Addition of low-dose liraglutide to insulin therapy is useful for glycaemic control during the peri-operative period: effect of glucagon-like peptide-1 receptor agonist therapy on glycaemic control in patients undergoing cardiac surgery (GLOLIA study).

AIM: To test the hypothesis that the addition of a glucagon-like peptide-1 receptor agonist that can decrease glucose levels without increasing the hypoglycaemia risk will achieve appropriate glycaemic control during the peri-operative period. METHODS: We studied 70 people with Type 2 diabetes who underwent elective cardiac surgery. Participants were randomized to either an insulin-alone or an insulin plus liraglutide 0.6 mg/day group. We evaluated average M values, which indicated the proximity index of the target glucose level from day 1 to day 10. RESULTS: The average M value in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (liraglutide plus insulin 5.8 vs insulin-alone 12.3; P < 0.001). The frequency of insulin dose modification in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (odds ratio 0.19, 95% CI 0.08-0.49; P < 0.001). The frequency of hypoglycaemia in the liraglutide plus insulin group tended to be lower than that in the insulin-alone group (odds ratio 0.57, 95% CI 0.15-2.23; P = 0.21). CONCLUSIONS: The results of this study showed that the addition of low-dose liraglutide to insulin achieved lower M values than insulin alone, suggesting that the addition of low-dose liraglutide may achieve better glycaemic control during the peri-operative period. (Clinical trials registry no.: UMIN 000008003).

Effect of basal insulin therapy on vascular endothelial function and adipokine profiles in people with Type 2 diabetes.

AIM: To compare the effects of the basal insulin analogues glargine and detemir on endothelial function and adipocytokine levels in people with Type 2 diabetes. METHODS: We studied 32 people with Type 2 diabetes whose blood glucose control was unsatisfactory while receiving only oral hypoglycaemic drugs. Participants were randomized to either insulin glargine or detemir for 24 weeks and then crossed over to the other treatment without a washout period. Flow-mediated vasodilatation, adipocytokine levels (plasminogen activator inhibitor-1 and leptin/adiponectin ratio), and fasting ghrelin levels were monitored. RESULTS: HbA1c levels were significantly decreased by both basal insulin therapies. Body weight was significantly increased by glargine but not by detemir. The proportion of flow-mediated vasodilatation was significantly increased by detemir but not glargine (glargine: from 5.17 ± 0.69 to 5.94 ± 0.83%; detemir: from 4.89 ± 0.78 to 7.92 ± 0.69%). Plasminogen activator inhibitor-1 level was significantly decreased by only detemir (glargine: from 16.4 ± 1.8 to 17.3 ± 2.1; detemir: from 19.2 ± 2.8 to 16.0 ± 1.6 ng/ml). The leptin/adiponectin ratio was significantly increased only by glargine. Acyl ghrelin level was significantly decreased by glargine but not detemir. CONCLUSIONS: These results suggest that the effect on endothelial function and adipocytokine profiles may differ between glargine and detemir in people with diabetes (Trial registration ID: UMIN000004973).

Impact of B-type natriuretic peptide (BNP) on development of atrial fibrillation in people with Type 2 diabetes.

AIMS: To examine if a simple biomarker can identify people with diabetes who are at high risk of atrial fibrillation. METHODS: A retrospective cohort study was conducted at a single centre in people with Type 2 diabetes referred to our department between January 2000 and December 2007. In 517 consecutive people without any history, signs or symptoms of atrial fibrillation at baseline, the association between baseline B-type natriuretic peptide level and future atrial fibrillation incidence was examined, with adjustments for other potentially confounding factors. RESULTS: A total of 28 people were diagnosed with new-onset atrial fibrillation during a median 6-year follow-up. When people were categorized into three groups according to B-type natriuretic peptide clinical thresholds (20 and 100 pg/ml), hazard ratios for the development of atrial fibrillation in the middle and highest B-type natriuretic peptide groups were 2.8 and 9.4, respectively, compared with the lowest B-type natriuretic peptide group. Time-dependent receiver-operating curve analysis identified a threshold for B-type natriuretic peptide to detect atrial fibrillation development of 52.8 pg/ml (sensitivity 75.2%, specificity 68.8%). The B-type natriuretic peptide predictive value was independent of and similar to that of left atrial size and ventricular dimension. CONCLUSION: In people with Type 2 diabetes, high baseline B-type natriuretic peptide levels were significantly associated with future atrial fibrillation development.

Germline deletion and a somatic mutation of the PRKAR1A gene in a Carney complex-related pituitary adenoma.

OBJECTIVE: The objective was to assess involvement of loss of the PRKAR1A gene encoding a type 1α regulatory subunit of cAMP-dependent protein kinase A located on 17q24 in a Carney complex (CNC)-related pituitary adenoma. DESIGN: We investigated aberrations of the PRKAR1A gene in a CNC patient with a GH-producing pituitary adenoma, whose family has three other members with probable CNC. METHODS: A gene mutation was identified by a standard DNA sequencing method based on PCR. DNA copy number was measured to evaluate allelic loss on 17q24 by quantitative PCR. The breakpoints of deletion were determined by cloning a rearranged region in the deleted allele. RESULTS: A PRKAR1A mutation of c.751_758del8 (p.S251LfsX16) was found in genomic DNA obtained from a pituitary adenoma, but not leukocytes from the patient. Reduced DNA copy number at loci including the PRKAR1A gene on 17q24 was detected in both the tumor and leukocytes, suggesting a deletion at the loci at the germline level. The deletion size was determined to be ∼ 0.5 Mb and this large deletion was also found in two other family members. CONCLUSION: This is the first case showing a CNC-related pituitary adenoma with the combination of somatic mutation and a large inherited deletion of the PRKAR1A gene. Biallelic inactivation of PRKAR1A appears to be necessary for the development of CNC-related pituitary adenoma.

Low-dose metformin improves hyperglycaemia related to myotonic dystrophy.

BACKGROUND: One of the clinical features of myotonic dystrophy is insulin resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity. CASE REPORT: A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA(1c) 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA(1c) was decreased to 7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA(1c) was maintained (7.5%). CONCLUSION: It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients.