DIABETES

Disease Burden of Diabetes Mellitus

Leading cause of blindness (12.5% of cases) Leading cause of ESRD (42% of cases) 50% of all non-traumatic amputations 2.5x increase risk of stroke 2-4x increase in cardiovascular mortality DM responsible for 25% of cardiac surgeries Mortality in DM: 70% due to Cardiovascular disease

ANATOMY AND PHYSIOLOGY

The second largest gland in the body and is both an endocrine and exocrine gland.

EXOCRINE FUNCTION
To produce digestive (pancreatic) juices and to release them into the duodenum via the pancreatic duct.

ENDOCRINE FUNCTION
One function is to control the amount of glucose in the blood. The cells that control blood glucose levels are called the islets of Langerhans

ISLET CELLS
Two types : Alpha and Beta. Alpha cells secrete glucagon. Beta cells secrete insulin. Insulin and glucagon work as a check and balance system regulating the bodys blood glucose level.

Regulation of Glucose

Insulin

Glucagon

Glucagon and Insulin are opposites (antagonists) of each other.

GLUCAGON
Glucagon accelerates the process of liver glycogenolysis (a chemical process by which glycogen stored in the liver is converted to glucose). This glucose then leaves the liver cells and enters the blood. This process tends to increase the concentration of glucose in the blood.

INSULIN
Insulin decreases the amount of blood glucose concentration. Insulin decreases blood glucose by accelerating its movement out of the blood through cell membranes and into cells. As glucose enters the cells at a faster rate, the cells increase their metabolism of glucose.

 All sugary and starchy foods are broken down into glucose. In this form every cell can absorb them in the body including the cells in the liver, one of whose major roles is to store glucose.

 Cells absorb glucose and burn it in structures called mitochonria, using the energy it contains and producing carbon dioxide as its by products. This burning up process is the bodys principal source of energy. It cannot take place without insulin.
Adapted from Torta (1996)

TYPE 1 DIABETES
Results from the destruction of the beta cells in the islets of Langerhans, which leads to insulin defficiency.

Pathophysiology of T1DM

antibodies attack islets!

TYPE 2 DIABETES
Important sites of glucose utilisation, such as adipose tissue, liver and skeletal muscle show a reduced response to normal circulating levels of insulin (a state of insulin resistance) Compensatory hyperinsulinaemia results, and together insulin resistance and resultant beta cell dysfunction progress to Type 2 diabetes.

Pathophysiology of T2DM

Hepatic glucose output

INSULIN

Blood glucose
diet

+
Peripheral Tissue Uptake

Natural History of Type 2 Diabetes

Insulin resistance Glucose level

F -cell dysfunction

Insulin production Time

Normal

Impaired glucose tolerance

Type 2 diabetes

Type 1 v.s. Type 2 Diabetes

Type 1 DM (< 10%) < 40 Yes Usually lean Type 2 DM (> 90%) > 40 No 80% overweight

Age of onset DKA Weight Cause

Autoimmune or No autoimmune unknown markers

Why is the prevalence of Type 2 Diabetes mellitus increasing?

The answer is magically ridiculous

FUNCTION OF INSULIN
Secreted in response to eating. Due to the absorption of glucose into the blood from carbohydrates, blood glucose normally rises in the hour after eating. This rise stimulates the pancreas to release insulin. Insulin is the hormone of fuel storage and cell growth, prevents the breakdown of fat, and promotes protein synthesis.

During fasting, blood glucose falls, insulin production shuts down and liver glycogen is broken down into glucose (glycogenolysis). A low level of glucose also signals for protein and fat to be broken down and used by the liver to synthesis glucose (gluconeogenesis). When fast is broken, insulin will be secreted, insulin feedback to the liver will switch off glycogenolysis or gluconeogenesis.

 Gluconeogenesis is an adaptive process, which allows us to skip meals without ill effect. It prevents blood glucose falling low during fasting. In diabetes when insulin is missing gluconeogenesis becomes unrestrained. Without insulin to stop lipolysis, stored fat is broken down and transferred to the liver.

 This leads to the formation of ketones. These can be used for energy, especially in the muscle. Tissue proteins are also broken down into amino acids to provide the liver with the carbon structure of sugar. This is released into the blood stream. Without insulin there is no glucose uptake into the tissues, resulting in overflow into the urine. The osmotic effect of urinary glucose draws water, sodium and potassium out causing polyuria and polydipsia.

 Glucose in the urine encourages yeasts to grow on the skin causing pruritis. Glucose also accumulates in the lens of the eye causing misting or blurring of vision as a result of fluid shift. Breakdown of muscle protein causes weakness and wasting and breakdown of fat causes weight loss. When beta cells fail completely glucose and ketone production causes marked hyperglycaemia and ketoacidosis.

DIAGNOSTIC CRITERIA
1. 2. 3. Fasting plasma glucose >126 mg\dl Random plasma glucose >200 mg\dl 2 hour plasma glucose (during OGTT) .200mg\dl American Diabetes Association 1997

Two abnormal test results (using any of the above methods) are required to make a diagnosis. Values near the diagnostic boundaries require confirmation either from a repeat measurement or oral glucose tolerance test. The diagnosis of diabetes has serious medical and legal implications for the patient. A diagnosis should never be made on a capillary sample, HBA1C or glycosuria. .

