[Transplantation of the pancreas].
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Denmark↗
Biomedical subjects
T Deckert
Publications and source records attributed to T Deckert.
Exercise as a provocative test in early renal disease in type 1 (insulin-dependent) diabetes: albuminuric, systemic and renal haemodynamic responses.
The value of exercise as a provocative test for early renal disease in Type 1 (insulin-dependent) diabetes was re-evaluated. Three carefully characterized groups of males were studied: 10 non-diabetic controls, 16 diabetic patients (group 1) with normal urinary albumin excretion (less than 15 micrograms/min) and 14 Albustix-negative diabetics (group 2) with increased urinary albumin excretion (15-122 micrograms/min). Assignment to a study group was made on the basis of three 24-h urine collections, and the groups were well matched for age, weight, height, and serum creatinine concentration. The two diabetic groups were similar with regard to duration of disease (13 +/- 6 versus 16 +/- 3 years), metabolic control (HbA1c: 8.4 +/- 1.4 versus 8.7 +/- 1.3%) and degree of diabetic complications (beat-to-beat variation and retinopathy). An exercise protocol of 450 and 600 kpm/min workloads was employed. In the resting state group 2 patients had elevated systolic blood pressure compared with the normal subjects (132 +/- 13 versus 119 +/- 9 mmHg), and their glomerular filtration rate was significantly reduced compared with group 1 (123 +/- 19 versus 138 +/- 15 ml/min per 1.73 m2, p less than 0.05). During exercise the urinary albumin excretion rate increased significantly in all three groups (normal subjects: 6 +/- 0.7 to 8 +/- 1.3 (microgram/min); group 1: 6 +/- 0.6 to 9 +/- 1 microgram/min and group 2: 48 +/- 10 to 113 +/- 23 micrograms/min), the relative increase being higher in group 2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus.
We followed 1,134 patients with Type 1 (insulin-dependent) diabetes, diagnosed between 1933 and 1952, until 1982 or death or until their emigration. Their age at onset of diabetes was under 31 years. Information concerning the development of persistent proteinuria was sought in every case. In 104 cases, the data were either questionable or the patient could not be traced. Twenty-nine patients developed non-diabetic proteinuria. Among the remaining 1,001 patients, 406 developed persistent proteinuria (350 died) and 595 did not (166 died). The incidence of persistent proteinuria was highest among men; it decreased with increasing year of diabetes onset from 1933 to 1952, and decreased with increasing age at onset. The relative mortality was extremely high among patients with persistent proteinuria, increasing to a maximum of about 100 at age 35 years. Patients not developing proteinuria had a relatively constant low relative mortality of about 2. The decreasing incidence of persistent proteinuria and the decreasing mortality with increasing calendar year of diabetes onset resulted in a 50% increase in life-expectancy among patients diagnosed in 1950 compared with patients diagnosed in 1935. In patients who developed persistent proteinuria, relative mortality was higher in women than men at all ages. In patients who did not develop proteinuria, relative mortality was similar in men and women after the age of 35. Uraemia was the main cause of death in patients with persistent proteinuria, although cardiovascular deaths were more frequent than in patients without proteinuria. Thus, proteinuria is associated not only with death from uraemia but also from cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Denmark↗
Relative mortality of type 1 (insulin-dependent) diabetes in Denmark: 1933-1981.
The relative mortality of Type 1 (insulin-dependent) diabetes in Denmark during the period 1933-1981 was studied using a modification of Cox's regression model on the basis of two patient populations, ascertained in different ways and independently of each other. Initial analysis showed that the two groups could be combined completely into one common analysis. Relative mortality was the same for both sexes. The additional variables studied were age at diagnosis, current age, calendar year at diagnosis and calendar time during follow-up. All these interrelated variables were accounted for in the analysis. The analysis showed that relative mortality decreased with increasing age at diagnosis; increased from 1933 to a maximum in about 1965, after which it decreased; increased with increased duration of diabetes to a maximum at 15-25 years, after which it declined.
Adolescent↗
The immunogenicity of new insulins.
Treatment with conventional insulin preparations results in appreciable insulin antibody formation in nearly all subjects. High titers of insulin antibodies are undesirable. They might induce insulin allergy and insulin resistance, and they influence metabolic regulation. Also, lipoatrophy is related to the immunogenicity of insulin preparations. Insulin antibodies are transferred from insulin-treated diabetic mothers to the fetus and contribute to the increase of free plasma insulin in the fetus, thus influencing the development of macrosomia and neonatal hypoglycemia. Therefore, the risk of insulin antibody formation should be reduced. This is possible by using purified, nonbeef insulin preparations. The risk of insulin allergy, insulin resistance, lipoatrophy, and prolonged hypoglycemia in mother and child is reduced by treating pregnant diabetic subjects with purified pork or human insulin preparations. The reduction of insulin requirement that accompanies the change from conventional insulin to purified nonbeef insulin treatment will compensate to some extent for the higher costs of new insulins.
Animals↗
Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy.
Thirty patients with insulin-dependent diabetes mellitus (IDDM) who had advanced background retinopathy were randomized to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 2 yr. The mean blood glucose and hemoglobin A1C (HbA1C) were significantly lower in the CSII group than in the UCT group. The mean blood glucose and HbA1C did not change from the first to the second year in either of the treatment groups in spite of less frequent home-monitoring of blood glucose and less frequent outpatient visits during the second year. Four patients in the CSII group and five in the UCT group developed proliferative retinopathy. However, a marginally significant trend was found toward more frequent improvement of retinal morphology in the CSII group (47%) than in the UCT group (13%). Beat-to-beat variation was found to deteriorate significantly with UCT compared with a nonsignificant improvement with CSII therapy. Vibration sense was unchanged in both treatment groups. It is concluded that near-normal blood glucose levels can be maintained with CSII therapy in spite of less frequent home-monitoring of blood glucose and outpatient visits. Furthermore, established background retinopathy may progress to proliferative retinopathy in spite of 2 yr of near-normal blood glucose levels. However, a marginally significant trend toward more frequent improvement of retinal morphology was found among CSII-treated patients compared with conventionally treated patients. Large-scale, prospective, randomized studies are needed to confirm these results.
Blood Glucose↗
A Cox regression model for the relative mortality and its application to diabetes mellitus survival data.
A Cox-type regression model for the ratio between the mortality in a cohort and that in a reference population is introduced. By means of the model it is possible to include in the survival analysis both individual (possibly time-dependent) characteristics for the study cohort and changing trends in the mortality in the reference population. This is particularly relevant in long-term follow-up studies where there may be considerable changes in the mortality in the reference population. Estimation procedures in the model are discussed and large-sample properties of the estimators are outlined. The model is applied to the analysis of two sets of data concerning the survival among insulin-dependent diabetics in Denmark.
Adolescent↗
Immune complexes in insulin-dependent diabetes.
Circulating immune complexes (IC) were studied in 40 newly-diagnosed insulin-dependent diabetics (IDDM), 40 long duration IDDM, and 16 healthy controls. IC were detected by the solid-phase Clq test (SP-Clq). IDDM patients at diagnosis (25%) showed a higher incidence of IC compared to the long duration IDDM patients (15%) and the control group (7%). There was no difference in the prevalence of circulating IC in long duration IDDM with clinical nephropathy and those without clinical nephropathy. IC detected by Sp-Clq, seem to be associated with the clinical onset of IDDM but not with the development of nephropathy.
Adult↗
Incipient nephropathy in type 1 (insulin-dependent) diabetes.
Patients with Type 1 (insulin-dependent) diabetes without proteinuria were studied to define those patients who will later develop persistent proteinuria (more than 0.5 g protein/24 h). Two investigations were performed; 71 patients were studied longitudinally for 6 years and another 227 patients were studied cross-sectionally. All were less than 50 years of age and had developed diabetes before the age of 40 years. At entry into the study they had no proteinuria (Albustix method), had normal blood pressure and urinary albumin excretion rates less than 200 micrograms/min (normal less than or equal to 20 micrograms/min). The best predictor of persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min was the initial urinary albumin excretion rate. During the longitudinal study, seven patients with an urinary albumin excretion rate of more than 70 micrograms/min at the start of the study developed persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min. In contrast, only three out of the remaining 64 patients with urinary albumin excretion rate less than or equal to 70 micrograms/min developed urinary albumin excretion rate greater than 200 micrograms/min. Patients with an urinary albumin excretion rate greater than 70 micrograms/min are thus at risk of developing diabetic nephropathy. We designate this stage of renal involvement incipient nephropathy. Patients with incipient nephropathy were further characterized in the cross-sectional study. Compared with normoalbuminuric patients, patients with incipient nephropathy had increased systolic and diastolic blood pressure, but normal serum creatinine. The glomerular filtration rate was higher than normal in patients with incipient nephropathy though not different from that of normoalbuminuric patients.
