Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights.

One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.

Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12. RESULTS: HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group. CONCLUSION: An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.

Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea.

We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20-64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58-5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15-2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26-3.26) than in the smoking group (OR 1.49, 95% CI 0.74-2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.

Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes.

BACKGRUOUND: The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications. METHODS: In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends. RESULTS: The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; p=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant. CONCLUSION: YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

Three-dimensional Multistructural Quantitative Photoacoustic and US Imaging of Human Feet in Vivo.

Background Monitoring the microcirculation in human feet is crucial in assessing peripheral vascular diseases, such as diabetic foot. However, conventional imaging modalities are more focused on diagnosis in major arteries, and there are limited methods to provide microvascular information in early stages of the disease. Purpose To investigate a three-dimensional (3D) noncontrast bimodal photoacoustic (PA)/US imaging system that visualizes the human foot morphologically and also reliably quantifies podiatric vascular parameters noninvasively. Materials and Methods A clinically relevant PA/US imaging system was combined with a foot scanner to obtain 3D PA and US images of the human foot in vivo. Healthy participants were recruited from September 2020 to June 2021. The collected 3D PA and US images were postprocessed to present structural information about the foot. The quantitative reliability was evaluated in five repeated scans of 10 healthy feet by calculating the intraclass correlation coefficient and minimal detectable change, and the detectability of microvascular changes was tested by imaging 10 healthy feet intentionally occluded with use of a pressure cuff (160 mm Hg). Statistically significant difference is indicated with P values. Results Ten feet from six healthy male volunteers (mean age ± standard deviation, 27 years ± 3) were included. The foot images clearly visualized the structure of the vasculature, bones, and skin and provided such functional information as the total hemoglobin concentration (HbT), hemoglobin oxygen saturation (SO2), vessel density, and vessel depth. Functional information from five independent measurements of 10 healthy feet was moderately reliable (intraclass correlation coefficient, 0.51-0.74). Significant improvements in HbT (P = .006) and vessel density (P = .046) as well as the retention of SO2 were observed, which accurately described the microvascular change due to venous occlusion. Conclusion Three-dimensional photoacoustic and US imaging was able to visualize morphologic and physiologic features of the human foot, including the peripheral microvasculature, in healthy volunteers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mezrich in this issue.

High-Density Lipoprotein Cholesterol and the Risk of Myocardial Infarction, Stroke, and Cause-Specific Mortality: a Nationwide Cohort Study in Korea.

OBJECTIVE: We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) level and the risk of myocardial infarction (MI), stroke, and cause-specific mortality. METHODS: Using the Korean National Health Insurance Service-National Sample Cohort, we identified 343,687 subjects (men, 176,243; women, 167,444) aged ≥20 years who underwent health examinations between 2009 and 2012. HDL-C levels were categorized based on the concentration with 10 mg/dL intervals, starting from levels <30 mg/dL, with levels ≥90 mg/dL considered the highest. The endpoints of the study were newly-diagnosed MI, stroke, or mortality. We used the Cox proportional hazards model with restricted cubic splines. RESULTS: During a median follow-up of 6.0 years, the number of cases of death, MI, and stroke were 6,617, 4,064, and 3,435 in men and 3,677, 2,804, and 2,891 in women, respectively. The risk of all-cause mortality, cancer mortality, other mortality, and stroke was the lowest at HDL-C concentrations of 57-76 mg/dL in the spline curves; inverse associations with increased risk were observed at the lower HDL-C levels. In contrast, the lowest risk of cardiovascular mortality and MI was observed at the extreme high end. In men, there was a significant inverse and graded increase in hazard ratios of all outcomes in the lower HDL-C categories compared to the reference group (50-59 mg/dL). In the higher HDL-C categories, no significant increase in outcomes was observed. Women showed similar trends. CONCLUSION: The risk of mortality, MI, and stroke was high at low HDL-C levels in the Korean general population. However, extremely high HDL-C levels were not associated with an increased risk of mortality, MI, and stroke.

Practical cardiovascular risk calculator for asymptomatic patients with type 2 diabetes mellitus: PRECISE-DM risk score.

BACKGROUND: Obstructive coronary artery disease (OCAD) is a significant predictor of adverse clinical events in asymptomatic patients with type 2 diabetes mellitus (T2DM). HYPOTHESIS: We sought to develop an easy-to-use risk scoring system to predict OCAD and long-term clinical outcome in asymptomatic patients with T2DM (PRECISE-DM). METHODS: A total of 2799 asymptomatic patients with T2DM and no prior coronary disease were consecutively enrolled. OCAD was defined as ≥50% coronary artery stenosis on coronary computed tomography angiography (CCTA). A new risk scoring system was developed in 933 patients undergoing CCTA (derivation cohort) and its performance to predict OCAD and major adverse cardiac and cerebrovascular event (MACCE) was compared with other risk estimates. The scoring system was externally validated in 1899 patients not undergoing CCTA (validation cohort). RESULTS: The PRECISE-DM scoring system was created using seven variables that were associated with increased risk of OCAD, with scores ranging from 0 to 9. The scoring system predicted presence of OCAD with a C-statistic of 0.680 and risk of MACCE with a C-statistic of 0.708. The UKPDS risk engine and the Framingham risk score showed unreliable performance in prediction of OCAD (C-statistics 0.531 and 0.577, respectively). Calcium score was highly predictive for OCAD (C-statistic 0.825) but showed only modest accuracy in predicting MACCE (C-statistic 0.675). In the external validation cohort, the PRECISE-DM score showed acceptable discrimination for prediction of MACCE (C-statistic 0.707). CONCLUSIONS: The PRECISE-DM scoring system accurately predicted presence of OCAD and risk of MACCE in asymptomatic patients with T2DM.

Effect of a Mobile Phone-Based Glucose-Monitoring and Feedback System for Type 2 Diabetes Management in Multiple Primary Care Clinic Settings: Cluster Randomized Controlled Trial.

BACKGROUND: Recent evidence of the effectiveness of mobile phone-based diabetes management systems is generally based on studies conducted in tertiary hospitals or professional diabetes clinics. OBJECTIVE: This study aimed to evaluate the clinical efficacy and applicability of a mobile phone-based glucose-monitoring and feedback system for the management of type 2 diabetes mellitus (T2DM) in multiple primary care clinic settings. METHODS: In this multicenter, cluster-randomized controlled, open trial, 13 primary care clinics in Seoul and other large cities in South Korea were voluntarily recruited. Overall, 150 (9 clinics) and 97 (4 clinics) participants with T2DM were assigned to the intervention and control groups, respectively (2:1 allocation). Every month, participants in both groups attended face-to-face physicians' consultation for the management of diabetes in the clinic. For the intervention group, participants were required to upload their daily self-monitoring of blood glucose (SMBG) results using the mobile phone app in addition to outpatient care for 3 months. The results were automatically transmitted to the main server. Physicians had to check their patients' SMBG results through an administrator's website and send a short feedback message at least once a week. At baseline and 3 months, both groups had anthropometry and blood tests, including hemoglobin A1c (HbA1c), and responded to questionnaires about treatment satisfaction and compliance. RESULTS: At 3 months, participants in the intervention group showed significantly more improvement in HbA1c (adjusted mean difference to control -0.30%, 95% CI -0.50 to -0.11; P=.003) and fasting plasma glucose (-17.29 mg/dL, 95% CI -29.33 to -5.26; P=.005) than those in the control group. In addition, there was significantly more reduction in blood pressure, and the score regarding treatment satisfaction and motivation for medication adherence increased more in the intervention group than in the control group. In the subgroup analyses, the effect on glycemic control was more significant among younger patients and higher baseline HbA1c levels. CONCLUSIONS: The mobile phone-based glucose-monitoring and feedback system was effective in glycemic control when applied in primary care clinic settings. This system could be utilized effectively with diverse institutions and patients. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) https://tinyurl.com/tgqawbz.

Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic ß-cell mass and function.

