[Type 2 diabetes complications]. / Complications du diabète de type 2.

People with type 2 diabetes are at increased risk of many complications, which are mainly due to complex and interconnected mechanisms such as hyperglycemia, insulino-resistance, low-grade inflammation and accelerated atherogenesis. Cardi-cerebrovascular disease are frequently associated to type 2 diabetes and may become life threatening, particularly coronaropathy, stroke and heart failure. Their clinical picture are sometimes atypical and silencious for a long time. Type 2 diabetes must be considered as an independent cardiovascular risk factor. Nephropathy is frequent in type 2 diabetes but has a mixed origin. Now it is the highest cause of end-stage renal disease. Better metabolic and blood pressure control and an improved management of microalbuminuria are able to slowdown the course of the disease. Retinopathy which is paradoxically slightly progressive must however be screened and treated in these rather old patients which are globally at high ophthalmologic risk. Diabetic foot is a severe complication secondary to microangiopathy, microangiopathy and neuropathy. It may be considered as a super-complication of several complications. Its screening must be done on a routine basis. Some cancer may be considered as an emerging complication of type 2 diabetes as well as cognitive decline, sleep apnea syndrome, mood disorders and bone metabolism impairments. Most of the type 2 diabetes complications may be prevented by a strategy combining a systematic screening and multi-interventional therapies.

Impact of altered alveolar volume on the diffusing capacity of the lung for carbon monoxide in obesity.

BACKGROUND: Studies on the diffusing capacity of the lung for carbon monoxide (DL(CO)) in obese patients are conflicting, some studies showing increased DL(CO) and others unaltered or reduced values in these subjects. OBJECTIVES: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (K(CO)) to DL(CO), and calculate DL(CO) values adjusted for VA. METHODS: We measured body mass index (BMI), waist circumference (WC), spirometry and DL(CO) in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. RESULTS: Using conventional reference values, mean DL(CO) and VA were lower (-6%, p < 0.05, and -13%, p < 0.001, respectively), and K(CO) was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas K(CO) increased with increasing BMI and WC in the obese group. Patients with lower DL(CO) had low K(CO) in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high K(CO), resulted in higher DL(CO). The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DL(CO) for VA. CONCLUSIONS: Using conventional reference equations, our obese patients show slightly lower mean DL(CO,) lower mean VA and higher mean K(CO) than controls, but with a large range of DL(CO) values and patterns. Adjusting DL(CO) for VA suggests that low lung volumes are the main cause of low DL(CO) and high K(CO) values in obese patients.

[Radical complications of obesity]. / Conséquences pathologiques de l'obésité.

Obesity increases overall morbidity mainly by the increased mass of fat tissues and by the hyperproduction of pro-inflammatory molecules by the abdominal tissue. Coronary artery disease, metabolic syndrome or diabetes mellitus are the main complications linked to the inflammatory low-grade syndrome whereas arthritis is linked to the adipocytes mass. Many other complications are associated with obesity: steato-hepatitis, glomerulo-sclerosis, digestive diseases such as gallstones, hypofertility, psychosocial dysfunction and depression and certain cancers. Obesity is also a risk factor for pregnancy and surgery. Most of these complications are reversible after a substantial weight loss.

[Nutrition approaches to prevent chronic disease]. / Prévention nutritionnelle des maladies chroniques.

Chronic diseases such as obesity, diabetes, macrovascular disease including coronaropathy and stroke, osteoporosis and various cancer have, in one way or another, food and nutritional determinants and may be considered as nutritionally or environmental-related diseases. There is a growing literature indicating that specific dietary constituents or diet are able to influence the development and the outcome of chronic disease. Long term prospective clinical trials are yet locking to confirm on evidences-based medicine criteria the correlation described between food and disease. However animal as well as epidemiological data suggest that high energy density and low nutrient density which characterized diet in developed countries are the main targets that must be fight. On the basis of current researches, Mediterranean diet seemed to be the best and the more applicable diet in order to have optimal health. Such a diet low in calories and saturated fat and high in fruit and vegetables and in whole grain should become a key composant for reduce the oxidant, inflammatory, atherogenic, mutagenic and hyperinsulinic status and then prevent or delay chronic diseases.

Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients.

