Thomas M. Facelle, MD
Mark L. Jordan, MD, FACS
BASICS
DESCRIPTION
• Hyperglycemia with secondary metabolic abnormalities
• Two subtypes including insulin deficiency (DM1) and insulin resistance (DM2)
EPIDEMIOLOGY
Incidence
• 30% with DM1 and 10–40% with DM2 will develop kidney failure.
• 59% with DM will have urologic complications/symptoms
Prevalence
8.3% of US population in 2010 was diabetic (1)
RISK FACTORS
• Likely genetic and environmental interplay for DM1
• Genetic predisposition for DM2
– Environmental: Visceral obesity for DM2
Genetics
• DM1: Approx one-third genetic contribution
– HLA-DR3, HLA-DR4
• Strong hereditary component for DM2
– 70% twin concordance after age 40
– Several loci identified affecting pancreatic B-cell function and propensity to visceral obesity
PATHOPHYSIOLOGY
• Urinary tract infections (UTIs)
– Neutrophil dysfunction due to hyperglycemia
– Patients with DM are at increased risk and are classified as “complicated” UTI due to risk of progression to more severe manifestations such as abscess, emphysematous pyelonephritis, and papillary necrosis
– UTI increased incidence in women with DM but not men
– 80% have upper tract infections
– Often atypical organisms, eg, yeast
– Risk of xanthogranulomatous pyelonephritis (XGP) with stones
• Erectile dysfunction (ED)
– 3× more common in men with DM
– 15% at age 30, 55% at age 60 (2)
– 12% of men diagnosed with DM due to declining sexual function
– Caused by peripheral neuropathy, arterial insufficiency, changes in cavernous smooth muscle, and endothelial dysfunction
– Increased rates of hypogonadism
• Voiding dysfunction
– Sensory and motor neuropathy
– Impaired sensation and detrusor function
– Chronic bladder distension or overactivity
– Incontinence prevalent in women (3)
• End-stage renal disease (ESRD)
– DM most common cause (44%)
– Preceded by onset of proteinuria
• Polyuria
– In setting of glycosuria—osmotic diuresis
• Infertility
– ED and androgen deficiency
• Bladder cancer
– Increased incidence and mortality seen in men and women with DM (4)
– DM medication pioglitazone associated with increased bladder cancer risk
ASSOCIATED CONDITIONS
• Obesity
• Metabolic syndrome
• New onset diabetes after transplant (NODAT)
– Seen in up to 30% of nondiabetic renal transplant patients
• Papillary necrosis
• Retrograde ejaculation
GENERAL PREVENTION
• Glycemic control
• Weight reduction
DIAGNOSIS
HISTORY
• General
– Polyuria, polydipsia
– Weight loss, malaise
– Family history
– ED, especially in younger man
• UTI
– Recurrent UTI (may be asymptomatic)
– Fever, nausea, vomiting, flank pain
– Dysuria, hematuria
• Voiding dysfunction
– Urgency, frequency, weak stream, retention
• Bladder cancer
– Hematuria, pioglitazone use
PHYSICAL EXAM
• Flank
– CVA tenderness
• Abdomen
– Distended bladder, bladder mass
• External genitalia
– Phimosis, balanitis, yeast dermatitis
– Testicular atrophy, varicocele
– Peyronie plaques
• Rectal
– Tone, bulbocavernosus reflex
• Prostate
– Symmetry, nodules, tenderness
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• General
– Fasting glucose >126 mg/dL
– Oral GTT, 2-hr value >200 mg/dL
– Microalbuminuria (30–300 mg/dL) predicts renal disease
• UTI
– Urinalysis, urine culture, and sensitivities
– BUN, creatinine
• ED
– Consider testosterone level, esp if low libido
if low, follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
• Voiding dysfunction
– UA, C&S
– Urine specific gravity if polyuric: Dilute if <1.007
– Metabolic panel including serum creatinine
• Infertility
– Testosterone, FSH, LH, prolactin
– Semen analysis
Imaging
• UTI
– Consider CT scan if symptoms severe to rule out urolithiasis and/or emphysematous pyelonephritis especially if flank pain
– R/O papillary necrosis
• ED
– Cavernosal Doppler ultrasound (select cases)
• Voiding dysfunction
– Renal and bladder ultrasound
Diagnostic Procedures/Surgery
• Voiding dysfunction
– Post-void residual (PVR)
Via straight cath or bladder scan
Generally acceptable if <150 mL
– Voiding diary: Voiding volumes and frequency
– Uroflow
Normal 20–25 mL/s in men, 25–30 mL/s in women
Diminished if <10 mL/s
– Cystometrogram (CMG): Capacity, voiding pressure, detrusor instability
Pathologic Findings
• Diabetic nephropathy
– Microangiopathy and glomerulopathy (5)
Thickened glomerlular capillary basement membrane; diffuse mesangial sclerosis; nodular glomerulosclerosis
– Ischemia leads to tubular atrophy and interstitial fibrosis
– Renal artery atherosclerosis
DIFFERENTIAL DIAGNOSIS
• UTI: Cystitis, pyelonephritis, emphysematous pyelonephritis, emphysematous cystitis, XGP, urolithiasis, papillary necrosis, perinephric abscess, sexually transmitted urethritis
• Voiding dysfunction: Bladder outlet obstruction, urethral stricture, neurogenic bladder, UTI, interstitial cystitis
• Polyuria: Excess fluid intake, diabetes insipidus, renal failure
• Infertility: Ejaculatory obstruction, retrograde ejaculation, varicocele, testicular causes
TREATMENT
GENERAL MEASURES
• Educate patients regarding urologic manifestations of diabetes
• Glycemic control
– Dietary improvement, weight loss, exercise
MEDICATION
First Line
• UTI
– DM is an underlying condition that makes any UTI a complicated UTI
– Antibiotics (oral vs. intravenous)
– Fluid resuscitation
• ED
– Oral phosphodiesterase inhibitors (sildenafil, vardenafil, tadalafil, avandafil)
• Voiding dysfunction
– α-Blockers if outlet obstruction (terazosin, doxazosin, tamsulosin, alfuzosin, silodosin)
Add 5α-reductase inhibitor (finasteride, dutasteride) if significant benign prostatic enlargement (eg, >40 g)
– Anticholinergics for detrusor overactivity
• Ejaculatory failure
– α-Agonist (pseudoephedrine)
• Diabetic nephropathy
– ACE inhibitor if proteinuria for renal protection
Second Line
• ED
– Intraurethral suppository (MUSE)
– Intracavernosal injection (alprostadil, Bimix, Trimix)
– Testosterone replacement if androgen deficient
• Voiding dysfunction
– α3-Agonist (mirabegron) for overactivity
SURGERY/OTHER PROCEDURES
• UTI
– Retention: Catheter placement, suprapubic tube
– Urolithiasis: Ureteral stent, nephrostomy tube, ureteroscopy, extracorporeal shock wave lithotripsy
– XGP: Nephrectomy
• ED
– Penile prosthesis
• Voiding dysfunction
– Sacral nerve stimulation (InterStim)—efficacy for overactivity and retention
– Bladder outlet obstruction: Transurethral resection of prostate, photoselective vaporization of prostate, etc.
