Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Home-measured blood pressure is more strongly associated with electrocardiographic left ventricular hypertrophy than is clinic blood pressure: the Finn-HOME study.

Electrocardiographic evidence of left ventricular hypertrophy (ECG-LVH) has a grave prognostic significance in hypertensive patients. The purpose of our study was to assess whether ECG-LVH is more strongly associated with home-measured blood pressure (BP) than with clinic BP, and whether the correlation between home BP and ECG-LVH increases with the number of home measurements performed. We studied a representative sample of the general adult population (1989 subjects 45-74 years of age) in Finland. Subjects included in the study underwent a clinical interview, electrocardiography and measurement of clinic BP (mean of two clinic measurements) and home BP (mean of 14 duplicate home measurements performed during 1 week). Home BP correlated significantly better than clinic BP with the Sokolow-Lyon voltage (home/clinic systolic: r=0.23/0.22, P=0.60; diastolic: r=0.17/0.12, P=0.009), Cornell voltage (systolic: r=0.30/0.25, P=0.004; diastolic: r=0.21/0.12, P<0.001) and Cornell product (systolic: r=0.30/0.24, P=0.001; diastolic r=0.22/0.14, P<0.001) criteria of ECG-LVH. The correlation between home BP and ECG-LVH increased slightly with the number of home measurements, but even the mean of the initial two home BP measurements correlated equally well (systolic BP), or better (diastolic BP) with ECG-LVH than did clinic BP. In conclusion, home BP measurement allows us to obtain a large number of measurements that have a strong association with ECG-LVH. Our data support the application of home BP measurement in clinical practice.

Biochemical markers of types I and III collagen and limited joint mobility in type 1 diabetic patients.

Limited joint mobility (LJM), a long-term complication of diabetes, has been shown to be associated with microvascular complications of diabetes. Connective tissue alterations may contribute to the development of LJM and other diabetic complications. We tested whether biochemical markers of types I and III collagen metabolism are associated with LJM in type 1 diabetes. We studied 28 male patients of mean age 43.4 years (SD=9.5) and with a duration of diabetes of 25.2 years (SD=9.7) years. LJM assessment included goniometric measurements of the joints and classification by Rosenbloom's method. We measured serum concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP); urinary excretion of crosslinked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) was also measured. Although average serum PIIINP tended to be higher in subjects with moderate-severe LJM (3.1 +/- 1.3 microg/l) than in subjects with mild LJM (2.5 +/- 0.7 microg/l) or without LJM (2.6 +/- 0.4 microg/l), no significant association was found (p<0.27). Concentrations of the other collagen markers were not different in subjects with or without LJM. We conclude that synthesis and degradation of types I and III collagen in diabetic subjects with LJM did not differ from those without LJM to reflect changes in the biochemical markers of these proteins.

Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects.

AIMS: Connective tissue alterations may contribute to the development of diabetic long-term complications in eyes, kidneys and peripheral nerves. Collagen deposition may be increased in micro- and macrovascular disease in diabetic subjects. We tested whether biochemical markers of type III and I collagen metabolism are associated with retinopathy and neuropathy in Type 1 diabetes. METHODS: A total of 28 patients, mean age 43.4 +/- 9.5 (sd) and duration of diabetes 25.2 +/- 9.7 years, were studied. Stereoscopic colour fundus photographs were taken for assessment of retinopathy which was classified as no, background or proliferative. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and urinary excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: Average serum PIIINP was higher in subjects with proliferative (3.2 +/- 1.1 microg/l) than without proliferative retinopathy (2.5 +/- 0.6 microg/l) (P = 0.03). Average serum PICP was higher in subjects without retinopathy (181.7 +/- 19.5 microg/l) than in subjects with background retinopathy (132.1 +/- 42.7 microg/l) (P = 0.02). Concentrations of other collagen markers were not different in subjects with or without retinopathy. No association between collagen markers and neuropathy was found. CONCLUSIONS: The increased synthesis of type III collagen, reflecting deposition of matrix and basement membrane connective tissue, may be involved in the pathogenesis of proliferative retinopathy in Type 1 diabetic subjects. On the other hand, we observed decreased synthesis of Type I collagen, which can result in weakened vascular integrity in subjects with retinopathy.

Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes.

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition.

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Dupuytren's disease in type I diabetic subjects: investigation of biochemical markers of type III and I collagen.

OBJECTIVE: To clarify whether biochemical markers of collagen type III and I metabolism show alterations in type I diabetic subjects with Dupuytren's disease (DD) compared to those without DD. METHODS: DD was assessed in a total of 28 type I diabetic subjects, mean age 43.4 +/- 9.5 (SD) and duration of diabetes 25.2 +/- 9.7 years. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: The prevalence of DD was 32% (9 of 28 diabetic subjects). Average serum ICTP was 2.7 +/- 0.8 micrograms/l in subjects without DD and 3.6 +/- 1.2 micrograms/l with DD (p = 0.0276). No significant association between other collagen markers and DD was found. The reference intervals of PIIINP and ICTP were exceeded only in 1 and 2 subjects, respectively, and they both had DD. CONCLUSION: The degradation of type I collagen might be increased in diabetic subjects with DD. The overall implication was that synthesis or degradation of type III and I collagen in diabetic subjects with DD did not differ enough from those without DD to reflect changes in the biochemical markers of type III and I collagen.

Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Little effect of ordinary antihypertensive therapy on nocturnal high blood pressure in patients with sleep disordered breathing.

The antihypertensive effects of four different antihypertensive medications (beta-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM). Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM. Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD+/-14) mm Hg with atenolol, 7 (SD+/-10) mm Hg with isradipine SRO, 3 mm Hg (SD+/-14) with HCTZ, and 6 (SD+/-15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50. Negative correlation was observed between the apnea time and the mean systolic 24-h (r = -0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = -0.590, P = NS). Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Response of serum total renin to ramipril and metoprolol in hypertensive patients.

Renin-angiotensin system has long been thought to be a classic endocrine negative feedback system in the pathophysiology of hypertension. Furthermore, angiotensin II formation was believed to be regulated by renin secreted from the kidneys. In contrast to these considerations is the identification of local angiotensin II production in other tissues than pulmonary vasculature. Prorenin, the molecular precursor of renin, has been assumed to be involved in local angiotensin II production because of its renin-like activity. Prorenin has also been found to be secreted from extrarenal sources, although a major part of it is derived from the kidneys. Increased concentration of total renin in serum has been proposed to be useful in identifying patients with active proliferative retinopathy in insulin-dependent diabetic patients. Renin-angiotensin system is strongly affected by angiotensin-converting enzyme (ACE) inhibitors and therefore the interfering effect of ACE inhibitor medication on total renin concentration should be known in order to interpret serum total renin concentrations. Nine hypertensive outpatients, all men, treated at the department of internal medicine in Turku University Central Hospital, received randomly 5 mg of ramipril or 95 mg of metoprolol once a day for 4 weeks. Ramipril significantly increased the mean value of total renin (191.9 ng/l vs 312.0 ng/l, p < 0.01), but the metoprolol-induced increase in the concentration of serum total renin was insignificant. We conclude that the negative feedback mechanism in regulating renin and prorenin secretion was inhibited by ACE inhibitor ramipril but beta 1-selective adrenoceptor antagonist metoprolol did not significantly change total renin concentration in serum.

Limited joint mobility in non-insulin-dependent diabetic (NIDDM) patients: correlation to control of diabetes, atherosclerotic vascular disease, and other diabetic complications.

