Serum ErbB2 concentration positively correlated to the glycemic variations in newly diagnosed Type 2 diabetic patients.

Evidences indicate that elevated levels of circulating ErbB2 are closely associated with increased incidence of diabetes. However, the relationship between ErbB2 concentration and glycemic variations (GV) in type 2 diabetic (T2D) patients remains elucidated. The aim of this study was to assess whether there is an association between serum ErbB2 concentration and GV in newly diagnosed T2D patients. This was a three-center, and observational study. Between April 2019 and July 2019, a total of 106 newly diagnosed T2D patients were recruited. All recruited subjects were admitted as inpatients and received anti-diabetes agents free during the study period. At baseline, fasting serum was collected for ErbB2 measurement and all recruited patients were subjected a prospective CGM for at least 3 days. The primary endpoint was the relationships between ErbB2 concentrations and GV in T2D patients. Data of a total of 95 subjects who met the inclusion criteria were analyzed at the endpoint. Subjects were divided into quartiles according to their serum ErbB2 concentrations. We observed that subjects with an elevated level of ErbB2 had a higher value of GV in terms of mean amplitude of glucose excursion (MAGE), standard deviation of mean glucose (SDMG), and the coefficient of variation (CV%) than those with lower levels (all P < 0.05). Multiple linear regression analyzes after adjusting for confounder factors indicate that serum ErbB2 levels were significantly positively correlated with the MAGE (ß = 0.664, t = 7.218, P < 0.01), SD (ß = 0.469, t = 5.125, P < 0.01) and CV% (ß = 0.337, t = 4.442, P < 0.01), respectively. Our data indicated that diabetic patients with higher ErbB2 concentrations may have large GV, which is an independent risk factor for microvascular and macrovascular complications.

Effects of Dapagliflozin Adjunct to Insulin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes: A Randomized, Controlled, Open-Labeled Trial.

BACKGROUND: This study is aimed at investigating whether dapagliflozin adjunct to insulin therapy further improves glycemic control compared to insulin therapy alone in patients with newly diagnosed type 2 diabetes (T2D). METHODS: This single-centre, randomized, controlled, open-labeled trial recruited newly diagnosed T2D patients. Subjects were randomized 1 : 1 to the dapagliflozin add-on to continuous subcutaneous insulin infusion (CSII) group (DAPA) or the CSII therapy group for 5 weeks. Standard meal tests were performed 3 times at days -3, 7, and 35 for glucose, C-peptide, and insulin level determination. Two-time continuous glucose monitoring (CGM) was performed at baseline and at the end of the study. The primary endpoint was the difference in the mean amplitude of glycemic excursions (MAGEs) between the groups. RESULTS: A total of 66 subjects completed the study, with 34 and 32 patients in the DAPA and CSII groups, respectively. Patients in the DAPA group exhibited significant decreases in MAGE levels at the endpoint. We also observed that patients in the DAPA group had a lower homoeostasis model assessment insulin resistance (HOMA-IR) and a higher homoeostasis model assessment B (HOMA-B) value at 1 week and 5 weeks compared to those with insulin therapy, respectively. In addition, our data showed that patients in the DAPA group showed a significantly lower insulin dose (0.07 U/kg) and weighed less than those in the CSII group. CONCLUSION: Our data indicate that dapagliflozin adjunct to insulin is a safe and effective therapy for improving glycemic variations, insulin sensitivity, and weight loss in newly diagnosed T2D patients.

Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin.

OBJECTIVE: To investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Seventy men with newly diagnosed drug-naive T2DM and HbA1c >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment. RESULTS: Total, free, and bioavailable testosterone increased significantly within 5 days (all P < 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P < 0.05). CONCLUSIONS: In men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.

Men with Latent Autoimmune Diabetes and Type 2 Diabetes May Have Different Change Patterns in Free Testosterone.

