Methodology for Quantifying Fasting Glucose Homeostasis in Type 2 Diabetes: Observed Variability and Lability

Background:

Increased glycemic variability is associated with an increase risk of adverse clinical outcomes in diabetes. Central to the understanding of diabetes is glucose homeostasis. “Good” homeostasis is equated to low glycemic variability, and “poor” homeostasis is linked to greater glycemic variability. We have, therefore, developed a method with the aim to objectively quantify the domain of glucose–insulin homeostasis. We have termed this method as Observed Variability And Lability (OVAL).

Method:

Blood samples for the measurement of glucose and insulin concentrations were acquired every 2 min for 120 min from 12 patients with type 2 diabetes mellitus [T2DM; median (range) age 35 (25–47) years and duration of diabetes 7 (2–9) years receiving oral hypoglycemic treatment] and 27 controls [aged 38(30–53) years] with an equal split of genders and equal distribution of body mass indexes. The insulin–glucose time variant data form the boundaries of OVAL, defined as the ellipse enclosing the 95% confidence intervals of the insulin and glucose concentrations plotted on an x−y scatter graph and normalized to ensure equal weighting of insulin and glucose.

Results:

Less precise OVAL homeostasis was observed in subjects with T2DM, by a factor of 4, in comparison with controls [OVAL, T2DM 7.8(3.8) versus controls 1.9(1.0); p =.0003]. The assessment remained statistically robust (p <.001) with increased sampling intervals up to 8 min.

Conclusion:

The OVAL model is a robust method for measuring glucose–insulin homeostasis in controls and T2DM subjects (available online at http://www.oval-calc.co.uk). Deranged glucose–insulin homeostasis is the hallmark of diabetes and OVAL has the capacity to quantify in the fasting state.     

Efficacy of continuous glucose monitoring in improving glycemic control and reducing hypoglycemia: a systematic review and meta-analysis of randomized trials

Objective

We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG).

Methods

We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model.

Results

Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews.

Conclusion

Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.     

Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males

Background:

A high-protein (HP), low-fat weight-loss diet may be advantageous for improving cardiometabolic health outcomes and body composition. To date, only limited research has been conducted in male participants.

Objective:

To evaluate the medium to long-term effects of two, low-fat, hypocaloric diets differing in carbohydrate:protein ratio on body composition and cardiometabolic health outcomes in overweight and obese males.

Design:

One hundred and twenty males (age 50.8±9.3 (s.d.) years, body mass index 33.0±3.9 kg m⁻²) were randomly assigned and consumed a low-fat, isocaloric, energy-restricted diet (7 MJ per day) with either HP (protein:carbohydrate:fat %energy, 35:40:25) or high carbohydrate (HC; 17:58:25). Body weight, body composition and cardiometabolic risk factors were assessed at baseline and after 12 and 52 weeks.

Results:

Sixty-eight participants completed the study (HP, n=33; HC, n=35). At 1 year both the groups experienced similar reductions in body weight (HP, −12.3±8.0 kg (−12%); HC, −10.9±8.6 kg (−11%); P=0.83 time × group interaction) and fat mass (−9.9±6.0 kg (−27%) vs −7.3±5.8 kg (−22%); P=0.11). Participants who consumed the HP diet lost less fat-free mass (−2.6±3.7 kg (−4%) vs −3.8±4.7 kg (−6%); P<0.01). Both groups experienced similar increases in high-density lipoprotein cholesterol (8%) and reductions in total cholesterol (−7%), low-density lipoprotein cholesterol (−9%), triglycerides (−24%), glucose (−3%), insulin (−38%), blood pressure (−7/−12%) and C-reactive protein (−29%), (P⩾0.14).

Conclusion:

In overweight and obese men, both a HP and HC diet reduced body weight and improved cardiometabolic risk factors. Consumption of a HP diet was more effective for improving body composition compared with an HC diet.     

Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

Objective

To determine the efficacy of cholinesterase inhibitors (ChEIs) in improving the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease (AD).

