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Fibroblast growth factor-21 (FGF-21) improves insulin sensitivity and lipid metabolism in obese or diabetic animal models and has been proposed as a potential therapeutic agent for treating T2DM, obesity, and their related complications. However, little is known about the changes of FGF21 levels in response to endogenous hyperinsulinemic hypoglycemia. To explore its relationship with parameters of glucose metabolism in patients with insulinoma, eleven subjects with pathological insulinoma and twenty-two healthy subjects were recruited for this study. Interestingly, we found that the serum FGF21 levels increased significantly in patients with insulinoma at baseline compared with the control group (381.36 ± 107.12 vs. 62.59 ± 10.48 pg/mL; P = 0.001). Furthermore, FGF21 was positively correlated with insulin (r = 0.80, P = 0.003) and proinsulin (r = 0.72, P = 0.012) in subjects with insulinoma. Multiple stepwise regression analysis showed that FGF21 was independently associated with insulin (β = 0.80, P = 0.003). In addition, FGF21 decreased significantly after surgery, and its change was still correlated positively with the changes in insulin (r = 0.61, P = 0.048) and proinsulin (r = 0.84, P = 0.001). These findings suggested that the serum FGF21 levels could be involved in a complex adaptive response to insulin secretion and glucose metabolism in humans. [ABSTRACT FROM AUTHOR]

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future. [ABSTRACT FROM AUTHOR]

Serum 1,5-anhydroglucitol (1,5-AG) levels can not only accurately reflect the mean blood glucose over the previous 1-2 weeks in diabetic patients but also offers the advantage of representing postprandial glucose. To evaluate the clinical significance of 1,5-AG in diabetes detection, especially when used in combination with fasting plasma glucose (FPG), a total of 3098 participants at high risk for diabetes (1467 men, 1631 women) were enrolled. A total of 1471 (47.5%) participants were diagnosed with diabetes, and the mean 1,5-AG level in the diabetic group was significantly lower than that in non-diabetic group [12.5 (7.8-17.5) μg/mL vs. 20.5 (15.3-26.4) μg/mL, P < 0.001]. The optimal cut-off point was 15.9 μg/mL, for which the sensitivity, specificity, and area under the curve (AUC) were 69.2%, 72.3%, and 0.781, respectively. For the combination of FPG and 1,5-AG, the sensitivity, specificity, and AUC improved to 82.5%, 83.5%, and 0.912, respectively. This method helped 75.8% of the participants avoid an oral glucose tolerance test (OGTT), reducing the need to carry out the OGTT by 43.9% compared to the use of the FPG criterion only. In conclusion, the addition of FPG to serum 1,5-AG improves the efficiency of diabetes screening in the Chinese population.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes. Susceptibility genes for type 2 diabetes may also impact the susceptibility of DR. This case-control study investigated the effects of 88 type 2 diabetes susceptibility loci on DR in a Chinese population with type 2 diabetes performed in two stages. In stage 1, 88 SNPs were genotyped in 1,251 patients with type 2 diabetes, and we found that ADAMTS9-AS2 rs4607103, WFS1 rs10010131, CDKAL1 rs7756992, VPS26A rs1802295 and IDE-KIF11-HHEX rs1111875 were significantly associated with DR. The association between CDKAL1 rs7756992 and DR remained significant after Bonferroni correction for multiple comparisons (corrected P = 0.0492). Then, the effect of rs7756992 on DR were analysed in two independent cohorts for replication in stage 2. Cohort (1) consisted of 380 patients with DR and 613 patients with diabetes for ≥5 years but without DR. Cohort (2) consisted of 545 patients with DR and 929 patients with diabetes for ≥5 years but without DR. A meta-analysis combining the results of stage 1 and 2 revealed a significant association between rs7756992 and DR, with the minor allele A conferring a lower risk of DR (OR 0.824, 95% CI 0.743-0.914, P = 2.46 × 10 -4 ).

Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30 and total cell death marker CK18 M65ED in monitoring the different stages of NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese subjects. Predictive performances for monitoring the different stages of NAFLD were assessed by logistic regression and receiver-operating characteristic (ROC) curves. We found baseline FGF21 but not CK18 level was an independent predictor for the development of simple steatosis. NAFLD patients who had remission during follow-up had significantly lower baseline M30 levels than those who sustained NAFLD (84.74U/L [53.26-135.79] vs. 118.47U/L [87.16-188.89], P = 0.012). M65ED was independently predictive of progressing to suspected non-alcoholic steatohepatitis (NASH) in NAFLD patients. These results suggest that FGF21 can be used for early identification of hepatic steatosis. On the other hand, CK18 including M30 and M65ED, are predictive of the prognosis of NAFLD patients. FGF21 and CK18 might play differential roles and have complementary value in non-invasive identification and monitoring the outcome of NAFLD patients.

The chloride/phosphate ratio (Cl/PO4) has been suggested to have a role in primary hyperparathyroidism (PHPT), but the associations between Cl/PO4 combined with ALP level and PHPT has not been well-studied. Our aim was to investigate the predictive value of combination Cl/PO4 with ALP for PHPT. A cross-sectional retrospective analysis was conducted to examine 172 patients diagnosed with PHPT categorized into two groups: normocalcaemic primary hyperparathyroidism (NPHPT) group and hypercalcaemia PHPT group. We found that Cl/PO4 levels and ALP levels in the NPHPT and hypercalcaemia PHPT group were both significantly higher than normal controls. Cl/PO4 and ALP levels were an independent risk factor for PHPT. Cl/PO4 combined with ALP increased the receiver-operating characteristic curves (ROC-AUC) and the diagnostic value in NPHPT and hypercalcaemia PHPT group (0.913; 95% CI, 0.744-1.000 and 0.932; 95% CI, 0.897-0.966, respectively), specificity of 92.8% and sensitivity of 98%. In conclusion, combination Cl/PO4 with ALP might be a low-cost, simple, available predictive marker of PHPT in Chinese individuals, particularly Chinese remote region where the method used to measure PTH cannot be done. Moreover, due to serum calcium level in NPHPT, Cl/PO4 combined with ALP level measurement have great potential to predict significant occurrence of NPHPT.

Previous studies have discussed the relationship between simple renal cysts (SRC) and serum uric acid level in healthy individuals. We performed a cross-sectional study to evaluate the association between serum uric acid level and fractional excretion of uric acid (FEUA) and simple renal cysts in males and postmenopausal females with type 2 diabetes. The overall prevalence of SRC was 18.1% in our population. SRC prevalence was significantly higher in hyperuricemic than normouricemic subjects (27.3% vs. 16.8%, P < 0.001). Subjects who overexcreted uric acid had a higher prevalence of SRC than underexcretors (total population: 21.6% vs. 16.3%; normouricemic subjects: 19.8% vs. 13.7%; hyperuricemic subjects: 50.0% vs. 22.7%, all P-values < 0.05). Hyperuricemia (odds ratio [OR] 1.824, 95% confidence interval [CI] 1.332-2.498, P < 0.001); FEUA (OR 1.046, 95% CI 1.002-1.091, P < 0.05); male gender (OR 1.922, 95% CI 1.489-2.480, P < 0.001); age (OR 1.049, 95% CI 1.035-1.064, P < 0.001); and albuminuria (OR 1.492, 95% CI 1.176-1.892, P < 0.01) were independent risk factors for SRC development. These findings suggested that hyperuricemia and high level of FEUA were both independent risk factors for SRC development in males and postmenopausal females with type 2 diabetes. Half of overproduction hyperuricemic patients had SRC.