Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with diabetes: a case-control study.

Pancreatic cancer is a highly lethal malignancy. CA19-9 is a well-known marker for diagnosis of pancreatic cancer, but the serum CA19-9 level is reported to be elevated in patients with poorly controlled diabetes. This study evaluated the sensitivity, specificity, and cut-off value of serum CA19-9 for detection of pancreatic cancer in patients with diabetes. A case-control study of 236 patients was performed. The case group was selected from diabetic patients with pancreatic cancer, while one control was selected for each case from among diabetic patients without pancreatic cancer during the same period. The case group (n = 118) and the control group (n = 118) were matched for age, sex, and pancreatic cancer risk factors. Receiver operating characteristic (ROC) curves were plotted to determine the serum CA19-9 level that predicted pancreatic cancer. Then the sensitivity and specificity of CA19-9 were calculated for the threshold value. There were no significant differences of age, sex, BMI, smoking, alcohol intake, and HbA1c between the case and control groups. According to ROC analysis, a serum CA19-9 level of 75 U/mL had the maximum sensitivity and specificity for separating diabetic patients with or without pancreatic cancer. Using this cut-off value, the sensitivity and specificity of CA19-9 for pancreatic cancer was 69.5% and 98.2%, respectively, while the area under the ROC curve was 0.875 [95%CI: 0.826-0.924]. We propose that a serum CA19-9 level of 75 U/mL should be used as the cut-off value when screening patients with diabetes for pancreatic cancer.

Short-term change of carotid intima-media thickness after treatment of hyperglycemia in patients with diabetes: a cross-sectional study.

BACKGROUND: The carotid artery intima-media thickness (CIMT) has been used as a predictor of cardiovascular events, but it remains unclear whether CIMT can change over the short term. We evaluated changes of CIMT in patients with diabetes during admission to hospital for 2 weeks. METHODS: A total of 279 inpatients with diabetes aged 61 ± 14 years were recruited. They were on treatment with insulin and/or oral agents, excluding drugs that influence the fluid balance and hemodynamics. CIMT was measured on the day after admission and on the day before discharge, and the association of ΔCIMT (calculated by subtracting the baseline value from that on the day before discharge) with clinical factors was evaluated. RESULTS: Based on the reported annual increase of CIMT (0.04 mm/year), the patients were divided into three groups, in which CIMT increased [I: ΔCIMT ≥ 0.04 mm, n = 64, ΔCIMT = 0.077 ± 0.048 (mean ± SD)], CIMT decreased (D: ΔCIMT ≤ -0.04 mm, n = 51, ΔCIMT = -0.090 ± 0.086), or CIMT was unchanged (N: -0.04 mm < ΔCIMT < 0.04 mm, n = 164, ΔCIMT = 0.002 ± 0.022). Binary logistic regression analysis showed that baseline CIMT and hemoglobin (Hb) were positively correlated, while Hb on the day before discharge was negatively correlated, with a decrease of CIMT. In contrast, baseline HbA1c and Hb were negatively correlated, while Hb on the day before discharge was positively correlated, with an increase of CIMT. CONCLUSIONS: CIMT may show plasticity in patients with diabetes and can change even after short-term treatment of hyperglycemia for 2 weeks.

Effect of sitagliptin on intrahepatic lipid content and body fat in patients with type 2 diabetes.

AIMS: To evaluate the effect of the DPP-4 inhibitor sitagliptin on intrahepatic lipid (IHL) content and body fat in overweight Japanese patients with type 2 diabetes. METHODS: A prospective, 24-week, single-center, open-label comparative study enrolled 20 Japanese patients with type 2 diabetes (male: 11, female: 9) with a BMI≥25 kg/m(2) or fatty liver. Subjects were randomly assigned to receive treatment with sitagliptin (25 mg titrated up to 50 mg: S) or glimepiride (0.5 mg titrated up to 1 mg: G). After starting each treatment, IHL and total fat mass were evaluated by (1)H-magnetic resonance spectroscopy ((1)H-MRS) and dual energy X-ray absorptiometry (DEXA), respectively at baseline and at 12 weeks and 24 weeks. RESULTS: After 24 weeks, HbA1c levels showed a similar significant decrease in both groups from 7.2 (7.0, 7.5) to 6.6 (6.4, 6.8)%, (54 (53, 56) to 48(47, 49) mmol/mol) with S and 7.3(6.8, 7.4) to 6.6 (6.3, 6.7)%, (55 (51, 56) to 48 (46, 49) mmol/mol) with G, median (interquartile range), p<0.05 vs. baseline, with no significant differences between the two groups. The IHL and total body fat mass were decreased in S group from 24.5(18.9, 36.6) to 20.5 (14.6, 28.5)% (p=0.009) and 22.5 (20.6, 33.7) to 21.6 (19.7, 32.4)kg (p=0.028), respectively, but not in G group. CONCLUSIONS: Our findings indicate that sitagliptin and glimepiride achieved similar glycemic control, but only sitagliptin reduced IHL and total body fat (UMIN: 000013356).

In Silico Analysis Identification of a Novel Germ-Line VHL Mutation in a Patient of Malignant Pheochromocytoma.

OBJECTIVE: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor syndrome caused by a VHL gene mutation. Here we report a novel mutation of VHL in a patient diagnosed with malignant pheochromocytoma at the age of 17. METHODS: A 17-year-old female was referred for paroxysmal supraventricular tachycardia and anemia. She was diagnosed with a left adrenal pheochromocytoma based on biochemical and imaging studies. A left adrenalectomy was performed. Six months after surgery, metastatic lesions were suspected in the lung. The histopathologic findings of thoracoscopic lung biopsy specimens confirmed metastasis of the malignant pheochromocytoma. RESULTS: Genetic analysis of VHL showed a novel missense mutation at codon 194 (V194G) in exon 3. This mutation was inherited from the paternal allele, and a loss of heterozygosity was noted in 3 of the patient's distinct tumors. Two independent in silico analyses suggested that this amino acid substitution was pathogenic. CONCLUSION: We identified a novel missense mutation of VHL in a young patient with malignant pheochromocytoma.

Comparison of the hypoglycemic effect of sitagliptin versus the combination of mitiglinide and voglibose in drug-naïve Japanese patients with type 2 diabetes.

OBJECTIVE: The postprandial glucose (PPG) level is reduced by α-GIs, glinides and DPP4Is through different pharmacological actions. The aim of this study was to compare the effect of sitagliptin (S) versus that of the combination of mitiglinide and voglibose (M+V) on markers of glycemic control. RESEARCH DESIGN AND METHODS: A randomized cross-over trial was performed in 20 patients with drug-naïve type 2 diabetes. The patients were randomized to receive S (50 mg/day) or M+V (1 tablet 3 times daily). Treatment was continued for 8 weeks, after which they were switched to the other regimen and treated for another 8 weeks. At baseline, after the first regimen, and after the second regimen, a meal test was performed. MAIN OUTCOME MEASURES: The markers of glycemic control were examined. RESULTS: Reduction of glucose excursion was significantly greater with M+V than with S. HbA1c did not change with either regimen. However, 1,5-anhydroglucitol showed a significant increase from baseline with both regimens (7.9 ± 4.3 µg/ml at baseline vs. 10.6 ± 5.5 with S, p < 0.05 and 15.1 ± 6.2 with M+V, p < 0.01). Compared with baseline, glycoalbumin was significantly reduced by M+V, but not S (19.6 ± 2.9% at baseline vs. 17.3 ± 3.8% with M+V, p < 0.05). CONCLUSION: M+V achieved better control of PPG excursion than S.