Diabetes Mellitus

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WHO Classification:

DM: Fasting glucose > 7.0 mmol/L, or HbA1c of >48 mmol/mol (>6.5%)

One reading with symptoms, or asymptomatic with two readings >7.0

Oral glucose tolerance test: >11.1 mmol/L 2hrs after 75 g anhydrous glucose

Impaired Glucose Tolerance:

a fasting blood glucose of less than 7 mmol/L, AND

a blood glucose of 7.8 mmol/L or more but less than 11.1mmol/L after a two-hour oral GTT

Impaired fasting glycaemia:

a fasting blood glucose between 6.1 to 6.9 mmol/L, AND

a blood glucose of less than 7.8 mmol/L after a two-hour oral GTT

Major types:

Type 1 diabetes mellitus: failure to produce sufficient insulin (autoimmune destruction of pancreatic islet beta cells)

Type 2 diabetes mellitus: resistance to insulin, often initially with normal or increased levels of circulating insulin.

Gestational diabetes: affects about 4% of all pregnant women. It may precede development of type 2 (or rarely type 1) diabetes.

Maturity-onset diabetes of the young (MODY) : monogenetic defects of beta-cell function (impaired insulin secretion), usually manifesting as mild hyperglycaemia at a young age, and usually inherited in an autosomal-dominant manner.

Late Autoimmune Diabetes of Adulthood (LADA) is form of Type 1 DM with slower progression and onset in adulthood

Secondary causes of diabetes: accounts for only 1-2% of patients with diabetes mellitus, caused by other disease processes

Pancreatic disease: cystic fibrosis, chronic pancreatitis, pancreatectomy, carcinoma of the pancreas.

Endocrine: Cushing's syndrome, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma.

Drug-induced: thiazide diuretics, corticosteroids, atypical antipsychotics, antiretroviral protease inhibitors.

Congenital lipodystrophy.

Acanthosis nigricans.

Genetic: Wolfram's syndrome (which is also referred to as DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy and deafness), Friedreich's ataxia, dystrophia myotonica, haemochromatosis, glycogen storage diseases.

Type 1 Diabetes:

weight loss, dehydration, ketonuria and hyperventilation.

more common in Caucasians

acute onset

Type 2 Diabetes:

often obesity-related, less likely to have high ketones

more common in South Asians, American-Indians, Middle Eastern, Afro-Carribbean ethnicity

subacute and gradual onset

All diabetes present with: polyuria, polydipsia, lethargy, boils, pruritus vulvae or with frequent, recurrent or prolonged infections.

Dietary advice

Type 1:

-diet mainly to avoid hypoglycaemic events (on insulin)

- Educational programmes - eg DAFNE (= Dose Adjustment For Normal Eating) to adjuct insulin doses with meals, along with self-monitoring

- Awareness of :

The effects of different alcohol-containing drinks on blood glucose excursions and calorie intake.

The use of high-calorie and high-sugar 'treats' (to treat hypoglycaemia)

The use of foods of high glycaemic index. (to treat hypoglycaemia)

Type 2:

- using low glycaemic index (low GI) food to improve glycaemic control without getting hypoglycaemic events

- if obesity is an issue, aim for 5-10% weight loss

- avoiding excess energy intake

- salt restriction to reduce BP

Evaluating diabetic control:

- HbA1C: between 6.5-7.5% is good control

-self-monitoring blood glucose testing (maintain between 7-11)

-urine testing (ketones, protein for kidney disease, nitrites for UTIs)

- Check eyes (retinopathy), kidneys (nephropathy), and peripheral limbs especially legs and feet (neuropathy, ulcers, gangrene)

- frequency and severity of hypoglycaemic events

- any events of ketoacidosis (DKA) or hyperosmolar hyperglycaemic non-ketotic coma (HONK)

Major Hyperglycaemic Events:

Diabetic Ketoacidosis (DKA): hyperglycaemia (>11mmol/L), acidosis (pH3mmol/L or >2+ on urine stick) usually in Type 1 DM patients

Hyperosmolar hyperglycaemic state (HHS): hyperglycaemia with significant hyperosmolarity without ketone production due to sufficient insulin production to prevent ketogenesis (usually in Type 2 DM)

Metabolic pathways in DKA:

Hyperglycaemia causes an osmotic diuresis with hyperosmolarity, leading to an osmotic shift of water into the intravascular compartment, resulting in severe intracellular dehydration

lack of insulin and corresponding elevation of glucagon leads to increased release of glucose by the liver from glycogen via glycogenolysis and also through gluconeogenesis

The absence of insulin also leads to the release of free fatty acids from adipose tissue (lipolysis), which are converted, again in the liver, into ketone bodies

Common causes for DKA:

Infection, eg pneumonia, urinary tract infection.

