Diabetes Mellitus Type II

epidemiology of DM-II

- DM-II patients account for 9% of the US population in 2012, a total of 29 million people - annual healthcare cost in the US ($13700 for people with, $5900 for people without diabetes) - many patients with DM-II are asymptomatic, leading to future problems

the diabetic foot

- about 50 - 70% of all non-traumatic lower extremity amputations occur in diabetic patients - the insensate, pooly perfused foot is at risk for ulcers from pressure necrosis and unnoticed minor trauma - can evolve into cellulitis or osteomyelitis and end in amputation

microvascular complications of DM-II

- affects microvascular beds - changes in vision - edema - abnormal kidney tests/swelling - diminshed sensation - impotence

pancreatic islets of langerhans

- alpha cells: produce glucagon - beta cells: produce insulin

visceral fat in DM-II

- belly fat - increases insulin resistance, decreases insulin sensitivity - huge risk factor in DM-II

normal glucose homeostasis

- beta cells of pancreatic islets release insulin when blood glucose is high, increasing glucose transport into cells - alpha cells of pancreatic islets release glucagon when blood glucose is low, causing the liver to release glucose into blood stream

type I diabetes insulin reaction

- body lacks the insulin requred to activate GLUT4 - body is unable to bring glucose into the cells and blood sugar levels remain high

diabetes mellitus type 2 (DM-II)

- chronic condition that affects the way the body processes blood sugar (glucose) - issues generated from issues with insulin - uninherited, developed over lifetime

obesity adverse effects

- combination of no exercise + obesity adds synergetic risk - increases the presence of stress hormones (norepinepherine), which are pro-diabetic

early insulin therapy for DM-II

- consists of daytime oral agent + 1x daily insulin - recommended to prevent islet cell burnout - daily multiple-injection schedule via premeal rapid-acting insulin or longer-acting basal insulin

pre-diabetes: diagnostic critera

- fasting blood glucose level of 100 - 125 mg/dL - seen as precursor for type 2 diabetes - increases risk for atherosclerosis + diabetes - very few symptoms

hemoglobin A1c

- glucose slowly couples to hemoglobin in red blood cells by non-enzymatic reactions - glycosylated hemoglobin is measured as HbA1c - related to weekly average blood glucose concentrations

hyperglycemia

- high blood sugar - leads to polyuria, polydipsia, nocturia, weight loss, and fatigue

palpitations

- in hypoglycemia, results from epinepherine - feelings of having a fast-beating, fluttering, or pounding heart

metabolic syndrom models

- in mice; obesity is induced in zucker rats with combined hypertension and DM-II (ob/ob mouse) - in humans, the same clinical symptoms are found

diabetic complications

- induced brain damage - cardiovascular disease - urinary and sexual dysfunction - neuropathy - diabetic coma - retinopathy - atherosclerosis - kidney malfunction

normal insulin reaction

- insulin interacts with receptors on the surface of the cell - causes the release of GLUT4 onto the surface, which facilitates transport of glucose across the membrane

insulin facilitated diffusion

- insulin regulates glucose uptake into muscle and fat cells - recruits membrane vesicles containing GLUT4 glucose transporters from the interior of cells to the surfaced - allows glucose to enter cells

type II diabetes insulin reaction

- insulin resistance/incorrectly formed insulin results in the inactivation of insulin receptors and GLUT 4 - body is unable to bring glucose into the cells and blood sugar levels remain high

hypoglycemia

- low blood sugar - leads to extreme hunger, difficulty thinking, confusion, fainting, shakes, sweating, and palpitations

diet and exercise for DM-II

- low carbohydrate foods reduce strain on beta cells - losing weight rids visceral fat, which then increases insulin sensitivity - increasing daily activity also reduces insulin resistance

glucagon

- major hormone controlling blood glucose levels - secreted from the alpha cells of pancreatic islets in response to low blood glucose levels

insulin

- major hormone controlling blood glucose levels - secreted from the beta cells of the pancreatic islets in response to a rise in blood glucose

impaired insulin folding

- makes up 1/3 of all DM-II cases - insulin folds incorrectly, resulting is defective function

impaired glucose utilization

- makes up 2/3 of all DM-II cases - muscle and fat cells in DM-II become unresponsive to the presence of insulin - without regular glucose intake, the body's cells cannot metabolize it to produce ATP

issues with thiazolidinediones

- may worsen heart failure; disrupt liver function; decrease effectiveness of birth control pills - avandia was linked to a greater risk of heart attack and death (per FDA safety alert in 2007) and bone fracture in females

diabetic retinopathy

- microvascular disease of the eyes, where hemorrhages, exudates, micro-aneurysms, and abnormally shaped blood vessels can occur - may result in loss of vision

sodium glucose co-trasnporter 2 (SGLT2) inhibitors

- newer drug class - 1x daily oral pill, which causes controlled osmotic diuresis - decreases systolic blood pressure by 5 mmHg - BUT increases urinary tract infections

prevalence of DM-II in the US

- onset at much older age (around 60 + years of age)

