Glucometabolic Control Research Articles

Effects of an acute bout of exercise on circulating extracellular vesicles: tissue-, sex-, and BMI-related differences.

Exercise is recognized to evoke multisystemic adaptations that, particularly in obese subjects, reduce body weight, improve glucometabolic control, counteract sarcopenia, and lower the risk of cardiometabolic diseases. Understanding the molecular and cellular mechanisms of exercise-induced benefits is of great interest due to the therapeutic implications against obesity. The aim of the present study was to evaluate time-related changes in size distribution and cell origin of extracellular vesicles (EVs) in obese and normal-weight subjects who underwent a moderate-intensity exercise on a treadmill (at 60% of their VO2max). Blood samples were drawn before, immediately at the end of the exercise and during the postexercise recovery period (3 and 24 h). Circulating EVs were analyzed by a nanoparticle tracking analysis and flow cytometry after labeling with the following cell-specific markers: CD14 (monocyte/macrophage), CD61 (platelet), CD62E (activated endothelium), CD105 (total endothelium), SCGA (skeletal muscle), and FABP (adipose tissue). In all subjects, acute exercise reduced the release of total (i.e., 30-700 nm) EVs in circulation, predominantly EVs in the microvesicle size range (i.e., 130-700 nm EVs). The postexercise release of microvesicles was higher in normal-weight than obese subjects; after exercise, circulating levels of exosomes (i.e., 30-130 nm EVs) and microvesicles were, respectively, lower and higher in females than males. In all experimental subgroups (males vs. females and obese vs. normal-weight subjects), acute exercise reduced and increased, respectively, CD61 + and SCGA + EVs, being the effect on CD61 + EVs prolonged up to 24 h after the end of the test with subjects in resting conditions. Total EVs, exosomes, and CD61 + EVs were associated with HOMA-IR. Though preliminary, the results of the present study show that a single bout of acute exercise modulates the release of EVs in circulation, which are tissue-, sex-, and BMI specific, suggesting that the exercise-related benefits might depend upon a complex interaction of tissue, endocrine, and metabolic factors.

Exenatide once-weekly improves metabolic parameters, endothelial dysfunction and carotid intima-media thickness in patients with type-2 diabetes: An 8-month prospective study

AimTo evaluate the effect of exenatide long acting release (LAR) on carotid intima-media thickness (IMT) and endothelial function in patients with type 2 diabetes mellitus. MethodsSixty subjects with type 2 diabetes mellitus were treated with exenatide LAR as add-on to stable doses of metformin for 8 months in an open label study. Anthropometric variables, lipid profile and glycemic parameters were assessed by routine analysis. Carotid IMT by Doppler ultrasound and endothelial function by flow-mediated dilation of the brachial artery were also assessed. ResultsExenatide significantly improved fasting glycaemia (from 8.8 ± 2.8 to 7.3 ± 2.2 mmol/L, p < 0.0001), HbA1c (from 8.0 ± 0.4 to 6.9 ± 1.1%, p < 0.0001), body mass index (from 33 ± 9 to 31 ± 6 kg/m2, p = 0.0348) and waist circumference (from 109 ± 13 to 106 ± 13 cm, p = 0.0105). There was a significant improvement of the lipid profile, except in triglyceride level where no changes were observed. Carotid IMT and flow-mediated dilation were also improved (from 0.98 ± 0.14 to 0.87 ± 0.15 mm and from 5.8 ± 1.3 to 6.8 ± 1.7%, respectively; p < 0.0001 for both). ConclusionsTreatment with exenatide LAR led to improved cardio-metabolic parameters, including carotid IMT and flow-mediated dilation, independently of glucometabolic control. These results may help to explain, at least in part, the cardiovascular safety of exenatide LAR, as recently reported in cardiovascular outcome trials.

Whey Proteins Reduce Appetite, Stimulate Anorexigenic Gastrointestinal Peptides and Improve Glucometabolic Homeostasis in Young Obese Women.