Adolescent↗
Renal changes in long-term type 1 (insulin-dependent) diabetic patients with and without clinical nephropathy: a light microscopic, morphometric study of autopsy material.
The relationship between clinical diabetic nephropathy and morphological renal changes was studied in autopsy material from 34 long-term Type 1 (insulin-dependent) diabetic patients of juvenile onset. Seventeen had no clinical signs of nephropathy (defined by persistent proteinuria, hypertension, and elevated serum creatinine) while a further 17 age-matched diabetic patients with a similar duration of diabetes had severe clinical nephropathy. The renal tissue was examined by morphometric light microscopy, using a point counting technique and the results compared with renal tissue from subjects who died without diabetes. In the diabetic patients without clinical nephropathy, arteriolohyalinosis was much more pronounced compared with non-diabetic subjects (2p less than 0.001) and within the glomeruli the amount of subcapsular fibrosis and glomerular mesangium was increased (2p less than 0.05 and less than 0.001, respectively). The area of open capillaries was decreased compared with non-diabetic subjects (2p less than 0.025), and the percentage of occluded glomeruli was significantly increased (2p less than 0.05). The diabetic patients with clinical nephropathy had significantly more interstitial tissue and glomerular mesangium (2p less than 0.001) and less open glomerular capillaries (2p less than 0.001) than diabetic subjects without clinical nephropathy, but severe glomerulosclerosis could be seen in the diabetic patients without any sign of clinical nephropathy. Serum creatinine correlated with the mesangial area (r = 0.792, 2 a less than 0.001). No difference was observed between the two diabetic groups regarding the degree of arteriolohyalinosis, the number of Kimmelstiel-Wilson lesions or exudative lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Portable detectors for 125I-insulin absorption measurement during subcutaneous infusion with portable pumps.
Programmed subcutaneous insulin infusion is a promising method for normalisation of the blood glucose concentration in insulin-dependent diabetics. To evaluate insulin availability the absorption rate from the depot is usually measured intermittently by radioactively-labelled insulin and stationary scintillation detectors. Small portable detectors are an alternative, however, and continuous absorption measurements could be made during normal life conditions. Contrary to conventional single injection therapy, the insulin depot initially expands during infusion treatment, changing the geometry during measurements. In the present study the methodological aspects and geometrical dependences were investigated. Simulated studies were made with various plane disc 125I sources in Perspex phantoms as well as 125I-insulin absorption studies in short-term subcutaneous infusion experiments with anaesthetised rabbits. Results from portable, end-window Geiger-Müller (GM) detectors fixed above the depots and close to the surfaces of phantom or skin were compared with results obtained by a conventional stationary NaI(Tl) detector 15 cm from the phantom or skin surface. With a 125I-insulin infusion site at 5 mm depth in the subcutaneous tissue of rabbits, an overall linear proportionality was found between the results obtained with a NaI(Tl) detector and a GM detector raised 15 mm above the skin surface inside the detector housing.
Animals↗
Smoking habits and prevalence of clinical diabetic microangiopathy in insulin-dependent diabetics.
All patients having insulin-dependent diabetes with onset before 30 years of age and a duration of disease of 12-40 years who visited a diabetes centre within one year were registered. 97% (n = 668) answered a WHO questionnaire on cigarette smoking. The smoking habits were compared to the frequency of proliferative retinopathy and/or diabetic nephropathy (persistent proteinuria). The prevalence of diabetic nephropathy was significantly higher among heavy smokers (greater than 10 cigarettes a day for more than one year) than among non-heavy smokers, 19.2% versus 12.1% (p less than 0.02). An increasing frequency of nephropathy was found with increasing cigarette consumption (p less than 0.01). No difference in the prevalence of proliferative retinopathy was found between smokers and non-smokers. It is concluded that cigarette smoking is a risk factor for the development of nephropathy in insulin-dependent diabetics.
Adult↗
Continuous subcutaneous insulin.
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Diabetes Mellitus↗
Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetics.
30 insulin-dependent diabetic patients with background retinopathy were randomised to conventional treatment (UCT) or treatment with continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 1 year with fortnightly seven-sample home blood glucose measurements and retinal examinations every 6 months. Mean blood glucose and stable haemoglobin A1c during months 3-12 were significantly lower in the CSII than the UCT group. Retinal morphology deteriorated during the year with no significant differences between UCT and CSII groups. The frequency of deterioration was highest in the CSII group, especially among the 10 patients with best glycaemic control. Proliferative retinopathy developed in 3 patients--2 of these were CSII treated. Retinal function (oscillatory potential, macular recovery time, and posterior vitreous fluorophotometry) improved significantly with CSII treatment and deteriorated significantly with UCT. Changes in retinal function were most pronounced in patients with the best and the poorest regulated glycaemic control.
Adult↗
Pharmacokinetics of continuous subcutaneous insulin infusion.
One of the reasons for the variability of blood glucose regulation in Type 1 (insulin-dependent) diabetic patients is the huge variation in subcutaneous absorption of intermediate-acting insulin. We have investigated the variation in insulin absorption during continuous subcutaneous insulin infusion in eight such patients. The content of insulin in the subcutaneous tissue was measured using 125I-labelled insulin. The concentration of free serum insulin and blood glucose was followed from 1 h before and from 7 h after breakfast on two consecutive days. The amount of insulin absorbed during 24 h differed in all cases by less than 3% from the daily insulin dose given by the pumps. Mean insulin absorption rates and mean free insulin concentration showed peak values 30-90 min after meal bolus injections; this was sufficient to maintain near-normal blood glucose. Mean free serum insulin correlated strongly with disappearance of insulin from the subcutaneous tissue (r = 0.98). From the insulin absorption rates and free insulin concentrations during basal constant insulin infusion, the half-time of serum insulin was calculated as 6 min. Compared with the known large variability in the absorption of intermediate-acting insulin, continuous subcutaneous insulin infusion offers a precise and reproducible way of insulin administration resulting in post-prandial serum insulin peaks sufficient to maintain near-normal blood glucose levels. The half-time of serum insulin during subcutaneous infusion corresponds to values for intravenous infusion given in the literature, indicating that local degradation of insulin in subcutaneous tissue is of minor importance.
Adult↗
Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: an epidemiological study.
A follow-up of 1475 Type 1 (insulin-dependent) diabetic patients diagnosed before 1953 (815 males, 660 females) and before the age of 31 years was conducted. All patients were seen at the Steno Memorial Hospital and were referred from all parts of Denmark; 91 (6%) could not be traced. The rest (94%) were followed until death or for at least 25 years; 249 (17%) were followed for greater than 40 years. Clinical diabetic nephropathy developed in 531 (41%) of the 1303 patients in whom sufficient information was available regarding proteinuria. Other causes of proteinuria were found in 3%, and 57% did not develop persistent proteinuria. The prevalence of diabetic nephropathy was 21% after 20-25 years of diabetes duration followed by a decline to 10% after 40 years. Two incidence peaks of the onset of proteinuria were seen, one after 16 and another after 32 years duration of diabetes and was low after 35 years duration. The cumulative incidence was 45% after 40 years of diabetes. A male preponderance was seen among patients with nephropathy. A significant difference in the pattern of annual incidence rates of diabetic nephropathy was seen, when groups with onset of diabetes before 1933, between 1933-1942, and 1943-1952, respectively, were compared. An association between daily insulin requirement and nephropathy incidence was found. Patients with nephropathy had a much poorer survival than those without proteinuria; 40 years after onset of diabetes, only 10% of patients who developed nephropathy were alive, whereas greater than 70% of patients who did not develop nephropathy survived.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Clinical factors influencing the absorption of 125I-NPH insulin in diabetic patients.
Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5 +/- 0.8 h (mean +/- SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2 +/- 3.1 h, p = 0.0001). Low bicarbonate levels increased the absorption (T1/2 3.9 +/- 2.3 h, p less than 0.05). Lean diabetics had a faster absorption (6.2 +/- 1.9 h) than normal weight diabetics (7.5 +/- 2.0 h, p less than 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r = 0.882, p less than 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intra-patient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics.
Absorption↗
Natural history of diabetic microangiopathies.
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Diabetes Mellitus, Type 1↗