To what extent should we lower HbA1c in diabetic subjects?

Current recommendations regarding glycemic control suggest that HbA(1c) should be lower than 6.5%. This is supported by data regarding microvascular disease, namely retinopathy rather than nephropathy. The question is not completely solved regarding cardiovascular diseases, where a strategy of very low HbA(1c) ("the lower the better") is expected to be effective. Some ongoing studies will help to answer these unsolved questions.

Maternal history of type 2 diabetes is associated with diabetic nephropathy in type 1 diabetic patients.

AIMS: Insulin resistance is a key feature of type 2 diabetes. It is also involved in the development and progression of microvascular complications. We analysed the relationship between parental history of diabetes, insulin resistance and diabetic nephropathy (DN) and assessed the specific maternal and paternal influences of history of type 2 diabetes on DN in type 1 diabetic offspring. METHODS: We recorded information regarding family history of type 2 diabetes and of cardiovascular disease in 160 consecutive, unrelated type 1 diabetic patients. Insulin resistance was assessed using a validated estimation of the glucose disposal rate (eGDR). RESULTS: Type 1 diabetic patients with a maternal history of type 2 diabetes were more likely to be insulin-resistant (P=0.043) and to have renal complications (P=0.0041) than those from the reference group (without parental history of diabetes), while patients with a paternal history were not different from those from the reference group, regarding eGDR and DN. Time to development of abnormal albuminuria was significantly affected by maternal history of type 2 diabetes (log-rank=12.66; P=0.0004) and by familial history of premature cardiovascular disease (log-rank=5.48; P=0.0234). In multivariate analysis, a maternal history of type 2 diabetes was independently associated with nephropathy after adjustment for sex, diabetes duration and familial history of premature cardiovascular disease. CONCLUSION: Maternal history of type 2 diabetes is independently associated with DN in type 1 diabetic patients. This might suggest the transmission of a maternal trait related to microvascular complications, raising the hypothesis of imprinted genes predisposing to diabetic renal disease.

Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test.

BACKGROUND: Adult growth hormone (GH) deficiency must be diagnosed before prescribing therapeutic recombinant human GH. We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency (GHD) using IGF-1 determination as a first step. METHODS: In 2000 and 2001, we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test (ITT), the reference test for the diagnosis of GHD, with concomitant Insulin-like growth factor-1 (IGF-1) determination, a marker of somatotropic function. Patients were classified as GHD (peak GH concentration<3 ng/ml with the ITT) or normal. SETTING: Monocenter prospective study in a tertiary referral center. RESULTS: GHD was diagnosed in 61 subjects. Using a ROC curve, a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5%. A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients, avoided 46/142 ITT and reduced the cost of diagnosis by 15%. CONCLUSION: We propose the use of a strategy consisting of IGF-1 determination followed, if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults.

Effect of dietary calcium intake on weight gain in type 2 diabetic patients following initiation of insulin therapy.

OBJECTIVES: This pilot study analyses weight gain in type 2 diabetic patients at initiation of insulin therapy, according to daily calcium intake. METHODS: Type 2 diabetic patients consecutively admitted for initiation of insulin therapy were studied between January and March 2004 in a monocenter study. Dietary intake was assessed by a 7-day food history before insulin treatment (initial visit) and 4 to 6 months later (final visit). RESULTS: Thirty-one patients were studied (18 males and 13 females; mean age 62+/-9 years, with diabetes duration 14+/-10 years). Weight significantly increased between initial and final visits (81.9+/-16.2 vs. 84.8+/-17.8 kg; P=0.0272). Median weight gain was 2.4 kg (IQR: -1.15 to +5.27 kg). Waist circumference increased by 2 cm (IQR: 0 to +4 cm). There was no difference between weight change and tertile of calcium intake adjusted on energy intake. We did not find any correlation between weight change and total calcium intake (Rho=0.186; P=0.3165) or dairy calcium intake (Rho=0191; P=0.3040). Similarly, we did not find any correlation between waist circumference change and total calcium intake (Rho=0.324; P=0.1205) or dairy calcium intake (Rho=0.285; P=0.0755). CONCLUSION: We found no relation between total or dairy calcium intake and weight change during initiation of insulin therapy in type 2 diabetic patients. Dietary calcium intake does probably not play a major role on insulin-induced body weight gain.

Determination of HbA1c concentrations in patients with acute myocardial infarction: comparison of the DCA 2000 device with the HPLC method.

BACKGROUND: Recent studies suggest that HbA1c is an important predictor of the glycometabolic state of patients admitted for acute myocardial infarction (AMI). OBJECTIVE: We aimed at comparing the results of HbA1c concentrations obtained by 2 different methods in patients with AMI. RESEARCH DESIGN AND METHODS: In a first study, HbA1c was measured in all patients consecutively hospitalized for AMI, during a 6 month period using the HPLC method and the DCA 2000 device in the biochemistry laboratory. In a second study, HbA1c measured by the DCA 2000 device in the intensive care unit was compared with HbA1c determined by HPLC in the biochemistry laboratory in a similar sample of patients. In patients without personal history of diabetes, those patients with HbA1c > 6.5% (HPLC method), were classified as possible diabetes. RESULTS: A total of 146 patients were included (119 males, 27 females; mean age: 63 +/- 15 years). Twenty-seven of the patients had a personal history of diabetes. HbA1c determined by 2 techniques were highly correlated (r = 0.939, P < 0.0001). The mean of the differences (Bland and Altman analysis) was 0.4 +/- 0.3%. Compared with the HPLC method, the sensitivity of DCA 2000 device for the detection of possible diabetes was 81.8 +/- 11.6 and the specificity was 99.1 +/- 0.9%. The diagnostic accuracy of DCA method was 97.5 +/- 1.4%. In the second study, the HbA1c concentrations of 21 additional subjects, determined in an intensive care unit, were not different from the first 21 patients of the first study. CONCLUSIONS: HbA1c can be effectively determined using the DCA 2000 device. This method is reliable and easy to be implemented in an intensive care unit.

Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas.

The presence of somatostatin receptors on TSH-secreting pituitary adenomas allows treatment of central hyperthyroidism with somatostatin analogs. Six women and 5 men (mean +/- SEM age, 43 +/- 3 yr) presented TSH-secreting pituitary adenomas (micro, n = 2; macro, n = 9). Seven patients had previously been treated with partial surgical removal (n = 6) and/or external radiation (n = 4) of their adenoma at least 1 yr before the study, whereas 4 patients had not been treated before somatostatin analog therapy. TSH, free T(4), and free T(3) levels were in the normal range during treatment with sc injections (n = 9) or continuous infusion (n = 2) of octreotide (280 +/- 25 microg/day). Mean thyroid hormone levels increased (P < 0.01) after the washout period (34 +/- 6 days). The patients received monthly im injections of 20 mg Octreotide-LAR. In patients with an elevated free T(4) level after 3 months (n = 1) the Octreotide-LAR dose was increased to 30 mg. After 3 months of Octreotide-LAR treatment, TSH, free T(4)/T(3), and alpha-subunit levels decreased, and 10 patients were euthyroid with normal free T(4) levels. These results remained at the same level over the next 3 months. There were no statistically significant differences in the TSH and free T(4) responses to sc octreotide or im Octreotide-LAR between previously untreated patients and patients who had undergone surgical resection and/or pituitary radiation before somatostatin analog treatment. During Octreotide-LAR treatment, minor digestive problems or moderate discomfort at the injection site, lasting less than 48 h, were reported in 6 and 5 patients, respectively. Gallbladder echographies did not reveal new gallstones during Octreotide-LAR treatment. In conclusion, this study shows that monthly im Octreotide-LAR is as effective as daily sc octreotide in controlling hyperthyroidism in patients with TSH-secreting pituitary adenomas, in both previously untreated patients and patients treated with surgery and/or pituitary radiotherapy. Octreotide-LAR is well tolerated, except for minor digestive problems or mild pain at the injection site. Therefore, Octreotide-LAR appears to be a useful therapeutic tool to facilitate medical treatment of TSH-secreting pituitary adenomas in patients who need long-term somatostatin analog therapy.

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Bilateral symptomatic adrenal myelolipoma.

Adrenal myelolipomas are rare, nonfunctioning benign tumors that consist of mature fat and bone-marrow elements. In the first half of this century, most adrenal myelolipomas were found incidentally at autopsy. These tumors are usually unilateral and asymptomatic. Today they are detected by ultrasonography, computerized tomography, or magnetic resonance imaging scan, done for other reasons. Adrenal myelolipomas can be diagnosed because of their characteristic images. Thus they are classified as "incidentalomas." We report the case of a 50-year-old man who had bilateral adrenal myelolipomas and whose right-side tumor was symptomatic. To our knowledge it is the third operated case reported in the literature. A right adrenalectomy was performed, keeping the asymptomatic left adrenal myelolipoma to preserve adrenal function.

