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What is the general definition of Type 1 Diabetes?

Pancreas makes too little or no insulin


What is the general definition of Type 2 Diabetes?

Cells do not use insulin well (insulin resistance). Ability for pancreas to make insulin decreases over time


What is the normal Islet function for glucose regulation when there is an increase in blood glucose?

Increase in insulin secretion (B-cell). Decrease in Glucagon secretion (a-cell)


What is the normal Islet function for glucose regulation when there is a decrease in blood glucose?

Decrease in Insulin secretion (B-cell). Increase in Glucagon secretion (a-cell)


What are the four main organs affecting plasma glucose insulin response?

Intestine (glucose absorption, cause Incretin release). Pancreas (insulin and glucagon secretion. Liver (glucose production and insulin action). Adipose tissue and muscle (glucose uptake insulin action)


What can C-peptide tell you about a patient?

C-peptide is the result from a cleavage creating insulin. If C-peptide is excessively high its an indication that your body is making too much insulin (usually a sign of type 2 DM (insulin resistance)). When C-peptide is too low it's usually a sign that your body isn't making enough insulin (type I DM)


What are the core defects resulting in Hyperglycemia?

Liver with increased Hepatic Glucose Production (HGP). Muscle cells with decreased glucose uptake. Pancreas with impaired insulin secretion and excess glucagon secretion


Besides the core contributors, what other organs can contribute to hyperglycemia?

GI tract with decreased Incretin effect. Increased lipolysis. Kidney with increased glucose reabsorption. Brain with neurotransmitter dysfunction. Islet a-cell with increased glucagon secretion


What are Incretins?

A hormone originating in the GI tract and released during nutrient absorption (food in stomach/intestines). Incretins augment insulin secretion at physiologic concentrations. The insulinotropic effects of Incretins are glucose dependent (do not cause hypoglycemia on their own). Some Incretins also decrease glucagon secretion from the a-cells


What is the general definition of GLP-1 and GIP?

Major Incretins in humans are Glucagon-Like Peptide (GLP-1) and Glucose-Dependent Insulinotropic Peptide (GIP)


What does GLP-1 do?

Increase insulin secretion and suppresses glucagon secretion. Regulates rate of gastric emptying. Affects CNS, resulting in increased satiety (sensation of fullness) and reduction of food intake


What does GIP do?

Increase insulin secretion


What are GLP-1 and GIP inactivated by?

Dipepidyl Peptidase 4 (DPP-4)


GLP-1 actions may extend beyond the pancreas. What other organs are affected?

Can increase cardio-protection and CO. Increases neuroprotection. Can actually increase B-cell proliferation and decrease B-cell apoptosis


Why is there a higher insulin response after PO glucose vs. IV glucose?

Glucose taken PO activate the Incretin Effect (Type 2 DM effect)


How does GLP-1 modulate insulin secretion?

GLP-1 potentiates glucose-dependent insulin secretion. GLP-1 enhances gene expression, synthesis, and release of insulin


How does GLP-1 also affect Insulin gene expression and B-cell function?

Upregulates insulin gene expression. Upregulates expression of genes essential for B-cell function. Promotes B-cell neogenesis and progenitor-cell differentiation (in animal models). Inhibits apoptosis (in animal models)


How does GLP-1 control glucagon secretion?

Suppresses glucagon release in glucose-dependent manner. Enhances glucagon release in response to hypoglycemia. Improves a-cell glucose sensing


What are the major Incretins?

GLP-1 and GIP


What is the major role of Glucagon?

Released from a-cells and have a positive effect on the liver, causing an increase in Hepatic Glucose Output (HGO). Ultimately increases glucose


What is the major role of Insulin?

Secreted by B-cells. Negatively acts on the liver, decreasing HCO. Acts positively on muscle cells/liver/fat cells to promote glucose uptake


What is the First-Phase Insulin Secretion?

Rapid and sharp increase. Begins 1-3 minutes after glucose rises. Returns to baseline within ~10 minutes. Derived from stored secretory granules docked on/near plasma membrane


What is the Late-Phase Insulin Secretion?

Gradual, several minutes to hours. Derived from stored secretory granules and de novo insulin synthesis. Persists as long as glucose levels remain elevated


What are the general roles of B-Cells?

Comprise about 70-80% of the endocrine mass of the pancreas. Located in the central portion of the islet. Produce insulin and amylin. Insulin released in response to elevated blood glucose levels


What are the general roles of a-Cells?

