Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects.

BACKGROUND: Herbal medicine has long been used as an alternative medicine for treatment of type 2 diabetes mellitus (T2DM). Recently, Moringa oleifera (MO or ma-rum in Thai) leaf has been widely used in T2DM patients. Several studies in diabetes rat model have shown that MO had effect on glucose metabolism. However study in humans is lacking. OBJECTIVE: Examine effects of MO on plasma glucose and insulin secretion. MATERIAL AND METHOD: Ten healthy volunteers were enrolled in this study (mean age 29 ± 5 years; BMI 20.6 ± 1.5 kg/m2; FPG 81 ± 5 mg/dl). After an overnight fast and every two weeks, subjects received an oral dose of MO at increasing dosages of 0, 1, 2, and 4 g. Plasma glucose (PG) and insulin were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 6 hours after each MO dosage administration. Insulin secretion rate was measured using area under the curve (AUC) of insulin and AUC of insulin/glucose ratio. RESULTS: After doses of 0, 1, 2, and 4 g MO, mean plasma insulin increased (2.3 ± 0.9, 2.7 ± 1.0, 3.3 ± 1.4, and 4.1 ± 1.7 µU/ml, respectively) despite there being no differences in mean PG (77 ± 6, 78 ± 5, 79 ± 6, and 79 ± 5 mg/dl, respectively). AUC of insulin was greater after high-dose MO (4 g) than after baseline or low-dose MO capsule (1 g) (24.0 ± 3.5 vs. 14.5 ± 1.8 or 16.1 ± 2.0, respectively; p = 0.03), while there was no difference in AUC of glucose. Accordingly, insulin secretion rate represented by AUC of insulin/glucose ratio after high-dose MO was significantly increased by 74% (P = 0.041), as compared with that of baseline. CONCLUSION: We concluded that high-dose (4 g) MO leaf powder capsules significantly increased insulin secretion in healthy subjects. These results suggest that MO leaf may be a potential agent in the treatment of type 2 diabetes. Further studies of MO in patients with T2DM are needed.

Cardiometabolic risk in Thai adults with type 2 diabetes mellitus: obese versus non-obese.

BACKGROUND: Adiposity is an inflammatory condition contributing to the morbidity and mortality of several disorders, including type 2 diabetes mellitus (T2D) and cardiovascular disease. OBJECTIVE: To compare cardiometabolic risk factors between obese and non-obese Thai patients with T2DM MATERIAL AND METHOD: The cross-sectional study was done in 20 obese (BM >25 kg/m2) and 20 non-obese (BMI 23 kg/m2) T2DM Researchers measured fasting plasma glucose and lipids, serum levels of insulin, leptin, adiponectin, and soluble tumor necrosis factor-alpha receptors type 1 and 2 (sTNF-R] andsTNF-R2). Insulin sensitivity check index (QUICIKI) and insulin resistance index (HOMA-IR) were calculated. RESULTS: Thai obese adults with T2DMhad greater amounts ofsTNF-R2 and HOMA-IR, higher ratios of leptin/adiponectin, and more incidences of hypertension and hypertriglyceridemia in comparison to non-obese counterparts. Additionally, HOMA-IR values in non-obese T2DMwere greater than those reported among non-diabetic Thai adults. A reverse association between inflammatory markers (both sTNF-Rs) andHDLC was detected. Leptin/adiponectin ratios correlated directly with HOMA-IR, serum insulin, plasma triglycerides and BMI, whereas HOMA-IR did not relate to any studied plasma lipid. CONCLUSION: The present study demonstrated an increased cardiometabolic risk in obese T2DM adults than non-obese T2DM adults among the Thai population. The leptin/adiponectin ratio may be more relevant to predict the risk of cardiovascular events in T2DMpatients than HOMA-IR.

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

Glycemic control, quality of life and self-care behavior among adolescents with type 1 diabetes who attended a diabetes camp.

