Diabetic Neuropathy

Cardiovascular system

• Resting tachycardia

• Reduced heart rate variability

• Orthostatic hypotension

• Exercise intolerance (inadequate increase of heart rate and blood pressure during physical activity)

• Perioperative instability with frequent drops in blood pressure and heart rate

• Reduced or absent perception of myocardial ischaemia during physical activity

• Silent myocardial infarction or myocardial infarction with few symptoms

• Prolongation of the QT interval

• Sudden cardiac death

Basic diagnostics

• HRV while breathing deeply and after change of position

• Orthostatic test

Further diagnosticsAutonomic function tests (test battery):

• Resting HRV (frequency and time domain)

• Exhalation/inhalation ratio while breathing deeply

• Max/min 30:15-ratio

• Valsalva ratio (Valsalva manoeuvre)

• Orthostatic test

24-h HRV, syncope work-up

Cardiovascular autonomic neuropathy

• In general, no special treatment necessary (important: diagnosis and therapy of coronary heart disease and heart failure)

• For sinus tachycardia cardioselective beta-blockers

Orthostatic hypotension

• General measures: liberal salt intake, physical training, compression stockings, avoidance of hypotensive medications

• Medications with short half-lives that increase blood pressure (Midodrine)

• Fludrocortisone (start with a low dose)

Gastrointestinal tract

All gastrointestinal manifestations

Basic GI tract diagnostics:

• Medical history

• Exclusion of structural and infectious diseases

Dysphagia and reflux disease

Further diagnostics:Stage 1:

• Esophagogastroduodenoscopy

• Other imaging examinations, as applicable

Stage 2:

• Oesophagus manometry

• 24-h pH monitoring with/without impedance measurement

Dysphagia:

• General measures: prokinetic agents in individual cases

Reflux:

• Proton-pump inhibitors

Diabetic gastropathy (dyspepsia, postprandial hypoglycaemia)

Stage 1:

• Esophagogastroduodenoscopy

• Abdominal sonography

• If necessary, other imaging examinations

• Laboratory tests

Stage 2:

• Gastric emptying scintigraphy

• ¹³C-octanoic acid breath test (solid food), ¹³C-acetate breath test (liquids)

Gastroparesis (gastropathy):

• Dietary change: frequent, small, low-fibre and low-fat meals

• Adjust injection-to-meal interval

• Prokinetic agents (all off-label): Metoclopramide, domperidone, possibly prucalopride, erythromycin for severe refractory symptoms

• Antiemetics can be added to the symptomatic therapy of nausea and vomiting (antihistamines, 5-HT3-antagonists), as applicable

• Gastric electrical stimulation (“gastric pacemaker”)

• Jejunal feeding tube

• Parenteral nutrition

Diabetic cholecystopathy

Laboratory tests, abdominal sonography

Cholecystectomy for symptomatic cholecystolithiasis as needed

Diabetic diarrhoea (enteropathy) and exocrine pancreatic insufficiency

Stage 1:

• Endoscopy

• Abdominal sonography

• Laboratory tests, including examination of stool for pathogenic organisms

• If necessary, other imaging examinations

Stage 2:

• Lactose/fructose/sorbitol hydrogen breath test

• Glucose hydrogen breath test

• Faecal elastase-1, if necessary

• Lactulose hydrogen breath test, if necessary

• D-xylose absorption test, if necessary

Diarrhoea:

• Bulking agents

• Loperamide

• Cholestyramine

• Clonidine

• Octreotide

• In case of bacterial overgrowth of the small intestine: broad-spectrum antibiotics, e. g. Rifaximin (off-label use) for 10 days with medicinal yeast (e. g. Perenterol);

Severe exocrine pancreatic insufficiency

• Pancreatic enzymes

Diabetic constipation (hypomotility of the colon)

Stage 1:

• Digital rectal examination

• Ileocolonoscopy

• Laboratory tests

• Abdominal sonography, if necessary

• If necessary, other imaging examinations

Stage 2:

• (MRI) defecography

• Anorectal manometry

• Hinton test

• Neurological examinations

Constipation:

• Sufficient liquid, fibre and physical activity

• Gelling agents (pectins, psyllium preparations)

• Fibre-rich foods (e. g. wheat bran, linseed)

