Soon Jib Yoo

Insulin degludec compared with insulin glargine in insulin‐naïve patients with type 2 diabetes: A 26‐week, randomized, controlled, Pan‐Asian, treat‐to‐target trial

Insulin degludec (IDeg) is an ultra‐long‐acting basal insulin with a consistent action profile of >42 h. This trial compared the efficacy and safety of IDeg with insulin glargine (IGlar) in insulin‐naïve Asian patients with type 2 diabetes.

Body mass index is the most important determining factor for the degree of insulin resistance in non-obese type 2 diabetic patients in Korea ☆

With obesity, increased insulin secretion is needed to compensate for the additional demands and to maintain euglycemia. In contrast to Caucasians, the majority of type 2 diabetic patients belong to the non-obese category in Korea. There appears to be an ethnic difference underlying the pathogenesis in type 2 diabetes mellitus. However, there is only limited data on these subjects. The degree of insulin resistance in 267 Korean non-obese (body mass index [BMI] < 25 kg/m(2)) >/= patients with type 2 diabetes mellitus was analyzed, and the factors responsible for the insulin resistance were examined. The mean age and BMI of the patients were 50.8 +/- 10.6 years and 22.6 +/- 1.8 kg/m(2). Homeostasis model assessment-insulin resistance (HOMA-IR) >/= 2.5 was defined as being insulin resistant according to our data (mean +/- 1.5 SD of 1,917 normal subjects). There was no significant difference according to age, the duration of disease, and the glycosylated hemoglobin (HbA(lc)) levels between the subjects with or without insulin resistance. The HOMA-IR values in the patients with insulin resistance and normal insulin sensitivity were 4.2 +/- 1.4 and 1.5 +/- 0.6, respectively. In the insulin-resistant group, the log-transformed triglyceride (TG) levels were higher and the high-density lipoprotein-cholesterol (HDL-C) levels were lower than those of the insulin-sensitive group (log-transformed TG: 5.2 +/-.6 v 4.9 +/-.7 and HDL-C: 1.13 +/- 0.3 v 1.25 +/- 0.3mmol/L). These differences were still observed after adjusting for BMI. The HOMA-IR value was independently predicted by BMI and HDL-C levels, which explained 7% and 3% in the variability of insulin resistance, respectively. However, the TG levels were not independently associated with the HOMA-IR. Logistic regression analysis showed that the significant factor associated with HOMA-IR was only BMI. These results suggest that the BMI is the most important determinant of insulin resistance, while TG and HDL-C levels might be good markers of insulin resistance in non-obese patients with type 2 diabetes mellitus in Korea.

Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

Background Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated. Methods We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels. Results HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group. Conclusion The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus

BackgroundHyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM.MethodsA total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women.ResultsThe visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high-density lipoprotein, serum triglyceride and hemoglobin A1c (β-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (β-coefficient = 0.061, p = 0.255).Conclusionsour data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM.

Predictors for diabetic retinopathy in normoalbuminuric people with type 2 diabetes mellitus.

BackgroundPrevious studies have reported that microalbuminuria is an independent risk factor for the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). For this reason, the clinical significance of DR in normoalbuminuric type 2 DM patients may be overlooked. The aim of this study was to investigate the prevalence of DR and predictors for DR in normoalbuminuric patients with type 2 DM.MethodsA total 310 patients with type 2 DM and normoalbuminuria, who were referred to the Department of Ophthalmology for screening of DR were included in this study. DR was clinically graded according to the International Clinical Diabetic Retinopathy guidelines. The urinary albumin excretion rate (UAER) was assessed via 24-hour urine collection and measured by immunoturbidimetric assay. Normoalbuminuria was defined as a UAER < 20 μg/min in 2 out of 3 consecutive tests taken within 2–3 months.ResultsDR of any grade was present in 64/310 (20.7 %) patients. Mild non-proliferative diabetic retinopathy (NPDR) was most prevalent in patients with DR of any grade (36/64, 56 %). The duration of diabetes (OR 1.01, 95 % CI, 1.01 – 1.02, p < 0.001), hemoglobin levels (OR 0.73, 95 % CI, 0.59 – 0.91, p = 0.004) and a higher tertile of UAER (OR 4.04, 95 % CI, 1.71 – 9.57, p = 0.001) had independently significant association with DR. NPDR as well as PDR was more prevalent in patients with higher tertile of UAER compared with those with lower tertile of UAER (NPDR, p = 0.002 and PDR, p = 0.027, respectively).ConclusionsOur findings suggest that patients with normoalbuminuric type 2 DM also require close monitoring for the early detection of DR, especially if they have a higher UAER, longer duration of diabetes, or lower hemoglobin levels.

