The Effect of a Smartphone-Based, Patient-Centered Diabetes Care System in Patients With Type 2 Diabetes: A Randomized, Controlled Trial for 24 Weeks.

OBJECTIVE: This study evaluated the efficacy of a smartphone-based, patient-centered diabetes care system (mDiabetes) for type 2 diabetes that contains comprehensive modules for glucose monitoring, diet, physical activity, and a clinical decision support system. RESEARCH DESIGN AND METHODS: We conducted a 24-week, multicenter, randomized controlled trial with adult patients with inadequately controlled type 2 diabetes. The patients were randomly assigned to the mDiabetes group or the paper logbook (pLogbook) group. The primary end point was the difference of the change in HbA1c from baseline between the two groups. RESULTS: HbA1c reduction from baseline was greater in the mDiabetes group (-0.40 ± 0.09%, n = 90) than in the pLogbook group (-0.06 ± 0.10%, n = 82). The difference of adjusted mean changes was 0.35% (95% CI 0.14-0.55, P = 0.001). The proportion of patients whose HbA1c fell below 7.0% (53 mmol/mol) was 41.1% for the mDiabetes group and 20.7% for the pLogbook group (odds ratio [OR] 2.01, 95% CI 1.24-3.25, P = 0.003). The percentage of patients who attained HbA1c levels below 7.0% (53 mmol/mol) without hypoglycemia was 31.1% in the mDiabetes group and 17.1% in the pLogbook group (OR 1.82, 95% CI 1.03-3.21, P = 0.024). There was no difference in the event numbers of severe hyperglycemia and hypoglycemia between the two groups. CONCLUSIONS: The implementation of the mDiabetes for patients with inadequately controlled type 2 diabetes resulted in a significant reduction in HbA1c levels, with tolerable safety profiles.

Effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on lipid metabolism and endotoxemia after a high-fat meal in patients with type 2 diabetes.

We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized, double-blind, placebo-controlled, crossover study. Ten people with type 2 diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic medications and/or lifestyle modification, were randomized to gemigliptin or placebo for 4 weeks. At the end of each treatment phase, the study participants underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue. The median (range) fasting and total area under the curve of apolipoprotein B48 (ApoB48) were significantly lower with gemigliptin than with placebo (2.9 [1.5-15.8] µg/mL vs 4.2 [1.3-23.4] µg/mL; P = .020; 35.3 [14.4-87.4] µg/mL × hour vs 42.2 [17.5-109.0] µg/mL × hour; P = .020, respectively), whereas apolipoprotein B100 showed no significant difference. Serum endotoxin levels were undetectable in 70% of the samples, so we were not able to evaluate the effect of gemigliptin on endotoxemia. The gene expression of inflammatory cytokines in subcutaneous adipose tissue was not affected by gemigliptin. Gemigliptin reduced ApoB48 levels after a high-fat meal in participants with T2DM. Whether systemic endotoxin levels can be reduced by gemigliptin requires further investigation.

Feasibility of a Patient-Centered, Smartphone-Based, Diabetes Care System: A Pilot Study.

BACKGROUND: We developed a patient-centered, smartphone-based, diabetes care system (PSDCS). This study aims to test the feasibility of glycosylated hemoglobin (HbA1c) reduction with the PSDCS. METHODS: This study was a single-arm pilot study. The participants with type 2 diabetes mellitus were instructed to use the PSDCS, which integrates a Bluetooth-connected glucometer, digital food diary, and wearable physical activity monitoring device. The primary end point was the change in HbA1c from baseline after a 12-week intervention. RESULTS: Twenty-nine patients aged 53.9±9.1 years completed the study. HbA1c and fasting plasma glucose levels decreased significantly from baseline (7.7%±0.7% to 7.1%±0.6%, P<0.0001; 140.9±39.1 to 120.1±31.0 mg/dL, P=0.0088, respectively). The frequency of glucose monitoring correlated with the magnitude of HbA1c reduction (r=-0.57, P=0.0013). The components of the diabetes self-care activities, including diet, exercise, and glucose monitoring, were significantly improved, particularly in the upper tertile of HbA1c reduction. There were no severe adverse events during the intervention. CONCLUSION: A 12-week application of the PSDCS to patients with inadequately controlled type 2 diabetes resulted in a significant HbA1c reduction with tolerable safety profiles; these findings require confirmation in a future randomized controlled trial.

Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion.

Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).

Radiographic Characteristics of Adrenal Masses in Oncologic Patients.

BACKGROUND: We aimed to assess the usefulness of pre-contrast Hounsfield unit (HU) and mass size on computed tomography to differentiate adrenal mass found incidentally in oncologic patients. METHODS: From 2000 to 2012, 131 oncologic patients with adrenal incidentaloma were reviewed retrospectively. Receiver operating characteristic (ROC) curves were applied to determine the optimal cut-off value of the mean HU and size for detecting adrenal metastasis. RESULTS: The median age was 18 years, and 80 patients were male. The initial mass size was 18 mm, and 71 (54.2%) of these were on the left side. A bilateral adrenal mass was found in 11 patients (8.4%). Biochemically functional masses were observed in 9.2% of patients. Thirty-six out of 119 patients with nonfunctional masses underwent adrenalectomy, which revealed metastasis in 13. The primary cancers were lung cancer (n=4), renal cell carcinoma (n=2), lymphoma (n=2), hepatocellular carcinoma (n=2), breast cancer (n=1), and others (n=2). The area under the curve for the size and HU for clinically suspicious metastasis were 0.839 (95% confidence interval [CI], 0.761 to 0.900; P<0.001) and 0.959 (95% CI, 0.898 to 0.988; P<0.001), respectively. The cut-off value to distinguish between metastasis and benign masses were 22 mm for size and 20 for HU. CONCLUSION: ROC curve results suggest that pre-contrast HU >20 can be used as a diagnostic reference to suggest metastasis in oncologic patients with adrenal masses.

Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased ß-Cell Function Similar to Impaired Glucose Tolerance.

BACKGROUND: Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (≥155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared ß-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT). METHODS: We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The ß-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2). RESULTS: Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The ß-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8±107.3 vs. 64.8±47.8 vs. 65.8±80.6 (P=0.141), oral DI was 3.5±4.2 vs. 1.8±1.4 vs. 1.8±3.1 (P<0.001), and ISSI-2 was 301.2±113.7 vs. 213.2±67.3 vs. 172.5±87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT. CONCLUSION: Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted ß-cell function to a similar degree as IGT subjects.

Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study.

BACKGROUND AND AIM: Effective medicines have not been introduced for insulin resistance-related fatty liver. The efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a 12-week, double-blind, randomized, placebo-controlled study on drug-naïve patients with impaired glucose metabolism and fatty liver were compared. METHODS: Fifty-two patients with fasting glucose 100-240 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 6.0% and alanine aminotransferase (ALT) 40-250 IU/L were randomized to receive metformin (250 mg t.i.d.), or metformin (250 mg t.i.d.) and carnitine-orotate complex (300 mg t.i.d.) for 12 weeks (n = 26 per group). The primary end-point was a change from baseline ALT level. Secondary end-points were changes in fasting glucose, HbA1c, aspartate aminotransferase levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. RESULTS: The combined treatment reduced ALT level significantly more than metformin alone (-51.5 ± 33.2 IU/L vs -16.7 ± 31.3 IU/L, P = 0.001). The HbA1c levels also decreased significantly in both groups but there was no significant difference between them (-0.9% ± 1.0% vs -0.7% ± 0.9%). Treatment with the complex decreased the urinary 8-hydroxy-2'-deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone (both P < 0.05). No severe adverse events were observed. CONCLUSION: A 12-week treatment with metformin and carnitine-orotate complex significantly improved liver function enzyme levels. This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver (clinical trial number: KCT0000193).

Identification and Functional Characterization of P159L Mutation in HNF1B in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5).

Mutation in HNF1B, the hepatocyte nuclear factor-1ß (HNF-1ß) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-1ß in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ß-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ß-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

Prevalence and clinical characteristics of recently diagnosed type 2 diabetes patients with positive anti-glutamic Acid decarboxylase antibody.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in ß-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. METHODS: We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. RESULTS: The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. CONCLUSION: The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.