Differential beta-cell response to glucose, glucagon, and arginine during progression to type I (insulin-dependent) diabetes mellitus.

Acute insulin responses to glucose (AIRG), glucagon (AIRGln), and arginine (AIRArg) were evaluated prospectively in nine subjects positive for islet-cell antibodies (ICAs) who later progressed to type I diabetes or impaired glucose tolerance (IGT) (progressors), 64 ICA-positive subjects at risk who did not develop type I diabetes, 365 ICA-negative relatives of diabetic patients who also remained free of the disease, and 89 control subjects. Seven progressors already had a low AIRG at entry into the study, and the other two became low responders 3 to 9 months before diabetes or IGT, with a progressive decline of AIRG over serial intravenous (IV) glucose tolerance tests. At entry into the study, the group of progressors displayed lower AIRG, AIRGln, and AIRArg than the other three groups (P<.001). However, AIRArg was less altered than AIRG. During the course of the prediabetic phase, there was a progressive decline in AIRG and AIRGln analyzed as a function either of time (P<.006) or of basal glycemia (P<.05), ie, two different ways of estimating worsening of the disease process. Conversely, there was no significant decrease in AIRArg with time or with increasing basal glycemia, so that AIRArg was not totally blunted in these prediabetic subjects even a few months before the onset of diabetes. The persistence of a substantial response to arginine, ie, higher than the fifth control percentile, even at a late stage, was confirmed in five of nine diabetic patients tested either at onset of the disease or during non-insulin-receiving remission. Whereas AIRG deteriorates during prediabetes, AIRArg appears to be less altered with time and increased basal glycemia, remaining substantial even at the onset of the disease. This reinforces the supposition that the prediabetic state may be associated with a glucose-specific beta-cell functional abnormality in addition to a decreasing beta-cell mass.

Retrospective study of 108 cases of botulism in Poitiers, France.

Botulism, a food-borne toxin-mediated disease caused by Clostridium botulinum is still a common disease, which is most frequent in the rural environment; 108 cases, 66 males and 42 females, average age 32 years, were recorded from 1965 to 1990 in the infectious disease department of the University Hospital of Poitiers (France). In 83% of patients, the food responsible was home-cured ham. Mean incubation time was 3.4 days; digestive symptoms were observed in 93% of cases, ocular symptoms in 92% and urinary tract dysfunction in 22%. A scale of severity was used to classify the patients into those suffering from severe (6), intermediate (50) and mild (52) forms of the disease. Botulinum toxin type B was found in 36 (52%) of 69 blood samples and in 41 (51%) of 81 samples of the suspected food. From 1965 to 1976, 44 patients were treated with both toxoid and heterologous equine serotherapy. Since 1976, 29 patients have been treated with guanidine hydrochloride (35 mg/kg daily) and 35 patients with guanidine hydrochloride plus heterologous serotherapy. All 108 patients recovered without any sequelae.

Prediction of major coronary events by coronary risk profile and silent myocardial ischaemia: prospective follow-up study of primary prevention in 72 diabetic patients.

UNLABELLED: The aim of this study was to examine the predictive value of coronary risk profile (CRP) for major coronary events in patients screened for silent myocardial ischemia (SMI). We studied 72 diabetic patients, aged 41 to 65 years, recruited consecutively at the Poitiers diabetes clinic. All patients had at least one cardiovascular risk factor associated with diabetes mellitus (type 1 diabetes duration > or =15 years, dyslipidaemia, smoking, hypertension, micro/macro-albuminuria). A structured questionnaire, physical examination and resting electrocardiogram provided no evidence of coronary heart disease. SMI was defined as positive exercise electrocardiogram and/or dipyridamole thallium myocardial scintigraphy. CRP was estimated using the Framingham equation adapted to the French population. We defined a high CRP value as annual CRP > or =1.5%. Major coronary events (MCE) were defined as myocardial infarction, ischaemic heart failure, unstable angina or sudden death. Twenty-one patients with type 1, and 51 with type 2 diabetes were followed up for 39+/-12 months: 30 women and 42 men, aged 55+/-7 years with diabetes duration of 16 +/- 11 years (mean +/- SD). SMI was detected in 8 patients. Major coronary events occurred in 8 patients, 2 of whom had SMI. High CRP was found in 18 patients, 3 of whom had MCE. CRP was significantly higher in those patients with a major coronary event (1.71 +/- 1.11 versus 1.03 +/- 0.56%; p=0.048), but not in those with SMI (1.19 +/- 0.72 vs 1.09 +/- 0.67%; p=0.654). In Kaplan-Meier survival analysis, a high CRP was associated with the risk of a major coronary event (log-rank=5.36; p=0.021), whereas SMI was not (log-rank=2.02; p=0.155). The cumulative incidence of MCE in those patients with high and low CRP was 8.08 (0.49-15.67) vs 2.15 (0.06-4.22) events per 100 patient year of follow-up, respectively. CONCLUSION: CRP had a good predictive value for major coronary events regardless the presence of SMI. Prevention should therefore be focused primarily on patients with high CRP, wether or not they have SMI.

