The venoarteriolar response in diabetics

Resting skin blood flow and the venoarteriolar response (VAR) were studied in 40 patients with diabetic microangiopathy and neuropathy, in 40 diabetics with microangiopathy, and in 30 normal subjects by means of laser-Doppler flowmetry. In patients with microangiopathy and neuropathy, resting flow (RF) was increased and the VAR was impaired to a greater extent than in patients without neuropathy. There was also a significant delay in the VAR in diabetics, particularly in patients with neuropathy. The microangiopathy index (VAR/RF) was on the average 71.3 in normal subjects, significantly lower (p less than 0.05) in diabetics without neuropathy (34.8), and even lower in those with neuropathy (13.6). The VAR was evaluated with different postural changes; The authors observed that in the passage from supine to standing the VAR is more evident. In conclusion these results confirm that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in patients with neuropathy. The increased skin blood flow and the impaired VAR are causes of edema and may contribute to the thickening of capillary basement membranes observed in diabetes.     

Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up.

Mortality rates are considerably higher in chronic ischemic heart disease (IHD) patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those who are nondiabetics. The relationship between different types of antihyperglycemic pharmacological therapy and mortality rate in this NIDDM population is uncertain. We aimed to examine the survival in NIDDM patients with IHD using various types of oral antidiabetic treatments over a 5-year follow-up period. The study sample comprised 11,440 patients with a previous myocardial infarction and/or stable anginal syndrome, aged 45-74 years, who were screened, but not included in the Bezafibrate Infarction Prevention study. Among them, 9,045 were nondiabetics and 2,395 diabetics. The diabetic patients were divided into four groups on the basis of their therapeutic regimen at screening: diet alone (n = 990), sulfonylureas (n = 1,041), metformin (n = 78) and a combination of a sulfonylurea and metformin (n = 266). All NIDDM groups were similar with regard to age, gender, hypertension, smoking, heart failure, angina and prior myocardial infarction. Crude mortality rate was lower in the nondiabetic group (11.21 vs. 21.8%; p < 0.001). In the diabetic group, mortality was 18.5% for patients on diet alone, 22.5% for those on sulfonylureas, 25.6% for patients on metformin, and 31.6% for the combined sulfonylurea/metformin group (p < 0.01). When analyzing age-adjusted mortality rate and actuarial survival curves, the lowest mortality was found in patients on diet alone and the highest in patients on metformin (alone or in combination with sulfonylureas). After adjustment for variables connected with long-term prognosis, the use of metformin was associated with increased relative risk (RR) for all-cause mortality of 1.42 (95% CI 1.10-1.85), whereas the use of sulfonylureas alone was not [RR 1.11 (95% CI 0.90-1.36)]. NIDDM patients with IHD using metformin, alone or in combination with sulfonylureas, exhibited a significantly increased mortality. Until the results of problem-oriented prospective studies on oral control of NIDDM will be available, alternative therapeutic approaches should be investigated in these patients.     

Hypertension in diet versus pharmacologically treated diabetics: mortality over a 5-year follow-up

The natural history of non-insulin-dependent diabetes mellitus (NIDDM) differs markedly between patients with diet treated and pharmacologically treated disease. However, the interrelationship between hypertension and these common diabetes types has not been specifically addressed in previous studies. This study was designed to evaluate the prognostic significance and prevalence of hypertension in coronary patients with diet versus pharmacologically treated NIDDM over a 5-year follow-up period. The study sample comprised 11 515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who had been screened but were not included in the Bezafibrate Infarction Prevention study. Among them, 9033 were nondiabetics and 2482, diabetics (987 diet treated and 1495 pharmacologically treated). The prevalence of hypertension among nondiabetics, diet-treated diabetics, and pharmacologically treated diabetics was 31%, 42%, and 43%, respectively. Crude all-cause mortality (CM) was lower in the nondiabetic patients (11.2% versus 22.0%; P<0.001). Among diabetics, 548 patients died: 81 diet treated normotensives (CM 14%); 100 diet-treated hypertensives (CM 24.4%); 205 pharmacologically treated normotensives (CM 24.2%); and 162 pharmacologically treated hypertensive patients (CM 25.0%). Age-adjusted mortality was lowest for the normotensive patients in the diet-treated group and highest for the hypertensive pharmacologically treated patients. Multivariate analysis shows that hypertension is a strong and independent predictor of increased CM in diet-treated but not in pharmacologically treated NIDDM: hazard ratio (HR) was 1.68 (95% confidence interval [CI] 1.24 to 2.29) for the diet-treated versus 1. 01 (95% CI 0.82 to 1.26) for the pharmacologically treated diabetics. The contribution of hypertension to stroke mortality was substantial for both diet treated and pharmacologically treated NIDDM: hazard ratios were 3.17 (95% CI 1.12 to 8.98) and 2.21 (95% CI 0.72 to 6.77), respectively. The increased risk of mortality associated with hypertension in relatively mild diet-treated NIDDM strongly supports the clinical benefit of early blood pressure control among diabetic patients with ischemic heart disease.     

