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Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.

Background Previous studies have reported the high prevalence of occult SpA in IBD patients. Objectives To investigate the presence of clinical and ultrasound peripheral entheseal abnormalities in a consecutive series of IBD patients. Methods 61 IBD consecutive patients [26 Crohn9s disease (CD) and 35 ulcerative colitis (UC), M/F 32/29, mean age 35.7+12.4 years, mean disease duration 57+93 months] entered the study. Gastroenterological examination consisted of the determination of bowel involvement, extraintestinal manifestations, MAYO and CDAI score. A complete rheumatological examination which included 66 peripheral join count, MASES and Leeds entheseal evaluation, BASDAI, BASFI and evaluation of spine mobility was done at study entry. ESR and CRP were evaluated at study entry. US examination was done using an Esaote MyLabClass, 18–6MHz linear multifrequence transducer both in gary scale and with PD. The following enthesis were separately studied clinical and US by two rheumatologist unaware of the other evaluation: lateral elbow epicondyle, distal quadricipital insertion at the patella, proximal and distal patellar tendon insertions, Achilles tendon an plantar fascia insertion at the calcaneous. Knee and ankle joints were evaluated for synovial hyertrophy, PD signal and fluid. Extensor and flexor tendons of the foot and ankle were evalutaed for the presence of tendon sheat fluid, synovial hypertrophy and PD signal. Quadriceps, patellar, Achille and plantar fascia entheses were scored according to the 0–36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. Results 29/61 (47.5%) patients had at leat one entheseal alteration at clinical examination and 56 (91.8%) presented almost one US entheseal abnormality with a mean 3.05±1.7 number of abnormal enthesis /patient. The mean MASEI was 11±9 and the mean GUESS 5.8±3.9 with 56/61 patients with value >1. The US evidence of enthesitis was higer in CD with ileo-colon localization as compared to ileo or colon involvement (100% vs 89% and 50%, p=0.03). Patients with disease duration >12 months have significantly grater number of cronical (2.48±1.5vs3.7±1.7, p=0.01) and acute enthseal alteration (3.0±1.3vs1.9±1.3,p=0.01) as compared with patients with disease duration Conclusions US entheseal abnormalities are present in a high percentage of IBD patients. US enthesopathy is associated with longer disease duration and topographical localization of gut disease. Disclosure of Interest None declared

The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.