Data sources

We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies.

Data extraction

We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF) guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis.

Results

We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confidence interval [CI]; −0.18, −0.01) and a weighted mean difference (WMD) of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46). In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66); and in studies with severe AD patients, the WMD was −0.06 (95% CI; −2.12, +0.57).

Conclusion

Cholinesterase inhibitors lead to a statistical significant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.     

A dietary intervention for chronic diabetic neuropathy pain: a randomized controlled pilot study

Background:

Diabetic neuropathy is a common and often debilitating condition for which available treatments are limited. Because a low-fat plant-based diet has been shown to improve glycemic control in individuals with type 2 diabetes, we hypothesized that such a diet would reduce painful symptoms of diabetic neuropathy.

Methods:

In this 20-week pilot study, individuals with type 2 diabetes and painful diabetic neuropathy were randomly assigned to two groups. The intervention group was asked to follow a low-fat, plant-based diet, with weekly classes for support in following the prescribed diet, and to take a vitamin B12 supplement. The control group was asked to take the same vitamin B12 supplement, but received no other intervention. At baseline, midpoint and 20 weeks, clinical, laboratory and questionnaire data were collected. Questionnaires included an analog ‘worst pain'' scale, Michigan Neuropathy Screening Instrument, global impression scale, Short Form McGill Pain Questionnaire, Neuropathy Total Symptom Score, a weekly pain diary and Norfolk Quality of Life Questionnaire.

Results:

After 20 weeks, body weight change with the intervention was −6.4 kg (95% confidence interval (CI) −9.4 to −3.4, P<0.001) in an effect size analysis. Electrochemical skin conductance in the foot improved by an average of 12.4 microseimens (95% CI 1.2–23.6, P=0.03) with the intervention in an effect size analysis. The between-group difference in change in pain, as measured by the McGill pain questionnaire, was −8.2 points (95% CI −16.1 to −0.3, P=0.04). Michigan Neuropathy Screening Instrument questionnaire score change was −1.6 points (95% CI −3.0 to −0.2, P=0.03).

Conclusions:

Improvements were seen in some clinical and pain measures. This pilot study suggests the potential value of a plant-based diet intervention, including weekly support classes, for treating painful diabetic neuropathy.     

A systematic review and meta-analysis of studies comparing laparoscopic and open distal pancreatectomy

Objectives

Currently, laparoscopic distal pancreatectomy (LDP) is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review compares outcomes of the laparoscopic technique with those of open distal pancreatectomy (ODP) and assesses the efficacy, safety and feasibility of each type of procedure.

Methods

Comparative studies published between January 1996 and April 2012 were included. Studies were selected based on specific inclusion and exclusion criteria. Evaluated endpoints were operative outcomes, postoperative recovery and postoperative complications.

Results

Fifteen non-randomized comparative studies that recruited a total of 1456 patients were analysed. Rates of conversion from LDP to open surgery ranged from 0% to 30%. Patients undergoing LDP had less intraoperative blood loss [weighted mean difference (WMD) −263.36.59 ml, 95% confidence interval (CI) −330.48 to −196.23 ml], fewer blood transfusions [odds ratio (OR) 0.28, 95% CI 0.11–0.76], shorter hospital stay (WMD −4.98 days, 95% CI −7.04 to −2.92 days), a higher rate of splenic preservation (OR 2.98, 95% CI 2.18–3.91), earlier oral intake (WMD −2.63 days, 95% CI −4.23 to 1.03 days) and fewer surgical site infections (OR 0.37, 95% CI 0.18–0.75). However, there were no differences between the two approaches with regard to operation time, time to first flatus and the occurrence of pancreatic fistula and other postoperative complications.

Conclusions

Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analyses. It may be a safe and feasible option for patients with lesions in the body and tail of the pancreas. However, randomized controlled trials should be undertaken to confirm the relevance of these early findings.     

