Metabolic Diseases (DM, Obesity, glycemia etc.)

Question 1

Diabetes Mellitus Type I: Definition, Pathophys, Stages, S/sxs

Answer 1

• Definition:
  
  • autoimmune disease causing absolute (to near absolute) insulin deficiency due to pancreatic beta cell destruction → uncontrolled blood sugar & ketoacids.
• Pathophys:
  
  • Genetic predisposition with HLA markers + exposure to trigger → autoimmune response directed against pancreatic islet cells → # of beta cells decreases→ progressive impairment in insulin release results in DM when ≥ 80% of mass destroyed; honeymoon phase is first 1-2 years after onset of DM associated with reduced insulin requirements
• Stages:
  
  • STage 1: genetic predisposition
  • Stage 2: beta cell injury after immune trigger with multiple antibody positive
  • Stage 3: diabetes, beta cell mass < 80%
• S/sxs:
  
  • polyuria, polydipsia, polyphagia
  • fatigue, poor wound healing, weight loss
  • blurred vision

Question 2

Diabetes Mellitus Type 1: Screening, Labs, Criteria for Dx, & Management

Answer 2

• Screening:
  
  • only recommended in the setting of a research trial or in 1st degree family members of a probland with T1DM
• Labs:
  
  • Anti-Islet Autoantibodies
  • HLA: genetic markers
    
    • DR & DQ
• Criteria for Dx of T1DM:
  
  • Presence of 1+ autoimmune markers: islet cell autoantibodies, insulin autoantibodies, GAD (GAD 65 or glutamic acid decarboxylase antibody), IA-2 (tyrosine phosphatase antibodies), ZnT8 (zinc-transporter 8)
• Management:
  
  • multiple daily injections of prandial & basal insulin or continuous SQ insulin infusion
  • Use of rapid-acting insulin to reduce hypoglycemia risk (Glulisine, Aspart, Lispro)
  • Education pt on how to match prandial insulin doses to carb intake, premeal blood glucose & anticipated physical activity
  • Pramlintide can be added to insulin for A1C reduction & weight loss
  • SGLT-2 not currently recommended & may increase ketoacidosis
• When to monitor:
  
  • blood glucose monitor:
    
    • before meals, before bedtime, 2 hours postprandial if testing insulin dose response

Question 3

When to Test Asymptomatic Patients for Diabetes:

Answer 3

• BMI ≥ 25 with 1+ Risk Factors:
  
  • 1st degree relative with DM
  • high-risk race
  • CVD, HTN, hyperlipidemia
  • PCOS (polycystic ovarian disease)
  • physical inactivity
• Prediabetes: test yearly
• Women with gestational diabetes: test q 3 years for the rest of their life
• All pts ≥ 45 yo q 3 years
• Youth > 85th percentile weight with 1+ risk factor

Question 4

Criteria For Dx of Diabetes & Pre-Diabetes

Answer 4

• Pre-Diabetes:
  
  • A1C: 5.7-6.4%
  • FPG: 100-125 mg/dL
  • OGTT: 140-199 mg/dL
• Diabetes Criteria:
  
  • A1C ≥ 6.5%
  • FPG ≥ 126
  • OGTT ≥ 200 (oral glucose tolerance test)
  • RPG ≥ 200 (random plasma glucose)

Question 5

Criteria for Gestational Diabetes

Answer 5

• Gestational Diabetes:
  
  • 1 step: OGTT 75g at 24-28 weeks of gestation + if fasting > 92, 1H > 180, 2H > 153 mg/dL
  • 2-step: OGTT 50g → OGTT 100g

Question 6

Diabetes Mellitus Type II: Definition, Risks, S/sxs, & PE

Answer 6

• Definition: combination of insulin resistance & relative impairment of insulin secretion → glucose builds up in the blood → nerve & blood vessel damage
• Risks:
  
  • obesity (#1 factor)
  • genetics, American Indians & alaskan natives, Age > 45, physically inactive, hx of birthing baby > 9lbs or gestational DM, hyperlipidemia, PCOS, CVD
• S/sxs:
  
  • polydipsia, polyurea, polyphagia
  • fatigue, poor wound healing, blurred vision
  • tingling/pain/numbness of hands/ feet
• PE:
  
