Hb Phnom Penh Showing Falsely High or Reasonable HbA1c Values Depending on the Type of High-performance Liquid Chromatography System.

We herein report a 50-year-old Chinese woman with Hb Phnom Penh (α117Phe-Ile-α118Thr) showing high or reasonable HbA1c values depending on the type of high-performance liquid chromatography (HPLC) system. A high HbA1c value of 7.5% (HPLC assay: G9) and a reasonable HbA1c value of 5.2% (assay unknown) were observed. Therefore, the patient was refereed to our hospital; the oral glucose tolerance test showed normal glucose tolerance. The HbA1c values measured by an enzymatic assay, immunoassay, and affinity assay, as well as most HPLC assays were within the reference range, whereas those measured by the Tosoh HPLC systems were high.

Isolated Adrenocorticotropic Hormone Deficiency and Severe Hypercalcemia After Destructive Thyroiditis in a Patient on Nivolumab Therapy With a Malignant Melanoma.

We describe a 58-year-old man with a malignant melanoma metastasis to the liver. After initiation of nivolumab therapy, he developed destructive thyroiditis and subsequently simultaneous isolated adrenocorticotropic hormone (ACTH) deficiency and severe hypercalcemia. Although isolated ACTH deficiency and hypercalcemia due to nivolumab therapy are both rare occurrences, these conditions can often cause a severe clinical course accompanied by a disturbance of consciousness. Therefore, clinicians should pay attention to these possible side effects of nivolumab if the patients have clinical symptoms, such as fatigue and a disturbance of consciousness.

Effect of canagliflozin on circulating active GLP-1 levels in patients with type 2 diabetes: a randomized trial.

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

Serum Betatrophin Levels and Clinical Features in Patients With Poorly Controlled Type 2 Diabetes.

BACKGROUND: Betatrophin is a hormone mainly secreted by the liver that influences lipid metabolisms. The main purposes of this study were to investigate the effect of canagliflozin (a sodium glucose transporter 2 inhibitor) on circulating betatrophin levels, and to investigate the correlation of various markers associated with glucose and lipid metabolisms with betatrophin in patients with poorly controlled type 2 diabetes. METHODS: Patients were randomly divided into a control group (n = 15) and a canagliflozin-treated group (n = 15). After hospitalization, the canagliflozin-treated group took 100 mg/day of canagliflozin for 3 days. Blood tests were performed at baseline and after 3 days of treatment. RESULTS: Canagliflozin treatment for 3 days did not significantly change fasting and postprandial serum betatrophin levels. On the other hand, betatrophin levels had a significant positive correlation with hemoglobin A1c, fasting plasma glucose, and high-density lipoprotein cholesterol levels at baseline. CONCLUSIONS: The current study suggests that short-term treatment by canagliflozin does not influence circulating betatrophin levels, and that betatrophin is positively associated with markers of glycemic control and high-density lipoprotein cholesterol in patients with poorly controlled type 2 diabetes.

Long-Term Effect of Alogliptin on Glycemic Control in Japanese Patients With Type 2 Diabetes: A 3.5-Year Observational Study.

BACKGROUND: The goal of the current study was to investigate the long-term effects (after 3 years or more) of alogliptin on glycemic control in Japanese patients with type 2 diabetes. METHODS: We retrospectively studied the effect of alogliptin on glycemic control in the patients with type 2 diabetes who had participated in our previous 3-month study and who continued to take alogliptin for at least 36 months. RESULTS: The mean duration of alogliptin treatment was 42.8 ± 2.2 months. In all 39 patients, a significant reduction in hemoglobin A1c (HbA1c) levels was noted between the baseline and final visit: 7.8±0.6% to 7.2±1.0% (P = 0.0001). A significant reduction in HbA1c levels was found in a subgroup of patients who did not change their anti-diabetic drugs or did decrease the dose of their sulfonylureas (SUs) or did change to a lower strength repaglinide (n = 32): 7.7±0.6% to 7.2±1.0% (P = 0.0005). A significant decrease in low-density lipoprotein cholesterol (LDL-C) levels was observed in all of the patients that had LDL-C levels determined (P = 0.0406) (n = 37), and in a subgroup of patients who had not taken either statins, fibrates, or pioglitazone, or who had taken one or more of these drugs but the doses were not changed during the observation period (P = 0.0250) (n = 27). CONCLUSION: The current study found that alogliptin performed well for glycemic control when evaluated by HbA1c levels in a long-term observation period exceeding 3 years in Japanese patients with type 2 diabetes. Alogliptin may also decrease circulating LDL-C levels with long-term use.

Circulating SerpinB1 levels and clinical features in patients with type 2 diabetes.

OBJECTIVE: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic ß cells, and may decrease insulin resistance. RESEARCH DESIGN AND METHODS: The study included 30 patients with type 2 diabetes hospitalized for glycemic control and 10 control subjects. RESULTS: SerpinB1 levels were significantly higher in patients with type 2 diabetes, compared with that in heathy control subjects (10.01±3.59 vs 5.69±1.64 ng/mL, p<0.0001). Serum SerpinB1 levels had a significant negative correlation with low-density lipoprotein cholesterol (LDL-C) (p=0.0123). Serum SerpinB1 levels had a significant positive association or trend toward a positive association with age and with hemoglobin A1c (HbA1c), and significant negative association with LDL-C levels in some multiple regression analysis models. Patients treated with statins had a tendency toward higher serum SerpinB1 levels, compared with those patients not treated with statins. During a 3-day observation period both with and without canagliflozin treatment, the serum SerpinB1 levels did not change. CONCLUSIONS: Serum SerpinB1 levels are elevated in patients with type 2 diabetes compared with that in healthy subjects and are negatively correlated with serum LDL-C.

Alterations of plant sterols, lathosterol, oxidative stress and inflammatory markers after the combination therapy of ezetimibe and statin drugs in type 2 diabetic patients.

UNLABELLED: The elevation of serum plant sterols in addition to serum LDL-cholesterol (LDL-C) is one of the important risk factors for coronary heart disease. We investigated how to alterations of serum hepatic synthesised cholesterol and plant sterols levels, clinical markers for inflammation and oxidative stress after combination therapy with ezetimibe, an inhibitor of cholesterol transporter in the small intestinal colon, and statin drugs in type 2 diabetic patients. Studies were conducted in 28 patients with type 2 diabetes mellitus complicated with dyslipidemia. Patients were divided into 3 groups as follows: the 1st group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with mild statin drug (MS+E group), and the 2nd group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with strong statin drug (SS+E group), and then the 3rd group is 14 patients treated with 10mg ezetimibe alone without pretreatment with any statin drugs (naïve E group). In addition to various metabolic markers, serum plant sterols such as sitosterol and campesterol, and hepatic synthesised cholesterol such as lathosterol were measured by the gas liquid chromatography. Serum highly sensitive CRP (hsCRP) as an inflammation marker, and then malonyldealdehyde (MDA) and carbonyl-modified protein (CMP) as an oxidative stress were assayed by the conventional method, respectively. Fasting plasma glucose and serum glucosylated HbA1c (JDS value) did not show any significant changes after administration of ezetimibe in whole groups. Serum LDL-C was reduced significantly and serum triglyceride exhibited a tendency of reduction in whole groups. Serum sitosterol and campesterol were decreased significantly, while serum lathosterol was increased significantly or markedly in whole patients and also in each group. There were no significant changes in serum hsCRP in whole groups. Both serum MDA and CMP revealed significant or marked reductions in each group. CONCLUSIONS: The present investigation suggests that the combination therapy of the ezetimibe and statin drugs is potential to remarkably reduce serum LDL-C, plant sterols, MDA and CMP, and therefore might lead to prevent atherosclerosis.

