Diabetes

-The Doctor who gave this lecture is Dr. Nesreen Saadeh, MDInternal medicine department/ J.U.S.T -This lecture is included in Mid exam Inshallah Definition of Diabetes: A metabolic disorder characterized by hyperglycemia (high glucose in blood ) usually the reason behind it will be either defects in Insulin production or other Autoimmune destruction of Beta cells which produce the insulin in the pancreas or may be insulin insensitivity(meaning that the body doesnt respond to the insulin produced by pancreas or impair action of insulin on target tissues. Why do we care about the diabetes ? because hyperglycemia chronically is associated with long term damage to multiple organs including : 1-Eyes 2- kidneys 3- Nerves 4- heart and blood vessels 5- Gums So talking about diabetes and Cardiovascular disease in particular, Cardiovascular disease is the leading cause of death in people who have diabetes. so in adults with diabetes:
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- 68% die of heart disease or stroke -the risk for stroke is twice to four times higher than people who dont have diabetes - 75%of those who have diabetes have associated increase in the blood pressure - SOMKING it would even Double the risk for heart disease. so thats mainly why we care about management of Diabetes. Now ,, Diabetes is the leading cause of: -kidney failure -new cases of adult blindness(this something that can be preventable as case of blindness -nontraumatic lower-limb amputations The people with diabetes have the risk for periodontal (gum) disease have that is two to three times higher than people who dont have diabetes 60 to 70 % of people who have advance disease that is not controlled have mild to severe nervous system damage Diabetes Epidemic: (wide prevalence) -Over 300 million affected in 2010 . -over 500 million within 20 years . - An increase of more than 50%
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-Most Rapid in Indian and Aisan subcontinents (according to distribution of Risk ). Calcification of Diabetes Type I -represent 5-10 % of people who have diabetes - autoimmune (affect children and aldsonse) early in life -Subset type I - latent Autoimmune Diabetes in Adults (LADA)-meaning it presentation would be milder and later in life than as autoimmune - idiopathic (we dont know exactly why there is destruction of beta cell of pancreas Type II -The more common ( 90-95% ) -Usually represents later in life in adult , and it would be managed with different ways -Gestational Diabetes (Pregnancy associated Diabetes) Other subtypes : -Maturity Onset Diabetes of the young (MODY) -Defect in insulin action -Disease of pancreas ( Inflammation like pancreatitis or maybe tumor that lead to this destruction

-Endocrine disorders (forenss acromegaly*: excessive secretion of growth hormone or cortisol like in cushing can lead to diabetes - Drug or chemical induced (some medication that are widely used like steroid can cause diabetes -Infections can lead to diabetes too Other forms ( you Dont need to know details about it just basically ) some genetic syndromes are associated with hyperglycemia and pathophysiology behind it different than the common types of diabetes that we know. Pathophysiology of Diabetes Lets say somebody doesnt have diabetes , if there is high blood glucose ---------- stimulate pancreas to produce Insulin and insulin has different sites of action 1- Liver a- decrease glyconeogenesis ( decreasing production of the glucose b- decrease glconolysis ( decreasing lyses or breakdown the glycogen c- INCREASING Glycogen synthesis 2- Fat cells: a- Increase glucose uptake b- free fatty acid release. 3- Muscles: utilize glucose and build up glycogen as a form of storing energy (see figure /slide10 )
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Now when somebody has Diabetes .. There will be rise in blood glucose but there will not be insulin released in the amount that is enough to produce action that we have described earlier So you see that the role not be any uptake of glucose in the liver and on the contrary *it will stimulate the liver to put even out more glucose in the system .also it applys to the muscle, it will cause the muscle to breakdown its protein to make some energy available to the system because it all like signal saying .we dont have energy stores in the body (see figure slide 11)

Pathogenesis of type I diabetes -Immunological activation -progressive beta-cell destruction -Insufficient beta-cell function and less and less insulin in system. -Genetic susceptibility - Immune Factors like having : a- autoimmune disease (diabetes I with hypothyroidism and hypopigmentation of the skin ) b- antigen- specific antibodies #Environmental trigger -viruses infections . - Bovine serum albumin - chemicals: vacor(rat poison), streptozotin, Nitrosamines Now how do we see type I diabetes ? 1st beta cell mass(Y axis ) over time (months-Years ) , when someone genetically predispose to have diabetes Type I , you see (figure slide14),the red line- Beta cell mass is fine and then the trigger happens (maybe virus infection) that can lead to immunologic abnormalities that will cause gradual decline in the beta cell function
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and thats what we call prediabetes , there is a time when the patient maybe having some changes in glucose metabolism , but they will not aware of (its not manifesting clinically),and then suddenly when there is enough destruction of Beta cell mass , the patient will present in presentation type I diabetes But then there will be slow- small time of recovery of Beta cell function (honey moon period) patient feels there is sort of recovery its diabetes as if he is as going be cured of diabetes , but later on the decline will go on,the pts go on chronic phase of disease . And if it was type I (non-autoimmune ),there will be : 1no autoimmune markers 2-permenant insulinopenia (lack of Insulin ) 3- ketoacidosis (this is the difference between type I and type II ) when there is damage or lack of insulin in the system,there will be* breakdown of protein& *muscle to cause a fatty acid to produce what we call ketoacidosis 4-people of African and Asian origin will be more predispose to what we call non autoimmune type I diabetes Incidence of type I -Geographic variation Incidence higher in northern hemispheres than in southern .
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: -Age of onset peaks -preschool -puberty -autum/ winter peaks

: Done By Ahmad khasati

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Type 2 diabetes: As we said 90-95% of people would have diabetes type ll , and usually its about insulin insensitivity meaning that they have insulin in their body but the muscles and the other organs that are supposed to respond to insulin dont respond well . And along the way theyll have what we call relative insulin deficiency ; its usually associated with obesity and overweight and theyll have complications of the disease at the time of diagnoses unlike type 1 in which most of the time the patients dont have complications at the presentation but rather develop throughout the disease course but in type ll diabetes theyll probably have some sort of complications presentation . The pathophysiology behind type ll : As we said there is a rise in the level of blood glucose and the insulin is not sufficiently working in the target organs and that will lead to increase in the breakdown of protein in the muscle and decreased uptake of glucose in the muscle.