A prospective study was conducted at the tenth Siriraj diabetes camp with the objectives of evaluating the effectiveness of diabetes camp on 1) glycemic control, 2) knowledge, 3) quality of life, and 4) self-care behavior of adolescents with type 1 diabetes (T1D) who participated in the diabetes camp. During the 5-day camp, twenty-seven participants (mean age 15.6 +/- 2.1 years, mean duration 6.3 +/- 3.0 years) were taught diabetes self-management education (DSME) and engaged in psychosocial support sessions. Post-camp activities were held every 3 months and participants were followed for 12 months post-camp. Glycemic control was assessed prior to the camp, then every 3 months. Knowledge level was assessed prior to the camp, at the end of the camp, and every 3 months. Diabetes self-care behavior and quality of life were evaluated prior to the camp, at 3 months and 12 months after the camp. After attending the camp, participants had improvement in knowledge but there were no changes in HbA1c levels or quality of life scores. Quality of life was not consistently associated with HbA1c. In general, participants did not perceive their quality of life was poor or feel having diabetes affected their social life. The issue participants worried about most was whether they would develop complications from diabetes. There were several weak points found among participant self-care behavior, particularly in diet-related matters. Despite no improvement in glycemic control, participants gained knowledge from attending the camp. Diet related self-care behavior is difficult for teenagers with T1D to be compliant.

Prevalence of osteoporosis and osteopenia in Thai COPD patients.

OBJECTIVE: To study the prevalence of osteoporosis and osteopenia in Thai COPD patients and the factors associated with osteoporosis. MATERIAL AND METHOD: A cross sectional study was used to evaluate 102 male stable COPD patients. Bone mineral density at lumbar spine (L2-4) and femoral neck were measured by dual energy x-ray absorptiometer scan. Demographic data including age, body mass index (BMI), inhaled corticosteroids use, tobacco smoke, force expiratory volume at 1 second (FEV1), and high sensitivity C-reactive protein (hs-CRP) were analyzed. RESULTS: The overall prevalence of osteoporosis and osteopenia according to the lowest T-score at either L2-4 or femoral neck were 31.4% and 32.4%, respectively. This prevalence of osteoporosis in COPD patients was higher than that in age-matched Thai males from historical data (31.4% vs. 12.6%, respectively). BMI and hs-CRP were significantly associated with osteoporosis. There was no association between osteoporosis and severity of COPD, age, smoking, and corticosteroid use. The predictive value of BMI < 20.5 kg/m2 and hs-CRP > 2.3 mg/L demonstrated risk of osteoporosis in COPD patients (adjusted Odds ratio 7.2 and 4.1, respectively). CONCLUSION: The prevalence of osteoporosis and osteopenia in Thai COPD patients was higher than that in normal age-matched Thai males. Osteoporosis was associated with low BMl and high level of hs-CRP when compared to COPD patients with normal bone mineral density.

The Effect of high temperature on the stability of basal insulin in a pen: a randomized controlled, crossover, equivalence trial.

INTRODUCTION: Insulin is an essential medicine in the management of diabetes. When stored at high temperatures(HTs), its efficacy could rapidly decline. Therefore, appropriate storage of in-use insulin is necessary to achieve its maximum therapeutic effects. However, the ambient temperature in tropical countries is normally relatively high. This study aimed to compare the efficacies of basal insulin in a pen previously kept at 37°C for 21 days and basal insulin in a refrigerated pen (2°C-8°C). Continuous glucose monitoring (CGM) was used to evaluate daily mean glucose levels (MGLs). RESEARCH DESIGN AND METHODS: This randomized controlled, crossover, equivalence trial recruited adults with type 2 diabetes mellitus and glycated hemoglobin levels <8% who had used insulin glargine for >3 months. Subjects were randomized for sequential use of refrigerated basal insulin followed by basal insulin kept at HT, with a 2-week washout between phases. The HT insulin pens were stored in a 37°C incubator for 21 days before use, while the refrigerated insulin pens were stored at 2°C-8°C. Study patients received 7-day CGM. The primary outcome was the difference in the groups' MGLs. The secondary outcome parameters were glucose variability represented by the standard deviation (SD), mean amplitude of glycemic excursion (MAGE), and percentage of time in range (TIR). The remaining quantity of insulin was evaluated by ultrahigh-performance liquid chromatography (UHPLC) assay. RESULTS: Forty patients completed the study. The MGLwas 158.7±30.5 mg/dL and 157.0±40.9 mg/dL in the HT and refrigerated insulin pen groups, respectively (p=0.72). The groups had no significant differences in MAGE7day, SD, percentage of TIR, carryover period, or treatment effects (all p>0.05). There was also no significant difference in the remaining quantity of insulin evaluated by UHPLC (p=0.97). CONCLUSIONS: HT basal insulin pens retain their potency and have biological activity comparable to that of refrigerated pens.Trial registration number TCTR20210611002.