Erythropoietin-dependent anaemia: a possible complication of diabetic neuropathy.

We report the case of a 52-year-old woman with long-term type 1 diabetes mellitus, complicated with proliferative retinopathy, autonomic neuropathy and microalbuminuria and moderate renal failure. A normochromic, normocytic are generative anaemia had been diagnosed for three years. Clinical and biological investigations for the aetiology of anaemia remained normal or negative. Anaemia was associated with a concentration of erythropoietin (EPO) in the normal range, but inappropriately low regarding anaemia. Treatment with recombinant EPO induced a rapid increase in haemoglobin level and improved the patient's quality of life. The role of diabetic neuropathy in the genesis of anaemia, in conjunction with a modest renal impairment is discussed.

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.

[Blink reflex and stimulus detection by the facial nerve in 21 diabetics. Testing before and after precise blood sugar normalization by the artificial pancreas]. / Réflexe de clignement et stimulodétection du nerf facial chez 21 diabétiques. Etude avant et après normalisation glycémique stricte par pancréas artificiel.

Study of the blink reflex and stimulodetection of the facial nerve in 21 diabetics with chronic hyperglycemia (HbA1C: 12.17 +/- 2.34%) shows normal or slightly prolonged R1, R2 and M latent periods in most cases. Forty-eight hour metabolic correction by artificial pancreas produces an overall improvement in the latent periods of the blink reflex, while the motor latent period of the facial nerve remained unchanged. The improvement, also observed in studies of limb responses, points towards a metabolic process directly related to the hyperglycemia.

[Prospective follow-up study of renal function in type 2 diabetes]. / Suivi prospectif de la fonction rénale des diabétiques de type 2.

Type 2 diabetes mellitus is the main cause of increase in patients suffering from end-stage renal failure in France. We performed an observational study of the change in renal function of type 2 diabetic patients, attending our diabetology clinic. Clinical and biological data were regularly entered in an informatic database (Pénélope, Poitiers University Hospital). We prospectively followed 351 type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months (extremes: 1-120). Renal function was graded in 4 stages according to plasma creatinine and urinary albumin excretion (UAE) determined by nephelometry on random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L), incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE = 200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L). Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal events as the change from one stage of nephropathy to a higher one. A total of 351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11 years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134 progressed in nephropathy. Progression of nephropathy was not related to the presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p = 0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%) had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic control is a risk factor for the progression in nephropathy of type 2 diabetic patients.

[Average level and variability of 24 hour blood pressure in the normotensive insulin-dependent diabetic patient]. / Niveau moyen et variabilité de la pression artérielle des 24 heures chez le diabétique insulinodépendant normotendu.

This prospective study was designed: 1. to determine both the mean level and the intrinsic variability of blood pressure (BP) and heart rate (HR) in normotensive patients with insulin-dependent diabetes mellitus (IDDM), by using a nonambulatory recorder; 2. to look for a relationship between these parameters and the indices of diabetic target-organ damage. The patient group consisted of 21 subjects with IDDM (6 females, 15 males), aged 19 to 70 years, who were normotensive according to WHO criteria. The duration of the diabetics ranged from 1.5 to 32 years. A control group of 17 age and sex-matched normal volunteers was also examined. Each subject underwent a 24 h non ambulatory BP recording, a 2-dimensional echocardiography and a pulsed doppler examination; furthermore, an index of autonomic nervous system dysfunction was established, as well as an index of microangiopathy. Twenty-four hour BP and HR mean levels appeared to be slightly higher in IDDM patients than in control group, but the difference was significant for night SBP and 24 h DBP only. No difference was found with regard to BP and HR absolute variabilities; the relative variability of night DBP was slightly lower in IDDM group (p less than 0.05). A loss of nocturnal decline in BP was noted in 2 control subjects and in 9 IDDM patients: 8 out of these IDDM patients had an autonomic dysfunction. An abnormal HR circadian pattern was seen in 1 control and in 2 IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

[Drug interactions in diabetic patients]. / Les interférences médicamenteuses chez le diabétique.