Pre-diabetes or Diabetes?

A casual plasma glucose > 200 with symptoms of hyperglycemia

A1C Blood Test

Hemoglobin A1c 6% 7% 8% 9% 10%

Average Blood Sugar 135 mg/dL 170 mg/dL 205 mg/dL 240 mg/dL 275 mg/dL

DIETARY GUIDELINES
The diet recommended for people with diabetes are the healthy eating guidelines recommended for the general population. Healthy eating is regarded as the cornerstone of diabetes management.

AIMS
To maintain blood glucose at as near normal levels as possible. To prevent hypoglycaemia. To achieve and maintain ideal bodyweight. To reduce the risk of diabetic complications.

PRINCIPLES
Eat regular meals include starchy food at each meal, e.g. bread, potato, cereal, rice or past. This helps to control blood glucose levels. Maintain a healthy weight. Reduce intake of sugar and foods high in sugar. Eat less fat. Eat more fibre. Eat fruit and vegetables or salad daily. Reduce salt intake.

Diabetes Medications

INSULIN TREATMENT
The main aim of treatment is to maintain near normal blood glucose as is practical and safe for the individual, to avoid hypoglycaemia and extreme hyperglycaemia.
Insulin should never be witheld or stopped without prior consultation with the diabetes team.

Hyperglycemia Can Cause Serious Long-Term Problems

INSULIN PREPARATIONS 1.
NAME Humalog Novorapid Actrapid Humulin S TYPE Rapid Acting Rapid acting Soluble SOURCE Human Human Human/Pork Human ONSET 0-15 minutes (inject with Meals) 30-45 minutes (inject 20-30 minutes before meals) 1-2 hours DURATION 4 hours 5 hours 6-8 hours

Insulatard Humulin I Lantus Levemir

Isophane Isophane Long acting analogue

Human/Pork Human Human Human

8-12 hours or longer 20-24 hours

1-2 hours

INSULIN PREPARATIONS 2.
NAME Mixtard 30/70 Humulin M3 TYPE A pre mixed combination of 30% SOURCE Human Human ONSET 30-45 minutes (inject 20mins before meal) As above DURATION 7-12 hours or longer

Hypurin 30/70 soluble and 70% isophane Novomix 30 A pre mixed combination of 30%analogue And 70% isophane

Pork

As above

Human

0-15 minutes (inject with meal)

7-12 hours or longer

Blood Glucose Targets for Adults

Pre-meal or fasting: 80-120 2 hours post-meal: 80-140 Bedtime: 80-140 or 100-140

Good News for Type 1 Diabetes

DRUG TREATMENT OF TYPE 2 DIABETES Sulphonylureas Gliclazide, Glimepiride, Glipizide Act by stimulating pancreatic production. Take before food. It is important not to miss meals as hypoglycaemia is a side effect.

Oral Medications for Type 2 Diabetes: Sulfonylureas

 BIGUANIDES Metformin Act by decreasing gluconeogenesis, stimulating peripheral glucose metabolism and impairing the absorption of glucose from the gut. Contraindicated where there is hepatic or renal dysfunction as use carries the risk of lactic acidosis. The most common side effect is of gastrointestinal upset, nausea, diarrhoea and flatus. Side effects can be reduced by taking after food.

Oral Medications for Type 2 Diabetes: Biguanides

 GLUCOSIDASE INHIBITOR Acarbose Retards glucose uptake from the intestines by inhibiting carbohydrate breakdown. Side effects are mainly gastrointestinal and are caused by increased gas formation due to fermentation of unabsorbed carbohydrate in the bowel.

Oral Medications for Type 2 Diabetes: Alpha-Glucosidase Inhibitors

 THIAZOLODINEDIONES Pioglitazone, Rosiglitazone Reduce peripheral insulin resistance, leading to a reduction of blood glucose concentration. Contraindicated in cardiac failure and liver impairment.

Oral Medications for Type 2 Diabetes: Insulin Sensitizers

Sites of Action of Currently Available Therapeutic Options

LIVER PANCREAS GLUCOSE PRODUCTION Metformin Thiazolidinediones PERIPHERAL GLUCOSE UPTAKE Thiazolidinediones Metformin ADIPOSE TISSUE MUSCLE

INTESTINE

INSULIN SECRETION Sulfonylureas: Glyburide, Gliclazide, Glimepiride Non-SU Secretagogues: Repaglinide, Nateglinide

GLUCOSE ABSORPTION Alpha-glucosidase inhibitors

HYPOGLYCAEMIA
Hypoglycaemia is defined as a blood glucose level below 4 mmol/l. Most body tissues can derive energy from other sources. The nervous system and the brain depend on a constant supply of blood glucose. A low blood glucose level activates an autonomic response in the sympathetic and parasympathetic nervous system, which leads to the autonomic symptoms of hypoglycaemia.

