Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Association of breastfeeding with thyroid function and autoimmunity in postmenopausal women.

OBJECTIVE: Whether breastfeeding influences thyroid function and autoimmunity is not elucidated. We examined the association of history of breastfeeding with thyroid hormones and thyroperoxidase antibody (TPOAb). DESIGN: Cross-sectional study of data from the 2013-2015 Korea National Health and Nutrition Examination Survey. METHODS: A total of 816 postmenopausal women were stratified into three groups according to the duration of breastfeeding and number of breastfed children. Thyroid hormones levels, TPOAb titers, and the prevalence of hypothyroidism and TPOAb positivity were evaluated in each group. RESULTS: Subjects with a history of prolonged breastfeeding had lower levels of thyrotropin (TSH) and TPOAb than the others. After adjusting for multiple confounding factors, the estimated means of TSH and TPOAb were associated with cumulative duration of breastfeeding. Duration of breastfeeding per child was associated with TSH levels, and number of breastfed children was associated with TPOAb titers. The odds ratio (OR) of hypothyroidism was significantly lower in group for ≥36 months of cumulative duration of breastfeeding, and the OR of TPOAb positivity was significantly lower in group with ≥3 breastfed children. In addition, duration of breastfeeding and the number of breastfed children were linearly correlated with log TSH and TPOAb each other in the multivariate model. CONCLUSIONS: The present study showed that prolonged breastfeeding was inversely associated with TSH and the prevalence of hypothyroidism. Moreover, TPOAb and the prevalence of TPOAb positivity were inversely associated with number of breastfed children. These results indicate that breastfeeding may exert a protective effect on thyroid function and autoimmunity.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study.

BACKGROUND: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). METHODS: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. RESULTS: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. CONCLUSION: This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Assessment of clinical risk factors to validate the probability of osteoporosis and subsequent fractures in Korean women.

This cross-sectional, observational study was designed to identify clinical risk factors of osteoporosis and fractures in Korean women to validate the probability of osteoporosis and subsequent fractures. A total of 1541 Korean women were recruited nationally. Fracture history of any site, risk factors of osteoporosis, and fall-related risk factors were surveyed and physical performance tests were conducted. Peripheral dual-energy X-ray absorptiometry was used to measure calcaneus bone mineral density (BMD). The number of positive responses on the modified 1-min osteoporosis risk test was related to the risk of osteoporosis. The frequency of osteoporosis was higher in those with a height reduction of >4 cm and a reduced body mass index (BMI). Multivariate analysis showed that older age and lower BMI were related to higher relative risk of osteoporosis. Time required to stand up from a chair and questions related to fall injury were significantly related to clinical fracture history of any site. Multivariate analysis showed that the relative risk of fractures at any site was higher in older subjects with a lower T-score and parental hip fracture history. This study shows that age and BMI are the most significant clinical risk factors for osteoporosis and that age, BMD, and parental history of hip fracture are highly applicable risk factors for validating the probability of osteoporotic fractures in Korean women.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes.

AIMS/INTRODUCTION: Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. MATERIALS AND METHODS: The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. RESULTS: Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were 'very satisfied' or 'satisfied' with the combined basal insulin and acarbose therapy. CONCLUSIONS: Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.

Effect of acupuncture on diabetic peripheral neuropathy: an uncontrolled preliminary study from Korea.

BACKGROUND: Diabetic neuropathic pain can severely influence quality of life, and patients may be dissatisfied with treatment. OBJECTIVE: To carry out an observational study of the effects of acupuncture for the treatment of diabetic neuropathic pain, in preparation for a full study. METHODS: Nine patients with diabetic neuropathic pain were recruited from a Korean diabetic clinic and given 12 sessions of acupuncture over 4 weeks. Their symptoms were evaluated using the Total Symptom Score (TSS) and Michigan Neuropathy Screening Instrument (MNSI) at baseline and 4 weeks after the last treatment. RESULTS: Mean TSS scores reduced from 7.99 (SD 3.55) at baseline to 4.95 (SD 4.41), at the 8-week follow-up-a statistically non-significant change (p=0.057). The MNSI scores improved from 6.33 (SD 1.31) before treatment to 4.33 (SD 3.00) after acupuncture treatment-a significant improvement (p=0.010). One participant experienced an exacerbation of diabetic neuropathy symptoms, but two patients gained complete relief of their diabetic peripheral neuropathy (DPN) symptoms. CONCLUSIONS: The results of this study justify further investigations into the effects of acupuncture on DPN.