Comprise about 15% of the endocrine mass of the pancreas. Located in the periphery of the islet. Produce glucagon. Glucagon released in response to low blood glucose levels


What can diabetes do to the heart?

A 2- to 4-fold increase in cardiovascular mortality


What can diabetes do to the kidneys?

The leading cause of new cases of end stage renal disease


What can diabetes do to the eyes?

The leading cause of new cases of blindness in working-aged adults


What can diabetes do to limbs?

The leading cause of nontraumatic lower extremity amputations


What are the Macrovascular complications of diabetes?

Angina. MI. Transient cerebral ischemia. Stroke. Intermittent claudication. Ischemic foot ulcers


What are the Microvascular complications of diabetes?

Retinopathy. Nephropathy. Peripheral and autonomic neuropathy. Hyperglycemia is the most identifiable risk factor for microvascular complications in patients with diabets


How do you differentiate the different levels of Albumin secretion?

Spot collection. Normal < 30. Microalbuminuria: 30-299. Macro (clinical)-albuminuria: > 300


What is a more specific definition of Type 1 DM?

B-cell destruction, usually leading to absolute insulin deficiency. Immune mediated. Idiopathic. Usually found in childhood and adolescence. Low undetectable C-peptide levels


What is a more specific definition of Type 2 DM?

May range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance. Adult onset. Obesity


What are the common symptoms of Type 1 DM?

Three Ps: Polyuria, Polydipsia, Polyphagia. Unusual weight loss. Fatigue. Irritability


What are the common symptoms of Type 2 DM?

Any type 1 symptoms. Blurred vision. Frequent infections. Poor wound healing. Tingling/numbness of hands or feet


What are the Non-Modifiable risk factors for Type 2 DM?

Genetics. Ethnicity. Age


What are the Modifiable risk factors for Type 2 DM?

Obesity. Physical inactivity. Diet. Elevated fasting and 2h glucose levels. Insulin resistance. Impaired insulin secretion


What are the criteria for diagnosing DM?

A1C > 6.5%. FPG > 126. A 2-hour plasma glucose > 200 during an oral glucose tolerance test using 75g glucose. Symptoms of diabetes


What is Gestational Diabetes?

Any degree of glucose intolerance during pregnancy. Re-evaluate patients six to twelve weeks after pregnancy and reclassify as diabetes, pre-diabetes, or normoglycemia. Most patients return to normoglycemia


What is done to determine Gestational DM?

Perform fasting (8h) 75g OGTT at 24-28 weeks. Diagnosis is made using any of the following: Fasting glucose > 92, 1h > 180, 2h > 153. No need to repeat to confirm GDM


What is Pre-Diabetes?

Relatively high risk for developing DM. Risk factor for DM and CVD. Associated with obesity, dyslipidemia of high TG and/or low HDL, and HTN. Need lifestyle modification increasing physical activity and producing 5-10% of body weight


What is the only drug approved for Pre-Diabetes?



What is the relationship between Obesity and Diabetes?

Excess body fat is associated with increased insulin resistance in adipose tissues and skeletal muscles. Liver develops insulin resistance and increase glucose output. Peripheral tissues become resistant to glucose uptake. Pancreas compensates by producing more insulin


Which ethnic groups seem to have the greatest prevalence of diabetes?

African-Americans. Native Americans/Alaska Natives


Which income group has the highest prevalence of type 2 diabetes?

Low income


What does the largest portion of costs for diabetes complications go to?

Macrovascular complications


What is the relationship between Diabetes and older people?

Half of all patients with diabetes > 60 years. Diabetes accelerate aging process such that a person with diabetes is 10 years older physiologically than their chronological age


What does Diabetes do to mortality?

Doubles the risk of death compared with that in nondiabetics of similar age. Seventh leading cause of death in the US


What is the Incretin secretion following a mixed meal like in patients with type 2 diabetes?

GLP-1 was much lower than those with normal glucose tolerance. GIP wasn't that much lower


What are the glucagon levels like in patients with type 2 diabetes?

Fasting plasma glucagon is higher in patients with type 2 DM. Postprandial glucagon levels are high in patients with type 2 DM


What type of vascular damage occurs first with diabetes?

Macrovascular changes occur before microvascular


What happens to the insulin supply and demand as diabetes progresses?

Insulin demand slowly increases while supply greatly decreases


What what A1c does the risk of sustained retinopathy vastly increase?

Once A1c is above 8%