– Urinary diversion (uncommon)
• Infertility
– Assisted reproduction
• Bladder cancer
– Transurethral resection, cystectomy
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Voiding dysfunction
– Bladder training, biofeedback, timed voiding
– Clean intermittent catheterization (CIC) for retention
• Erectile dysfunction
– Vacuum erection device
Complementary & Alternative Therapies
• UTI
– Cranberry extract
• Voiding dysfunction
– Acupuncture to sacral dermatome
ONGOING CARE
PROGNOSIS
• Good with tight glycemic control
• Onset of proteinuria typically heralds future renal failure
• Diabetic cystopathy typically permanent
COMPLICATIONS
• UTI
– Upper tract infection
– Staghorn calculi; XGP
– Renal failure
• Voiding dysfunction
– UTI
– Upper tract damage/renal failure
– Incontinence
– Bladder stones
– Atonic bladder
• Diabetic nephropathy
– ESRD
– Dialysis dependence
FOLLOW-UP
Patient Monitoring
• General
– Periodic serum glucose
– Hemoglobin A1C
– Creatinine
– Urine protein and microalbumin
• ED
– Testosterone replacement: Check serum testosterone, prostate-specific antigen (PSA), serial hematocrit for elevation
• Voiding dysfunction
– Symptomatology
– BUN/creatinine
– PVR
– Repeat urodynamics as needed
Patient Resources
• Centers For Disease Control and Prevention, Diabetes Public Health Resource: http://www.cdc.gov/diabetes
• American Diabetes Association: http://www.diabetes.org
• National Diabetes Education Foundation: http://ndep.nih.gov/
REFERENCES
1. Masharani U. Diabetes mellitus and hypoglycemia. In: Papadakis MA, McPhee SJ, eds. Current Medical Diagnosis and Treatment. New York, NY: McGraw Hill, 2013.
2. Lue T. Physiology of penile erection and pathophysiology of erectile dysfunction. In: Wein, A, ed. Campbell-Walsh Urology, 10th ed. Philadelphia, PA: Saunders, 2011.
3. Goldstraw MA, Kirby MG, Bhardwa J, et al. Diabetes and the urologist: A growing problem. Br J Urol. 2006;99:513–517.
4. Zhu Z, Zhang X, Shen Z, et al. Diabetes mellitus and risk of bladder cancer: A meta-analysis of cohort studies. PLOS One. 2013;8(2):e56662.
5. Alpers CE. The Kidney. In: Kumar V, Abbas AK, Fausto N, Aster J, eds. Robbins & Cotran Pathologic Basis of Disease, 8th ed. Philadelphia, PA: Saunders, 2009.
ADDITIONAL READING
• Brown JS, Wessells H, Chancellor MB, et al. Urologic complications of diabetes. Diabetes Care. 2005;28:177–185.
• Costabile R. Optimizing treatment for diabetes mellitus induced erectile dysfunction. J Urol. 2003;170:S35–S38.
• Michel MC, Mehlburger L, Schumacher H, et al. Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia. J Urol. 2000;163(6):1725–1729.
See Also (Topic, Algorithm, Media)
• Diabetes Mellitus, Urologic Considerations Image 
• Erectile Dysfunction (ED)/Impotence
• Infertility, Urologic Considerations
• Neurogenic Bladder, General
• Pyelonephritis, Emphysematous
• Pyelonephritis, Xanthogranulomatous
• Urinary tract infection (UTI), Complicated, Adult
• Urinary tract infection (UTI), Complicated, Pediatric
CODES
ICD9
• 250.40 Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
• 250.41 Diabetes with renal manifestations, type I [juvenile type], not stated as uncontrolled
• 585.6 End stage renal disease
ICD10
• E10.29 Type 1 diabetes mellitus w oth diabetic kidney complication
• E11.29 Type 2 diabetes mellitus w oth diabetic kidney complication
• N18.6 End stage renal disease
CLINICAL/SURGICAL PEARLS
• DM predisposes to urinary infections of greater severity with likely upper tract involvement.
• Most common voiding symptom is overactivity.
• ED may be the presenting sign of DM.
• Tight glycemic control is necessary to reduce progression of symptoms.