Low-salt diet downregulates plasma but not tissue kallikrein-kinin system.

The kallikrein-kinin system (KKS) is involved in the regulation of blood pressure and in the sodium and water excretion. In humans, the KKS is divided functionally into a plasma KKS (pKKS) generating the biologically active peptide bradykinin and into the tissue (glandular) KKS (tKKS) generating the active peptide kallidin. The objective of this study was to examine the effect of a low-NaCl diet on the concentration of both pKKS and tKKS in plasma and urine in 10 healthy volunteers. After a 4-day low-NaCl diet, the urinary sodium and chloride excretions had decreased from 234 to 21.2 mmol/24 h and from 198 to 14.6 mmol/24 h, respectively. The plasma levels of ANG I, aldosterone, and angiotensin converting enzyme (ACE) significantly increased from 50.4 to 82.8 pg/ml, from 129 to 315 pg/ml, and from 46.4 to 59.8 U/ml, respectively, demonstrating the physiological adjustment to the low-salt diet. In plasma, the levels of bradykinin and plasma kallikrein had significantly decreased from 13.7 to 7.57 pg/ml and 14.4 to 7.13 U/ml, respectively. However, the levels of high-molecular-weight kininogen (HMW kininogen) remain unchanged (101 vs. 112 microg/ml, not significant). Contrary to plasma kallikrein, the plasma levels of tissue kallikrein increased (0.345 vs. 0.500 U/ml; P < 0.01). The plasma kallidin levels, however, did not change (64.7 vs. 68.6 pg/ml, not significant). This can be explained by a simultaneous decrease in the plasma low-molecular-weight kininogen (LMW kininogen) levels (89.9 vs. 44.4 microg/ml; P < 0.05). As in plasma, we find increased urinary concentrations of renal (tissue) kallikrein (23.3 to 42.8 U/24 h; P < 0.05) that contrast with, and are presumably counterbalanced by, urinary LMW kininogen levels (77.0 vs. 51.8 microg/24 h; P < 0.05). Consequently, in urine low-NaCl diet caused no significant change in either bradykinin or kallidin (9.2 vs. 10.8 microg/24 h, and 10.9 vs. 10.3 microg/24 h). It is concluded that the stimulation of the renin-angiotensin system on a low-NaCl diet is associated with a decrease in pKKS (bradykinin and plasma kallikrein) but not in tissue and renal KKS. Although tissue kallikrein is increased, there is no change in kallidin, as LMW kininogen in plasma and urine is decreased. These data suggest a difference in the regulation of pKKS and tKKS by low-salt diet.

The KID Study. I: Structural baseline characteristics of the Federal Insurance for Salaried Employees' Institution (BfA) diabetic patients in inpatient rehabilitation. Kissingen Diabetes Intervention Study.

% of type I diabetics are not administering insulin according to the intensified conventional therapy schedules, only 16.8% of all type II diabetics are treated with diet only. Type II diabetics are much too often treated with pre-mixed insulins of too high dosage (26.2%) or with oral hypoglycemics (46.2%) of which 90% were sulphonylureas and nearly exclusively glibenclamide. Oral hypoglycemics with extrapancreatic activity or combined therapies were not common among the patients.

The KID Study. III: Impact of inpatient rehabilitation on the metabolic control of type I and type II diabetics--a one-year follow-up.

The Kissingen Diabetes Intervention Study (KID) evaluated 1050 diabetic patients of the German Federal Insurance Institution for Salaried Employees (BfA) admitted for inpatient rehabilitation. The data for the prospective longitudinal study (which was collected in a single center) relate to the structure of the patient cohort, socio-economic and psychological factors and the mode of medical management at the time of admission and discharge. Data regarding the same variables was checked by random testing six and twelve months after discharge and used in this part of the study. This cohort of patients is especially interesting for aspects of health policy because it comprises rather young diabetics engaged in highly qualified professional work. Therapy modifications entailing a more intensive insulin regimen were necessary in 20.7% of all type I diabetics. Most of these alterations were maintained over the following 12 months of management by the general practitioner. Improvement of HbA1 levels was related to the number of daily insulin administrations. The results obtained during inpatient treatment in patients on ICT are maintained even one year after their discharge. For type I diabetics, the first training measure especially results in a long-term improvement of the metabolic situation, whereas patients who have already received training several times previously benefit continuously less with increasing repetition of training. After twelve months the intensified insulin therapy of type I diabetics had no further effect on the BMI or the already previously normal serum lipids. In 55.5% of all type II diabetics, the therapy had to be modified. Inpatient rehabilitation resulted in raising the low number of type II diabetics treated just with diet by 5.3%. This proportion was again slightly reduced 12 months later. During inpatient residence the number of overweight type II diabetics treated with drugs was reduced both in the group on oral hypoglycemics and in the group on pre-mixed insulin, according to the weight loss achieved. On the other hand, it was often necessary to intensify the usual insulin regimen twice daily in the group of younger patients with normal body weight. These modifications were maintained twelve months after the stay in hospital for most of these patients. Virtually all type II diabetics on oral hypoglycemics are overweight as a reflection of too early prescriptions of oral hypoglycemics which often neglects the chance of a dietary management only. In this group, therapy modifications were directed towards treatment with diet only and with oral hypoglycemics having an extra-pancreatic action. On metformin, the HbA1 was reduced by 0.3% and the BMI by 0.9 kg/m2 even 12 months later. In the 90% of type II diabetics previously treated with sulphonylureas (almost exclusively glibenclamide), re-modification of therapy from metformin back to the old regimen (16:9%) was especially high. This is probably due to the uncertainty with and general restrictions in the prescription of metformin in the relevant period 1991 to 1995. The results 12 months after inpatient treatment show the small improvement of HbA1 and serum lipids as already seen in other larger interventional studies. The BMI does not change significantly within the relatively short follow-up period. The best long-term results are achieved by a combined therapy with sulphonylurea compounds and metformin. The KID study demonstrates major deficits in intensifying the insulin regimen of type I diabetics and in the individual adaptation to therapy of type II diabetes in Germany, even when younger patients of higher professional status are considered. Interventional inpatient rehabilitation improves their metabolic situation with lasting effect and can compensate deficits in outpatient management by the general practitioner. However, future concepts have to be improved at all levels of diabetic management, with a view to achieving an optimum interaction.