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.

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.

No major monoclonal lymphocyte population in the thyroid of patients with Graves' disease: study of gene rearrangement by restriction fragment length polymorphism and polymerase chain reaction.

The present study aimed at determining the mono-, oligo-, or polyclonal nature of intrathyroid lymphocytes at the DNA level in patients with Graves' disease. Two techniques were used to seek monoclonal rearrangement in DNA derived from intrathyroidal lymphocytes obtained from six patients. The first was restriction fragment length polymorphism using two specific probes from the B-chain of T-cell receptor and the other from the heavy chain immunoglobulin gene; the second was polymerase chain reaction using a couple of specific primers from the variable and joining regions of heavy chain immunoglobulins. The results for the patients with Graves' disease were compared with those obtained for circulating T-and B-lymphocytes, granulocytes (negative controls), and T- and B-leukemic cells (positive controls). The results with restriction fragment length polymorphism favored a polyclonal origin for the lymphocytes in all cases, since no rearrangement was visualized. The results with polymerase chain reaction were analogous, and the technique was 10 times more sensitive in the detection of rearrangement.

A prospective study of the relationship between relapse of hyperthyroid Graves' disease after antithyroid drugs and HLA haplotype.

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9, and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed for 2 yr after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission; 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease.

HLA and Graves' disease: an association with HLA-DRw3.

HLA-A, -B, and -C antigens were tested by a standard lymphocyte microcytotoxicity technique in 86 Caucasians patients from western France with Graves' disease, and the data were compared with findings in 356 healthy controls. For HLA-DR antigen typing performed by lymphocyte microcytotoxicity testing using a long incubation time, the data were compared to findings in 100 healthy controls. An increase was found in the frequency of HLA-DRw3 [51.16% of patients vs. 20% of controls, corrected P (Pc) < 0.0003; relative risk (rr), 4.19) associated with an increased frequency of HLA-B8 (44.19% of patients vs. 22.47% of controls; Pc < 0.001; rr, 2.73) and HLA-A1 (40.7% of patients vs. 28.93% of controls; Pc < 0.03; rr, 1.71). In contrast, a diminished frequency was found for HLA-B12 (12.79% vs. 31.74%; Pc < 0.01). The antigen combination B8-DRw3 was noted in 37 of the 86 Graves' disease patients compared with 13 of 100 controls (Pc < 0.00003). No association was observed between HLA antigens and the different manifestations of the disease, such as the presence of goiter and/or exophthalmos, or the severity of clinical or biochemical signs. The present findings confirm the reported increase in the frequency of HLA-B8 in patients with Graves' disease. The most striking finding was the prevalence of HLA-DRw3, which, together with recent reports on lymphocyte-defined D locus determinants pointing to an increase frequency of HLA-Dw3, suggests that the gene or genes conferring susceptibility to Graves' disease may be located close to the HLA-D (DR) region of the sixth chromosome.

T lymphocyte subsets at various stages of hyperthyroid Graves' disease: effect of carbimazole treatment and relationship with thyroid-stimulating antibody levels or HLA status.

Markers of autoimmunity in hyperthyroid Graves' disease were studied at various stages of the disease in connection with HLA status. The 148 patients studied were included in a long term prospective evaluation of antithyroid drug treatment. The proportions of total T lymphocytes and OKT4 and OKT8 positive cells in peripheral blood and circulating thyroid-stimulating antibodies were determined before treatment (M0; 46 patients), after 6 (M6; 50 patients), and 18 months (M18; 22 patients) of carbimazole treatment, at relapse (15 patients) and after 2 yr of euthyroidism after drug withdrawal (remission; 23 patients). Twenty-seven patients were sequentially studied between M0 and M6, and M6 and M18. As compared to matched normal subjects, the mean proportion of OKT8 positive cells was significantly decreased in every group of patients, even in those in remission, and the mean OKT4/OKT8 cell ratios were increased in all groups except the patients in remission. However, OKT4/OKT8 cell ratios in individual M0 patients were widely distributed, being normal in 50%. No correlation was found between the proportions of T cell subsets and thyroid-stimulating antibody values, and the two measures varied independently in patients studied sequentially. OKT8 lymphocyte subset was dependent on HLA status. In DR3-positive patients, the mean OKT4/OKT8 cell ratio was high at all stages of the study; in DR3-negative patients it decreased significantly at M18 and was normal in those patients who had a remission. However, in the DR3-positive and -negative groups of patients, the mean OKT4/OKT8 ratios at M0 and at relapse were similar. In conclusion, the proportions of circulating OKT8 positive lymphocytes reflect only poorly the activity of the immune abnormalities in Graves' disease, but do correlate with HLA-DR3 status.

Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration.

A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years.

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.

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.

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.

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.

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.

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.

Plasma malondialdehyde in type 1 and type 2 diabetic patients.

Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substances (TBARS) in 117 diabetic patients and 53 controls. Patients were divided into groups and subgroups according to the type of diabetes (type 1 and type 2) and the existence or not of vascular complication (macro- or micro-angiopathy). Results showed that TBARS concentrations were significantly higher in type 1 (P < 0.0001) and type 2 (P < 0.001) diabetic patients than in the control group. The plasma TBARS concentrations in type 1 and type 2 diabetic patients did not differ significantly. Among the patients with vascular disease, type 2 diabetic patients with macroangiopathy had significantly higher TBARS concentrations than patients with no vascular complication (P < 0.05). Whichever the type of diabetes, there was no correlation between TBARS concentrations and glycaemic control: glycosylated haemoglobin, fasting blood glucose. This study confirmed the existence of lipid peroxidation disorders in diabetic patients.

Serum lysosomal acid hydrolase activities in Graves' disease.

The activities of seven lysosomal enzymes (alpha-D-glucosidase, beta-D-galactosidase, beta-D-glucuronidase, hexosaminidase, alpha-L-fucosidase, alpha-D-mannosidase, acid phosphatases) were studied in the serum of 31 untreated patients with Graves' disease, 30 treated hyperthyroid patients whose clinical abnormalities had disappeared and whose hormones had returned to euthyroid levels, and 34 controls. The hyperthyroid state is characterized by increased serum levels of alpha-D-glucosidase, beta-D-glucuronidase, hexosaminidase and especially of alpha-L-glucosidase and alpha-D-mannosidase. In contrast, neither beta-D-galactosidase nor acid phosphatases serum levels were significantly modified. After antithyroid treatment, the activities of these enzymes returned to normal levels, except for alpha-D-mannosidase. The interpretation of these changes in serum acid hydrolases activities is controversial.

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.

[Screening for the familial form of medullary cancer of the thyroid]. / Le dépistage des formes familiales du cancer médullaire de la thyroïde.

Several questions concerning the diagnosis of medullary carcinoma of the thyroid (MCT) arise from two studies of kindred of a patient with MCT carried out in 1977 and 1983. Diagnosis is based on calcitonin level determination after stimulation by pentagastrine. This method should be proposed for all kindred every time a positive diagnosis of MCT has been made for the first time in a given family. When calcitonin levels are normal it is necessary to repeat this test once a year in all individuals over 5 years of age with a high risk of MCT. Surgical removal should be proposed in cases where calcitonin levels are high. But in practice, this may be difficult and screening must be adapted to each individual case.

[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.

[Susceptibility of LDL to lipid peroxidation in non-insulin-dependent diabetes mellitus with or without macroangiopathy]. / Susceptibilité des LDL à la peroxydation lipidique dans le diabète non insulino-dépendant avec ou sans macroangiopathie.

Since oxidized LDL may play a role in the genesis of atheroma, which is the primary complication of non-insulin-dependent diabetes mellitus (NIDDM), we investigated whether the LDL of diabetic patients were more prone to oxidation than those of healthy controls. We therefore studied the susceptibility of LDL to oxidation by phenylhydrazine (LDL-PO) in NIDDM patients with or without macroangiopathy, and in controls. Results showed that the LDL of patients with macroangiopathy (n = 50) were more susceptible to oxidation than those of both NIDDM patients without vascular complications (n = 50) and controls (n = 50). In diabetic patients, there was a positive correlation between LDL-PO and the following parameters: total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B. In contrast, there was no correlation between LDL-PO and the parameters of glycemic control (fasting glucose, HbAlc). After analyzing the composition of LDL, it appeared that LDL-PO values in diabetic patients were positively correlated with those of all LDL constituents. The increase in LDL-PO observed in the group of NIDDM patients with macroangiopathy could be a consequence of an increase in the LDL triglyceride content in these patients.

["Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes]. / Les "rosettes diabétiques": un marqueur d'immunité cellulaire chez des sujets à risque de diabète de type I.

The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes.