SM_185-186b: Diabetes I and II Flashcards
Normal is fasting glucose of ____ and 2 hour plasma glucose of ____
Normal is fasting glucose of < 100 and 2 hour plasma glucose of < 140
Diabetes is fasting glucose of ____ and 2 hour plasma glucose of ____
Diabetes is fasting glucose of ≥ 126 and 2 hour plasma glucose of ≥ 200
Probability of fasting glucose and 2 hour plasma glucose begins to rise above levels of ____
Probability of fasting glucose and 2 hour plasma glucose begins to rise above levels of 116-185
Attachment of glucose to hemoglobin (glycation) is directly proportional to ___
Attachment of glucose to hemoglobin (glycation) is directly proportional to amount of glucose in the blood over time
Red blood cells circulate for 3-4 months so irreversible glycation of hemoglobin reflects ____ in the blood for the previous several months and indicates the degree of diabetes of control
(HbA1c correlates with self glucose monitoring)
Red blood cells circulate for 3-4 months so irreversible glycation of hemoglobin reflects the average levels of glucose in the blood for the previous several months and indicates the degree of diabetes of control
Type 1 diabetes is ____ usually leading to ____
Type 1 diabetes is beta-cell destruction usually leading to absolute insulin deficiency
(immune mediated or idiopathic)
Type 2 diabetes ranges from ___ to ___
Type 2 diabetes ranges from predominant insulin resistance with relative insulin deficiency to predominantly secretory defect with insulin resistance
Type 1 diabetes occurs due to ___
Type 1 diabetes occurs due to autoimmune destruction of beta cells in pancreatic islets
Describe immunologic history of Type 1 diabetes
Type 1 diabetes immunologic history
- Innate immune cells enter pancreatic islets (priming)
- Antigens in pancreatic lymph node trigger T cells
- T cells arrive from lymph nodes causing insulinitis
- Destructive insulinitis
- Disease onset w/o intervention
Type 1 diabetes is largely mediated by ___
Type 1 diabetes is largely mediated by T cells
(autoimmune destruction of pancreatic beta cells)
Patients with Type 1 diabetes are ___
Patients with Type 1 diabetes are insulinopenic
- Depend on exogenous insulin for life
- Ketosis prone under basal conditions
Type 1 diabetes has greatest incidence at age ____ and presents with ____, ____, and ____
Type 1 diabetes has greatest incidence at age 10-14 and presents with polyuria, weight loss, and fatigue
Type 1 diabetes is associated with ____ or ____ allele expression
Type 1 diabetes is associated with HLA DR3 or DR4 allele expression
- HLA locus demonstrates strong association with T1DM consistent with autoimmune etiology
- Variation in many genes
____, ____, and ____ are environmental risk factors for T1DM
Enteroviral infections, dietary factors, and beta cell stress secondary to insulin demand are environmental risk factors for T1DM
____ frequently present at diagnosis of Type 1 diabetes
Circulating islet cell antibodies frequently present at diagnosis of Type 1 diabetes
- Marker of autoimmunity useful for predicting and diagnosing disease when presentation not classic for Type 1 diabetes
- Presents years to months before onset of clinical type 1 diabetes
Islet specific antibodies that present with Type 1 diabetes are ____, ____, ____, ____, and ____
Islet specific antibodies that present with Type 1 diabetes are islet cell autoantibodies, glutamic acid decarboxylase autoantibodies, insulinoma associated 2 autoantibodies, insulin autoantibodies, and ZnT8 autoantibodies
Antibody ___ and age ___ lead to faster progression to T1DM
Antibody IA2A/GADA and age <12 lead to faster progression to T1DM
Stage 1 of T1DM involves ____, ____, and ____
Stage 1 of T1DM involves B cell autoimmunity, normoglycemia, and no symptoms
(secondary prevention)
Stage 2 of T1DM involves ____, ____, and ____
Stage 2 of T1DM involves B cell autoimmunity, dysglycemia, and no symptoms
(secondary prevention)
Stage 3 of T1DM involves ____, ____, and ____
Stage 3 of T1DM involves B cell autoimmunity, dysglycemia, and symptoms
(intervention)
Teplizumab acts by ____
Teplizumab acts by preventing effector T cells from acting on beta cells
(delays onset of diabetes)
Describe acute effect of lack of insulin
Acute effect of lack of insulin
- Inhibits conversion of protein to amino acids
- Promotes kidney excretion of glucose, water, and electrolytes
- Prevents conversion of triglycerides to glycerol and FFA
- Decreases pH
Describe pathogenesis of diabetic ketoacidosis
Pathogenesis of diabetic ketoacidosis
- Insufficient insulin action -> hyperlipolysis -> ketoacidosis -> ketonuria
- Ketoacidosis -> polyuria -> hyperosmolality -> dehydration
- Ketoacidosis -> polyuria -> hypovolemia -> renal hypofunction
Describe therapeutic objectives for diabetic ketoacidosis
Therapeutic objectives for diabetic ketoacidosis
- Immediate
- Insulin therapy: catabolism -> anabolism
- Fluid: replace losses
- Electrolytes: Na, K, Cl
- After recovery: continued anabolism, restore lost nitrogen and intracellular electrolytes
Describe fluid therapy for diabetic ketoacidosis
Fluid therapy for diabetic ketoacidosis
- Loss of water > salt: replete vascular and extravascular volume first with isotonic fluid, then replete with hypotonic fluid
- Acidosis: NaHCO3 therapy to correct
- Blood glucose: use fluid with 5% glucose as glucose falls to 250-300 mg/dl
In diabetic ketoacidosis, there is a ___ K despite initial ___
In diabetic ketoacidosis, there is a deficiency of > 200 meq K despite initial hyperkalemia
- Relief of acidosis and increased glucose utilization with insulin therapy will shift K from extracellular to intracellular space with resulting hypokalemia
- Add K supplements to fluid when K enters normal range
- Monitor EKG
Diabetic ketoacidosis ____ H+ levels so ____
Diabetic ketoacidosis increases H+ levels so K+ leaves the cell via the H+/K+ antiporter
(excreted in urine)
Insulin inhibits action of ____ so K+ ____
Insulin inhibits action of H+/K+ antiporter so K+ enters cell
Describe type 2 diabetes
Type 2 diabetes
- Not absolutely dependent upon exogenous insulin
- Not prone to ketoacidosis
- Often obese
- May be relatively free of classical symptoms
- Strong FMHx of diabetes
- Increasingly recognized in childhood due to childhood obesity
Greater ____ score is associated with greater prevalence of Type 2 Diabetes
Greater polygenic risk score is associated with greater prevalence of Type 2 Diabetes
Describe causes of hyperglycemia in type 2 diabetes
Causes of hyperglycemia in type 2 diabetes
- Insulin resistance -> decreased glucose uptake by peripheral tissues
- Pancreas: impaired insulin secretion
- Liver: increased glucose production
Insulin resistance is ____
Insulin resistance is decreased ability of insulin to lower circulating glucose concentrations
- Impaired stimulation of glucose utilization by muscle and fat, impaired suppression of glucose production by the liver
- Complex metabolic disorder: multiple factors contribute to insulin resistance
Glucose disposal is ____ and hepatic glucose output is ____ in patients with type 2 diabetes
Glucose disposal is lower and hepatic glucose output is greater in patients with type 2 diabetes
(Hepatic glucose output greater in T2DM who are nonobese)
Hepatic glucose output is ____ with fasting serum glucose levels
Hepatic glucose output is directly associated with fasting serum glucose levels
Insulin resistance results from ___ and ___ factors
Insulin resistance results from inherited and acquired factors
- Inherited: mutation in several genes (common), mutation in insulin receptor / glucose transporter / signaling proteins (rare)
- Acquired: inactivity, overeating, aging, medications, hyperglycemia, and elevated FFAs
Insulin sensitivity decreases with ____ BMI
Insulin sensitivity decreases with increasing BMI
Most of diabetes risk is attributable to ____
Most of diabetes risk is attributable to excess weight
Describe fat induced insulin resistance
Fat induced insulin resistance
- Decreased lipid storage capacity in visceral adipose tissue -> portal circulation -> increased lipotoxicity and increased gluconeogenesis in lvier -> insulin resistance
- Decreased lipid storage capacity in subcutaneous adipose tissue -> systemic circulation, increased lipotoxicity, decreased fat oxidation / insulin action / glucose uptake in skeletal muscle -> insulin resistance
There is ___ in insulin resistance
There is dysregulated glucose metabolism in insulin resistance
Insulin resistance is associated with adipose tissue ____
Insulin resistance is associated with adipose tissue inflammation
There is altered ____ receptor signaling in the setting of insulin resistance
There is altered insulin receptor signaling in the setting of insulin resistance
Describe the pancreatic B cell response to insulin resistance
Pancreatic B cell response to insulin resistance
- Normal B cells -> hyperinsulinemia (normal glucose)
- Abnormal B cells -> hyperglycemia (relative insulin deficiency)
Describe the feedback loop between pancreatic B-cells and insulin sensitive tissues
Feedback loop between pancreatic B-cells and insulin sensitive tissues
- Insulin resistant with normal glucose tolerance -> impaired glucose tolerance -> type 2 diabetes
Glucose trends ____ and insulin sensitivity and B cell function trend ____ before T2DM
Glucose trends up and insulin sensitivity and B cell function trend down before T2DM
