Dataset Information

Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.

ABSTRACT:

Aim

The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1) receptor (GLP1R) gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM) is unclear.

Methods

Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then received a combination therapy with injections of the GLP-1 analogue, exenatide, for another 3 days. All 13 exons and intron-exon boundaries of the GLP1R gene were amplified to investigate the association.

Results

The short tandem repeat at 8GA/7GA (rs5875654) had complete linkage disequilibrium (LD, with r2 = 1) with single nucleotide polymorphism (SNP) rs761386. Quantitative trait loci analysis of GLP1R gene variation with clinical response of GLP1 analogue showed the missense rs3765467 and rs761386 significantly associated with changes in the standard deviation of plasma glucose (SDPG(baseline) - SDPG(treatment with GLP-1 analogue)) (P = 0.041 and 0.019, resp.). The reported P values became insignificant after multiple testing adjustments.

Conclusion

The variable response to the GLP-1 analogue was not statistically correlated with polymorphisms of the GLP1R gene in patients with poorly controlled type 2 DM.

SUBMITTER: Lin CH

PROVIDER: S-EPMC4345081 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.

Lin Chia-Hung CH Lee Yun-Shien YS Huang Yu-Yao YY Hsieh Sheng-Hwu SH Chen Zih-Syuan ZS Tsai Chi-Neu CN

Journal of diabetes research 20150215

<h4>Aim</h4>The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1) receptor (GLP1R) gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM) is unclear.<h4>Methods</h4>Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then recei ...[more]

PMID: 25785276

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Project description:PurposeAerobic fitness, as reflected by maximal oxygen (O2) uptake (VO2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence O2 supply including O2 delivery and release to active muscles during maximal exercise.MethodsTwo groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA1c <7.0%; T1D-I, n = 12 with inadequate glycemic control, HbA1c >8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine VO2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O2 transport and factors able to shift the oxyhemoglobin dissociation curve.ResultsArterial O2 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, VO2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A.ConclusionsPoorly controlled patients displayed lower VO2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.

Project description:Background & aimsAcute hyperglycemia delays gastric emptying in patients with diabetes. However, it is not clear whether improved control of glycemia affects gastric emptying in these patients. We investigated whether overnight and short-term (6 mo) improvements in control of glycemia affect gastric emptying.MethodsWe studied 30 patients with poorly controlled type 2 diabetes (level of glycosylated hemoglobin, >9%). We measured gastric emptying using the [(13)C]-Spirulina platensis breath test on the patients' first visit (visit 1), after overnight administration of insulin or saline, 1 week later (visit 2), and 6 months after intensive therapy for diabetes. We also measured fasting and postprandial plasma levels of C-peptide, glucagon-like peptide 1, and amylin, as well as autonomic functions.ResultsAt visit 1, gastric emptying was normal in 10 patients, delayed in 14, and accelerated in 6; 6 patients had gastrointestinal symptoms; vagal dysfunction was associated with delayed gastric emptying (P < .05). Higher fasting blood levels of glucose were associated with shorter half-times of gastric emptying (thalf) at visits 1 (r = -0.46; P = .01) and 2 (r = -0.43; P = .02). Although blood levels of glucose were lower after administration of insulin (132 ± 7 mg/dL) than saline (211 ± 15 mg/dL; P = .0002), gastric emptying thalf was not lower after administration of insulin, compared with saline. After 6 months of intensive therapy, levels of glycosylated hemoglobin decreased from 10.6% ± 0.3% to 9% ± 0.4% (P = .0003), but gastric emptying thalf did not change (92 ± 8 min before, 92 ± 7 min after). Gastric emptying did not correlate with plasma levels of glucagon-like peptide 1 and amylin.ConclusionsTwo-thirds of patients with poorly controlled type 2 diabetes have mostly asymptomatic yet abnormal gastric emptying. Higher fasting blood levels of glucose are associated with faster gastric emptying. Overnight and sustained (6 mo) improvements in glycemic control do not affect gastric emptying.

Dataset Information

Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.

Aim

Methods

Results

Conclusion

Publications

Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.

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