Cluster analysis of Thai patients with newly diagnosed type 2 diabetes mellitus to predict disease progression and treatment outcomes : A prospective cohort study.

INTRODUCTION: Type 2 diabetes mellitus (T2D) is highly heterogeneous in disease progression and risk of complications. This study aimed to categorize Thai T2D into subgroups using variables that are commonly available based on routine clinical parameters to predict disease progression and treatment outcomes. RESEARCH DESIGN AND METHODS: This was a cohort study. Data-driven cluster analysis was performed using a Python program in patients with newly diagnosed T2D (n=721) of the Siriraj Diabetes Registry using five variables (age, body mass index (BMI), glycated hemoglobin (HbA1c), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C)). Disease progression and risk of diabetic complications among clusters were compared using the Χ2 and Kruskal-Wallis test. Cox regression and the Kaplan-Meier curve were used to compare the time to diabetic complications and the time to insulin initiation. RESULTS: The mean age was 53.4±11.3 years, 58.9% were women. The median follow-up time was 21.1 months (9.2-35.2). Four clusters were identified: cluster 1 (18.6%): high HbA1c, low BMI (insulin-deficiency diabetes); cluster 2 (11.8%): high TG, low HDL-C, average age and BMI (metabolic syndrome group); cluster 3 (23.3%): high BMI, low HbA1c, young age (obesity-related diabetes); cluster 4 (46.3%): older age and low HbA1c at diagnosis (age-related diabetes). Patients in cluster 1 had the highest prevalence of insulin treatment. Patients in cluster 2 had the highest risk of diabetic kidney disease and diabetic retinopathy. Patients in cluster 4 had the lowest prevalence of diabetic retinopathy, nephropathy, and insulin use. CONCLUSIONS: We were able to categorize Thai patients with newly diagnosed T2D into four clusters using five routine clinical parameters. This clustering method can help predict disease progression and risk of diabetic complications similar to previous studies using parameters including insulin resistance and insulin sensitivity markers.

Young-onset diabetes patients in Thailand: Data from Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN).

AIMS/INTRODUCTION: There is a lack of current information regarding young-onset diabetes in Thailand. Thus, the objectives of this study were to describe the types of diabetes, the clinical characteristics, the treatment regimens and achievement of glycemic control in Thai patients with young-onset diabetes. MATERIALS AND METHODS: Data of 2,844 patients with diabetes onset before 30 years-of-age were retrospectively reviewed from a diabetes registry comprising 31 hospitals in Thailand. Gestational diabetes was excluded. RESULTS: Based on clinical criteria, type 1 diabetes was identified in 62.6% of patients, type 2 diabetes in 30.7%, neonatal diabetes in 0.8%, other monogenic diabetes in 1.7%, secondary diabetes in 3.0%, genetic syndromes associated with diabetes in 0.9% and other types of diabetes in 0.4%. Type 1 diabetes accounted for 72.3% of patients with age of onset <20 years. The proportion of type 2 diabetes was 61.0% of patients with age of onset from 20 to <30 years. Intensive insulin treatment was prescribed to 55.2% of type 1 diabetes patients. Oral antidiabetic agent alone was used in 50.8% of type 2 diabetes patients, whereas 44.1% received insulin treatment. Most monogenic diabetes, secondary diabetes and genetic syndromes associated with diabetes required insulin treatment. Achievement of glycemic control was identified in 12.4% of type 1 diabetes patients, 30% of type 2 diabetes patients, 36.4% of neonatal diabetes patients, 28.3% of other monogenic diabetes patients, 45.6% of secondary diabetes patients and 28% of genetic syndromes associated with diabetes patients. CONCLUSION: In this registry, type 1 diabetes remains the most common type and the prevalence of type 2 diabetes increases with age. The majority of patients did not achieve the glycemic target, especially type 1 diabetes patients.