Introduction: Proteins, particularly whey proteins, represent the most satiating macronutrient in animals and humans. A dietetic regimen based on proteins enriched preload before eating might be a strategy to counteract obesity. Aims and Methods: The aim of the present study was to evaluate the effects of an isocaloric drink containing whey proteins or maltodextrins (preload) on appetite (satiety/hunger measured by a visual analogue scale or VAS), glucometabolic control (blood glucose/insulin), and anorexigenic gastrointestinal peptides (pancreatic polypeptide or PP, glucagon-like peptide 1 or GLP-1 and peptide YY or PYY) in a cohort of obese young women (n = 9; age: 18.1 ± 3.0 years; body mass index, BMI: 38.8 ± 4.5 kg/m2). After two and a half hours, they were administered with a mixed meal at a fixed dose; satiety and hunger were measured by VAS. Results: Each drink significantly augmented satiety and reduced hunger, and the effects were more evident with whey proteins than maltodextrins. Similarly, there were significant increases in GLP-1 and PYY levels (but not PP) after the ingestion of each drink; these anorexigenic responses were higher with whey proteins than maltodextrins. While insulinemia identically increased after each drink, whey proteins induced a lower glycemic response than maltodextrins. No differences in satiety and hunger were found after the meal, which is presumably due to the late administration of the meal test, when the hypophagic effect of whey proteins was disappearing. Conclusions: While whey proteins actually reduce appetite, stimulate anorexigenic gastrointestinal peptides, and improve glucometabolic homeostasis in young obese women, further additional studies are mandatory to demonstrate their hypophagic effects in obese subjects, when administered as preload before eating.

Nonfunctioning and subclinical cortisol secreting adrenal incidentalomas and their association with metabolic syndrome: A systematic review

Background:A growing body of evidence suggests that nonfunctioning and subclinical cortisol secreting adrenal incidentalomas (AIs) are associated with several components of metabolic syndrome resulting in increased cardiometabolic risk. The long-term metabolic outcome of these AIs is largely unknown and their most appropriate management remains controversial.Objectives:To undertake a systematic review of the prevalence of cardiometabolic abnormalities in nonfunctioning and subclinical cortisol secreting AIs and long-term outcome of conservative treatment and adrenalectomy.Methods:MEDLINE, Cochrane Controlled Trials Register, and EMBASE were searched for relevant studies and systematic review was performed. National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies was used to assess the risk of bias in the studies.Results:Of the 65 studies screened, 18 (10 retrospective, 5 prospective, 2 cross-sectional studies, and 1 randomized controlled trial) were included in the systematic review. Prevalence of hypertension (HTN), impaired glucose metabolism, dyslipidaemia, and raised body mass index (BMI) was higher in subclinical cortisol secreting AIs as compared with nonfunctioning AIs. Surgical intervention had a beneficial effect on blood pressure, glucometabolic control, and obesity in patients with subclinical Cushing's syndrome. The results for lipid metabolism were equivocal. There was no significant improvement in cardiometabolic risk factors after adrenalectomy in nonfunctioning AIs. The quality of evidence was found to be low to moderate.Conclusions:The systematic review demonstrated increased prevalence of components of metabolic syndrome in patients with subclinical cortisol secreting and nonfunctioning AIs. A beneficial role of adrenalectomy on HTN, glucometabolic control, and BMI was observed in patients with subclinical cortisol secreting AIs.

Serum resistin and adiponectin relationships with glucometabolic control in patients with type 2 diabetes mellitus

Introduction/Objective. Adiponectin and resistin are important adipokines that play an important role in the regulation of blood sugar, beta-oxidation in muscles, and insulin resistance. This study aimed to assess and compare the relationships of resistin and adiponectin concentrations with glucometabolic control in patients with type 2 diabetes mellitus (T2DM). Methods. A total of 191 subjects were studied. The final selection included 107 patients with T2DM (67 males and 40 females) and 84 healthy control subjects (45 males and 39 females). Fasting venous blood samples were analyzed for glucose (FBG), glycosylated hemoglobin (HbA1c), insulin, lipids, adiponectin and resistin levels. Body composition was evaluated in all subjects by the body mass index (BMI) and waist?hip ratio (WHR). Results. BMI, WHR, FBG, HbA1c, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, and triglycerides were significantly higher in individuals with T2DM compared to healthy volunteers. Serum resistin levels were significantly higher (p = 0.0259) and serum adiponectin levels were significantly lower (p = 0.0001) in T2DM patients than in control subjects. Adiponectin levels were significantly lower (p = 0.0411) in diabetes patients with poor glycemic control, compared to those with good glycemic control, while the difference was non-significant for resistin (p = 0.8899). Serum adiponectin levels were discordant with HbA1c (r = -0.274, p = 0.004). Linear-by-linear association showed significant trend of better glycemic control at increasing quartiles of adiponectin levels (p = 0.042), while the trend was not significant for resistin levels (p = 0.904). Multiple regression analysis revealed FBG, insulin, HOMA-IR, and HbA1c as significant predictors of adiponectin. Conclusions. T2DM patients have significantly higher resistin and lower adiponectin levels compared to healthy controls. Adiponectin levels were significantly lower in patients with poor glycemic control.

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.

Background Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods One hundred seven frail, obese older adults were randomized into the control (N = 27), diet (N = 26), exercise (N = 26), and diet-exercise (N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2 = 0.140 and 0.107) and diet-exercise (∆R2 = 0.427 and 0.243) groups (P < 0.05 for all). Conclusions Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover.

Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T-cell (Treg) defect. Vitamin D deficiency is highly prevalent in T1D, which can aggravate immune dysfunction. High-dose vitamin D treatment may enhance Tregs and improve metabolism in T1D patients. In a randomized double-blind placebo-controlled trial with crossover design, patients received either for 3 months cholecalciferol 4000 IU/d followed by 3 months placebo or the sequential alternative. Thirty-nine T1D patients (19 women and 20 men) completed the trial. Primary outcome was a change of Tregs, secondary HbA1C, and insulin demand. Effects were evaluated based on intra-individual changes between treatment and placebo periods for outcome measures. Exploratory analyses included vitamin D system variant genotyping and C-peptide measurements. Median 25(OH)D3 increased to 38.8 ng/ml with males showing a significantly stronger increase (p = .003). T-lymphocyte profiles did not change significantly (p > 2); however, the intra-individual change of Tregs between males and females was different with a significantly stronger increase in men (p = .017), as well as between genotypes of the vitamin D receptor (Apa, Taq, and Bsm: genotypes aa, TT, and bb; p = .004-0.015). Insulin demands declined significantly (p = .003-.039) and HbA1C improved (p < .001). Random C-peptide levels were low but rising (median, 0.125 ng/ml; range, 0.02-0.3) in 6 patients. No toxicity was observed. A daily vitamin D dose of 4000 IU for 3 months was well tolerated and enhanced Tregs in males. Glucometabolic control improved in all. Subsequent larger trials need to address ß-cell function and genotyping for individualized vitamin D doses.

Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry.

The aim of this study was to characterize the phenotype and treatment of young patients (manifestation <30 years) with diabetes of mitochondrial origin (DMO), based on the German/Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry. Only 13 (0.02 %) of all patients with diabetes in this cohort were identified with DMO, mainly due to the Kearns-Sayre (n = 5), Pearson (n = 3), or mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 2). The onset of DMO (14.2, interquartile range (IQR) 7.1-16 years) was later than diabetes onset in individuals with T1D but earlier than in T2D. At manifestation, patients exhibited a mild elevation of blood glucose concentrations (251, IQR 178-299 mg/dl) without ketoacidosis. They had lower body mass index (BMI) values (-1.39 ± 0.28 kg/m(2)) than peers with T1D or T2D (p < 0.0001) and higher triglycerides (211, IQR 134-574 mg/dl) than in T1D (p = 0.04) while there was a high rate of dyslipidemia (86 %). Insulin requirements (0.58, IQR 0.37-0.90 U/kg/d) were between T1D and T2D while glucometabolic control (glycated hemoglobin A1c (HbA1c) 7.4 ± 0.52 %) in DMO was comparable to age-matched T2D and stable over a 5-year follow-up. Primary mitochondrial disorders are a rare cause of juvenile diabetes and likely to be underdiagnosed. As there is clinical overlap with T1D and T2D, dyslipidemia and low body weight may help to identify further DMO cases. • In adults diabetes of mitochondrial origin (DMO) is a rare cause of non-autoimmune diabetes, affecting about 0.8 % of diabetes cases. • Common features are a maternal family history of diabetes, hearing loss and neurological abnormalities. What is New: • In our juvenile cohort 0.02 % of diabetes patients (age < 30 years) were affected by DMO, while Kearns Sayre, MELAS and Pearson syndrome were the most frequent entities. • Juvenile DMO patients exhibited dyslipidemia, higher triglycerides and a lower BMI than peers with T1D or T2D, while some patients also showed retinal changes.

