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Biomedical subjects

P Gaede

Publications and source records attributed to P Gaede.

At least 19 recordsLinked to original sources
PubMed2005

Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk: what are we waiting for?

Results from many single risk factor intervention trials and the multi-targeted Steno-2 trial in the last few years have provided a strong case that management of type 2 diabetes in all age groups requires a structured and intensified approach that is far more than just glucocentric, an approach addressing additional cardiovascular risk factors including hypertension, dyslipidaemia, sedentary behaviour, smoking and dietary habits causing insulin resistance and pro-inflammation. This type of integrated therapy applied for almost 8 years to high-risk type 2 diabetic patients has cut the relative risk of macro-and microangiopathy by half. The treatment algorithms for multifactorial therapeutic packages do not harbour any revolutionizing novel drugs or previously untested behaviour modelling, but the success criteria seem to include an individualized and stepwise introduction of target-driven polypharmacy and simple but focused behaviour modelling with continuous education, motivation and trouble-shooting for treatment barriers identified for the patient and the care giver. It is high time we transfer these experiences and major health benefits gained in the 'green house' of controlled clinical trials to the community level. To facilitate this process it is of crucial importance to offer not only postgraduate training of diabetes care providers but also to identify and eliminate treatment barriers.

Clinical Trials as Topic↗
PubMed2004

Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.

AIMS/HYPOTHESIS: We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes. METHODS: A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2 Study examining the effect of multifactorial treatment, and were divided into two groups according to baseline levels of plasma NT-proBNP below or above the median for the cohort, which was followed for an average of 7.8 years. Cardiovascular outcome was a composite of cardiovascular mortality, myocardial infarction, stroke, revascularisation procedures in the heart or legs, and amputations. RESULTS: In the whole group, plasma NT-proBNP being above the median was associated with an increased risk of cardiovascular disease during follow-up, with an unadjusted hazard ratio of 4.4 (95% CI 2.3-8.4; p<0.0001). A decrease in plasma NT-proBNP of 10 pg/ml during the first 2 years of intervention was associated with a 1% relative reduction in the primary endpoint (p<0.001). Despite polypharmacological treatment targeting cardiovascular disease, the mean plasma NT-proBNP level increased during follow-up. CONCLUSIONS/INTERPRETATION: We conclude that high plasma NT-proBNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.

Albuminuria↗
PubMed2001

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h). No changes were seen in serum creatinine, haemoglobin A1C or blood pressure. Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment (mean vitamin C 79.4 micromol/L (SD 27.8) vs. 41.9 micromol/L (18.4) and vitamin E 47.0 micromol/L (19.8) vs. 29.5 micromol/L (15.3), P < 0.000001). Except for two patients that started additional blood pressure lowering treatment during the run-in period, no changes in medication, food and exercise habits or in the number of smokers occurred during the study. CONCLUSION: Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria. Further long-term, large-scale studies of this albuminuria reducing treatment modality are warranted.

Albuminuria↗
PubMed2001

Limited impact of lifestyle education in patients with Type 2 diabetes mellitus and microalbuminuria: results from a randomized intervention study.

AIMS: To assess the effect of intensified education on lifestyle (diet, exercise and smoking) as part of an intensified multifactorial intervention over a 4-year period in patients with Type 2 diabetes mellitus with microalbuminuria. METHODS: Patients, aged 45-65 years, were randomly assigned either to an intensive group focusing on change of behaviour as well as polypharmacological treatment (n = 80) or to a control group receiving conventional treatment (n = 80). Diet intervention focused on dietary fat and carbohydrate. Food intake was estimated by dietary history interviews and nutrients were calculated from food tables. Exercise and smoking habits were evaluated by interviews. RESULTS: Mean follow-up was 3.8 (SD 0.3) years. The decrease in total fat intake (% of energy intake) was larger in the intensive group as compared to the control group (41.2 (6.2) to 34.2 (6.0) vs. 41.9 (6.5) to 38.3 (6.4)%, P = 0,0001). The decrease in saturated fatty acids (% of total fat intake) was from 47 (4) to 44 (6)% with intensive therapy vs. 45 (5) to 46 (5)%, P = 0.001 and the increase in polyunsaturated fatty acids was from 14 (4) to 18 (6) vs. 16 (5) to 14 (4)%, P < 0.0001. Also the increase in carbohydrate was larger with intensive therapy. However, changes in exercise and smoking habits did not differ between groups. CONCLUSION: Despite the many resources invested in behaviour modification in this study, only modest changes were obtained in nutrient intake. Further studies are required to determine the best method of inducing long-lasting changes in behaviour in Type 2 diabetic patients.

Aged↗
PubMed2001

Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria.

BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups according to baseline plasma von Willebrand factor levels below or above the median. The main outcome was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal myocardial infarction, coronary artery bypass graft and revascularization or amputation of legs), progression to diabetic nephropathy or progression in diabetic retinopathy. RESULTS: At baseline the two groups were comparable for HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s-triglycerides, systolic and diastolic blood pressure, gender, known diabetes duration, smoking habits, previous cardiovascular disease and antihypertensive therapy as well as retinopathy. Odds ratio for cardiovascular disease was 1.11 (95% CI 0.45-2.73, P=0.82) (multiple logistic regression), odds ratio for progression to nephropathy was 1.08 (0.41-2.85, P=0.87) and odds ratio for progression in retinopathy was 0.96 (0.46-2.00, P=0.92), all with plasma von Willebrand factor levels above the median. CONCLUSIONS: Our results do not support the suggestion that the combination of high plasma levels of von Willebrand factor and microalbuminuria is a stronger predictor for cardiovascular disease, progression to diabetic nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria.

Adult↗
PubMed1999

Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.

BACKGROUND: In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial. We carried out a randomised trial of stepwise intensive treatment or standard treatment of risk factors in patients with microalbuminuria. METHODS: In this open, parallel trial patients were allocated standard treatment (n=80) or intensive treatment (n=80). Standard treatment followed Danish guidelines. Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was the development of nephropathy (median albumin excretion rate >300 mg per 24 h in at least one of the two-yearly examinations). Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy. FINDINGS: The mean age was 55.1 years (SD 7.2) and patients were followed up for 3.8 years (0.3). Patients in the intensive group had significantly lower rates of progression to nephropathy (odds ratio 0.27 [95% CI 0-10-0.75]), progression of retinopathy (0.45 [0.21-0.95]), and progression of autonomic neuropathy (0.32 [0.12-0.78]) than those in the standard group. INTERPRETATION: Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy, and progression of retinopathy and autonomic neuropathy. However, further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality.

Albuminuria↗
PubMed1997

White coat hypertension in NIDDM patients with and without incipient and overt diabetic nephropathy.

OBJECTIVE: Early data have suggested a high prevalence of white coat hypertension (approximately 50%) in NIDDM patients. To study this phenomenon further, we determined the prevalence of white coat hypertension in NIDDM patients with normo- or microalbuminuria or with diabetic nephropathy. RESEARCH DESIGN AND METHODS: Three groups of hypertensive NIDDM patients (repeated clinic blood pressure > 140/90 mmHg or antihypertensive treatment) attending the Steno Diabetes Center were investigated in a cross-sectional study. Group 1 had normoalbuminuria (a urinary albumin excretion [UAE] rate < 30 mg/24 h, n = 30, age 61 +/- 7 [mean +/- SD] years, 20 men), group 2 had microalbuminuria (UAE rate 30-300 mg/24 h, n = 51, age 55 +/- 7 years, 35 men), and group 3 had diabetic nephropathy (UAE rate > 300 mg/24 h, n = 47, 62 +/- 7 years, 36 men). If given, all previous antihypertensive medication was withdrawn at least 2 weeks before the study (48%). The prevalence of white coat hypertension (clinic hypertension with normal blood pressure values at home) was determined by comparison of clinic blood pressure (Hawksley Random sphygmomanometer) and the ambulatory daytime (7:00 A.M. to 11:00 P.M.) blood pressure (A&D TM2420). By applying established criteria, white coat hypertension was confirmed if daytime blood pressure was < 135/85 mmHg. RESULTS: The clinic blood pressure was 155/86 (SE 3/2) mmHg, 156/89 (2/1) mmHg, and 171/90 (3/2) mmHg in group 1, 2, and 3, respectively (P < 0.05 comparing group 3 with groups 1 and 2). The prevalence of white coat hypertension was significantly higher in group 1 as compared with groups 2 and 3, 23% (95% CI 10-42) vs. 8% (2-19) and 9% (2-20) (P < 0.05), with no difference between the latter two groups. CONCLUSIONS: The prevalence of white coat hypertension in normoalbuminuric NIDDM patients resembles that observed in nondiabetic subjects with essential hypertension, whereas the prevalence is significantly lower in NIDDM patients with incipient or overt diabetic nephropathy, suggesting a difference between primary and secondary hypertension.

Albuminuria↗
PubMed1984

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.

Administration, Topical↗
PubMed1978

Extremely low placental lactogen hormone (hPL) values in an otherwise uneventful pregnancy preceding delivery of a normal baby.