There are numerous lines of clinical evidence that inhibition of the renin-angiotensin system (RAS) can prevent and delay the development of diabetes. Also, the role of RAS in the pathogenesis of diabetes, including insulin resistance and ß-cell dysfunction, has been extensively investigated. Nevertheless, this role had not yet been fully shown. A variety of possible protective mechanisms for RAS blockers in the regulation of glucose homeostasis have been suggested. However, the direct effect on pancreatic islet fibrosis has only recently been spotlighted. Various degrees of islet fibrosis are often observed in the islets of patients with type 2 diabetes mellitus, which can be associated with a decrease in ß-cell mass and function in these patients. Pancreatic stellate cells are thought to be deeply involved in this islet fibrosis. In this process, the activation of RAS in islets is shown to transform quiescent pancreatic stellate cells into the activated form, stimulates their proliferation and consequently leads to islet fibrotic destruction. In this article, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of RAS, and review the responsible local RAS signaling pathways in pancreatic stellate cells. Finally, we propose possible targets for the prevention of islet fibrosis.

Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. METHODS: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. RESULTS: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). CONCLUSION: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Effect of visit-to-visit LDL-, HDL-, and non-HDL-cholesterol variability on mortality and cardiovascular outcomes after percutaneous coronary intervention.

BACKGROUND AND AIMS: Visit-to-visit variability in biological measures has been suggested as an independent predictor of cardiovascular disease (CVD). Although low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) are important risk factors of CVD, there are few studies investigating the effect of variability in LDL-C and HDL-C on cardiovascular outcomes. We investigated the association between visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C and major adverse cardiovascular and cerebrovascular events (MACCE) in patients who underwent percutaneous coronary intervention (PCI). METHODS: Data from 1792 subjects who underwent PCI from January 2004 to December 2009 were analyzed. Visit-to-visit variability was calculated using various indices: standard deviation (SD), coefficient of variation, and corrected variability independent of mean (cVIM). MACCE comprised all-cause death, non-fatal myocardial infarction, and stroke. RESULTS: During a median follow-up period of 65 months, 114 subjects (6.4%) experienced MACCE: 68 (3.8%) all-cause death; 43 (2.4%) stroke, and 15 (0.8%) non-fatal myocardial infarction. Visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C was significantly higher in the MACCE group compared to the non-MACCE group. In multiple regression analysis, all LDL-C, HDL-C, and non-HDL-C variability parameters were independent predictors for MACCE after adjusting for potential confounding factors. Each 1-SD increase of cVIM in LDL-C, HDL-C, and non-HDL-C increased the risk of MACCE by 34% (HR 1.34 [95% CI, 1.18-1.52]), 50% (HR 1.50 [95% CI 1.32-1.71]), and 37% (HR 1.37 [95% CI, 1.20-1.57]), respectively. These relationships were observed in various subgroups according to age, sex, and diabetes status. CONCLUSIONS: Visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C is associated with MACCE in subjects with previous PCI.

Study Time after School and Habitual Eating Are Associated with Risk for Obesity among Overweight Korean Children: A Prospective Study.

OBJECTIVE: To investigate behavioral factors that contribute to the development of obesity among overweight children. METHODS: Among a community sample of 884 children aged 9-13 years, 833 children completed a baseline and 1-year follow-up examination that included anthropometrics, physical fitness, and behavioral factors. RESULTS: During the follow-up period, BMI for most children with normal weight or obesity did not change. However, among overweight children (n = 100), about one-third developed obesity (n = 26), while the others were categorized as normal weight (n = 32) or overweight (n = 42) after 1 year. Characteristics of overweight children at baseline and follow-up were analyzed. Those who developed obesity showed a notable increase in blood pressure as well as in BMI, waist circumference, and body fat over 1 year. At baseline, this group spent more time studying after school compared to overweight children who did not develop obesity, while there were no differences in time spent viewing television or engaging in vigorous physical activity. Eating outside the home, fast food consumption, and habitual eating in the absence of hunger were more common at baseline in those who did versus those who did not develop obesity. After adjusting for age, sex, and BMI, spending more time studying after school and habitual eating without hunger were associated with the development of obesity. CONCLUSION: Among Korean overweight children, study time after school and habitual eating without hunger were associated with an increased risk for development of obesity.

Improvement of islet function and survival by integration of perfluorodecalin into microcapsules in vivo and in vitro.

Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained. Furthermore, the best islet function represented by glucose-stimulated insulin secretion was observed for the PFD-alginate capsules in hypoxic condition. For the in vivo study, the same number of naked islets and encapsulated islets (alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic mice. Nonfasting blood glucose levels and the area under the curve for glucose based on intraperitoneal glucose tolerance tests in the PFD-alginate group were lower than in the alginate group. The harvested islets stained positive for insulin in all groups, but the ratio of dead cell area was 4 times higher in the alginate group than in the PFD-alginate group. In conclusion, integration of PFD in alginate microcapsules improved islet function and survival by minimizing the hypoxic damage of islets after intraperitoneal transplantation.

Effectiveness and safety of exenatide in Korean patients with type 2 diabetes inadequately controlled with oral hypoglycemic agents: an observational study in a real clinical practice.

BACKGROUND: Randomized clinical trials have shown the efficacy and safety of short-acting exenatide in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to investigate the effectiveness and safety of exenatide twice a day in Korean patients with T2DM who are suboptimally controlled with oral hypoglycemic agents. METHODS: This study was a post hoc analysis of multi-center (71 centers), prospective, observational, single-arm, post-marketing study of short-acting exenatide 5 to 10 µg twice a day from March 2008 to March 2014 and analyzed those who finished the follow-up over 20 weeks of medication. Changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight values before and after exenatide treatment were analyzed. Adverse events and adverse drug reactions were estimated in patients who were treated with exenatide at least once and for whom follow-up for safety has been completed. RESULTS: After 20 weeks treatment with exenatide, mean HbA1c and body weight were significantly reduced from 8.4% to 7.7% and from 83.4 kg to 80.2 kg, respectively (both p < 0.001). Subjects with higher baseline glucose and HbA1c levels showed an independent association with a greater reduction in glucose level. In addition, short duration of diabetes less than 5 years was an independent predictor for the improvement in glucose level. The majority of study subjects showed a reduction in both body weight and glucose level (63.3%) after exenatide treatment. In terms of safety profile, exenatide treatment was generally well-tolerated and the incidence of severe adverse event was rare (0.8%). The gastrointestinal side effects were most common and hypoglycemia was reported in 1.7% of subjects. CONCLUSION: In real clinical practice, 20 weeks treatment with short-acting exenatide was well tolerated and showed a significant body weight and glucose reduction in Korean patients with T2D who are suboptimally controlled with oral hypoglycemic agents. TRIAL REGISTRATION: ClinicalTirals.gov , number NCT02090673 , registered 14 February 2008.

The stress hyperglycemia ratio, an index of relative hyperglycemia, as a predictor of clinical outcomes after percutaneous coronary intervention.

BACKGROUND: We aimed to investigate the outcome-predicting value of a novel index of stress hyperglycemia in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). METHODS: This was a retrospective observational study. Four-thousand-three-hundred-sixty-two subjects from the COACT registry were used to estimate the risk of major adverse cardiovascular and cerebrovascular events (MACCE), which are defined as composites of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke. The stress hyperglycemia ratio (SHR) was calculated by dividing the random serum glucose at admission with the estimated average glucose derived from HbA1c. RESULTS: Over a median follow-up of 2.5years, 344 (7.9%), 43 (1.0%), and 89 (2.0%) cases of death, non-fatal MI, and non-fatal stroke occurred, respectively. Compared with the subjects in the lower three quartiles of SHR, the HR (95% CI) for the highest SHR quartile (Q4) group for MACCE was 1.31 (1.05, 1.64) in the total population and 1.45 (1.02, 2.06) in the non-diabetic population after adjusting for potential covariables. The risk of MACCE in the SHR Q4 group was significantly higher in patients presenting with ST-elevation MI (STEMI), which was not the case for patients presenting with other CAD types. The prognostic impact of SHR was more prominent for the 30-day MACCE. Similar results were observed in another cohort consisting of patients who only presented with acute MI. CONCLUSIONS: SHR is a useful predictive marker of MACCE after PCI, especially in non-diabetic patients with STEMI, which could be utilized to identify high-risk patients for adverse outcomes.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment.

BACKGROUND: There were a limited number of studies about ß-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of ß-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. RESULTS: Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. CONCLUSION: Long-acting basal insulin replacement could improve the glycemic status and restore ß-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.