INTRODUCTION From a Greek word meaning ‘To pass through’. Group of disorders exhibiting a defective or deficient insulin

secretory response, glucose underutilization, and consequently, hyperglycaemia.

Due to Absolute or Relative Insulin deficiency; Insulin resistance. Carbohydrate, protein and fat metabolism is affected. Long-term complications : Diabetic angiopathies (nephro, neuro

and retino). Hyperglycaemia is also caused by over-production of hormones

like glucagon, adrenal hormones or overactivity of Insulinase. FBG (3.9 to 5.5 mmol/L or 60 – 90 mg/dl); RBG (3.9-6.9 mmol/L or 90 – 110 mg/dl); PPBG (3.9-8.1 mmol/L or 120 – 180 mg/dl). Onset : Type-I (20% of cases; early age); Type-II (80%; occurs later - maturity onset). CLASSIFICATION : Primary / Idiopathic DM Secondary DM

Fasting blood glucose:

Less than or equal to 6.1 mmol/L (110 mg/dL);

2 hours after

eating (postprandial):

age 50 and younger: <7.8 mmol/L (140 mg/dL); ages 50-60:<8.3 mmol/L (150 mg/dL); age 60 and above: <8.9 mmol/L (160 mg/dL)

Random (casual): Levels vary depending on when and how much you ate at your last meal. In general: • before meals or when waking up: 4.4-6.6 mmol/L (80-120 mg/dL); • at bedtime 5.5-7.7 mmol/L (100-140 mg/dL)

CLASSIFICATIONPRIMARY / IDIOPATHIC DM Most common; unknown cause. Further divided into:

• Type-I DM (Insulin-dependent / IDDM / Juvenile onset)• Type-II DM (Non- Insulin-dependent / NIDDM / Adult /

Maturity onset)• Potential DM • Latent DM • Gestational DM • Asymptomatic DM

Type-I DM - Absolute Insulin deficiency; mostly in people < 40 yrs. - Exhausted pancreatic β cells can’t produce insulin. - Unknown cause, but could be due to …. Immunological destruction of β cells, genetic susceptibility,

viruses, chemicals and environmental toxins. - Rapid onset of symptoms

Type-II DM - More common subtype (80%); mostly in people > 40 yrs. - These days, it can occur at any age. - Inadequate insulin secretion; Peripheral tissues develop resistance to insulin. - Etiology: Hereditary, genetic makeup, obesity, etc. - Slow onset of symptoms Note: Type-I and Type-II are collectively called Clinical DM.

Potential DM - Person w/ normal glucose tolerance but, positive familial history. - Age-related occurrence is very high. - Must have good diet control and avoid precipitating factors.

Latent DM - Diabetic type of Glucose tolerance without any consistent

elevation of blood glucose level.

Gestational DM - Temporary elevation of blood glucose level during

gestational period. - Automatically disappears post-delivery.

Asymptomatic DM - Glucose tolerance curve resembles a diabetic patient but, actual clinical symptoms are absent. - Can occur in the future.

SECONDARY DM Minor type Has definite causes. Causes: Pancreatic disorders, Pancreatic damage, Insulin antagonist (Excess of Growth Hormone). Insulin secretion inhibited (by epinephrine). May or may not be insulin-dependent.

Foods (mainly high carbs) → ↑ed Glucose in blood; (used as fuel) ↓ Insulin released (to counter rising blood glucose levels) Insulin regulates glucose uptake from the blood into most cells

(muscle and fat cells, but not CNS cells). Roles of Insulin: a] Regulates glucose absorption from blood (for use as fuel). b] Stimulates conversion of excess glucose to glycogen (in liver and muscle). c] Stimulates cell growth, protein synthesis and fat storage.

Insulin deficiency / insensitivity of it’s receptors is vital in all forms of DM.

Lowered glucose levels → reduced insulin release & reverse

conversion of glycogen to glucose [Mainly controlled by the hormone Glucagon which acts in an opposite manner to insulin].

PATHOPHYSIOLOGY

• Insufficient or deficient insulin / Insulin resistance ↓ Inadequate absorption and storage of glucose

NET EFFECTS Persistent high levels of blood glucose Poor protein synthesis Derangements in carbohydrate, protein and fat

metabolism Acidosis

CLINICAL FEATURES Elevated Blood sugar levels (nil/inadequate/ underutilization

of insulin). Glycosuria Polyuria / Excessive urination (response to glycosuria;

kidneys excrete additional water to dilute the excess glucose).

Polydipsia / Excessive thirst (due to polyuria). Polyphagia / Excessive hunger (due to energy loss). Weakness and weight loss (excess loss of calories in urine). Nausea, blurred vision, drowsiness, RF, opportunistic

infections, easily fatigued. Gangrene develops (Amputate affected part – toes, legs).

COMPLICATIONS OF DM Diabetic ‘pathies’ / angiopathies (retino,

neuro and nephro) Atheroscelorsis (incl. peripheral and coronary

blood vessels) Hypertension (persistent systolic HTN) Hyperglycaemia-induced cataract Altered GI function Impaired WBC function → Immunity

compromised Deep Infections (Diabetic foot ulcers) with

poor healing Diabetic and Hypoglycaemic coma

DIABETIC RETINOPATHY No early warning signs. Damage to retina → Blindness. Macular edema → blurred vision; can’t read, write, drive

vehicle. Proliferative Diabetic Retinopathy (PDR) : New blood vessels

formed at the back, hemorrhage and leak blood and proteins. Not severe at first (Blood specks or spots vanish after a few hours). Becomes worse gradually. Person can’t distinguish light from dark.