Systematic review of surgical treatment of subclinical Cushing's syndrome.

Subclinical Cushing's syndrome (SCS) is a condition of biochemical cortisol excess without the classical clinical features of overt hypercortisolism; it may be associated with some consequences of metabolic syndrome. The most appropriate treatment remains controversial. This study aimed to assess the outcomes of adrenalectomy for SCS. A systematic review was performed. MEDLINE, Embase and Cochrane Databases (1980-2013) were searched for studies reporting the outcomes of unilateral adrenalectomy with respect to hypertension, diabetes, dyslipidaemia, obesity and osteoporosis in patients with SCS. Studies with a questionable diagnosis of SCS, bilateral adrenal involvement and insufficient data were excluded. Of the 105 papers screened, seven were selected; there were six retrospective studies and one randomized clinical trial, including 230 patients. Data analysis was limited by heterogeneity in definition of SCS and endpoints. Hypercortisolism was cured in all operated patients. Laparoscopy was the preferred approach, with a morbidity rate of 0·8 per cent. A beneficial effect of surgery on blood pressure, glucometabolic control and obesity was evident in all studies, with cure or improvement in 72, 46 and 39 per cent of patients respectively, compared with conservative management. The results for lipid metabolism were equivocal, because of a decrease in triglyceridaemia but discordant effects on cholesterol metabolism among the different studies. No beneficial effects on osteoporosis were found. Laparoscopic adrenalectomy seems to be beneficial in reversing several metabolic effects of hypercortisolism, with a low morbidity rate. However, the heterogeneity and low quality of the available studies preclude definitive recommendations.

Insulin levels and HOMA index are associated with exercise capacity in patients with type 2 diabetes and coronary artery disease

BackgroundPrevious studies on type 2 diabetes have shown an association between exercise capacity and insulin resistance. In patients with coronary artery disease (CAD) exercise capacity is often reduced due to exercise-induced ischemia. We have investigated the association between glucometabolic control, including the homeostatic model assessment (HOMA) of insulin resistance, and exercise capacity in patients with type 2 diabetes and CAD with and without exercise-induced ischemia.MethodsIn 137 patients (age 63.1 ± 7.9) cardiopulmonary exercise testing on treadmill was performed using a modified Balke protocol. The highest oxygen uptake (VO2peak) was reported as 30-s average. Fasting blood samples were drawn for determination of glucose, insulin and HbA1c. Insulin resistance (IR) was assessed by the HOMA2-IR computer model. Exercise-induced ischemia was defined as angina and/ or ST-depression in ECG ≥ 0.1 mV during the exercise test.ResultsHOMA2-IR was inversely correlated to VO2peak (r = -0.328, p < 0.001), still significant after adjusting for age, gender, smoking and BMI. Patients with HOMA2-IR above the median value (1.3) had an adjusted odds ratio of 3.26 (95 % CI 1.35 to 7.83, p = 0.008) for having VO2peak below median (23.8 mL/kg/min). Insulin levels were inversely correlated to VO2peak (r = -0.245, p = 0.010), also after adjusting for age and gender, but not after additional adjustment for BMI. The correlation between HOMA2-IR and VO2peak was also significant in the subgroups with (n = 51) and without exercise-induced ischemia (n = 86), being numerically stronger in the group with ischemia (r = -0.430, p = 0.003 and r = -0.276, p = 0.014, respectively). Fasting glucose and HbA1c were not correlated with VO2peak or AT.ConclusionsInsulin resistance, as estimated by fasting insulin and the HOMA index, was inversely associated with exercise capacity in patients with type 2 diabetes and CAD, the association being more pronounced in the subgroup with exercise-induced ischemia. These results indicate that insulin resistance is related to exercise capacity in type 2 diabetic patients with CAD, possibly even more so in patients with exercise-induced ischemia compared to those without.

