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P Rossing

Publications and source records attributed to P Rossing.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy.

OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated cardiovascular morbidity and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P<0.05). In addition, more patients with nephropathy, as compared with the normoalbuminuric group, had at least one parent with fatal/nonfatal cardiovascular disease (46% [95% CI 38-54] vs. 36% [28-44], P = 0.05). Fathers of patients homozygous for the I-allele of the ACE/ID polymorphism had significantly less myocardial infarction as compared with other genotypes (P = 0.03), regardless of the nephropathic state of the offspring. CONCLUSIONS: Cardiovascular morbidity and early mortality clusters in parents of type 1 diabetic patients with diabetic nephropathy The ACE/ID polymorphism helps explain the increased morbidity from cardiovascular disease.

Adult↗
PubMed2000

Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy.

OBJECTIVE: To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed a 4-year prospective, randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter. The study included 51 hypertensive type 1 diabetic patients with diabetic nephropathy. Three patients dropped out during the first month; results for the remaining 48 patients are presented. RESULTS: At baseline, the two groups were comparable: glomerular filtration rate (GFR) was 85 +/- 5 and 85 +/- 6 ml x min(-1) x [1.73 m](-2); mean 24-h ambulatory blood pressure was 108 +/- 3 and 105 +/- 2 mmHg, and albuminuria was 1,554 mg/24 h (95% CI 980-2,465) and 1,033 mg/24 h (760-1,406) in the lisinopril and nisoldipine groups, respectively. Mean 24-h arterial blood pressure during the study did not differ between the lisinopril and nisoldipine groups (100 +/- 2 and 103 +/- 1 mmHg, respectively). The time-course of albuminuria differed between groups (P < 0.001). Whereas initiation of treatment with lisinopril resulted in a reduction from baseline albuminuria by 52% (95% CI 14-73), albuminuria in the nisoldipine group did not change throughout the study GFR declined in a biphasic manner with an initial (0-6 months) reduction of 1.3 +/- 0.3 ml x min(-1) x month(-1) in the lisinopril group compared with 0.2 +/- 0.4 ml x min(-1) x month(-1) in the nisoldipine group (P < 0.01). The subsequent sustained decline (6 to 48 months or the end of treatment) was identical in the two groups: 0.5 +/- 0.1 ml min(-1) x month(-1) (NS). Two patients in the lisinopril group and three patients in the nisoldipine group entered therapy for end-stage renal failure. CONCLUSIONS: Long-term treatment with lisinopril or nisoldipine has similar beneficial effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients.

Adult↗
PubMed2000

Role of patient factors in therapy resistance to antiproteinuric intervention in nondiabetic and diabetic nephropathy.

Reduction of proteinuria is a prerequisite for successful long-term renoprotection. To investigate whether individual patient factors are determinants of antiproteinuric efficacy, we analyzed individual responses to different modes of antiproteinuric intervention in nondiabetic and diabetic patients, obtained in prior studies comparing the efficacy of various pharmacological regimens. The individual antiproteinuric response to angiotensin-converting enzyme (ACE) inhibition positively correlated to the response to angiotensin type I (AT1) receptor blockade in diabetic (r = 0.67, P < 0.01, N = 16) as well as nondiabetic patients (r = 0.75, P < 0.01, N = 12). This corresponded to the correlations for antihypertensive efficacy between ACE inhibition and AT1 receptor blockade in diabetic (r = 0.73, P < 0.001) as well as nondiabetic patients (r = 0.55, P < 0.05). Remarkably, the antiproteinuric response to ACE inhibition also correlated positively to the antiproteinuric response to indomethacin (r = 0.63, P < 0.05, N = 9). Thus, patients responding favorably to one class of antiproteinuric drugs also respond favorably to other classes of available drugs, supporting a main role for individual patient factors in responsiveness or resistance to antiproteinuric intervention. In the search for strategies to improve response in these high risk patients, combination-treatment (combining different drugs, and combining drugs with dietary measures like sodium and protein restriction), and the use of higher doses may provide more fruitful strategies to optimize renoprotection than shifting to other classes of the available drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To determine the natural course of kidney function and to evaluate the impact of putative progression promoters in Caucasian Type 2 diabetes mellitus (DM) patients with diabetic nephropathy who had never received any antihypertensive treatment. METHODS: A long-term observational study of 13 normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr-EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2-4 times per year and serum cholesterol every second year. RESULTS: The patients (12 males/one female), age 56+/-9 (mean +/- SD) years, with a known duration of diabetes of 10+/-6 years, were followed for 55 (24-105) (median (range)) months. GFR decreased from 104 (50-126) to 80 (39-112) ml x min(-1) x 1.73 m(-2) (P = 0.002) with a median rate of decline of 4.5 (-0.4 to 12) ml x min(-1) x year(-1). During follow-up, albuminuria rose from 494 (301-1868) to 908 (108-2169) mg/24 h (P = 0.25), while BP, HbA1c and serum cholesterol remained essentially unchanged. In univariate analysis the rate of decline in GFR did not correlate significantly with neither baseline nor mean values during follow-up of BP, albuminuria, HbA1c and serum cholesterol. CONCLUSIONS: Our study suggests that normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy have a rather slow decline in kidney function, but we did not unravel the putative progression promoters responsible for the variation in rate of decline in GFR.