SYMPTOMS
AUTONOMIC SYMPTOMS (MILD) Sweating Pounding heart Shaking/trembling Hunger Tingling of lips/fingers Anxiety

NEUROGLYCOPENIC SYMPTOMS (Moderate) Confusion Drowsiness Odd behaviour Speech difficulty Difficulty in thinking

 NEUROGLYCOPENIC SYMPTOMS (severe) Loss of consciousness Seizures

TREATMENT
Mild symptoms can be treated with simple carbohydrate (quick acting) , followed by complex carbohydrate (longer acting) such as a plain biscuit. If symptoms persist after 10 minutes this treatment can be repeated.

 If mild symptoms are not recognised and treated the blood sugar may continue to fall and symptoms increase or change. Confusion or aggressive behaviour may occur leaving patients unable to treat themselves. Moderate hypoglycaemia may require help from others.

CAUSES OF HYPOGLYCAEMIA
Inappropriate treatment dose insulin or sulphonylureas Diet Delayed or missed meals Inadequate intake of carbohydrate Insulin treated patients should have bed time snack Exercise Unplanned or sustained Alcohol

NOCTURNAL HYPOGLYCAEMIA
May be difficult to diagnose if the patient sleeps alone and does not wake. Most episodes of nocturnal hypoglycaemia are asymptomatic but morning headache or tiredness along with morning hyperglycaemia are an indicator.

KETOACIDOSIS
Diabetic Ketoacidosis is a serious condition and a medical emergency. DKA occurs as a result of very low insulin levels, and is therefore mainly occur with Type 1 diabetes. People with Type 2 diabetes may develop DKA.

INITIAL SIGNS AND SYMPTOMS

Polyuria Polydipsia Polyphagia Blood glucose levels >300 Ketones present in blood/urine (check) At this stage it is possible to return to normal blood glucose levels by administering short acting insulin.

Progression
Nausea and vomiting Moderate/large ketones in urine Kussmaul respiration Breath smells of acetone Drowsiness, confusion,unconsciousness

Diabetic Ketoacidosis
Inadequate insulin Increased Blood Sugar Cells Cant Burn Glucose Polyphagia Cells Burn Fat

Osmotic Diuresis

Ketone Bodies Polyuria Volume Depletion Shock

Metabolic Acidosis

Polydipsia
Kussmaul Breathing

Fruity Breath

CAUSES
Intercurrent illness (the increased need for insulin occurs even when patient is unable to eat.Hepatic glucogenesis is stimulated by lack of insulin) Stoppage/reduction of insulin (Patients are advised never to stop/reduce their insulin when unwell) Undiagnosed diabetes No obvious cause

Management
get iv access. Start fluid (normal saline 0.9%)replacement immediately,give one litre stat. then 1 litre over one hour, 1 litre over 2 hours,1 litre over 4 hours, 1 litre over 12 hours Use dextrose 5 % or dextrose/saline when blood glucose >15mmol/litre Those with heart failure be cautious with fluids Potassium enters cells when insulin is given so add potassium 20-40 mmol/litre to fluids from the next 2 hours

 Soluble (Actrapid) Insulin given as stat.dose 8-10 units if glucose is >20mmol/litre then sliding scale according to plasma glucose level. It can be given intravenously in a pump or subcutaneously Check glucose,K+ ,bicarbonate and urea frequently hourly if possible Give antibiotic if infection is suspected Nasogastric tube may be considered

DIABETIC HYPEROSMOLAR NON KETOTIC COMA

Often occurs in the elderly Type 2 patient or those undiagnosed. Characterised by severe water loss as a result of the osmotic diuresis secondary to hyperglycaemia. Precipitants include: Diuretic therapy High Carbohydrate drinks Underlying cause e.g. infection or MI Ketone formation is suppressed by circulating insulin so they do not become acidotic. Has a high mortality secondary to thrombotic events resulting from the increased blood viscocity.

Take Steps to Reduce Risk Factors for Heart Disease

Future
Non-invasive BS testing Continuous BS monitor + insulin pump
Artificial Pancreas

Islet cell transplants

Stem-cell research

GESTATIONAL DIABETES NEED FOR EXTRA INSULIN DURING PREGNANCY

HORMONES PRODUCED BY THE THE PLACENTA CAUSE RESISTANCE TO THE ACTION OF INSULIN

Diabetes
Dental aspects Unidentified disease Link specific findings to more widespread symptoms Oral bacterial infections, candidiasis

Diabetes
Dental aspects Diagnosed disease Impaired wound healing Higher likliehood of infection

Diabetes
Dental aspects Diagnosed disease Recognise emergencies If impaired consciousness treat for hypoglycaemia Hospitalise Always if hyperglycaemia

 Dental aspects Diagnosed disease Prevent emergencies If significant surgery, any restriction of oral intake required SEEK ADVICE Minor surgery DO NOT ADVISE TO STOP INSULIN DO NOT ADVISE AGAINST ORAL INTAKE

Diabetes