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104 Cards in this Set
- Front
- Back
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what does diabetes mean?
diabetes mellitus? |
Diabetes = excess urinary output
Diabetes Mellitus = excess urinary output of sugar |
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what level of fasting blood glucose is considered prediabetic?
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112 mg/dL
100-125 (nih.gov) |
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what level of fasting blood glucose is diabetic?
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126+ (nih.gov)
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above what level of glucose in the blood is considered diabetic?
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>200mg/dL
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what is an OGTT?
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oral glucose tolerance test
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what level of blood glucose is diabetic for an OGTT?
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>200 mg/dL
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how is an OGTT administered?
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patient fasts 8 hours, drinks glucose-rich drink, blood glucose measured twice (once within 2 hours of ingestion)
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how quickly is insulin released?
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almost instantaneously
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what is the most robust reservoir for insulin? why?
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skeletal muscle
there is so much of it that it provides an extraordinary amount of glucose uptake ability |
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what is the progression of insulin resistance in type II diabetes?
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progressive loss of peripheral function of insulin leads to progressive overcompensation, which will wear down the pancreas until it gives out and begins to decompensate due to dying beta-cells
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what is NIDDM?
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non-insulin dependent diabetes mellitus
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what is IDDM?
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insulin dependent diabetes mellitus
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what are the three differences in insulin response between normal and type II diabetics?
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much higher resting glucose
scale of increase is greater (as is absolute increase) high levels last longer b/c they are generally constantly eating |
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why does the blood glucose concentration go below fasting level in normal conditions shortly after eating?
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insulin is so effective that it deposits too much glucose initially in cells
glucagon brings glucose back out |
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when a type II diabetic has 300-400 mg/dL of glucose in their blood, what disorder are they in danger of?
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Hyperosmolar Hyperglycemic syndrome (HHS)
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what causes insulin deficiency in Type I diabetics?
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autoimmune destruction of beta-cells
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what is causing diabetes mellitus to become more common in children?
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pre-pubescent obesity
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what is the name for the group of disorders which genetically cause insulin resistance in young, non-obese people?
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maturity onset diabetes in youth (MODY)
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what disorder is a genetic defect in insulin action which causes leprechaunism?
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Donohue Syndrome
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what disorder is characterized as a renal disfunction resulting in Type II diabetes?
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Cushing syndrome
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what are the three primary antigens on beta-cells attacked by immune cells?
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IAA
GAD2 ICA512 |
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what are the two major HLA loci which confer increased susceptibility to Type I Diabetes mellitus?
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DR3-DQ2
DR4-DQ8 |
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what symptom results from improper insulin therapy
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episodic ketoacidosis
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what is GAD?
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glutamic acid decarboxylase
(converts glutamic acid to GABA) |
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what is the mechanism for ketoacidosis?
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high glucagon in blood stimulates adipocytes to release TAGs, which the liver then oxidizes until it can no longer oxidizeanymore and then begins to convert them to ketone bodies
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what is the effect of IDDM on hepatic glucose output?
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increase
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what is the effect of IDDM on hepatic glycogenolysis?
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increase
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what is the effect of IDDM on hepatic gluconeogenesis?
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increase
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what is the effect of IDDM on hepatic ketogenesis?
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increase
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what is the effect of IDDM on hepatic glycogen synthesis?
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decrease
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what is the effect of IDDM on skeletal muscle proteolysis?
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increase
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what is the effect of IDDM on skeletal muscle FFA oxidation?
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increase
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what is the effect of IDDM on skeletal muscle ketone body oxidation?
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increase
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what is the effect of IDDM on skeletan muscle glycogen synthesis?
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decrease
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what is the effect of IDDM on adipose tissue lipolysis?
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increase
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what is the effect of IDDM on adipose tissue lipogenesis?
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decrease
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what complication from IDDM arises in the eyes?
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sorbitol accumulation in cornea
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what other tissues does the hyperglycemia damage?
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glomerulus
nerve cells |
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what is polydipsia?
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excessive thirst
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why do IDDM patients often exhibit polydipsia?
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electrolytes and water are lost with increased glucose output
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what is polyphagia?
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eating too much
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why do IDDM patients experience polyphagia?
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negative caloric balance
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what causes hyperlipoproteinemia in IDDM patients?
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low lipoprotein lipase activity
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what causes low levels of malonyl-CoA so that it cannot inhibit fatty acid oxidation?
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low levels of ACC
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what causes ketoacidosis?
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increased lipolysis
increased acetyl-CoA generation constant signal (glucagon) for "brain food" |
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what causes Type 2 Diabetes?
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insulin resistance in periphery, followed by insulin deficiency caused by decompensation of beta cells
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what is causing the average age of onset of type II diabetes to shift to a younger age (younger than 40?
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obesity
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what is more detrimental about the hyperglycemia caused by type II diabetes than that caused by type I diabetes?
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though the hyperglycemia in type II diabetes is milder than type I, it is sustained or persistent for much longer, which is much more detrimental
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what molecules impair insulin-mediated functions?
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FFAs
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what are the three main causes of insulin resistance in muscle?
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genes
aging obesity |
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what causes hyperinsulinemia in type II diabetes?
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beta-cell overcompensation for high glucose levels after insulin is already released
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what further exacerbates the elevated blood glucose?
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increased hepatic gluconeogenesis
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what molecules impair the ability of insulin to initiate post-receptor signalling in adipocytes and skeletal muscle?
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FFAs
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what can lead to increased insulin sensitivity?
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reduction in central adiposity
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what is central adiposity?
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fat around waste/gut
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what is the main thesis of the Randle Hypothesis?
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FFAs interfere with insulin action in liver and muscle in type II diabetes
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what is the downstream process of FFA on glucose uptake?