Increased kidney size,glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

Summary Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured by constant infusion technique using I¹²⁵-iothalamate and ¹³¹I-hippuran. Kidney size was determined by means of ultrasound. GFR, RPF and kidney volume were increased in the diabetic patients compared to the normal controls, 144 versus 113 ml/ min×1.73m² (p<0.0005), 627 versus 523 ml/ min×1.73 m² (p<0.0025) and 278 versus 224 ml/ 1.73 m² (p<0.0005) respectively. Combining results from diabetic patients and controls revealed a positive correlation between kidney size and GFR (r= 0.70, p<0.001) and between kidney size and RPF (r=0.61, p<0.001). Within the groups kidney size and RPF correlated significantly in the diabetics (p< 0.01) and the same was found for kidney size and GFR (0.025< p<0.05), while no correlations were found in the normal group. GFR and RPF correlated in the diabetics when evaluated separately (r=0.81, p<0.001) and in the controls (r=0.73, p<0.001). The previous and present data suggest that the mechanisms of the elevated GFR in insulin-dependent diabetics are enhanced RPF, increased transglomerular hydrostatic pressure gradient and increased glomerular ultrafiltration coefficient. The increased kidney size is probably the main cause of the above alterations in the GFR determinants.     

Glomerular filtration rate changes in normoalbuminuric and microalbuminuric Type 2 diabetic patients and normal individuals A 10-year follow-up

AIM: To analyze the changes in the glomerular filtration rate (GFR) in a cohort of normoalbuminuric Type 2 diabetic (DM 2) patients and nondiabetic individuals. METHODS: Sixty-five normoalbuminuric DM 2 patients [urinary albumin excretion rate (UAER) <20 microg/min] and 44 nondiabetic individuals recruited at baseline were followed for a mean period of 10 +/- 1 years. In addition to conventional clinical and metabolic variables, GFR ((51)Cr-EDTA technique) and UAER (immunoturbidimetric method) measurements were performed at baseline and at follow-up. We also evaluated the presence of diabetic retinopathy, hypertension, and cardiovascular disease. Multiple linear regression was performed to assess variables independently associated with GFR evolution in patients with Type 2 diabetes. RESULTS: Fifty DM 2 patients and 32 nondiabetic individuals were included in the follow-up evaluation. Fourteen out of the 50 patients with Type 2 diabetes developed microalbuminuria. They presented a faster GFR decline (-0.39+/-0.24 ml/min/month; ANOVA, P=.0013) than did persistently normoalbuminuric (-0.16+/-0.16 ml/min/month) and nondiabetic individuals (-0.13+/-0.14 ml/min/month). Multiple linear regression analysis disclosed baseline fasting plasma glucose (FPG) along with the development of microalbuminuria as factors significantly related to a higher GFR decline. CONCLUSIONS: Persistently normoalbuminuric patients and normal individuals presented a similar degree of GFR reduction related to the aging process. The slope was significantly enhanced in patients who developed microalbuminuria and was influenced by worse baseline glucose control.     

Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study.