Insulin secretion ___ as insulin sensitivity increases
Insulin secretion decreases as insulin sensitivity increases
(failure of adequate B cell compensation with glucose intolerance and T2DM)
Describe therapeutic approaches in Type 1 diabetes
Therapeutic approaches in Type 1 diabetes
- Exogenous insulin mandatory
- Conventional treatment: remain symptom free, minimal hypoglycemia, metabolic restoration incomplete
- Tight control: frequent blood glucose monitoring, multiple doses subcutaneous injection or CSII, higher risk of hypoglycemia, near normal metabolic profiles
Basal insulin secretion increases when ___
Basal insulin secretion increases when basal glucose increases
Describe insulin preparations
Insulin preparations
- Rapid-acting analog insulins: lispro, aspart, glulisine
- Short-acting insulin: human regular insulin
- Intermediate-acting human insulin: NPH
- Long-acting analog insulin: detemir
- Long-acting analog insulin: glargine
- Long-acting analog insulins: U-300 glargine, degludec
____ and ____ are common insulin regiments
Split-mixed (lispro/NPH) and glargine-lispro are common insulin regiments
Describe options for insulin treatment and blood glucose monitoring
Insulin treatment and blood glucose monitoring
- Treatment: insulin syringes, insulin pump, and insulin pen
- Blood glucose monitoring: self monitoring, continuous glucose monitoring
Describe lifestyle treatment of T2DM
Lifestyle treatment of T2DM
- Nutrition therapy
- Exercise (moderate intensity)
- Reduce CV risk factors (smoking cessation)
- Training in self-management and SMBG
Describe therapeutic approaches in Type 2 diabetes
Type 2 diabetes therapeutic approaches
- Decrease glucose absorption in intestine
- Decrease hepatic glucose output
- Increase renal glucose excretion
- Increase insulin levels: stimulate insulin secretion
- Enhance glucose uptake: increase insulin sensitivity
Strategies to stimulate insulin secretion are ____ and ____
Strategies to stimulate insulin secretion are interacting with beta cell sulfonylurea receptor and enhance GLP-1 levels
- Interact with B cell sulfonylurea receptor: sulfonylureas, meglitinides
- Enhance GLP-1 levels: GLP-1 receptor agonists, DPP4 inhibitors
Metformin ___ hepatic glucose output
Metformin decreases hepatic glucose output
Thiazolidinediones activate ____ to enhance ____
Thiazolidinediones activate a nuclear receptor to enhance insulin sensitivity
Alpha-glucosidase inhibitors inhibit ___
Alpha-glucosidase inhibitors inhibit glucose absorption
SGLT2 is responsible for 90% of ____
SGLT2 is responsible for 90% of glucose reabsorbed in the renal tubules
SGLT2 inhibitors act by ____ and ____
SGLT2 inhibitors act by shifting the glucose threshold for excretion to the left such that glucosuria occurs at physiologic glucose levels and appear to reduce the affinity of the transporter for glucose
(decreases A1c and decreases cardiovascular disease)
Management of hyperglycemia in T2DM can be ___ or ___
Management of hyperglycemia in T2DM can be more or less stringent
Vascular complications of diabetes are ____, ____, and ____
Vascular complications of diabetes are proliferative diabetic retinopathy, nephropathy, and neuropathy
Diabetic neuropathy has ___
Diabetic neuropathy has a wide spectrum
Intensive insulin treatment in Type 1 diabetes ____ risk of retinopathy, nephropathy, and neuropathy
Intensive insulin treatment in Type 1 diabetes decreases risk of retinopathy, nephropathy, and neuropathy
As A1c increases, risk of microvascular complications ___
As A1c increases, risk of microvascular complications increases
Intensive management ___ of microvascular complications
Intensive management reduces risk of microvascular complications
Intracellular hyperglycemia occurs through the ____
Intracellular hyperglycemia occurs through the GLUT-1 transporter
Microvascular complications result when ____
Microvascular complications result when increased oxidative stress from intracellular hypergluycemia leads to DNA strand breaks and activation of poly (ADP ribose) polymerase (PARP)
- Increased flux through the polyol pathway
- Increased advanced glycation end products (AGE formation)
- Activation of protein kinase C isoforms
- Increased flux through hexosamine
Hyperglycemia causes tissue damage via ____ and ____
Hyperglycemia causes tissue damage via repeated acute changes in cellular metabolism and cumulative long-term changes in stable macromolecules
Most people with diabetes die from ____
Most people with diabetes die from ischemic heart disease
As weight decreases, waist circumference ____
As weight decreases, waist circumference decreases
- Decreased HbA1c
- Decreased SBP and DBP
- Decreased TG
- Increased HDL-c
- No change in LDL-c
