Part1

Question 1

What is Diabetes Mellitus

Answer 1

Its a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both
Associated with abnormalities in carbohydrate, fat and protein metabolism
may result in chronic complications including microvascular, microvascular and neuropathic disorders

Question 2

Type 1 DM

Insulin Dependent DM (IDDM)

Answer 2

Due to B cell destruction, usually leading to absolute insulin deficiency

Question 3

Type 2 DM
Non Insulin Dependent DiM
(NIDDM)

Answer 3

Due to progressive loss of insulin secretion FREQUENTLY on the background of insulin resistance

Question 4

Gestational Diabetes Mellitus

GDM

Answer 4

Diabetes diagnosed in the 2nd or 3rd trimester of pregnancy that is not clearly overt diabetes
Hormone changes during pregnancy results in increased insulin resistance, and GDM may ensure when the mother cannot adequately compensate with increased insulin secretion to maintain normoglycemia

Question 5

Other specific type of diabetes due to other causes

Answer 5

-Monogenic Diabetes Syndrome: such as neonatal diabetes and maturity onset diabetes of the young (MODY)
MODY is characterized by impaired insulin secretion with minimal or no impairment in insulin action. Patients show mild hyperglycemia at an early age. Onset usually before age 25 and may mimic type 1 or 2 DM
-Diseases of the exocrine pancreas: ex cystic fibrosis and pancreatitis
-Drug-or chemical induced diabetes: such as diabetes resulting from glucocorticoid use, treatment of HIV/AIDS, or medications used after organ transplantation

Question 6

Whats the normal body process after carbohydrate ingestion?

Answer 6

There is an increase in plasma glucose concentration and the following occurs:
-Stimulation of the B pancreatic cells-hyperinsulinemia
-Resultant hyperinsulinemia causes the following :
Suppress hepatic glucose production
Stimulate glucose uptake by the peripheral tissues
Suppress glucagon release (in conjunction with incretin hormones)

Question 7

Pathophysiology of Type 1 DM

Answer 7

Autoimmune destruction of the B cells of the pancreas mediated by macrophages and T lymphocytes:
-Hyperglycemia develops when 8-90% of B cells are destroyed
-This process occurs in genetically susceptible subjects
One or more of these autoimmune markers are present:
-Glutamic Acid Decarboxylase Autoantibodies (GADA)
-Tyrosine Phosphatases IA-2 and IA-2b
-Zinc transporter (ZnT8)
-Insulin Autoantibodies (IAA)
Usually progresses over many months or years during which the subject is asymptomatic and euglycemic

Question 8

Diabetic Ketoacidosis (DKA) in Type 1 DM

Answer 8

DKA can occur in patients with DM1 due:
-if insulin (main therapy) is withheld
-under severe stress with an excess of insulin counter-regulatory hormones
During DM I disease development, glucose and HbA1C levels rise well making diagnosis feasible well before the onset of (DKA)

Question 9

Pathophysiology of Type 2 DM

Answer 9

T2DM is characterized by multiple defects including:

• Impaired insulin secretion
• Insulin resistance involving muscle, liver, and the adipocyte
• Excess glucagon secretion
• Glucagon-like- peptide-1 (GLP-1) deficiency and possible resistance
• Brain: Impaired satiety
• Kidney: Decrease in glucose exertion

Question 10

Pathophysiology of Type 2 DM

-Pancreas

Answer 10

• Increased glucagon secretion by alpha cell

- Impaired insulin and amylin secretion by B cells

Question 11

Pathophysiology of Type 2 DM

-Brain

Answer 11

• Impaired Satiety

- Decreased dopamine

Question 12

Pathophysiology of Type 2 DM

-Liver

Answer 12

• Hepatic Insulin resistance

- Increased hepatic glucose production

Question 13

Pathophysiology of Type 2 DM

-Peripheral Tissues

Answer 13

• Decreased GLUT-4 transporters

- Impaired insulin signaling

Question 14

Pathophysiology of Type 2 DM

-GI tract

Answer 14

-Decreased GLP-1

Question 15

Impaired Insulin Secretion in DM 2

Answer 15

A hallmark finding in type 2 DM.
When the insulin released can no longer normalize plasma glucose, including prediabetes and diabetes, can appear.
Both B-cell mass and function in the pancreas are reduced
-B cell failure is progressive and starts years prior to the diagnosis of diabetes
-People with type 2 diabetes lose 5-7% of B cell function per year
The reason for B cell loss is likely multifactorial
-Glucose toxicity: involving glucose levels chronically exceeding 140mg/dl
-Lipotoxicity
-Insulin resistance
-Age / Genetics
-Incretin Deficiency

Question 16

Incretin Deficiency in DM 2

Answer 16

its a glucagon like peptide 1 (GLP-1) secreted from L cells of the intestine upon food ingestion that:
-Regulates gastric emptying
-Enhances glucose-dependent insulin secretion
-Decreases glucagon secretion postprandial
-Promotes satiety and reduction in appetite with weight loss
Patients with DM type 2 has a reduced stimulus for insulin secretion from gut hormones (GLP-1)

Question 17

Clinical Presentation of Type 1 DM

Answer 17

Occurs at any age mainly before age 20 years
Patients are thin
Prone to develop DKA symptoms such as polyuria, polydipsia, polyphasic, weight loss, and lethargy accompanied by hyperglycemia

Question 18

Clinical Presentation of Type 2 DM

Answer 18

Asymptomatic with a slow onset over 5-10 years
More often patients are overweight or obese
High frequency of micro and macro vascular complications

Question 19

Diagnostic Test for DM I and DM II

-Fasting Blood Glucose (FBG)

Answer 19

• Fasting is defined as no caloric intake for at least 8 hrs
• Reflects hepatic glucose production, which depends on insulin secretary capacity of the pancreas
• Easy and the preferred method

Question 20

Diagnostic Test for DM I and DM II

-Oral Glucose Tolerance Test (OGTT)

Answer 20

• Performed 2 hrs after 75g of oral glucose solution
• More costly, less convenient
• More sensitive and specific than FBG
• Can be performed alternatively or in addition to fasting plasma glucose when a high index of suspicion for the disease is present
• Post prandial glucose reflects uptake of glucose in peripheral tissues (muscle and fat) and depends on insulin sensitivity of these tissues

Question 21

Advantages of Hba1C

Answer 21

• Hba1C: Evaluates the average amount of glucose in the blood over the last 2-3 months
• Greater pre-analytical stability and less day-to-day perturbations during stress and illness
• Greater convenient (fasting not required)

Question 22

Disadvantages of Hba1C

Answer 22

-Greater cost
-Lower sensitivity
-Limited availability of A1C testing in certain regions of the world
-Imperfect correlation between A1C and average glucose in certain individuals:
Therefore in conditions associated with increased red blood cell turnover such as sickle cell disease, pregnancy, hemodialysis, recent blood loss or transfusion or erythropoietin therapy, only blood plasma glucose criteria should be used to diagnose diabet

Question 23

Testing and Screening for Type 1 DM

Answer 23

Blood glucose rather than A1C should be used to diagnose individuals with symptoms of hyperglycemia
Screening for type 1 diabetes with a panel of autoantibodies is currently recommended only in the setting of a research trial or in first degree family members with type 1 DM
-Persistence of 2 or more autoantibodies predicts clinical diabetes and may serve as an indication for intervention in the setting of a clinical trial