S. Baillot-Rudoni

Circulating Apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycaemic control

Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism.

Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes

Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I (apoA-I) with 13C leucine was performed at the end of each treatment period. Moreover, a similar kinetic study was carried out in eight nondiabetic normolipidemic controls. Rosuvastatin significantly reduced plasma LDL-cholesterol (−51%), triglycerides (TGs) (−38%), and HDL-TG (−23%). HDL-apoA-I fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 ± 0.06 vs. 0.32 ± 0.07 pool/day, P = 0.011), leading to an increase in plasma HDL-apoA-I residence time (4.21 ± 1.02 vs. 3.30 ± 0.73 day, P = 0.011). Treatment with rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate values in diabetic patients on rosuvastatin were not different from those found in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR and restores to normal the increased HDL turnover observed in type 2 diabetes. These kinetic modifications may have beneficial effects by increasing HDL plasma residence time.

Real-time continuous glucose monitoring (CGM) integrated into the treatment of type 1 diabetes: Consensus of experts from SFD, EVADIAC and SFE

P.-Y. Benhamou, B. Catargi, B. Delenne, B. Guerci, H. Hanaire, N. Jeandidier, R. Leroy, L. Meyer, A. Penfornis, R.-P. Radermecker, E. Renard, S. Baillot-Rudoni, J.-P. Riveline, P. Schaepelynck, A. Sola-Gazagnes, V. Sulmont, N. Tubiana-Rufi, D. Durain, I. Mantovani Coordination: A. Sola-Gazagnes, J.-P. Riveline Societe Francophone du Diabete (SFD), Societe Francaise d’Endocrinologie (SFE) and EVADIAC group (EVAluation dans le Diabete des Implants ACtifs)

Endogenous chronic hyperinsulinemia does not increase the production rate of VLDL apolipoprotein B: proof from a kinetic study in patients with insulinoma.

OBJECTIVE It is currently suggested that chronic hyperinsulinemia is a causal factor for the increased production rate of very-low-density lipoproteins (VLDL) associated with metabolic syndrome. However, the involvement of hyperinsulinemia independently of the other abnormalities also observed in metabolic syndrome has never been proven in humans. DESIGN We used patients with insulinoma showing hyperinsulinemia but no insulin resistance as a model and conducted an apolipoprotein B (apoB) kinetic study in seven patients with insulinoma, seven insulin-resistant (IR) obese patients, and 12 controls. RESULTS Insulinemia was higher in patients with insulinoma or IR than in controls both in the fasting state [2.4-fold (P = 0.039) and 3.1-fold (P = 0.003), respectively] and in the fed state [3.5-fold (P = 0.006) and 2.6-fold (P = 0.05), respectively]. Patients with insulinoma were not IR (steady state plasma glucose = 80 ± 46 mg/dl, a value lower than in IR subjects (231 ± 75, P = 0.0013). In the fed state, triglyceridemia and VLDL apoB pool size were higher in IR subjects compared with controls and patients with insulinoma [208 ± 56 vs. 89 ± 30 mg/dl (P < 0.0001) and 96 ± 42 mg/dl (P < 0.0001), respectively, for triglyceridemia and 3.56 ± 0.60 vs. 1.85 ± 0.88 mg/kg (P = 0.004) and 2.32 ± 1.79 (P = 0.052) mg/kg for VLDL apoB pool size]. The production rate of VLDL apoB in subjects with insulinoma was not significantly different from that in controls (14.56 ± 7.43 vs. 16.40 ± 7.70 mg/kg · d) but was higher in IR subjects compared with these two groups [25.66 ± 12.84 mg/kg · d (P = 0.046 and 0.035, respectively)]. CONCLUSION Chronic endogenous hyperinsulinemia is not directly responsible for any increase in the production rate of VLDL apoB in humans.

Chronic Hyperinsulinemia Does Not Increase the Production Rate of High-Density Lipoprotein Apolipoprotein AI Evidence From a Kinetic Study in Patients With Insulinoma

Objective—In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome. Approach and Results—We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× (P<0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× (P<0.05) higher in the fed state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3±5.4 versus 59.6±7.7 mg·kg−1; P<0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30±0.07 versus 0.20±0.04 pool·d−1; P<0.0001 and 14.6±1.5 versus 11.5±1.9 mg·kg−1·d−1; P<0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3±8.6 versus 49.3±5.4 mg·kg−1; P=0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20±0.06 versus 0.30±0.07 pool·d−1; P<0.01 and 11.1±1.6 versus 14.6±1.5 mg·kg−1·d−1; P<0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance. Conclusions—Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.

P129 Sclérodermie cutanée et diabètes : une association non fortuite potentiellement dangereuse

Introduction La sclerodermie cutanee ou scleroedeme de Buschke peut etre associee a la maladie diabetique. Sa physiopathologie et son lien avec le diabete ne sont pas clairement identifies. A partir des donnees de patients diabetiques atteints de cette dermatose, nous avons examine certaines de leurs caracteristiques afin de preciser les elements plus souvent associes au scleroedeme de Buschke. Patients et methodes Nous avons inventorie de maniere descriptive 7 patients diabetiques atteints de sclerodermie cutanee suivis dans notre service. Resultats Voir le tableau 1 ci-dessous. Discussion La sclerodermie cutanee peut etre associee a tous les types de diabete : type 1, type 2 ou mitochondrial pour le sujet 1. Par ailleurs, nos donnees confirment celles des quelques cas souvent uniques rapportes dans la litterature ou les malades, plus souvent des femmes, obeses, ont un diabete ancien multicomplique, desequilibre (sauf les 2 sujets masculins 6 et 7). De plus, 4/7 patients souffrent de coronaropathie, plus particulierement en cas de diabete type 2 ou d’origine genetique. Conclusion Le scleroedeme de Buchke peut etre associe a tous les types de diabete ; il est retrouve chez des sujets obeses avec un profil d’insulinoresistance. Tableau 1. 1 2 3 4 5 6 7 Sexe F F F F F M M Type de diabete mitochondrial 1 2 1 2 2 2 Anciennete/diabete (ans) 35 36 17 33 38 20 11 Microangiopathie (nombre) 2 2 3 2 2 3 2 Coronaropathie (oui/non) Oui Non Non Non Oui Oui Oui IMC (kg/m 2 ) 29 28 39 32 40 40 36 HbA1c ( % 4,3 a 6,1) 8,2 9,3 10,3 10,3 9,2 6,4 6,5 Dose d’insuline (U/j) 100 90 95 95 54 82 44