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.

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.

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.

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.

Glomerular hyperfiltration in microalbuminuric NIDDM patients.

Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarce in microalbuminuric non-insulin-dependent diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i.v. bolus injection of 51Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and 20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected (ml/min) and the adjusted (ml. min-1. 1.73 m-2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 +/- 29 and 117 +/- 24 as compared to 115 +/- 19 and 99 +/- 15; 111 +/- 23 and 98 +/- 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml. min-1. 1.73 m-2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients (n = 96): 119 +/- 22 as compared to 100 +/- 14 and 98 +/- 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM patients) was demonstrated in 37 (95% confidence interval 30-45)% of the microalbuminuric patients. Multiple regression analysis revealed that HbA1c, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric NIDDM patients (r2 = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also characterized by an additional putative risk factor for progression, glomerular hyperfiltration.

Hormonal contraception in women with IDDM. Influence on glycometabolic control and lipoprotein metabolism.

OBJECTIVE: Safe and effective contraceptive methods are essential for women with insulin-dependent diabetes mellitus (IDDM), but opinions on the use of hormonal oral contraceptives by these women are conflicting. We evaluated the effects on glycometabolic control and lipoprotein metabolism in women with IDDM treated with an oral contraceptive not previously studied in a diabetic population. RESEARCH DESIGN AND METHODS: A total of 22 women with IDDM received a monophasic combination of ethinyl estradiol and gestodene for 1 year; 20 women of comparable diabetic status using nonhormonal contraception were selected as control subjects. Evaluation was performed before and after 1, 3, 6, and 12 months of hormonal intake using nonparametric statistical methods. RESULTS: Except for a higher median age of the control group, the baseline values for all clinical and metabolic variables were similar in the two groups, and in neither of the groups were changes in blood pressure, body mass index, or glycemic control observed. In the oral contraceptive group, decreased serum levels of low-density lipoprotein (LDL) cholesterol and increased levels of triglycerides and lipoprotein A were noted, whereas total cholesterol and high-density lipoprotein cholesterol levels were unchanged. In the control group, a decrease of LDL cholesterol was observed. No effect of tobacco smoking on glycometabolic control or lipoprotein metabolism could be demonstrated during hormonal intake. CONCLUSIONS: No evidence of impaired glycometabolic control or adverse changes in serum levels of lipoproteins known to be associated with atherosclerosis was observed in women with well-controlled IDDM during 1 year of oral contraception with ethinyl estradiol and gestodene.

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment.

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from diabetic patients showed a normal total glycogen synthase activity but a 48% decrease (p = 0.006) in glycogen synthase fractional velocity (0.1 mmol/l glucose 6-phosphate) (FV0.1) and a 45% increase (p = 0.01) in the half-maximal activation constant of glycogen synthase (A0.5). The activity of phosphofructokinase and the specific mRNA and immunoreactive protein levels of both glycogen synthase and phosphofructokinase were similar in the two groups. The 2.8-fold increase in serum insulin levels and the halving of the plasma glucose level for at least 15 h were associated with a normalization of glycogen synthase fractional activity (FV0.1) and of the half-maximal activation constant (A0.5) whereas the enzyme activity of phosphofructokinase and the mRNA and protein levels of both glycogen synthase and phosphofructokinase remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of intensive insulin therapy on the insulin-regulatable glucose transporter (GLUT4) expression in skeletal muscle in type 1 diabetes.

Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels. The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble insulin for 24 h the fasting plasma glucose concentration decreased from 20.8 +/- 2.3 (SD) to 8.7 +/- 2.3 mmol 1-1, whereas the fasting serum insulin level increased from 0.06 +/- 0.02 to 0.17 +/- 0.09 nmol 1-1. However, despite a 2.8-fold increase in serum insulin levels and more than a halving of the plasma glucose concentration for at least 15 h no significant alterations occurred in the amount of GLUT4 protein (0.138 +/- 0.056, poor control vs 0.113 +/- 0.026 arb. units, improved control, p = 0.16) or GLUT4 mRNA (96432 +/- 44985, poor control vs 81395 +/- 25461 arb. units, improved control, p = 0.54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients.

Five-year follow up of patients with cervical intra-epithelial neoplasia in the cone margins after conization.