OBJECTIVE: Type 2 diabetic (T2D) male patients with low total testosterone (TT) levels are at an increasing risk of all-cause mortality. However, the levels of TT in male patients with latent autoimmune diabetes in adults (LADA) remain largely unknown. Research Design and Methods. This was a single-center, open, observational study. The inclusion criteria were male patients who were diagnosed with LADA, and sex, body mass index, C-peptide, and glycated hemoglobin (HbA1c) levels matched with those of T2D patients. Islet function/sensitivity and sex hormone concentrations were determined at baseline and 1-year follow-up. The primary endpoint was the changes in androgen levels from baseline to 1-year follow-up in patients with LADA. RESULTS: Our data showed that TT and Bio-T levels remained unchanged, while FT levels significantly decreased from baseline to 1-year follow-up in patients with T2D. However, TT, Bio-T, and FT concentrations dramatically increased in the LADA group from baseline to 1-year follow-up. Furthermore, a Spearman analysis showed that changes of TT, FT, and Bio-T levels from baseline to endpoint were significantly negatively correlated with Δ homeostasis model assessment-2 IR (ΔHOMA2-IR), respectively. CONCLUSIONS: The FT change patterns in patients with LADA may differ from those in patients with T2D. Our data also indicated the significant negative correlation between insulin sensitivity and changes of TT, FT, and Bio-T levels along with the diabetic duration in patients with T2D and LADA.

Sexual Differences in response to Mid- or Low-Premixed Insulin Analogue in Patients with Type 2 Diabetes.

OBJECTIVE: To observe whether there are sexual-related differences in response to mid- or low-premixed insulin in type 2 diabetic patients. METHODS: This was an analysis of CGM data of a previous study. After screening, patients with longstanding T2D receive a 7-day continuous subcutaneous insulin infusion (CSII) therapy, and then subjects were randomly assigned 1 : 1 into two groups receiving Novo Mix 30 or Humalog Mix 50 regimen for a 2-day phage, followed by a 4-day cross-over period. A 4-day continuous glucose monitoring (CGM) was performed during the cross-over period. The primary endpoint was the differences in glycemic control between male and female patients receiving mid- or low-premixed insulin therapy. RESULTS: A total of 102 patients (52 men and 50 women) completed the study. Our data showed that male patients had significant decrease in mean glucose levels monitored by CGM after three meals during Humalog Mix 50 treatment period compared to those received Novo Mix 30 regimen (0900: 11.0 ± 2.5 vs. 12.2 ± 2.8, 1000: 9.9 ± 2.9 vs. 11.3 ± 3.1, 1200: 8.0 ± 1.9 vs. 9.1 ± 2.5, 1400: 9.2 ± 2.3 vs. 10.3 ± 2.5, and 2000: 7.3 ± 2.1 vs. 8.2 ± 2.4 mmol/L, p < 0.05, respectively). In addition, male patients receiving Novo Mix 30 experienced a significantly increased hypoglycemic duration compared to those of receiving Humalog Mix 50 (0 (0, 4.8) vs. 0 (0, 0), p < 0.05, respectively). In addition, male patients receiving Novo Mix 30 experienced a significantly increased hypoglycemic duration compared to those of receiving Humalog Mix 50 (0 (0, 4.8) vs. 0 (0, 0). CONCLUSION: Our data indicate that male patients with T2D receiving mid-premixed insulin analogue regimen may have a potential benefit of improvement in glycemic control compared to female patients. This trial is registered with ClinicalTrials.gov ChiCTR-IPR-15007340.

Lipoprotein-associated phospholipase A2 is a risk factor for diabetic kidney disease.

