C014 - Plasma amino acid pattern can be influenced by age and diabetes

Communications libres

Ann. Endocrinol.

été déjà montré que l’efflux du cholestérol cellulaire (cellules FU5AH) est altéré chez les patients diabétiques de type 2, nous avons voulu vérifier si, en présence d’une coronaropathie, cette altération serait modulée. Pour cela, trois groupes de sujets ont été comparés : témoins (T : n = 7), diabétiques (D : n = 9) et diabétiques cardiaques (DC : n = 9). Les résultats montrent que les patients DC ont une triglycéridémie élevée par rapport à celle des T et des D (respectivement : 2,6 ± 0,7 ; 1,4 ± 0,5 ; 2,0 ± 0,7 mmoles/l, p < 0.01). Le C-HDL est plus bas chez les patients DC quant à celui des T (p < 0,05) et des D (NS), alors que les concentrations des phospholipides-HDL restent comparables dans les trois groupes. La mesure de la capacité du sérum à promouvoir le cholestérol cellulaire montre que, comme attendu, les patients D ont un efflux significati-

vement moins important que celui des T (p < 0.05). Par contre, l’efflux chez les sujets DC est non significativement différent de celui des T (T : 28,4 ± 4,2 ; D : 22,1 ± 5,5 ; DC : 27,3 ± 5,7 %). Aucune corrélation n’a été trouvée entre le niveau de l’efflux du cholestérol et l’état glycémique (glycémie et HbA1c) ainsi que la composition des HDL. Ces résultats suggèrent que : 1) l’altération du l’efflux dans le diabète de type 2 est indépendant de l’équilibre glycémique ainsi que de la composition HDL en phospholipides ; 2) le rétablissement de l’efflux chez les patients DC à des valeurs comparables à celles des témoins pourrait être favorisé par leur hypertriglycéridémie générant des particules de prébéta-HDL, connues par leur pouvoir élevé à capter le cholestérol à partir des cellules périphériques.

EFFECTS OF CHOLINERGIC BLOCKADE BY PIRENZEPINE ON INSULIN AND GLUCOSE RESPONSE TO ORAL GLUCOSE IN OBESE PRE-MENOPAUSAL WOMEN (1)

(1)

C013

(1)

F. Vignati , O. Disoteo , G. Di Sacco (1) Divisione di Endocrinologia, Ospedale Niguarda, piazza Ospedale Maggiore 3 -20162- Milano Italia. e-mail : [email protected]

110

Parasympathetic nervous system is known to affect insulin secretion in animal and in humans. Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses in normal humans. We studied the effects of pirenzepine on plasma insulin and glucose responses to standard (75g) oral glucose tolerance test (OGTT) in 6 obese pre-menopausal women (BMI range=30,50-32,68Kg/m2, age range 28-35-years). Patients underwent, in random sequence after an overnight fast and on two separate occasions, OGTT alone or OGTT preceded by pirenzepine 100mg, 60 minutes before starting OGTT. Blood samples were collected at –30min and 0min and, subsequently, every 15 minutes for 2 hours. Results: The mean insulin response to OGTT (expressed as area under the curve, AUC) was significantly reduced after pirenzepine administration (insulin AUC=7297±3160mcU/ 120min vs 10913±3290 p<0.05). After pirenzepine insulin

levels were significantly reduced at time -30 (10.2±5mcU/ mL vs 14.8±6.2; p<0.01) and insulin and glucose levels were both significantly reduced at time 0’(11.8±4.9mcU/ mL vs 15.2±6.2; p<0.05 and 85.8±10mg/dL vs 91.5±13.7; p<0.02 respectively) in comparison to the control day. In two patients we also measured plasma glucagon-like peptide (GLP-1) levels and in both cases a reduced response of the hormone after OGTT was observed when the test was preceded by pirenzepine administration. Conclusions: The present study confirms that the cholinergic system plays a role in the exaggerated insulin secretion in obese subjects. Interestingly the reduction of insulin secretion induced by pirenzepine was not followed by worsening of glucose response to OGTT. This finding might be consistent with the existence of indirect mechanisms, probably involving GLP-1 secretion pathways. 479 — 23/01/04 — Federico1074855390.

