Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18 to 34-week, open-label, extension period.

AIM: The aim of this trial was to obtain further data on the efficacy and safety of benfluorex as an add-on therapy in type 2 diabetic patients insufficiently controlled by sulfonylurea monotherapy who had a limitation for the use of metformin during a 4-month extension period following a 4-month double-blind trial. METHODS: Patients who completed the 18-week double-blind period entered the 16-week extension period. Patients in the benfluorex group during the double-blind period continued benfluorex 450 mg/day (B-B group), whilst patients in the placebo group switched to benfluorex 450 mg/day (P-B group). The main efficacy criterion was HbA(1c), analyzed as the change from week 18 (W18) to the end of treatment using a two-sided Student paired t-test. Secondary criteria were fasting plasma glucose (FPG), insulin resistance and lipids. RESULTS: Between W18 and the end of treatment, HbA(1c) decreased in the P-B group from 8.53+/-1.37% to 7.49+/-1.04% (P<0.001) and remained stable in the B-B group from 7.52+/-1.07% to 7.53+/-1.14% (NS). In the P-B group, parameters of glycemic control showed improvements from W18 to week 34 (W34) which were similar to those observed from baseline to W18 in the B-B group. Overall, the target HbA(1c) (

The epidemiology of childhood-onset type 1 diabetes mellitus in Romania. ONROCAD Study Group. National Romanian Organisation for the Care of Diabetic Children and Adolescents.

The ONROCAD Study group was established to provide descriptive epidemiological information on type 1 diabetes mellitus (DM) in Romania. Data on all new patients with type 1 DM with onset before age 15 years during the four-year period 1992-1995 in Romania were submitted from all members of the ONROCAD Study Group, representing all doctors and clinics that manage children with DM in Romania. Age- and sex-specific incidence rates were estimated, using available demographic data. A total of 706 new patients with type 1 DM and onset 0-14 years was registered. The overall completeness of ascertainment was estimated at 93.5%. For all Romania, the incidence of childhood-onset type 1 DM was estimated at 3.57/100,000/year. The incidence in the three regions was statistically significantly different (p = 0.002), with high rates in Transylvania and low rates in Muntenia. Girls had a significantly higher incidence than boys for each of the age groups 0-4, 5-9 and 10-14 years. Between these age groups, the incidence increased significantly with age. The incidence of childhood-onset type 1 DM is among the lowest recorded in Europe. Significant, but unexplained, geographical variation exists within Romania. Searches for factors to explain this heterogeneity may provide clues to the etiology of childhood-onset type 1 DM.

Diabetes mellitus and chronic HCV infection.

UNLABELLED: The aim of our paper was to assess the prevalence of anti HCV antibodies among diabetics from Romania. MATERIAL AND METHOD: We performed two studies: a prospective randomized one, on 559 diabetics from Timisoara, and a second, retrospective-descriptive one, on 625 diabetics from Petrosani, who were tested for anti HCV antibodies. RESULTS: I. In Timisoara, 559 diabetics were prospectively evaluated, 4.5% (25p.) were anti HCV positive. There were no statistically significant differences between the proportions of type I DM in the anti HCV positive group (4%-1p.) as compared to the entire group (12%-67p.) (p=0.3429), nor in the F: M ratio, 1.3:1 vs. 1.5:1 (p=0.838). II. In Petrosani, 625 diabetics were retrospectively evaluated, 7.7% (48p.) were anti HCV positive. There were no significant differences between the proportions of type I DM in the anti HCV positive group (6%-3p.) vs. the entire group (8%-53p.) (p=0.788), nor in the F: M ratio, 1.7:1 vs. 1.7:1 (p=1). CONCLUSION: The prevalence of anti HCV antibodies among diabetics from Romania is rather high (4.5% in a randomized prospective trial and 7.7% in a retrospective descriptive trial) so that this special population (especially type II DM) should be screened for HCV infection, even if the aminotransferases are normal.

