Epidemiology and Pathophysiology (Diabetes) Flashcards
What is glucose?
carbon-based, efficient fuel molecule used for energy
The brain needs a continuous supply to work
What is the average normal fasting blood glucose?
70-99 mg/dL
After a meal, what happens to blood glucose levels?
Increase
The majority of glucose from a meal gets ____.
stored
storage molecule for glucose in the liver, skeletal muscle
glycogen
if liver and skeletal muscle are saturated with glycogen, what happens to the excess sugar?
formed into triglycerides
During fasting periods when blood glucose levels fall, what happens with glucose?
Glycogen is broken down to release glucose
Glucose from skeletal muscle can be used by muscle cell
Liver makes new glucose with gluconeogenesis from amino acids, glycerol, and lactic acid
What happens in fat metabolism?
Triglycerides are converted to fatty acids and glycerol
What happens to glycerol?
What happens to fatty acids?
What happens in protein metabolism?
Excess amino acids are converted to fatty acids, ketones, or glucose
Most are stored in form of proteins manufactured by the body
What is the function of the exocrine pancreas?
secrete digestive enzymes
What is the function of pancreatic acini?
secrete digestive juices into the duodenum
Whaat is the function of the islets of langerhans?
secrete hormones into the blood
what is the function of beta cells?
Alpha cells?
Insulin is made by the _____ in the _____
beta cells, islets of langerhans
Insulin
insulin
insulin
C-peptide is a _____ and can be used to determine if patient is ____
waste product, actually releasing insulin or not
Slide questionns
Slide questioms
What does glucose bind to?
GLUT transporter proteins (GLUT-2 and GLUT-4)
Why are GLUT-2 transporters important?
Why are GLUT-4 transporters important?
Found on skeletal muscle, adipose tissue
As glucose is phosphorylated,
glucose-mediated release of insulin from the beta cell picture
What is the biggest role of insulin in the body?
Glucose metabolism
Encourages glucose transport into skeletal muscle and adipose tissue
Increases synthesis of glycogen and decreases gluconeogenesis
What is the role of insulin in fat metabolism?
Increases transport of fatty acids into adipose cell
What is the role of insulin in protein metabolism
Where is glucagon produced?
Alpha cells in islets of langerhands in the pancreas
what is the impact of glucagon on glucose metabolism?
increased gluconeogenesis
increased glycogen breakdown
Fat metabolism
Protein metabolism
What is amyline?
released by beta cells along with insulin and c-peptide
works with insulin to regulate plasma glucose concentrations
decreases postprandial glucagon secretion
slows gastric emptying and increases satiety
What is somatostatin?
inhibits release of many hormones, including insulin and glucagon
what is incretins?
gut-derived hormones that promote insulin release after oral nutrient load
How is epinephrine related to glucose?
promotes glycogenolysis in liver and muscle tissue; lipolysis in adipose tissues
Decreases release of insulin in pancreas
How is growth hormone related to glucose?
Normally inhibited by insulin and elevated glucose levels
How are glucocorticoids related to glucose?
increases gluconeogenesis in liver
Check online slides for a question
Disorder characterized by an imbalance between insulin availability and insulin need
Diabetes Mellitus
What is in common between diabetes mellitus and diabetes insipidus?
Both make a lot of urine
Diabetes is the _____ cause of death in US
8th (and contributes to the development of other chronic diseases)
Most patients in the US have type ___ diabetic
2
15% of adults have _____ and 11% of adults have ____
diabetes, prediabetes
Type of diabetes characterized by near-absence or total absence of insulin
Type I DM
Most type1 diabetes are type ____
1A
Associated with insulin resistance, inadequate insulin secretion and increased glucose production
Type II DM
What can cause other forms of diabetes?
destruction of pancreas, genetic defects in glucose or insulin metabolism, gestational
how common is gestational DM?
7% of US pregnancies
Why do you think we avoid terms like “NIDDM” or “juvenile DM” in modern medicine?
It can be present in kids or adults so terms are not accurate
What causes type IA DM?
most autoimmune destruction of beta cells
What causes type IB DM?
Idiopathic, no associated autoantibodies
What are the underlying causes of Type IA DM?
HLA genes and environment
What environmental factors could increase TYpe IA DM?
cow’s milk, hygiene hypothesis, certain viruses
very slow progression of type IA DM
latent autoimmune diabetes in adults
How are beta cells destroyed in type IA DM?
Islets of langerhans become infiltrated by lymphocytes
Exact mechanism not fully understood, immunologic
What are immunologic markers of type IA DM?
autoantibodies to islet molecules: anti-GAD65, anti-ZnT8, Islet cell, autoantibodies, and anti-insulin
What are limitations of use of immunologic markers of type IA DM?
decline with increasing duration of disease
+ in about 5% of pts with T2DM and gestational diabetes
Low IAA levels in many patients after treatment with exogenous insulin
Why would we see declining autoantibodies as type IA progresses
In type II diabetes, what happens to insulin?
Patient’s make enough insulin but tissues are resistant leading to inadequate insulin secretion
What are the underlying causes of type II DM?
Genetic: multiple loci associated with increased risk
environmental: obesity, nutrition, physical activity, high or low birth weight
Over 80% of T2DM patients overall are obese (visceral)
How do you think we could distinguish visceral and subcutaneous obesity?
Distribution of fat or calipers
What metabolic abnormalities are present in type II DM
impaired insulin secretion and insulin resistance
Excessive hepatic glucose production
Abnormal fat/lipid and muscle metabolism
What is the pathogenesis of early type II DM
insulin resistance leads to compensatory hyperinsulinemia
What happens in type II DM over time?
Pancreatic beta cells are no longer able to maintain hyperinsulinemic state, causing prediabetic abnormalities
Impaired glucose tolerance
Impaired fasting glucose
What causes impaired glucose tolerance?
Decreased peripheral tissue glucose uptake and use
What causes impaired fasting glucose?
Higher than expected fasting glucose levels
As disease progresses, what happens in type II DM?
further decline in insulin secretion and insulin resistance constribute to consistent, worsening hyperglycemia causing type II DM
What is the diabetes triumvirate?
Abnormal insulin secretion, increased hepatic glucose production, decreased peripheral glucose uptake
Describe the ominous octet of DM
Diabetes triumvirate 4) increased lipolysis
5) Decreased incretin effect
6) increased glucagon secretion
7) increased renal glucose reabsorption
8) neurotransmitter dysfunction: insulin normally acts as a appetite suppressant
how is increased lipolysis related to type II DM?
resistance to insulin’s antilipolytic effect causes release of free fatty acids to stimulate gluconeogenesis
What is the pathogenesis of gestational DM?
insulin resistance due to metabolic changes of pregnancy
causes increased risk of T2DM in next 10-20 years
What is the pathogenesis of maturity-onset diabetes of the young
autosomal dominant; genetically mediated impaired insulin secretion in response to glucose
Type 1 diabetics are going to end up requiring ____ for survival
insulin
jhb
What does metabolic syndrome increase risk of?
atherosclerosis, heart disease, stroke, cancer, dementia, type 2 DM, erectile dysfunction
What is the criteria for metabolic syndrome?
Waist circumference >40 in men >35 in women
Fasting triglycerides >150 mg/dL, or on medication
HDL cholesterol <40 (men) <50 (women)
Blood pressure: 130 mm systolic or >85 mm diastolic or on medication
fasting plasma glucose >100 mg/dL or on medication
Metabolic syndrome is also associated with ____
small, dense LDL; hyperuricemia; prothrombotic state; proinflammatory state; PCOS; NAFLD
What is the prevalence of metabolic syndrome in US?
22% of patients
What are risk factors for metabolic syndrome?
Overweight/obesity
Physical inactivity
Aging- >50
T2DM
Cardiovascular disease: especially women
Lipodystrophy
What is the etiology of metabolic syndrome?
insulin resistance: increased circulating free fatty acids that feed into insulin resistance, resistance to leptin
glucose intolerance: increased levels of postprandial and fasting glucose
hypertension: loss of insulin’s normal vasodilatory effect, without impacting its mild sodium retention effect
Waist circumference: greater effect of circulating free fatty acids on hepatic metabolism
Dyslipidemia: influx of free fatty acids to liver causing abnormal lipid production
Proinflammatory cytokines: increased production due to the increased overall mass of adipose tissue
Etiology
Etiology
Etiology
Etiology
What are the clinical manifestations of metabolic syndrome?
increased waist circumference, hypertension
acanthosis nigricans
hepatic enlargement
hyperuricemia
polycystic ovarian syndrome
obstructive sleep apnea
velevety darkening of skin folds associated with insulin resistance
acanthosis nigricans
A patient with metabolic syndrome may have PCOS, what symptoms might you see?
constellation of infertility, menstrual irregularities, obesity, and hirsutism
What is the treatment of metabolic syndrome?
diet
physical activity
anti-obesity drugs, bariatric surgery, support groups
dyslipidemia
HTN
hyperglycemia