Attainment of American Diabetes Association clinical practice recommendations in 722 Thai type 2 diabetes patients.

BACKGROUND: Each year the American Diabetes Association (ADA) publishes the update clinical practice recommendation. However, the achievement of these practice recommendations remained suboptimal in several studies. The purpose of this study is to determine the degree diabetes patients achieved optimal clinical practice recommendations and to determine factors associated with reduced attainment of these recommendations in T2DM patient. MATERIAL AND METHOD: We conducted retrospective review medical records of Thai type 2 diabetes patients who were followed-up at out-patient department of internal medicine department, Siriraj hospital, Thailand, during January to December 2006. RESULTS: Of 722 diabetes patients who were recruited, 64.5% and 60% had received HbA1c and plasma lipid profiles measurements, respectively, whereas blood pressure measurement was done in all patients. Forty-nine percent achieved the target HbA1c of less than 7%, 64% achieved LDL-C and HDL-C targets and 58% achieved the triglycerides target, whereas only 31% of the patients achieved the BP target recommendation. Fifty-two percent of patients achieved at least 3 items according to ADA practice recommendation and 47.8% achieved only 0-2 items of clinical recommendation. Category of health care provider and elderly patients were independent factors for attainment of clinical practice recommendations. Moreover, patients who were diagnosed with diabetes for longer than 10 years and who used insulin treatment were independent factors for achieving good glycemic control. CONCLUSION: These data demonstrated a substantial proportion of diabetes patients did not achieve ADA clinical practice recommendations. This apparent gap was depended on categories of health care provider and patients' age. The novel and more effective strategies targeted these groups are needed to improve achievement of these recommendations.

Assessment and prevalences of diabetic complications in 722 Thai type 2 diabetes patients.

BACKGROUND: The purpose of this study is to determine the percent of patients who have been assessed as having diabetic complications as recommended by American Diabetes Association. The secondary goals were to determine factor(s) associated with reduced assessment of diabetic complication and to determine the prevalence of diabetic complications in Thai type 2 diabetes patients. MATERIAL AND METHOD: We conducted a retrospective review of medical records of Thai type 2 diabetes patients who were followed up at the out-patient department (OPD) of Department of Internal Medicine at Siriraj Hospital Mahidol University Thailand during 1st January to 31st December 2006. RESULTS: Of 722 diabetes patients who were recruited, 7.5% were treated by general practitioners (GP), 10.4% by internal medicine residents (Res), 49.9% by internist (Int), 11.8% by endocrinologist (Endo) and 20.5% was indeterminate because they could not identify the field of the health care provider. 38.4% of patients received an eye examination by an ophthalmologist. 42% were screened for diabetic nephropathy. Serum creatinine level was measured in 83.5%. Foot examination was done in only 125 patients (17.3%). We founded that patients taken care by GP and Int received less intensive and less extensive assessment for diabetic complications than those taken care by Res and Endo. The prevalences of diabetic nephropathy and chronic kidney disease of at least stage 3 were 37 and 48.2%, respectively. Diabetic retinopathy occurred in 31.2%, cardiovascular disease in 28.9%, cerebrovascular disease in 10.6% and diabetic foot in 40%. CONCLUSION: There was a high prevalence rate of diabetic complications in patients with type 2 diabetes. Screening for diabetic complications will help to identify patients at high risk of concomitant complications eventhough some practitioners are not initially aware of the importance of the diabetic complication screening. These data may help the physician decide to modify treatment to prevent disabilities.

