Diabetic UropathyJoseph Michael A. Ursua, MD, FPUA

Definition

• Diabetic Uropathy - range of debilitating urologic

complications secondary to diabetes

• Bladder dysfunction

• urinary tract infection

• sexual dysfunction

• 70% - lower urinary tract complications

• 50% nephropathy

• 35% to 75% develop sexual dysfunction.

Diabetes and UTI• asymptomatic women - 2 consecutive voided urine

specimens with isolation of the same bacterial strain in quantitative counts ≥ 100,000 cfu/mL.

• In men - single, clean-catch voided urine specimen with one bacterial species isolated in a quantitative count ≥ 100,000 cfu/mL identifies bacteriuria.

• single catheterized urine specimen with one bacterial species isolated in a quantitative count ≥ 100 cfu/mL identifies bacteriuria.

Philippine Clinical Practice Guidelines on UTI 2015 Update: Part 2

Diabetes and UTI

DM NON DMAsymptomatic Bacteuria

26% 6%

Bacteremia 26% 13%Urinary tract source 8.7% 2.2%

Higher incidence of Asymptomatic bacteuria and Comlicated UTIassociated with symptomatic Bacteremia

Diabetes and UTI

Why?

• Different Bacteria

• Glucosuria

• Impairment of granulocyte function

Diabetes and UTI

Different BacteriaSame number of virulence

factors

No difference in microbial resistance

Geerling et al, International Journal of Antimicrobial Agents 19 (2002)

Diabetes and UTI

Glucosuria In Vitro In Vivo

Diabetes and UTI

Impairment of granulocyte function

Equal granulocyte function test:chemotaxis

OpsonisationPhagocytosis

Diabetes and UTI

Pathogenesis

• Lower urinary concentration of IL-6 and IL-8

• E. Coli with type 1 fimbriae adheres better to

patients with high level of glycosylated HbA1C

Geerling et al, International Journal of Antimicrobial Agents 19 (2002)

Diabetes and UTI

Treatment• Asymptomatic Bacteruria:• No progression• No reduction of Renal function

• Screening and Treatment is not warranted• Treatment depends on clinical presentation

Harding et al, N Engl J Med 2002;

Diabetes and UTI

Antimicrobial Agent

• Same as non diabetic

• Tmp/Smx may induce hypoglycemic effect

• Treatment duration 7-14 days

Philippine Clinical Practice Guidelines on UTI 2015 Update: Part 2

Diabetes and UTI

Philippine Clinical Practice Guidelines on UTI 2015 Update: Part 2

Diabetes and UTI

Emphysematous Pyelonephritis• Urologic emergency• Necrotizing parenchymal infection caused by gas

forming pathogens• Usually occurs in diabetic patients• Mortality rate 19% to 47%

Diabetes and UTI

Emphysematous Pyelonephritis• Severe acute pyelonephritis• Triad of fever, flank pain and vomiting• E. coli is most commonly identified

Diabetes and UTI• X-ray shows mottled gas

pattern over affected kidney

• Streaky or mottled gas with or without bubbly and loculated gas - 50% to 60% motality rate• Renal scan

Diabetes and UTI

Treatment• Surgical emergency• If the kidney is functioning, medical therapy can be

considered• Nephrectomy for patients who do not improve

after a few days of therapy

Diabetic Bladder dysfunction

Diabetic Bladder dysfunction

• spectrum of clinical symptoms

• bladder overactivity

• impaired bladder contractility

Diabetic Bladder dysfunction

• 55% have detrusor hyperreflexia

• 23% have reduced detrusor contractility

• 10% detrusor areflexia

• 11% indeterminate findings

Kaplan et al, 1995

Diabetic Bladder dysfunction

Storage VoidingUrgency Hesitancy Overflow

incontinence

Urge incontinence Weak Stream Bilateral hydronephrosis

Frequency Post void dribbling Rising serum creatinine

Nocturia

Diabetic Bladder dysfunction

Role of Detrussor

muscle

Role of Neuronal Damage

Role of Urothelium

Golbidi et al 2010

Diabetic Bladder dysfunction

Role of Detrusor Muscle

• The detrusor muscle shows an enhanced response

to muscarinic agonists in diabetes. It may be due to

an increased muscarinic receptor density or

increases in smooth muscle sensitivity to calcium

(Saito et al., 1997)

Diabetic Bladder dysfunction

• Glucosuria and osmotic diuresis both lead to increased bladder stretch, elevated intravesicalpressure, leading to bladder hypertrophy, which upon decompensation can cause increased

residual volume

(Daneshgari et al., 2006).

