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Diabet. Med. 27, 804–811 (2010) Abstract Aims To examine the association between cardiac autonomic neuropathy and hypertension and the role of this association in diabetic complications. Methods We included 310 patients, 138 with Type 1 and 172 with Type 2 diabetes, 62 of them with hypertension. Cardiac autonomic neuropathy was assessed by analysing heart rate variations during three standard tests (deep breathing, lying to standing and Valsalva) and looking for postural hypotension. Results Cardiac autonomic neuropathy was present in 123 patients and 39 also had hypertension. The prevalence of a cardiac autonomic neuropathy/hypertension association was higher in Type 2 patients (P

In type 2 diabetic patients with no cardiac history or symptoms, 1) to evaluate whether the soluble forms of Fas (sFas) and Fas-ligand (sFasL), involved in apoptosis, may be markers of silent coronary disease or related to hypertension or microangiopathic complications; 2) to examine the effect of short-term glycemic control on sFas and sFasL.(1) sFas and sFasL were measured with the ELISA method in 44 asymptomatic diabetic patients, 33 with hypertension, and with a normal myocardial scintigraphy (n=14), with silent myocardial ischemia (SMI) and without (n=15) or with (n=15) significant coronary stenoses; and in 14 controls; (2) sFas and sFasL were measured in 15 poorly controlled diabetic patients before and after 7 days of CSII treatment.(1) sFas and sFasL differed in the four groups of patients (p=0.003 each). sFas was significantly higher in the patients with SMI without (p=0.035) and with coronary stenoses (p=0.002) than in the control group. sFasL was lower in the three groups of diabetic patients (p0.05 each) than in control group. In the diabetic population, sFas correlated positively with hypertension (p=0.021), and sFasL negatively with hypertension (p=0.027) and HOMA index in the non-insulin treated patients (p=0.049); (2) sFas did not differ before or after CSII, and there was a marginal decrease in sFasL.Fas-mediated apoptosis is involved in type 2 diabetes and might be associated with hypertension and/or its vascular consequences. sFasL might be affected by insulin resistance. sFas and sFasL are not effective markers of SMI.

Aims To determine whether performing a myocardial scintigraphy immediately after a maximal electrocardiogram (ECG) stress test is effective in detecting silent coronary stenoses and predicting cardiovascular events. Methods Asymptomatic patients (n = 262) aged 57.6 ± 8.8 years, with diabetes for 12.0 years (5–39) [median (range)] and no history of a cardiac event, underwent a maximal ECG stress test followed by a myocardial scintigraphy. The patients with an abnormal ECG stress test or abnormal imaging underwent a coronary angiography. Cardiac events were assessed in 250 (95.4%) patients followed for 37.8 months (3–101). Results The ECG stress test was abnormal in 54 patients. Among them, 18 had coronary stenoses and seven had a cardiac event. Despite a normal ECG stress test, the myocardial scintigraphy was abnormal in 42 additional patients, including 16 patients with coronary stenoses. Four of these 42 patients experienced a cardiac event. Follow-up showed a poor prognosis in subjects who were abnormal on the two tests. Univariate predictors of the 15 cardiac events were the ECG stress test [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.3, 11.4, P = 0.008], myocardial scintigraphy (OR 3.8, 95% CI 1.3, 11.0, P = 0.009), coronary stenoses (OR 26.6, 95% CI 7.6, 90.7, P

The current study sought to examine in a large series of diabetic patients the prevalence of symptoms of autonomic neuropathy and subclinical cardiac autonomic neuropathy (CAN) and their determinants, particularly the influence of diabetes duration, obesity, and microangiopathic complications. Three hundred ninety-six patients, 245 type 1 and 151 type 2, were recruited in 7 French departments of diabetology. CAN was detected by measuring heart rate variability during 3 standardized tests: deep-breathing, Valsalva, and lying-to-standing tests. At least 24.5% of the patients had one or more symptoms suggesting overt autonomic neuropathy. They were older than those free of dysautonomic symptom (P

To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet.A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study.In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMIor=28 kg/m(2)) were randomized to treatment with orlistat (n=346) or placebo (n=350).Body weight, anthropometry, lipid and glycemic control parameters and blood pressure.After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lostor=10% of their initial weight (P=0.04). A significantly greater number of patients receiving orlistat treatment maintained thisor=10% weight loss compared to those receiving placebo (28.1 vs 13.8%; P0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18 mmol/l; P0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%; P0.001).A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.