Adult↗
PubMed1999

Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction. RESULTS: Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3-3.1)%, but it increased by 0.5 (-1.0-1.9)% in group 2, mean difference (95% CI), -2.1 (-4.0 to -0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0-25.0)% in group 1 but rose by 7.7 (-9.7-28.4)% in group 2, mean difference (95% CI), -19.6 (-35-0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.

Aged↗
PubMed1999

Progression of diabetic nephropathy in normotensive type 1 diabetic patients.

BACKGROUND: The first aim of our long-term study was to describe the natural history of diabetic nephropathy in 59 normotensive type 1 diabetic patients. Secondly, we evaluated genetic and nongenetic progression promoters. METHODS: The following progression promoters were determined: the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene, blood pressure, albuminuria, hemoglobin A1c, cholesterol, smoking, height, and gender. We studied the natural history by measuring 51Cr-EDTA plasma clearance at yearly intervals at least three times during [median (range)] 5.5 (2.2 to 18.3) years. RESULTS: At baseline the three groups (II, N = 11; ID, N = 25, and DD, N = 23) had comparable GFR (103 +/- 16; 99 +/- 19; 113 +/- 22 ml/min/1.73 m2, respectively; mean +/- SD), arterial blood pressure, albuminuria, and hemoglobin A1c. During the follow-up there was a median rate of decline in GFR in all 59 patients of 1.2 (range 12.9 to -4.4) ml/min/year. During the study period no significant differences were observed in: the rate of decline in glomerular filtration rate [median (range) 0.9 (10.6 to -1.9); 2.5 (12.9 to -4.4); 1.4 (10.8 to -1.9 ml/min/year)], arterial blood pressure, albuminuria, hemoglobin A1c or cholesterol between the three groups (II, ID and DD), respectively. At baseline, multiple linear regression analysis including the above-mentioned putative risk factors revealed that albuminuria, short stature, and male gender independently predict an enhanced decline in GFR [R2 (adjusted) = 0.33; P < 0.002]. During the follow-up period, only albuminuria acted as an independent progression promoter [R2 (adjusted) = 0.37; P < 0.0001]. CONCLUSIONS: Our study revealed a rather slow progression of kidney disease in normotensive type 1 diabetic patients with diabetic nephropathy. Albuminuria, short stature, and male gender act as progression promoters in such patients.

Adult↗
PubMed1999

Cyclosporine nephrotoxicity in type 1 diabetic patients. A 7-year follow-up study.

