Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015).

This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was -1.62%±0.07% in the vogmet group and -1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (-1.63 kg vs. -0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

Angelica gigas Ameliorates Hyperglycemia and Hepatic Steatosis in C57BL/KsJ-db/db Mice via Activation of AMP-Activated Protein Kinase Signaling Pathway.

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats.

Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p < .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 µm vs. 6.66 ± 1.07 µm, and 59.04 ± 15.16 µm2 vs. 35.71 ± 11.2 µm2, respectively, p < .05). Based on these results, the neuropathic manifestation and therapeutic responses of DPN may be different from other peripheral neuropathies. Therefore, specific pathogenic consideration according to peripheral neuropathy classification in addition to common treatments needs to be developed for management strategies of peripheral neuropathies.

Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Red ginseng is prepared by steaming raw ginseng, a process believed to increase the pharmacological efficacy. Further bioconversion of red ginseng through fermentation is known to increase its intestinal absorption and bioactivity, and bioconversion diminishes the toxicity of red ginseng's metabolite. This study was conducted to investigate the effects of daily supplementation with fermented red ginseng (FRG) on glycemic status in subjects with impaired fasting glucose or type 2 diabetes. METHODS: This study was a four-week long, randomized, double-blind, placebo-controlled trial. Forty-two subjects with impaired fasting glucose or type 2 diabetes were randomly allocated to two groups assigned to consume either the placebo or fermented red ginseng (FRG) three times per day for four weeks. Fasting and postprandial glucose profiles during meal tolerance tests were assessed before and after the intervention. RESULTS: FRG supplementation led to a significant reduction in postprandial glucose levels and led to an increase in postprandial insulin levels compared to the placebo group. There was a consistently significant improvement in the glucose area under the curve (AUC) in the FRG group. However, fasting glucose, insulin, and lipid profiles were not different from the placebo group. CONCLUSION: Daily supplementation with FRG lowered postprandial glucose levels in subjects with impaired fasting glucose or type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01826409.

Beneficial effects of Korean traditional diets in hypertensive and type 2 diabetic patients.

The prevalence of metabolic syndrome, hypertension, and diabetes has been increasing rapidly in Korea. The rate of increase has paralleled the replacement of Korean traditional diets (KTD), which emphasize vegetables and fermented foods, with western style dietary patterns that are rich in animal foods and saturated fat. We aimed to investigate the efficacy of the KTD in controlling fasting plasma glucose, blood pressure, and cardiovascular disease risk factors in hypertensive and type 2 diabetic (T2D) patients. Forty-one patients (61.8±1.5 years) who were taking medications prescribed for respective diseases were recruited from the Chonbuk National University Hospital for participation in a 12-week, parallel, controlled clinical trial. The control group (n=20) was advised to "eat as usual," whereas the experimental KTD diet group (n=21) was fed the KTD three times a day for 12 weeks. At the end of the trial, both groups had lower body mass index, % body fat, and waist-hip ratio compared to the baseline values (P<.05). Compared to the control group, the KTD group had a greater mean change (P<.05) from the baseline for glycated hemoglobin (HbA1c) (-0.72% vs. -0.25%) and heart rate (-7.1 vs. +1.6). Regular consumption of the KTD for 12 weeks by hypertensive and T2D patients resulted in favorable changes in cardiovascular risk factors.

Comparison of acarbose and voglibose in diabetes patients who are inadequately controlled with basal insulin treatment: randomized, parallel, open-label, active-controlled study.

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% ± 0.71% to 7.71% ± 0.93%) and voglibose groups (from 8.38% ± 0.73% to 7.68% ± 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 ± 69.38 to 176.80 ± 46.63 mg/dL) compared with the voglibose group (from 224.18 ± 70.07 to 193.01 ± 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528).

The influence of the Korean traditional Chungkookjang on variables of metabolic syndrome in overweight/obese subjects: study protocol.

BACKGROUND: Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The primary target of treatment of patients with metabolic syndrome is therapeutic lifestyle change. Numerous preclinical study have reported positive effects of chungkookjang in in vivo models of diabetes and obesity, but there is a paucity of controlled clinical trials on variables of metabolic syndrome in obese subjects. Thus, the objective of this trial is to examine the effect of chungkookjang compared to placebo on variables of metabolic syndrome in overweight/obese subjects. METHODS: This double-blind randomized controlled crossover trial will be conducted on 120 overweight/obese subjects; aged 19-29 years. Subjects will be recruited from the Chonbuk National University, Jeonju, South Korea. Enrolled subjects will be randomly assigned to two groups of equal number; one group received 35 g of chungkookjang (n = 60) and the other group received placebo (n = 60) on a regular daily basis for 12 weeks. After a 12-week washout period, the groups will be crossed over. In addition to anthropometric measures and blood pressure, glucose parameter, lipid profile, adipocytokine, and carnitine assay will be determined at baseline and 12 week. Also, safety will be assessing by measuring total bilirubin, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, total protein, albumin, blood urea nitrogen, creatinine, and creatine kinase at baseline and 12 weeks. 24-hour dietary recalls were collected at the baseline and at the end of the trial. DISCUSSION: This trial will evaluate the effects of chungkookjang on variables of metabolic syndrome in overweight/obese subjects. The results of this study may contribute to the reduction of risk factor for metabolic syndrome caused by obesity. TRIAL REGISTRATION: Clinical trials NCT01811511.

Neuroprotective effects of Vitis vinifera extract on prediabetic mice induced by a high-fat diet.

BACKGROUND/AIMS: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). METHODS: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). RESULTS: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls (40.95 ± 5.40), HD (28.70 ± 6.37), HD with 100 mg/kg (41.14 ± 1.12), and HD with 250 mg/kg (48.98 ± 7.01; p < 0.05, HD with VVE vs. HD). CONCLUSIONS: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.

Therapeutic Potential of Dioscorea Extract (DA-9801) in Comparison with Alpha Lipoic Acid on the Peripheral Nerves in Experimental Diabetes.

DA-9801, a mixture of extracts from Dioscorea japonica Thunb. and Dioscorea nipponica Makino, was reported to have neurotrophic activity. Therefore, we investigated the therapeutic potential of DA-9801, in comparison with alpha lipoic acid (ALA), for peripheral nerves preservation in experimental diabetes. Experimental animals were divided into 4 groups, and each group was designated according to the type of treatment administered as follows: normal, DM, DM+DA-9801, and DM+ALA. After 16 weeks, response thresholds to tactile and thermal stimuli were higher in DM+DA-9801 group than in nontreated DM group. This degree of increase in DM+DA-9801 group indicates more therapeutic potency of DA-9801 than ALA. Western blot analysis showed more significant increase in NGF and decrease in TNF-α and IL-6 in DM+DA-9801 group than in DM or DM+ALA groups (P < 0.05). IENF density was reduced less significantly in the DM+DA-9801 group than in other DM groups (7.61 ± 0.32, 4.2 ± 0.26, and 6.5 ± 0.30 in DM+DA-9801, DM, and DM+ALA, resp., P < 0.05). Mean myelinated axonal area in the sciatic nerves was significantly greater in DM+DA-9801 group than in other DM groups (69.2 ± 5.76, 54.0 ± 6.32, and 63.1 ± 5.41 in DM+DA-9801, DM, and DM+ALA, resp., P < 0.05). Results of this study demonstrated potential therapeutic applications of DA-9801 for the treatment of diabetic peripheral neuropathy.

The protective effects of DA-9801 (Dioscorea extract) on the peripheral nerves in streptozotocin-induced diabetic rats.

It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.