Blood glucose may be another index to initiate insulin treatment besides glycated hemoglobin A1c after oral antidiabetic medications failure for glycemic control: A real-world survey.

Objective: The inertia of insulin initiation is a barrier to achieving glycemic control when oral antidiabetic drugs fail to control glucose during the treatment of type 2 diabetes (T2D). Insulin initiation is usually based on glycated hemoglobin A1c (A1C). To investigate whether there is another index for insulin initiation besides A1C, we conducted a cross-sectional survey in the real world. Methods: We conducted a multicenter cross-section survey with a total of 1034 T2D patients. All patients, at the time of the survey, decided to initiate insulin therapy due to failure of controlling glucose using only oral antidiabetic drugs. We analyzed the differences of blood glucose between patients who were tested for A1C and those who were not. Results: 666 (64.4%) patients were tested A1C and 368 (35.6%) were not. Neither fasting blood glucose (FBG) (12.0 ± 2.9 vs 12.3 ± 2.9 mmol/L, t = 1.494, P = 0.135) nor postprandial blood glucose (PBG) (18.4 ± 4.8 vs 17.9 ± 4.8 mmol/L, t = 1.315, P = 0.189) were significantly different between patients with and without A1C. Conclusion: Our results demonstrated that initiating insulin based on FBG or PBG is a common clinical practice, at least in China; moreover, since it is easier to obtain than A1C, it can be a simple and effective way to overcome clinical inertia for initiating insulin.

Moderators of the Association Between Serum Parathyroid Hormone and Metabolic Syndrome in Participants with Elevated Parathyroid Hormone: NHANES 2003-2006.

This cross-sectional study extracted data of 392 NHANES participants with elevated serum parathyroid hormone (PTH) concentrations from 2 cycles of the US National Health and Nutrition Examination Survey (NHANES) 2003-2006 and evaluated the association between serum (PTH) concentration and metabolic syndrome (MetS) to identify dietary and lifestyle factors that may modify that association. The primary outcome was MetS severity scores. Results of univariate linear regression analyses revealed that serum PTH concentrations correlated positively and significantly with MetS severity scores (ß=0.399, p=0.030). After adjusting for gender, age, race, and alcohol consumption, results of multivariate analysis revealed that increased serum PTH concentration correlated significantly with higher MetS severity scores (ß=0.413, p=0.045) in participants with moderate physical activity over the past 30 days. Serum PTH concentration also correlated significantly with higher MetS severity scores in participants with serum 25-hydroxyvitamin D deficiency (ß=0.456 and p=0.014), those without vitamin D supplementation (ß=0.524, p=0.028) and with higher protein intake (ß=0.586 and p=0.030). In conclusion, increased serum PTH concentration is associated with higher MetS severity scores in participants with elevated serum PTH at baseline. The association between PTH concentration and MetS severity is moderated by participants' physical activity levels, status of serum vitamin D, vitamin D supplementation, and daily protein intake.

Sugar-sweetened beverage intake and serum testosterone levels in adult males 20-39 years old in the United States.

BACKGROUND: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20-39 years old. METHODS: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. RESULTS: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m2 (aOR = 3.68, p = 0.044). CONCLUSION: SSB consumption is significantly associated with low serum testosterone in men 20-39 years old in the United States.

[Assessment of hypoglycemic status among hospitalized elderly patients with type 2 diabetes].