The Effect of Temperature on the Stability of In-Use Insulin Pens.

BACKGROUND: Improper storage of insulin could decrease its potency. Manufacturers recommend that in-use insulin pens should be kept at between 25-30°C, but room temperature in tropical countries often exceeds this range. This study investigates the effect of temperature on the stability of basal insulin in cartridges 28 days after opening. METHODS: Four different basal insulins were evaluated. Five opened pens of each insulin type were included for each of three storage conditions and 5 unopened insulin pens of each type were stored in the refrigerator as a control. The opened pens were stored for 28 days in either a refrigerator (2-8 °C), at room temperature, or in an incubator (37 °C). Each day insulin pens were mixed 20 times and 2 units were discarded to mimic daily usage. Insulin quantity was evaluated using an ultra-high-performance liquid chromatography assay. RESULTS: The average room temperature during the study period was 29.7 °C. After 28 days, the percentage amount of insulin stored at refrigerator, room temperature or incubator, compared with control was 99.0, 99.7, 101.1% for long-acting insulin; 97.4, 97.2, 99.0% for NPH-1; 101.4, 101.5, 100.7% for NPH-2; and 98.7, 97.8, 98.5% for NPH-3. There were no statistically significant differences. However, we observed a trend toward different stability between clear insulin analog and turbid NPH insulin. CONCLUSIONS: Temperature as high as 37°C and cyclic temperature,had no effect on the stability of in-use insulin pen.

Type 1 diabetes management and outcomes: A multicenter study in Thailand.

AIMS/INTRODUCTION: The Thai Type 1 Diabetes and Diabetes Diagnosed Before Age 30 Years Registry, Care and Network was established in 2014 and involved 31 hospitals. The objective of the registry was to evaluate glycemic control and complications of patients with type 1 diabetes. MATERIALS AND METHODS: Patients' demographics, clinical data, frequencies of daily self-monitoring of blood glucose (SMBG), glycemic control and complications were collected. RESULTS: Among the 1,907 type 1 diabetes patients, the mean age was 21.2 ± 11.3 years. The mean glycated hemoglobin level was 9.35 ± 2.41%, with significant variations among age groups (P < 0.001). Conventional insulin treatment and intensive insulin treatment were used in 43 and 57% of patients, respectively. Mean glycated hemoglobin levels were significantly higher in patients treated with conventional insulin treatment compared to those treated with intensive insulin treatment (9.63 ± 2.34 vs 9.17 ± 2.46%, P = 0.002). Compared to the conventional insulin treatment group, significantly more patients in the intensive insulin treatment group achieved good glycemic control (P < 0.001), and fewer had diabetic retinopathy (P = 0.031). The prevalence of microvascular complications increased significantly with age (P < 0.001). Multivariate analysis showed good glycemic control to be associated with age 25 to <45 years, intensive insulin treatment with SMBG three or more times daily and diabetes duration of 1 to <5 years. CONCLUSIONS: Most Thai type 1 diabetes patients were not meeting the recommended glycemic target. As a result of this study, the national program to improve the quality of diabetes treatment and education has been implemented, and the results are ongoing.

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study.

Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively. Twelve type 2 diabetic, eight obese, and eight lean subjects exercised on a cycle ergometer for 40 min. Muscle biopsies were done before, during, and after exercise. Subjects underwent this protocol on two occasions, at low (50% Vo(2max)) and moderate (70% Vo(2max)) intensities, with a 4-6 week interval. Exercise had no effect on LKB1 activity. Exercise had a time- and intensity-dependent effect to increase AMPK activity and AS160 phosphorylation. Obese and type 2 diabetic subjects had attenuated exercise-stimulated AMPK activity and AS160 phosphorylation. Type 2 diabetic subjects had reduced basal PGC-1 gene expression but normal exercise-induced increases in PGC-1 expression. Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects.

Incretins: the novel therapy of type 2 diabetes.

