Insulin resistance and beta-cell dysfunction in newly diagnosed type 2 diabetes: Expression, aggregation and predominance. Verona Newly Diagnosed Type 2 Diabetes Study 10.

AIMS: We investigated quantitative expression, mutual aggregation and relation with hyperglycemia of insulin resistance (IR) and beta-cell dysfunction (BCD) in newly diagnosed type 2 diabetes. METHODS: We assessed IR with euglycemic hyperinsulinemic clamp and BCD with modelled glucose/C-peptide response to oral glucose in 729 mostly drug-naïve patients. We measured glycated hemoglobin, pre-prandial, post-prandial and meal-related excursion of blood glucose. RESULTS: IR was found in 87.8% [95% confidence intervals 85.4-90.2] and BCD in 90.0% [87.8-92.2] of subjects, ranging from mild to moderate or severe. Approximately 20% of subjects had solely one defect: BCD 10.8% [8.6-13.1] or IR 8.6% [6.6-10.7]. Insulin resistance and BCD aggregated in most subjects (79.1% [76.2-82.1]). We arbitrarily set nine possible combinations of mild, moderate or severe IR and mild, moderate or severe BCD, finding that each had a similar frequency (∼10%). In multiple regression analyses parameters of glucose control were related more strongly with BCD than with IR. CONCLUSIONS: In newly-diagnosed type 2 diabetes, IR and BCD are very common with a wide range of expression but no specific pattern of aggregation. Beta-cell dysfunction is likely to play a greater quantitative role than IR in causing/sustaining hyperglycemia in newly-diagnosed type 2 diabetes.

Identification of the Inappropriate Clinical Actions (DON'T) to Improve the Management of Patients with Type 2 Diabetes Failing Basal Insulin Supported Oral Treatment: Results of Survey for a Panel of Diabetes Specialists in Italy.

INTRODUCTION: Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT). METHODS: A panel of diabetes specialists was assembled to identify a list of ten corrective actions, "things not to do," for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration. RESULTS: A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues-do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient's adherence; (5) do not stop listening to the patient and verify learning. CONCLUSION: A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients' needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care.

Glomerular filtration rate decline in T2DM following diagnosis. The Verona newly diagnosed diabetes study-12.

AIMS: Nephropathy is a complication of type 2 diabetes, with increased albuminuria and reduced glomerular filtration rate (GFR) as biomarkers. Rates of progression to end-stage-renal disease are variable among patients. In this study we have examined the GFR decline in newly diagnosed T2DM. METHODS: A cohort of 410 patients with newly diagnosed T2DM and with at least four serum creatinine during the follow-up period were recruited. A linear model was used to calculate the decline in eGFR. A multivariable logistic model was used to identify independent predictors of rapid eGFR decline. RESULTS: Average follow-up was 12.4 years. The eGFR change was -0.80 ±â€¯2.23 ml/min/1.73 m2 per year. Patients were arbitrarily stratified into rapid decliners (≤-3.0 ml/min/1.73 m2 per year), moderate decliners (-2.9/-1 ml/min/1.73 m2 per year) and slow/no decliners (>-1.0 ml/min/1.73 m2 per year). Subjects in the 3 categories were 11.4%, 27.3%, and 61.3%, respectively. Albuminuria was the stronger predictor of rapid eGFR decline. CONCLUSIONS: A rapid decline in eGFR occurs in approximately 1 out of 10 newly diagnosed subjects. This rapid decline can be predicted by widely accessible clinical features, such as albuminuria. Identification of rapid decliners may help to reduce progression toward advanced stages of nephropathy.

Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9.

