Diabetes Mellitus Flashcards
2.4
what is diabetes mellitus
Group of metabolic disorders sharing the common Hyperglycemia.(defects in insulin secretion, insulin action or both.)
* Metabolic derangement associated with secondary damage in multiple organs -
kidneys, eyes, nerves & blood vessels.
what have contributed to the
increases in diabetes and obesity, also know as Diabesity epidemic
Increasingly sedentary lifestyles and poor eating habits
define prediabetes
elevated blood sugar that does not reach the criterion accepted for an outright diagnosis of
diabetes
Diagnostic criteria for:
Diabetes Mellitus
➢Random blood glucose concentration >200 mg/dL
➢Fasting blood glucose concentration greater than 126 mg/dL
➢Oral glucose tolerance test (OGTT)
➢Glycated hemoglobin(HbA1c)>6.5%
- A fasting plasma glucose between 100 and 125 mg/dL and/or
- A 2-hour plasma glucose between 140 and 199 mg/dL during an OGTT test, and/or
- HbA1C level between 5.7% and 6.4%
is termed as:
Impaired glucose tolerance (prediabetes)
Pathogenesis of Type I DM
- Autoimmune disease islet destruction is caused primarily by T cells reacting against endogenous β-cell antigens.
“insulin-dependent diabetes mellitus” is what type of DM
- Absolute lack of insulin *
TYPE 1 DM
TYPE 1 DM accounts for _________-% of cases
5-10%
TYPE ____DM Develops in childhood and peaks at puberty
type 1 DM
_____ and ______ – late in course of illness ( >90% β cell loss) for type 1 DM
Ketoacidosis and coma
genetic susceptibility of type 1 DM: HLA
✓HLA: Strongest association class II MHC coded on Chr 6p21 (HLA-DR3 and DR4)
genetic susceptibility of type 1 DM: NON-HLA
Insulin gene- reduced expression in thymus & reduced elimination of self reactive T cells
CTLA4 + PTPN22 ==> inhibit T cell response
genetic susceptibility of type 1 DM: NON-HLA
Insulin gene- reduced expression in thymus & reduced elimination of self reactive T cells
CTLA4 + PTPN22 ==> inhibit T cell response
loss of self tolerance lead to __________- against a variety of beta cell antigens, including insulin and the beta cell enzyme glutamic acid decarboxylase detected in
70-80% patients
autoantibodies,
loss of self tolerance lead to __________- against a variety of beta cell antigens, including insulin and the beta cell enzyme glutamic acid decarboxylase detected in
70-80% patients
autoantibodies,
what are Initiating triggers for Type 1 DM
Mumps, Rubella & Coxsackie B viruses - Molecular mimicry to β cell antigens
what are Intestinal dysbiosis for type 1 DM
Change in GUT flora ? Cause or effect of hyperglycemia
determine if APS1 or APS2
- Mutations in the autoimmune regulator (AIRE) gene - chromosome 21q22.
- In the absence of AIRE function, central T-cell tolerance to peripheral tissue antigens is
compromised, promoting autoimmunity.
APS1 or APECED (Autoimmune polyendocrinopathy, candidiasis, & ectodermal dystrophy)
describe APS2
- starts in early adulthood
- combination of adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes
describe APS2
- starts in early adulthood
- combination of adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes
determine if type 1 or type 2 DM:
Accounts for 90% to 95% of diabetic cases
multifactorial complex disease.
interactions of genetics, environmental risk factors, and inflammation
Primary defect
❖ Insulin resistance:
- derrangement of B cell secretion
type 2 DM
describe what insulin resistance
decreased response of peripheral tissues to insulin
-Insulin resistance predates hyperglycemia and is accompanied by compensatory beta cell
hyperfunction and hyperinsulinemia in the early stages
environmental factors of type 2 DM
sedentary Life style, dietary habits, obesity.
insulin resistance :
Failure to inhibit endogenous glucose production (____________) in the liver, which
contributes to _____________ blood glucose levels
gluconeogenesis , high fasting blood glucose
insulin resistance :
Abnormally low _____________ and ________- synthesis in skeletal muscle following a meal, which contribute to a high ____________-blood glucose level
low glucose uptake, and glycogen
postprandial
insulin resistance :
Failure to inhibit hormone-sensitive______ in adipose tissue, leading to excess circulating __________ - insulin resistance
lipase ,free fatty acids (FFAs)
insulin resistance :
Failure to inhibit hormone-sensitive______ in adipose tissue, leading to excess circulating __________ - insulin resistance
lipase ,free fatty acids (FFAs)
what is the Direct role of FFA :
Excess FFA are taken up in muscle and liver leading to increased intracellular triglyceride ____________ (acquired insulin resistance state)
potent inhibitors of insulin signaling
what is the Indirect ( Inflammatory Cytokines) role of FFA :
Excess FFAs within macrophages and beta cells activate the inflammasome (multiprotein cytoplasmic complex) that leads to secretion of the cytokine ________ that promotes insulin resistance
interleukin IL-1β
list the mechanisms of B cell dysfunction
- Excess FFA
- Chronic hyperglycemia
- Amyloid replacement in >90% islets (?cause / effect)
End result: by inadequate insulin secretion
Adiponectin levels _____ in obesity – insulin resistance
decreased
____________ release of hormones from adipocytes in relation to metabolic state
Adipokine Cytokines: