Epidemiological analysis of patients with Type 2 diabetes in France.

This paper presents the baseline epidemiological data from 5548 patients with type 2 diabetes enrolled in a French observational study that aims to examine the safety, tolerability and use of acarbose as prescribed by general practitioners (GPs). Patients were recruited and monitored by a representative sample of GPs. Recruitment did not depend on a patient's suitability for acarbose treatment. The data revealed that the mean age of the patient population was 63 years, and that more than 50% of patients were over 65 years old. The population was markedly overweight [mean body mass index(BMI): males, 28.4 kg/m(2); females, 29.1 kg/m(2)] and the mean duration of diabetes was 10 (+/-7.3) years. Over 37% of patients had at least one diabetic complication, and the frequency of complications increased with both age and the duration of diabetes. The most frequently reported complications were cardiac (17.8%), vascular (14.5%) and ocular (12%). At recruitment, almost 90% of patients were being treated with oral antidiabetic agents (OADs). Sulphonylureas (74%) and biguanides (50%) were the most commonly prescribed agents. Acarbose was used to treat 17% of patients and 1% were receiving insulin. GPs set glycaemic treatment goals for 44% of patients in the study. Fasting glycaemia was the primary goal for 37% of the total study population, and HbA(1c) levels for 21% of patients. Postprandial glycaemia was generally given as a secondary or tertiary goal. In conclusion, this study provides the most up-to-date epidemiological data for patients with type 2 diabetes in France.

GH deficiency in adults: an epidemiological approach.

OBJECTIVE: The prevalence of adult onset GH deficiency (GH-D) is poorly documented. Epidemiological data are now required to estimate the financial cost of GH treatment in adults. The aim of the present study was to estimate the prevalence of GH-D, from a cohort of 1652 adult patients with hypothalamo-pituitary diseases. DESIGN: The hormonal status of all patients presenting with pituitary diseaseand observed during the year 1994 in 15 endocrine units was retrospectively analyzed, irrespective of the date of disease onset, of the nature and date of pituitary investigations, and whether or not they included specific testing of the GH axis. Of the whole population of 1652 patients, a selected group (RG2) was chosen after exclusion of patients with active acromegaly (n=1414). RESULTS: GH stimulation tests had been performed in 549 patients of the RG2 group and a documented GH-D was found in 301. A relationship between the value of the GH peak and the number of pituitary deficits was evaluated. For instance, it was shown that 93% of patients with three deficits had GH-D. These results constituted the basis for estimating the number of GH-D in the group of untested patients. The number of GH-D deduced from the number of established GH-D (n=301) and from the number of GH-D hypothesized from other pituitary deficits (n=406) was 707 cases. Prevalence and annual incidence were calculated from data recorded in a referral center with a well-defined catchment area, Marseilles (Bouches du Rhône department). We projected a prevalence of 2638 for France and an annual incidence of 12 GH-D per million of the adult population.

Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease.

Adhesion molecules, such as Intercellular Adhesion Molecule-1 (ICAM-1), play an important role during the autoimmune process of Graves' disease (GD). So the objective of the study was to evaluate the time-course of the soluble ICAM-1 (sICAM-1) in GD. Concentrations of sICAM-1, thyroid hormones and TSAb (thyroid-stimulating antibodies) were determined in sera from 30 healthy controls, 41 untreated GD patients and after 3, 6, 12, 18 months of carbimazole therapy (no.=30), at relapse (no.=11) or 2 years after the end of therapy when remission (no.=13). Mean sICAM-1 concentration was significantly higher in untreated GD patients than in controls (mean+/-SD: 371+/-108 ng/ml vs 243+/-47 ng/ml, p<0.0001) until 6 months of therapy (289+/-102 ng/ml; NS). The number of positive patients (sICAM-1 levels>mean of the controls+2 SD) declined from 56% (23/41) at the time of the diagnosis to 10% (3/29) at 18 months. At relapse, mean sICAM-1 level significantly increased compared to that at 18 months of therapy (288+/-65 vs 236+/-59 ng/ml, p=0.005). At remission mean sICAM-1 level was significantly lower than in relapse patients (240+/-48 ng/ml, p=0.04); no patient displayed sICAM-1 positive values. In conclusion, sICAM-1 concentrations were increased in sera of newly diagnosed GD patients, declined significantly during carbimazole therapy and could again be increased at relapse. sICAM-1 could reflect an ongoing immune process and help to affirm the presence of an autoimmunity notably in some cases of TSAb negative patients. However its precise interest in clinical practice remains to be determined in further studies.

Antithyroid drugs and Graves' disease--prospective randomized assessment of long-term treatment.

OBJECTIVE: Although antithyroid drugs (ATD) are widely used in the treatment of Graves' disease, management protocols, especially treatment duration, remain a subject of debate. The rate of relapse after short-term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months. As no prospective study has provided data on even longer protocols exceeding 2 years, we conducted a prospective trial to determine potential benefits of a 42-month treatment compared with an 18-month treatment. DESIGN, PATIENTS AND MEASUREMENTS: The aim of this prospective randomized trial was to compare relapse rates achieved two years after treatment withdrawal in patients who received carbimazole at decreasing doses for 18 months (n = 62) vs 42 months (n = 72). In addition to clinical relapse rate, the percentage of patients who normalized antithyroperoxidase (TPO) antibody and anti-TSH receptor stimulating antibody (TSAb) levels and early iodine uptake at the end of treatment were assessed as outcome criteria. RESULTS: The relapse rate two years after discontinuation of treatment did not differ significantly in patients treated for 18 months from those treated for 42 months (36% vs 29%, NS). At the end of treatment, there was no significant difference between the two groups in the percentage of anti-TPO positive patients (53% vs 46%, NS) or early iodine uptake (27% vs 21%, NS). Although the percentage of patients with TSAb was significantly lower in the 42-month treatment group (18% vs 42%, P = 0.004) at treatment withdrawal, the percentage of TSAb-positive patients did not significantly decrease between 18 and 42 months in this group (27% vs 18%, NS). CONCLUSION: Treatment duration greater than 18 months did not improve remission rate determined 2 years after treatment withdrawal or immunological variables or early iodine uptake measured at the time of discontinuation of treatment. These findings would indicate that, when a defined duration treatment is planned, prolonging treatment beyond 18 months does not provide any additional benefit.

Combined analysis of long-term anti-beta-cell humoral reactivity in type 1 diabetes with and without thyroid disease.

The prevalence and levels of islet-cell antibodies (ICA) decrease in the years following diabetes onset but may persist, particularly in patients with concomitant autoimmune disease. The aim of this cross-sectional study was to investigate the frequencies, associations and levels of the major anti-beta-cell antibodies in long-standing diabetic patients (median duration: 14 years; range 5-47 years) with and without autoimmune thyroid disease (ATD) in order to consider the specific antipancreatic immunologic features associated with endocrine autoimmunity. Both ICA and glutamic acid decarboxylase (GAD) antibody (GAD-A) frequencies were increased in diabetic patients with ATD (38 vs 23%, p = 0.03 and 70 vs 21%, p < 10(-4) respectively). Although IA2-A frequency tended to be higher in diabetic patients with ATD, no significant difference was seen (37 vs 26%, p = 0.14). GAD median level was significantly higher in the diabetic group with ATD (15 vs 5 units, p < 10(-4)). IA2-A and ICA median levels were similar in both groups. Regardless of the combined analysis performed (ICA/GAD-A, ICA/IA2-A or GAD-A/IA2-A), the prevalence of combined antibody positivity was higher in diabetic patients with than without ATD. In both diabetic populations, ICA and GA-DA were significantly associated (p < 10(-4), and their levels were correlated (r = 0.42, p < 10(-4) and r = 0.584, p < 10(-4) respectively). No significant correlation was seen between IA2-A levels and either ICA or GAD-A titres. It is concluded that Type 1 diabetes mellitus with ATD is characterised by increased persistent humoral islet-related reactivity, particularly directed towards GAD.

Clinical and statistical evaluation of self-monitoring blood glucose meters.