INTRODUCTION: We explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated with complications were also investigated. RESEARCH DESIGN AND METHODS: The comprehensive assessment of microvascular and macrovascular complications included detailed medical history, resting ECG, ultrasonography of carotid and lower limb arteries, quantitative neurological evaluation, cardiovascular autonomic tests, ophthalmoscopy, kidney function tests. Insulin sensitivity and beta-cell function were assessed by state-of-the-art techniques (insulin clamp and mathematical modeling of glucose/C-peptide curves during oral glucose tolerance test). RESULTS: We examined 806 patients (median age years, two-thirds males), of whom prior clinical cardiovascular disease (CVD) was revealed in 11.2% and preclinical CVD in 7.7%. Somatic neuropathy was found in 21.2% and cardiovascular autonomic neuropathy in 18.6%. Retinopathy was observed in 4.9% (background 4.2%, proliferative 0.7%). Chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) was found in 8.8% and excessive albuminuria in 13.2% (microalbuminuria 11.9%, macroalbuminuria 1.3%).Isolated microvascular disease occurred in 30.8%, isolated macrovascular disease in 9.3%, a combination of both in 9.1%, any complication in 49.2% and no complications in 50.8%.Gender, age, body mass index, smoking, hemoglobin A1c and/or hypertension were independently associated with one or more complications. Insulin resistance and beta-cell dysfunction were associated with macrovascular but not microvascular disease. CONCLUSIONS: Despite a generally earlier diagnosis for an increased awareness of the disease, as many as ~50% of patients with newly diagnosed type 2 diabetes had clinical or preclinical manifestations of microvascular and/or macrovascular disease. Insulin resistance might play an independent role in macrovascular disease. TRIAL REGISTRATION NUMBER: NCT01526720.

Depressive symptoms and glycaemic control in adults with type 1 diabetes: an exploratory study on the role of family functioning.

AIMS: Psychological distress and family functioning have a considerable impact on diabetes self-management and glycaemic control in individuals with type 1 diabetes (T1D). However, the influence of both individual and family factors on glycaemic control has not been adequately investigated yet. This study aimed at examining the relationship between perceived family functioning and depressive symptoms with the frequency of capillary self-monitoring of blood glucose (SMBG) and glycaemic control (HbA1c) in a large sample of adults with T1D. METHODS: In a cross-sectional study design, we consecutively enrolled 90 adults with T1D diagnosis from at least 1 year and currently living in their family of origin or conjugal family from at least 1 year before the enrolment. Questionnaires were administered to assess family functioning and depressive symptoms. The SMBG frequency over the past 3 months and the most recent HbA1c measurement were also collected in each individual. Correlation and mediation analyses were carried out. RESULTS: Glycaemic control showed a positive relationship with depressive symptoms and family balanced cohesion, while SMBG frequency was correlated with family balanced flexibility and rigidity, but not with depressive symptoms. Mediation analyses showed that family rigidity mediates the effect of depressive symptoms on glycaemic control. CONCLUSIONS: This exploratory study highlighted the significance of a cohesive family context to facilitate the achievement of individual glycaemic goals in individuals with T1D. These observations, if confirmed in larger data sets, would timely call for a comprehensive family care assessment as part of the evaluations routinely carried out in the ambulatory care of these individuals.

Effects of Aerobic and Resistance Training on Circulating Micro-RNA Expression Profile in Subjects With Type 2 Diabetes.

CONTEXT: Structured exercise programs are of great benefit for the treatment of type 2 diabetes (T2DM). However, whether aerobic (AER) or resistance (RES) exercise training exerts specific epigenetic changes through the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown. OBJECTIVE: To assess whether the c-miRNAs profile changes after either AER or RES training in subjects with T2DM. DESIGN: Twenty-four patients with T2DM randomized to AER or RES training protocols were randomly selected from the Resistance vs. Aerobic Exercise in Type 2 Diabetes (RAED2) Trial (NAER = 12; NRES = 12). The baseline and post-training levels of 179 c-miRNAs were initially measured by RT-PCR in 6 individuals (NAER = 3; NRES = 3). C-miRNAs exhibiting ≥40% fold change variation and/or nominal significance from baseline were measured in the whole group. RESULTS: Nineteen c-miRNAs were eventually assessed in the whole group. Compared with baseline, the post-training levels of miR-423-3p, miR-451a, and miR-766-3p were significantly up-regulated, irrespective of exercise type (P < 0.0026; 0.05/19), and targeted upstream pathways relevant to fatty acids biosynthesis and metabolic regulation. MiR-451a and miR-423-3p were significantly correlated with fat loss (ρ = 0.45 and 0.43, respectively) and resulted, alone or in combination, in being predictors of fat loss in generalized linear regression models including exercise type as covariate. Only the association with miR-451a eventually retained significance after further correction for age, sex, body mass index, and HbA1c. CONCLUSIONS: Exercise training in T2DM is associated with substantial c-miRNAs profile changes, irrespective of exercise type and other relevant metabolic covariates. The mechanistic significance of the observed relationship between fat loss and the epigenetic modifications induced by exercise warrants further investigation in larger datasets.