The importance of the relationship between microalbuminuria, subclinical proteinuria and arterial hypertension in diabetics.

Arterial hypertension represents, among others, an important risk factor for the development of microalbuminuria in diabetics. On the other hand, with microalbuminuria, it has been observed an important rise in the prevalence of high blood pressure. This study stresses the importance of the relationship between subclinical proteinuria and microalbuminuria, on one hand, and arterial hypertension on the other hand. There have been studied 343 diabetics hospitalized in our Clinic. We estimated the presence of hypertension (according to WHO criteria) and the values of subclinical proteinuria (biuret method) and microalbuminuria (MICRAL-test). We observed that 70.8% of hypertensives and 49.4% of normotensives presented values of proteinuria that ranked between 300 and 500 mg/24 h (p < 0.001). Meanwhile, 25.8% of proteinuric patients and 14.8% of non-proteinuric ones were hypertensives (p < 0.05). In hypertensive diabetics the prevalence of subclinical proteinuria is higher than in normotensive ones. The prevalence of hypertension is significantly higher in microalbuminuric patients than in normoalbuminuric ones.

Determinants of microalbuminuria in diabetics.

Several risk factors for the development of microalbuminuria such as: blood glucose unbalance, high blood pressure, dyslipidemia, genetic susceptibility have been described and discussed. The object of this study was to ascertain the importance of these factors. To this end albuminuria was measured using MICRAL-test in two groups of subjects: 100 diabetics (43 type I (insulin-dependent) and 57 type II (non insulin-dependent), and 54 controls. According to diabetes duration, the cases were divided into four sub-groups (less than 5 years; 5-9 yrs; 10-19 yrs; over 20 yrs). The mean values of albuminuria were assessed in the two groups (diabetics and controls) and also for each subgroup of diabetes duration. It was found that in insulin-dependent diabetes mellitus (IDDM), the duration of the disease is an important determinant of albuminuria, a significant increase in its values being observed after 10 yrs of diabetes evolution. The importance of diabetes duration, glucose unbalance and high blood pressure (BP) as possible determinants of microalbuminuria was assessed by comparing the micro- and normoalbuminuric diabetics. Our results are similar to those reported by many other authors, showing that these are important risk factors for microalbuminuria, especially in IDDM.

[Diabetic nephropathy. I]. / Nefropatia diabetica. Partea I.

The paper reports on the present knowledge in the diabetic nephrosis (DN) with emphasis on three problems: evolution by stages, possibility of detecting the diabetics with high risk of developing clinic DN, and the prophylactic and therapeutic measures required for a resting or, at least, for slowing down the evolution of this complication. The functional changes, manifested mainly by increasing the glomerular filtration, are detected in many insulin-dependent diabetics even from the diagnosis of the disease and they are predictive elements for the clinic DN; that is the reason why they must be reduced by a correct and prolonged control. Microalbuminuria, defined as a urinary excretion of albumin of less than 250 mg/24 hours (18-74 micrograms/minute) is another characteristic of the precocious stages of the DN. Exceeding the above-mentioned values means the transition to the clinic DN, that subsequently progresses in all cases. The paper also describes the characteristics of the clinic DN and the therapeutic ways both in the incipient and clinic DN, with emphasis on their features in the diabetes mellitus and its complications.

GADA and islet cell antibodies in Romanian children and adolescents with diabetes mellitus.