Abdominal adiposity and daily step counts as determinants of glycemic control in a cohort of patients with type 2 diabetes mellitus

Objective:

Favorable effects of walking levels on glycemic control have been hypothesized to be mediated through reductions in abdominal adiposity, but this has not been well studied. We addressed this issue in patients treated for type 2 diabetes.

Design:

Cross-sectional analysis.

Subjects:

A total of 201 subjects with type 2 diabetes underwent assessments of pedometer-measured daily step counts, blood pressure, A1C and anthropometric measures (2006–2010). Associations of anthropometric indicators of abdominal adiposity (that is, waist circumference; waist-to-hip ratio (WHR)) with A1C were evaluated through linear regression models adjusting for age, ethnicity, sex and the use of insulin and oral hypoglycemic agents. Models including waist circumference were additionally adjusted for body mass index (BMI). A similar approach was used to examine A1C and daily step associations.

Results:

Among the 190 subjects (mean age 60 years; mean BMI 30.4 kg m⁻²), mean values (s.d.) for waist circumference and WHR were respectively, 99.1 cm (13.3) and 0.88 (0.07) in women, and 104.5 cm (13.1) and 0.97 (0.06) in men. Mean A1C and daily step count were respectively, 7.6% (1.4) and 5 338 steps per day (2609), and were similar for both sexes.There was a 0.51% (95% confidence interval (CI): 0.10, 0.93) A1C increment per s.d. increase in waist circumference and a 0.32% (95% CI: 0.08, 0.56) A1C increment per s.d. increase in WHR in fully adjusted models. Each s.d. increase in daily step count was associated with clinically significant reductions in waist circumference and BMI. Each s.d. increase in daily steps was associated with a 0.21% (95% CI: 0.02, 0.41) A1C decrement that declined to 0.16% (95% CI: −0.35, 0.04) with further adjustment for anthropometric indicators of abdominal adiposity.

Conclusion:

Higher daily steps may be associated with lower A1C values both directly and via changes in abdominal adiposity.     

Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial

Background:

Phosphorus status is inversely correlated with body weight; however, the effect of phosphorus supplementation on body weight in a controlled design has not been studied.

Methods:

This is a double-blind, randomized, placebo-controlled trial of 63 adults aged 18–45 years with a body mass index (BMI) of ⩾25 kg m⁻² and normal kidney function at the American University of Beirut. Participants were randomly assigned to the placebo or phosphorus group where daily placebo or phosphorus supplements were ingested with three main meals (breakfast, lunch and dinner) for a period of 12 weeks. Primary outcomes were changes in anthropometric measures, blood metabolites (including lipid profile, glucose and insulin) and subjective appetite scores. The trial is registered with Clinical Trial.gov, {"type":"clinical-trial","attrs":{"text":"NCT02329990","term_id":"NCT02329990"}}NCT02329990.

Results:

Body weight was significantly lower in the phosphorus group when compared with the placebo group (−0.65 kg (95% confidence interval (CI) −1.69 to 0.40) vs 1.13 kg (95% CI 0.19 to 2.06), P=0.01). Similarly, BMI and waist circumference were significantly lower in the phosphorus group when compared with the placebo group (−0.24 kg m⁻² (95% CI −0.59 to 0.12) vs 0.42 kg m⁻² (95% CI 0.05 to 0.78), P=0.01; −3.62 cm (95% CI−4.90 to −2.33) vs 0.38 cm ( 95% CI−0.44 to 1.20), P<0.001; respectively). Several parameters of subjective appetite scores were decreased in the phosphorus-supplemented group.

Conclusions:

Phosphorus supplementation for 12 weeks significantly decreases body weight, BMI, waist circumference and subjective appetite scores. These findings support a promising role of the mineral phosphorus in the prevention and management of obesity, especially abdominal adiposity. The exact mechanisms of action and longer-term effects still need to be elucidated.     

