Chapter 9 Diabetes mellitus
Diabetes mellitus is a metabolic condition characterised by hyperglycaemia (high blood glucose level) due to defective insulin secretion, or insulin action, or both. Hyperglycaemia can lead to acute and chronic complications. Long standing hyperglycaemia affects multiple organs leading to chronic complications.
9.1 Prevalence of diabetes mellitus
537 million people are living with diabetes globally as per International Diabetes Federation and around 100 million of them are from India. One in 10 adults in India suffer from Diabetes mellitus making it a signficant public health problem.
9.2 Types of diabetes mellitus
9.2.1 Type 1 diabetes mellitus
Type 1 diabetes mellitus occurs due to autoimmune destruction of β-cells in pancreas leading to absolute deficiency of insulin. Type 1 diabetes accounts for 5-10% of all cases of diabetes mellitus. Type 1 diabetes usually develops in younger age.
9.2.2 Type 2 diabetes mellitus
Type 2 diabetes mellitus is characterised by relative insulin deficiency i.e., insulin is secreted in lesser amount than what is required by the body. Action of insulin is impaired in type 2 diabetes (insulin resistance) and there is a progressive decrease in insulin secretion from beta-cells. Type 2 diabetes usually develops at an older age (>35 years). Multiple genetic and environmental factors including obesity Iincreases the risk of Type 2 diabetes mellitus.
9.3 Clinical features of diabetes mellitus
Following are the classical signs of diabetes mellitus
- Polyphagia – Increased hunger
- Polydipsia – Increased thirst
- Polyuria – Increased urination
- Weight loss
Patients can also present with acute or chronic complications of diabetes mellitus
9.4 Complications of diabetes mellitus
9.4.1 Acute complications
9.4.1.1 Diabetic ketoacidosis
Usually occurs in untreated or poorly controlled diabetes mellitus patients. It is more common in Type 1 diabetes mellitus. Diabetic ketoacidosis is characterised by increased production of a metabolite called ketone bodies. Ketone bodies are acids and it leads to acidosis. It is also characterised by high levels of blood glucose and dehydration.
9.4.2 Chronic complications
9.4.2.1 Microvascular complications
OccurS due to damage of the small blood vessels supplying various organs.
Diabetic retinopathy: Diabetic retinopathy is the leading cause of blindness in adults.It affects the capillaries of the retina.
Diabetic nephropathy: Diabetic nephropathy is the most common cause of chronic kidney disease. It affects the glomerulus and is characterized by excretion of protein in urine (proteinuria).
Diabetic neuropathy: Diabetes can damage the nerve fibers resulting in sensory neuropathy, and autonomic neuropathy.Clinical manifestations include loss of sensation, numbness, tingling sensation, pain, orthostatic hypotension etc.
9.4.2.2 Macrovascular complications
Macrovascular complications ococurs due to damage of the large blood vessels supplying various organs.
Heart: Coronary artery disease. Diabetes mellitus increases the risk of cardiovascular diseases by several times compared to people without diabetes.Hyperglycaemia along with dyslipidaemia and other factors promote the formation of atherosclerosis leading to cardiovascular diseases.
Limbs: Peripheral vascular disease. Affects foot, leg, intestine etc.
Brain: Damage of the blood vessel supplying brain leads to stroke
9.4.3 Non-vascular complications
Infection: Diabetes increase the risk of infection due to an abnormal immune system and damage to blood vessels supplying tissues
Dermatological manifestations: People with diabetes experience xerosis (dry skin) and pruritis (itching)
9.4.4 Mechanism of complications of diabetes mellitus
Sorbitol pathway
Tissues such as lens, retina, kidney and nerves convert glucose to sorbitol when glucose is present at high concentration, but they lack sorbitol dehydrogenase to convert sorbitol to fructose. In Diabetes Mellitus, accumulation of sorbitol causes osmotic damage to these tissues leading to cataract, retinopathy, nephropathy and neuropathy.
Advanced glycation end products
Increased glucose levels leads to increased non-enzymatic attachment of glucose (glycation) to proteins present inside and outside the cell. This results in a number of effects damaging the tissues.
9.5 Laboratory investigations for diabetes mellitus
9.5.1 Laboratory investigations to diagnose diabetes mellitus
Fasting plasma glucose: Glucose level in blood sample taken after at least 8 hours of calorie restriction (usually overnight fasting)
Random plasma glucose: Glucose level in blood sample without any specific restriction on fasting/eating
Oral glucose tolerance test (OGTT)/ Procedure:
Fasting plasma glucose level is measured
Then a standard amount of glucose (usually 75g of glucose) is dissolved in water and given to patients for drinking it
Plasma glucose levels is measured at 1 and 2 hr after administering the glucose
Use: To diagnose gestation diabetes mellitus
HbA1c (Glycated haemoglobin)
HbA1c is produced in the body by a non-enzymatic addition of glucose to haemoglobin
% of HbA1c in blood reflects the average concentration of blood glucose present over the life time of RBCs
HbA1c usually reflects the average blood glucose level for the past 8 to 12 weeks of the patient
9.5.1.1 Criteria for diagnosis of diabetes mellitus – By American Diabetes Association
| Fasting plasma glucose ≥126 mg/dL |
|---|
| OR |
| 2-hour plasma glucose ≥200 mg/dL during OGTT |
| OR |
| HbA1c ≥6.5% |
| OR |
| In a patient with classic symptoms of hyperglycemia a random plasma glucose ≥200 mg/dL |
9.5.2 Investigations for monitoring blood glucose level (glycemic control) in patients diagnosed with diabetes mellitus
Fasting plasma glucose
Plasma glucose measured 2 hours after eating a meal (post-prandial)
HbA1c
Self-monitoring of blood glucose (SMBG): Patients can monitor their blood glucose themselves by using a point of care testing device, called glucometer
9.5.3 Investigations for monitoring complications of diabetes mellitus
Lipid profile
Lipid profile includes measuring LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol level in blood
Dyslipidemia (abnormal lipid profile) increases the risk of macrovascular complications of diabetes mellitus
Regular monitoring of lipid profile and management aids in reducing the risk of developing macrovascular complications.
Serum creatinine: Serum creatinine is measured to monitor for development of chronic kidney disease
Urine protein: Measurement of protein levels in urine aids in early detection of diabetic nephropathy
9.6 Principles of treatment of diabetes mellitus
Aim of the treatment is to maintain the blood glucose level within target levels to prevent complications. This involves regular monitoring of glycaemic control. It can be achieved by a combination of lifestyle modifications and pharmacological interventions. Lifestyle modifications include modifications in diet and physical activity, smoking and alcohol cessation. Pharmacological interventions include oral hypoglycaemic agents which act by multiple mechanisms e.g., Sulfonylurea class of drugs increase insulin secretion.For type 1 diabetes and uncontrolled type 2 diabetes, insulin injections are necessary.