OBJECTIVE: Our objective was to compare statistical and clinical methods for the evaluation of five self-monitoring blood glucose (SMBG) meters. RESEARCH DESIGN AND METHODS: Two successive capillary blood glucose measurements were performed, and a simultaneous laboratory venous glucose measurement was used as the reference value. Accuracy was studied by comparing each of the two successive meter values with the reference value by 1) a Spearman's correlation test, 2) a Wilcoxon's paired test, 3) the percentage of values within the 10% interval of the reference value according to the American Diabetes Association consensus statement, and 4) the error grid analysis. RESULTS: The first two methods did not discriminate between the SMBG systems: r was >0.92 for the five meters, and a significant difference between the meter and reference values was found for all but one meter. The two other methods allowed classification of the devices into three groups according to their accuracy: good (two meters), acceptable (two meters), and unacceptable (one meter). These two methods gave consistent results and both had a good reproducibility, because the classification was similar for the two successive measurements. CONCLUSIONS: Both the Spearman's and Wilcoxon's paired tests, although commonly used, are inappropriate to evaluate SMBG systems. The percentage of SMBG values within the +/-10% interval and the error grid analysis are more accurate, because they consistently classified the five glucose meters tested in our study with a high degree of reproducibility.

[Primary adrenal lymphoma with latent adrenal insufficiency: a case report and literature review]. / Lymphome primitif des surrénales avec insuffisance surrénalienne latente: à propos d'un nouveau cas et revue de la littérature.

We report a new case of primary adrenal lymphoma with latent adrenal insufficiency and long-term remission after hydrocortisone replacement therapy. We have analyzed 29 other cases described in the literature. This disease with poor prognosis can be revealed by an incidentally discovered, frequently bilateral, adrenal mass. Adrenal insufficiency may be latent and the diagnostic procedure should include both cortisol and ACTH determination with an additional ACTH stimulation test if appropriate. Early adrenal substitution can improve patient survival.

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients.

The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes. Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis. To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

Increased prevalence of thyroid autoantibodies and subclinical thyroid failure in relatives of patients with overt endocrine disease-associated diabetes but not type 1 diabetes alone.

The purpose of this study was to determine the prevalence of thyroperoxidase (TPO) and thyroglobulin (Tg) antibodies, using a sensitive and specific radioimmunoassay method in a large cohort of 254 first-degree relatives of Type 1 diabetic patients with or without other autoimmune endocrinopathy, and to evaluate the predictive value of thyroid antibodies for impaired thyroid function in these groups. TPO and Tg antibodies were found at similar frequencies (12%) in the 254 relatives, and both antibodies were present in 23 cases (9%). Seven subjects displayed subclinical thyroid dysfunction without an abnormal free T4 level. Among first-degree relatives of probands with Type 1 diabetes alone, TPO or Tg antibodies were found in 8 subjects (6%), including 6 with both antibodies. The prevalence of TPO antibodies was significantly greater among relatives of TPO-positive than TPO-negative probands (p < 0.01). In relatives of diabetic patients with other endocrinopathy, frequencies of TPO (20%), Tg (19%) and a combination of both antibodies (15%) were significantly higher than in relatives of Type 1 diabetic patients without endocrinopathy (p < 0.001). TSH levels were abnormal in only one relative of the group without endocrinopathy but occurred in 6 relatives of the proband with overt endocrinopathy-associated diabetes (p < 0.02) in marked association with TPO antibodies (p < 10(-4). It is concluded that relatives of probands with overt endocrine autoimmune disease-associated diabetes, unlike those of probands with diabetes alone, showed increased prevalence of thyroid antibodies and thyroid dysfunction. These results argue for a different risk of thyroid autoimmunity and clinical disease in families of diabetic patients without or with overt endocrine disease. A screening of thyroid autoimmunity is highly recommended for the latter group.

Multiple antibody status in type 1 diabetic patients and subjects at various risk with islet-cell antibodies.

The frequency of 37/40 kD antibodies and their association with other pancreatic humoral markers were studied in 109 recently diagnosed Type 1 diabetic patients and 116 subjects with islet-cell antibodies (ICA) at various risk for this disease (64 relatives of Type 1 diabetic patients, 23 schoolchildren with no family history of diabetes, and 29 patients with Graves' disease). At the time of diagnosis, 37/40 kD antibodies were detected in 45% of Type 1a and 77% of Type 1b diabetic patients (p = 0.03). Antibodies to glutamic acid decarboxylase (GAD) and/or 37/40 kD were present with the same frequency as ICA (86%). The frequency of 37/40 kD antibodies was not significantly different between the 3 groups at risk, in contrast with GAD antibodies which were found at a lower frequency in schoolchildren (p < 0.02). Frequencies of other pancreatic markers (ICA cross-reactive with mouse pancreas and insulin autoantibodies) and the combination of ICA with at least two other markers were significantly higher in relatives than in the other groups at risk (p < 0.02). Out of 116 ICA-positive non-diabetic subjects, 10 developed diabetes. All 10 displayed 37/40kD and/or GAD antibodies during the prediabetic phase. In 8 of these 10 patients, ICA was combined with at least two other markers, whereas this association was detected in only 17 of the remaining 106 subjects who did not progress to diabetes (p < 10(-4). Thus, 37/40 kD antibodies were found in about half of Type 1 diabetic patients, and with a higher-frequency in Type 1b than 1a. In ICA-positive non-diabetic subjects, our date confirm that a combination of multiple antibodies, including GAD antibodies and 37/40 kD antibodies, can enhance the predictive value for diabetes. Comparison of ICA-positive relatives of diabetic patients, schoolchildren and patients with Graves' disease revealed distinct frequencies and combinations of markers of diabetes. This might reflect different patterns of progression among these 3 groups.

Impaired leucocyte functions in diabetic patients.

This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.

[Management of a thyroid nodule]. / Conduite à tenir devant un nodule thyroïdien.

Whenever a thyroid nodule is detected, the crucial question is whether it is benign or malignant. Apart from surgery, the most accurate assessment is provided by cytologic result. Provided the limitations and constraints of the procedure are understood, especially the need to repeat fine needle aspiration biopsy with time and to have the specimens read by highly experienced cytologists a significant number of surgical operations can be avoided according to circumstances. Except in some special cases, scintigraphy may be discarded because echography is more accessible, lest costly and more discriminating with regard to the surrounding parenchyma. Also, it is not necessary to prescribe hormonal therapy either before or after surgery, if the gland remains under euthyroid conditions; the epidemiological data available are not conclusive enough to justify such a prescription.

Genetic heterogeneity between type 1a and type 1b insulin-dependent diabetes mellitus: HLA class II and TAP gene analysis.

The aim of this study was to compare the genetic susceptibility linked to the HLA Class II region genes of the Major Histocompatibility Complex in isolated insulin-dependent diabetes mellitus (1a-IDDM) and insulin-dependent diabetes mellitus associated with another autoimmune endocrinopathy (1b-IDDM). HLA genes DRB1, DQA1 and DQB1 were studied at the genomic level, as well as genes TAP1 and TAP2. One hundred and seventy-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM patients. While it appeared that common genetic traits characterize diabetes regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM. Extending the analysis of risk haplotypes DRB1*03 and DRB1*04 to TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplo-type DRB1*03 was thus characterized in 1a-IDDM patients by a lower frequency of alleles TAP1-B (13.5%) and TAP2-B (16.2%), not found in 1b-IDDM patients (33.3% for each allele). Likewise, haplotype DRB1*04 is characterized in 1b-IDDM patients by a lower frequency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in 1a-IDDM patients (22.2% and 25.9%, respectively). In total, this study showed that extending the characterization of HLA Class II haplotypes to TAP genes discriminates between the forms of diabetes restricted to a specific pancreatic affection and those reflecting a wider autoimmune disorder affecting several organs.

[Exploration of the various steps of polymorphonuclear neutrophil function in diabetic patients]. / Exploration des différentes étapes du fonctionnement des polynucléaires neutrophiles chez les patients diabétiques.

UNLABELLED: Vascular complications in diabetic patients is a complex, probably multifactorial phenomena involving cellular phagocytosis. The aim of this study was to evaluate polymorphonuclear performance in 61 infection free diabetic patients based on tests of the different cell functions: 1) adhesion:adhesion molecule expression CD11a, CD11b, CD11c; adhesion test on nylon fibers. 2) chemotaxis:chemotaxis under aragose to FMLP (bacteria oligopeptide) and complement fractions. 3) Phagocytosis:latex beads. 4) Bacteriocidal power:chemoluminescence photometric oxidative potential before and after stimulation with opsonized zymosan and PMA; reduction of tetrazolium nitroblue. RESULTS were analyzed according to type of diabetes, glucose control, duration of the disease, history of infection and presence of vascular complications. RESULTS: compared with a group of 30 controls, the diabetic patients had a significant impaired polynuclear chemotaxis function (p < 0.001) with both spontaneous adhesion and increased expression of adhesion molecules (CD 11b, CD 11c). The chemoluminescence test was increased at the baseline level due to spontaneous polynuclear adhesion and increased production of free radicals. This response decreased after stimulation compared with controls. The type of diabetes, Hb A1c level and history of infection did not appear to have an effect. Inversely, changes in chemotaxis and chemoluminescence were greater in patients with vascular complications. In summary, all the functions of polynuclear neutrophils tested were altered in diabetic patients and could favor vascular complications and infections episodes.

Combined analysis of islet cell antibodies that cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in type I diabetic patients.

OBJECTIVE: A combined analysis of whether islet cell autoantibodies (ICAs) are cross-reactive with mouse pancreas, with glutamate decarboxylase (GAD) antibodies, and with 64K antibodies was performed in a large sample of recently diagnosed type I diabetic patients. The disappearance rates of these different autoantibodies were compared in some patients after onset of the disease. The aims were to determine patterns in GAD/64K antibodies with regard to cross-species reaction of ICA and to assess whether GAD could contribute to ICA positivity in mouse and human pancreases and whether the simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma. RESEARCH DESIGN AND METHODS: ICA detected by immunofluorescence in human and mouse pancreases, antibodies immunoprecipitating the 64K rat islet antigen, and antibodies immunotrapping brain GAD activity were quantified at diagnosis of diabetes in 95 patients and in sequential samples during 1 year after diagnosis in 13 patients. The contribution of GAD to ICA positivity in mouse and human pancreases was evaluated by the analysis of correlations between tests and by the ability of brain homogenate to block ICA reactivity in pancreases from both species. RESULTS: ICAs were detected in human pancreases in sera from 63 (66%) patients, among which 61% bound also to a mouse pancreas. GAD and 64K antibodies were strongly correlated (P < 0.0001) and were detected in 69 and 73% of the patients, respectively. All but two patients with ICA in human pancreas also displayed either ICA in mouse pancreas or GAD/64K antibodies. Among 32 patients without ICA in human pancreas, 54% displayed either GAD/64K antibodies or ICA in mouse pancreas. Only 16% of the patients displayed neither ICA nor GAD/64K antibodies. A correlation (P < 0.005) was found between ICA in human and mouse pancreases. GAD or 64K antibodies were strongly correlated with ICA in human pancreas (P < 0.0001), but not with ICA in mouse pancreas. After preincubation of six sera with GAD-containing brain homogenate, ICA titers were unaffected in mouse pancreas but reduced in human pancreas. ICA titers in mouse pancreas were decreased after 3 months (P < 0.01) in diabetic patients, contrasting with the stability of ICA in human pancreas and GAD antibodies by 1 year after diagnosis. CONCLUSIONS: According to cross-species reaction, we confirm the heterogeneity of ICA in a large series of type I diabetic patients, ICAs that cross-reacted with mouse pancreas being more frequent than ICAs without cross-species reactivity. GAD and 64K antibodies were also present in a majority of patients. The simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma so that only a few patients did not display any autoantibody at diagnosis. GAD is not the target of ICAs in mouse pancreas, whereas GAD accounts for ICA positivity in human pancreas. The conclusion that ICAs in mouse pancreas are not GAD-reactive is reinforced by the fact that they are more transient after onset of diabetes than are GAD antibodies or the complex mixture of ICAs in human pancreas.