Diabetes Flashcards
What is diabetes mellitus?
chronic metabolic disorder characterized by increased blood glucose (hyperglycemia) resulting from impaired insulin secretion and/or action
What is diabetes a risk factor for?
cancer, Alzheimers, digestive, and more
What is impaired glucose tolerance?
between ‘normal’ and ‘diabetes’ in level of blood glucose
What was type I diabetes previously called?
insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes
What was type 2 diabetes previously called?
non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes
- people now end up on insulin
When do people get type I vs. type 2 diabetes?
type 1: can get at any age, but most commonly at 14
type 2: generally occurs in adulthood (adult-onset), but more and more children are being diagnosed
Which type of diabetes is the non-autoimmune form?
type 2
Which type of diabetes is most often associated with obesity?
type 2
What is gestational diabetes?
occurs during some pregnancies (related to type 2 diabetes)
What is gestational diabetes caused by?
caused by hormonal changes, leading to excess stress on beta cells (from burden from carrying fetus)
What are people who had gestational diabetes more susceptible to later in life?
type 2 diabetes
What are other rare forms of diabetes caused by?
single gene mutations
- neonatal diabetes (permanent or transient)
- maturity onset diabetes of the young (MODY) (2-5 % of diabetes)
Which type of diabetes is more common?
type 2 (90%)
What is type I diabetes characterized by?
lack of beta cells (and therefore insulin secretion)
What is the likely cause of type 1 diabetes?
combination of genetic susceptibility and ‘environmental’ triggers and suppressors
What happens if type 1 diabetes is not treated?
ketoacidosis and eventually death follows
What do type 1 diabetes patients require for survival?
require exogenous insulin (insulin-dependent diabetes)
but using insulin to manage glucose levels does NOT cure diabetes
How effective is type 1 diabetes treatment?
aggressive insulin therapy (better glucose control) reduces diabetes complications by 50%
What is type 1 diabetes?
autoimmune disease involving selective destruction of pancreatic beta cells by inappropriately activated T lymphocytes
tricks pancreatic beta-cells into committing cellular suicide
cause of autoimmune attack is not well understood, but it appears that both genetic and acquired (environmental) factors are important
What is found in type 1 diabetic patients?
several circulating autoantibodies against beta-cell proteins (including insulin itself)
What are ‘environmental’ factors (acquired factors) involved in type 1 diabetes?
factors still unclear, but several candidate triggers have been investigated:
- viruses
- sources of non-human insulin
What is the greatest risk factor of type 1 diabetes?
(genetic) alleles of major histocompatibility complex (MHC) genes (encoding human leukocyte antigens, HLA)
What do HLA-DR and HLA-DQ alleles do?
can either increase risk of diabetes, or protect against disease
What are the genetic factors that contribute to genetic risk of type 1 diabetes?
- MHC genes
- insuline gene
What are MHC genes?
important in processing and presentation of foreign antigens by macrophages
How does the insulin gene itself contribute genetic risk to type 1 diabetes?
- both protective and ‘at-risk’ alleles exist
- mechanism is unknown
What are some acute symptoms/complications of diabetes? (5)
- glucosuria
- polyuria
- polydipsia
- polyphagia
- ketoacidosis
What is glucosuria?
blood glucose level exceeds renal threshold for glucose absorption and glucose appears in urine
What is polyuria?
(frequent urination) glucose in urine causes osmotic diuresis
What is polydipsia?
(excessive thirst) excess fluid lost from body leads to dehydration
What is polyphagia?
(excessive food intake) despite increased food intake, cells are starved due to lack of insulin (insulin is required for glucose uptake)
What is ketoacidosis caused by?
lack of insulin increases lipolysis, increases triglyceride breakdown, increases plasma fatty acids, which liver turns into ketone bodies, leading to ketoacidosis
Are chronic complications more often see in type 1 diabetes or type 2 diabetes?
type 1 diabetes (which is often longer-term)
What are some chronic complications of diabetes? (5)
- neuropathy
- cardiovascular disease
- microvascular disease
- nephropathy
- retinopathy
What is neuropathy?
loss of sensation especially in periphery
What is cardiovascular disease?
cardiovascular problems – atherosclerosis, high blood pressure
leading cause of heart disease
What is microvascular disease?
common in foot
diabetes is leading cause of non-traumatic amputations
What is nephropathy?
has slow onset but is leading cause of kidney failure
What is retinopathy?
diabetes is leading cause of adult blindness
Are complications reduced when glucose levels are controlled?
Diabetes Control and Complications Trial (DCCT/UKPDS) Major Findings:
- maintaining tight control of blood glucose levels slows or prevents development of diabetic complications in this group of post-pubertal subjects
- tight glucose control does not completely prevent complications, and is associated with 3x increased risk of hypoglycemia (hypoglycemia is usually what takes people to the hospital)
How does type 2 diabetes affect insulin?