AIMS: This study aimed to determine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker for inflammation in the vessel wall and independently associated with atherosclerosis, and the incidence of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). METHODS: A total of 1452 patients were enrolled in this retrospective cross­sectional study. We recruited patients with T2D who were tested for glycated hemoglobin, fasting and 2 h post-meal serum C-peptide, blood lipid profile, 24 h urine albumin excretion rate (UAER), blood creatine, blood albumin, uric acid, and Lp-PLA2. RESULTS: Among the patients with T2D, 40.3% were diagnosed with DKD and the correlation between DKD and Lp-PLA2 was the most significant one compared to other diabetic complications (odds ratio = 1.651, P < 0.001). Plasma Lp-PLA2 level in patients with DKD was significantly higher and increased Lp-PLA2 level was independently associated with the incidence of DKD after adjustment for age, gender, duration of diabetes, glycated hemoglobin, body mass index, blood lipids, blood pressure, presence of coronary heart disease and carotid plaque, and use of statins (odds ratio = 1.545, P = 0.013). Lp-PLA2 was found to be positively correlated with UAER (r = 0.123, P < 0.001) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.71, P = 0.009). CONCLUSIONS: Increased plasma level of Lp-PLA2 is associated with incidence and development of DKD in patients with T2D. Lp-PLA2 should be considered as a biomarker for early detection and follow-up of DKD. TRIAL REGISTRATION: clinicaltrials.gov, No. NCT03362112, Registered 30 November 2017, retrospectively registered.

Association of high circulating testosterone with increased glycaemic variability in type 2 diabetes: A cross-sectional study in China.

BACKGROUND: Testosterone affects insulin resistance, but the effect of testosterone treatment on type 2 diabetes (T2D) remains controversial. We aimed to investigate the association between circulating total testosterone (TT) and glycaemic variability using continuous glucose monitoring (CGM) in patients with T2D. METHODS: A total of 248 men with T2D were enrolled in the study. Clinical characteristics and plasma for glycated haemoglobin (HbA1c) and C-peptide assessment were collected. TT was measured using a chemiluminescent immunometric assay. All patients were subjected to a 3-day CGM before making adjustments for hypoglycaemic therapy. RESULTS: TT positively correlated with the standard deviation of mean blood glucose (SDBG) (P < 0.05), especially in older patients. Linear regression analysis showed that SDBG was associated with HbA1c (ß = 0.354, P < 0.001) and TT (ß = 0.164, P = 0.008) after adjusting for age, duration of diabetes, body mass index, fasting/postprandial C-peptide, and use of different hypoglycaemic drugs. The cut-off value of TT for predicting glycaemic variability was 14.76 mmol/L according to receiver operating characteristic (ROC) analysis. SDBG, the coefficient of variation, the incremental area under the curve of glucose (AUC) > 10 mmol/L, and AUC night were increased in the group with TT > 14.76 nmol/L (P < 0.01 for all variables). Body mass index and fasting/postprandial C-peptide were lower in the group with TT > 14.76 nmol/L than in the group with TT ≤ 14.76 nmol/L (P < 0.05). CONCLUSIONS: Circulating TT levels should be assessed in patients with T2D in addition to HbA1c for predicting glycaemic variability. More frequent blood glucose monitoring or CGM is suggested for patients with T2D and high testosterone levels. CLINICAL TRIALS REGISTRATION: NCT03519529, ClinicalTrials.gov.

Glycemic variation in uncontrolled Graves' disease patients with normal glucose metabolism: Assessment by continuous glucose monitoring.

PURPOSE: To observe the glycemic variation (GV) in uncontrolled Graves' disease (GD) patients with normal glucose metabolism measured by continuous glucose monitoring (CGM). METHODS: This was a single-center, open-label, observational study. From January 2017 to October 2017, 20 GD patients with normal glucose metabolism and 24 healthy control subjects were recruited. Serum samples were obtained at 0, 30, and 120 min after oral glucose loading for glucose, insulin, and C-peptide level measurements. Fasting plasma fasting free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone concentrations were also detected. All participants were subjected to a 3-day CGM after baseline data were collected. The primary endpoint was the difference in the mean amplitude of the glycemic excursions between the two groups. RESULTS: Compared with the healthy subjects, the GD patients had higher mean amplitude of glycemic excursions (MAGE) (P < 0.01). Multiple linear stepwise regression analysis showed that FT4 level was an independent factor for the MAGE. Interestingly, the GD patients had a significant prolongation in the time to peak glucose, especially after breakfast (P < 0.01), and the elevation in the incremental area under the curve of glucose after breakfast till 4 hours later. CONCLUSIONS: Uncontrolled GD patients with normal glucose metabolism had a greater GV, and the FT4 level may contributed to the increased GV.

Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes.

PURPOSE: To determine if the TSH is related to estimated glomerular filtration rate (eGFR) in T2D patients without overt thyroid dysfunction. METHODS: A cohort study of 5936 T2D patients was assessed for thyroid and kidney functions, in whom 248 with subclinical hyperthyroidism and 362 with subclinical hypothyroidism. Serum creatinine and 24-hour urine albumin excretion (UAE) were collected. Chronic kidney disease (CKD) was defined as eGFR < 60 ml/min/1.73 m2. RESULTS: Compared with euthyroid subjects, the patients with subclinical hypothyroidism had lower eGFR (82.7 ± 22.4 vs. 90.5 ± 22.4 ml/min/1.73 m2, p < 0.01), higher UAE (114 ± 278 vs. 88 ± 229 mg/24 h, p < 0.05), and high incidence of CKD (16.0% vs. 10.1%, p < 0.05). The participants with a TSH level between 0.55 and 3.0 µIU/ml had a higher eGFR (91.4 ± 22.2 ml/min/1.73 m2) and a lower prevalence of CKD (9.5%) than those with higher TSH (3.01-4.78 µIU/ml, 85.6 ± 22.7 ml/min/1.73 m2, p < 0.01 and 13.1%, p < 0.01). Linear logistic regression analysis showed that the eGFR was significantly negatively associated with TSH (OR: 0.519, 95% CI: 0.291-0.927, p < 0.05), after adjustment of confounders. CONCLUSION: High TSH was independently associated with decreased eGFR in type 2 diabetes patients without overt thyroid dysfunction. Our findings indicate that doctors who treat T2D patients should routinely measure the thyroid function.

Male Patients with Longstanding Type 2 Diabetes Have a Higher Incidence of Hypoglycemia Compared with Female Patients.

INTRODUCTION: To explore whether there was a gender difference in the risk of hypoglycemia during intensive insulin therapy in patients with longstanding type 2 diabetes (T2D). This was a post hoc analysis of a single-center, open-label and prospective trial. METHODS: All subjects were admitted as inpatients, underwent a standard bread meal test at baseline and received a 7-day continuous subcutaneous insulin infusion (CSII) therapy for achieving glycemic control. Patients then were randomized 1:1 to two groups receiving (1) 4 days of Novo Mix 30 followed by 2 days of Humalog Mix 50; (2) 4 days of Humalog Mix 50 followed by 2 days of Novo Mix 30. All patients were subjected to 4-day retrospective continuous glucose monitoring (CGM) during the last 4 days in this study. The primary outcome was the incidences of hypoglycemia monitored by CGM at the end point. RESULTS: A total of 102 patients met the inclusion criteria and completed the study. Our data revealed that 29 patients (28%) experienced hypoglycemia as detected by CGM at the end point. Binary logistic stepwise regression analysis showed that only gender significantly correlated with hypoglycemia (B = 1.17, p = 0.017). Importantly, male patients had a significantly higher incidence of hypoglycemia than female patients (male = 20/52, female = 9/50, p = 0.022), although male patients required significantly lower insulin doses to maintain glycemic control than female patient (p = 0.00). CONCLUSION: Male patients with longstanding T2D had a higher incidence of hypoglycemia than female patients during intensive insulin therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR-IPR-15007340.

Metformin add-on continuous subcutaneous insulin infusion on precise insulin doses in patients with type 2 diabetes.

To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed data from our two randomized, controlled open-label trials. Newly diagnoses T2D patients were randomized assigned to receive either CSII therapy or Met + CSII therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed. The primary endpoint was differences in insulin doses and GV between the two groups. A total of 188 subjects were admitted as inpatients. Subjects in metformin add-on therapy required significantly lower total, basal and bolus insulin doses than those of control group. CGM data showed that patients in Met + CSII group exhibited significant reduction in the 24-hr mean amplitude of glycemic excursions (MAGE), the standard deviation, and the coefficient of variation compared to those of control group. Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.

Comparison of Efficacy and Safety of Lispro and Aspart Evaluated by Continuous Glucose Monitoring System in Patients with Newly Diagnosed Type 2 Diabetes.