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FFA enters through FATP-1
FFA is converted to FA-CoA FA-CoA, through DAG and PKC, activates NFkappaB which inhibits IRS phosphorylation and therefore inhibits GLUT-4 migration less GLUT-4 on surface means that less glucose will be absorbed |
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what is the defect in signalling caused by FFAs?
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inability to tyrosine-phosphorylate IRS1
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what is the process of the Glucose FFA cycle?
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FFA enters through FATP-1
FFA is converted to FA-CoA FA-CoA enters mito FA-CoA oxidized to give ACoA ACoA/CoA ration rises ACoA enters TCA citrate concentration rises citrate inhibits PFK-1 allosterically NADH/NAD ratio rises NADH/NAD ratio inhibits PDH backed up glycolytic intermediates cause G6P concentration to increase glucose not brought into cell |
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what is PCOS?
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polycystic ovary syndrome
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what causes PCOS?
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insulin effects on ovaries convert progesterone to testosterone and reduce SHBG
this leads to follicular atresia and ovulatory dysfunction and large cysts on ovaries |
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what is SHBG?
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serum hormone binding globulin
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what is follicular atresia?
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death of follicular cells
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what was the first gene correlated with polymorphisms for diabetes?
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Calpain 10 (CAPN10)
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what is the role of Calpain 10?
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beta-cell biogenesis
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what important diabetic condition does a defect in HNF-4alpha cause?
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MODY1
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What is HNF-4alpha?
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hepatocyte nuclear factor-4alpha
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what are the five genes highly correlated with type II diabetes?
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CAPN10
HNF4alpha KCNJ11 PPARgamma TCF7L2 |
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the inherited mutations of what gene were first identified in familial type II diabetes?
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PPARgamma
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polymorphisms in which gene are more correlated with diabetes type II than any other gene?
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TCF7L2
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what does TCF7L2 control?
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proglucagon gene expression (via wnt activation)
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what is the cause of MODY-1?
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mutation in HNF-4alpha
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what is the cause of MODY-2?
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mutation in pancreatic glucokinase
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what is the cause of MODY-3?
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mutations in HNF-1alpha
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what is the cause of MODY-4?
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mutation in insulin promoter factor-1 (IPF-1)
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what is the cause of MODY-5?
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mutations in HNF-1beta (TCF2)
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what is the cause of MODY-6?
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mutations in the bHLH transcription factor NeuroD1 (beta2) gene
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how is type I diabetes controlled?
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give insulin
control diet |
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what are seven classes of drugs to treat type II diabetes?
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Biguanides
Sulfonylureas alpha-glucosidase inhibitors Meglitinides Thiazolidinediones (TZDs) DPP IV inhibitors GLP-1 mimetics |
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what class of diabetes drug is best for obese patients with no liver complications?
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biguanides
ex. metformin (Glucophage) |
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what class of diabetes drugs block potassium channel?
(it is good in thin patients without ketonuria, and only for obese patients unable to use other drugs) |
Sulfonylureas
ex. glipizide (Glucotrol) Meglitinides ex. repaglinide (Prandin) |
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what class of diabetes drugs inhibits digestion of carbs?
(it is used only when other drugs aren't useful) |
alpha-Glucosidase inhibitors
ex. acarbose (Precose) |
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what are secretagons?
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potassium channel blockades
sulfonylureas & meglitinides |
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what class of diabetes drugs activates PPARgamma transcription factors?
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Thiazolidinediones (TZDs)
ex. Pioglitazone (Actos) |
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what is the major problem with TZDs?
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promotes fat storage in adipocytes (because causes differentiation of cells to adipocytes)
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what are two examples of drugs in the class of DPP IV inhibitors?
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Januvia (sitaglipin)
Onglyza (saxagliptin) |
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what is the advantage of DPP IV inhibitors? (especially over GLP-1 mimetics)
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oral administration
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what is the best indicative test of blood glucose?
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glycosylated hemoglobin (HbA1c)
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what are the potential problems with DPP IV inhibitors?
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as the other name of DPP IV indicates, CD26, DPP IV has responsibilities in T cell enhancement, so inhibiting this could hinder the immune system
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what is an example of a drug in the GLP-1 mimetics class of diabetes drugs?
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BYETTA (exenetide)
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what is the advantage to lizard exendin-4 over GLP-1?
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longer lived in the blood
(at only 53% matched, exenetide is not a substrate for DPP IV) |
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what is the main disadvantage to BYETTA over Januvia?
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patient compliance, because drug is injected
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what is FGF21?
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fibroblast growth factor 21
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what class of novel diabetes drugs augments the activity of fibroblasts to lower fasting glucose and decrease serum lipids?
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FGF21 agonists
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what class of novel diabetes drugs inhibits the sodium-glucose transporter in the kidney, allowing more glucose to be excreted in urine?
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SGLT2 antagonists
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which class of novel drugs has an activation associated with longevity and reduces circulation blood glucose?
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SIRT1 agonists
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where is SGLT2 expressed exclusively?
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S1 segment of proximal tubule
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what enzyme is responsible for 90% of the renal glucose reabsorption?
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SGLT2
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what enzyme is an NAD+-dependent deacetylase that modulates the activities of proteins downstream from good effects of calorie restriction?
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SIRT1
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what two enzymes work in concert to increase the rate of fatty acid ox?
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SIRT1
AMPK |
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how does resveratrol work?
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activates SIRT1
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what is the definition of the metabolic syndrome (MetS)?
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clustering of atherosclerotic cardiovascular disease risk factors that include visceral adipocity, insulin resistance, low levels of HDLs and a systemic proinflammatory state
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what pecentage of U.S. population over 50 suffers from MetS?
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45%
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what are the key components of MetS?
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chronic inflammation
procoagulation impaired fibrinolysis dyslipidemia hypertension |
