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T Deckert

Publications and source records attributed to T Deckert.

At least 73 records · Page 4Linked to original sources

Glomerular size and charge selectivity in insulin-dependent diabetes mellitus.

The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects. These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional IgG compared to patients with normal albumin excretion, while fractional IgG4 and albumin clearances were increased three- to fourfold; indicating unchanged glomerular pore size, but a decrease in anionic pore charge. In patients demonstrating urinary albumin excretion of greater than 100 mg/24 hr fractional IgG clearance increased to the same extent as fractional albumin clearance, indicating an increase in large pore area. Fractional beta 2-microglobulin clearances were similar to that of control subjects in the different patient groups indicating unchanged tubular reabsorption of proteins. Thus, the increase in large pore area seen in patients with clinical nephropathy is preceded by loss of anionic charge in the glomerular basement membrane. It is likely that this loss of anionic charge is due to loss of heparan sulphate-proteoglycan.

Adult↗

Metabolism of albumin and fibrinogen in type 1 (insulin-dependent) diabetes mellitus.

The metabolism of albumin and fibrinogen was studied in 24 long-term diabetic Type 1 (insulin-dependent) patients, using a double tracer technique. The patients were divided into three groups according to their urinary albumin excretion. Group 1 had normal albumin excretion (less than 30 mg/24 h), group 2 had persistent microalbuminuria (30-300 mg/24 h), and group 3 had clinical nephropathy (greater than 300 mg/24 h). Eight normal persons served as control subjects. Except for slightly lower distribution fractions of both proteins (intravascular mass/total mass), group 1 did not differ from normal subjects. In groups 2 and 3 the relative catabolism of albumin was increased, as denoted by an increase in the fractional catabolic rate. Albumin synthesis was unaltered, resulting in lower plasma concentrations and lower intravascular and total body masses of albumin. Oppositely, fibrinogen synthesis was augmented, leading to an increase in plasma fibrinogen concentration and total fibrinogen body mass, in spite of increased catabolism. The fractional catabolic rates were unaltered. The study demonstrates that long-term diabetic patients with normal urinary albumin excretion have normal albumin and fibrinogen metabolism, but that grave alterations in plasma protein metabolism are present in patients with only slightly increased urinary albumin excretion.

Adult↗

Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors.

Fifty-nine Type 1 (insulin-dependent) diabetic patients with (group I) and 59 patients without nephropathy (group II) pair-matched according to sex (30 males and 29 females), age (33 years, range 15-48) and diabetes duration (19 years, range 6-42) were followed for a period of 10 years from about 5 years before to 5 years after onset of proteinuria. The cumulative incidence of coronary heart disease was estimated, and blood pressure and serum cholesterol were followed. Within six years after onset of proteinuria the cumulative incidence of coronary heart disease was increased eight-fold in group I (40%) compared with group II (5%), (p less than 0.001). Blood pressure was higher in group I compared with group II from before onset of proteinuria (135/86 +/- 17/9 mmHg vs 129/80 +/- 15/8 mmHg, p less than 0.001), and serum cholesterol elevated from onset of proteinuria in group I (6.3 +/- 1.2 mmol/l) vs. group II (5.5 +/- 1.0 mmol/l), (p less than 0.005). Patients in group I who developed coronary heart disease had similar age (36 years, range 21-51, vs 38 years, range 21-53), sex (50% males vs. 52% males), smoking frequency (50% vs 49%), diabetes duration (22 years, range 9-39, vs 24 years, range 10-42) and serum creatinine (110 mumol/l, range 69-284, vs 108 mumol, range 72-1024) compared with patients not developing coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus.