  • dry skin
  • vision changes
  • peripheral vascular & neural deficits
  • poor oral health
  • ophthalmic eval: retinopathy, cotton wool spots, hemorrhages
  • CV exam: murmurs, S3, S4, irregular rhythm, carotid bruits
  • Foot Exam: skin integrity & renal problems

Question 7

Tx of Diabetes Mellitus Type II

Answer 7

• increased insulin levels early in the disease but may diminish with disease progression
  
  • beta cells unable to keep producing elevated levels
• Goal Setting:
  
  • A1C target < 7%
  • Preprandial BG: 80-130
  • Postprandial BG: <180
  • refer to diabetes ed & specialists as needed
• Diet & exercise
• Pharm therapy:
  
  • metformin (initial), SU, meglitinides, TZDs, DPP-4 inhibitors, GLP-1 agonists, SLGT-2 inhibitors, insulin
• Bariatric surgery:
  
  • consider if BMI > 35, normalizes glycemia
• *A1C test twice year if meeting goals, if not q → 3 months

Question 8

Vaccines for Diabetes

Answer 8

• Hep B in adults < 60yo
• Influenza annually
• Pneumococcal:
  
  • PPSV23 for 19-64, AND again > 65 yo:
  • PCV13 if >65 yo

Question 9

Criteria for Metabolic Syndrome

Answer 9

• Criteria (* Need for at least 3 )
  
  • HDL < 40 mg/dL (male) or <50 mg/dL (female)
  • Triglycerides > 150 mg/dL
  • BP > 135/85
  • Fasting Plasma glucose: >100 mg/dL
  • Waist circumference > 40in (males) or >35 inches (females)

Question 10

Classification of BMI

Answer 10

Underweight: <18.5

Normal: 18.5-24.9

Overweight: 25-29.9

Obese Class 1: 30-34.9

Obese Class II: 35-39.9

Obese Class III: > 40

Question 11

Obesity: Definition, Causes, Weigh hx, Physical Activity Assessment, Psychosocial assessment

Answer 11

• Definition:
  
  • BMI > 30 kg/m2 or body weight 20% over the ideal body weight
• Causes:
  
  • Primary: Leptin deficiency, POMC deficiency, Prader-Willi Syndrome
  • Secondary = most common, environment, endocrine, neurologic, drug induced
• Weight Hx:
  
  • child, teen & adult weights
  • patterns of weight loss & gain
  • Past attempts at weight loss
• Physical Activity Assessment:
  
  • FITT (Frequency, Intensity, Time, Type)
• Psychosocial Assessment:
  
  • identify significant life events, traumas, deaths, abuse
  • hx of counseling or psychiatric care/tx
  • identify correlations with weight loss, gain, or retention

Question 12

Obesity: PE, Dx, & Tx

Answer 12

• PE:
  
  • BMI, waist circumference, signs of nutrient deficiency, papilledema, acanthosis nigricans, thyromegaly, excess body hair, disorderd sleep patterns, joint problems, CV/GI complaints, high LFTs, metabolic syndrome
• Dx:
  
  • BMI > 30 kg/m2 or body weight 20% over the ideal body weight
  • Obstructive Sleep Apnea:
    
    • STOP-BANG questionnaire: 3-4 = intermediate risk, 5-8 high risk
    • Polysomnography
• Tx:
  
  • tx tools:
    
    • RD consult
    • Diet hx: 24 hour food recall, food frequency, food journalling
  • Behavior Modification: for all pts with a BMI > 25, exercise & dietary changes, group therapy, phone apps
  • Anti-obesity meds:
    
    • options for BMI > 30 or BMI > 27 with comorbidities, ~ 5% weight loss
    • Phentermine: short-term use, may increase BP, do not use with MAO, EtOH
    • Orlistat: decreases GI fat digestion, need fat soluble vitamin replacement (A,D,E,K)
    • Liraglutide: SC injection, GLP-1 receptor agonist, may cause thyroid tumors
    • Phentermine/Topiramate: fetal toxic, sympathomimetic + anticonvulsant
    • Naltrexone/Buproprion: SE suicidal ideation

Question 13

Surgery Options for Obesity

Answer 13

option for BMI > 40 or BMI > 35 with comorbidity

• Comorbidities:
  
  • obstructive sleep apnea, non-alcoholic fatty liver disease, gallbladder disease, abnormal menses, infertility, PCOS, osteoarthritis, gout, HTN, stroke, Cataracts, DM, CAD, pancreatitis, cancer
• Roux-en-Y (gastric bypass): gold standard
  
