GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

Novel ceruloplasmin gene mutation causing aceruloplasminemia with diabetes in a Chinese woman: a case report.

Hereditary aceruloplasminemia (ACP) is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin (CP) gene mutation and defective or absent CP function. In the present study, we report a case of ACP in a 34-year-old Chinese woman with diabetes, fatigue, anxiety, and progressive membrane loss with low hemoglobin associated with microcytosis. The fasting glucose level was 5.6-7.96 mmol/L. Postprandial blood glucose ranged from 6.8 to 9.6 mmol/L. The Stumvoll first-phase and second-phase insulin secretion disposition indices were very low, and the serum iron content was low, even though transferrin levels were normal. Moreover, the transferrin saturation was low (5%), and the ferritin level was extremely high, above 2,000 µg/L in the patient. Furthermore, her serum CP level was extremely low (<0.0183 g/L). Abdominal computed tomography (CT) examination showed moderate iron overload in the liver. Brain CT also showed a mildly increased density of the bilateral thalami and basal ganglia. Finally, gene analysis showed a rare homozygous mutation (c.146+1G>A) in the CP gene and was diagnosed with ACP. To date, less than 60 family cases of ACP have been reported worldwide, and only two cases of ACP have been reported in China. Here, we report a case of ACP accompanied by diabetes with a novel mutation of the CP gene, which suggests that increased awareness should be highlighted in this disorder as diabetes is an important typical symptom.

Factors associated with lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus: A case-control study.

Early detection and treatment of lower extremity atherosclerotic disease (LEAD), and controlling its risk factors are critical in preventing amputation and death in diabetic patients. This study aimed to investigate the factors associated with LEAD in Chinese diabetic patients.In this case-control study, patients with type 2 diabetes mellitus (T2DM) (N = 1289) were divided into 2 groups according to the ultrasonic Doppler examination: with (LEAD+, n = 737) and without (LEAD-, n = 552) LEAD. In subgroup analysis, the LEAD+ group was divided based on the diameter of lower-extremity arteries: LEAD+A (1%-49% reduction) and LEAD+B (≥50% reduction). Clinical and demographic data of patients were analyzed.Compared with the LEAD- group, serum creatinine levels were significantly increased (P < 0.001), whereas glomerular filtration rate (GFR) was significantly decreased (P < 0.001) in the LEAD+ group. Multivariate analysis results showed that GFR (odds ratio [OR] 0.991, 95% confidence interval [CI] 0.986-0.997, P = 0.003), diabetes duration (OR 1.055, 95% CI 1.026-1.084, P < 0.001), age (OR 1.123, 95% CI 1.104-1.142, P < 0.001), and uric acid (OR 1.002, 95% CI 1.000-1.004, P = 0.031) were independently associated with LEAD in patients with T2DM. Furthermore, multivariate analysis showed that age (OR 1.078, 95% CI 1.048-1.109, P < 0.001) and GFR (OR 0.985, 95% CI 0.975-0.994, P = 0.002) were independently associated with the severity of arterial lesions in patients with T2DM and LEAD.The risk factors of LEAD in Chinese patients with T2DM include age, course of disease, uric acid, and GFR. Patients with T2DM, high uric acid levels, and declined GFR could be listed in the high-risk group for LEAD.