Exam 2 Metabolism Part 1 - Diabetes Flashcards
T1DM cause
Autoimmune destructions of ß-cells manifesting when 80-90% destruction with metabolic disease and insulin deficiency
T1DM genetics
10-20% FHx +
Risk: HLA DR3 and DR4
Protection: HLA DR2, DQA1, DQB1
Insulin gene: increased # tandem repeats increases thymus exposure and decreases risk
T1DM environment
Infant diet: decreased breastfeeding -> increased risk
Accelerator hyp: increased obesity leads to increased oxidative stress on ß-cells
Hygiene hyp: decreased immune exposure leads to overactive immune system
Autoimmune associations (and dx test)
Autoimmune thyroid dz: 15-20% (TSH)
Celiac dz: 5-10% (TTG)
Addison’s dz: 1-1.5% (21-OH)
Diabetes presetnation
Polyuria Polydipsia Weight loss/fatigue Blurry vision DKA - more with T1DM, acute onset (10% mortality)
Diagnostic tests
Fasting glucose, OGTT, HbA1C
Autoantibodies in T1DM
Decreased C-peptide in T1DM
T1DM Islet cell autoantibodies
mIAA (to insulin) IA-2 GAD65 (GAA) ZnT8 (last three in granule) Presence of two or more = 100% progression
Type of damage in T1DM
T-cell mediated (CD4 and CD8)
Lobular (not uniform) ß-cell destruction
3 parts of insulin deficiency pathophys
Decreased GLUT4
Increased glucose production via glycogen and gluconeo
Increased hormone sensitive lipase (FFA and ketones)
Consequences of diabetes
Macrovascular (CAD - main cause of death, 80%)
Microvascular:
1. Retinopathy
2. Nephropathy - microalbuminemia (elevated urine alb/cr ratio)
3. Neuropathy
Diabetic Foot Disease: combination of macro and micro
Pyschosocial: depression and anxiety
Consequences of prediabetes
Macrovascular risk
No microvascular risk
LADA
30-70 yr old
6 months of non-insulin requiring diabetes
Presence of autoantibodies
T2DM causes
Insulin resistance with eventual ß-cell destruction (decreased production)
T2DM associations
obesity
lipid abnormalities
PCOS
non-alcoholic fatty liver disease
T1DM prevention
Primary: genetically at risk, diet/lifestyle
Secondary: antibody positive, oral insulin when IAA>80
Tertiary: early in clinical dz, preserve ß cells, intensive insulin
Signs: prandial glucose vs. fasting glucose
Prandial glucose rises fist
Fasting glucose levels rise later
Signs: insulin resistance and ß-cell function
Insulin resistance rises while at risk “pre-diabetes”, plateaus after onset
ß cells begin to fail with onset of diabetes (approx 50% fxn is gone at clinical diagnosis)
Main determinant of fasting blood glucose in T2DM
Hepatic glucose output (important to control with treatment)
Due to increased hepatic insulin insensitivity (should decrease output with insulin)
Normal vs diabetic meal response
Normal: increase insulin, decrease glucagon
Diabetes: insulin stays low, glucagon remains high
Incretin effect
Greater increase in C-peptide (insulin) with oral compared to IV glucose
Due to effect of GLP-1
MODY
Inherited DM - autosomal dominant
Mutation in glucokinase gene, defect in glucose sensor, less insulin secretion
Treat with sulfonureas or insulin
Diagnostic labs in DKA
Blood sugar >200/300 and ketones >5 Acidosis <7.3 Apparent hyponatremia (need to correct 2 Na/100 glucose) Apparent hyperkalemia (H/K shift to correct acidosis)
Adrenergic hypoglycemia symptoms
Sweating Tremor Tachycardia Anxiety Hunger
Neuro hypoglycemia symptoms
Dizzy HA Confusion Convulsions LoC