Three hundred eighty-five women treated with conization due to repeated CIN I, CIN II or CIN III of the cervix uteri have been followed up for 5 years. All cones were classified according to diagnosis and status of the resection margins. A significantly greater recurrence rate of 16.2% was found in the group with neoplasia in the resection margins, in contrast to 3.9% in the group with normal resection margins. However, 83.8% (75.4-92.2%) of patients with neoplasia in the resection margins can be expected to be free of recurrence after a 5-year postoperative follow-up period. Whether the non-free resection margins were endocervical, ectocervical or both, did not influence the recurrence rate. While the prevalence of non-free resection margins increased significantly with increasing dysplasia, this could not be found with increasing age. The risk of recurrence could not be correlated with the grade of dysplasia. We conclude that neoplasia in the resection margins of the cone represents an increased risk of recurrence. Therefore, we changed the normal smear check-up with a cotton-swab to smear with cyto-brush, supplemented with colposcopy in the non-free resection margin group, but it remains to be proven that this procedure is safer.

Breathing zone concentrations of methylmethacrylate monomer during joint replacement operations.

By use of a methylmethacrylate (MMA) Dräger tube and bellow bump, the breathing zone concentrations of MMA monomer were measured for the operating surgeon during cementation of the components of hip and knee joint prostheses. The highest recordings (50-100 p.p.m.) were encountered during cementation of the acetabular cups with conventional polymethylmethacrylate cement. Such exposure could be eliminated by the use of personal protection equipment, local punctual field suction or change to a MMA/n-decylmethacrylate/isobornylmethacrylate bone cement.

Evoked potentials in urology: a method to make an exact diagnosis?

Due to the complex innervation of the lower urinary tract, many neurological diseases will lead to disturbances in the function of the lower urinary tract. The usual urodynamic procedures leave a group of patients where definitive diagnosis is impossible. Fifty-three patients were evaluated with evoked potentials of the bulbocavernosus reflex at the Urological Laboratory, Herlev Hospital. In 5 cases (2 with operative sequelae after prolapsed intervertebral discs, 1 with tethered cord syndrome and 2 with early multiple sclerosis) the examination gave a definitive diagnosis. The cases are reported.

Arterial lesions in major knee trauma: pedal pulse a false sign of security?

In major knee trauma fractures and/or dislocations can be associated with arterial lesions. Two case reports demonstrate the difficulties in the diagnosis of intimal lesions in the popliteal artery. The presence of a pedal pulse present at the time of admission can be a false sign of security. The importance of prompt diagnosis and treatment is emphasized. The use of arteriography is discussed.

Skin protection against methylmethacrylate.

Ordinary surgical rubber gloves are penetrated by methylmethacrylate monomer (MMA) in less than 1 minute, as demonstrated by gas chromatographic measurements. A three-layered PVP glove, 0.07 mm thick--consisting of an outer layer of polyethylene, an intermediary layer of ethylene vinyl alcohol copolymer, and an inner layer of polyethylene--was impervious for 20 minutes, whereas a viton-butyl rubber glove, 0.27 mm thick, was impervious for 15 minutes. The PVP glove is recommended to orthopedic surgeons, nurses, and other handling acrylic bone cements to avoid sensitization, and is especially recommended to persons with known contact allergy to MMA.

Fractures of the femoral neck treated with a bipolar endoprosthesis.

Seventy-five patients with 77 bipolar hip endoprostheses were reexamined and had roentgenograms taken at an average of 51 months postoperatively. The average age of the patients was 77 years. All prostheses had been inserted due to intracapsular fractures of the femoral neck. Three prostheses had been revised to a total hip arthroplasty at the time of follow-up examination. Radiologically, three cases of protrusion and ten cases with a radiolucent zone greater than 2 mm around the femoral stem were found. Functionally, the result was excellent or good in about 75% of the active ambulators. As acetabular erosion and protrusion appears to have been reduced to some extent, a bipolar hip prosthesis is found to be a good alternative to conventional hemiarthroplasty in elderly patients with a fracture of the femoral neck.

Contact dermatitis to methyl methacrylate.

2 cases of contact dermatitis to methyl methacrylate monomer are presented. The patients are nurses who mixed bone cement at orthopedic operations. During the procedure, they used 2 pairs of gloves (latex). Butyl rubber gloves are recommended for methyl methacrylate monomer to avoid sensitization and/or cumulative irritant contact dermatitis on the hands.

Surgical rubber gloves impervious to methylmethacrylate monomer.

Conventional surgical rubber gloves are permeable to the methylmethacrylate monomer (MMM) of acrylic bone cement. An in vitro technique was used which proved butyl rubber gloves, 0.48 mm thick, to be impervious to MMM. to avoid sensitization, butyl rubber gloves may be recommended to persons who are in contact with MMM. Such gloves should be worn by persons with known contact sensitization to MMM.