This study examined the association between limited joint mobility (LJM) and diabetic control, atherosclerotic vascular disease and other diabetic complications in non-insulin-dependent diabetic (NIDDM) patients. LJM was studied in 139 [age (mean +/- SD) 61.3 +/- 12.3 years] NIDDM patients. Limitation of several joints was examined with a goniometer and LJM was classified by the Rosenbloom method. The NIDDM patients were examined for the following diseases: history of myocardial infarction, coronary heart, cerebrovascular and peripheral vascular diseases. The diabetic complications, background and proliferative retinopathy, nephropathy, and neuropathy, were also assessed. The metabolic control of the diabetes was evaluated by the average glycosylated hemoglobin Alc (GHbA kappa) concentration and lipid values were also measured. Mean levels of GHbAlc were 8.9 vs. 8.2% (p < 0.05) in NIDDM patients with and without LJM. NIDDM patients with LJM had a 3.1- (95% confidence interval, 1.2-7.7) and a 4.0-fold risk (95% confidence interval, 1.2-13.0) for coronary heart and cerebrovascular disease respectively, when the confounding effects of age, duration of diabetes and control of diabetes were controlled using stepwise logistic regression analysis. Patients with LJM had a 9.3- (95% confidence interval, 1.1-79.0) and a 3.3-fold risk (95% confidence interval, 1.0-10.5) of proliferative retinopathy and nephropathy respectively, when the confounding effects of age and duration of diabetes were controlled, but the correlation disappeared when control of diabetes was included in the model. In conclusion, the presence of LJM is associated with the control of diabetes and with the presence of coronary heart and cerebrovascular diseases in NIDDM patients.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.

A randomised, double-blind trial comparing mibefradil and amlodipine: two long-acting calcium antagonists with similar efficacy but different tolerability profiles. Mibefradil International Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mibefradil and amlodipine in patients with uncomplicated mild-to-moderate essential hypertension. DESIGN: A double-blind, randomised, parallel group multicentre trial. METHODS: 239 patients received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks. Patients then entered a 4-week withdrawal period either on therapy or switched to placebo. RESULTS: Statistically equivalent reductions in trough sitting diastolic blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with 50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9 mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased 23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately 74% in both groups). Patients on mibefradil or amlodipine during the withdrawal period had significantly larger decreases in SDBP than those on placebo. Patients on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had no change in heart rate; however, cessation of amlodipine was associated with a decrease in heart rate. CONCLUSIONS: Mibefradil was as effective as amlodipine in reducing BP; both compounds were effective treatments of hypertension.

Effects of low-dose transdermal scopolamine on autonomic cardiovascular control in healthy young subjects.

We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double-blind, placebo-controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat R-R interval and systolic, mean and diastolic pressures. R-R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R-R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R-R interval and its mid- (0.07-0.15 Hz) and high- (0.15-0.40 Hz) frequency band power in the standing position during controlled breathing at 0.25 Hz. In the supine position, scopolamine did not affect R-R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory-inspiratory R-R interval ratio. This study showed that low-dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects.

Dupuytren's disease: association with chronic diabetic complications.

OBJECTIVE: To evaluate the prevalence of Dupuytren's disease and its association with the clinical characteristics in subjects with type I (insulin dependent) and II (non-insulin dependent) diabetes. To examine the association between Dupuytren's disease and chronic diabetic complications. METHODS: We studied 297 patients with type I [age (mean +/- SD) 33.2 +/- 10.0 yrs] and 139 with type II diabetes [age 61.3 +/- 12.3 yrs]. We investigated the presence of Dupuytren's disease, limited joint mobility, and the following complications: retinopathy, micro- and macroalbuminuria, and somatic peripheral symmetrical polyneuropathy (neuropathy). RESULTS: The prevalence of Dupuytren's disease was 14% in type II patients; prevalence was the same in both sexes. Dupuytren's was associated with age and duration of diabetes in type I patients (p < 0.001). Its presence was significantly related to retinopathy, neuropathy, limited joint mobility, and shoulder capsulitis in type I and to macroalbuminuria in type II patients, by chi-squared test. However, all these associations, except to macroalbuminuria in type II subjects, disappeared when the confounding effect of age and duration of diabetes was controlled by logistic regression analysis. CONCLUSION: The prevalence of Dupuytren's was the same in type I and II subjects although type I subjects were younger. No sex difference of the prevalence of Dupuytren's was seen in patients with diabetes. The disease was associated with macroalbuminuria in type II subjects independent of time related variables. Other associations between Dupuytren's disease and diabetic complications were explained by time related variables in type I and in type II subjects.