Sex differences in the association of psychological status with measures of physical activity and sedentary behaviour in adults with type 2 diabetes.

AIM: To assess the association of psychological variables on leisure-time physical activity and sedentary time in men and women with type 2 diabetes mellitus (T2D). METHODS: In this cross-sectional study, we evaluated 163 patients with T2D, consecutively recruited at the Diabetes Centre of the Verona General Hospital. Scores on depression and anxiety symptoms, psychosocial factors (including self-efficacy, perceived interference, perceived severity, social support, misguided support behaviour, spouse's positive behaviour), physical activity and time spent sitting were ascertained using questionnaires responses to the Beck Depression Inventory-II, Beck Anxiety Inventory, Multidimensional Diabetes Questionnaire, International Physical Activity Questionnaire. RESULTS: Physical activity was significantly associated with higher social support in women and with increased self-efficacy in men. Sedentary time was significantly associated with higher perceived interference, anxiety and depressive symptoms, and with reduced diabetes self-efficacy in women, while it was associated solely with anxiety in men. Depressive symptoms and self-efficacy in women and anxiety symptoms in men were independent predictors of sedentary time when entered in a multivariable regression model also including age, BMI, haemoglobin A1c, diabetes duration, perceived interference and self-efficacy as covariates. CONCLUSIONS: Lower self-efficacy and higher symptoms of depression were closely associated with increased sedentary time in women, but not in men, with T2D. It is possible that individualized behavioural interventions designed to reduce depressive symptoms and to improve diabetes self-efficacy would ultimately reduce sedentary behaviours, particularly in women with T2D.

The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes.

An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes.A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality.Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14-2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38-4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables.The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR.

Metabolic Effects of Exercise.

Exercise has a powerful action on metabolism, and adaptation of the body to changes induced by exercise is fundamental to be able to provide the energy required for muscle contraction and physiological functions of vital tissues. Depending on the intensity and duration of exercise, different mechanisms are called on to make energy available, and under homeostatic control, this is guaranteed by rapid and coordinated changes in the secretion of several hormones. Molecular mechanisms controlling muscle function and fiber phenotype are related to the specific mode of muscle activation. We can distinguish between two fundamental types of physical activity, endurance exercise and strength exercise, although there is a continuum between these exercise modalities. Besides the acute changes induced by a single exercise session, regular exercise may induce chronic adaptations, improving exercise capacity and affecting energy metabolism. Notably, although acute metabolic effects of exercise are mostly due to insulin-independent effects, exercise training may improve muscle insulin sensitivity and is considered a key tool in the prevention and treatment of metabolic disorders. This chapter focuses on the biochemistry of energy supply to the exercising muscle, on molecular mechanisms involved and on the physiology of energy metabolism during exercise in healthy subjects and patients with insulin resistance and/or diabetes.

Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: The Verona Diabetic Foot Screening Program.

AIMS: Somatic neuropathy is a chronic complication of diabetes. The purpose of our study was to determine prevalence and clinical variables associated with somatic neuropathy applying a simple screening method. METHODS: All outpatients with type 2 diabetes attending our diabetic clinic were offered to participate into a diabetic foot screening program, in the period January 2004-December 2012. A total of 3,591 diabetic patients (55.5% men, age 68±10years) underwent detection of somatic neuropathy using the Michigan Neuropathy Screening Instrument in its parts of symptoms (administering a questionnaire) and clinical assessment slightly modified (evaluating foot inspection, vibration sensation by biothesiometer, ankle reflexes). RESULTS: The prevalence of somatic neuropathy was 2.2% in men and 5.5% in women (p<0.001) when assessed by symptom questionnaire, whereas it was 30.5% in men and 30.8% (p=NS) in women when identified by clinical assessment. In subjects with somatic neuropathy macro- and microvascular complications of diabetes were significantly more common. In multivariate logistic regression analyses BMI, HbA1c and ankle/brachial index independently predicted the presence of neuropathy. CONCLUSION: The prevalence of somatic neuropathy in type 2 diabetes is nearly 30% when searched with clinical examination. Poor metabolic control, excess body weight and peripheral arteriopathy are independent markers of somatic neuropathy.

Serum testosterone predicts cardiorespiratory fitness impairment in normal-weight women with polycystic ovary syndrome.

OBJECTIVE: Limited literature has shown that maximal oxygen consumption (V'O2max), that is the maximal capacity of an individual to perform aerobic work, may be lowered in overweight/obese women with polycystic ovary syndrome (PCOS). However, it remains unclear whether this impairment is associated with PCOS per se or is entirely due to body fat excess. Our objective was to assess whether cardiorespiratory fitness is altered in normal-weight PCOS women and to investigate which factors are associated with this phenomenon. SUBJECTS: Fifteen normal-weight PCOS women and 15 age- and BMI-matched healthy controls. Fourteen subjects in each group completed the protocol. MEASUREMENTS: V'O2max and ventilatory thresholds (maximal incremental cycle ergometer test with breath-by-breath analysis of gas exchange), insulin sensitivity (hyperinsulinaemic euglycaemic clamp) and androgenaemia (serum total and free testosterone, measured by liquid chromatography mass spectrometry and equilibrium dialysis) were accurately assessed. RESULTS: Maximal V'O2 and power were strikingly impaired in normal-weight PCOS individuals, as compared with healthy controls (29·4 ± 1·5 vs 35·8 ± 1·6 ml O2/kg/min, P = 0·008; 138 ± 6 vs 170 ± 10 W, P = 0·011, respectively). Similarly, oxygen consumption and power at both the first and second ventilatory thresholds were significantly lower in PCOS subjects than in healthy women. In multiple regression analysis, V'O2max was negatively predicted by serum-free testosterone levels, but not by body fat mass and glucose disposal rate (R(2) = 0·45 P = 0·013). CONCLUSIONS: Cardiorespiratory fitness is impaired in normal-weight PCOS women. Androgen excess but not insulin sensitivity is associated with this alteration.

Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS).

OBJECTIVE: Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN. RESULTS: In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment. CONCLUSIONS: CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes.

Lower levels of 25-hydroxyvitamin D3 are associated with a higher prevalence of microvascular complications in patients with type 2 diabetes.

OBJECTIVE: Low levels of serum 25-hydroxyvitamin D [25(OH)D] are commonly found in type 2 diabetes. We examined whether there is an association between circulating 25(OH)D concentrations and the presence of microvascular complications in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 715 outpatients with type 2 diabetes who regularly attended our clinic. Participants were evaluated for the presence of microvascular complications (namely retinopathy and/or nephropathy) by clinical evaluation, fundus examination, urine examination and biochemical tests. Serum 25(OH)D levels were also measured for each participant. RESULTS: Hypovitaminosis D (ie, a serum 25(OH)D level <30 ng/mL) was found in 75.4%, while deficiency (ie, a 25(OH)D level <20 ng/mL) was found in 36.6% of these patients. Serum 25(OH)D levels decreased significantly in relation to the severity of either retinopathy or nephropathy or both. In multivariate logistic regression analysis, lower 25(OH)D levels were independently associated with the presence of microvascular complications (considered as a composite end point; OR 0.758; 95% CI 0.607 to 0.947, p=0.015). Notably, this association remained significant even after excluding those with an estimated glomerular filtration rate <60 mL/min/1.73 m(2). CONCLUSIONS: We found an inverse and independent relationship between circulating 25(OH)D levels and the prevalence of microvascular complications in patients with type 2 diabetes. However, vitamin D may be simply a marker and causality cannot be implied from our cross-sectional study. Whether vitamin D supplementation in patients with type 2 diabetes may have beneficial effects on the risk of microvascular complications remains to be investigated.