BACKGROUND: Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice. AIM: The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD. METHODS: In a multicentre study carried out from 2001-2004 in France, 96 participating physicians were randomized into a "trained" group, which included 398 "educated" patients, and a "non-trained" group, which included 242 "non-educated" patients. Educated patients received six hospital-based educational sessions, four collective and two individual. Framingham score, smoking, lipid levels, glycaemia, blood pressure, dietary intake and drug compliance, as well as quality of life, were evaluated at baseline (M0) and 6 months (M6). The primary endpoint of the study was the efficacy of the PEGASE program in reducing global CVD risk in high-risk patients. RESULTS: The Framingham score was calculated for 473 patients. The Framingham score improved significantly at M6 vs M0 in the educated group (13.0 +/- 8.21 vs 13.6 +/- 8.48, d = -0.658, p = 0.016), but not in the non-educated group (12.5 +/- 8.19 vs 12.4 +/- 7.81, d = +0.064, p = 0.836); the mean change between the two groups did not reach significance. Quality of life, LDL-c level and diet scores improved in the "educated" group only. CONCLUSIONS: The PEGASE education program improved risk factors for CVD, although global assessment by Framingham score was not significantly different between groups. This program, aimed at meeting needs and expectations of patients and physicians, was easily implemented in all hospital centres.

Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway?

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.

Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years.

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking.

OBJECTIVE: The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects. DESIGN: A prospective multicenter study. PATIENTS: Three hundred and seventy-five clinically euthyroid subjects. METHODS: We used five different C(T) immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies. RESULTS: Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C(T) levels and age or body mass index (BMI) (primarily in men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C(T) values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion In clinical practice (and after having excluded the usual causes of raised C(T) levels), the interpretation of C(T) assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.

Diet and physical activity profiles in French preadolescents.

Dietary patterns have been identified in adults, but less is known about children and adolescents. For the first time, we have investigated lifestyle patterns combining diet and physical activity in 12-year-old French preadolescents and examined their association with sociodemographic factors. Physical activity, sedentary activities and dietary habits were assessed by questionnaires given to 2724 students in 2001. Family income tax and parents' educational level, as indicators of socio-economic status, and the size of the residence commune were obtained from parents. After adjusting for socio-economic status, physical activity was positively associated with a consumption of fruit/vegetables/fruit juice on more than four occasions in the previous 24 h (P<0.001). Sedentary activities were positively associated with the consumption of French fries or potato chips (P<0.001), with sweetened drink as the most usual drink (P<0.001) and with nibbling while watching television (P<0.001), and inversely associated with a high consumption of fruit/vegetables/fruit juice (P=0.04). Multiple correspondence analysis identified two independent axes and specific combinations of behaviour: one axis characterised by sedentary activity, sweetened drink as the most usual drink, the consumption of French fries or potato chips and nibbling while watching television; a second one associating physical activity and the consumption of fruit/vegetables/fruit juice. Both socio-economic proxies were associated with the former axis (P<0.001). The size of the residence commune was associated with the latter (P<0.1). Combinations of diet and physical activity habits were identified in adolescents, indicating that prevention programmes targeting both behaviours may have an enhanced outcome.

Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents.

BACKGROUND: Together with adiposity, plasma fatty acid (FA) composition can modulate the development of the metabolic syndrome (MS). OBJECTIVE: Our aim was to investigate the relations of FA composition in plasma phospholipids and cholesterol esters (CEs) with weight status, MS, and inflammation in adolescents. DESIGN: Plasma FA composition was measured by gas-liquid chromatography in 120 (60 normal-weight and 60 overweight) 12-y-old adolescents. We also measured the presence of MS, insulin resistance with the homeostasis model assessment, and interleukin 6 and C-reactive protein concentrations in the adolescents. RESULTS: MS was present in 25% of the overweight adolescents but in none of the normal-weight adolescents. Compared with overweight adolescents, normal-weight adolescents had lower saturated FAs (SFAs) in both phospholipids (P < 0.001) and CEs (P < 0.01) and higher docosahexaenoic acid in phospholipids (P < 0.001). In overweight subjects, FA composition was associated with MS features independent of body fat. The odds ratios of MS for a 0.1 increase in the ratio of polyunsaturated FAs (PUFA) to SFAs (PUFA:SFA) were 0.91 in phospholipids (P = 0.03) and 0.90 in CEs (P = 0.06). In phospholipids, PUFA:SFA and linoleic acid were associated positively with HDL cholesterol (P < 0.01 for both). PUFA:SFA in phospholipids and CEs were associated inversely with interleukin 6 (P < 0.05 for both). Eicosapentaenoic acid in phospholipids (P = 0.06) and CEs (P < 0.05) and linolenic acid in CEs (P < 0.05) were inversely related to C-reactive protein. These relations remained significant after adjustment for the waist-to-hip ratio. No significant relation between FA composition and the homeostasis model assessment was observed. CONCLUSIONS: Plasma FA composition is associated with weight status in healthy adolescents. High intake of long-chain PUFAs, especially n-3 PUFAs, may protect obese subjects against MS and low-grade inflammation as early as adolescence.