  • but can cause vitamin deficiency
• Gastric Sleeve: most common
  
  • comparable with gastric bypass but risk of acid reflux & cannot undo those
• Lap Band:
  
  • high preoperative rate
• intragastric balloon:
  
  • may pop

Question 14

Nephropathy Associated with DM

Answer 14

• Screening annually with spot urine for albumin: Cr ratio & eGFR (if DM type I can start surveillance 5 yrs after initial dx)
• Pathophys:
  
  • progressive kidney deterioration → albuminuria = UACr > 30mg/g
• Dx:
  
  • urine dipstick positive for proteinuria (24 H urine protein loss b/w 30-300mg)
• Tx:
  
  • optimize glycemic & BP control
  • Daily dietary protein ~0.8 g/kg body weight (no need to limit)
  • ACEI or ARBs for UACr > 30mg/g
  • Refer to nephrology: if eGFR < 30 mL/min

Question 15

Retinopathy & DM

Answer 15

• Initial Screening: dilated comprehensive eye exam by ophtho at time of diagnosis for DMII and within 5 years of onset for DM1 .
  
  • if retinopathy is absent do a f/u eye exam after initial & then q 2 years
  • if retinopathy is PRESENT, do eye exam annually
• Tx:
  
  • prompt referral to an ophtho if:
    
    • any level of macular edema
    • severe non-proliferative diabetic retinopathy
    • any proliferative diabetic retinopathy
  • Therapy determined by an ophthalmologist:
    
    • laser photocoag
    • intravitreal injections

Question 16

Neuropathy & Foot Care and DM

Answer 16

• Initial screening at time of diagnosis for DMII & within 5 years of onset for DM type 1
• annually thereafter
• teach general foot care for all pts
• s/sxs:
  
  • progressive distal sensory loss in a “stocking-glove” pattern: involving the distal lower extremities at first
• Risk factors for ulcers:
  
  • prior foot ulceration, foot deformities, callus or corns, peripheral neuropathy, PAD, smoking, visual impairment
  • **If pt has risks → foot exam EVERY visit
• ABI testing:
  
  • 1.0-.14 = normal
  • <0.9 = PAD
  • 0.4-0.9 = moderated PAD
  • <0.4 = severe PAD, limb threat

Question 17

Peripheral Artery Disease & DM

Answer 17

• s/sxs:
  
  • decreased walking speed
  • leg fatigue
  • claudication
• PE:
  
  • assess pedal pulses at time of foot exams
• Dx:
  
  • Ankle-brachial index testing
    
    • perform if (+) sxs, > 50 yo, or hx of smoking/HTN/HLP/DM > 10 years

Question 18

Gastrointestinal Neuropathy & DM

Answer 18

• DM affects the entire GI tract: esophageal dysmotility, gastroparesis (impaired neural control of gastric funx), constipation, diarrhea, & fecal incontinence
• S/sxs:
  
  • Constipation = most common
  • lower GI sxs, may alternate with episodes of diarrhea
  • N/V, abd bloating
  • upper abd discomfort
• PE:
  
  • suspect gastroparesis if pt has erratic glucose control or with upper GI sxs without an identified cause
• Dx:
  
  • gastric emptying breath test
  • Double-isotope scintigraphy:
    
    • may be abnormal in the setting of recent uncontrolled hyperglycemia
• Tx:
  
  • optimize glycemic control
  • diet: low fat, low fiber
  • limit use of prokinetic agents metoclopramide (prokinetic) may cause irreversible tardive dyskinesia: extrapyramidal effects
  • Refer to GI: gastric stimulator for severe sxs

Question 19

Diabetic Ketoacidosis

Answer 19

• Pathophys:
  
  • acute absence of insulin → rapid breakdown of stores of muscle & fats → amino acid release → amino acids made into glucose & fatty acids (ketones)
• Triggers:
  
  • illness (infx, MI), med non-adherence, trauma, surgery, drug/EtOH use
• Epidemiology:
  
  • occurs in DM type 1 if extreme stress
• S/sxs:
  
  • **Acute onset
    
    • polyuria, polydipsia, dry mouth
    • fruity smell on breath, N/V/ abdpain
    • AMS, fatigue
• PE:
  
  • hypotension, tachycardia/tachypnea
• Dx:
  