Type 2 diabetes mellitus is a worldwide health problem. Adequate glycemic control can help to prevent many chronic diabetic complications. Despite the availability of several classes of oral hypoglycemic agents and insulin, many patients fail to achieve adequate glycemic control. Incretins are gut hormones produced in response to ingestion of nutrients. Glucagon-like peptide-1 (GLP-1), one of the incretin hormones, has pleiotropic actions on the control of blood glucose. Clinical trials with the incretin mimetic and Dipeptidyl peptidase-IV inhibitors demonstrate promising results in the improvement of glucose homeostasis.

Decreased health-related quality of life in patients with diabetic foot problems.

PURPOSE: The aim of this study was to investigate health-related quality of life (HRQoL) in patients with diabetic foot problems and compare the HRQoL between diabetic patients with: 1) diabetic foot problems (DF), including diabetic foot ulcer (DFU) or amputation (AMPU); 2) other diabetic complications (COM), such as diabetic retinopathy (DR), end-stage renal disease (ESRD), or coronary artery disease (CAD); and 3) no diabetic complication (CON). PATIENTS AND METHODS: A total of 254 diabetic patients were studied in a cross-sectional setting. HRQoL was evaluated using Thai version of the Euro Quality of Life Questionnaire (EuroQoL), with five dimensions and five-level scale (EQ-5D-5L). Utility scores were calculated using time trade-off methods. RESULTS: A total of 141 patients in the DF group (98 DFU and 43 AMPU groups), 82 in the COM group (27 DR, 28 ESRD, and 27 CAD groups), and 31 in the CON group were interviewed. The mean age was 63.2±12.1 years, body mass index was 24.9±4.7 kg/m2, mean hemoglobin A1c was 7.7±2.1%, duration of diabetes was 13.1±9.9 years, and the mean utility scores were 0.799±0.25. After having DF, 21% of patients had lost their jobs. The COM group had lower utility scores than the CON group. Among the diabetic complications, the DF group had the lowest mean utility scores as compared to the COM and CON groups (0.703±0.28 in the DF group, 0.903±0.15 in the COM group, and 0.961±0.06 in the CON group, P<0.01). There was no difference in the mean utility scores between DFU and AMPU groups. Patients in the DF group reported moderate-to-severe problem in all dimensions more than the other groups. CONCLUSION: DF have the greatest negative impact on HRQoL. Therefore, diabetic foot care should be emphasized in clinical practice to prevent foot complications.

Correlation Between Third Trimester Glycemic Variability in Non-Insulin-Dependent Gestational Diabetes Mellitus and Adverse Pregnancy and Fetal Outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic complication. Despite optimal glycemic control from self-monitoring blood glucose (SMBG) in non-insulin-dependent GDM, variations in pregnancy outcomes persist. Glycemic variability is believed to be a factor that causes adverse pregnancy outcomes. Continuous glucose monitoring system (CGMS) detects interstitial glucose values every 5 minutes, and glycemic variability data from CGMS during the third trimester may be a predictor of fetal birth weight and pregnancy outcomes. The aim of this study was to investigate correlation between third trimester glycemic variability in non-insulin-dependent GDM and fetal birth weight. METHOD: This prospective study was conducted in 55 pregnant volunteers with non-insulin-dependent GDM that were recruited at 28 to 32 weeks' gestation from the outpatient clinic of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital during the study period of August 1 to December 31, 2016. Patients had CGMS installed for at least 72 hours and glycemic variability data were analyzed. RESULTS: Of 55 enrolled volunteers, the data from 47 women were included in the analysis. Mean CGMS duration was 85.5 ± 12.83 hours. No statistically significant correlation was identified between glycemic variability in third trimester and birth weight percentiles, or between third trimester CGMS parameters and pregnancy outcomes in the study. CONCLUSION: Based on these findings, third trimester glycemic variability data from CGMS are not a predictor of fetal birth weight percentile, and no significant association was found between CGMS parameters and adverse pregnancy outcomes; thus, CGMS is not necessary in non-insulin-dependent GDM.

