Case 6: Robert Kealoha

Question 1

What is T2DM?
Common?
Body habitus?

Answer 1

End-organ insulin resistance leading to metabolic disorder characterized by hyperglycemia
90% of diabetes cases
Usually obese

Question 2

Theories of pathogenesis of T2DM

Answer 2

• Environmental factors: obesity, sedentary lifestyle, bad dietary habits
• Genetics: Insulin resistance related to receptor/post-receptor problems; Defective insulin secretion (mutation in insulin/proinsulin genes)

Question 3

Diagnosis of T2DM

Answer 3

Fasting plasma glucose >126
Random plasma glucose >200
Glucose tolerance test >200, 2hr
HbA1c >6.5%

Question 4

Signs/Symptoms of T2DM

Answer 4

Lethargy/malaise
Blurry vision
Polyuria
Polydipsia
Frequent infections
Acanthosis nigricans

Question 5

Treatment of T2DM

Answer 5

Initially, lifestyle modifications (diet + physical activity to achieve weight loss)
Meds: Metformin, sulfonylureas
Exogenous insulin

Question 6

Complications of T2DM

Answer 6

Nephropathy - microalbuminuria
Neuropathy - sensory* & motor function; examine legs/feet/gait & monofilament test
Retinopathy-blurred/sudden loss of vision; annuals screening
Cardiovascular disease- increased atherosclerosis; BP 130/80; lipid lowering agents

Question 7

What is metabolic syndrome?

Answer 7

Obesity (central adiposity) is the main driver. Group of risk factors that Increases risk for CVD, diabetes, and overall mortality
Presence of any 3:
-Abdominal waist circumference
-Hypertriglyceridemia
-Low HDL
-Hypertension
-Impaired fasting glucose/diabetes

Question 8

Pharmacology of Metformin

Answer 8

Antidiabetic, glucophage
Contraindication: T1DM
Absorbed into muscle/adipose
Uncouples mitochondrial oxidative phosphorylation
Increase insulin sensitivity
Increase AMPK
-Decrease gluconeogenesis
-Increase insulin sensitivity
-Decrease glucose absorption

Question 9

Pharmacology of Glyburide

Answer 9

Antidiabetic; 2nd generation sulfonylurea (more potent)
MOA: binds to ATP-sensitive K+ channel on pancreatic B cells
Decrease K+ efflux
Membrane depolarization
Open voltage-gated Ca2+ channels & Ca2+ influx
Insulin release

Question 10

Pharmacology of Lisinopril

Answer 10

ACE inhibitor
Anti-HTN
Discontinue if pregnant
MOA: Competitively inhibits ACE (competes with AT I)
Decreased effects of ATII
ALSO:
-Dilates renal efferent arteriole to decrease hyperfiltration
-Increase selective permeability of filtering membrane -> decrease mesangial expansion

Question 11

Pharmacology of Lovastatin

Answer 11

HMG-CoA Reductase Inhibitor
Hypercholesterolemia
MOA:
-Metabolized in liver to active B hydroxyacid
-Competitively inhibits HMG-CoA reductase
-Decrease cholesterol synthesis
-Increase expression of LDL receptors
-Increase uptake of cholesterol 
-Decrease serum cholesterol

Question 12

Pharmacology of Sildenafil

Answer 12

PDE-V inhibitor
ED;pulmonary HTN
Contra: Nitrates (unsafe BP drop)
MOA: -inhibit PDE-V in corpus cavernosum
-Unable to degrade cGMP
-Reduce intracellular Ca2+
-Smooth muscle relaxation
-Increased blood flow
-Continued erection

Question 13

What is the Atkins diet?

Answer 13

• Attempts to convert burning carbs to fat

- High protein diet, with initial drop in carbs & gradual increase

Question 14

What is the Waianae diet?

Answer 14

• Seek health via diet, physical activity, positive attitude
• Emulates Hawaiian diet (pre-Western contact)
• Emphasis on ola lokahi (connection) and pono
• Non-restrictive (except animal protein)

Question 15

Ke Ola Mamo

Answer 15

• 1 of 5 Native Hawaiian Health Care systems established under Native Hawaiian Health Care Act 1988
• Clinical services: Dental (education, counseling, referrals), Kuakini offers primary care
• ‘Imi Hale: cancer info
• Breast/cervical cancer program
• Research: PILI ohana, Native Hawaiian Diabetes Intervention Program

Question 16

Mechanism of Thirst

Answer 16

Loss of H2O

• Increase plasma osmolarity signals osmoreceptors in anterior hypothalamus to activate thirst center
• Hypovolemia signals baroreceptor reflex and ATII signals thirst center
• Renal hypoperfusion causes decrease NaCl sensed by macula densa cells

Question 17

Mechanism of Micturition

Answer 17

Sympathetic activity causes relaxation of detrusor muscle/contraction of internal sphincter (external sphincter voluntarily contracted to inhibit reflex) causes filling of bladder. Bladder wall mechanoreceptors sense fullness, afferent neurons transmit info to spinal cord/brain stem, where midbrain coordinates info. Parasympathetic activation causes contraction of detrusor muscle, relax internal sphincter (voluntarily relax external sphincter) to empty bladder (micturition)