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.

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

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.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial.

BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. METHODS: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 µU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 µU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. REGISTRATION NUMBER: ChiCTR-TRC-13003776.

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.

Efficacy and safety of glimepiride as initial treatment in Chinese patients with Type 2 diabetes mellitus.

OBJECTIVE: To investigate the efficacy and safety of glimepiride as initial mono-therapy in type 2 diabetes patients in China. METHODS: This is a multi-center, open-label, single arm study. A total of 391 subjects were enrolled to receive glimepiride treatment for 16 weeks, the initiation dose was 1 mg/d, with titration to 2 mg/d and 4 mg/d according to the fasting blood glucose (FBG) level measured at each visit. The change in HbA1c, fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPPG), HOMA-IR, weight, waist circumference and the incidence of hypoglycemia were evaluated. An exploratory analysis was conducted to identify the potential population prone to achieve target glycemic control. RESULTS: HbA1c was reduced significantly from 8.6 ± 1.6% to 6.9 ± 0.9% (p < 0.001); 60.9% of the subjects achieved HbA1c <7% at study endpoint. The reduction in FPG and 2hPPG were 2.3 mmol/L and 4.4 mmol/L (p < 0.001) respectively. Insulin resistance was improved significantly with HOMA-IR decreasing from 2.5 ± 2.3 to 2.2 ± 1.9 (p = 0.009). The incidence of confirmed hypoglycemia (BG ≤ 3.9 mmol/L) was 3.1%. CONCLUSIONS: Glimepiride treatment as initial mono-therapy could effectively improve blood glucose control in type 2 diabetic patients, with a favorable safety profile. Lack of control group was the major limitation of this study. ClinicalTrial.gov identifier: NCT00908921.

[Effect of different dietary loads on glucose-dependent insulinotropic polypeptide in subjects with normal glucose tolerance].

OBJECTIVE: To investigate the secretion patterns of glucose-dependent insulinotropic polypeptide (GIP) after different dietary loads in subjects with normal glucose tolerance (NGT) and their relation to insulin secretion and plasma glucose levels. METHODS: Fourteen subjects with normal glucose tolerance underwent 75 g glucose tolerance test(OGTT) followed by mixed meal tolerance test(MMT) one week later. Blood glucose, insulin, and GIP were measured in the fasting state and at 0, 15, 30, 60, 90 and 120 min after glucose load or mixed meal load. RESULTS: The first peak value of GIP after glucose load occurred at 15 min (45.09∓4.67 pmol/L). After a brief decline, GIP continued to increase till reaching 59.66∓11.73 pmol/L at 120 min after the load. After the mixed meal load, GIP secretion presented with two peaks: the first peak appeared at 15 min (71.69∓14.19 pmol/L) with a level significantly higher than that at 15 min following glucose load (P<0.05), and the second occurred at 90 min (55.35∓13.19 pmol/L). The area under curve of GIP showed no significant difference between the two loads (P>0.05). Compared with glucose load, mixed meal load resulted in an increase of the first GIP peak and an earlier insulin peak (30 min vs 60 min), but a significant decrease of blood glucose at 15 min (P<0.05). CONCLUSION: Compared with glucose load, mixed meal (containing fat) can strongly stimulate GIP release and cause earlier occurrence of the insulin peak, which might be an important reason for the lower blood glucose after mixed meal.

Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor.

BACKGROUND: Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. METHODS: 83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. RESULTS: Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. CONCLUSIONS: Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.

[High glucose up-regulates GRK2 gene expression in H9C2 cardiomyoblasts in vitro].

OBJECTIVE: To study the effect of high glucose on GRK2 gene expression in H9C2 cardiomyoblasts in vitro. METHODS: H9C2 cardiomyoblasts were cultured for 72 h in the presence of 0, 5.5, 12.5, 25 or 33 mmol/L glucose (with the osmotic pressure adjusted with monnitol). Semi-quantitative detection of GRK2 gene expression in H9C2 cardiomyoblasts was carried out using RT-PCR and phosph-Akt (Ser473) protein level was measured by Western blotting. RESULTS: Glucose in the culture medium (5.5 to 33 mmol/L) concentration-dependently increased the mRNA expression of GRK2 concentration and decreased phosphorylation Akt (ser473) level in in H9C2 cardiomyoblasts. CONCLUSION: Increased GRK2 gene expression may play an important role in cardiac dysfunction in diabetes.

[A survey of glucose and lipid metabolism and concomitant diseases among inpatients in Guangdong province].

OBJECTIVES: To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients. METHODS: A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004. The fasting blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and concomitant disorders of the first screen during the hospitalization period were recorded. Those who had FBG level from 5.6 to 6.9 mmol/L and not been previously diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTT). RESULTS: Of the 8753 inpatients investigated, 1067 cases had complete medical records (CMR case) including PDM cases and previously non-diagnosed diabetes ones with FBG > or = 5.6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels from 5.6 to 6.9 mmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM, 21.7% was newly diagnosed diabetes mellitus (NDM), 29.1% had impaired glucose regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05, respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P < 0.05, respectively). Only 22.8% of the PDM inpatients underwent treatment of dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP-III. BMI was higher and waistline longer in the PDM and NDM inpatients than those in the NGT cases (P < 0.05, respectively). Seventy-two point eight percent of the PDM inpatients was complicated with more than one type of vascular diseases. Nine point seven percent and 0.2% of the NDM inpatients were tormented by diabetic nephropathy and diabetic retinopathy respectively. CONCLUSIONS: More inpatients with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which included hypertriglyceridemia, hypo-high-density lipoproteinemia and metabolic syndrome. Concomitant vascular diseases were more frequently found in PDM inpatients than in the others. Some of the NDM and IGT inpatients were complicated with microvascular diseases.

Inadequate glycaemic control and antidiabetic therapy among inpatients with type 2 diabetes in Guangdong Province of China.

BACKGROUND: Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. METHODS: Inadequate glycaemic control in diabetic patients was defined as HbA1c = 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents (OA), insulin plus OA (insulin + OA), or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. RESULTS: Among 493 diabetic inpatients with known history, 75% had HbA1c = 6.5%. Inadequate glucose control rates were more frequently seen in patients on insulin + OA regimen (97%) than on OA regimen (71%) (P < 0.001), and more frequent in patients on combination therapy (81% - 96%) than monotherapy (75%) (P < 0.05). Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI (P < 0.01). CONCLUSIONS: This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed. It is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.

[A multicenter clinic study of slow-release-gliclazide in type 2 diabetes mellitus].

OBJECTIVE: To evaluate the efficacy and safety of 30 mg slow-release-gliclazide (Diamicron MR) on type 2 diabetes patients with the level of blood glucose poorly controlled formerly. METHODS: 154 type 2 diabetes patients with the level of blood glucose poorly controlled formerly were enrolled and treated with Diamicron MR for 16 weeks. The efficacy of slow-release-gliclazide was evaluated through HbA1c, FPG and 2 h PBG after 16 weeks of treatment period. The safety was evaluated through the adverse events including hypoglycemic episodes and the change of vital signs and clinic laboratory parameters. RESULTS: After 16 weeks of treatment period, the HbA1c, FPG and 2 h PBG were decreased by 1.89%, 2.31 mmol/L and 3.94 mmol/L respectively, cutting down 21.6%, 24.5% and 27.8% relatively in comparison with pre-treatment. Glucose metabolism could be significantly improved by taking once-daily Diamicron MR. CONCLUSION: Slow-release-gliclazide offers the significant treatment safely, which is important to optimize type 2 diabetes mellitus management.