Shoulder capsulitis in type I and II diabetic patients: association with diabetic complications and related diseases.

OBJECTIVE: To examine the association between shoulder capsulitis and chronic diabetic complications and diseases closely related to diabetes. METHODS: A cross sectional study in 291 type I [mean (SD) age 33.2 (9.9) years] and 134 type II [61.1 (12.4) years] diabetic patients. The presence of shoulder capsulitis, Dupuytren disease, and limited joint mobility was sought. The patients were assessed for background and proliferative retinopathy, nephropathy, autonomic neuropathy, and peripheral symmetrical somatic polyneuropathy. Diseases closely related to diabetes (hypertension, history of myocardial infarction, coronary heart disease, and peripheral vascular disease) were also recorded. RESULTS: Prevalence of shoulder capsulitis was 10.3% in type I and 22.4% in type II diabetic subjects. Shoulder capsulitis was associated with the age in types I (P < 0.01) and II (P < 0.05) diabetic patients, and with the duration of diabetes in type I patients (P < 0.01). Odds ratios for autonomic neuropathy in type I and type II diabetic subjects with shoulder capsulitis were 4.1 (95% confidence interval, 1.6 to 10.9) and 2.7 (95% CI, 1.1 to 7.0), respectively, after controlling for age and duration of diabetes. Odds ratio for history of myocardial infarction in type I diabetic subjects with shoulder capsulitis was 13.7 (95% CI, 1.3 to 139.5) after controlling for age, duration of diabetes, hypertension, and smoking habits. Other associations between shoulder capsulitis and diabetic complications, related diseases, and other hand abnormalities were fully explained by age and the duration of diabetes. CONCLUSIONS: Shoulder capsulitis is common in type I and type II diabetic patients. It is associated with age in type I and II diabetic patients and with the duration of diabetes in type I patients. It is associated with autonomic neuropathy in type I and II diabetic patients and with history of myocardial infarction in type I diabetic patients, independently of time related variables.

Limited joint mobility is associated with the presence but does not predict the development of microvascular complications in type 1 diabetes.

Previous cross-sectional studies have shown that limited joint mobility (LJM) is associated with microvascular complications in diabetic patients. This study was performed to see whether LJM predicts the development of other diabetic complications and which factors predispose to the development of LJM. A total of 206 Type 1 diabetic patients (mean age 30.0 +/- 9.5 (SD) years) was studied at baseline. The follow-up study was performed 5 years later in 167 of 206 (81.1%) patients. At the baseline the presence of LJM was assessed by asking patients to approximate the palmar surfaces of fingers in a praying position with fingers fanned and the wrists maximally flexed. LJM was confirmed by passive extension. At the follow-up LJM was first reassessed by the same method and then further studied by goniometer and classified by the method of Rosenbloom. The diabetic patients were assessed in terms of the following complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, and clinical nephropathy. The prevalence of LJM was 52.9% at baseline. The odds ratio for proliferative retinopathy was 3.3 (95% confidence interval 1.2-9.5) and for neuropathy 2.5 (95% confidence interval 1.2-5.3) in diabetic patients with LJM compared to patients without LJM, when the confounding effect of the duration of diabetes, age and the body mass index was excluded. LJM developed in 30 patients during the 5-year follow-up (7% per year) and its development was not predicted by any of the microvascular complications at baseline. Proliferative retinopathy developed in 4 of 51 (7.8%) patients with and 3 of 63 (4.8%) patients without LJM at baseline (p = 0.3). Nephropathy developed in 11 of 56 (19.6%) patients with and 11 of 66 (16.7%) patients without LJM at baseline (p = 0.7) and peripheral symmetrical neuropathy in 14 of 45 (31.1%) and 20 of 64 (31.3%) patients respectively (p = 1.0). LJM did not predict diabetic microvascular complications or vice versa. Since LJM is associated with microvascular complications in cross-sectional studies, the clinical value of the assessment of LJM is limited to an orienteering examination in the clinical evaluation of a diabetic patient.