OBJECTIVE: To evaluate extracellular water (ECW) in the recumbent and the upright position, in overweight and lean women with swelling syndrome, and to correlate the excess in ECW with an increase in capillary filtration of albumin (CFA). PATIENTS: Fifty-one women with a swelling syndrome were investigated, 26 of whom were overweight. MEASUREMENTS: ECW was measured by the bioelectrical impedance method, in the recumbent position and again after a postural test which consisted of walking around for 30 min. CFA was studied by an isotopic test using 99m technetium-labelled albumin. RESULTS: ECW increased (>107% of the theoretical value) in 22 of the 26 overweight patients and 23 of the 25 lean patients. The CFA isotopic test was abnormal in half (11/22) of the overweight patients with increased ECW and in three of the four overweight patients with a normal ECW value. It was abnormal in 18 of the 23 lean patients with increased ECW and in the two lean patients with a normal ECW value. During the postural test, a significant (by≥4%) increase in ECW occurred in a higher proportion of overweight patients tested (14/22) than among the lean women tested (0/5; P=0.04). CONCLUSIONS: The swelling syndrome is indeed related to an increase in ECW in lean and overweight subjects and to a further increase in ECW after a postural test only in the overweight patients. It is also associated with microcirculatory disorders in most of the lean patients who complain of swelling and in only half of the overweight patients with the same complaints, which suggests that other factors (e.g. hormonal disorders) may be involved in the overweight patients.

OBJECTIVE: To investigate blood pressure (BP) and heart rate (HR) responses to an isometric exercise test in obese non diabetic patients and to correlate the results with vagal function and plasma insulin concentration. SUBJECTS: 63 obese patients, 36 of whom had abnormal cardiac parasympathetic control (PS+), and 35 healthy control subjects. METHODS: Analysis of HR variations during three standardized tests: deep-breathing, lying-to-standing and Valsalva. Isometric contraction (handgrip) for 5 min. RESULTS: In the PS+ obese patients, resting HR and body mass index (BMI) were significantly higher than in the PS− subjects and there was a trend to higher plasma insulin concentrations. Age-matched comparison showed that during the handgrip test, the increase in HR at the first minute was significantly higher in the PS− obese patients than in the controls. The increase in BP was significantly lower in the PS+ obese patients than in age-and-BMI-matched PS− obese patients. CONCLUSION: These data suggest that 1) there is an increase in cardiac vagal tone in PS− obese patients, since the early increase in HR at 1 min of the handgrip test, results from the withdrawal of vagal tone; 2) BP response to an isometric contraction is impaired in PS+ obese patients due to a lower sympathetic activation; 3) high plasma insulin concentrations may also contribute to limiting the BP response; and 4) autonomic disorders may account for alterations in the haemodynamic changes during exercise.

Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m2). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 mumol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NIDDs, n = 15) when compared to controls (n = 42) (0.21 +/- 0.03, 0.33 +/- 0.03 and 0.30 +/- 0.02, respectively, mean +/- SEM). However, this activity was lower in IDDs when compared to NIDDs (P < 0.05). In obese patients, with (n = 13) or without (n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol (r = 0.42, P < 0.0001), triglycerides (r = 0.44, P < 0.0001) and BMI (r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.

The handgrip test has long been used as a test for investigating cardiac autonomic neuropathy in diabetic patients. However, the factors involved in the hemodynamic response to the handgrip test have not been thoroughly studied. The aim of this study was to investigate blood pressure (BP) and heart rate (HR) responses to an isometric test in non-insulin-dependent diabetics (NIDDs) and to correlate the results with vagal function evaluated by three standardized tests and with plasma insulin levels. Fifty-five NIDDs, 35 of whom had one to three abnormal parasympathetic tests (PS+), were compared with 10 healthy control subjects. Fasting and postprandial plasma insulin levels were significantly higher in the PS+ than in the PS- patients. Resting HR correlated significantly with log fasting and postprandial insulin. In PS+ NIDDs, resting HR was significantly higher than in PS- patients. Age-matched comparisons also showed that resting systolic BP was significantly higher in PS+ patients than in controls. In PS- patients, the mean acceleration of HR was significantly higher than in the control group from the second to the fifth minute, and the BP response was also higher than in controls. These data suggest that (1) sympathetic response to an isometric exercise is increased in PS- NIDDs; (2) cardiac parasympathetic dysfunction is associated with a more severe insulin resistance; and (3) the subsequent higher plasma insulin level may contribute to the increase in resting HR and BP through sympathetic activation while limiting the hemodynamic response to an isometric exercise through its vasodilative effect.