The prevalence of stage 3 to 5 chronic kidney disease (CKD) in Japan (18.7%) is considerably higher than that in the United States (4.5%). This study investigated in the Japanese general population whether this higher prevalence of CKD might reflect to a progressive decline of renal function, and in turn to the increased risk of end-stage renal disease. A decline in renal function over 10 years was examined in 120,727 individuals aged 40 years or older who participated in the annual health examination program of the two periods over 10 years, 1988-1993 and 1998-2003. Renal function was assessed with estimated glomerular filtration rate (GFR) using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation modified by a Japanese coefficient. The rate of GFR decline in the participants was 0.36 mL/min/1.73 m2/year on average. In the male population aged 50-79, the mean rate of GFR decline was significantly higher in the presence of hypertension than in its absence. The rate of GFR decline was more than two times higher in participants with proteinuria than in those without proteinuria in both sexes. The rate was significantly higher in participants with an initial GFR<50 mL/min/1.73 m2 among the groups younger than age 70 and in participants with an initial GFR<40 mL/min/1.73 m2 in the group with age 70-79. Based on the slow rate of GFR decline, we concluded that the decline in renal function progresses slowly in the Japanese general population. Hypertension, proteinuria and lower GFR were found to be significant risk factors for a faster decline of GFR.     

Skin capillary metrics and hemodynamics in the hairless mouse.

The transparency of the homozygous hairless mouse ear permits detailed study of the intact skin microcirculation without surgical interventions to the skin tissue. It is useful to study many microvascular phenomena and has the potential to provide data to clarify issues related to human skin microcirculation. The aim of this investigation was to quantify the normal capillary geometric and hemodynamic parameters. In each of 36 capillary pairs (10 mice), capillary diameter (D), length (L), and velocity (V) were measured and blood flow (Q) and shear rate (S = 8V/D) were calculated. Loops were chosen such that each branch of the capillary pair had a common arteriolar origin, venule confluence, and thus a common pressure difference across each branch, thereby eliminating the confounding effects of these variables on perfusion differences in each of the branches. Temporal and overall distributions for each parameter were determined and comparisons between paired capillaries made. Overall mean +/- SEM were for D, L, V, Q, and S, respectively, 4.8 +/- 0.2 microns, 161 +/- 5 microns, 192 +/- 5 microns/sec, 3.6 +/- 0.3 pl/sec, and 43 +/- 3 sec-1. Symmetry between paired capillaries was assessed by parameter ratios (smaller/larger); for D, V, Q, and S, respectively, these were 0.85 +/- 0.02, 0.66 +/- 0.03, 0.60 +/- 0.04, and 0.64 +/- 0.04 with corresponding distribution medians of 0.86, 0.72, 0.63, and 0.64. Similar comparisons were made for parameters in smaller/larger diameter capillary pairs yielding for V, Q and S; 1.14 +/- 0.12, 0.82 +/- 0.09, and 1.37 +/- 0.14 with corresponding medians of 0.9, 1.07, and 0.69. These composite results provide baseline data on the naturally occurring animal-to-animal variability, temporal variation, and overall parameter value distributions in the capillary network of this experimental model of skin microcirculation. They thus provide the necessary initial framework for subsequent assessments of pharmacological interventions and the study of various pathological processes on capillary perfusion parameters.     

Evaluation of skin blood flow and venoarteriolar response in patients with diabetes and peripheral vascular disease by laser Doppler flowmetry

Skin blood flow in the distal foot was evaluated in patients with peripheral vascular disease and diabetes and compared with skin blood flow in normal volunteers by use of laser Doppler flowmetry. Resting blood flow (RBF) and standing blood flow (SBF) were recorded in a room at a constant temperature (20-22 degrees C). The RBF was found to be different in the five groups (normal, diabetics, patients with intermittent claudication, those with rest pain and those with impending gangrene. In diabetics RBF was significantly higher than in normal subjects. Even on standing, SBF in diabetics was higher and not different from RBF, indicating an ineffective venoarteriolar response (VAR). The VAR was also reduced in patients with claudication and was abolished in patients with rest pain and impending gangrene. In patients with rest pain SBF was increased. Laser Doppler flowmetry is a useful technique for evaluating skin perfusion in patients with peripheral arterial disease and for discriminating among different classes of patients.     