Relationship between vascular reactivity and lipids in Mexican-Americans with type 2 diabetes treated with pioglitazone.

CONTEXT: Vascular dysfunction and insulin resistance precede atherosclerosis in type 2 diabetes (T2DM). Better knowledge of the interaction between these is of considerable clinical interest. OBJECTIVE: The objective of this study was to examine the association between inflammation, glucose, and lipid metabolism and vascular dysfunction. DESIGN AND SETTING: We conducted a randomized, double-blind, controlled trial of pioglitazone vs. placebo and other therapies aimed at equal glycemic control for 24 wk at an academic tertiary referral clinic. PATIENTS AND INTERVENTIONS: Mexican-American subjects with T2DM and no complications were randomly assigned to pioglitazone 45 mg daily (PIO, n=16) or placebo (CON, n=15) and matched for age, gender, body mass index, diabetes duration, and glycemic control. All subjects completed the study. MAIN OUTCOME MEASURE: We looked for improved vascular reactivity independent of glycemic control but closely related to plasma adiponectin, lipids, and insulin sensitivity. RESULTS: After 24 wk, there was an equal decrease in fasting plasma glucose (approximately 135 mg/dl), glycosylated hemoglobin (approximately 7.0%), and glucose production (approximately 15%). The decrease in free fatty acids (30 vs. 10%) and increase in glucose disposal (40 vs. 25%) were greater in PIO vs. CON (P<0.05). In PIO, plasma high-density lipoprotein rose by 15% (P<0.05), and low-density lipoprotein and high-density lipoprotein particle size rose significantly (P<0.01). Plasma adiponectin doubled in PIO (from 6.1+/-0.8 to 12.7+/-2.1 microg/ml). Forearm blood flow rose equally (approximately 130%) during reactive hyperemia in both groups, although after therapy, the increase was greater (P<0.001) in PIO (153%) than in CON (137%); vasodilation was greater (P=0.01) in PIO (92, 160, and 204%) than in CON with acetylcholine (74, 130, and 144%) and with sodium nitroprusside (PIO=164 and 253% vs. 116 and 230%; P=0.04). The elevation in diameter was also greater in PIO (13 vs. 10%; P<0.05). Vascular responses correlated with plasma free fatty acids, adiponectin, and low-density lipoprotein particle size but not with glycemic control. CONCLUSION: These data indicate that pioglitazone improves vascular reactivity irrespective of glycemic control and suggest a close association with changes in fat cell metabolism.

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

High prevalence of diabetes and abnormal glucose tolerance in Thai women with previous gestational diabetes mellitus.

AIM: To determine the prevalence of and risk factors for abnormal glucose tolerance (AGT) in previous gestational diabetes mellitus (pGDM) women. METHODS: 100 pGDM women randomly selected from the database of the Department of Obstetrics/Gynecology. 75 g-OGTT were performed in subjects without known diabetes. AGT was diagnosed using the American Diabetes Association criteria. RESULTS: The mean age, pre-gestational BMI, and time since delivery were 38 ± 5 years, 24.5 ± 5.7 kg/m2, and 46 ± 26 months. Overall, 81% of the subjects had AGT, including IGT (38%), IGT + IFG (5%), T2DM (38%). Plasma glucose (PG) at 1 h after a 50 g-glucose challenge test (GCT), PG at 1 h after 100 g-OGTT, HbA1c, and HOMA-IR were significantly greater in women with AGT than normal glucose tolerance (NGT) women. The proportion of women with ≥3 abnormal PG values during 100 g-OGTT was greater in AGT than NGT group (50.7% vs. 15.8%). Multivariate analysis showed that PG ≥ 150 mg/dl at 1 h after a 50 g-GCT and ≥3 abnormal PG values in 100 g-OGTTs were risk factors for developing AGT. CONCLUSIONS: Eighty-one percent of pGDM women developed AGT within 4 years after delivery. Risk factors for AGT were PG ≥ 150 mg/dl at 1 h after a 50 g-GCT and ≥3 abnormal PG values in a 100 g-OGTT.