OBJECTIVE: To evaluate kidney function 7 years after the end of treatment with cyclosporine A (CsA) (initial dosage of 9.3 tapered off to 7.0 mg.kg-1.day-1) in young patients (mean age 20 years) with newly diagnosed type 1 diabetes participating in a randomized, double-blind, placebo-controlled CsA trial. RESEARCH DESIGN AND METHODS: In this study, 21 patients received CsA for 12.5 +/- 4.0 months (mean +/- SD) and 19 patients received placebo for 14.4 +/- 3.8 months. The two groups were similar with regard to mean arterial blood pressure (BP), urinary albumin excretion rate (UAER), serum creatinine, and estimated glomerular filtration rate (GFR [Cockcroft and Gault]) at initiation of CsA treatment (baseline). HbA1c (mean +/- SEM) during 7 years of follow-up was also the same: 8.7 +/- 0.4 vs. 8.3 +/- 0.4% in the CsA and placebo groups, respectively. RESULTS: During the 7 years after cessation of study medication, two CsA group patients and one control patient were lost to follow-up. One placebo-treated patient developed IgA nephropathy (biopsy proven) and was excluded. Four CsA-treated patients developed persistently elevated UAER > 30 mg/24 h (n = 3 with microalbuminuria), whereas all the 17 placebo-treated patients had normal UAER (< 30 mg/24 h) after 7 years of follow-up. At the end of follow-up, the CsA group had a more pronounced rise in UAER: 2.5-fold (95% CI 1.4-4.5) higher than baseline value vs. 1.1-fold (0.7-1.7) in the placebo-treated group (P < 0.05). Estimated GFR (ml.min-1.1.73 m-2) declined from baseline to end of follow-up (1994) by 6.3 +/- 6.0 in the former CsA group, whereas it rose by 7.4 +/- 5.0 in the placebo group (P = 0.05). In 1994, 24-h blood pressure was nearly the same: 131/77 +/- 4/2 vs. 127/75 +/- 2/2 mmHg (NS) in the CsA and placebo groups, respectively. Five randomly selected CsA-treated patients had a kidney biopsy performed shortly after the CsA treatment was stopped. Interstitial fibrosis/tubular atrophy and/or arteriolopathy were present in two subjects who both subsequently developed persistent microalbuminuria. CONCLUSIONS: The results of our 7-year follow-up study suggested that short-lasting CsA treatment in young, newly diagnosed type 1 diabetic patients accelerated the rate of progression in UAER and tended to induce a loss in kidney function. Longer term follow-up is mandatory to clarify whether CsA-treated patients are at increased risk of developing clinical nephropathy.

Adult↗
PubMed1999

Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy.

OBJECTIVE: To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months. Three patients dropped out and seven patients were excluded due to technical difficulties. RESULTS: The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group (P = 0.06) and from 85 to 80 mmHg in the lisinopril group (P = 0.02). The decline in systolic blood pressure was not significant with any of the two treatments, and no difference in reduction of blood pressure was seen between groups. LVM corrected for body surface area (LVMI) was comparable between groups at baseline and increased from 96 +/- 5 to 107 +/- 6 g/m2 (mean +/- SEM; P = 0.007) in the nisoldipine group and from 95 +/- 4 to 103 +/- 5 g/m2 (P = 0.03) in the lisinopril group. The mean difference between the change in LVMI in the two groups was 2.9 (95% CI 6.8 to 12.7) g/m2. The prevalence of left ventricular hypertrophy rose from 18 (95% CI 6-30) to 30% (16-44) during the study period. A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril, respectively, and did not change during follow-up. CONCLUSIONS: Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy.

Adult↗
PubMed1998

[The significance of deletion polymorphism in the ACE gene for progression of diabetic nephropathies treated with ACE inhibitors].

The aim of the study was to evaluate the effect of an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene on progression of diabetic nephropathy. We performed an observational follow-up study of 35 patients with insulin-dependent diabetes and diabetic nephropathy. Patients were investigated during captopril treatment for a median of seven (range three to nine) years. Eleven patients were homozygous for the deletion allele (DD) and 24 were hetero- or homozygous for the insertion allele (ID + II). The two groups had comparable glomerular filtration rate, albuminuria and blood pressure at baseline and captopril induced nearly the same mean reduction in blood pressure--to 103 (SD 5) mm Hg in the DD-group and 102 (8) mm Hg in the ID + II-group. The rate of decline in glomerular filtration rate was significantly steeper in the DD group than in the other group (mean 5.7 (SD 3.7) versus 2.6 (2.8) ml/min/year, p = 0.01). In conclusion, the deletion polymorphism in the ACE gene reduces the long term beneficial effect of ACE inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.