Can a relatively low-intensity intervention by health professionals prevent weight gain in mid-age women? 12-Month outcomes of the 40-Something randomised controlled trial

Background:

Weight gain in perimenopausal women results in increased visceral adipose tissue, leading to metabolic syndrome and associated comorbidities. Despite a high prevalence of weight gain at this life stage, interventions to prevent menopausal obesity are lacking.

Aim:

To test the effectiveness of an intervention delivered by health professionals using a motivational interviewing (MI) counselling style in preventing weight gain in non-obese (body mass index (BMI) 18.5 and 29.9 kg m⁻²) women in late premenopause.

Methods:

In a randomised controlled trial, 54 women (mean (s.d.) age 47.3 (1.8) years; BMI 25.1 (2.4) kg m⁻²) who had menstruated within the preceding 3 months were randomly assigned to an MI intervention (n=28) (five health professional MI counselling sessions) or a self-directed intervention (SDI) (print materials only) (n=26). The primary outcome, body weight (kg) and secondary outcomes (blood lipids, glucose, body fat %, lean mass % and waist circumference) were measured at baseline and postintervention (12 months), and intention-to-treat analysis was conducted.

Results:

Forty women completed all measures and adhered to all protocols. The weight at 12 months for the MI group of 65.6 kg (95% CI: 64.5; 66.8) was significantly different (P=0.034) from the SDI group of 67.4 kg (95% CI: 66.2; 68.6). When stratified by baseline BMI category, the MI group lost significantly more weight (−2.6 kg; 95% CI: −3.9; −1.2) than the SDI group (−0.1 kg; 95% CI: −1.2; 1.0, P=0.002) for the healthy weight women. The overweight women lost weight regardless of the intervention group, with no between-group difference (−3.5 kg; 95% CI: −6.1, −1.0 and −2.3; 95% CI: −4.1, −0.5, P=0.467).

Conclusion:

This relatively low-intensity intervention, incorporating MI into health professional counselling, not only effectively prevented weight gain but also achieved significant weight loss and decreased diastolic blood pressure. Further refinements are required to optimise outcomes for overweight women.     

Noninvasive Skin Fluorescence Spectroscopy is Comparable to Hemoglobin A1c and Fasting Plasma Glucose for Detection of Abnormal Glucose Tolerance

Aim:

We compare performance of noninvasive skin fluorescence spectroscopy (SFS), fasting plasma glucose (FPG), and hemoglobin A1c (A1C) for detection of abnormal glucose tolerance (AGT).

Methods:

The NSEEDS trial evaluated SFS, FPG, and A1C in an at-risk population of 479 previously undiagnosed subjects from nine US centers, each of whom received a 75 g, 2 h oral glucose tolerance test (OGTT). Skin fluorescence spectra were collected and analyzed with SCOUT DS^® devices. Disease truth was AGT, defined as OGTT ≥140 mg/dl. Abnormal glucose tolerance sensitivity, false positive rate (FPR), and receiver operating characteristic (ROC) curves were computed for each measurement technique. Skin fluorescence spectroscopy reproducibility was also assessed.

Results:

The AGT sensitivity of SFS was 68.2%, higher than that of FPG (thresholds of 100 and 110 mg/dl) and A1C (thresholds of 5.7% and 6.0%). The FPR of SFS was 37.7%, comparable to A1C at the 5.7% threshold (30.7%). Partial ROC areas of SFS, FPG, and A1C were similar for FPRs of 20–50% (average sensitivities of 64.0%, 59.0%, and 68.6%, respectively). The interday coefficient of variation for SFS was 7.6%.

Conclusions:

Skin fluorescence spectroscopy has similar screening performance to FPG and A1C and is a viable approach for detection of AGT.     

Yacon diet (Smallanthus sonchifolius,Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

Objective:

Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose.

Methods:

We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study.

Results:

Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl⁻¹ (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg⁻¹ per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats.

Conclusion:

These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state.     

A randomized comparison of a commercially available portion-controlled weight-loss intervention with a diabetes self-management education program

Objective:

This study examined the efficacy of a commercially available, portion-controlled diet (PCD) on body weight and HbA_1c over 6 months in obese patients with type 2 diabetes.