We studied 73 Type 1 (insulin-dependent) diabetic patients, 18 to 50 years of age, with a diabetes duration of more than five years. Group 1: normal urinary albumin excretion below 30 mg per 24 h (n = 19); group 2: microalbuminuria, 30-300 mg per 24 h (n = 36); and group 3: diabetic nephropathy, above 300 mg per 24 h (n = 18). Fifteen nondiabetic persons matched for sex and age served as control subjects. The sodium intake evaluated on the basis of 24-h urine sodium excretion was similar in patients and control subjects. Blood pressure in groups 1 and 2 and control subjects was below 160/95 mmHg. The blood pressure was increased in group 3 as compared with the other groups (systolic/diastolic 161 +/- 22/101 +/- 9 mmHg vs 131 +/- 13/84 +/- 10, mean +/- SD, p less than 0.0001). Exchangeable sodium was increased in patients (p less than 0.01) and correlated to the mean blood pressure (n = 70, r = 0.41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p less than 0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n = 68, r = -0.24, p less than 0.05), and exchangeable sodium and aldosterone (n = 66, r = -0.36, p less than 0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Transcapillary escape rate and relative metabolic clearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus.

The transcapillary escape rate and relative plasma disappearance of glycated and non-glycated albumin were measured in 25 male Type 1 (insulin-dependent) diabetic patients using a double tracer technique. The patients were divided into three groups on the basis of their urinary albumin excretion: group 1, normal albumin excretion (less than 30 mg/24 h) (n = 8); group 2, microalbuminuria (30-300 mg/24 h) (n = 9); and group 3, clinical nephropathy (greater than 300 mg/24 h) (n = 8). Six male age-matched non-diabetic persons served as control subjects. The transcapillary escape rate of glycated albumin was similar in group 1 and control subjects (4.7 +/- 2.1 versus 5.1 +/- 1.7%), but significantly increased in group 2 (7.0 +/- 1.7%, p less than 0.05) and in group 3 (7.9 +/- 3.1%, p less than 0.05). The transcapillary escape rate of glycated albumin was slightly lower than that of non-glycated albumin in all groups, but significant only in normal control subjects. No difference in the catabolic rate of glycated and non-glycated albumin was found. We conclude that the in vivo effects of glycation on the clearance and transcapillary passage of albumin are small and not likely to play any significant role in the development of late diabetic microvascular complications.

Capillary Permeability↗

Cardiovascular risk factors in type I (insulin-dependent) diabetic patients with and without proteinuria.

In diabetes mellitus cardiovascular mortality among patients with increased urinary albumin excretion seems to be higher than in patients with normal urinary albumin excretion. Therefore we investigated blood pressure, total cholesterol, fibrinogen and in vivo platelet adhesion in 61 patients with type I (insulin-dependent) diabetes, 39 without complications, such as retinopathy or proteinuria and 22 with proteinuria and slightly elevated serum creatinine. The two groups had similar age, sex, diabetes duration and glucose control. Blood pressure, total cholesterol, fibrinogen and in vivo platelet adhesion were all significantly elevated in patients with proteinuria (p less than 0.01), whereas these parameters were normal in the uncomplicated diabetic patients, independent of diabetes duration. The mortality of cardiovascular disease during 20 years' follow-up was significantly higher among patients with proteinuria compared with patients without proteinuria (p less than 0.001), indicating that these risk factors contribute to the increased cardiovascular mortality in patients with clinical nephropathy.

Adolescent↗

Declining incidence of persistent proteinuria in type I (insulin-dependent) diabetic patients in Denmark.