Many diabetic patients take medications which can interfere with the effect of insulin or oral antidiabetic agents. Glucocorticoid administration is not contraindicated in diabetic subjects, but it usually necessitates a pharmacotherapic adjustment. Most of the other potential diabetogenic drugs do not show evidence of any significant changes in glycaemic control in diabetic individuals; however, their prescription does require appropriate monitoring of blood glucose. Low dose combined oral contraceptives have little or no effect on blood glucose level; however, their prescription is not recommended in diabetic patients because of modifications in haemostasis and lipid metabolism. Oestrogen replacement therapy in post-menopausal women does not reduce glucose tolerance and it may reduce the risk of cardiovascular disease. Drug interactions which induce hypoglycaemia affect mostly non-insulin-dependent diabetic patients who take sulphonylureas. Combined insulin and sulphonylurea therapy is sometimes prescribed in poorly controlled type II diabetes. The efficacy of this combination is modest compared to insulin therapy alone. The influence of human insulin on symptoms and awareness of hypoglycaemia has been debated for several years. Today, the literature survey does not really support the hypothesis that the risk of severe hypoglycaemia is increased after transferring diabetic patients from animal insulin to human insulin. Many medications induce other side effects (e.g. orthostatic hypotension, hyperkaliemia, impotence...) in patients with diabetic complications.

[Pharmacokinetics of sulindac in aged patients presenting with inflammatory joint disease]. / Pharmacocinétique du sulindac chez des patients âgés présentant une pathologie articulaire inflammatoire.

The kinetic of sulindac and its two metabolites (sulfide and sulfone) was investigated in twelve elderly patients, following multiple oral dose administration of 400 mg/d. Data were compared to those obtained previously in ten healthy volunteers who received the same dosage regimen. Following multiple dose administration, accumulation ratios indicate that sulindac do not accumulate either in elderly patients (R = 1.35; R = AUC0-24 J8/AUC0-24 J1) or in healthy young subjects (R = 1.38; R = U0-24 J1). No significant modification of sulindac and sulfide kinetic parameters was observed. The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients (p less than 0.05). We conclude that there is no need to modify the dosage regimen of Arthrocine (400 mg once a day) in elderly patients.

[Transient loss of consciousness in an internal medicine unit. Study of the initial evaluation and medium-term outcome]. / Pertes de connaissance brèves dans un service de médecine interne. Etude du bilan initial et du devenir à moyen terme.

The authors report the results of a study concerning 90 patients admitted to an Internal Medicine Unit for transient loss of consciousness. The cause of this event was found in 74 cases (82%), including 73 where the initial evaluation had been simple, consisting of physical examination, electrolytogram, blood glucose level, electrocardiogram and test for postural hypotension. Patients and physicians reported different frequencies of recurrence (17 and 51% respectively) and complications (27 and 96% respectively). Recurrences were usually multiple and appeared soon after the initial event. A 4% mortality rate was recorded over 21 months, but only one death was due to a cardiovascular cause. No death was observed in the group of patients without initial aetiological diagnosis. Apart from cardiac syncopes, the consequences of transient loss of consciousness seem to be psychological rather than physical. A simple initial evaluation is often sufficient.

[Remission induced at the early stage of insulin-dependent diabetes: do predictive factors exist?]. / Les rémissions induites à la phase précoce du diabète insulinodépendant: existe-t-il des facteurs prédictifs?

The induction of a remission has been attempted in 28 patients with insulin-dependent diabetes of less than 3 months' duration by strictly normalizing glycemia either with a period of external artificial pancreas followed by continuous subcutaneous insulin infusion (22 patients) or with continuous subcutaneous insulin infusion alone (6 patients). HLA A, B and DR antigens were determined in every patient. Residual beta-cell function was evaluated by measuring C peptide and the ratio of C peptide to glycemia, and by testing the response to a glucagon stimulation before initiating and after withdrawing insulin treatment. Oral treatment with 15 mg glibenclamide and 840 mg metformin daily was administered when insulin had been stopped. A remission was obtained in 17 of the 28 cases. The likelihood of a remission was greater if: (1) the patient was older (mean age was 25.6 years in case of success and 16.6 Years in case of failure); (2) initial daily needs for insulin were smaller (0.88 v. 1.23 U/kg); and (3) stimulated secretion of C peptide was larger (0.22 v. 0.11 mmol/l).