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats.

For sufficient antihypertension with less adverse effects, numerous clinical trials have recommended combination therapy using two or more hypertensive drugs. Chungsinoryungsan (CSORS) is a polyherbal complex based on oriental medicine, which has shown therapeutic potentials for antihypertension and additional renal improvement. Therefore, the affect of CSORS on the pharmacokinetic profiles of perindopril, an antihypertensive drug, was analyzed as a novel combination of hypertensive drugs. Rats received perindopril with CSORS as the combination or distilled water as the control. The co-administration of perindopril with CSORS or distilled water was performed by single dosing or repeated dosing for a week at a 2-h interval. The analyzed pharmacokinetic parameters included peak concentration (Cmax), time to reach the Cmax (Tmax), area under the plasma concentration-time curve, terminal half-life (t1/2) and mean residence time to infinity (MRTinf). In the single oral co-administration within 5 min, the pharmacokinetics of perindopril demonstrated an increased Tmax and MRTinf but reduced t1/2 in the combination compared to the control treatment, indicating drug-drug interactions between perindopril and CSORS. However, in the repeated co-administration for a week at a 2-h interval, which was more than perindopril MRTinf in the control treatment (1.5±0.1 h), the initial co-administration showed no differences in the pharmacokinetics between the combination and control treatments. Furthermore, the repeated co-administration also showed no differences between the combination and control treatment. The results indicate that CSORS can be co-administered at a 2-h interval that was more than perindopril MRTinf and further clinical studies may provide detailed information for developing a drug regimen that generates enhanced combination effects of CSORS with hypertensive drugs.

Trend analysis of diabetic prevalence and incidence in a rural area of South Korea between 2003-2008.

UNLABELLED: Aims/Introduction: This study determined the change in prevalence of diabetes and prediabetes over a period of 5 years in South Korea. The incidence of diabetes and prediabetes and risk factors associated with the development of diabetes were also investigated. MATERIALS AND METHODS: The Dalseong population-based cohort survey recruited 1806 subjects who were over 20-years-old in 2003. Five years later, 1287 of the original subjects were re-evaluated and 187 new subjects were added to the study. All participants completed a questionnaire, were given a physical examination, and provided blood samples for analysis including 2 h oral glucose tolerances. RESULTS: Age-adjusted prevalence of diabetes rose from 6.7% in 2003 to 9.1% in 2008. The prevalence of prediabetes also increased from 18.5% in 2003 to 28.4% in 2008. The incidence rates of diabetes and prediabetes were 18.3 per 1000 person-years and 55.4 per 1000 person-years, respectively. The development of diabetes was associated with impaired fasting glucose (IFG) (odds ratio [OR] 5.661), impaired glucose tolerance (IGT) (OR: 6.013), age (OR 1.013), and waist-to-hip ratio (OR 1.513). After excluding the IFG and IGT, systolic blood pressure (OR 1.023), high-sensitivity C-reactive protein (hsCRP; OR 1.097), triglyceride (OR 1.002) and waist-to-hip ratio (OR 1.696) were statistically significant risk factors in a multivariate logistic regression analysis. CONCLUSIONS: A significant rise in the prevalence of diabetes and prediabetes was observed between 2003 and 2008. In addition, this study newly demonstrated that waist-to-hip ratio and hsCRP were associated with the development of diabetes after adjusting for several confounding factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00045.x, 2010).