  • Serum glucose > 350 mg/dL
  • Serum Ketones: B-hydroxybutyrate positive (best b/c not elevated in HHS), acetoacetate, acetone
  • Arterial pH: LOW (<7.3)
  • Hyponatreamia: <130
  • Hyperkalemia: >5 → due to the H/K shift
  • Anion Gap acidosis
  • CO₂: <15
  • serum osmolality: increased (if > 330 mOsm/kg = AMS)
• Tx:
  
  1. IV fluids first!! 4-6 L in the first 8 hours, use NS until blood glucose falls to ~250 mg/dL then switch to D5 ½ NS
  2. replacement of electrolytes K & phosphate, measure q 4-6 hours during first 24 hours
  3. Tx the underlying cause
  4. Insulin drip: started after at least 2L of IV fluids & K> 3.3mg/dL → then transition to SQ injections once pt can eat
  5. Keep Pt NPO until anion gap closes

Question 20

Hyperosmolar Hyperglycemic Syndrome

Answer 20

• Pathophys: relative/ partial insulin deficiency → increased glycogenolysis → hyperglycemia → glycosuria → water follows the glucose → dehydration → decreased fluid intake → hyperosmolarity
• Triggers:
  
  • illness (infx, MI), med non-adherence, trauma, surgery, drug/EtOH use, meds that increase BG
• Epidemiology:
  
  • occurs in DM type II
• s/sxs:
  
  • *subacute onset
  • polyuria, polydipsia, dry mouth
  • AMS, fatigue, & weakness, N/V
• PE:
  
  • dehydration, hypotension
• Dx:
  
  • Serum glucose: > 500 mg/dL (usually > 800 mg/dL)
  • Arterial pH: > 7.3
  • Hyponatremia: < 125 mEq/L
  • Serum Osmolality: > 300 mOsm/kg (usually > 330)
  • Serum ketones: acetoacetate & acetone mildly elevated, b-hydroxybutyrate is NEGATIVE
• Tx:
  
  1. IV fluids first!! 6L in first 10 hours, use NS until blood glucose falls to ~250 then switch to D5 ½ NS
  2. replace electrolytes: monitor BMP & Phos q 4-6 hours during the first 24 hours
  3. tx the underlying cause
  4. insulin drip: starter after at least 2L of IV fluids & K levels > 3.3mg/dL → transition to SQ injections once pt is able to eat
  5. Pt kept NPO until the anion gap closes

Question 21

Hypoglycemia

Answer 21

• Definition: blood glucose ≤ 70 mg/dL. Complication of DM
• Classification:
  
  • Level 1: glucose 54-70 mg/dL
  • Level 2: glucose < 54 mg/dL
  • Level 3: severe event characterized by AMS &/or physical status requiring assistance for tx of hypoglycemia
• S/sxs:
  
  • Autonomic (< 70)
    
    • sympathetic: tachycardia, palpitations, sweating, tremors
    • parasympathetic: nausea, hunger
  • Neuroglycopenic (< 50)
    
    • fatigue
    • HA
    • blurry vision
    • irritability & confusion
  • ALOC: (<30)
    
    • coma, convulsions
• PE:
  
  • ASSESS cognition
• Dx:
  
  • Whipple’s Triad:
    
    • Sxs consistent with hypoglycemia
    • low plasma glucose concentration (Plasma blood glucose best)
    • Relief of those symptoms after the plasma glucose levels are raised
• Tx:
  
  • “15-15” rule: give 15g oral glucose → repeat fingerstick BG after 15minutes (if normal give pt a snack, if low repeat dose)
  • if Unable to take PO:
    
    • inject 1mg IM glucagon x 1 into the thigh or buttock (pt may vomit & only raises BG by ~36mg/dL) OR 25-50mL D5 IV if in healthcare setting
  • Re-evaluate tx regimen
    
    • → may need to raise the glycemic targets or start pt on continuous glucose monitoring
  • Home Glucagon kit!!
    
    • only works if pt has a store of glucose in the liver (b/c glucagon mobilizes glycogen stores in the liver into glucose)
      
      • won’t work after a week of vomiting/diarrhea etc.

Question 22

Whipple’s Triad

Answer 22

Associated with hypoglycemia

1. sxs consistent with hypoglycemia
2. low plasma glucose concentration (plasma blood glucose best)
3. Relief of those sxs after the plasma glucose levels are raised