The decreasing relative mortality among type I (insulin-dependent) diabetic patients during the last 50 years might be related to the incidence of clinical diabetic nephropathy. We therefore followed 2890 type I diabetic patients (1607 males and 1283 females) diagnosed between 1933 and 1972 and before the age of 31, from admission to death, emigration, or January 1, 1984. All patients had been admitted to the Steno Memorial Hospital. Information on development of proteinuria was obtained in 2658 patients (92%). Five hundred twenty-five patients developed proteinuria due to diabetes and 49 developed nondiabetic proteinuria. When comparing patients diagnosed between 1933 and 1942 with those diagnosed between 1953 and 1962, the incidence of proteinuria decreased by 30% (P less than .03). This might explain the decrease of relative mortality in type I diabetic patients. The incidence decreased with increasing age at onset but was always highest in males. Insulin dose (U/kg) and diabetes duration at admission did not influence the incidence of proteinuria. The incidence peaked after 15-17 yr of diabetes duration independent of sex, age at diagnosis, or calendar year of diagnosis. However, the majority of patients did not develop proteinuria during 40 yr of diabetes. This suggests individual renal susceptibility to the deleterious effect of hyperglycemia.

Denmark↗

Changes in blood pressure and renal function in patients with type I (insulin-dependent) diabetes mellitus prior to clinical diabetic nephropathy.

58 type I (insulin-dependent) diabetic patients who in the period 1975 to 1981 developed clinical diabetic nephropathy (urinary protein excretion greater than 0.5 g/day) (group I) were matched in pairs to 58 patients not developing nephropathy (group II) according to sex (29 males and 29 females), age (33 years (18-46) vs. 33 years (15-48] and diabetes duration (19 years (6-39) vs. 19 years (6-42]. Supine blood pressure measured during hospitalization and weight X 100/serum creatinine were evaluated as to diabetes duration in the periods greater than 10, 10-6, 5-1 years prior to and at the onset of proteinuria. There was no difference in initial blood pressure (124/78 +/- 11/10 mmHg (group I) vs. 125/79 +/- 11/10 mmHg (group II]. Diastolic blood pressure was higher from 10-6 (85 +/- 9 vs. 80 +/- 7 mmHg; p less than 0.05) and systolic blood pressure from 5-1 (138 +/- 17 vs. 129 +/- 17 mmHg; p less than 0.01) years before onset of proteinuria in group I compared with group II. There was no difference in weight X 100/serum creatinine initially (87 +/- 17 kg/mumol/l (group I) vs. 88 +/- 13 kg/mumol/l group II) but from the period 5-1 years prior to the onset proteinuria it was reduced in group I (80 +/- 14 kg/mumol/l vs. group II (86 +/- 14 kg/mumol/l); (p less than 0.05). In conclusion, there was no initial difference in blood pressure and renal function between type I diabetic patients who later developed clinical diabetic nephropathy and those who didn't. Increase in blood pressure starts 5-10 years and renal function impairs 1-5 years before the onset of proteinuria.

Adolescent↗

Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes.

36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years. The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventional-treatment group (median 8.6%, range 7.2-13.4) (p less than 0.001). Clinical diabetic nephropathy (a urinary albumin excretion rate above 300 mg/24 h in at least two of three 24 h urine collections) developed in 5 patients in the conventional-treatment group, but not in the insulin-infusion group (p less than 0.05, two-tailed). Fractional albumin clearance (mean and range X 10(7] increased in the conventional-treatment group from 160 (35-468) to 360 (29-1580) and was unchanged in the insulin-infusion group (170 [31-608] before to 160 [26-460] after) (p less than 0.05). Insulin infusion had an overall beneficial effect on the annual increase in urinary albumin excretion (p less than 0.05), and the mean glycosylated haemoglobin values correlated positively with annual change in albumin excretion (r = 0.57, p less than 0.0001). The diastolic blood pressure rose significantly in the conventional-treatment group (p less than 0.001), and annual change in mean blood pressure correlated with change in urinary albumin excretion (r = 0.49, p less than 0.001).

Adolescent↗

Kidney function during 12 months of strict metabolic control in insulin-dependent diabetic patients with incipient nephropathy.