OBJECTIVE: To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. METHODS: This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group). They all received CSII and metformin therapy. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. C-peptide and insulin and fructosamine were determined. CGMS was continuously applied for 4 days after reaching the glycemic target. RESULTS: There were no significant differences in daily dosages of insulin, fasting plasma C-P and 2 h postprandial C-P and insulin, and fructosamine at the baseline and endpoint between the groups Asp and Lis. No significant differences were seen in the 24 h mean amplitude of glycemic excursions (MAGE), 24 h mean blood glucose (MBG), the standard deviation of the MBG (SDBG), fasting blood glucose, number of glycemic excursion (NGE), and the incidence of hypoglycemia between the two groups. Similarly, no significant differences were found in areas under the curve (AUC) of glucose above 10.0 mmol/L or the decremental area over the curve (AOC) of glucose below 3.9 mmol/L between the two groups. CONCLUSIONS: Lispro and aspart had the similar ability to control the glycemic variations in patients with newly diagnosed T2DM. This study was registered with ClinicalTrials.gov, number ChiCTR-IPR-17010338.

The real world of blood glucose point-of-care testing (POCT) system running in China teaching hospital.

BACKGROUND:  The blood glucose point-of-care testing (POCT) system is important in the decision-making process involving patients suspected of having hypoglycemia. To investigate the real world of the POCT system being used in teaching hospitals in China. METHODS: The survey was conducted by Hisend Research Group from May 2015 to July 2015 in four teaching hospitals in China. The survey questions were referred to the ISO 15197:2013 standard requirements for the use of the POCT system in a hospital setting. RESULTS: A total of 170 subjects were included from 4 hospitals, which included nursing staff, nurse unit managers, employees from the department of medical instruments, and staff members employed by the clinical laboratories in the Tianjin Metabolism Hospital, Nanjing First Hospital, First Affiliated Hospital of Dalian Medical University, and the First hospital affiliated with the Xi'an Transportation University. The average score for the four hospitals surveyed in this study was 66.6, which varied from 46.1 to 79.7. The main factors influencing the scores were the multiple choices of blood-glucose meters, and the quality control assessment. CONCLUSION: Our data indicates that the real world use of the POCT system in hospital settings in China needs more closer adherence to a quality management framework.

Pre-exercise blood glucose affects glycemic variation of aerobic exercise in patients with type 2 diabetes treated with continuous subcutaneous insulin infusion.

AIMS: Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). METHODS: A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC0-60 min). RESULTS: The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC0-60 min (standardized ß = -0.386, P < 0.001) and incremental AUC of blood glucose ≤ 4.4 mmol/L (standardized ß = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Δglucose AUC0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P < 0.05 for all). CONCLUSIONS: PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. CLINICAL TRIALS REGISTRATION: ChiCTR-ONC-17010400, www.chictr.org.cn.

Management of glycemic variation in diabetic patients receiving parenteral nutrition by continuous subcutaneous insulin infusion (CSII) therapy.

To compare the continuous subcutaneous insulin infusion (CSII) or insulin glargine based multiple injections (MDI) therapy on glycemic variations in diabetic patients receiving PN outside of intensive care settings. This was a single-center, randomized, open-label trial. Patients with type 2 diabetes (T2D) who were receiving parenteral nutrition (PN) were recruited. After baseline data were collected, recruited patients were then randomized 1:1 to a CSII group or a MDI group. All patients were subjected to a 4-day retrospective Continuous Glucose Monitoring (CGM). The primary endpoint was the differences of the 24-hrs mean amplitude of glycemic excursion (MAGE) in patients receiving the PN therapy between the two groups. A total of 102 patients with T2D receiving PN were recruited. Patients in the CSII group had a significantly decreased mean glucose level (MBG), the standard deviation of MG (SDBG), MAGE, and the coefficient of variation (CV%) compared to those in MDI group (all P < 0.01). Furthermore, we found that the patients who received a bolus insulin dose required maintaining euglycemic control was gradually decreased during the PN period in both groups at the endpoint. The administration of insulin via CSII led to a significant decrease in glycemic variations in patients receiving PN.