• Laxatives (e. g. sodium picosulfate, bisacodyl, macrogol, lactulose/lactitol) depending on tolerance and efficacy

• Biofeedback for rectal emptying disorder, if necessary

• Prucalopride for delayed transit (a prokinetic agent, approved for laxative-refractory constipation)

Diabetic faecal incontinence

Stage 1:

• Digital rectal examination

• Rectal endosonography

• (MRI) defecography

Stage 2:

• Anorectal manometry

• Neurological examinations, if necessary

Faecal incontinence:

• Antidiarrheal medications

• Pelvic floor gymnastics

• Biofeedback

• Sacral nerve stimulation in refractory cases, if necessary

Urogenital tract

Diabetic cystopathy (bladder emptying dysfunction)

Basic diagnostics

• Micturition diary over 48 h

Cystopathy:

• Behavioural changes

• Electrical stimulation

• Biofeedback

• Antimuscarinic drugs

• Beta-3 adrenergic receptor agonists

• Alpha receptor blockers

• Antibiotic therapy, as applicable

• Bladder neck incision

• Self-catheterisation

• Suprapubic cystostomy

Further diagnostics

• Specific questionnaire (e. g. International Prostate Symptom Score (IPSS)) questionnaire

• Uroflowmetry

• Residual urine measurement

• Digital rectal examination for men

• Urodynamic testing, as applicable

Erectile dysfunction

Basic diagnosticsStage 1:

• Sexual history, IIEF-5

• Laboratory tests

• Total testosterone (optional free testosterone), prolactin, FSH, LH

Stage 2 (optional):

• Test with a PDE-5 inhibitor (sildenafil, vardenafil, tadalafil, avanafil)

Erectile dysfunction:

• Avoidance of medication side effects (caused by antihypertensives, tranquilisers, antidepressants)

1) Step:

• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil)

2. Step:

• Erection aid system (vacuum pump)

• Corpus cavernosum auto-injection therapy

• Intraurethral alprostadil gel

3. Step:

• Corpus cavernosum implant

Further diagnosticsStage 3 (only if surgical therapy is planned/indicated):

• Intracavernosal injection test

• Doppler/duplex sonography

• Cavernosometry/cavernosography

• Nocturnal tumescence measurement

Hypogonadism:

• Testosterone substitution

Neuroendocrine system (endocrine dysfunction)

Hypoglycaemia-associated autonomic dysfunction

• Blunted or absent hormonal counterregulation

• Impaired hypoglycaemia perception

• Increased glucose threshold for hypoglycaemia symptoms at falling blood glucose

• Decreased catecholamine secretion when standing or upon physical exertion

• Tight blood glucose control (in particular self-monitoring), in particular during the night

• Avoidance of symptomatic and asymptomatic (often nocturnal) hypoglycaemia

• Hypoglycaemia awareness training (blood glucose awareness training; BGAT)

Sudomotor and vasomotor functions

• Dyshidrosis, anhidrosis (“dry feet”)

• Gustatory sweating

Sweat tests:
QSART: Quantitative sudomotor axon reflex test
TST: Thermoregulatory sweat test
SSI: Silastic sweat imprint
ACHSST: Acetylcholine sweatspot test
Neuropad: Indicator plaster
Sudoscan: Cutaneous electrochemical conductivity

• Topical agents containing fat or urea

• Avoidance of exposure to intense heat

• Prophylaxis in case of identified cause of sweating (dietary components)

• Anticholinergic drugs, clonidine (low dose)

• Topical glycopyrrolate cream

• In focal hyperhidrosis, botulinum toxin (Botox) can be tried

Pupillomotor system

• Miosis

• Impaired pupil reflexes

• Reduced dark adaptation

• Clinical examination

• Infrared pupillography (constriction rate, dilatation rate, latency of pupillary light reflex)

• Advise patient of impaired dark adaptation and danger of night blindness

• Danger of glaucoma (check intraocular pressure)

Respiratory system

• Central respiratory dysregulation with reduced respiratory drive in response to hypercapnia or hypoxemia

• Sleep apnoea syndrome

• Respiratory arrest

Sleep laboratory, as applicable

Continuous positive airway pressure (CPAP) therapy, as applicable