damages blood vessels
Classic Hyperglycemic Triad (the 3 P’s of diabetes):
Additional Symptoms of Hyperglycemia
Poor wound healing
Dry or itchy skin
Kussmaul hyperventilation: deep, rapid breathing
Fruity/acetone smell on the breath
Glucose cycle: glucose in the bloodstream is made available to cells in the body
glucose entering the bloodstream
insulin allowing appropriate uptake into the cells of the body.
Both require management.
compliance is an issue
relies on user lifestyle change
often on regular sampling and measuring of blood glucose levels
Many of the long-term complications of diabetes, especially microvascular complications, result from many years of elevated blood glucose levels.
Good glycemic control, (70-130 mg/dl, or 3.9-7.2 mmol/L) is the important goal of diabetes care.
The hemoglobin A1c (glycosylated hemoglobin) reveals “average” glucoses over the preceding 2-3 months.
In normal glucose metabolism, the glycosylated hemoglobin is usually 4-6% by the most common methods (normal ranges may vary by method).
"Perfect glycemic control"
glucose levels were always within the normal range (70-130 mg/dl, or 3.9-7.2 mmol/L)
“ Perfect” glycemic control very difficult, and even "good glycemic control" usually describes blood glucose levels that average somewhat higher than the normal range.
“ Poor glycemic control”
Persistently elevated blood glucose and glycosylated hemoglobin levels
May persist over months and years before severe complications develop.
Diabetes occurs when either there is inadequate insulin production in the pancreas or there is inadequate absorption of insulin into the cells.
Insulin is needed for metabolism of glucose for energy at the cellular level
Lack of glucose for metabolism metabolism of fat and protein for energy, polyuria, polydipsia, and polyphagia (classic symptoms of diabetes) and others listed earlier
Chronic condition that can lead to multiple serious complications
Goal: glycemic control
Dizziness or light-headedness
Another clue to nocturnal hypoglycemia is postprandial hyperglycemia after breakfast
Hypoglycemia can also happen during sleep
crying out or having nightmares
finding pajamas or sheets damp from perspiration
feeling tired, irritable, or confused after waking up
Hypoglycemia, also called low blood glucose or low blood sugar,
occurs when blood glucose drops below normal levels.