PLASMA AMINO ACID PATTERN CAN BE INFLUENCED BY AGE AND DIABETES (1)

(2)

(2)

C014

(1)

G. Di Sacco , R. Accinni , C. Della Noce , F. Muratori (1) Divisione di Endocrinologia, Ospedale Niguarda, Milan, Italy. e-mail : [email protected] (2) Institute of Clinical Physiology, CNR Sezione di Milano, Niguarda Hospital, Milan, Italy.

It is well known that age and diabetes may affect protein metabolism, but few data are so far available on plasma amino acid pattern (AAP) in these conditions. The present study was performed to search for differences,

if any, in AAP in adult young and elderly subjects with or without diabetes. We measured, by HPLC, morning plasma amino acid pattern after an overnight fast, in 4 groups of subjects.

Vol. 65, n° 1, 2004

Group A: 7 normal adults (NA), mean age 38±7 yrs, mean BMI 22±1.8kg/m2. Group B: 5 obese adults with non insulin dependent diabetes (ANIDD), mean age 48±8, mean BMI 31±2.4. Group C: 9 elderly normal (EN) subjects, mean age 64±5, mean BMI 20±1. Group D: 6 elderly subjects with non insulin dependent diabetes (ENIDD), mean age 66±8 yrs, mean BMI 19.5±2. Results: Isoleucine levels were significantly increased in ENIDD, EN and ANIDD vs NA (63±11, 67±16, 77±7μmol/L respectively vs 45±10; p<0.02), whereas leucine levels were higher but not significantly in ENIDD and ANIDD. Valine levels were significantly higher in ENIDD in respect to NA (288±40 vs 215±44μmol/L; p<0.02). Cystine levels were significantly higher in ENIDD in respect to EN

Communications libres

and NA (55±25μmol/L vs 19±14 and 12±16; p<0.01). Glutamine levels were significantly higher in ENIDD in respect to all other groups (814±74μmol/L vs 483±100, 661±152, 502±56; p<0.02). Arginine levels were significantly lower in ENIDD than in NA (51±2μmol/L vs 79±24; p< 0.05). The present data show that plasma branched chain amino acids, cystine and glutamine levels may be influenced by age and diabetes. On considering the protective action of arginine on heart and the increased cardiovascular risk in diabetes, the finding of reduced levels of this amino acid in ENIDD group is of particular clinical interest and might suggest the need of further studies on arginine metabolism/availability in elderly diabetic patients.

WEIGHT LOSS AND IMPROVEMENT OF GLYCEMIC CONTROL IN DIABETIC OBESE PATIENTS TREATED WITH SIBUTRAMINE

C015

F. Vignati (1), O. Disoteo (1), G. Di Sacco (1) (1) Divisione di Endocrinologia, Ospedale Niguarda, Milano, Italia. e-mail : [email protected]

Diabetes mellitus type 2 (DM2) is strictly related to overweight and obesity. It’s demonstrated that a reduction in the body weight is useful to prevent the development of this pathology and to improve the glycemic control. In this study, after obtaining informed consent, we have instructed 14 obese patients with onset of DM2 (12 females and 2 males), to follow hypo caloric diet (1 200Kcal-1 600Kcal) and regular physical activity for 6 months. To improve diet adherence, during the first 4 months, sibutramine 10mg/die was prescribed. Subjects were followed up every month during sibutramine treatment and two months after sibutramine discontinuation. All patients well tolerated the drug. Patients showed a statically significant reduction (table 1) of body weight (p<0,001), of glycemia (P<0,001) and of glycated hemoglobin (HbA1c) (P<0,001). After drug withdrawal, patients continued

diet and regular physical activity, showing a good maintenance of glycemic levels even if body weight showed little increase. Our results confirm that body weight reduction is the first step in obese DM2 patients to obtained a good glycemic control. Intermittent use of obesity drugs may be proposed in those patients who showed weight regain when on diet and physical activity alone. Table 1

Body Weight (kg) 2

BMI (kg/m ) Glycemia (mg/dL) HbA1c

Basal

4 month

6 month

86,5 (±13,5)

73,1 (±12,3)

74,3 (±12,4)

33 (±2,3)

27,9 (±2,5)

28, 4 (±2,9)

181,8 (±34,1)

103,3 (±18,9)

113,8 (±30,8)

7,9 (±1,2)

5,9 (±0,5)

5,9 (±0,4)

111