Diabetes Mellitus - Endocrine - Medbullets Step 1

Snap Shot

A 56-year-old woman comes to your clinic for her annual physical exam. She reports increased urinary frequency and thirst, but is otherwise feeling generally well. She is obese, does not exercise, and regularly eats fried foods. A random blood glucose is 223 ml/dL. Her hemoglobin A1c is 9.2.

Introduction

Type 1 diabetes
- immune-mediated destruction of β-cells and loss of insulin production by pancreas
  - may also have antibodies against insulin
- 10% of diabetes cases
- classically occurs in thin people younger than 30
- sudden onset (after about 90% β-cells destroyed)
- result of self-reactive T-cell destruction of β-cells
- not necessary to have a family history
- associated with HLA-DR3 and -DR4
  - also seen concurrently with other autoimmune diseases (e.g., Graves', Hashimoto, etc.)
Type 2 diabetes
- insulin insensitivity in peripheral organs requiring increased insulin production
  - pancreas cannot produce enough insulin
- gradual onset
- 90% of diabetes cases
- typically in older individuals, though increasingly found in children with obesity
- common to have a family history
- associated with obesity
- amyloid deposition in β-cells
Complications are due to poor glycemic control
- if diabetic maintains glucose in normal range prognosis is good
- damage mediated by
  - non-enzymatic glycosylation which makes vessels more permeable
  - increased synthesis of type IV collagen in basement membrane
  - osmotic damage which is secondary to glucose conversion to sorbitol by aldose reductase
    - cause of cataracts and neuropathy

Presentation

Symptoms
- type I
  - polyuria
  - polydipsia
  - polyphagia
  - fatigue
  - weight loss
  - DKA
- type II
  - blurry vision
  - candidal infections (especially vaginitis)
  - hyperosmolar nonketotic coma
  - acanthosis nigricans: a velvety hyperpigmentation of the skin and found in body folds

Evaluation

Labs: 4 options
- hemoglobin A1c > or equal to 6.5%
- random blood glucose of > or equal to 200mg/dL AND diabetic symptoms
- 2 separate fasting glucoses of > or equal to 126 mg/dL (fasting means no intake for > 8 hours)
- 2-hour postprandial glucose (glucose tolerance test) of > or equal to 200 mg/dL

Treatment

See Diabetes pharmacology
Complications of treatment
- peripheral neuropathy
  - duloxetine (serotonin/norepinephrine reputake inhibitor), pregabalin, or gabapentin
- diabetic kidney disease
  - ACE-inhibitor
- gastroparesis
  - metoclopramide

Prognosis, Prevention, and Complications

Macrovascular complications
- coronary artery disease
  - 4 times more likely in DM patients
- peripheral vascular disease
- stroke
Microvascular complications
- nephropathy
  - arteriosclerosis leading to hypertension
  - nodular sclerosis
    - Kimmelstiel-Wilson nodules
  - progressive proteinuria
  - chronic renal failure
- ocular
  - retinopathy
    - proliferative changes involve neovascularization of retina
    - nonproliferative changes involve microaneurysms
  - cataracts
  - glaucoma
  - blindness
- peripheral neuropathy
  - numbness and paresthesias
  - burning sensation
  - ↓ deep tendon reflexes
  - ↓ vibration sense
- central neuropathy
  - 3rd nerve palsy sparing the pupil
    - also CN IV and VI
- autonomic dysfunction
  - impotence
  - bladder retention and incontinence
  - gastroparesis
  - GI discomfort
  - postural hypotension
- skin dysfunction
  - necrobiosis lipoidica diabeticorum
    - yellow plaques on legs
- diabetic foot
  - combination of vascular and nerve disease
  - higher likelihood of infection, pressure ulcers
  - can lead to amputation
- infectious disease
  - urinary tract infections
    - due to increased glucose in urine
  - rhinocerebral mucormycosis
  - Pseudomonas malignant external otitis

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²