A case of a normal pregnancy and delivery with extremely low placental lactogen hormone (hPL) values in maternal blood is presented. The low hPL-values were due to the fact that the placenta only produced about 1/25 of the normal estimated output, calculated on the basis of the hPL-concentration in the intervillous spaces. The concentrations of progesterone, the placenta-specific beta-glycoprotein (SP1) and total estriol in serum were normal, while prolactin and chorionic gonadotropin (hCG) were considerably elevated. Glucose levels were normal. At the ultrastructural level the actual placenta under study did not differ from a normal term placenta. In spite of the very low concentrations of hPL there was a good milk secretion, and the mother was still breast-feeding her baby 11 months after the delivery. Basal level of prolactin was at this time normal.

Adult↗
PubMed1977

Estriol concentrations in urine and serum in patients with various intestinal diseases.

Pregnant women with ulcerative colitis shows frequently low estriol values in both serum and urine. 18 patients with ulcerative colitis, 4 patien;s with mb. Crohn, and 3 patients with a by-pass operation were examined. Low estriol concentrations were seen only in the patients with ulcerative colitis especially in patients, where an operation has been performed. In one patient with severe diarrhea the estriol concentration in serum was low until the intestinal function normalised and the estriol concentration went up exactly when the diarrhea stopped. However, no unequivocal connection between low estriol concentrations and diarrhea could be demonstrated.

Colitis, Ulcerative↗
PubMed1976

The prognostic and diagnostic value of total estriol in urine and in serum and of human placental lactogen hormone in serum in the last part of pregnancy.

The benefit to the antenatal care from using estriol and human placental lactogen (hPL) determinations is emphasized and likewise that special attention must be paid to values below the reference intervals. Referring to biosynthesis and place of production, a survey is given of the various causes of low estriol and/or low hPL values, and a number of clinical cases illustrate the matter. A follow-up study of children from pregnancies with low estriol values has disclosed an alarming number of cases of severe handicaps.

Estriol↗
PubMed1976

Human placental lactogen hormone in serum from pregnant women with rhesus (anti-D) isoimmunization.

Determination of human placental lactogen hormone (HPL) was performed in 346 serum samples from 59 rhesus isoimmunized pregnant women. In all cases of fetal death-either intrauterine or in the first seven days after birth-we find a high level of HPL in maternal serum several weeks before death. All patients with normal HPL concentrations in the maternal serum, and who were treated by intrauterine transfusions, had surviving infants. If the indication for intrauterine transfusion is combined with an elevated HPL level in materal serum one must weigh the risk of the procedure against the poor prognosis for the fetus before deciding whether to intervene. Serum concentrations of human chorionic gonadotropin (HCG) and progesterone were of no clinical use, but we find a correlation between progesterone and HPL differing from the same correlation found in normal and diabetic pregnancies. A possible explanation is discussed in relation to the endoplasmic reticulum in the syncytiotrophoblast.

Blood Transfusion, Intrauterine↗
PubMed1976

Method for monitoring plasma progesterone concentrations in pregnancy.

We present a time-series model for monitoring concentrations in plasma of hormones produced in the placenta, progesterone being chosen as an example. The model, which is based on the assumption that variations in plasma progesterone concentration in pregnant subjects mainly reflect variations in the growth rate of the placenta, was applied to eight series of progesterone values measured during pregnancy in eight subjects. In the model, which was found to fit the data, it is assumed that progesterone concentration is proportional to the size of the placenta and that the growth rate of the placenta varies at random, with a mean value alpha. The variation of alpha was of the same magnitude among and within the subjects. If the average of many subjects alpha values is used, a single subject may be used as her own reference, based on only one previous observation. When two observations are available, an individual's own alpha value may be estimated and used for the prediction. The predictive power of the new method was found to be far superior to the conventional method in which a single sample reference material is used. Furthermore, one need not know the gestational age in order to use the method.

Abortion, Spontaneous↗
PubMed1975

Human placental lactogen concentration during physiological fluctuations of serum glucose in normal pregnant and gestational diabetic women.

Oral glucose tolerance tests (OGTT) were carried out in 9 normal pregnant women and 11 non-obese gestational diabetics in late pregnancy. All samples were analysed for the content of glucose, insulin and placental lactogen hormone (HPL). Furthermore, spontaneous changes in the serum HPL concentration during a 3 h period were studied in 6 normal women in the 2nd half of pregnancy. During OGTT only small and insignificant changes in the level of HPL were observed in both the normal subjects and the gestational diabetics. Furthermore, the mean HPL concentration curves of the normal subjects and the gestational diabetics were superimposed although the mean glucose concentration curves were significantly different. The study of spontaneous changes in HPL revealed only small and insignificant fluctuations in the serum HPL level, and the mean concentration curve resembled those obtained from the OGTT-study. It is concluded that neither the absolute serum glucose level, nor physiological fluctuations in the serum glucose concentration seemed to influence the serum concentration of HPL in this type of patients.

Adult↗