OBJECTIVE: To investigate the hypoglycemic characteristics of hospitalized elderly patients with type 2 diabetes mellitus (T2DM). METHODS: From January, 2014 to December, 2015, the data of 58 565 blood measurements using a standard blood glucose monitoring system (BGMS) were collected from 1187 cases of patients with type 2 diabetes during hospitalization in the Department of Endocrinology, Guangdong General Hospital (Guangzhou, China). Stratified analyses were conducted by dividing the patients into 3 age groups, namely <45 years group (128 cases), 45-64 years group (594 cases), and ≥65 years group (465 cases). The incidence and time distribution of hypoglycemia in these patients were compared among the 3 age groups. RESULTS: The risk of hypoglycemia increased with age. Compared with those below 45 years of age, the patients beyond or equal to 65 years had a significantly increased hypoglycemic density (0.95% vs 0.40%, P<0.001), a higher proportion of patients with hypoglycemia (28.17% vs 10.94%, P<0.001), and greater patient-days with hypoglycemia (4.48% vs 1.76%, P<0.001). In the elderly patients, hypoglycemia occurred most frequently before dawn, at which time the hypoglycemic density was 2.66% in patients ≥65 years of age, significantly higher than that in patients below 45 years (1.09%, P<0.05) and between 45 and 64 years (1.90%, P<0.05); the proportion of patients with hypoglycemia was also significantly higher in the elderly patients (14.57%) than in those below 45 years (3.77%, P<0.02) and between 45 and 64 years (9.42%, P<0.02). The proportion of patients with recurrent hypoglycemia (≥2 times) was significantly higher in patients ≥65 years (13.33%) than in younger patients (2.34% in <45 years group and 9.43% in 45-64 years group, P<0.05). CONCLUSION: The hypoglycemic risk in hospitalized elderly patients with T2DM is significantly higher than that in younger patients, especially before dawn and in terms of recurrent hypoglycemia. Clinicians should develop differential blood glucose monitoring and management strategies for these elderly patients to improve the clinical safety.

Continuous positive airway pressure and diabetes risk in sleep apnea patients: A systemic review and meta-analysis.

BACKGROUND: The study assessed the effect of continuous positive airway pressure (CPAP) therapy on the risk of developing type 2 diabetes by evaluating change in the homeostasis model assessment of insulin resistance (HOMA-IR) fasting blood glucose (FBG) and fasting insulin following CPAP treatment in non-diabetic patients and pre-diabetic with obstructive sleep apnea (OSA). METHODS: Medline, PubMed, Cochrane, and EMBASE databases were searched until August 24, 2015. The analysis included randomized controlled trials (RCTs), two arm prospective studies, cohort studies, and retrospective studies. The primary outcome measure was change of HOMA-IR in pre-diabetic patients receiving CPAP treatment. RESULTS: Twenty-three studies were included with 965 patients who had OSA. Nineteen studies were prospective studies and four were RCTs. CPAP therapy resulted in a significant reduction in the pooled standard difference in means of HOMA-IR (-0.442, P=0.001) from baseline levels compared with the control group. Change in FBG and fasting insulin from baseline levels was similar for the CPAP and control groups. For RCT studies (n=4), there was no difference in change in HOMA-IR or FBG levels from baseline between CPAP and control groups. The combined effect of RCTs showed that CPAP was associated with a significant reduction in change from baseline in fasting insulin than the control group (standardized diff. in means between groups=-0.479, P value=0.003). CONCLUSION: These findings support the use of CPAP in non-diabetic and pre-diabetic patients with OSA to reduce change of HOMA-IR and possibly reduce the risk of developing type 2 diabetes in this patient population.

Predictors of cardiorespiratory fitness in female and male adults with different body mass index: National Health and Nutrition Examination Survey 1999-2004 dataset.

BACKGROUND: The aim of this study was to explore factors affecting cardiorespiratory fitness in males and females with different body mass index (BMI). METHODS: The National Health and Nutrition Examination Survey 1999-2004 data were used for this retrospective study. Estimated maximal oxygen uptake (VO2max) is surrogate for cardiorespiratory fitness (CRF). Univariate and multivariate linear regression analyses were performed to explore whether study variables were associated with estimated VO2max stratified by gender and BMI categories. RESULTS: A total of 3292 subjects 20-49 years of age were included in the analysis. CRF significantly decreased as BMI increased in both females and males. Ethnic difference was found in normal BMI in both genders and obese females; homocysteine was significantly negatively associated with estimated VO2max, as was total cholesterol. Obese male subjects with diabetes had a lower estimated VO2max than those without diabetes, and C-reactive protein (CRP) level and vitamin B12 level were significantly negatively associated with CRF. Female subjects with diabetes had higher estimated VO2max than those without diabetes. Folate was significantly positively correlated with estimated VO2max, whereas CRP was negatively correlated in obese female. CONCLUSIONS: There are different predictors of CRF in males and females, and in individuals with different BMI. Key messages Different BMI classes are associated with different predictors of cardiorespiratory fitness. Indicators of cardiorespiratory fitness differ between sexes.

[Efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and factors affecting the therapeutic effect].

OBJECTIVE: To evaluate the clinical efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and analyze the factors affecting the efficacy. METHODS: Ultrasound-guided lauromacrogol sclerotherapy was performed in 97 patients with a total of 99 benign thyroid cysts. The changes in cystic volume and other thyroid parameters were evaluated at 1, 3, 6, and 12 months after sclerotherapy. According to changes in the cystic volume, the efficacy of sclerotherapy was defined as therapeutic failure (with a volume reduction <50%), treatment success (volume reduction ≥50%) and cure (volume reduction ≥90%). The factors of affecting the efficacy of sclerotherapy was analyzed using COX regression. RESULTS: The mean cystic volume at 1, 3, 6 and 12 months after sclerotherapy were reduced from the baseline volume of 12.08∓11.56 cm3 to 5.63∓8.51 cm3, 5.96∓8.42 cm3, 3.80∓5.50 cm3 and 2.85∓3.98 cm3, respectively, with an average cystic volume reduction rate of (70.02∓33.72)%. Therapeutic success was achieved 82 of the 99 cysts (82.83%) and cure was achieved 63cysts (63.64%) at 12 months after the procedure. A second sclerotherapy was performed for 13 cysts which did not show a volume reduction at 1-3 months after the initial procedure. A disease course of over 12 months was an independent risk factor for a second sclerotherapy (23.7% [9/38] vs 6.6% [4/61], OR=4.473 [1.238-16.169], P=0.022). The efficacy of sclerotherapy was related to cystic cavity separation, cystic fluid viscosity, cystic/solid ratio and cystic wall thickness. COX regression analysis revealed that cystic cavity separation (HR=2.25, 95%CI: 1.19-4.25) and cystic fluid viscosity (HR=2.02, 95%CI: 1.19-3.43) were the major factors affecting the treatment efficacy. CONCLUSION: Ultrasound-guided lauromacrogol sclerotherapy is effective and safe for treatment of benign thyroid cysts, and the maximal treatment effect can be achieved at 6 months after sclerotherapy and in cases of uncomplicated cysts with non-viscous cystic fluid, no solid cystic cavity separation and a disease course of less than 12 months.

Single-dose acarbose decreased glucose-dependent insulinotropic peptide and glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus after a mixed meal.

BACKGROUND: Acarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: In this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n = 11) and the mixed meal test (MMT) group (n = 12). Fourteen subjects with normal OGTT were included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0 (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later, controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose, and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers were measured again. RESULTS: No significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of glucose (P < 0.01), insulin (P < 0.01), glucagon at 15 min (P < 0.05), glucagon area under the curve (AUC) (P < 0.05), GIP levels at 30 min (P < 0.05), and GIP AUC (P < 0.05) were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change. CONCLUSIONS: Single-dose acarbose could reduce the secretion of GIP and glucagon after a mixed meal in patients with newly diagnosed T2DM. The influence of acarbose on incretin levels could be related to the types of carbohydrate being consumed. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR-TRC-14004260 , Date of Registration: 2014-01-19).

Effects of sulfonylurea as initial treatment on testosterone of middle-aged men with type 2 diabetes: A 16-week, pilot study.

AIMS/INTRODUCTION: To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes. MATERIALS AND METHODS: As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study. After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks. Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group. RESULTS: Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index. Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values. Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline. CONCLUSIONS: It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.

Effect of lifestyle intervention in patients with type 2 diabetes: a meta-analysis.

OBJECTIVE: The effect of lifestyle intervention on clinical risk factors in patients with type 2 diabetes is unclear. The aim of this meta-analysis was to evaluate the effects of comprehensive lifestyle change, such as diet, exercise, and education, on clinical markers that are risk-factors for cardiovascular disease in patients with type 2 diabetes. METHODS: We searched Medline, Cochrane, EMBASE, and Google Scholar (up to August 31, 2013) for randomized controlled trials that compared standard of care (control group) with treatment regimens that included changes in lifestyle (intervention group). The primary outcome was reduction in risk factors of cardiovascular disease including body mass index (BMI), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). RESULTS: A total of 16 studies were included in the meta-analysis. The standardized difference in means of change from baseline significantly favored the intervention compared with the control group in BMI (-0.29; 95% CI, -0.52 to -0.06, P=0.014), HbA1c (-0.37; 95% CI, -0.59 to -0.14, P=0.001), SBP (-0.16: 95% CI, -0.29 to -0.03, P=0.016), DBP (-0.27, 95% CI=-0.41 to -0.12, P<0.001). There was no difference between the intervention and control groups in HDL-c (0.05; 95% CI, -0.10 to 0.21; P=0.503) and LDL-c (-0.14; 95% CI, -0.29 to 0.02; P=0.092). CONCLUSIONS: The meta-analysis found that lifestyle intervention showed significant benefit in risk factors that are known to be associated with development of cardiovascular disease in patients with type 2 diabetes.

Effects of continuous positive airway pressure treatment on glycaemic control and insulin sensitivity in patients with obstructive sleep apnoea and type 2 diabetes: a meta-analysis.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a prevalent disorder characterised by repetitive upper-airway obstruction during sleep, and it is associated with type 2 diabetes. Continuous positive airway pressure (CPAP) is the primary treatment for OSA. Prior studies investigating whether CPAP can improve insulin resistance or glucose control in OSA patients have resulted in conflicting findings. This meta-analysis investigated whether CPAP treatment could improve glucose metabolism and insulin resistance in patients with OSA and type 2 diabetes. MATERIAL AND METHODS: We performed a systematic literature search using Medline, Cochrane, EMBASE, and Google Scholar databases for randomised controlled prospective studies that investigated the effect of CPAP on glycaemic control or insulin sensitivity in subjects with type 2 diabetes. RESULTS: The combined standard (STD) paired difference in mean change in the levels of glycated haemoglobin (HbA1c) was -0.073% (standard error (SE): 0.126), indicating that CPAP treatment did not alter HbA1c levels. The combined STD paired difference in mean change of insulin sensitivity was observed as 0.552 µmol/kg • min (SE = 0.196) and indicated insulin sensitivity significantly increased with CPAP treatment (p = 0.005). CONCLUSIONS: We found that the CPAP treatment did not alter HbA1c levels but did significantly improve insulin resistance, indicating treating OSA can positively impact the symptoms of type 2 diabetes.

[Preventive effects of pioglitazone on diabetes and relevant mechanisms, experimental study on non-obese diabetic mice].

OBJECTIVE: To explore the effects of pioglitazone on insulitis and diabetes and relevant mechanism. METHODS: Seventy-three female non-obese diabetic (NOD)/Lt mice aged 4 weeks were randomly divided into 3 groups, control group (n = 25, fed with regular diet), low dosage pioglitazone group (n = 23, pioglitazone of the concentration of 0.01% was added into the feed) and high dosage pioglitazone group (n = 25, pioglitazone of the concentration of 0.04% was added into the feed). The mice were killed when diabetes developed or they reached the age of 30 weeks. The body weight and amount of food intake were measured every week and the amount of drug intake was calculated. Urine glucose was checked weekly from week 10 to week 30. When urine glucose was positive and relevant symptoms appeared, blood glucose was measured. The criterion of diagnosis of diabetes was the consecutive blood glucose level > or = 16.7 mmol/L for 2 times. At the 12th week 4-7 mice from the 3 groups respectively were killed and their pancreases were removed to be scored on insulitis by HE staining, the spleen cells were cultured. The IL-4 and IFN-r levels in serum and supernatants of spleen cell cultures were measured by ELISA. The pancreatic IFN-r mRNA level was tested using RT-PCR method. RESULTS: (1) At the age of 30 weeks, the diabetes incidence rates was 80% (20/25) in the control group, 60.9% (14/23) in the low dose group, and 60% (15/25) in the high dose group (P > 0.05). At the following time points the diabetes incidence rates of the 2 treated groups were lower than that of the control group (all P < 0.05): (1) 0% in the low dose group vs 16%: of the control group at the age of 100 days, and 39% vs 68% at the age of 185 days; and (2) 0% in the high dose group vs 16% in the control group at the age of 110 days, 4% vs 24% at the age of 120 days, and 12%vs 36% at the age of 135 days. (2) There was no difference in insulitis scores between the control group and low dose or high dose groups at the age of 12 weeks (1.99 +/- 0.75 vs 1.01 +/- 0.68 and 1.19 +/- 0.84, both P > 0.05), however, the score of the combined pioglitazone group (low dose group + high dos group) was significantly higher than that of the control group (1.12 +/- 0.75 vs 1.99 +/- 0.75, P < 0.05). (3) There was no differences in the IL-4/IFN-r ratios in serum and splenocyte culture supernatant and pancreatic IFN-r mRNA levels among the three groups (all P > 0.05). CONCLUSION: Pioglitazone, to some extent, lessens the insulitis severity and delays the diabetes onset. Its mechanism may be unrelated to immune deviation of Th1 to a Th2.

[Mechanisms of human glutamic acid decarboxylase 65 DNA vaccine preventing diabetes in non-obese diabetic mice].

OBJECTIVE: To investigate the mechanisms of human GAD65 DNA vaccine preventing insulitis and diabetes in NOD mice. METHODS: Female NOD mice at 4 weeks of age were randomly divided into PBS (n = 21), pcDNA (n = 20), and hGAD65 (n = 21) groups. Mice in each group received two intramuscular injections of 0.05 ml PBS alone, 50 microg pcDNA3.1 and 50 microg DNA vaccine emulsified in 0.05 ml PBS 7 days apart respectively. The accumulative diabetes incidence was followed-up to 30 weeks of age in each group of NOD mice. Pancreas was removed from NOD mice at 12 weeks of age in each group (n = 10) to score insulitis severity by routine H-E staining. The apoptotic beta cells in islets were observed with double-labeling technique of TUNEL in situ combined standard sensitive avdin-biotin complex (sABC) immunohistochemical method. Their spleens were for cell culture and total RNA extraction. Spleen IL-4, IFN-gamma, NF-ATc and NF-ATp mRNA levels were tested by RT-PCR. IL-4 and IFN-gamma levels in sera and supernatants of spleen cells were measured by ELISA. RESULTS: (1) At 30 weeks of age, the diabetes incidence was 95.2%, 80.0% and 61.9% in PBS, pcDNA and hGAD65 group respectively. The diabetes incidence in the PBS group was higher than that in hGAD65 group (P = 0.008). (2) At 12 weeks of age, the insulitis scores in hGAD65 group was lower than that in PBS group (P = 0.001) and pcDNA group (P = 0.027) respectively. (3) The apoptotic beta cell rates in hGAD65 group was lower than that in PBS group (P = 0.014) and pcDNA group (P = 0.023). (4) IL-4 levels in sera, spleen IL-4 and NF-ATc mRNA level in hGAD65 group were higher than those in PBS group (all P < 0.05) and pcDNA group (all P < 0.05) respectively, NF-ATp mRNA level in hGAD65 group was lower than that in PBS group (P < 0.05). CONCLUSION: Human GAD65 DNA vaccine via downregulating NF-ATp and upregulating NF-ATc and IL-4, makes Th cells deviate to Th2, and sequently prevents insulitis, beta-cell apoptosis and diabetes onset in NOD mice.