Skin blood flow and veno-arteriolar response in essential hypertension]

High arteriolar resistance and vasoconstriction are considered an important factor in essential hypertension. In 98 patients with essential hypertension and 60 normals we evaluated skin flow at rest (RF) and the veno-arteriolar response (VAR = the vasoconstriction due to leg dependency) using laser-Doppler flowmetry. Measurements were repeated after four weeks in normals and after treatment with nifedipine (10 mg tid) in hypertensives. At the beginning of the study in hypertensives RF and VAR were lower than in normals. After nifedipine treatment a decrease in blood pressure was associated with an increase in RF and VAR. A difference was also observed between responders and non responders (16.3%). RF and VAR at the beginning of the study were both higher in non responders and did not change after treatment indicating that the degree of vasoconstriction in these patients was lower. In conclusion microcirculation changes in hypertension may be quantified by laser-Doppler flowmetry and used to evaluate vasoconstriction and the effects of drugs.     

Experience with Silastic prostheses in the rheumatoid hand. A 5-year follow-up.

Nine patients with rheumatoid arthritis, who had Silastic prostheses (Swanson's) introduced into 34 metacarpophalangeal joints, were reviewed 5 years after surgery. The most important long-term advantage conferred by the introduction of prostheses was pain relief; functional benefit was marginal. The majority of prostheses eventually fractured but this did not necessarily lead to a functional deterioration. Impairment of function was usually the result of loss of flexion at the metacarpophalangeal joints, but it was sometimes due to excessive instability after fracture of the prostheses. It is suggested that Silastic joint replacement may be a worthwhile procedure in rheumatoid patients with moderate destruction or deformity of the metacarpophalangeal joints when pain is a predominant feature. Significant functional improvement can be anticipated only when secondary to pain relief.     

Causes of death in Japanese diabetics. A 20-year study of death certificates

Death certificates filed between 1960 and 1979 in Osaka, Japan were analyzed to study causes of death in diabetic patients. It was observed that diseases of the circulatory system increased continuously from 15.2% in 1960-1964 to 27.2% in 1975-1979. Cerebrovascular disease and disease of heart were the leading causes of death throughout the study period. The rate of increase was much faster for disease of heart than for cerebrovascular disease, and there was only a small difference between them as cause of death in diabetic patients at the end of the observation period. Malignant neoplasms, cirrhosis of the liver, and pneumonia and bronchitis increased, whereas tuberculosis decreased sharply according to age-adjusted mortality rate during the 20-year period. Analysis based on O/E ratios suggested higher risk of dying from ischemic heart disease, tuberculosis and cirrhosis of the liver in Japanese diabetics than in the general population in this country.     

Dietary intake and physical performance in healthy elderly women: A 3-year follow-up

Background

Aging is generally accompanied by changes in body composition, muscle mass and strength, leading to a decline in motor and functional performance. Physical activity and eating habits could be involved in modulating this paraphysiological deterioration. Aim of our study was to investigate changes in body composition, diet and physical performance in healthy, elderly females over a 3-year follow-up.

Methods

92 healthy elderly females (70.9 ± 4.0 years) attending a twice-weekly mild fitness program were eligible for the study. They were assessed at baseline and again after 3 years in terms of clinical history, diet, body composition by DEXA, resting energy expenditure, handgrip strength, knee extensor isometric/isotonic strength, and functional performance measured using the Short Physical Performance Battery (SPPB).

Results

After 3 years, women had a significant decline in muscle strength (? isotonic: − 1.4 ± 4.3 kg, ? isokinetic: − 2.0 ± 6.3 kg, ? handgrip: − 3.2 ± 5.0 kg; p < 0.001) and physical performance (? walking time: 0.71 ± 0.9 s, ? walking speed: − 0.25 ± 0.35 m/s; p < 0.001), while their weight and body composition parameters did not change, except for a small decrease in appendicular skeletal muscle mass (− 0.4 ± 1.4 kg). There was a significant drop in calorie (?:− 345.7 ± 533.1 kcal/d; p < 0.001) and protein intake (?:− 0.14 ± 0.23 g/d; p < 0.001), while resting energy expenditure remained stable. ? calorie intake correlated with the variation in 4-meter walking time (r: 0.34; p < 0.01).

Conclusions

With advancing age, physical performance declines even in healthy, fit females despite a spare of weight and body composition. This decline in physical activity could lead to a lower calorie intake, which would explain why there is no variation in body weight.     

