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E14 Endocrinology
Disorders of Glucose Metabolism Toronto Notes 2019
Treatment and Prevention
• appropriateglycemiccontrol
• appropriatebloodpressurecontrol(<130/80mmHg)
• useeitherACEIorARBtodelayprogressionofCKD(oftenusedfirstlinefortheirCVDprotection) • limit use of nephrotoxic drugs and dyes
DIABETIC NEUROPATHY Epidemiology
• approximately50%ofpatientswithin10yrofonsetofType1DMandType2DM
Pathophysiology
• canhaveperipheralsensoryneuropathy,motorneuropathy,orautonomicneuropathy
• mechanismpoorlyunderstood
• acute cranial nerve palsies and diabetic amyotrophy are thought to be due to ischemic infarction of
peripheral nerve
• themorecommonmotorandsensoryneuropathiesarethoughttoberelatedtometabolic,vascular,and
perhaps hormonal factors
Screening
• 128 Hz tuning fork or 10 g monofilament
• beginscreeningannuallyatdiagnosisforallType2DM,and>5yearsafterdiagnosisofDM1forpost-
Effect of a Multifactorial Intervention on Mortality in Type 2 DM: The Steno-2 Study NEJM2008;358:580-591
Study: Single centre RCT.
Patients: People (n=160) with type 2 DM and persistent microalbuminuria.
Intervention: Random assignment to receive either conventional multifactorial treatment or intensified, target- driven therapy involving a combination of medications and focused behaviour modification. Targets included an HbA1c level of <6.5%, a fasting serum total cholesterol level of <4.5 mmol/L, a fasting serum triglyceride level of <1.7 mmol/L, a sBP of <130 mmHg, and a dBP of <80 mmHg. Patients were treated with blockers of the renin– angiotensin system because of their microalbuminuria, regardless of blood pressure, and received low-dose Aspirin® as primary prevention.
Outcomes: The primary end point was the time to death from any cause. Other endpoints examined were death from CV causes and various CV events along with diabetic neuropathy, nephropathy, and retinopathy.
Results: Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional- therapy group (hazard ratio, 0.54; 95% confidence interval [CI] 0.32-0.89; p=0.02). Intensive therapy was associated with a lower risk of death from CV causes (hazard ratio, 0.43; 95% CI 0.19-0.94; p=0.04) and of CV events (hazard ratio, 0.41; 95% CI 0.25-0.67; p<0.001). One patient in
the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (p=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI 0.23-0.86; p=0.02). Conclusions: In at-risk patients with type 2 DM, intensive intervention with multiple drug combinations and behaviour modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from CV causes.
pubertal patients
Clinical Features
Table 14. Clinical Presentation of Diabetic Neuropathies
RIGHT
LEFT
Peripheral Sensory Neuropathy
Paresthesias (tingling, itching), neuropathic pain, radicular pain, numbness, decreased tactile sensation
Bilateral and symmetric with decreased perception of vibration and pain/ temperature; especially true in the lower extremities but may also be present in the hands
Decreased ankle reflex
Distal-predominant – longest nerves affected first
Classic stocking-glove distribution
May result in neuropathic ulceration of foot
Treatment and Management
Motor Neuropathy
Less common than sensory neuropathy and occur later in the disease process
Delayed motor nerve conduction and muscle weakness/atrophy
May involve one nerve trunk (mononeuropathy) or more (mononeuritis multiplex)
Some of the motor neuropathies spontaneously resolve after 6-8 wk
Reversible CN palsies: III (ptosis/ ophthalmoplegia, pupil sparing), VI (inability to laterally deviate eye), and VII (Bell’s palsy)
Diabetic amyotrophy i.e. Bruns-Garland Syndrome: refers to pain, weakness, and wasting of hip flexors or extensors
Autonomic Neuropathy
Postural hypotension, tachycardia, decreased cardiovascular response to valsalva maneuver
Gastroparesis and alternating diarrhea and constipation
Urinary retention and erectile dysfunction
Figure 7. Monofilament testing for diabetic neuropathy
Effects of Treatments for Symptoms of Painful Diabetic Neuropathy: Systematic Review
BMJ 2007;335:87
Purpose: To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy.
Study Selection: RCTs comparing topically applied and orally administered drugs with a placebo in adults with painful diabetic neuropathy.
Results: 25 included reports compared anticonvulsants (n=1,270), antidepressants (94), opioids (329), ion channel blockers (173), NMDA antagonist (14), duloxetine (805), capsaicin (277), and isosorbide dinitrate spray (22) with placebo. The odds ratios in terms of 50% pain relief were 5.33 (95% CI 1.77-16.02) for traditional anticonvulsants, 3.25 (95% CI 2.27-4.66) for newer generation anticonvulsants, and 22.24 (95% CI 5.83-84.75) for tricylic antidepressants. The odds ratios in terms of withdrawals related to adverse events were 1.51 (95% CI 0.33-6.96) for traditional anticonvulsants, 2.98 (95% CI 1.75-5.07) for newer generation anticonvulsants, and 2.32 (95% CI 0.59-9.69) for tricyclic antidepressants. Conclusion: Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy. Tricyclic antidepressants and traditional anticonvulsants are better for short-term pain relief than newer anticonvulsants. Evidence of the long-term effects of antidepressants and anticonvulsants is lacking. Further studies are needed on opioids, NMDA antagonists, and ion channel blockers.
• tightglycemiccontrol
• forneuropathicpainsyndromes:tricyclicantidepressants(e.g.amitriptyline),pregabalin,duloxetine,
anti-epileptics (e.g. carbamazepine, gabapentin), and capsaicin
• footcareeducation
• Jobst® fitted stocking and tilting of head of bed may decrease symptoms of orthostatic hypotension
• treatgastroparesiswithdomperidoneand/ormetoclopramide(dopamineantagonists),erythromycin
(stimulates motilin receptors)
• medical,mechanical,andsurgicaltreatmentforerectiledysfunction(seeUrology,U32)
Other Complications
Dermatologic
• diabeticdermopathy:atrophicbrownspotscommonlyinpretibialregionknownas“tibiaspots”, secondary to increased glycosylation of tissue proteins or vasculopathy
• eruptive xanthomas secondary to increased triglycerides
• necrobiosislipoidicadiabeticorum:rarecomplicationcharacterizedbythinningskinovertheshins
allowing visualization of subcutaneous vessels
Bone and Joint Disease
• juvenilecheiroarthropathy:chronicstiffnessofhandcausedbycontractureofskinoverjointssecondary to glycosylated collagen and other connective tissue proteins
• Dupuytren’scontracture
• increasedfractureriskinbothDM1andDM2duetoincreasedbonedemineralization • adhesive capsulitis (“frozen shoulder”)
© Madeline Spacher 2016