- insulin resistance
- decreased response to insulin in insulin target tissues (liver, muscle and adipose tissue)
- specific defects in glucose-stimulated insulin secretion
What is hyperinsulinemia?
in type 2 diabetes, basal insulin secretion is increased early in disease
some believe hyperinsulinemia is compensation for insulin resistance, but mechanism linking these features remain unclear
What factors are important in causing type 2 diabetes?
early life (and prenatal) factors
Does type 2 diabetes have a slow or fast onset?
slow
Is type 1 or type 2 diabetes more severe?
type 1
Is ketoacidosis common in type 2 diabetes?
no
Do most type 2 diabetic patients initially require exogenous insulin?
no – (non-insulin-dependent)
How does type 2 diabetes affect glucose?
- decrease in glucose uptake (muscle, fat)
- increase in glucose production (liver) associated with insulin resistance results in hyperglycemia
What is important in the etiology of type 2 diabetes?
both loss of functional beta-cells and insulin resistance are important
- mechanisms underlying insulin resistance and beta-cell dysfunction are not clear
What might contribute to insulin resistance?
insulin receptor and post-insulin receptor defects
What are genetic factors of type 2 diabetes?
- diabetes is polygenic
- thrifty gene hypothesis
What does it mean for diabetes to be polygenic?
- most of these genes play important roles in beta-cell
- each gene contributes very little risk on its own
- much of inheritability of diabetes is unaccounted for
What is the thrifty gene hypothesis?
genetic susceptibility has little effect in absence of ‘environmental stress’
What are environmental factors of type 2 diabetes? (2)
- increase in sugar consumption is associated with increase in obesity and diabetes
- saturated fats are also on the rise and may play a role
What is the critical role for insulin in physiological mechanisms of obesity?
lower insulin prevents hyperinsulinemia, which causes obesity
How does obesity affect insulin and beta cells?
larger weight…
- increasing predisposition to hyperinsulinemia and insulin resistance
- increasing predisposition to beta cell failure
Is gestational diabetes similar to type 1 or type 2 diabetes?
type 2
What is gestational diabetes characterized by?
- abnormal glucose-tolerance test
- slightly higher levels of insulin
Why are women less sensitive to their own insulin during pregnancy?
several hormones partially block actions of insulin
Can gestational diabetes be well-managed?
yes – by special diet and/or supplemental injections of insulin
What are the main treatments for type 1 diabetes (and advanced type 2)? (2)
- insulin
- pancreatic islet transplantation (still experimental)
What are future therapies for type 1 diabetes (and advanced type 2)? (3)
beta-cell regeneration
stem cell therapy
gene therapy
Insulin as Treatment for Type 1 Diabetes (and Advanced Type 2)
- patients administer exogenous insulin by multiple daily injections or pumps
- insulin cannot be currently administered as pill since it would be degraded in GI tract, but some companies are working on it
- engineered insulins are now used – may include glucose sensitive and liver-specific insulins in the future
- inhaled powder insulin could eventually replace injections, although disadvantage of unpredictable absorbance from lungs has not been overcome
Pancreatic Islet Transplantation as Treatment for Type 1 Diabetes (and Advanced Type 2)
(still experimental)
- isolated islets from pancreas are transplanted to diabetic patient
- more long-term studies required to show efficacy
What is the advantage of pancreatic islet transplantation?
provides endogenous source of insulin
What is the disadvantage of pancreatic islet transplantation?
needs life-long immunosuppressive therapy – insufficient donor islets
What are the main treatments for most type 2 diabetes? (3)
- exercise, diet, and weight loss
- oral hypoglycemic drugs
- injectable anti-diabetic drugs
Oral Hypoglycemic Drug
What do biguanides do?
suppress liver glucose output
ie. metformin
Oral Hypoglycemic Drug
What do DPP IV inhibitors do?
are enzyme that breaks down GLP-1
Oral Hypoglycemic Drug
What do SGLT2 inhibitors do?
prevent reuptake of glucose at kidney (allow you to urinate more glucose)
Oral Hypoglycemic Drug
What do sulfonylureas inhibitors do?
work on K+-ATP channel
stimulate insulin secretion from beta cells
ie. glyburide
Oral Hypoglycemic Drug
What do thiazolidinediones do?
ie. rosiglitazone (increase insulin sensitivity in insulin target tissues, but most have been removed from market)
What are the two injectable anti-diabetic drugs used to treat most type 2 diabetes?
- GLP-1 analogs (now produced in oral formulation)
- insulin
