Since 1987, 101 patients with insulin dependent diabetes mellitus aged 18 to 65 yrs have been followed-up; Duration of diabetes ranged from 0 to 60 yrs. Intense therapy was performed by PEN (4-6 daily insulin injections) or by continuous subcutaneous insulin infusion, controlled by 4 or more glucose tests daily.
56 of 101 pts had DN, usually more than 10 yrs after the diagnosis of diabetes. Symptoms (paraesthesia, pain, numbness) were reported in 65%. Decreased or absent tendon reflexes were found in 95%; hypo- or analgesia in 49%, hypo- or anaesthesia in 43%, loss of vibration in 41%, weakness of leg muscles in 5% only. The severity of neuropathy correlated with the HbA1 c-value ( mean value over the past years ). During follow-up ( mean 6.5 yrs ) clinical improvement occurred in 13 of the 56 pts with neuropathy, and no change of signs or symptoms occured in 11 pts; these 24 pts had a mean HbA1c-value of 7%. In 32 pts the neuropathy deteriorated; their mean HbA1 c was 7.8%.
Nerve conduction studies were performed of sural, median and ulnar sensory nerves and peroneal, tibial and median motor nerves. In general, nerve conduction velocities (NCV) correlated to clinical signs of neuropathy, although not all pts with DN had a pathological nerve conduction. Patients with normal NCV had lower HbA1c-values (mean 6.7% ) than patients with pathological NCV (mean 7.8% ).
However, during follow-up all patients with or without DN showed progressive slowing of NCV:
At start Follow-up
NCV F-wave NCV F-wave
(m/s) (ms) (m/s) ( /ms)
57 pts with Sural 49 - 45.9 -
normal NCV
Peroneal 46.6 49.8 44.5 50.0
Tibial 46.1 50.0 44.5 53.5
25 pts with Sural 40.6 - 35.9 -
pathol NCV Peroneal 38.3 57.4 36.2 56.3
Tibial 36.1 50.2 35.1 62.5
Under intense insulin therapy, the neuropathy improved in few patients and deteriorated in others. The main influence factor for development and progression of DN is the glucose level (as indicated by the HbA1 c-value). There does not seem to be a glycemic threshold for the development of neuropathy, as indicated by the follow-up of NCV.