Severe Epidermal Nerve Fiber Loss in Diabetic Neuropathy Is Not Reversed by Long-Term Normoglycemia After Simultaneous Pancreas and Kidney Transplantation.

Whether nerve fiber loss, a prominent feature of advanced diabetic neuropathy, can be reversed by reestablishment of normal glucose control remains questionable. We present 8-year follow-up data on epidermal nerve fiber (ENF) density and neurological function in patients with type 1 diabetes after simultaneous pancreas and kidney transplantation (SPK) with long-term normoglycemia. Distal thigh skin biopsies with ENF counts, vibration perception thresholds (VPTs), autonomic function testing (AFT) and electrophysiological examinations were performed at time of SPK and 2.5 and 8 years after SPK in 12 patients with type 1 diabetes. In comparison to controls, baseline ENF density, VPT and AFT results of patients indicated severe neuropathy. At follow-up, all SPK recipients were insulin independent with excellent glycemic control and kidney graft function; however, the severe ENF depletion present at baseline had not improved, with total ENF absence in 11 patients at 8-year follow-up. Similarly, no amelioration occurred in the VPT and AFT results. Numerical improvement was seen in some electrophysiological parameters; however, statistical significance was achieved only in median motor nerve conduction velocity. ENF loss and functional deficits in advanced diabetic peripheral neuropathy are rarely reversible, even by long-term normoglycemia, which underscores the importance of neuropathy prevention by early optimal glycemic control.

[Hashimoto's encephalopathy]. / Hashimotova encefalopatie.

Hashimoto's encephalopathy (HE) is not an often complication of autoimmune thyroiditis, usually at the time the patient is already euthyroid i.e. with normal TSH-value but positive antibodies to thyroid hormones. Signs and symptoms are acute or sub-acute, such as cerebrovascular accident, epileptic seizures generalised, myoclonic or partial, cognitive function disorder with dementia and psychical disorders. Pathological findings, even non-specifical, can be found in cerebrospinal fluid, by electroencefalography (EEG) or by brain scan with magnetic resonance (MR). Pathogenesy of the disease is unclear; however, corticoid treatment is usually succesful. Therefore, HE should be taken into consideration after elimination of all other causes of encephalopathy, with thyroiditis in family history in particular.

[Clinical development of unstable (brittle) diabetes mellitus, its therapy and prognosis]. / Klinický prubeh nestabilního (brittle) diabetes mellitus, jeho lécba a prognóza.

Treatment of labile (brittle) diabetes characterized by variations of the blood sugar level, liability to develop ketoacidosis and in susceptible subjects the development of organ complications, was always a serious problem. The objective of the present work is to evaluate the results of a long-term study concerned with the relationship of compensation, vascular and neurological complications of labile insulin-dependent diabetics. The authors investigated indicators of compensation, and in collaboration with an ophthalmologist, and neurologist also signals of possible damage of the eye, central and peripheral nerves, kidneys. The results achieved by treatment were evaluated systematically. Consistent with the actual situation, treatment with conventional insulin or less common regimes were selected, and the authors reacted also to findings pertaining to organ complications. The cause of lability was assessed and eliminated. During the average period of treatment of 10.6 +/- 2.7 years a significant (p < 0.001) drop of glycated haemoglobin occurred from the baseline value of 12.3 +/- 2.5% to 8.8 +/- 1.3%. The development of organ complications can be influenced favourably to certain extent in particular by satisfactory control of diabetes during the first 10 years of the disease. Treatment is ensured in collaboration with a neurologist, ophthalmologist and indicators of glomerular and tubular kidney function are monitored. The assumption was confirmed that at present it is possible to treat successfully labile (brittle) diabetes and eliminate deteriorating the life of diabetics.

[Long-term treatment of diabetes with transplantation of a pancreatic segment]. / Dlouhodobá lécba diabetu transplantací segmentu pankreatu.

BACKGROUND: Successful transplantation of the pancreas is at present the only way how to ensure on a long-term basis an almost physiological regulation of the carbohydrate metabolism in type 1 diabetics. So far it is, however, indicated mainly in patients with already advanced microangiopathy where at the same time also renal transplantation is planned and long-term experience is so far limited. The objective of the submitted paper is to report on the development of metabolic compensation and its impact on the development of microangiopathic changes in type 1 diabetics where the complete function of both grafts persisted more han five years. METHODS AND RESULTS: From a group of 34 combined transplantations of a pancreatic segment with an obliterated duct and a kidney, implemented in 1983-1988 in the Institute of Clinical and Experimental Medicine, a group of nine type 1 diabetics was followed up where the independence on exogenous insulin and haemodialyzation treatment persisted for or still persists for 5-8 years. After annual intervals the blood sugar level was examined, the intravenous glucose to tolerance test, free insulin levels, glycosylated haemoglobin, an ophthalmological and neurological examination was made, incl. the peripheral and autonomous system, and by means of a standard questionnaire the quality of life before and after transplantation was assessed. In all examined subjects normal blood sugar levels were recorded. The fasting insulin levels in transplant recipients were higher than in healthy subjects (22 vs. 10.2 microU/ml, p < 0.01) while in the course of the blood sugar curve corresponding levels were recorded. Glycosylated haemoglobin remained after 5 years quite or almost normal (4.2-7.2%). The coefficient of glucose assimilation after 5 years varied in the range from 0.7 to 1.9% min. Hypoglycaemic states were not recorded. In none of the recipients in the course of the investigation deterioration of the ophthalmological finding was observed and in three patients improvement was recorded. Symptoms of somatic polyneuropathy improved in all patients but signs of vegetative neuropathy remained unchanged. In all recipients psychic, physical and social rehabilitation as well as the general quality of life improved markedly. CONCLUSIONS: Although the group of investigated patients is so far small, the authors provided evidence that combined transplantation of the pancreas and kidney can influence in a very favourable way the quality of life and development of microangiopathic complications. As the success rate of transplantations of the pancreas in increasing and the risk of surgical complications is declining due to improving surgical techniques, the authors conclude that combined transplantation of the pancreas and kidney is at present the optimal therapeutic procedure in type 1 diabetics with chronic renal insufficiency and that indication for transplantation of the pancreas could be moved to earlier stages of diabetes when it would be possible to influence the development of diabetic microangiopathy more favourably.