Aneurysms and Brittle blood vessels (Neovascularization) cause Retinal scarring and detachment.

Glaucoma and cataracts O/E: Cotton wool spots, Flame hemorrhages, Spot

hemorrhages

‘Cottonwool’ spots

DIABETIC NEUROPATHY Due to diabetic vascular injury to small blood vessels that

supply nerves (Vasa nervorum). Limited blood flow to the nerve → nerve damage or death.

Signs and symptoms : • Numbness and tingling of extremities (patients are

unaware of injuries to any part supplied by damaged nerves).

• Dysesthesia (loss of or decreased sensation to a body part)

• Diarrhea, Muscle weakness, Dysphagia (difficulty in swallowing)

• Erectile dysfunction, Impotence • Urinary incontinence.• Vision changes, Speech impairment • Facial, mouth and eyelid drooping. • Dizziness, Fasciculation (muscle contractions). • Burning (especially in evenings), Electric Stabbing Pains.

DIABETIC NEPHROPATHY Kimmelstiel-Wilson syndrome Inter-capillary glomerulonephritis. Progressive kidney disease caused by capillaries’

angiopathy in the kidney glomeruli. Characterized by nephrotic syndrome and nodular glomerulosclerosis.

Proteinuria; kidneys lose filtering and cleansing ability (toxins remain in the body).

Signs & Symptoms : • Oedema (initially around the eyes; later - general body

swelling legs are mostly affected); Unintentional weight gain.

• Urine (foamy appearance or excessive frothing). • Anorexia, NV, Malaise, Fatigue, Headache.• Frequent hiccups, Generalized itching.

DIABETIC KETOACIDOSIS Very severe form of DM complication. Occurs in Type-II DM; glucose can’t be used as an energy

source. So, fats are used for energy. Excess liberation of FFAs from adipose tissue and hepatic oxidation → Ketonic body production (Butyric Acid and

Acetoacetic acid) → Blood becomes acidic (Diabetic Ketoacidosis)

Acetone smell in patient’s breath, Ketonaemia, Ketonuria → Diabetic Coma.

[FFA= Free Fatty Acids]

HYPOGLYCAEMIC COMA

DIABETIC COMA

Sudden onset(Insulin Overdose)

Delayed onset (prolonged illness and lack of insulin)

Sweating, tremors, headache, mental

confusion

Dehydration, abdominal pain, vomiting

Moist skin, normal respiration and slightly

elevated B.P.

Dry skin, low pulse and low B.P.

No ketonuria Ketonuria

For Blood Glucose levels : Glucometers FBS, RBS and PPBS Glucose Tolerance Tests (GTT): Oral or I.V.

HbA1c (Glycosylated Hb) • To identify average plasma glucose conc. over prolonged

time periods. • Ratio of Glycosylated Hb to total Hb. • Hb exposed to high plasma blood glucose levels.• Estimated by : HPLC and Immunoassays.• Reference range : 4.0 – 5.9% (normal); < 6.5% (good control); Higher for DM (> 6.5%). • Checking blood sugar control in Pre-diabetics; Monitoring blood sugar control in DM patients. • Far more revealing information on glycemic behavior than a fasting blood sugar value.

Interpretation of HbA1c test

HbA1c Mean Blood Sugar (mg/dl)

6 135

7 170

8 205

9 240

10 275

11 310

12 345

Urine tests : Glycosuria, Ketonuria (severity of DM). Blood glucose estimation : GTT

Glucose Tolerance Test [ GTT ] • OGTT is the standard for the diagnosis of Type-II DM. • 3 days before test, the person should have eaten a diet high

in carbohydrates (150- 200 grams per day). • Person fasts overnight (8 - 16 hours). • The morning of the test, the person should not smoke or

drink coffee. • The FPG is tested. • Then, the person receives 75 grams of glucose (100 grams

for pregnant women). Usually, the glucose is in a sweet-tasting liquid that the person drinks.

• Blood glucose levels are measured five times over a period of 3 hours.

RESPONSES AND DIAGNOSES OF OGTT

Normal response: • all values between 0 – 2 hours < 200 mg/dl • 2-hour glucose level <140 mg/dl

Impaired glucose tolerance (IGT): • Fasting plasma glucose < 126 mg/dl • 2-hour glucose level is between 140 – 199 mg/dl

Diabetes: • 2 diagnostic tests done on different days show high blood glucose

levels • fasting glucose > 126 mg/dl; 2 hour levels > 200 mg/dl

Gestational diabetes: • For 100g OGTT, a fasting plasma glucose > 95 mg/dl;• 1-hour glucose level > 180 mg/dl, 2-hour glucose level of > 155

mg/dl, or 3-hour glucose level > 140 mg/dl

Health Screening Height, weight and B.P. measurements Thyroid examination Examination of hands, fingers, feet, and toes for

circulatory abnormalities Blood tests for fasting blood sugar, HbA1c and cholesterol Family history of diabetes, cardiovascular disease, and

stroke. Prior infections and medical conditions A list of current medications, including: Prescription

medications, OTC medications, Vitamins and herbal supplements

Health Screening (contd’.)

Smoking history, including encouragement to stop smoking (if applicable).

Signs of complications with pregnancy. Eating and exercise habits Vision abnormalities, to check for eye health issues Urination abnormalities, which can indicate kidney disease.

TO BE CONTINUED…