The result of insufficient insulin :

In the muscles : - Increased protein breakdown amino acids - Decreased glucose intake In the liver : - Increased Gluconeogenesis - Increased Glycogenolysis - Decreased uptake of glucose - Decreased Glycogenesis In the fat cells :
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- Some increased uptake of glucose - Reducing the release of free fatty acids from the fat cells

Pathogenesis of type ll diabetes :

- The genes involved in causing type ll disease are multiple - , also patients with type ll are having hyperinsulinaemia meaning that theyre having high amount of insulin produced by the pancreases to try and compensate for the insulin resistance but its still not efficient. - Some theories say that poor foetal nutrition may decrease the beta cell formation , - and other have associated it with the low weight of the baby at birth and the baby weight change over time . - mothers exposed to high glucose levels when theyre pregnant also may play a role . - Thrifty gene the dr. didnt talk about it. - B-cell loss the dr.didnt talk about it.

Looking at the graph above , we have four lines ; the insulin resistance , the insulin secretion , the Postprandial glucose ( after meals ) and Fasting glucose ( which is in the blood ) .

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Looking at the graph at the stage of impaired glucose tolerance : here we have abnormal handling of glucose in the system ( this stage comes ahead the diagnoses in the case of type ll ) and at this stage the body is trying to compensate for this abnormality by increasing the secretion ( see graph ) and also well have a relative resistance at this stage ( see graph ) . And as the time goes by and well have the diagnoses of diabetes established the secretion will decrease because the pancreases is now tired ( see graph ) but the resistance will increase ( see graph ) . Initially the rise in glucose level will be after meals ( postprandial ) but eventually the rise will be all the time (fasting glucose ) . We also have at the bottom of the graph mirocovascular complications meaning that complications affecting small vessels in the eyes , kidneys and nerves . And we also have Macrovascular compactions which is affecting heart , cerebral vascular accidences ( or strokes ) , so from the graph we can notice that these complications might occur at any stage ( the impaired glucose tolerance and the undiagnosed or the known stage ) .

Epidemiology of type 2 :
- Dramatic increase in overall prevalence - Increase attributed to globalization , urbanization and aging population - trends parallel to obesity epidemic ( meaning trends are increasing with the increase of the obesity worldwide ) - Per cent increase is greater in low and middle income countries - Concerning increase in prevalence of type 1 and type 2 diabetes in children and adolescents

Risk factors for type 2 :

Non-Modifiable risk factors : - Age older than 40 - Family history or genetic predisposition
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- Ethnicity ( e.g. African American and us population) - History of impaired glucose tolerance , impaired fasting glucose ( well talk about it shortly , but the values are : Fasting glucose more than 126 mlg/dl . Diabetes Less than 100mlg/dl normal 100-126 paired fasting ( something in middle ) has much more risk than the normal to develop - Vascular diseases - History of gestational diabetes or delivery of macrocosmic baby ( 40% increased risk) - Polycystic ovary disease ( endocrine associated disease occurring in females , one of its complications is insulin resistance ) - Schizophrenia ( this is a physcatric complication which is developed by using some kind of medications ) - Hypertension - Dyslipidemia (for e.g. like high cholesterol level) Modifiable risk factors : - Abdominal or central obesity ( for e.g. decreased mobility and sanitary lifestyle and way of eating .. etc ) - Overweight - Physical inactivity - Dietary factors ( in order to reduce the chance of having diabetes we should eat high fibers meals and fresh vegetables than having processed meals ) .

Diagnosis of diabetes :

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** Note in the table : A1c is the glycgated hemoglobin in the body in past 3 months .

Impaired glucose tolerance and Impaired fasting glucose:

Intermediate states high risk of developing diabetes increased risk of cardiovascular disease Prevention strategies must be implemented to prevent or delay progression ( for e.g. reduce weight , increases physical activity ..etc)

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Oral glucose tolerance test :

Give the patient an oral amount of glucose and see how they respond to it by measuring the glucose level in the body and then comparing it to the values in the table we talked about earlier . The following lines were not read by the dr but I wrote them anyway : - 75g glucose load after 8-10 hours fasting - readings taken in fasting state and at 1 and 2 hours - some factors such as previous carbohydrate intake , illness , smoking and activity level may affect result

Tests for differential diagnosis ( dr didnt talk about it too ) :

- Urinary ketones - Antibodies - C-peptide

Summary for both types :

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The meal of the patient should consist of half protein and scratch/cereal and the other half is vegetable . With fruit and milk/yoghurt

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Aims of treatment :

And as you know the major complication of diabetes is cardiovascular disease which can lead to death .

the adjacent graph shows the result of a research called UKPDS which is a research done on a large number of type 2 patients . Theyve found that using intensive ways of prevention can reduce the risk significantly than using the conventional methods.

For the last table in the slides you dont need to know about it . ( medications table ) . only know insulin :

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