A defect in the fibrinolytic system results from an increase in type 1 plasminogen activator inhibitor (PAI-1) in diabetes. It can be considered an independent risk factor for the development of cardiovascular disease. In obese and type II diabetic patients, plasma PAI-1 level correlates with fasting insulinemia. However, during the euglycemic clamp, acute hyperinsulinemia does not increase PAI-1 production. The present study was undertaken to investigate the effect of optimized glycemic control by continuous subcutaneous insulin infusion (CSII) on the hypofibrinolytic state for 14 days in 16 type II diabetic patients with poor metabolic control despite maximal oral antidiabetic treatment. Plasma PAI-1 activity levels decreased from 13.38 ± 2.85 IU/mL to 6.77 ± 1.81 IU/mL ( P = .002) during CSII, along with a concurrent improvement in insulin sensitivity (index obtained by basal glycemia — nadir glycemia/basal glycemia) during the insulin sensitivity test (0.121 ± 0.03 v 0.057 ± 0.02, P = .02). These results suggest that insulin resistance rather than hyperinsulinism may be involved in the hypofibrinolytic state in type II diabetic patients. The positive correlation between the changes in triglycerides and in PAI-1 activity ( r = .589, P = .026) strongly suggests a role for triglycerides in the impairment of fibrinolysis, which could be a link between insulin resistance and hypofibrinolysis.

OBJECTIVE: To study the regulation of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) in obese and lean women with a swelling syndrome. PATIENTS: Thirty-four obese women and 12 lean women with a swelling syndrome and an abnormal isotopic test of capillary permeability to albumin were investigated. MEASUREMENTS: After 10 nocturnal hours of fluid restriction, subjects were asked at 8 am to ingest a tap water load of 20 ml/kg within 10 min and to remain strictly recumbent until twelve noon on the first day, and to remain standing and to walk around until twelve noon on the second day. Free water clearance and the cGMP/creatinine and albumin/creatinine ratios were determined hourly in the morning. RESULTS: The total 4 h-urinary volume/ingested water volume ratio was significantly lower on the second day both in the lean and the obese patients, the differences being slightly larger in the obese patients. The increase in free water clearance was significantly less on the second day in the obese patients. The increase in cGMP/creatinine ratio was also significantly lower on the second day in the obese patients. The maximum level of the urinary albumin/creatinine ratio was significantly higher on the second day in the obese patients. CONCLUSION: In obese women with a swelling syndrome: (1) The higher increase in the urinary albumin excretion rate after water loading followed by a sustained upright position suggests a widespread alteration in capillary function, which is also indicated by the isotopic test of capillary permeability to albumin. (2) The water load-induced inhibition of ADH secretion and stimulation of ANP secretion or ANP activity, more defective in the upright position than in the recumbent one, is probably another major contributing factor to orthostatic oedema.

The sympathetic nervous system regulates peripheral blood flow. This study investigated sympathetic vascular control in diabetic patients by measuring cutaneous blood flow (CBF) with a laser Doppler device at rest and during three sympathetic activation tests: deep-breathing, changing positions from sitting to standing, and using the Valsalva maneuver. The influence of various factors, particularly rheological changes, was also assessed. Forty-two type II diabetes mellitus (non—insulin-dependent [NIDDM]) patients and 14 control subjects were studied. The mean value and standard deviation (SD) of basal CBF at rest were not significantly different in the two groups. In 12 NIDDM patients, the SD was less than the lowest limit found in the controls. During the three tests, the reduction in CBF and its downward slope were lower in NIDDM patients than in controls, with the greatest difference occurring during the deep-breathing test. During this test, the downward slope of CBF was less than the lowest control level in 14 NIDDM patients. The log SD of basal CBF correlated with the decrease in CBF during the sitting-to-standing and Valsalva tests in control subjects and during all three tests in NIDDM patients. In NIDDM patients, log mean basal CBF correlated negatively with the log erythrocyte filtration index ([FI] an index of rigidity) and positively with hemoglobin A 1 c = (HbA 1 c ). The log downward slope of CBF during the deep-breathing test correlated negatively with log erythrocyte FI. The log downward slope of CBF during the sitting-to-standing and Valsalva tests correlated positively with total cholesterol and triglycerides, respectively. Basal CBF and the CBF response to these tests did not correlate with retinopathy, nephropathy, peripheral neuropathy, or heart rate variations during these tests. This study suggests that CBF assessment by laser Doppler flowmetry affords an attractive noninvasive way to investigate sympathetic nervous function in diabetic patients. The amplitude of changes in basal CBF and the decrease in CBF during the deep-breathing test show that this is a simple and sensitive procedure for detecting sympathetic nerve dysfunction. Moreover, rheological blood properties and metabolic factors seem to strongly influence resting CBF and vasomotor reflexes.