Research Design and Methods:

One-hundred participants with a mean±s.d. age of 55.6±10.6 year, body weight of 102.9±18.4 kg and HbA_1c of 7.7±1.3% were randomly assigned to a 9-session group lifestyle intervention that included a PCD or to a 9-session group program of diabetes self-management education (DSME). Participants in the two groups were prescribed the same goals for energy intake (1250–1550 kcal per day) and physical activity (200 min per week).

Results:

While both groups produced significant improvements in weight and HbA_1c after 6 months of treatment, PCD participants lost 7.3 kg [95% confidence interval (CI): −5.8 to −8.8 kg], compared with 2.2 kg (95% CI: −0.7 to −3.7 kg) in the DSME group (P<0.0001). Significantly more PCD than DSME participants lost ⩾5% of initial weight (54.0% vs 14.0%, P<0.0001) and ⩾10% (26.0% vs 6.0%, P<0.0001). HbA_1c declined by 0.7% (95% CI: −0.4 to −1.0%) in the PCD group, compared with 0.4% (95% CI: −0.1 to −0.7%) in DSME (P<0.026). Across both groups, larger weight losses were associated with greater reductions in HbA_1c (r=0.52, P<0.0001).

Conclusions:

These findings demonstrate that a commercially available portion-controlled meal plan can induce clinically meaningful improvements in weight and glycemic control in obese individuals with type 2 diabetes. These data have implications for the management of obesity in primary care, as now provided by the Centers for Medicare and Medicaid Services.     

High saturated-fat and low-fibre intake: a comparative analysis of nutrient intake in individuals with and without type 2 diabetes

Objective:

The aim of dietary modification, as a cornerstone of type 2 diabetes (T2DM) management, is to optimise metabolic control and overall health. This study describes food and nutrient intake in a sample of adults with T2DM, and compares this to recommendations, and to intake in age, sex, body mass index (BMI) and social-class matched adults without T2DM.

Design:

A cross-sectional analysis of food and nutrient intake in 124 T2DM individuals (64% male; age 57.4±5.6 years, BMI 32.5±5.8 kg m⁻²) and 124 adults (age 57.4±7.0 years, BMI 31.2±5.0 kg m⁻²) with no diabetes (ND) was undertaken using a 4-day semiweighed food diary. Biochemical and anthropometric variables were also measured.

Results:

While reported energy intake was similar in T2DM vs ND (1954 vs 2004 kcal per day, P=0.99), T2DM subjects consumed more total-fat (38.8% vs 35%, P⩽0.001), monounsaturated-fat (13.3% vs 12.2% P=0.004), polyunsaturated-fat (6.7% vs 5.9% P<0.001) and protein (18.6% vs 17.5%, P⩽0.01). Both groups exceeded saturated-fat recommendations (14.0% vs 13.8%). T2DM intakes of carbohydrate (39.5% vs 42.9%), non-milk sugar (10.4% vs 15.0%) and fibre (14.4 vs 18.9 g) were significantly lower (P<0.001). Dietary glycaemic load (GL) was also lower in T2DM (120.8 vs 129.2; P=0.02), despite a similar glycaemic index (59.7 vs 60.1; P=0.48). T2DM individuals reported consuming significantly more wholemeal/brown/wholegrain breads, eggs, oils, vegetables, meat/meat products, savoury snacks and soups/sauces and less white breads, breakfast cereals, cakes/buns, full-fat dairy, chocolate, fruit juices, oily fish and alcohol than ND controls.

Conclusion:

Adults with T2DM made different food choices to ND adults. This resulted in a high saturated-fat diet, with a higher total-fat, monounsaturated-fat, polyunsaturated-fat and protein content and a lower GL, carbohydrate, fibre and non-milk sugar content. Dietary education should emphasise and reinforce the importance of higher fibre, fruit, vegetable and wholegrain intake and the substitution of monounsaturated for saturated-fat sources, in energy balanced conditions.     

Maternal history of diabetes is associated with increased cardiometabolic risk in Chinese

Objective:

Positive family history is associated with increased type 2 diabetes (T2D) risk, and reflects both genetic and environmental risks. Several studies have suggested an excess maternal transmission of T2D, although the underlying mechanism is unknown. We aimed to examine the association between maternal diabetes and cardiometabolic risk in the offspring.

Methods:

Parental history of diabetes and clinical data including anthropometric traits, fasting plasma glucose and insulin (FPG, FPI), blood pressure and lipid profile were collected from 2581 unrelated Chinese offspring (2026 adolescents from a population-based school survey and 555 adults from a community-based health screening programme). A subset of subjects (n=834) underwent oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min for evaluation of the areas under the curve (AUC) of glucose and insulin at 0–120 min, homoeostasis model assessment of insulin resistance (HOMA-IR) and bell-cell function, insulinogenic index, insulin sensitivity index (ISI) and oral disposition index (DI).

Results:

A positive parental history of diabetes was associated with increased risk of obesity (odd ratios (OR) (95% confidence interval (CI))=1.48 (1.10–2.00)), central obesity (OR (95% CI)=1.67 (1.21–2.32)), higher FPI, HOMA-IR, 2-h insulin, AUC of glucose at 0–120 min, triglycerides, reduced ISI and DI. Compared with individuals without parental diabetes, offspring with diabetic mother had significantly increased risk of obesity (OR (95% CI)=1.59 (1.07–2.35)), central obesity (OR (95% CI)=1.88 (1.23–2.88)), higher glucose levels and BP, were more insulin resistant but also had impaired first-phase insulin response and worse lipid profile. However, paternal history of diabetes had no effect on any of the studied traits, except higher body mass index, waist circumference in females and FPG.

Conclusions:

Our findings suggested that maternal history of diabetes conferred increased risk of cardiometabolic abnormalities, and was associated with both insulin resistance and impaired first-phase insulin secretion. Further investigation into the mechanism of transgenerational diabetes is warranted.     

The origin of circulating CD36 in type 2 diabetes

Objective:

Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.

Design:

An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m⁻²; age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m⁻² and 33.5±5.9 kg m⁻², respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.

Results:

CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A_1c. By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml⁻¹ and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

Conclusions:

Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.     

Does roflumilast improve dyspnea in patients with chronic obstructive pulmonary disease? A meta-analysis

Introduction

Although several large studies showed roflumilast (Rof) has demonstrated efficacy in patients with chronic obstructive pulmonary disease (COPD), the efficacy of Rof in dyspnea remains unclear. We therefore undertook a meta-analysis to assess the efficacy of Rof in dyspnea for COPD patients.

Methods

A computerized search through electronic databases was performed to obtain randomized controlled trials (RCTs). Dyspnea was assessed by the transition dyspnea index (TDI) and the UCSD Shortness of Breath Questionnaire (SOBQ). The quality of the included studies was assessed by the Jadad score. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I² test. The effect sizes were compared with the minimum clinically important difference (MCID).

Results

Four RCTs involving 4,767 patients with forced expiratory volume in one second (FEV₁) <80% predicted met the inclusion criteria. The Jadad score of each study was 5 scores. Rof statistically improved the TDI focal score (WMD =0.30 units; 95% CI: 0.14-0.46), but failed to decrease the SOBQ (WMD =–1.10 units; 95% CI: –4.24 to 2.04). The overall effect sizes were lower than the MCID of the TDI and the SOBQ, respectively.

Conclusions

Sufficient evidence to support Rof relieving dyspnea in COPD patients is currently lacking. Further studies are needed to investigate the effects of Rof in dyspnea, especially for COPD patients with a different phenotype.KEY WORDS : Chronic obstructive pulmonary disease (COPD), roflumilast (Rof), dyspnea, meta-analysis     

Predicting future weight status from measurements made in early childhood: a novel longitudinal approach applied to Millennium Cohort Study data

Background/Objective:

There are reports that childhood obesity tracks into later life. Nevertheless, some tracking statistics such as correlations do not quantify individual agreement, whereas others such as diagnostic test statistics can be difficult to translate into practice. We aimed to employ a novel analytic approach, based on ordinal logistic regression, to predict weight status of 11-year-old children from measurements at age 5 years.