[The effect of a combined transplantation of the pancreas and kidney on the course of peripheral diabetic neuropathy]. / Vliv úspesné kombinované transplantace pankreatu a ledviny na prubeh periferní diabetické neuropatie.

Sixteen type I diabetics were followed up from the neurological aspect and by electromyography for 6 to 42 months following successful combined transplantation of the pancreas and kidney. Before transplantation all patients suffered from medium severe to severe peripheral polyneuropathy, grade 3-5 according to the commonly used quantitative classification. All patients reported after transplantation subjective improvement, e.g. of the muscular strength or steadiness of gait. In six patients the clinical and in eight patients the electromyographic finding improved by one grade, in four patients at least the conductivity in the nerves of the upper extremities improved. In four patients the neurological and electromyographic finding did not change; none of the patients after successful transplantation deteriorated. The authors discuss the favourable effect not only of elimination of the uraemic syndrome, but also the effect of the improved carbohydrate metabolism on regenerating processes in the peripheral nervous system.

[Relation of diabetic polyneuropathy to vascular and organ complications in type I diabetes mellitus]. / Vztah diabetické polyneuropatie k cévním a orgánovým komplikacím u diabetu mellitu I. typu.

The authors investigated in 194 type I diabetics the incidence and severity of diabetic polyneuropathy in relation to other organ and vascular complications, incl. autonomous neuropathy. It was revealed that the increasing severity of polyneuropathy was significantly v séru (Cr equal to or less than 130-200 mumol/l); 4--Cr greater than 200 mumol/l; associated with severe stages of nephropathy and proliferative retinopathy with amaurosis. The concurrent presence of hypertension and polyneuropathy was surprising and striking--even in patients with the mildest grade 1 polyneuropathy hypertension was present in 10% and the incidence increased significantly with the increasing severity of polyneuropathy. Ischaemic heart disease and ischaemia of the lower extremities was significantly more frequent only in patients with grade 5 polyneuropathy. In patients with grade 4 and 5 neuropathy there was a 100% incidence of autonomous neuropathy in the cardiovascular sphere. The authors did not reveal significant differences between men and women as regards the relationship between the incidence of polyneuropathy and organ and vascular complications.

[Factors affecting the incidence and severity of polyneuropathy in type I diabetes mellitus]. / Nekteré faktory ovlivnující výskyt a tízi polyneuropatie u diabetu mellitu I. typu.

194 type I diabetics were subjected to neurological and electromyographic examinations. In 161 patients, i.e. in 83%, signs of polyneuropathy were detected, the severity of which was evaluated according to a 5-grade scale where grade 1 was the mildest and the 5th grade the most severe one. The authors proved a statistically significant correlation of the incidence and severity of polyneuropathy and the duration of diabetes. It was found that the decisive period of persistence of diabetes was 6-10 years. During this period the incidence of polyneuropathies increased from 30 to 87%. After 20 years duration of diabetes there was not only a 100% incidence of polyneuropathy, but severe affections--grade 3-5--predominated in 78%. In patients with severe grades of polyneuropathy diabetes was manifested at a significantly lower age than in patients without polyneuropathy and with a milder affection. The authors did not detect a significant relationship between the height of the patients and the incidence of polyneuropathy nor significant differences between men and women.

[The relation between peripheral and autonomic neuropathies in insulin-dependent diabetics]. / Vztah periferní a autonomní neuropatie u inzulíndependentního diabetu.

Eighty-eight type I diabetics were subjected to neurological and myographic examination and tests were performed assessing the condition of the vegetative nervous system. Forty-four patients (50% of the group) suffered from diabetic nephropathy with different expression in the stage of chronic renal failure. The authors revealed significant positive correlation between the results of tests of vegetative neuropathy and all evaluated parameters of the neurological and electromyographic finding. In patients with a S-creatinine level above 125 mumol/l in both tests of vegetative neuropathy and in all examined parameters of peripheral nerves highly significantly lower values were recorded than in diabetic patients with normal renal function. In diabetics without renal insufficiency, however, the correlations between the findings on the autonomous and peripheral nervous system were also statistically significant.