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.

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.

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.

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.

Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects.

PURPOSE: The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. METHODS: Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. RESULTS: Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL24h 195±17 vs 139±27, P<.001; SD24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE24h 94 [58, 153] vs 54 [16, 179], P=.01). CONCLUSION: Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV24h were associated with sepsis severity.

Effect of Moringa oleifera Leaf Capsules on Glycemic Control in Therapy-Naïve Type 2 Diabetes Patients: A Randomized Placebo Controlled Study.

BACKGROUND: Studies showed effects of Moringa oleifera (MO) on lowering blood sugar levels in animal and diabetes patients. The aims of this study were to determine the effect of MO leaf capsules on glucose control in therapy-naïve type 2 diabetes mellitus (T2DM) and to evaluate its safety. METHOD: This was a prospective randomized placebo controlled study. Therapy-naïve T2DM was randomly assigned to receive either 8 grams per day of MO leaf capsules (MO leaf group) or placebo for 4 weeks. Clinical and laboratory characteristics were recorded at screening and at the end of 4-week study. 9-point plasma glucose was obtained before and every week during the study. RESULTS: Thirty-two T2DM patients were enrolled. The mean age was 55 years and the mean HbA1C was 7.0%. There was no significant difference in FPG and HbA1C between groups. MO leaf group had SBP reduction by 5 mmHg as compared to baseline but this difference had no statistical significance. There were no adverse effects of MO leaf. CONCLUSIONS: Moringa oleifera leaf had no effect on glycemic control and no adverse effects in T2DM. Interestingly, this study demonstrated that MO leaf had a tendency on blood pressure reduction in T2DM, and this result needs further investigation.

Rare Cause of Recurrent Hypoglycemia: Insulin Autoimmune Syndrome.

We report a case of insulin autoimmune syndrome associated with several autoantibodies, presenting with recurrent hypoglycemia, predominantly in the postprandial period, which improved by dietary management and spontaneously resolved within two months. Differentiation from other causes of hyperinsulinemic hypoglycemia, such as insulinoma, is important to avoid unnecessary invasive procedures or surgical interventions. The 75-gram oral glucose tolerance test (OGTT) and mixed meal test showed a typical pattern, which may be useful indirect evidence of insulin autoimmune syndrome.

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.

A 33-Year-Old Man with Gynaecomastia and Galactorrhea as the First Symptoms of Graves Hyperthyroidism.

Graves' hyperthyroidism has a various number of well-recognized manifestations. Galactorrhea is a rare manifestation in this disease. We describe a 33-year-old man who presented with the symptoms of hyperthyroidism, gynaecomastia, and galactorrhea for 2 months. Physical examination revealed goitre, gynaecomastia, and galactorrhea, bilaterally. Laboratory investigations demonstrated high free thyroxine with suppressed thyroid-stimulating hormone level together with elevated anti-TSH receptor; therefore, the diagnosis of Graves' disease was confirmed. Other investigations to elucidate the etiology of galactorrhea were normal, so the galactorrhea was hypothesized to be caused by Graves' disease. The gynaecomastia and galactorrhea resolved with the successful treatment of hyperthyroidism. Although the galactorrhea is extremely rare in thyrotoxicosis male patients, to the best of our knowledge, this is the third case which reported gynaecomastia and galactorrhea in male patient who presented with thyrotoxicosis.

Type of dyslipidemia and achievement of the LDL-cholesterol goal in chronic kidney disease patients at the University Hospital.

BACKGROUND: Chronic kidney disease (CKD) has been defined as a coronary artery disease risk equivalent. Therefore, the current guideline has been recommended for CKD patients to reach and maintain a low-density lipoprotein-cholesterol (LDL-C) goal of less than 100 mg/dL. However, the data regarding the achievement of LDL-C goal in these patients is lacking. OBJECTIVE: This study was conducted to evaluate the types of dyslipidemia affecting patients with CKD stages 3 and 4 and to determine whether these patients achieved LDL-C goal. METHODS: We performed a retrospective chart review of patients with CKD stage 3 or 4 and dyslipidemia who were followed-up at Siriraj Hospital between October 2011 and September 2012. RESULTS: In total, 150 patients with CKD stage 3 or 4 and dyslipidemia were recruited. The mean age was 72±10 years, and the body mass index was 25.6±4 kg/m(2); 60% had CKD stage 3 with an estimated glomerular filtration rate of 34±12 mL/min/1.73 m(2), and 54% had type 2 diabetes. The percentage of patients with hypercholesterolemia was 78%, hypertriglyceridemia 54%, and low high-density lipoprotein-C 36%. Of these, 52% had mixed hyperlipidemia. Statin treatment was prescribed to 87% of the patients, of which only 31.3% achieved the LDL-C goal according to the National Cholesterol Education Program and the European Society of Cardiology/European Atherosclerosis Society recommendations. Patients who did not achieve the LDL-C goal had a higher cholesterol level at diagnosis and higher prevalence of type 2 diabetes and stroke than those who achieved it. CONCLUSION: Two-thirds of CKD patients with hyperlipidemia had mixed hyperlipidemia. Despite the high frequency of statin treatment, only one-third of patients with CKD achieved the LDL-C goal. Thus, a developmental plan for the management of dyslipidemia in patients with CKD should be implemented to increase their achievement of the LDL-C goal.

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.

Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long-term sulfonylurea and insulin combination therapy results in deterioration of glycemic control: a randomized controlled trial.

BACKGROUND: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. METHODS: In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. RESULTS: Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5-40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%±0.5% (62±5 mmol/mol) to 8.6%±1.2% (71±13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%±0.5% (61±5 mmol/mol) to 7.9%±1.2% (63±13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. CONCLUSION: Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion.

Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects.

Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.