UNLABELLED: Childhood type 1 diabetes is defined by autoimmunity and insulinopenia. Etiopathogenic definition based on biochemical characteristics has recently replaced the clinical definition based on insulin requirement for treatment. The aim of this study was to describe biochemical and clinical characteristics of children with clinically diagnosed type 1 diabetes, hospitalized at the "Cristian Serban" Center in Buzias. PATIENTS AND METHODS: Fasting C peptide, HbA1c, islet cell autoantibodies (ICA) and antibodies against glutamic acid decarboxylase (GADA) were measured in 278 subjects aged (mean +/- SD; range) 15.1 +/- 4.8 (4-28) years, with a disease duration of 2.1 +/- 0.7 (1.1-3.1) years. GADA and ICA positivity was defined by values higher than the 95th percentile in 99 age-matched non-diabetic controls (0.4 units for ICA and 1.4 for GADA). RESULTS: As many as 66.2% of all patients had positive GADA and 10.1% had positive ICA. While 68.7% had at least one positive antibody, only 7.6% had both antibodies positive. As expected, most of the children (79.9%) had fasting C peptide values in the low range (<0.5 ng/ml), but 3 patients (1.1%) had biochemical signs of insulin resistance (C peptide concentrations >3 ng/ml). Two of the three insulin resistant children had positive GADA and one of them had positive ICA, therefore showing "mixed" features of both type 1 (autoimmunity) and type 2 diabetes (insulin resistance). CONCLUSIONS: Childhood diabetes is now acknowledged to be a complex disorder with heterogeneity in its pathogenesis, clinical course and outcomes. While type 1 diabetes is the most frequent form of diabetes among Caucasian children, measurement of diabetes autoantibodies and C peptide is necessary to better define the types of diabetes in youth.

The value of basal C peptide and its relationship with pancreatic autoantibodies in young adults with type 2 diabetes mellitus.

UNLABELLED: It is well known that sometimes it is difficult to distinguish between type 1 and 2 diabetes mellitus using clinical criteria, in subjects with disease onset relatively early in adult life. The measurement of C peptide level and of immunological markers may represent important additional tools for establishing the correct diagnosis. The aim of the study is to assess the trend of basal C peptide in patients with clinical diagnosis of type 2 diabetes and to relate it to the type of treatment, the body weight and the positivity for pancreatic autoantibodies. PATIENTS AND METHOD: we studied a group of 268 patients with type 2 diabetes, aged between 30 and 50 years, with a diabetes duration of less than 5 years. In all patients, we measured basal C peptide, islet cell autoantibodies and antibodies against glutamic acid decarboxylase, computed the body mass index and recorded the current antidiabetic treatment. RESULTS: Based on basal C peptide value, diabetic subjects fell under 3 categories: a) low C peptide (<0.58 ng/ml): 7.5%, b) normal C peptide (0.58-2.70 ng/ml): 57.8%, and c) high C peptide (>2.70 ng/ml): 34.7%. Patients with low C peptide were treated more often with insulin, while those in high C peptide group received more often biguanides. A direct correlation between C peptide and body weight was established. Mean C peptide was lower in patients positive for at least one pancreatic autoantibody, compared to those who were negative for antibodies CONCLUSION: Low basal C peptide can be considered criterion for transferring the patients, initially diagnosed as type 2 diabetes, in the type 1 diabetes group.

Apolipoprotein (a) concentrations in type 1 (insulin-dependent) diabetes mellitus.

It has been suggested that insulin-dependent diabetes mellitus (IDDM) patients have higher values of lipoprotein (a)-Lp (a) that may account for their increased atherogenic risk, as related to non-diabetic subjects. We compared the plasma values of apolipoprotein (a)-(apo) (a) in type 1 diabetic patients (n = 26) hospitalized in our department and in non-diabetic subjects (n = 20) from Timisoara, Romania. IDDM patients had higher levels of apo (a) than controls [115(102-227) vs 58 (51-106) U/l; medians with 95% confidence intervals]; (p = 0.0083). Diabetes duration, the levels of hemoglobin A1 (Hb A1) and the values of body mass index (BMI) were not significantly related to apo(a) concentrations, while no correlations were found between apo (a) and plasma lipid values (total cholesterol (TC), low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglyceride. A significant association was noticed between apo (a) and apo B both in IDDM patients (r = 0.43; 0.02 < p < 0.05), and in controls (r = 0.83; p < 0.001). We conclude that apo (a) levels are higher in IDDM patients than in non-diabetic subjects, but they are not related to the degree of glycemic control. Apo (a) and apo B are significantly correlated, both of them being well-known atherogenic risk factors.

Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic patients from Romania.

Several studies suggested that lipoprotein (a)-Lp(a) is an independent atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is characterized by an increased risk of coronary heart disease (CHD) as related to the general population, the main purpose of our study was to compare the plasma levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our department, and in 20 non-diabetic controls from Timisoara. Apo (a) values were similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for microalbuminaria with the MICRAL-test and we compared apo (a) levels in those having albumin excretion values above and under the cut-off point (20 mg/l). Apo (a) concentrations were similar in both samples. We found no association between apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have similar apo (a) concentrations to non-diabetic subjects and they do not seem to be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid values Apo (a) and apo B are significantly correlated, both in diabetic and non-diabetic subjects.

Contribution to the early diagnosis of diabetes mellitus.

The authors present the results of an investigation for diabetes mellitus (DM), in a selected group of 9,901 persons at high risk for the disease, using oral glucose tolerance test (OGTT). In the group investigated they included 4,753 diabetic blood relatives, 4,123 obese patients and 935 women who delivered big babies. The percentage of diagnosed DM was 30.58 for the entire group, with variations between: 39.47 in the obese, 27.27 in women with macrosomia, and 23.35% in the diabetic blood relatives. The results showed the value of OGTT as a diagnostic tool, the importance of early diagnosis and the necessity of careful long time follow-up of the newly diagnosed diabetics.

Apolipoproteins AI and B and plasma lipid values in well-treated diabetic patients from Romania.

This review is aiming to study the values of apolipoprotein AI and B and plasma lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride) in well-treated diabetic patients, and their possible relationship with hemoglobin A1, body mass index and insulin levels. The study groups were 26 insulin-dependent diabetic (IDDM) patients, 30 non-insulin-dependent diabetic (NIDDM) subjects and 20 non diabetic subjects (controls). Apolipoprotein AI concentrations were similar in the three groups, but apolipoprotein B values and apo B/apo AI ratio were significantly higher in IDDM as related to NIDDM patients (p < 0.001) and to non-diabetic subjects (p < 0.001). We were not able to find significant differences concerning plasma lipid values between the three groups. We found a weak correlation between apo B and hemoglobin AI in IDDM (r = 0.45; 0.02 < p < 0.05), but not in NIDDM patients. Body mass index was not related to the values of apolipoproteins AI and B. We found a positive but weak correlation between insulin levels and triglyceride (r = 0.42), and an inverse one with HDL cholesterol (r = 0.57; 0.02 < p < 0.05) in non-diabetic subjects only, while in NIDDM patients these associations were even less significant. Plasma insulin values strongly correlate to body mass index in both NIDDM (r = 0.64; p < 0.001) and in control subjects (r = 0.73; 0.001 < p < 0.001).

[The early detection of diabetes mellitus and the active dispensary care of 1200 subjects with a genetic predisposition]. / Depistarea precoce a diabetului zaharat si dispensarizarea activa la 1200 subiecti cu predispozitie genetica.

Diabetes mellitus (DM) is a metabolic disease with a long-lasting chronic course, attending during its development by complications which affect the state of health and require additional measures from the social and economic point of view. The current strategy consists in the earliest possible detection of disease in groups of population selected according to the existent risk of developing a DM. This action is followed by an active dispensary care and by lessons of health education, aimed at preventing metabolic decompensations and the early occurrence of degenerative chronic complications. Taking into account these considerations in the present paper, authors analyse the possibility of detection of DM in 1,200 subjects genetically predisposed, a special stress being laid on the means of prevention, on the role of active dispensary care and on the place of health education in the therapy of DM and in the prevention of complications of this disease with an invalidating potential.