Inadequate insulin or non-compliance.

Other medical illnesses, eg pancreatitis, pulmonary embolism, hypothyroidism.

Cardiovascular disease, stroke, myocardial infarction.

Cause unknown (4-33%).

Any physiological stress (including pregnancy, trauma or surgery)

Medication (notably corticosteroids, sympathomimetics, α- and β-blockers and diuretics)

menstruation

Hypoglycaemia

Autonomic symptoms:

Shaking and trembling

Sweating

Hunger

Anxiety and palpitations (tachycardia)

Neuroglycopaenic symptoms:

Headache (occasionally),

Blurred or double vision

difficulty in concentrating

Slurring of speech

confusion or ataxia (in-coordination)

change of personality, inappropriate behaviour

Severe cases: fainting, seizures, stupor or coma

Major counter-regulatory hormone response:

- increase in glucagon leading to glycogenolysis and gluconeogenesis in the liver to raise blood glucose

- free fatty acids released from adipose tissues converted into ketones as an alternative fuel source

Why hypoglycaemia occurs:

- Excess insulin medication (increased dose, reduced dietary intake of carbs, increased activity and glucose demand)

- oral hypoglycaemic medications (sulfonylureas)

- Other drugs and toxins including pentamidine, quinine, paracetamol and toadstools

-Other rare causes:

Pancreatic endocrine tumours - eg, insulinoma.

Extrapancreatic IGF-II-secreting neoplasms - eg, adrenal tumours.

Autoimmune hypoglycaemia (endogenous antibodies reacting with insulin or the insulin receptors).

Reactive hypoglycaemia: may be caused by upper gastrointestinal surgery or congenital enzyme deficiencies such as hereditary fructose intolerance, galactosaemia or leucine sensitivity of childhood.

Hormone deficiencies - eg, hypoadrenalism, hypopituitarism.

Starvation.

Management:

a quick-acting carbohydrate needs to be given (e.g IV glucose, or oral dextrose/glucagon gel) , followed by longer-acting carbohydrate.

Microvascular complications:

Eyes (Retinopathy): small blood vessel damage to the back layer of the eye, the retina, leading to progressive loss of vision, even blindness.

Kidney (nephropathy): damage to small blood vessels in the kidneys, can cause kidney failure, and eventually lead to death.

Nerves (neuropathy): direct damage by the hyperglycemia and decreased blood flow to nerves by damaging small blood vessels. Lead to sensory loss, damage to limbs, and impotence in diabetic men.

Good diabetic control can delay onset and progression of these complications. Longer duration of diabetes will make these complications more likely. Early detection via screening and early intervention is necessary.

Peripheral sensorimotor neuropathy:

Sensory nerves are affected more than motor.

Touch, pain and temperature sensation and proprioception in lower limbs in a glove and stocking distribution.

Loss of ankle jerks and, later, knee jerks.

Hands are only affected in severe long-standing neuropathy.

Equal prevalence in types 1 and 2.

Consequences:

- major cause of morbidity and increased mortality

- increases the risk of burns, injuries and foot ulceration ( and hence limb amputations)

Accelerated macrovascular disease:

Hyperglycemia damages blood vessels through a process called “atherosclerosis”, or clogging of arteries.

This narrowing of arteries can lead to decreased blood flow to heart muscle (MI), or to brain (leading to stroke), or to extremities (leading to pain and decreased healing of infections).

Common risk factors for vascular disease in people with diabetes, specifically type 2 diabetes, include hyperglycemia, insulin resistance, dyslipidemia, hypertension, tobacco use, and obesity.

Mechanisms for vascular disease in diabetes include the pathologic effects of advanced glycation end product accumulation, impaired vasodilatory response (nitric oxide inhibition), smooth muscle cell dysfunction, overproduction of endothelial growth factors, chronic inflammation, hemodynamic dysregulation, impaired fibrinolytic ability, and enhanced platelet aggregation.

Diabetic foot:

Peripheral neuropathy in people with diabetes results in abnormal forces being applied to the foot (loss of sensation, unaware of pain)

diabetic ischaemia renders the skin less able to withstand those forces

Other complications: poor vision, limited joint mobility, and the consequences of cardiovascular and cerebrovascular disease

most common precipitant is accidental trauma, especially from ill-fitting footwear.

defective healing: bacterial infection, tissue ischaemia, continuing trauma, and poor management.

Consequences:

-Charcot's foot

- recurrent ulceration

- tissue necrosis (gangrene)

- limb amputation

DM

Metabolic Complications

Vascular complications