Diabetic Bladder dysfunction

Role of Neuronal Damage

• activation of the polyol pathway increases

• production of free radicals

• activates protein kinase C

• formation of advanced glycated end products

Fedele, 2005

Diabetic Bladder dysfunction

Role of Neuronal Damage• Decreased synthesis of nerve growth factor• defective transport of nerve growth factor

Diabetic Bladder dysfunction

• Gastrointestinal complications of diabetes• Pressure from an over-distended bladder can

reflexively inhibit parasympathetic activity, a stimulus for fecal retention and soiling• Straining to defecate can affect pelvic floor muscles

and lead to rectocele, cystocele (in women), and an increased risk of stress incontinence and incomplete bladder emptying

Diabetic Bladder dysfunction

Role of Urothelium• interruption of barrier function of the urothelium• toxic substances can diffuse to the underlying

tissues to induce symptoms of urgency, frequency, and pain during bladder filling and voiding

Diabetic Bladder dysfunction

Deneshgari et al,Diabetic Bladder Dysfunction: Current Translational Knowledge J Urol. 2009 December

Diabetic Bladder dysfunction

Diagnosis• History• Physical

Examination• Laboratories• Urodynamic studies

Diabetic Bladder dysfunction

Diagnosis• Good History taking

SymptomsHesitancy

Weak streamDribbling

Incomplete emptyingInfrequent voiding

Urgency and nocturia

Diabetic Bladder dysfunction

Physical Examination• Complete physical exam• Genitourinary• Obstetric • Neurologic

Diabetic Bladder dysfunction

Laboratories• Urinalysis/ Urine culture• Serum glucose/ HBA1c• Bun/Creatinine• KUBP Ultrasound – post void residual,

hydronephrosis

Diabetic Bladder dysfunction

Urodynamics• Cornerstone in diagnosis of DBD• Differentiate between bladder pathology and

bladder outlet obstruction• Detrussor overactivity• Detrussor Hypoactivity

Diabetic Bladder dysfunction

• relief of symptoms

• prevention and treatment of urinary tract infections

• adequate bladder emptying.

Goals of treatment

Diabetic Bladder dysfunction

• Behavioral

• Pharmacologic

• Surgical

Strategies

Diabetic Bladder dysfunction

Behavioral• weight reduction• avoiding bladder irritants e.g caffeinated drinks• Pelvic floor exersizes• Timed voiding• Crede’s or valsalva• Clean intermittent catheterization

Diabetic Bladder dysfunctionPharmacologicAntimuscarinic• Tolterodine• Oxybutynin• SolifenacinAnticholinergic• Fesoterodine• Trospium chloride

Diabetic Bladder dysfunction

Surgery• Vesical neck resection• Selective pudendal nerve block• Sacral neuromodulation

Diabetic Bladder dysfunction

Sexual Dysfunction

• Diabetes is associated with sexual dysfunction both in men and in women• threefold increased risk of erectile dysfunction (ED)

Sexual Dysfunction

Erectile Dysfunction• persistent inability to achieve or maintain penile

erection for successful sexual intercourse• 10–15 years earlier in men with diabetes and

usually more severe• less responsive to oral drugs

Sexual Dysfunction

• Hyperglycemia as risk factor

• diabetes is commonly associated with hypertension, hyperlipidemia, obesity, metabolic syndrome, smoking

Sexual Dysfunction

Pathogenesis of ED• Vasculopathy• Neuropathy• visceral adiposity• insulin resistance• hypogonadism.

Sexual Dysfunction

Treatment• Glycemic control and lifestyle modification• weight reduction• smoking cessation• physical exercise

• Pharmacological Therapy• PDE5 inhibitors• Intracavernosal or transurethral vasoactive

Sexual Dysfunction

Thank you