Determinants for the development of hypertension in adolescents. A 6-year follow-up

OBJECTIVE: This study was aimed to evaluate the determinants of elevated blood pressure (BP) in adolescents. DESIGN AND METHODS: We retrospectively evaluated the BP and anthropometric data in 419 Japanese students (268 males and 151 females) during high school and university. Their annual health records were analysed for BP, heart rate, height and body weight between the ages of 15 and 21 years. RESULTS: The number of hypertensive students did not vary significantly during the 6 years. Concerning changes in BP categories according to the modified JNCVI classification between the ages of 15 to 21 years, 150 males kept a normal BP (keeping normal BP group); 39 males developed high BP (developing high BP group); 37 males kept high BP (keeping high BP group); and 42 males became normal BP (becoming normal BP group). The majority of females (n = 144, 95.4%) were included in the keeping normal BP group. In male students, both the keeping and becoming normal BP groups, especially the latter, showed a significant decrease in heart rate over the 6 years, while the other two groups showed no change. The height and body weight of each of the four groups showed a significant increase, but the body mass index (BMI) of the males in the becoming normal BP group did not increase over the 6 years. Body weight and BMI at the age of 15 years in the male keeping normal BP group were significantly below that of the other three groups; this difference persisted at the age of 21 years. Furthermore, male university students who showed a BP above 'high-normal' at the age of 21 years exhibited a significantly higher BP, heart rate, body weight and BMI than did the normotensives, when they were high school students. Stepwise regression analysis of the data showed that the best predictors of BP at the age of 21 years were the initial high school BP and BMI levels and changes in BMI and heart rate during the 6-year period for male students. CONCLUSION: Results indicate that the BP and BMI during high school and the changes in BMI and heart rate from high school to university influenced the BP at the age of 21 years in male students. Data indicate that information on the prevention and management of hypertension including weight control should begin early, especially in male adolescents.     

Functional changes in patients with spondylarthropathy. A controlled trial of the effects of short-term rehabilitation and 3-year follow-up

A cohort of 25 patients with spondylarthropathy (SpA) participated in a 3-year follow-up study of functional changes before and after an intensive 3-week inpatient course. They answered questions in the following functional status/disability indices: Bath ankylosing spondylitis functional index (BASFI), Dougados functional index (DFI), health assessment questionnaire for spondylarthropathy (HAQ-S), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis patient global assessment (BAS-G), and horizontal visual analogue scale for stiffness (stiffness VAS) before and after the course and 3 years later by mail. A control group of 18 consecutive SpA patients from the waiting list for an inpatient course filled in the same questionnaires as study patients 3 months before entry and again 3 weeks later at home without rehabilitation. During the waiting time for the inpatient course, control group global assessments (BASDAI, BAS-G, and stiffness-VAS) worsened slightly, and BASFI but not HAQ-S and DFI scores remained unchanged in the 3 weeks without treatment. The results of the 25 study patients showed small and not significant improvements in all functional index scores (BASFI -0.5 points, DFI -1.1, and HAQ-S 0.17), whereas improvements were significant in BAS-DAI, BAS-G, and stiffness-VAS (-13 mm, 13 mm, and -11 mm, respectively) after the 3-week inpatient course. At 3-year follow-up, these small changes had disappeared and the changes were not significant. The global indices and BASFI worsened slightly (0.4) from baseline results, while DFI was slightly better (-0.4) and HAQ-S remained at the post-treatment level after 3 years. Thus, BASFI was the most sensitive to changes, whereas DFI and HAQ-S were relatively insensitive. All six indices correlated highly significantly with each other (ICC 0.53-0.94). The natural course of spondylarthropathy leads to progression of functional impairments, which seems to be preventable with intensive rehabilitation, at least in the short term. Among the three functional indices, BASFI seems to be the most sensitive tool.     

A new method for determining capillary filtration coefficients in tissues. 1. Methodologic principles

A new method for measurement of the capillary filtration coefficient (CFC) is developed which avoids the errors of the known method of Pappenheimer and Soto-Rivera. The principle of our method consists in installation of the prepared tissue into a plethysmograph where it becomes exposed to a one step-pressure increase by which the tissue is pressed out. The CFC measurement is carried out by continuous weighing of the blood as it flows out of the arterial and venous parts of the prepared tissue vessels. The basic theoretical conception of this method is proven by means of tissue model.