Dupuytren's disease in type 1 diabetic patients: a five-year prospective study.

OBJECTIVE: To clarify which are the underlying factors in the development of Dupuytren's disease (DD) in diabetic patients and to evaluate if the presence of DD can predict the development of diabetic complications. METHODS: A total of 207 type 1 diabetic patients [age (mean +/- SD): 29.9 +/- 9.5 years] was studied at baseline. A follow-up study was performed five years later in 166 patients. The presence of DD was examined and the patients were assessed in terms of the following diabetic complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, and clinical nephropathy. RESULTS: The prevalence of DD was 4% at the baseline study. DD was significantly associated with the age of the patient and the duration of diabetes, but not with the age at the onset of diabetes, BMI or the control of diabetes. DD was associated with somatic peripheral symmetrical polyneuropathy (p < 0.01), a history of myocardial infarction (p < 0.01) and limited joint mobility (LJM) (p < 0.05), but all of these associations could be exclusively explained by the age of the diabetic patients and the duration of diabetes. DD developed in 17 new subjects (2% per year) during the five years of the study. The subjects' age and the duration of diabetes were associated with the development of DD. There was a predominance of the development of DD in women (p < 0.05), and in subjects with retinopathy (p < 0.05), nephropathy (p < 0.05), neuropathy (p < 0.05) or hypertension (p < 0.01), but these associations could also be exclusively explained by the time-related variables. The presence of DD at the baseline study did not predict the development of diabetic complications or hypertension when the confounding effects of age and the duration of diabetes were controlled by logistic regression analysis. CONCLUSION: This study shows that the patient's age and the duration of diabetes are the most important factors predicting the development of DD in diabetic patients. The associations between DD and diabetic complications were exclusively explained by the age and the duration of diabetes. The presence of DD did not predict the development of diabetic complications.

Limited joint mobility in type 1 diabetic patients: correlation to other diabetic complications.

OBJECTIVES: To examine the association between limited joint mobility (LJM) and complications of diabetes in adult patients with type 1 diabetes. DESIGN: Cross-sectional study in diabetic patients and healthy controls. SETTING: The study was performed at the department of medicine in Turku University Hospital (n = 103), a private diabetes outpatient clinic (n = 153) and the municipal health centre of Turku (n = 29), Finland. SUBJECTS: We studied 285 diabetic patients [age (mean +/- SD): 33.4 +/- 10.0 years] and 288 healthy nondiabetic controls [age (mean +/- SD): 32.3 +/- 9.2]. MAIN OUTCOME MEASURES: The limitations of several joints were examined with a goniometer. The diabetic patients were assessed in terms of the following complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, autonomic neuropathy, impotence as well as clinical and incipient nephropathy; serum lipid values were also measured. RESULTS: The prevalences of LJM were 58% and 14% in diabetic patients and in healthy controls, respectively. The diabetic patients with LJM had a 2.8-fold risk of proliferative retinopathy [95% confidence interval (CI): 1.1-7.3] and a 3.6-fold risk of nephropathy (95% CI: 1.4-9.3) compared to patients without LJM, when the confounding effect of the duration of diabetes was excluded. LJM was not related to metabolic control of diabetes, microalbuminuria, autonomic neuropathy or impotence. The association between LJM and peripheral symmetrical polyneuropathy was exclusively explained by the duration of diabetes. The correlation between LJM and serum total and low-density lipoprotein cholesterol was dependent on the association between LJM and nephropathy. LJM did not relate to serum high-density lipoprotein cholesterol or triglyceride values. CONCLUSIONS: The diabetic patients with LJM had an increased risk of proliferative retinopathy and nephropathy compared to patients without LJM.