Autonomous exercise game use improves metabolic control and quality of life in type 2 diabetes patients - a randomized controlled trial

BackgroundLifestyle intervention in type 2 diabetes mellitus (T2DM) is effective but needs a special local setting and is costly. Therefore, in a randomized-controlled trial we tested the hypothesis that the autonomous use of the interactive exercise game Wii Fit Plus over a period of 12 weeks improves metabolic control, with HbA1c reduction as the primary outcome, and weight loss, reduction of cardiometabolic risk factors, physical activity and quality of life (secondary outcomes) in T2DM patients.MethodsParticipants (n = 220) were randomized into an intervention and a control group. The intervention group was provided with a Wii console, a balance board and the exercise game Wii Fit Plus for 12 weeks. The control group remained under routine care and received the items 12 weeks later. At baseline and after 12 weeks (and for the control group additionally after 12 weeks of intervention) the participants’ health parameters, medication, physical activity and validated questionnaires for quality of life (PAID, SF12, WHO-5, CES-D) were requested and compared in a complete case analysis using the Mann–Whitney test and the Wilcoxon signed rank test.Results80% of participants completed the 12-week study. Patients in the intervention group significantly improved HbA1c (from 7.1 ± 1.3% to 6.8 ± 0.9%; -0.3 ± 1.1%; p = 0.0002) in comparison to the control group (from 6.8 ± 0.9% to 6.7 ± 0.7%; -0.1 ± 0.5%) and also significantly reduced fasting blood glucose (from 135.8 ± 38.9 mg/dl to 126.6 ± 36.6 mg/dl; p = 0.04), weight (from 97.6 ± 19.2 kg to 96.3 ± 18.7 kg; p < 0.001) and body mass index (from 34.1 ± 6.5 kg/m2 to 33.5 ± 6.5 kg/m2; p < 0.001). Daily physical activity increased significantly (p < 0.001). Diabetes-dependent impairment, mental health, subjective wellbeing and quality of life also improved significantly, and the number of patients with depression decreased. Similar improvements were seen in the control group after exercise game intervention.ConclusionsIn this trial a low-threshold intervention with the interactive exercise game Wii Fit Plus was able to motivate T2DM patients to improve physical activity, glucometabolic control and quality of life.Trial registrationClinicalTrials.gov NCT01735643.

ROSSO-in-praxi-international: Long-Term Effects of Self-Monitoring of Blood Glucose on Glucometabolic Control in Patients with Type 2 Diabetes Mellitus Not Treated with Insulin

Effects of lifestyle change on blood glucose levels can be monitored by self-monitoring of blood glucose (SMBG) in type 2 diabetes mellitus (T2DM) patients. We analyzed whether the SMBG-structured lifestyle intervention program ROSSO-in-praxi-international can improve glucometabolic control in the short and the long term. One hundred twenty-four SMBG-naive ambulatory non-insulin-treated T2DM patients were randomly assigned to an SMBG group (n=63) and a control group (n=61). Both groups received a 12-week structured lifestyle guidance manual. The SMBG group additionally got a blood glucose meter with 150 test strips and was instructed to measure blood glucose regularly as well as event-driven. Glucometabolic parameters were assessed at baseline, after 12 weeks, and after 1.5 years. During the 12 weeks of intervention the SMBG group significantly improved glycated hemoglobin (HbA1c) levels (from 7.4 ± 1.6% to 6.9 ± 1.1% [P<0.001]) and weight (-0.9 ± 1.9 kg [P<0.05]), whereas HbA1c reduction (from 7.5 ± 1.0% to 7.3 ± 1.0%) and weight loss (-0.6 ± 2.4 kg) were not significant in the control group. Of the 124 patients, 122 completed the 1.5-year follow-up. In the control group HbA1c increased again, reaching baseline values (7.5 ± 0.7%). In the SMBG group HbA1c remained stable (6.9 ± 0.9% [P=0.0003 for trend]), and weight (-1.6 ± 3.0 kg vs. baseline [P=0.0003 for trend]) improved further. Eighty-seven percent of participants in the SMBG group continued to perform SMBG. Those who measured their blood glucose more than three times per week (n=24) demonstrated an overall reduction in HbA1c of 1.0% (P=0.006 vs. three times or fewer per week) after 1.5 years. Integration of SMBG into basic therapy of T2DM for monitoring the effect of lifestyle changes improves glucometabolic control and has long-term effects.

The Relationship Between Diabetes, Metabolic Syndrome, and Platelet Activity as Measured by Mean Platelet Volume

OBJECTIVEThe association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control.RESEARCH DESIGN AND METHODSThis is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression.RESULTSMPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control.CONCLUSIONSMean platelet volume is strongly and independently associated with the presence and severity of diabetes.

ROSSO-in-Praxi Follow-Up: Long-Term Effects of Self-Monitoring of Blood Glucose on Weight, Hemoglobin A1c, and Quality of Life in Patients with Type 2 Diabetes Mellitus

Self-monitoring of blood glucose (SMBG) is a simple tool to monitor the effects of lifestyle change on blood glucose. Recently, the ROSSO-in-praxi Study demonstrated that addition of SMBG to a 12-week lifestyle intervention was associated with significant improvements in glucometabolic control and quality of life in insulin-naive patients with type 2 diabetes mellitus (T2DM). So far it is unknown if this short-term intervention also has long-term effects. Therefore, participants were followed up for a mean period of 2 years. Participants (n=327) were asked by mail for current weight, hemoglobin A1c (HbA1c), performance of SMBG, and quality of life (SF36 and CES-D questionnaires). Participants who did not reply were contacted by phone. Two hundred twenty-eight participants (70%) completed the follow-up. During the 12-week lifestyle intervention they had significantly reduced weight (2.2 kg) and HbA1c (0.3%; P<0.001 each). After 2 years they achieved a further reduction of weight (0.2 kg; P<0.001), whereas HbA1c increased again, remaining 0.1% lower than baseline. The numbers of depressed participants remained stable during follow-up, whereas physical and mental health-related quality of life remained better compared with baseline. During follow-up 20% of participants continued SMBG daily, 35% several times a week, and 33% irregularly. It is interesting that participants with daily SMBG demonstrated an HbA1c decrease of 0.3% at time of follow-up, whereas in those who stopped SMBG HbA1c increased by 0.1% (P=0.05). Integration of a short-term, motivational, and low-cost intervention into basic therapy of T2DM has had beneficial long-term effects on weight and quality of life and, if SMBG was continued daily, also on HbA1c.

A randomized cross-over study of the metabolic and hormonal responses following two preoperative conditioning drinks

Objective Preoperative conditioning with carbohydrate-based drinks attenuates postoperative insulin resistance and leads to clinical benefits. The use of metabolic conditioning agents such as glutamine and antioxidants, in addition to carbohydrate, may benefit patients undergoing major surgery, because glutamine and antioxidant supplementation have been shown to improve gastrointestinal perfusion, immune function, morbidity, and gluco-metabolic control in critically ill patients. We investigated the postprandial responses after ingestion of a clear carbohydrate drink (CCD) containing 50 g of carbohydrate (preOp, Nutricia, Trowbridge, UK) and that of another drink containing 50 g of carbohydrate, 15 g of glutamine, and antioxidants (ONS; Fresenius Kabi, Bad Homburg, Germany). Methods Twelve overnight-fasted healthy male subjects ingested one of the drinks in a randomized, double-blinded, cross-over manner, after which blood was sampled for 360 min for measurement of glucose, insulin, glucagon, non-esterified fatty acids, β-hydroxybutyrate and glutamine. Results The means ± standard errors for age and body mass index of participants were 21 ± 0.9 y and 23.2 ± 0.5 kg/m 2. After CCD ingestion, glucose and insulin concentrations peaked within 40 min (8.4 ± 0.4 mmol/L and 43.9 ± 3.8 mIU/L, respectively) and returned to baseline at 80 min (glucose 4.9 ± 0.3 mmol/L) and 140 min (insulin 5.5 ± 0.5 mIU/L). After ONS ingestion, peak glucose and insulin concentrations occurred within 40 min but were of a lower magnitude (6.6 ± 0.1 mmol/L and 29.6 ± 2.9 mIU/L, respectively). Glucose concentrations after ONS were higher than after CCD at 100 min. Conclusion Peak insulin and glucose concentrations were higher after CCD ingestion; in contrast, responses after ONS ingestion were “blunted” and prolonged.