Subjects/Methods:

The UK 1990 growth references were used to generate clinical weight status categories of 12 076 children enrolled in the Millennium Cohort Study. Using ordinal regression, we derived the predicted probability (percent chances) of 11-year-old children becoming underweight, normal weight, overweight, obese and severely obese from their weight status category at age 5 years.

Results:

The chances of becoming obese (including severely obese) at age 11 years were 5.7% (95% confidence interval: 5.2 to 6.2%) for a normal-weight 5-year-old child and 32.3% (29.8 to 34.8%) for an overweight 5-year-old child. An obese 5-year-old child had a 68.1% (63.8 to 72.5%) chance of remaining obese at 11 years. Severely obese 5-year-old children had a 50.3% (43.1 to 57.4%) chance of remaining severely obese. There were no substantial differences between sexes. Nondeprived obese 5-year-old boys had a lower probability of remaining obese than deprived obese boys: −21.8% (−40.4 to −3.2%). This association was not observed in obese 5-year-old girls, in whom the nondeprived group had a probability of remaining obese 7% higher (−15.2 to 29.2%). The sex difference in this interaction of deprivation and baseline weight status was therefore −28.8% (−59.3 to 1.6%).

Conclusions:

We have demonstrated that ordinal logistic regression can be an informative approach to predict the chances of a child changing to, or from, an unhealthy weight status. This approach is easy to interpret and could be applied to any longitudinal data set with an ordinal outcome.     

Efficacy and safety of endobronchial valves for advanced emphysema: a meta analysis

Objective

A meta-analysis was undertaken to evaluate the efficacy and safety of bronchoscopic lung volume reduction with endobronchial valves (EBV) for advanced emphysema.

Methods

A systematic search was performed from PubMed, EMBASE, CNKI, Cochrane Library database. Randomized control clinical trials on treatment of emphysema for 3-12 months with the EBV compared with standard medications and sham EBV were reviewed. Inclusion criteria were applied to select patients with advanced emphysema treated with EBV. The primary outcome was the percentage of the forced expiratory volume in the first second (FEV₁%). Secondary outcomes included St George’s Respiratory Questionnaire (SGRQ) score, the distance of the 6-minute walk (6MWD) test, the Modified Medical Research Council (MMRC) dyspnoea score, cycle ergometry workload, and the rate of the six major complications at 3 or 12 months. Fixed- or random-effects models were used and weighted mean differences (WMD), relative risks (RR) and 95% confidence intervals (CI) were calculated.

Results

Three trials (565 patients) were considered in the meta-analysis. EBV patients yielded greater increases in FEV₁% than standard medications (WMD =6.71; 95% CI, 3.31 to 10.10; P=0.0001), EBV patients also demonstrated a significant change for SGRQ score (WMD =−3.64; 95% CI, −5.93 to −1.34; P=0.002), MMRC dyspnoea score (WMD =−0.26; 95% CI, −0.44 to -0.08; P=0.004), and cycle ergometry workload (WMD =4.18; 95% CI, 2.14 to 6.22; P<0.0001). A similar level was evident for 6MWD (WMD =11.66; 95% CI, −3.31 to 26.64; P=0.13). EBV may increase the rate of hemoptysis (RR =5.15; 95% CI, 1.16 to 22.86; P=0.03), but didn’t increase the adverse events including mortality, respiratory failure, empyema, pneumonia, pneumothrax. The overall rates for complications compared EBV with standard medications and sham EBV was not significant (RR =2.03; 95% CI, 0.98 to 4.21; P=0.06).