Thirty-six patients with insulin-dependent diabetes mellitus who had Albustix-negative urine but elevated urinary albumin excretion (30 to 300 mg per 24 hours) were matched in pairs according to their urinary albumin level, blood glycosylated hemoglobin level, and sex and assigned randomly to either unchanged conventional treatment or continuous insulin infusion. During the next 12 months a significant improvement in glycemic control was observed in the insulin-infusion group, with a reduction in the mean glycosylated hemoglobin level from 9.5 to 7.3 percent. There was no change in the control group (9.3 to 9.2 percent). No significant change in albumin excretion was observed in either group. The mean blood pressure increased slightly in both groups (from 98 to 101 mm Hg in the insulin-infusion group and from 98 to 103 mm Hg in the control group). Kidney size was significantly reduced in all patients during insulin infusion, but no consistent change was observed in the control group. No significant change was observed in the glomerular filtration rate. Our data suggest that the pathologic processes causing microalbuminuria in early renal disease are not reversed during 12 months of strict metabolic control.

Adolescent↗

Evidence of changes in renal charge selectivity in patients with type 1 (insulin-dependent) diabetes mellitus.

Altered filtration of macromolecules due to decreased electrical charge of the glomerular basement membrane might be the initial step in the development of albuminuria in patients with Type 1 (insulin-dependent) diabetes mellitus. We therefore investigated the selectivity index, i.e. renal clearance of non-glycated plasma albumin/clearance of glycated plasma albumin in 38 patients with Type 1 diabetes mellitus. The two albumin molecules differed slightly in charge, non-enzymatic glycated albumin being more anionic at physiological pH compared with unmodified plasma albumin. Glycated albumin in plasma and urine was determined by a specific, sensitive and highly reproducible chromatographic procedure. In diabetic patients with normal urinary albumin excretion, the selectivity index was increased three-fold compared with that of non-diabetic subjects (2 p less than 0.01). A significant correlation (r = 0.53, 2 p less than 0.01) between haemoglobin A1c and selectivity index was demonstrated in these patients, indicating a change in charge-dependent renal filtration could possibly be attributed to non-enzymatic glycation of components in the glomerular basement membrane and tubuli. Diabetic patients with increased albumin excretion rate had a significantly lower selectivity index compared with patients with normal albumin excretion (2 p less than 0.01). A significant negative correlation (r = 0.85, 2 p less than 0.001, exponential curve fit) was seen between urinary albumin excretion and selectivity index in the diabetic patients, indicating that the capability of differentiating between macromolecules of different charges is again lost with increasing urinary albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mortality of type 1 (insulin-dependent) diabetes mellitus in Denmark: a study of relative mortality in 2930 Danish type 1 diabetic patients diagnosed from 1933 to 1972.

This study included 2930 (1642 male, 1288 female) Type 1 (insulin-dependent) diabetic patients diagnosed before the age of 31 years and between 1933 to 1972. The patients were followed from first admission to Steno Memorial Hospital until death, emigration, or until 1 January 1983. Relative mortality was studied, and the influence of calendar year of diagnosis, diabetes duration, age at diagnosis, current age and sex were studied. Relative mortality decreased continuously during the period, and patients diagnosed after 1956 had a relative mortality 30-40% lower than patients diagnosed from 1933 to 1946. Relative mortality increased with increasing diabetes duration until about 20 years of duration, after which it declined. It also increased with increasing age until 31-40 years. It decreased with increasing age at diabetes onset. Factors like calendar year of diabetes onset, age at diagnosis, current age and sex had no influence on relative mortality within the first 15 years of duration, although the relative mortality increased with diabetes duration. In the interval of 16 to 40 years of diabetes duration, the relative mortality decreased with increasing calendar year of diagnosis and age at diagnosis. In patients with a diabetes duration of more than 40 years, the relative mortality decreased with increasing age and diabetes duration. These results show that the prognosis of Type 1 diabetic patients has improved considerably during the last 40 years. Furthermore, they show that diabetes duration is the most important determinant of relative mortality.

Adult↗

HLA associations in insulin-dependent diabetes: search for heterogeneity in different groups of patients from a homogeneous population.