Adult↗
PubMed1998

[Risk factors for mortality in patients with insulin-dependent diabetes].

The prognostic significance of microalbuminuria, macroalbuminuria and other putative risk factors for mortality in insulin-dependent diabetic patients were evaluated in a 10 year prospective study. We identified 939 insulin-dependent diabetic patients; 593 patients had normoalbuminuria (< or = 30 mg/24 h), 181 had microalbuminuria (31-299 mg/24 h), and 165 had macroalbuminuria (> or = 300 mg/24 h). Fifteen percent of patients with normoalbuminuria, 25% with microalbuminuria and 44% with macroalbuminuria at baseline died during follow-up (p < or = 0.01). Significant predictors of all-cause mortality were male sex, age, height, smoking, low social class, urinary albumin excretion, hypertension, serum creatinine, and HbA1c. Age, smoking, microalbuminuria, overt nephropathy, and hypertension were significant predictors of cardiovascular mortality. The mortality in patients with microalbuminuria was only slightly increased compared to patients with normoalbuminuria. Median survival after onset of overt diabetic nephropathy was 13.9 (11.8 to 17.2) years. Abnormally elevated urinary albumin excretion and other potentially modifiable risk factors such as hypertension, smoking, poor glycaemic control and social class predicts increased mortality in insulin-dependent diabetic patients.

Adult↗
PubMed1998

Promotion, prediction and prevention of progression of nephropathy in type 1 diabetes mellitus.

The scope of the present review is to discuss the prognosis of diabetic renal disease, putative progression promoters and the possibilities for treatment and prediction of treatment efficacy. The recent changes in the incidence of diabetic nephropathy in Type 1 diabetes mellitus are discussed. Promoters of progression in diabetic nephropathy are evaluated, in particular arterial blood pressure, glycaemic control, albuminuria and cholesterol levels. Potential treatment modalities are discussed, with special focus on antihypertensive therapy, including a discussion of a specific renoprotective action of certain antihypertensive agents. Furthermore putative predictors of treatment efficacy are evaluated, demonstrating that the ability to lower the urinary albumin excretion rate after onset of treatment heralds a slow progression of the renal disease. The prognosis in diabetic renal disease has improved with an increase in median survival after onset of nephropathy from 6 to 15 years. This has exposed the importance of cardiovascular morbidity and mortality. The identification and treatment of cardiovascular risk factors has become essential. Although the prognosis has improved remarkably, the primary goal should be prevention of diabetic nephropathy, as it is unlikely that the increased risks associated with this complication can be eliminated.

Animals↗
PubMed1998

Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy.

1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2. We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure was reduced to the same extent in both groups: nisoldipine, 113+/-2.1 to 105+/-1.6 mmHg (P<0.001); lisinopril, 110+/-2.7 to 101+/-2.1 mmHg (P<0.002) (controls, 88+/-2.2 mmHg; P<0.0001 compared with diabetic patients). Nisoldipine improved the skin vascular distensibility from 28+/-3.3 to 43+/-3.8% (P<0.005) and decreased skin minimal vascular resistance from 16.9+/-1.0 to 13.6+/-0.8 mmHg.ml-1.min.100 g (P<0. 02). Lisinopril had no significant effect on skin vascular distensibility (40+/-4.0% and 41+/-4.4%), but minimal vascular resistance tended to diminish (18.1+/-0.9 to 15.8+/-1.3 mmHg.ml-1. min.100 g (P=0.09). Nisoldipine significantly increased the skin distensibility (P=0.05) after 1 year of antihypertensive treatment compared with lisinopril.4. The control group had a skin vascular distensibility of 54+/-3.2% and a minimal vascular resistance of 10. 8+/-0.7 mmHg.ml-1.min.100 g, both significantly different from the values in the diabetic groups (P<0.0001 for all). Skeletal muscle vascular distensibility was unaltered after 1 year of treatment with both nisoldipine (22+/-3.3% and 19+/-2.7%) and lisinopril (19+/-2.1% and 24+/-2.5%), but was reduced compared with a control value of 43+/-3.7% (P<0.0001 for diabetes patients versus controls). However, neither nisoldipine nor lisinopril had any effect on the increased minimal vascular resistance or the reduced skeletal muscle distensibility.5. Enhanced thickening of the basement membranes of the terminal arteriolar wall was found in skin biopsy specimens in 91% of diabetic patients and 38% only in control subjects (P<0. 000001 both before and after treatment for diabetic patients versus controls). There was no significant effect of antihypertensive treatment on arteriolar hyalinosis.6. The reduction in systemic blood pressure was identical during 1 year of treatment with nisoldipine or lisinopril. The abnormal arteriolar stiffness was more pronounced in the group treated with nisoldipine than with lisinopril and only nisoldipine compared with lisinopril improved the abnormal arteriolar stiffness and minimal vascular resistance in the skin. This suggests that nisoldipine can reverse the peripheral skin perfusion and thereby improve the local protection against development of ischaemic skin lesions in Type I diabetes patients with clinical diabetic nephropathy.

Adult↗
PubMed1998

Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of 51Cr-EDTA.

Plasma clearance of 51Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total 51Cr-EDTA plasma clearance (C(T)). Simplified methods, using the final mono-exponential part of the plasma curve, have been suggested, e.g. four samples, taken 180 to 240 min after injection (C(IV)), or using one sample taken at 240 min (C(I)). Our aim was to evaluate the agreement between measurements of GFR and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq 51Cr-EDTA by determining the radioactivity in venous blood samples taken 5, 7, 10, 15, 30, 45, 60, 90, 120, 150, 180, 200, 220, and 240 min after the injection. Rate of decline in GFR was assessed using 12 (6-17) determinations of GFR over a period of time of 8 (4-10) years. Mean (SD) GFRT was 123 (21) ml x min(-1) compared to GFR(IV) 123 (21) ml x min(-1) (NS) and GFR(I) 115 (17) ml x min(-1) (p < 0.00001). The mean difference (95% limits of agreement) between GFR(T) and GFR(IV) was +0.6 (-16.6 to +17.7) ml x min(-1), and between GFR(T) and GFR(I) +8.0 (-6.0 to +22.2) ml x min(-1). The difference between GFR(T) and GFR(I) was significantly correlated with their mean value (r = 0.56, p < 0.00001), indicating increasing underestimation by GFR(I) with increasing GFR levels. The mean (SD) rate of decline in GFR(T) was 2.3 (3.9) ml x min(-1) x year(-1), compared to a mean rate of decline in GFR(IV) of 2.4 (3.6) ml x min(-1) x year(-1) (NS), and a mean rate of decline in GFR(I) of 2.2 (3.5) ml x min(-1) x year(-1) (NS). The mean difference (95% limits of agreement) between rate of decline in GFR(T) and rate of decline in GFR(IV) was +0.16 (-1.59 to +1.91) ml x min(-1) x year(-1), and between rate of decline in GFR(T) and rate of decline in GFR(I) -0.01 (-1.64 to +1.61) ml x min(-1) x year(-1), respectively. In conclusion, our cross-sectional study revealed a close agreement between GFR(T) and GFR(IV) with acceptable limits of agreement (precision), while GFR(I) lacked accuracy. However, a close agreement between rate of decline in GFR(T) and rate of decline in GFR(IV), and between rate of decline in GFR(T) and rate of decline in GFR(I), with acceptable limits of agreement (precision), suggests that both simplified methods are applicable for long-term follow-up.

Chromium Radioisotopes↗
PubMed1998

Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy.

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hypertensive IDDM patients suffering from diabetic nephropathy were investigated during three months before and for the initial six month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were measured three (1 to 6) times before and three (1 to 13) times during ACE inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/- SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenced the decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01). A significant association between changes in MABP and albuminuria was demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are particularly susceptible to commonly advocated renoprotective treatment.

Adult↗
PubMed1998

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

OBJECTIVE: To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. RESEARCH DESIGN AND METHODS: All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). RESULTS: Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. CONCLUSIONS: The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Adult↗