ROSSO-in-praxi: A Self-Monitoring of Blood Glucose-Structured 12-Week Lifestyle Intervention Significantly Improves Glucometabolic Control of Patients with Type 2 Diabetes Mellitus

As healthy diet and physical activity can improve glucometabolic control in patients with type 2 diabetes, lifestyle changes should be the basis for each therapy. The only tool to visualize immediate effects of food pattern and exercise on blood glucose levels is self-monitoring of blood glucose (SMBG). Therefore, the aim of the 12-week lifestyle intervention ROSSO-in-praxi was to evaluate the impact of an SMBG-structured motivation and education program on glucometabolic and health parameters in diabetes patients not treated with insulin. Participants (n = 405) generated a seven-point blood glucose diurnal profile every 4 weeks, including actual weight, waist circumference, and steps/day. At baseline and the end of the study, glycated hemoglobin A1c (HbA1c), blood pressure, and cholesterol levels, lifestyle changes, and well-being (SF36 and Center for Epidemiologic Studies Depression Scale questionnaires) were assessed. Three hundred twenty-seven participants (81%) completed the program and significantly improved quality of diet and physical activity, accompanied by an increase of >2,300 steps/day. Participants significantly reduced weight, body mass index, waist circumference, blood glucose, blood pressure, low-density lipoprotein cholesterol, and HbA1c by 0.3% (all P < 0.001), accompanied by increased physical and mental health and reduced depression measurements. Weight loss was significantly associated with overall improvements of glucometabolic and health parameters and mean reduction of 0.05% HbA1c/kg. The evaluated SMBG-structured lifestyle intervention is applicable to motivate individuals with type 2 diabetes for lifestyle changes. Integration of this short-term, highly motivational, and low-cost intervention into basic therapy for patients without insulin therapy could strengthen patient empowerment in order to change lifestyle and to improve glucometabolic and general health.

Depresión y diabetes: de la epidemiología a la neurobiología

Worldwide, diabetes mellitus and depression are among the most prevalent diseases in their respective fields, metabolism and psychiatry. However, there is evidence that patients with diabetes are at increased risk of developing depression, although a bidirectional relationship might also exist.To present a comprehensive review of the clinical, epidemiological, psychosocial, emotional, and neurobiological basis of the relation between diabetes and depression.Epidemiological studies indicate that there is not only an augmented risk of developing depression in diabetic patients, but that this association increases the morbidity and mortality of these patients. While there is a considerable number of clinical studies that support this relation, little is known about the neurochemical mechanisms that would constitute its biological basis.Alterations in monoamines (serotonin and noradrenaline), the increases in cortisol by the hypothalamus-pituitary-adrenal axis, and trophic agents such as the brain-derived neurotrophic factor, through glycogen synthase kinase-3, constitute some of the abnormalities documented in diabetic patients and in animal models that could explain the association between depression and diabetes. Additionally, we briefly consider the psychoemotional factors that might underlie the depression-diabetes relation. The effects (most of them deleterious) of the antidepressive therapy in glucometabolic control are also discussed.

Bone involvement in clusters of autoimmune diseases: Just a complication?