Young onset type 2 diabetic patients might be more sensitive to metformin compared to late onset type 2 diabetic patients.

It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes) require similar insulin doses for intensive insulin therapy with a metformin add-on to achieve glycemic control. We analyzed data from our two previously performed randomized, controlled open-label trials. Patients were randomized to receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII combined with metformin therapy for 4 weeks. The studies concentrated on the differences in the insulin doses used for the two groups. We included 36 YOD (age < 40 yrs) and 152 LOD (age > 40 yrs) patients. YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD. A multivariate analysis, controlled for gender and the fasting blood concentration, was performed to determine the significance of the differences between groups, particularly with respect to the total and basal insulin doses. There was a trend toward improvement in ß-cell function and insulin resistance in terms of ΔHOMA-B and ΔHOMA-IR in patients with YOD compared to those with LOD. Newly diagnosed T2D patients with YOD required significantly lower insulin doses, particularly basal insulin doses, to maintain glycemic control compared to the LOD patients.

Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

INTRODUCTION: To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. METHODS: This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. RESULTS: A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. CONCLUSION: Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

Glucose metabolism before and after radioiodine therapy of a patient with Graves' disease: Assessment by continuous glucose monitoring.

Hyperthyroidism causes impaired glucose tolerance, insulin resistance (IR) and insulin secretion. However, the glucose variability affected by thyroid dysfunction remains unclear. Glucose variability was assessed by continuous glucose monitoring (CGM) in a non-diabetic patient with Graves' disease (GD), to the best of our knowledge, for the first time. A 28-year-old man with GD, who had been taking methimazole for 4 years, was treated with radioiodine on August 17th 2016. Although the patient exhibited normal glycated hemoglobin (HbA1c; 5.3%) and blood glucose values during the oral glucose tolerance test (OGTT; fasting and 120 min blood glucose were 5.38 and 6.39 mmol/l, respectively) before radioiodine therapy, CGM exhibited high 24 h mean glucose and nocturnal hyperglycemia. An increased fasting insulin level, suppressed levels of blood glucagon and high homeostatic model assessment of IR were also observed. The disordered glucose metabolism improved as soon as the patient's thyroid function turned to hypothyroidism 4 months after radioiodine therapy. The glucose intolerance in patients with hyperthyroidism, missed by the OGTT and HbA1c tests, may be more common than anticipated.

Features of glycemic variations in drug naïve type 2 diabetic patients with different HbA1c values.

To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P < 0.05, 7.44 ± 3.00 vs. 5.20 ± 2.35, P < 0.01, respectively). The 24-hr mean glucose concentrations increased incrementally in the patients with lower, moderate and higher HbA1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

Continuous Glucose Monitoring in Newly Diagnosed Type 2 Diabetes Patients Reveals a Potential Risk of Hypoglycemia in Older Men.

Objectives. We performed continuous glucose monitoring (CGM) to define the features of patients with newly diagnosed type 2 diabetes (T2D) before and after Continuous Subcutaneous Insulin Infusion (CSII) therapy. Methods. This was a retrospective analysis. Newly diagnosed T2D patients (106) were admitted from eight centers in China. They were divided into a younger patient group (<60 years) and an older patient group (≥60 years). Each group was further divided into male and female patients. CSII therapy was maintained for 3 weeks after the glycemic target was reached. CGM was performed 2 times before and after completion of insulin treatment. Results. CGM data showed the expected significant improvement of mean amplitude glycemic excursion (MAGE) with CSII therapy. The older patients had lower hourly glucose concentrations from 0200 to 0700 o'clock compared to the younger patients at baseline. Surprisingly, in the older patient group, the male patients had a potential risk of hypoglycemia after CSII therapy, especially during periods from 2300 to 2400 and 0400 to 0600. Conclusions. Our data suggested that older male patients with newly diagnosed T2D may have lower nocturnal glucose concentrations. This may potentially increase the risk of nocturnal hypoglycemia during CSII therapy. This study was registered with Chinese Clinical Trial Registry, number CliCTR-TRC-11001218.