The objective of the present study was to investigate the effects of a purified micronized flavonoid fraction (Daflon 500 mg) on the increased capillary filtration of albumin (CFA) which is an early change in the microcirculation of patients with diabetes. A placebo controlled trial lasting 30 to 42 days including two equal groups of 20 patients, following a 15-day initial placebo run-in phase. The CFA test employed consisted of injecting albumin labelled with technetium (99mTc) intravenously, applying a venous tourniquet to one arm, and counting the radioactivity on the ipselateral forearm using an external gamma camera. The disappearance of radioactivity was analysed by means of two parameters after the tourniquet had been released, i.e. albumin retention (AR) and the LF/HF index which indicates lymphatic function in interstitial protein clearance. All patients included exhibited an increase in these two indices before the initial placebo run-in phase and at the end of the run-in period. At the end of the treatment phase, AR had significantly decreased in the group treated by the flavonoid fraction (FF) by comparison with the placebo group, and had normalized in 65% of patients in the FF group, compared with 25% of patients in the placebo group (p = 0.010). The LF/HF index normalized in 55% of cases in the FF group, compared with no patients on placebo (p = 0.00001). This study suggests that the flavonoid fraction tested here can improve and even normalize capillary filtration of albumin in diabetic patients.

Aims Malnutrition is frequent in Vietnamese people and may influence cardiac autonomic neuropathy (CAN). The aim of the present study was to investigate cardiac autonomic function in healthy subjects living in Vietnam and the prevalence of CAN in Vietnamese diabetic patients. Methods One hundred and five diabetic patients (BMI = 19.8 ± 0.3 kg/m2), 50 Type 1 and 55 Type 2, living in Hue (Vietnam) were selected and compared with 60 non-diabetic healthy Vietnamese controls (BMI = 20.8 ± 0.2 kg/m2) and also European controls. CAN function was evaluated by five standardized tests: three tests for heart rate variations (HRV) which depend mainly on parasympathetic activity, and two tests for blood pressure (BP) response which depend mainly on sympathetic activity. Results With age taken into account, 41 of the 60 Vietnamese controls had at least mild CAN, as defined by one abnormal test for HRV when compared with the European control series, and 11 of them had two or three abnormal tests. Among the Vietnamese control men, those with abnormal HRV had lower BMI than those without (P = 0.036). Seven Vietnamese controls had postural hypotension and 16 had an abnormal BP response to the handgrip test. Compared with the Vietnamese controls, 71 diabetic patients (67.6%), 40 Type 1 and 31 Type 2, had at least mild CAN, 37 of them had two or three abnormal HRV tests, and 56 diabetic patients (53.3%) had an abnormal BP response to the sympathetic tests. Abnormal HRV were associated with significantly lower BMI, waist and hip circumferences, longer diabetes duration and higher fasting blood glucose. In the logistic regression analyses, abnormal HRV were associated significantly with duration of diabetes and BMI in patients with Type 2 diabetes. Conclusions Cardiac autonomic dysfunction is frequent in normal Vietnamese subjects. CAN appears to be a more frequent complication of diabetes in Vietnam than in Western countries and diabetic parasympathetic dysfunction is frequently associated with sympathetic disorders. This confirms the deleterious effect a poor nutritional state has on cardiac autonomic function.

Summary Objective In France, diabetic subjects were not allowed to dive. The principal risk is hypoglycemia during immersion. However scuba diving is allowed in many countries. To follow blood glucose changes, food intake and insulin adjustments in type 1 diabetic patients when diving, and to propose specific guidelines for such patients willing to practice recreational scuba diving. Methods Fifteen well-controlled (mean HbA 1c : 7.2 %) type 1 diabetic patients without complications were volunteer to dive under strict medical monitoring. They dove 8 times in 4 days in autumn at a depth of 20 meters, in 12°C to 16°C water. A strict protocol based on blood glucose was implemented to prevent hypoglycaemia. Results No case of hypoglycemia was observed and no faintness was reported underwater. Mean blood glucose before diving was 200 mg/dl (11 mmol/l). There was a mean fall in blood glucose of 40 mg/dl (2.2 mmol/l) during dives, a mean decrease in daily insulin doses by 19.3% on the last day. Daily energy intake was 3 225 Kcal in average. A continuous glucose monitoring (CGMS) was performed in one patient and showed a rather stable glycemia during immersion but a decrease within the 8 hours after. Conclusion When respecting a strict protocol to prevent hypoglycaemia, the risk of hypoglycaemia appears quite low. We recommend an ideal glycemic goal of 200-250 mg/dl (11-13.75 mmol/l) before immersion, a higher reduction of insulin doses (-30%) and taking carbohydrates on board in any case. The present data have recently led the French diving federation (FESSM) to allow type 1 diabetic patients to dive with some restrictive qualification requirements: dives within the “safety curve” (no decompression curve), in above 14°C water, depth limited to the median space range (6 to 20 meters), plus mandatory guidance by a diving instructor.