Bone loss, described in individual groups of patients with Type 1 diabetes (T1D), autoimmune thyroid disease (ATD) or celiac disease (CD) is usually viewed as a complication of these diseases. There is increasing evidence that alterations in the immune system may directly affect bone mass. Clustering of autoimmune diseases in the same individual might predispose to higher risk of osteopenia due to imbalance in immune regulation. The aim of this study was to evaluate bone involvement in clusters of the most common autoimmune diseases (T1D, ATD and CD) in children.The study was performed at a tertiary care center for the care of pediatric diabetes. One-hundred-two patients with T1D alone or associated with ATD and/or CD were studied; 13 patients had cluster of three autoimmune diseases. Amplitude-dependent speed of sound (AD-SoS) was measured by phalangeal quantitative ultrasound and expressed as standard deviation score (SDS). AD-SoS SDS < −2 was considered indicative of osteopenia.Osteopenia was equally distributed among children with T1D alone (8.1%), T1D associated with ATD (7.7%) or CD (10.3%), while it was 53.8% in patients presenting with three autoimmune diseases. Poor compliance to gluten-free diet increased osteopenia to 18.8% in patients with T1D and CD and 80% in patients with three autoimmune disorders. No difference among groups was found with regard to gluco-metabolic control, calcium metabolism, thyroid function.In conclusion bone impairment in multiple autoimmune diseases might be considered not only a complication due to endocrine or nutritional mechanisms, but also a consequence of an immunoregulatory imbalance. Alterations of homeostatic mechanisms might explain an imbalance of osteoclast activity leading to osteopenia.

Sex-related psychological effects on metabolic control in type 2 diabetes mellitus

Women are at higher risk of diabetes-related cardiovascular complications than men. We tested the hypothesis that there are sex-specific differences in glucometabolic control, and in social and psychological factors. We also examined the influence of these factors on glucometabolic control. We examined 257 (126 men/131 women) consecutive patients (64 +/- 9 years, means +/- SD) of a metropolitan diabetes outpatient service employing clinical testing and standardised psychological questionnaires. Mean HbA(1c) (7.6 +/- 1.2%) was not different between women and men. Women patients on oral hypoglycaemic agents were better informed about diabetes (p = 0.012). They employed more strategies for coping with diabetes, including religion (p = 0.0001), active coping (p = 0.048) and distraction (p = 0.007). Women reported lower satisfaction with social support (p = 0.034), but not more depression than men. Although no differences were observed in compliance, insulin-treated patients were more satisfied with their therapy (p = 0.007). Variables predicting poor metabolic control were different in men (R(2) = 0.737, p = 0.012) and women (R(2) = 0.597, p = 0.019). Major predictors of high HbA(1c) included depressive coping, lower sexual desire, quality of life and internal locus of control, but high external doctor-related locus of control in women and frequent emotional experiences of hyperglycaemia in men. Lower quality of life, internal control and socioeconomic status, and higher prevalence of negative emotions probably prevented woman patients from achieving improved glucose control despite their better knowledge of and greater efforts to cope with diabetes. We suggest that women patients would benefit from individualised diabetes care offering social support, whereas men would benefit from knowledge-based diabetes management giving them more informational and instrumental support.

Which contraceptive methods are recommended for young women with type 1 diabetes mellitus?: A survey among gynaecologists in Greece

Background: Type 1 diabetes mellitus is common in Europeans. Optimal glucometabolic control at conception and during early pregnancy is necessary to reduce the risk of early miscarriage and congenital malformations. Safe and effective contraceptive methods are essential for these women in order to have a “planned pregnancy” under optimal conditions. Aim: To find out which recommendations Greek gynaecologists give to young patients with type 1 diabetes mellitus with respect to contraception. To regard the experience of Greek gynaecologists in counselling with women. To compare the Greek gynaecologists with German gynaecologists in a previously published similar survey. Subjects and methods: A structured questionnaire containing questions about attitude, health care and contraception in young women with type 1 diabetes was given to 400 Greek gynaecologists working in Athens. Results: Only 70 (17.5%) of the Greek gynaecologists returned the questionnaire. Condoms were the preferred recommendation as contraceptive method for young women with diabetes mellitus type 1 in 64%. About 57% of the gynaecologists recommended this type of contraception as first line contraceptives for young women with diabetes type 1 who smoke. The two most important criteria for selection of a contraceptive method for Greek gynaecologists were the safety and the diabetes specific problems. The Greek gynaecologists had only limited experience in regard to counselling and treating young and adolescent women with type 1 diabetes. Conclusion: There was no consensus with respect to contraception among Greek gynaecologists. This is similar to our previous findings in a survey involving German gynaecologists. Practical experience in counselling and treating adolescent and young women with type 1 diabetes was limited among the gynaecologists who participated in this study. Working out proper recommendations for contraception crucial for optimal medical care for type 1 diabetic women in Europe.