DM-II: laboratory results

- patient with symptoms presents with blood glucose levels of > 200 mg/dL is diagnostic - the oral glucose tolerance test is no longer recommended - fasting blood sugar level of > 126 mg/dL on 2 separate occasions is diagnostic for diabetes

pancreas

- performs two main functions - secrete hormones insulin and glucagon - secrete digestive enzymes into the duodenum of the small intenstine

metabolic syndrome

- pre-diabetic state - can be caused by central obesity, high blood pressure, high triglycerides, low HDL-cholesterol, and insulin resistance - clinically seen as a precursor to DM-II

hyper-insulinemia

- present in pre-diabetics - high levels of insulin in the blood can predict the onset of DM-II

glycogenolysis

- releases glucose - facilitated by hormones such as glucagon, epinephrine/adrenaline, and cortisol

diabetic nephropathy

- results in the abnormal deposit of proteins (exudate) which chokes of blood flow to the kidneys

rosiglitazone (avandia) mechanism of action

- stimulates nuclear receptors to up-regulate the transcription of genes involved in the response to insulin in muscle, fat, and liver

distribution of glucose

- storage in liver (17g) as glycogen, fat (2g) as TG, and muscle (25g) as glycogen - used in ATP synthesis in brain (15g), kidneys (8g), and kidneys (23 g)

islet transplantation

- surgical transplantation of pancreatic islets from one patient to another - new islets in patient are able to produce proper, effective insulin

macrovascular complications of DM-II

- systolic hypertension - heart disease - stroke - claudication

importance of blood glucose level testing

- the goal is to maintain normal blood glucose levels - frequent testing allows patients to adjust lifestyle

risk factors of DM-II

- too much food/sugar in diet - genetic contribution - overweight/obesity - not enough exercise

classical treatment strategy of DM-II

1. diet and exercise 2. oral monotherapy (1 drug administered orally) 3. oral combination (2+ drugs administered orally) 4. oral + insulin (1 oral drug + insulin administered daily) 5. intensive insulin

consequences of diabetic retinopathy

1. increased vascular permeability 2. vascular occlusion + retinal ischemia 3. proliferation of new, malformed blood vessels 4. hemorrhage and scarring

drugs for DM-II

1. sulfonylureas 2. biguanides 3. thiazolidinediones

polydipsia

abnormally great thirst; symptom of disease

impotence in DM-II

commonly affects men in DM-II, results in sexual dysfunction

coronary atherosclerosis in DM-II

diabetes increases the risk of MI by 2 times in men, and 4 times in women

pathology of DM-II

divided into two states: micro and macrovascular disease

nocturia

excessive urination at night

thiazolidinediones

increases muscle uptake (Rosiglitazone or Avandia; Pioglitazone or Actos)

vasa nervorum

blood vessels supplying the nerves

vascular beds affected by DM-II

brain, skin, nerves (vasa nervorum), heart, and feet

result of tight blood glucose level control

reduces cardiovascular disease in diabetics

cortisol

known as the stress hormone, which raises blood sugar; pro-diabetic

glycogen

polymer chain of glucose; primary form of storage in body

polyuria

production of abnormally large volumes of dilute urine

peripheral vascular disease risk in DM-II

risk of peripheral vascular disease is 4 times that of people without diabetes

biguanides

slow sugar release from the liver, increase muscle uptake (Meltformin or Glucophage)

sulfonylureas

stimulated beta cells to make more insulin (Glipizide or Glucotrol)

microvascular disease

subtle injury to the vascular endothelium; results in leaks and microthrombi

macrovascular disease

subtle injury to vascular endothelium causes accelerated atherosclerosis in diabetics

edema

swelling

stroke risk in DM-II

the risk of stroke in diabetic patients is double that of non-diabetic individuals