Conclusions

EBV lung volume reduction for advanced emphysema showed superior efficacy and a good safety and tolerability compared with standard medications and sham EBV, further more randomized controlled trial (RCT) studies are needed to pay more attention to the long-term efficacy and safety of bronchoscopic lung volume reduction with EBV in advanced emphysema.     

Clinical efficacy of a medically supervised outpatient high-protein,low-calorie diet program is equivalent in prediabetic,diabetic and normoglycemic obese patients

Objective:

Type 2 diabetes mellitus (T2DM) affects approximately 10% of Americans, while 79 million Americans are estimated to have glucose intolerance or prediabetes (pre-DM). The present study was designed to determine whether obese patients with pre-DM or T2DM would lose weight as effectively as obese normoglycemic patients, in a medically supervised high-protein, low-calorie-weight management program.

Method:

Patients enrolled in a self-paid, university-based, outpatient weight loss program using prescribed very-low-calorie diet (VLCD) (500–800 cal per day) or LCD diet (800–1200 cal per day), recommended exercise and group behavioral counseling were studied retrospectively. Patients entering the program for the first time and attending weekly clinic visits for more than 4 weeks were included in the analysis.

Results:

A total of 2093 obese patients, of whom 583 patients with pre-DM (fasting glucose ⩾100 and <126 mg dl⁻¹), 367 patients with T2DM and 1143 normoglycemic patients entered the program from 1991 to 2010, who met all the inclusion criteria were included in the analysis. The body weight at baseline was 104.0±20.0 kg for DM, 101.4±18.4 for pre-DM and 99.0±18.8 kg for non-DM. Weight loss and percent of weight loss within 12 months were analyzed using a linear mixed-effects model. There was no significant difference in weight loss between DM vs non-DM (P=0.4597) and pre-DM vs non-DM (P=0.6006) in 12 months. The length of enrollment in the program was positively correlated to weight loss rates in all patients (P<0.001).

Conclusion:

This study demonstrates that obese, pre-DM and DM patients all lost weight as effectively with VLCD or LCD over 12 months. Given the impact of weight loss on the progression of comorbid conditions, these data support the hypothesis that medically supervised diets, including VLCD and LCD, should be more widely used in the prevention and treatment of obese patients with pre-DM or T2DM.     

Association of Self-Monitoring of Blood Glucose Use on Glycated Hemoglobin and Weight in Newly Diagnosed,Insulin-Na?ve Adult Patients with Type 2 Diabetes

Background

Clinical trials have shown that self-monitoring of blood glucose (SMBG) combined with patient education and medication titration can lead to improved glycated hemoglobin (HbA1c) and reduced weight in recently diagnosed non-insulin-treated type 2 diabetes mellitus (T2DM) patients. This retrospective matched cohort study assessed the association of SMBG with achieving long-term clinical outcomes in these patients in a real-world clinical setting.

Methods

Using electronic medical records (2008–2011), we selected a population of adult patients recently diagnosed with T2DM not receiving insulin who were SMBG users and a population of non-SMBG controls with similar demographic and clinical characteristics using propensity score matching. The main study outcomes compared between the two groups were time to achieve (1) HbA1c <7% for patients with baseline HbA1c ≥7% and (2) a ≥5% reduction in weight from baseline.

Results

Of the 589 patients identified in each group, 113 in each group had a baseline HbA1c ≥7% (mean, 8.2%). The SMBG users were more likely to achieve an HbA1c <7% (12 months: 58.4% versus 38.9%, p = .0037; 36 months: 84.0% versus 70.0%, p = .0013) and to do so faster (median, 6.5 versus 20.5 months; log-rank p = . 0016). Self-monitoring of blood glucose was associated with faster weight reduction (median time to achieve a ≥5% reduction, 23.5 versus 35.9 months for SMBG and non-SMBG, respectively; log-rank p = .0005).

Conclusions

In newly diagnosed T2DM insulin-naïve patients, SMBG users had an improved rate of achieving long-term glycemic control and weight loss in a real-world clinical setting.