Effect of combination therapy with alogliptin and lansoprazole on glycemic control in patients with type 2 diabetes.

The main purpose of the current study was to investigate the effect of a combination of alogliptin [a dipeptydil peptidase (DPP)-4 inhibitor] and lansoprazole [a proton pump inhibitor (PPI)] compared with alogliptin mono-therapy on glycemic control in patients with type 2 diabetes. This study was a multicenter randomized open-label study. One hundred type 2 diabetic patients were randomly assigned to either the alogliptin with lansoprazole group or the alogliptin mono-therapy group. After 3 months of treatment, the changes in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), serum gastrin, homeostasis model assessment (HOMA)-ß, and HOMA-insulin resistance (IR) were evaluated. A significant decrease in HbA1c and FPG, and a significant increase in HOMA-ß were observed in both groups (all with P <0.0001). However, there were no significant differences in changes in HbA1c, FPG, or HOMA-ß before and after therapy between the combination and alogliptin mono-therapy group (P =0.2945, P =0.1901, P =0.3042, respectively). There was a significant elevation of serum gastrin in the combination group compared with the alogliptin mono-therapy group (P =0.0004). This study showed that, although combination therapy with alogliptin and lansoprazole more effectively elevated serum gastrin levels compared with alogliptin mono-therapy, the effect of the combination therapy on glycemic control was equal to that of alogliptin mono-therapy during a 3-month study period.

Oxidative stress and antioxidative potency are closely associated with diabetic retinopathy and nephropathy in patients with type 2 diabetes.

OBJECTIVE: To examine involvement of oxidative stress in the pathogenesis and vascular complications of diabetes. METHODS: This cross sectional study was conducted at the Joint Laboratory Office (JLO), Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan from April 2010 to December 2011. Fasting glucose, glycosylated hemoglobin (HbA1c), serum lipids, urinary albumin excretion (UAE), ankle brachial index and pulse wave velocity were measured in 51 patients with type 2 diabetes and 20 healthy controls. The fundus oculi and Achilles` tendon reflex were also examined in the patients. Oxidative stress was measured by a reactive oxygen metabolites (ROM) test and antioxidant potency was evaluated by a biological antioxidant potential (BAP) test in the Free Radical Analytical System (FRAS)-4. Superoxide dismutase (SOD) activity was assayed using electron spin resonance (ESR). RESULTS: Diabetic patients tended to have increased ROM compared with healthy subjects, and ROM showed a marked increase with progression of diabetic retinopathy. A significant reduction of BAP was found in patients who were smokers, and BAP was significantly negatively correlated with UAE (p=0.029). Serum SOD activity significantly decreased with progression of diabetic retinopathy (p=0.017). CONCLUSION: The FRAS-4 measurements showed that increased oxidative stress and decreased antioxidative potency are linked to deteriorated blood glucose control, heavy smoking, and progression of retinopathy and nephropathy in patients with type 2 diabetes.

Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea.

Dipeptidyl peptidase 4 (DPP-4) inhibitors is a new class of antihyperglycemic agents that is now available for the treatment of type 2 diabetes. We investigated the relationship between the baseline serum level of soluble CD 26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over 24 weeks in patients who had type 2 diabetes inadequately controlled by metformin and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. All patients were given 50 mg/day of sitagliptin and were followed at monthly intervals for 24 weeks. Treatment with sitagliptin decreased significantly hemoglobin A1c (HbA1c) from 7.91 ± 1.08% at baseline to 6.96 ± 1.18% at 8 weeks, 7.04 ± 0.77% at 16 weeks, and 7.08 ± 0.80% at 24 weeks. The baseline serum level of sCD26 was correlated positively with HbA1c at both 16 weeks and 24 weeks. Furthermore, the serum sCD26 level at baseline was also correlated positively with the changes from baseline of HbA1c at 16 and 24 weeks (r = 0.318, P = 0.0296 and r = 0.516, P = 0.0003, respectively). In a multivariate logistic regression model that explained 56.1% (R(2) = 0.561) of the variation of the changes from baseline of HbA1c at 24 weeks, the baseline HbA1c (ß = -0.638, P < 0.001) and serum sCD26 (ß = 0.357, P = 0.041) were independent determinants of the change of HbA1c at 24 weeks. In conclusions, a higher serum level of sCD26 is associated with a worse response to sitagliptin in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea therapy.

Comparison of effects of insulin aspart three times a day versus insulin detemir once a day on oxidative stress in patients with type 2 diabetes.

The main purpose of this study was to investigate whether treatment with long-acting insulin once a day or short-acting insulin three times before each meal daily has a stronger antioxidative effect in patients with type 2 diabetes. These patients had not been treated previously with insulin and were hospitalized for initiation of glycemic control by insulin injection. The patients (n=43) were assigned consecutively and alternately to a group treated with insulin aspart injection three times daily just before each meal and a group treated with insulin detemir injection once daily before bedtime. The results showed that insulin aspart three times a day produced a greater improvement in plasma glucose, and particularly in mean postprandial plasma glucose, compared with insulin detemir once a day (p = 0.0006 for comparison of changes between the two insulin treatments). The amount of insulin needed to approach the target levels of plasma glucose was larger in the insulin aspart group (26.0 ± 10.7 U/day vs. 13.7 ± 4.9 U/day; p < 0.0001). However, only insulin detemir significantly decreased oxidative stress evaluated based on the level of urinary 8-iso-prostaglandin F2α (p = 0.0079), although the mechanisms are not fully evident.

Relationship of body fat weight and body fat ratio determined by bioelectric impedance to serum adipocytokines in patients with type 2 diabetes mellitus.

OBJECTIVE: Various adipocytokines are closely associated with both obesity and insulin resistance. We investigated how body fat weight (BFW) and body fat ratio (BFR) affected serum adipocytokines in patients with type 2 diabetes mellitus. METHODS: Studies were conducted in type 2 diabetic patients (n = 41) and age-matched healthy subjects (n = 18). BFW and BFR were determined using a high-frequency bioelectric impedance method. We measured the adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α in serum. RESULTS: BFW and BFR showed significant positive correlations with BMI and serum leptin concentrations in diabetic patients. A significant positive correlation was found between BFW and serum FFA. Multivariate analysis identified only BMI a significant independent determinant of BFW. Stepwise analysis disclosed a significant positive correlation between HOMA-R and serum leptin. CONCLUSIONS: In diabetic patients, accumulation of body fat may increase serum leptin and FFA, which in turn would contribute to insulin resistance.

Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes.

An increase of serum ferritin, an indicator of body iron store, is associated with insulin resistance and with an increased risk of type 2 diabetes in the general population. A low serum adiponectin is also associated with insulin resistance. Recently, hepcidin was identified as a regulator of iron metabolism. We investigated whether serum adiponectin was associated with serum ferritin or prohepcidin, a precursor of hepcidin, in healthy subjects and patients with type 2 diabetes. We studied 65 healthy subjects and 104 patients with type 2 diabetes. A serum ferritin concentration ≥ 300 ng/ml for men or ≥ 150 ng/ml for women was defined as hyperferritinemia. Serum ferritin was significantly higher and serum prohepcidin was significantly lower in diabetic patients than in control subjects. Serum total and high molecular weight (HMW) adiponectin correlated negatively with serum ferritin in control subjects or diabetic patients, while serum total and HMW adiponectin correlated positively with serum prohepcidin in diabetic patients, but not in control subjects. Serum total and HMW adiponectin were lower in patients with hyperferritinemia than in those without it. In conclusion, serum ferritin was increased in type 2 diabetic patients, while serum prohepcidin was decreased. A high serum ferritin was associated with insulin resistance, and with low serum total and HMW adiponectin in patients with type 2 diabetes.