Lixisenatide in type 1 diabetes: A randomised control trial of the effect of lixisenatide on post-meal glucose excursions and glucagon in type 1 diabetes patients.

AIMS: The GLP1 agonist lixisenatide is glucagonostatic and reduces post-prandial blood glucose (PPBG) in type 2 diabetes. This study investigates its impact in type 1 diabetes (T1D). METHODS: In a blinded, crossover trial, 25 patients with T1D were randomised to 4 weeks adjunctive treatment with lixisenatide (L) or placebo (P), with a 4-week washout period. The primary outcome was percentage of 3 hours PPBG in target (4-10 mmol/L) assessed by CGM before and after treatment. Participants also underwent post-treatment standardised mixed meal test (MMT, n = 25) and hyperinsulinaemic hypoglycaemic clamp (n = 15). RESULTS: PPBG CGM readings in target were similar between L vs P (Mean % ± SE, breakfast 45.4 ± 6.0 vs 44.3 ± 6.0, P = .48, lunch 45.5 ± 5.8 vs 50.6 ± 5.3, P = .27 and dinner 43.0 ± 6.7 vs 47.7 ± 5.6, P = .30). HbA1C was similar between L vs P (64.7 ± 1.6 vs 64.1 ± 1.6 mmol/mol, P = .30). Prandial insulin fell after lixisenatide (dose change -0.7 ± 0.6 vs +2.4 ± 0.7 units/d, P = .004), but basal insulin dose was similar between groups. The post-MMT glucose area under the curve (AUC) was lower with L than P (392.0 ± 167.7 vs 628.1 ± 132.5 mmol/L × min, P < .001), as was the corresponding glucagon AUC (140.0 ± 110.0 vs 304.2 ± 148.2 nmol/L × min, P < .001). Glucagon and counter-regulatory hormone values at a blood glucose of 2.4 mmol/L during the hypoglycaemic clamp were similar between L and P. CONCLUSION: In T1D, PPBG values were not altered by adjunctive lixisenatide although prandial insulin dose fell. Glucose and glucagon level during an MMT were significantly lower after lixisenatide, without affecting counter-regulatory response during hypoglycaemia.

Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes.

The antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment crossover design to ASA 100 mg/day, 200 mg/day, or 100 mg twice daily for 2-week treatment periods. Platelet function tests compared were as follows: light transmission aggregometry (LTA)-0.5 mg/mL of arachidonic acid (AA) and 10 µM adenosine diphosphate (ADP); multiplate whole blood aggregometry (WBA)-0.5 mM AA and 6.5 µM ADP; platelet function analyzer (PFA)-100™-collagen and ADP (CADP) and collagen and epinephrine (CEPI); VerifyNow™-ASA; and urinary 11-dehydro-thromboxane B2 (TxB2) and serum TxB2. All cyclo-oxygenase (COX-1)-dependent tests and some COX-1-independent tests (PFA-CEPI, LTA-ADP) demonstrated significant reductions in platelet reactivity with all ASA doses. Two COX-1-independent tests (WBA-ADP and PFA-CADP) showed no overall reduction in platelet reactivity. Overall classifications for detecting all ASA doses, compared to baseline, were as follows: very good-LTA-AA (k = 0.95) and VerifyNow™-ASA (k = 0.85); good-serum TxB2 (k = 0.79); moderate-LTA-ADP (k = 0.59), PFA-100™-CEPI (k = 0.56), urinary TxB2 (k = 0.55), WBA-AA (k = 0.47); and poor-PFA-100™-CADP (k = -0.02) and WBA-ADP (k = -0.07). No significant kappa statistic differences were seen for each test for each ASA dose. Correlations for each test with serum TxB2 measurements were as follows: very good-VerifyNow™-ASA (k = 0.81, R2 = 0.56) and LTA-AA (k = 0.85, R2 = 0.65); good-PFA-100TM-CEPI (k = 0.62, R2 = 0.30); moderate-urinary TxB2 (k = 0.57, R2 = 0.51) and LTA-ADP (k = 0.47, R2 = 0.56); fair-WBA-AA (k = 0.31, R2 = 0.31); and poor-PFA-100™-CADP (k = 0.04, R2 = 0.003) and WBA-ADP (k = -0.04, R2 = 0.0005). The platelet function tests we assessed were not equally effective in measuring the antiplatelet effect of ASA and correlated poorly amongst themselves, but COX-1-dependent tests performed better than non-COX-1-dependent tests.

Evaluation of a self-administered oral glucose tolerance test.

OBJECTIVE: To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS: Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS: The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS: Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.