A total of 317 unrelated Danish patients with insulin-dependent diabetes mellitus (IDDM) have been HLA-DR typed and the antigen and phenotype frequencies compared with those in 1177 unrelated Danish controls. The strong positive associations with DR3 and 4 and the strong negative one with DR2 were confirmed, and the remaining antigens showed a hierarchy from weakly positive to strongly negative associations: DRw9, w8, 1, 5, w6, 7. The study population included various special groups of patients selected in order to study heterogeneity: very early (less than 5 years) and very late (greater than 40 years) onset IDDM, pregnancy-induced IDDM, IDDM nephropathy, and long-term (greater than 40 years) survivors without complications. When comparing these groups, the following minor differences were seen: the DR3,4 phenotype is significantly (p = .02) more frequent in IDDM with onset before age 20 (35%) than in other cases (24%), and in familial IDDM (48%) than in other cases (28%); the frequency of the DR4 antigen was significantly (p = .008) more frequent in long-term survivors (86%) than in other patients (69%), while it was significantly (p = .02) less frequent in IDDM nephropathy (63%) than in long-term survivors. However, apart from the age-at-onset heterogeneity, which was suspected a priori, these differences may be due to chance, and the main conclusion of this study is that the HLA-DR associations in IDDM are indeed extraordinarily homogeneous irrespective of the clinical characteristics at onset and course of the disease.

Age Factors↗

Effects of pregnancy hormones on pancreatic islets in organ culture.

Pregnancy is associated with hyperinsulinaemia and decreased glucose tolerance which may lead to gestational diabetes. Sera from pregnant women in the last trimester were found to stimulate insulin secretion of mouse pancreatic islets maintained in organ culture suggesting a direct effect of pregnancy hormones and/or metabolites on the endocrine pancreas. Previous studies have shown that progesterone and human placental lactogen (hPL) had direct effects on isolated islets and in the present study the effects of combined addition of these hormones to the cultured islets were evaluated. hPL, 1 microgram/ml was found to prevent the decrease in the islet insulin content due to progesterone 100 ng/ml, and hPL induced an increase in the DNA-content compared with the progesterone treated islets. The effect of the hormones on the DNA synthesis was evaluated by incorporation of [3H]thymidine into newborn rat islets. Progesterone in a high concentration, 1 microgram/ml, inhibited while 0.1 and 1 microgram/ml hPL stimulated the [3H]thymidine incorporation. These results indicate that progesterone may contribute to the increased glucose-induced insulin release during pregnancy and hPL to the beta-cell hyperplasia. Since progesterone and hPL counteracted each other with regard to both insulin content and DNA-synthesis in the islets, the direct interaction between these two hormones on the beta-cell may be of importance for the changes in glucose metabolism during pregnancy.

Animals↗

Diabetic nephropathy--susceptible to care? A cohort-study of 641 patients with type 1 (insulin-dependent) diabetes.

The aim of the study was to investigate the influence of diabetes care on the incidence and course of clinical nephropathy in patients with Type 1 (insulin-dependent) diabetes mellitus. After hospitalization at a diabetes care unit within 15 yr after diabetes onset, 246 patients were followed at the care unit, whereas 395 patients were non-attenders. The 2 groups were comparable with regard to age and calendar year at diagnosis, insulin dose and body weight. After 40 yr of diabetes duration the cumulative incidence of persistent proteinuria was significantly lower among patients treated at the unit (31.9% vs 44.8%, p less than 0.003). The median survival after onset of persistent proteinuria was significantly longer among patients followed at the diabetes care unit (p less than 0.003). Among patients not developing diabetic nephropathy, no difference in survival was found between the 2 groups, since 72% of the patients in each group survived 40 yr with Type 1 diabetes. It is concluded that patient care seems to be highly important for the incidence and the course of clinical nephropathy, whereas no such influence could be demonstrated in patients not developing clinical nephropathy.

Body Weight↗