The current study sought to investigate the factors, in particular anthropometric parameters, associated with an impairment of capillary permeability and lymphatic function in a large series of women complaining of a swelling syndrome. One hundred ninety-seven women with a swelling syndrome were investigated, 43 of whom were obese (body mass index [BMI]30 kg/m2), 77 overweight (BMI=25 to 30 kg/m2). Thirty-five of the 197 women had abdominal adiposity (waist-to-hip ratio [WHR]0.85). Capillary filtration of albumin and lymphatic function were studied by means of an isotopic test using 99mtechnetium-labeled albumin and venous compression. This test allowed measurement of interstitial albumin retention (AR) and the evaluation of lymphatic function by analyzing the radioactivity disappearance curve after removal of venous compression with the fast Fourier transform (low frequency/high frequency [LF/HF]). Body composition was studied by the bioelectrical impedance method. WHR correlated with fasting blood glucose (P=.03), serum triglyceride (P.0001), and apoprotein B (P=.008) levels. AR was increased (or =8 %) in 117 women (59.4%) and LF/HF (or =1 %) in 149 cases (75.6%). Extracellular water (ECW) was increased (107% of the theoretical value) in 144 cases (73.1%). LF/HF correlated negatively with age (P=.001), BMI (P=.006), WHR (P.0001), and fat mass (P=.002). In the multivariate analysis taking age, BMI, and WHR as independent variables, LF/HF correlated significantly with WHR (P.005). There was a trend to a higher prevalence of an increase in AR in the women with an increase in ECW (61.8 %) as compared with those without an increase in ECW (52.8%). We conclude that abdominal adiposity is associated with metabolic disorders secondary to insulin resistance as previously demonstrated, whereas lymphatic dysfunction is mainly associated with gynoid adiposity. Besides microcirculatory disorders, changes in the secretory regulation of hormones involved in salt and water retention are likely to play an important role in ECW excess.

OBJECTIVE: The aim of this study was to look for a relationship between autonomic dysfunction and alterations in glucose- induced thermogenesis (GIT) and lipid oxidation rate in obese non-diabetic women. SUBJECTS: 37 obese women, 20 with impaired cardiac autonomic function tests (group 1) were matched with 17 women with normal tests (group 2) according to age, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass (FM) and fat free mass (FFM). MEASUREMENTS: A series of five standardized tests was carried out, three of which were based mainly on cardiac parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip). Energy expenditure (EE), lipid and glucose oxidation rate were determined by indirect calorimetry at fasting and after an oral glucose load (75 g). Blood glucose, insulin and catecholamines responses to glucose were examined. RESULTS: There was no significant difference in plasma glucose, insulin, catecholamines, metabolic rate, glucose and lipid oxidation rate at fasting and plasma glucose, insulin and catecholamine responses to glucose. GIT was slightly but not significantly lower in group 1 (24.7±10.4 kJ) than in group 2 (46.8±9.0 kJ). The cumulative glucose oxidation rate did not differ significantly in the two groups. The cumulative lipid oxidation rate was significantly lower in group 1 than in group 2 (−49.4±4.1 vs −30.8±8.0, respectively, P=0.033). It correlated negatively with the area under the curve of insulin response (r=−0.37, P=0.04). In the multivariate analysis, both autonomic dysfunction and the area under the curve of insulin response correlated significantly with the cumulative lipid oxidation rate. CONCLUSION: This study suggests that 1) the glucose-induced inhibition of the lipid oxidation rate in obese women is greater in the patients with autonomic dysfunction; 2) a decrease in sympathetic activity is likely to be involved in this phenomenon.

The aim of this study was to investigate the factors associated with an increase in capillary filtration of albumin (CFA) in a large series of diabetic patients and its relationship with gender, hypertension, microangiopathy, and neuropathy. One hundred sixty-three unselected diabetic patients, 74 type I and 89 type II, were included. An isotopic test of CFA was performed with 99m technetium—labeled albumin injected intravenously. Radioactivity was counted externally at the forearm with a gamma camera before, during, and after venous compression. After removal of venous compression, interstitial albumin retention (AR) was calculated and the radioactivity disappearance curve was analyzed by the Fast Fourier transform, which provides an index for lymphatic uptake of interstitial albumin (low-frequency to high-frequency amplitude peak ratio [LFHF]). An increase in AR and LFHF was found in 65 (39.9%) and 117 (71.7%) patients, respectively. Increased AR was significantly more frequent in women than in men ( P = .018) and in patients without microangiopathic complications than in those with them ( P = .028). In men, it was significantly more frequent in type I versus type II diabetic patients ( P = .004), and AR was significantly higher in patients with peripheral neuropathy than in those without ( P = .004). The LFHF was also significantly higher in men with peripheral neuropathy ( P = .045). In women, the AR level correlated negatively with postprandial glycemia ( P = .006) and was significantly higher in patients without microangiopathic complications ( P = .003). These data suggest the role of hormonal factors, both sex steroids and insulin, and the major role of peripheral neuropathy in the increase in CFA. The highly prevalent increase in CFA before the onset of microangiopathic complications is consistent with the presence of a functional microcirculatory disorder that might contribute to the occurrence of microangiopathic lesions.

