Aims/hypothesis Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. Methods Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. Results The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/ lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. Conclusions/interpretation The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

OBJECTIVE -To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA 1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI).RESULTS -The mean A1C and HFI were significantly lower in the intervention group (n ϭ 40) than in the control group (n ϭ 40). (A1C [mean Ϯ SD] 6.9 Ϯ 0.9 vs. 7.5 Ϯ 1.0%, P ϭ 0.009; HFI 0.47 Ϯ 0.23 vs. 0.78 Ϯ 0.51, P ϭ 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1C Ն7% (n ϭ 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P ϭ 0.022). Control patients with a basal A1C Ͻ7% (n ϭ 15) showed the characteristic bimodal distribution of A1C levels, whereas the A1C levels in the intervention group remained stable throughout the study with low HFI.CONCLUSIONS -Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability. Diabetes Care 29:2625-2631, 2006M any controlled clinical trials have shown that prolonged maintenance of the appropriate HbA 1c (A1C) level reduces the risk of developing diabetes complications in individuals with type 1 and type 2 diabetes (1-3). However, data from the National Health and Nutrition Examination Surveys in the U.S. showed that overall glycemic control did not improve between the assessment periods of 1988 -1994 and 1999 -2000 (4,5). Similar findings have been reported in other countries (6,7).Therefore, to achieve and maintain the target level of A1C, new approaches for a medical delivery system are necessary. For this purpose, different strategies using electronic technologies or educational programs have been proposed to improve the quality and efficiency of care for people with diabetes (8 -15). In our previous study (16), we introduced a new bidirectional communication tool for diabetes management referred to as the Internet-based glucose monitoring system (IBGMS) and demonstrated its short-term effects over 3 months. The IBGMS comprises an electronically organized circuit for diabetes management that includes both online and offline systems. This management system provides a close doctor-patient relationship, offers more educational opportunities, and enhances patient feedback.In this study, we demonstrated the long-term effectiveness of the IBGMS on glucose stability and A1C reduction.RESEARCH DESIGN AND METHODS -Initially, 120 individuals with type 2 diabetes were screened by a review of their medical reco...

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.

OBJECTIVE -The Internet is used worldwide as a communication tool. To improve the quality of diabetes control, we investigated the effectiveness of an Internet-based blood glucose monitoring system (IBGMS) on controlling the changes in HbA 1c levels.RESEARCH DESIGN AND METHODS -We conducted a randomized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary's Hospital for 3 months. The study subjects were treated with IBGMS for 12 weeks, and the control group received the usual outpatient management over the same period. HbA 1c and other laboratory tests were performed twice, once at the beginning of the study and again at the end of the study.RESULTS -The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age, sex, diabetes duration, BMI, blood pressure, HbA 1c , and other laboratory data. On follow-up examination 12 weeks later, HbA 1c levels were significantly decreased from 7.59 to 6.94% within the intervention group (P Ͻ 0.001). At the end of the study, HbA 1c levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA 1c (6.94 vs. 7.62%; P Ͻ 0.001, respectively). Among patients with baseline HbA 1c Ͻ7.0%, the patients in the intervention group had lower HbA 1c than those in the control group (6.38 vs. 6.99%; P Ͻ 0.05). Among the patients with a baseline HbA 1c Ն7.0%, the difference between the two groups appeared more obvious: HbA 1c levels at the end of the study were 8.12%.CONCLUSIONS -This new IBGMS resulted in a significant reduction of HbA 1c during the study period. We propose that this IBGMS be used as a method for improving diabetes control. Diabetes Care 27:478 -483, 2004T he importance of tight blood glucose control for the subsequent prevention of diabetes complication is well established (1,2). In addition, improving glucose control will also reduce the enormous economic burden associated with the disease (3,4). Therefore, various strategies for diabetes management have been designed to improve the quality and efficiency of care for patients with diabetes. To promote adherence for patients and providers to follow practical guidelines, studies have been carried out to establish educational programs for patients and health care workers. Other studies, including giving feedback to the providers as well as programs that remind providers and their patients of these guidelines, have been experimented with (5-8). Recently, a small number of computer-based or electronic management systems have been reported to improve diabetes care (9 -11). However, many barriers are recognized in providing this care system into the community health care system (12,13). Diabetes care means managing vulnerable patients with chronic disease consistently in the outpatient setting. Chin et al. (13) reported that providers in health care centers indicated a need to enhance behavioral changes in diabetic patients to improve the health care de...

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

BackgroundRenal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes.MethodsDapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue.ResultsAfter treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P < 0.05). The urine angiotensin II (Ang II) and angiotensinogen levels were significantly decreased following treatment with dapagliflozin or voglibose, but suppression of urine Ang II level was more prominent in the OL-DA than the OL-VO group (P < 0.05). The expressions of angiotensin type 1 receptor and tissue oxidative stress markers were markedly increased in OL-C rats, which were reversed by dapagliflozin or voglibose (P < 0.05, both). Inflammatory cell infiltration, mesangial widening, interstitial fibrosis, and total collagen content were significantly increased in OL-C rats, which were attenuated in OL-DA group (P < 0.05).ConclusionDapagliflozin treatment showed beneficial effects on diabetic nephropathy, which might be via suppression of renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

Huntington disease (HD) model mice with heterozygous knock-in (KI) of an expanded CAG tract in exon 1 of the mouse huntingtin (Htt) gene homolog genetically recapitulate the mutation that causes HD, and might be favoured for preclinical studies. However, historically these mice have failed to phenotypically recapitulate the human disease. Thus, homozygous KI mice, which lack wildtype Htt, and are much less relevant to human HD, have been used. The zQ175 model was the first KI mouse to exhibit significant HD-like phenotypes when heterozygous. In an effort to exacerbate HD-like phenotypes and enhance preclinical utility, we have backcrossed zQ175 mice to FVB/N, a strain highly susceptible to neurodegeneration. These Q175F mice display significant HD-like phenotypes along with sudden early death from fatal seizures. The zQ175 KI allele retains a floxed neomycin resistance cassette upstream of the Htt gene locus and produces dramatically reduced mutant Htt as compared to the endogenous wildtype Htt allele. By intercrossing with mice expressing cre in germ line cells, we have excised the neo cassette from Q175F mice generating a new line, Q175FΔneo (Q175FDN). Removal of the neo cassette resulted in a ∼2 fold increase in mutant Htt and rescue of fatal seizures, indicating that the early death phenotype of Q175F mice is caused by Htt deficiency rather than by mutant Htt. Additionally, Q175FDN mice exhibit earlier onset and a greater variety and severity of HD-like phenotypes than Q175F mice or any previously reported KI HD mouse model, making them valuable for preclinical studies.

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 ± 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.Graphical Abstract