Interactions between traditional regional determinants and socio-economic status on dietary patterns in a sample of French men.

The aim of the present study was to assess the respective contributions of regional and socio-economic factors to dietary pattern. We used the data from the final MONICA (MONItoring of trends and determinants in Cardiovascular disease) population survey conducted in the three French centres in 1995-7 among a representative sample of 976 men aged 45-64 years. Dietary intake was assessed using a 3-d record method. Dietary patterns were identified by a factor analysis, based on fifteen food items. An analysis of variance was then used to study their relationship with regional and socio-economic determinants. Two major dietary patterns were identified: a 'Western diet', characterized by high intakes of sugar and sweets, grains, butter, added fats, eggs, potatoes and cheese; a 'prudent diet', mainly distinguished by high intakes of fruit, vegetables, olive oil and fish and low intakes of alcohol, high-fat meat and potatoes. Strong associations were mostly observed with the 'prudent diet' pattern, with a significant relationship with region, educational and income-tax levels, leisure-time physical activity and smoking status. There was also a statistically significant interaction between region and educational level (P=0.05), and between region and income-tax level (P=0.03), indicating that the influence of socio-economic factors is different among regions. In conclusion, these results indicate large regional and socio-economic differences in the dietary patterns of this French male population. When considering the 'prudent diet' pattern, they also suggest that traditional regional influences may now be overcome by socio-economic determinants.

Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease.

OBJECTIVES: To verify the cut-off values and to determine the clinical sensitivity of antithyroglobulin (TgAb) determinations using our routine RIA and the new electrochemiluminescent Elecsys assay. DESIGN AND METHODS: We used the DYNOtest anti-Tgn manual RIA from BRAHMS and the new automated Elecsys electrochemiluminescent immunoassay from Roche Diagnostics. We analyzed 452 sera from the following subjects: 193 euthyroid controls, 163 with treated and untreated autoimmune thyroid diseases (AITD) (108 Graves' disease and 55 thyroiditis), 50 with differentiated thyroid carcinoma, 13 with nonautoimmune thyroid disease and 33 with type 1 diabetes mellitus. RESULTS: As expected, using the proposed thresholds (BRAHMS 60 kIU/L, Elecsys 115 kIU/L) approximately 6% of the control subjects were positive for TgAb with both methods. In AITD patients, the sensitivity of TgAb determination was significantly higher with the Elecsys assay (51.5%) than with the BRAHMS assay (39.3%). This difference was not observed in the other patient groups. CONCLUSION: The Elecsys assay can be preferred not only because it is automated and rapid, but also because of its better clinical performance in AITD patients.

Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized, double-blind, placebo-controlled trial by the French Thyroid Research Group.

The efficacy of suppressing TSH secretion with levothyroxine (L-T(4)) in reducing solitary thyroid nodule growth is still controversial. In this prospective multicenter, randomized, double-blind, placebo-controlled trial, 123 patients with a single palpable benign nodule were included and randomly allocated to an 18-month treatment with L-T(4) or placebo. Individual dose was adjusted to allow a serum TSH level below 0.3 mIU/liter. Clinical and ultrasonographic nodule characteristics were assessed before treatment and 3, 6, 12, and 18 months thereafter. The largest mean nodule size assessed on palpation and largest volume, assessed by ultrasonography, decreased in the L-T(4) group and increased slightly in the placebo group [size, -3.5 +/- 7 mm vs. +0.5 +/- 6 mm (P = 0.006); volume, -0.36 +/- 1.71 ml vs. +0.62 +/- 3.67 ml (P = 0.01), respectively]. The proportion of clinically relevant volume reduction (> or =50%) rose significantly in the L-T(4) group [26.6% vs. 16.9% (P = 0.04)]. The proportion of patients with a reduced number of infraclinical additional nodules was significantly higher in the L-T(4) group [9.4% vs. 0 (P = 0.04)]. It is concluded from this study that suppressive L-T(4) therapy is effective in reducing solitary thyroid nodule volume and improving infraclinical extranodular changes.

Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature.

BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Bénichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05). CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality.

The ectopic expression of the gastric inhibitory polypeptide receptor is frequent in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia, but rare in unilateral tumors.

Control of cortisol secretion by the abnormal expression of the gastric inhibitory polypeptide receptor (GIP-R) have been observed in some rare cases of ACTH-independent, food-dependent Cushing's syndrome (FD-ACS) due to adrenal adenoma (AA) or bilateral macronodular hyperplasia (AIMAH). This study was performed to determine the prevalence of GIP-R ectopic expression in ACS and its correlation with fasting cortisol levels. GIP-R expression was studied by RT-PCR in 30 unilateral adrenal tumors [16 AA and 14 adrenocortical cancer (AC)] and 8 AIMAH tissues. Fasting and postprandial cortisol levels were assayed, respectively, at 0800 and 1200 h in AA, AC, and AIMAH, and 1 h after a morning standard meal in 6 AIMAH patients. Similar expression of 2 GIP-R isoforms was observed in 1 of 16 AA, 0 of 14 AC, and 4 of 8 AIMAH as well as in the 4 insulinomas used as positive controls. In vitro study of the GIP-R-expressing AA showed stimulation of cortisol secretion and cAMP production by GIP. The fasting 0800-h plasma cortisol level was above 276 nmol/liter in all patients except 1 AA case and 1 AIMAH case, both of whom expressed GIP-R. In the 3 additional AIMAH cases that expressed the GIP-R, fasting plasma cortisol levels were above 276 nmol/liter. This study demonstrates that ectopic expression of GIP-R is rare in AA and is usually associated with the low fasting plasma cortisol levels that characterize FD-ACS. In contrast, GIP-R expression is frequent in AIMAH and might not always be associated with a low fasting plasma cortisol level. This suggests that maintenance of hypercortisolemia in GIP-R- expressing AIMAH does not always depend solely on GIP-R, and that simultaneous abnormal expression of other membrane receptors might be present. The expression of GIP-R could not be observed during malignant transformation of the adrenal cortex. This study highlighted the major role of cAMP alterations secondary to GIP-R ectopic expression in the pathophysiology of AIMAH and in some rare cases of well differentiated benign adrenocortical tumors.

Nonchemotherapy drug-induced agranulocytosis in elderly patients: the effects of granulocyte colony-stimulating factor.

PURPOSE: Elderly patients with nonchemotherapy drug-induced agranulocytosis present commonly with severe infections, and have a mortality of at least 20%. We studied whether granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor that shortens the duration of neutropenia, is useful in these patients. SUBJECTS AND METHODS: We studied 54 patients > or =65 years of age who had drug-induced agranulocytosis, some of whom had been treated with G-CSF. We determined the times until hematologic recovery (defined as a neutrophil count >1.5 x 10(9)/L), tolerance of G-CSF, and clinical outcomes. RESULTS: Of the 54 patients, 20 received G-CSF. Two patients who had not been treated with G-CSF died of uncontrolled septic shock and extensive pneumonia. The mean (+/- SD) time until hematologic recovery was significantly less in patients treated with G-CSF (6.6 +/- 3.9 days vs. 8.8 +/- 4.9 days, P <0.04). Compliance with G-CSF therapy was good; only mild flu-like symptoms and transient bone pain were reported in 12 patients. CONCLUSION: Our findings suggest that G-CSF therapy may be beneficial in the management of drug-induced agranulocytosis in elderly patients.