Introduction L'incidence du diabete (D) et du pre-diabete (preD) est en constante augmentation, rendant necessaire de concevoir des programmes pratiques et fiables de depistage precoce. Le but de cette etude est d'analyser la cinetique de la reponse glycemique au glucose oral comparee a la prise d'un petit-dejeuner a la francaise (PDF). Patients et methodes 55 patients, en surpoids (n=10) ou obeses (n=45), âges de 45,8±13,9 ans, sans anomalie glycemique connue. Le profil du glucose interstitiel a ete enregistre par holter (CGMS) apres 75 g de glucose per os a J1 et apres un PDF (pain, confiture, jus d'orange, cafe) contenant l'equivalent de 75 g de glucose a J2. Resultats D'apres la charge en glucose, les patients se repartissaient en 28 normoglycemiques (NG), 9 D et 18 preD dont 17 intolerants au glucose et 1 hyperglycemique a jeun. L'augmentation maximale de la glycemie (Gmax-Go) et l'aire sous courbe incrementale de la glycemie jusqu'au retour a la valeur a jeun G0 (ASC globale) correlaient significativement a J1 et J2 (r=0,865 et r=0,568, respectivement). L'ASC globale, la glycemie a 120 minutes (G120) et le temps global pour le retour a G0 etaient plus eleves a J1 qu'a J2 (p e decile de l'ASC de 0 a 120 minutes a J1 des patients NG, on trouvait a J1 les 9 D (sensibilite Se 100 %) et 12 preD (Se 67 %), et a J2 les 9 D (Se 100 %) et 10 preD (Se 56 %). Les courbes ROC se superposent a J1 et J2. Au seuil d'ASC O-120 de 857 mmol/l.120 min, Se=100 et 65 % et specificites=68 et 66 % a J1, Se=90 et 62 % et specificites=70 et 69 % a J2, pour le depistage du D et du preD respectivement. La meme demarche avec Gmax-Go confere une sensibilite plus faible a J1 et J2 pour ce depistage. Conclusion En considerant l'ASC 0-120, PDF et charge en glucose permettent de depister une anomalie glycemique avec une sensibilite comparable. Le PDF pourrait etre utilise comme test diagnostique a condition d'utiliser un holter glycemique pendant 2 heures.

Introduction Il s’agit de la premiere etude randomisee evaluant l’interet d’une utilisation ponctuelle de l’enregistrement continu de la glycemie au moyen du GlucoDay ® pour ameliorer l’equilibre glycemique, en particulier chez des diabetiques de type 2 avec ou sans insuline. Materiels et methodes Un total de 46 diabetiques (31 de type 2 sous antidiabetiques oraux ± 1 injection d’insuline ; 15 de type 1 sous au moins 3 injections d’insuline), sans ajustement therapeutique depuis au moins 3 mois et suivis depuis au moins un an dans le service recruteur, avec un taux d’HbA1c entre 8 et 10,5 %, ont ete randomises en deux groupes apres avoir effectue un enregistrement GlucoDay ® pendant 48 heures. Dans le groupe GlucoDay ® , les courbes glycemiques servaient au diabetologue d’outil educatif et d’adaptation therapeutique, tandis que dans le groupe controle, seules les auto-surveillances capillaires etaient utilisees. Le critere principal etait la variation d’HbA1c a 3 mois. Un nouvel enregistrement GlucoDay ® etait effectue a ce terme pour analyse des courbes (en cours a ce jour). Resultats Douze patients ont ete exclus, 3 dans le groupe controle pour sortie d’etude, 7 et 3 dans le groupe GlucoDay ® pour graphe ininterpretable lors de la premiere consultation et sortie d’etude respectivement. A 3 mois, l’HbA1c a diminue dans le groupe GlucoDay ® (n = 14, -0,63 ± 0,27 %, p = 0,023) mais pas dans le groupe controle (n = 20, -0,28 ± 0,21 %, NS). Chez les diabetiques de type 2 (n = 25), la diminution d’HbA1c etait significative dans le groupe GlucoDay ® (-0,63 ± 0,34 % p = 0,05), mais pas dans le groupe controle (-0,31 ± 0,29 %, NS). Chez les diabetiques de type 1 (n = 9), la variation d’HbA1c n’etait pas significative que ce soit dans le groupe GlucoDay ® (-0,53 ± 0,27 %, NS), ou dans le groupe controle (-0,22 ± 0,23 %, NS). Conclusion Nous avons montre pour la premiere fois que l’utilisation ponctuelle d’un enregistrement de GlucoDay ® permettait l’amelioration de l’equilibre glycemique chez le diabetique de type 2.