Relationship of visceral and subcutaneous adiposity with renal function in people with type 2 diabetes mellitus

BACKGROUND Obesity and diabetes mellitus (DM) are established risk factors for the development of chronic kidney disease. Visceral adiposity (VAT) and subcutaneous adiposity (SAT) may be associated with the differential metabolic risk. Our study was performed to determine whether VAT or SAT was associated with the decrease of renal function in people with type 2 DM. METHODS Nine hundred and twenty-nine people with type 2 DM and who had undergone abdominal computed tomography assessment of the SAT and VAT areas were included. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease (MDRD) four-variable equation at the time of the assessment of the SAT and VAT areas. RESULTS VAT was negatively associated with eGFR using the MDRD equation after adjustment for the clinical variables (β-coefficient = - 0.075, P = 0.034), while SAT was not significantly associated with eGFR. There was no significant association between the abdominal adiposity measurements and the eGFR using the Cockcroft-Gault formula. When stratifying the individuals by the body mass index groups, VAT was negatively associated with eGFR by the MDRD equation and the Cockcroft-Gault formula in the overweight and obese subjects after adjustment for the clinical variables, while there was no significant association between the VAT and the eGFR in the normal weight subjects. SAT was not significantly associated with eGFR in the normal weight, overweight and obese subjects. CONCLUSIONS Our data suggest that VAT may be an additional prognostic factor for the decrease of renal function especially in the overweight or obese subjects with type 2 DM.

Differentially up-regulated genes in proliferating porcine neonatal pancreas cells caused by epidermal growth factor

Pancreatic duct cells are considered to be a major source for β‐cell regeneration or neogenesis. Although epidermal growth factor (EGF) is a well‐known important growth factor for pancreas development, the control of pancreatic duct cell growth and differentiation by EGF is poorly understood. In this study, we focused on identifying the genes that were differentially up‐regulated in response to EGF stimulation using monolayer cultured porcine neonatal pancreas cells. Cells were obtained from 1 to 3 day old pigs, dispersed and cultured for 8 days. Monolayer cultured porcine pancreas cells were comprised of duct cells and some endocrine and mesenchymal cells (75.2 ± 15.1, 19.6 ± 4.9, and 9.5 ± 3.1%, respectively). After 16 h in serum free media, cells were treated with 100 μg/L EGF for 24 h. Differentially expressed genes were screened by subtractive hybridization. 3H‐thymidine uptake was significantly increased by EGF with time (untreated vs. 24 h treated, untreated vs. 48 h treated: 305.5 ± 3.5 cpm vs. 380.3 ± 17.3 cpm (P < 0.05), 309.2 ± 4.51 vs. 929 ± 9.19 cpm, (P < 0.005), respectively). Three hundred and fify cDNA clones were obtained by subtractive hybridization and the inserts were confirmed in 161 colonies and then sequenced. Finally, we found increased mRNA expression of five unknown and five known genes, including cytochrome c oxidase subunit I (COI), cyclooxygenase‐2 (COX‐2), matrix metalloproteinase‐13 (MMP‐13), Wiskott–Aldrich syndrome protein interacting protein (WASPIP), and hyaluronan synthase‐2 (HAS‐2). We confirmed the up‐regulation of these genes by Northern blot and semi‐quantitative RT‐PCR at various time points. The present findings opened new targets for the research on the mechanisms of pancreatic duct cell proliferation by EGF.

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes

The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.

The Effect of Early Intensive Insulin Therapy on Body Fat Distribution and β-Cell Function in Newly Diagnosed Type 2 Diabetes

Objectives. The aim of this study was to evaluate the effects of early intensive insulin therapy on body fat distribution, lean body mass and β-cell function in patients with newly diagnosed type 2 diabetes. Methods. Thirty-eight subjects with newly diagnosed type 2 diabetes participated in a 12-week course of intensive insulin therapy. Patients were administered a 75 g oral glucose tolerance test (OGTT), underwent measurement of visceral and subcutaneous adipose tissues (VAT and SAT) using computed tomography and appendicular skeletal muscle (ASM) mass was assessed using dual-energy X-ray absorptiometry. Results. After intensive insulin therapy, fasting plasma glucose and HbA1c levels decreased. Homeostasis model assessment (HOMA)-B, the insulinogenic index, and the C-peptide-to-glucose area under the curve (AUC) ratio increased. The insulin sensitivity index and the glucose AUC decreased after 12 weeks. The body composition analysis revealed that the VAT and the ratio of VAT to SAT decreased, whereas body weight and total fat mass increased nonsignificantly. The ASM/weight and skeletal muscle mass index increased. The restoration of β-cell function, as identified by HOMA-B, the insulinogenic index, and the C-peptide-to-glucose AUC ratio, was correlated with the changes in VAT when controlled for age and gender. In multiple regression analyses, the decrease in VAT was shown to independently contribute to improved HbA1c over the study period, after adjusting for confounding factors. Conclusions. These results suggest that a shift in fat distribution from visceral to subcutaneous fat after early intensive insulin therapy is associated with improvements in glycemic control and β-cell function in patients with newly diagnosed type 2 diabetes.