An increase of arterial rigidity and sympathetic activity has been suggested to contribute to essential hypertension. We have shown that vagal control of heart rate (HR) variations during standardized tests is similarly impaired in normotensive obese and type 2 diabetic patients. The aim was to compare cardiovascular vagosympathetic balance and the link between pulse pressure, an index of arterial rigidity, and sympathetic activity in normotensive and hypertensive obese and type 2 diabetic patients. Groups 1 and 2 consisted of 70 normotensive and 32 hypertensive obese patients, groups 3 and 4 of 18 normotensive and 14 hypertensive diabetic patients respectively. HR and blood pressure (BP) variations were studied with a plethysmographic system and spectral analysis (Finapres). During a 5 min-period at a controlled breathing rate, in the 4 groups, the high frequency peak of HR variations (vagal control) was significantly lower than in controls (19 healthy subjects), and the mid/high frequency peak ratio of HR variations was significantly increased. During a standing test, the mid-frequency peak of systolic BP variations (sympathetic activity) did not differ significantly in obese or diabetic patients, either normotensive or hypertensive, and in controls. This peak correlated significantly with pulse pressure in groups 2 and 4 and in the control group but not in groups 1 and 3. In conclusion, 1) spectral analysis confirms that in obese and diabetic patients vagal control of HR variations is similarly reduced and suggests that sympathetic activity is relatively increased ; 2) in hypertensive patients sympathetic tone is not higher than in normotensive ones, but may contribute to arterial rigidity.

Capillary permeability to albumin (CPA) was studied by performing an isotopic noninvasive test with venous compression on 87 nonselected diabetics with no edema, no cardiac failure, and no peripheral vascular disease. Excessive albumin retention (AR ≥ 8%) ten minutes after removal of the compression was found in 27 patients (31%). The radioactivity disappearance curve was then analyzed using the Fast Fourier Transform (FFT). An abnormal isotopic CPA test was thus found in at least 45 out of the 87 patients. The prevalence of an abnormal test was not different in type 1 and type 2 diabetics. We studied the independent effects of hypertension, presence of specific clinical signs of microangiopathy (retinopathy and/or significant proteinuria), and duration of diabetes. Among diabetics free of specific clinical signs of microangiopathy, the prevalence of an AR ≥8% was significantly higher in those with hypertension ( 11 19 ) than in those with normal blood pressure ( 2 28 ) and in nondiabetic hypertensive patients ( 0 16 ). Among normotensive diabetics, the prevalence of an abnormal test was higher, but not significantly, in patients with specific clinical signs of microangiopathy ( 8 11 ) than in those free of them ( 7 18 ). Seven normotensive diabetics without specific clinical signs of microangiopathy had an abnormal test; five of them had had diabetes for more than five years. The prevalence of diabetes of more than five years duration was significantly higher in patients with an abnormal test ( 35 45 ) than in normotensive diabetics free of specific clinical signs of microangiopathy with a normal test ( 4 11 ). These results show (1) the high prevalence of an abnormal CPA in a nonselected diabetic population, (2) the major independent roles of hypertension, microangiopathy, and duration of diabetes in this abnormality, and (3) with the FFT, evidence of a late abnormal phenomenon in the radioactivity disappearance curve, which may be due to a deficient lymphatic wash-out of albumin preceding overt albumin retention.

We have previously shown that silent coronary stenoses (CS) were predictors of subsequent major cardiac events in diabetic patients with silent myocardial ischemia (SMI). The aim of this study was to determine their correlates and their prognostic value for other cardiovascular events.362 asymptomatic diabetic patients, without prior myocardial infarction, withor =1 additional risk factor and a normal resting electrocardiogram underwent a myocardial scintigraphy to detect SMI. The patients with SMI subsequently underwent a coronary angiography to detect CS. A total of 345 (95.3%) patients were followed up for 41 +/- 24 months with regard to the occurrence of stroke, gangrene or a peripheral revascularization procedure, exercise occurrence of angina, and nonfatal arrhythmia.121 patients had SMI and 44 had CS. The univariate correlates of CS were age65 years (Odds Ratio 2.1 [CI 95%: 1.1-4.0]; p=0.021), male gender (OR 3.1 [1.5-6.3]; p=0.001), smoking (OR 2.8 [1.4-5.6]; p=0.004),or =2 risk factors (OR 2.1 [1.09-4.09]; p=0.024) and peripheral arterial disease (OR 3.2 [1.2-8.7]; p=0.018). Logistic regression showed that age65 years (p=0.034), male gender (p=0.001) andor =2 risk factors (p=0.013) were independently associated with the presence of CS. The univariate predictors of the 16 minor events were peripheral arterial disease (OR 8.8 [2.7-28.5]; p0.001), CS (OR 4.9 [1.7-14.2]; p=0.002), SMI (OR 3.7, [1.3-10.5]; p=0.009) and smoking (OR 3.2 [1.1-9.2]; p=0.024). In the multivariate analysis, arterial occlusive disease (p0.001), smoking (p0.036) and CS (p=0.044) were independent predictors of events.Silent CS predict major cardiac events but also other cardiovascular events and are more common in diabetic patients65 years-old, of male gender and withor =2 risk factors.

Silent myocardial ischemia (SMI) and silent coronary stenoses (CS) are two to seven times more frequent in diabetic patients than in non-diabetic patients. In addition to this, they have a higher predictive value for cardiovascular events than the classical cardiovascular risk factors, either taken alone or combined. Coronary arterial disease is the leading cause of mortality and morbidity in the diabetic population. Altogether, these data suggest that screening for SMI and silent CS is an important issue. We assume that detecting SMI and silent CS improves patient management, and leads to optimised follow-up, action taken on nutrition, exercise and lifestyle, management of the cardiovascular risk factors, and revascularisation procedures whenever possible. However, screening for SMI and silent CS is expensive and may induce morbidity. Selecting the patients with a high a priori risk of SMI and silent CS is therefore of major concern. Carotid or lower limb peripheral arterial disease, proteinuria, male gender, an age greater than 60 years, and two or more cardiovascular risk factors among smoking, microalbuminuria, dyslipidemia, hypertension, a family history of premature cardiac disease, and cardiac autonomic neuropathy have been demonstrated to be the best current predictors of SMI and silent CS. New markers, such as adhesion molecules, Lp(a), inflammation parameters or homocysteine, and endothelium function assessment might be of further help in the future.

Summary Aim The benefit of treating gestational diabetes mellitus (GDM) has recently been shown. The aim of this study was to compare offspring and maternal health benefits from selective or universal screening for GDM. Methods The incidence of outcomes was compared in three series of pregnant women: 1) the 159 consecutive women with GDM out of the 1909 women who delivered between October 2000 and September 2001: during this period screening for GDM was based on risk factors (risk factor-GDM); 2) the 265 consecutive women with GDM out of the 2111 women who delivered during the year 2002: during this period screening for GDM was universal (universal-GDM); 3) 1255 women with no GDM during year 2002 (controls). Results After adjustment for age, pregravid body mass index, parity, and ethnicity, the risk of large for gestational age (Odds ratio 2.19[95% confidence interval 1.36-3.54], P −3 ), delivery before 37 weeks of gestation (OR 2.44 [95CI 1.32-4.51], P=0.004), jaundice (OR 3.31[95CI 1.58-6.93], P=0.002), hospitalization in the department of pediatrics (OR 2.35 [95CI 1.53-3.61], P −3 ) was higher in the GDM-risk factor group than in the control group, whereas it was similar in the universal-GDM group and the control group. Compared with the control group, the risk of anticipated delivery and hospital stay > 4 days after delivery was increased in the GDM-risk factor group (OR 2.69[1.88-3.84], P −3 ; and OR 2.6 [1.82-3.71], P −3 respectively) and the universal-GDM group (OR 1.54 [1.15-2.07] P=0.004; and OR 1.49 [1.13-1.97], P=0.005 respectively). Conclusion This observational study suggests that universal rather than selective screening for GDM may improve outcomes. Universal screening might reduce delay of diagnosis and care.

To investigate, by thallium-201 scanning, circulation in the muscles of the lower limb (LL) in diabetic patients without clinical peripheral vascular disease but with a high cardiovascular risk profile.A total of 80 diabetic patients (76 patients with type 2 diabetes, mean age 57.3 years, duration of diabetes 13.0 +/- 7.5 years) with more than one additional cardiovascular risk factor but no claudication were investigated. After stress testing, 1.5 MBq/kg thallium-201 was administered to perform myocardial single-photon emission computed tomography followed by LL scanning. Muscle blood flow was considered abnormal if the asymmetry in thallium-201 uptake between the two buttocks and/or thighs and/or calves was10%.Muscle perfusion defects were found in 42% of the patients, mainly in the calves. These defects correlated with retinopathy (P = 0.042) and the HbA1c level (P = 0.044). In patients with defects in the buttock and/or thigh, the prevalence of nephropathy and retinopathy was higher than in those with isolated defects in the calf (P = 0.032 and 0.023, respectively).This study suggests that LL scanning coupled with myocardial scintigraphy is a convenient method of investigating peripheral muscle circulation. Proximal perfusion defects in patients without clinical arterial disease are associated with increased prevalence of retinopathy and nephropathy and, therefore, may be due to microvascular disease of LL muscle. Distal defects may indicate silent macrovascular disease of the LL.