Relationships between cardiorespiratory fitness, metabolic control, and fat distribution in type 2 diabetes subjects.

Factors contributing to the reduced cardiorespiratory fitness typical of sedentary subjects with type 2 diabetes are still largely unknown. In this study, we assessed the relationships between cardiorespiratory fitness and abdominal and skeletal muscle fat content in 39 untrained type 2 diabetes subjects, 27 males and 12 females (mean ± SD age 56.5 ± 7.3 year, BMI 29.4 ± 4.7 kg/m(2)). Peak oxygen uptake (VO2peak) and ventilatory threshold (VO2VT) were assessed by maximal cycle ergometer exercise test, insulin sensitivity by euglycemic-hyperinsulinemic clamp, and body composition by dual-energy X-ray absorptiometry. Magnetic resonance imaging was used to evaluate visceral, total subcutaneous (SAT), superficial (SSAT) and deep sub-depots of subcutaneous abdominal adipose tissue, and sagittal abdominal diameter (SAD), as well as femoral quadriceps skeletal muscle fat content. In univariate analysis, both VO2peak and VO2VT were inversely associated with BMI, total fat mass, SAT, SSAT, and sagittal abdominal diameter. VO2peak was also inversely associated with skeletal muscle fat content. A significant direct association was observed between VO2VT and insulin sensitivity. No associations between cardiorespiratory fitness parameters and metabolic profile data were found. In multivariable regression analysis, after adjusting for age and gender, VO2peak was independently predicted by higher HDL cholesterol, and lower SAD and skeletal muscle fat content (R (2) = 0.64, p < 0.001), whereas VO2VT was predicted only by sagittal abdominal diameter (R (2) = 0.48, p = 0.025). In conclusion, in untrained type 2 diabetes subjects, peak oxygen uptake is associated with sagittal abdominal diameter, skeletal muscle fat content, and HDL cholesterol levels. Future research should target these features in prospective intervention studies.

Glycated haemoglobin is inversely related to serum vitamin D levels in type 2 diabetic patients.

OBJECTIVE: A correlation between glucose control and 25(OH)D metabolism has been suggested by previous studies. However, this correlation has not yet been evaluated considering the impact of chronic complications of type 2 diabetes, especially the presence of nephropathy. Thus, the aim of this study was to determine the correlation between A1C and 25(OH)D in a well characterized cohort of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We cross-sectionally examined the association between A1C and serum 25(OH) D in 715 type 2 diabetic patients attending our clinic during the years 2011-2012. The average age was 68±12 years (range 26-94 years). The relation between A1C and serum 25(OH)D levels was modelled by multiple linear regression analyses. RESULTS: Serum 25(OH)D levels were inversely associated with A1C levels (r = -0.116, p = .003). This relation maintains its independence in the multivariate analysis after adjusting for age, sex, A1C, BMI, treatment and duration of diabetes and nephropathy. CONCLUSIONS: In type 2 diabetic patients, high A1C levels are associated with low concentrations of serum 25(OH)D independently of duration of diabetes, diabetic treatment and nephropathy. Future studies are needed to clarify the biological relation between glucose control and vitamin D metabolism in type 2 diabetes.

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).

UNLABELLED: Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4-month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual-energy X-ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in-opposed-phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups. CONCLUSION: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD.

Differences in the acute effects of aerobic and resistance exercise in subjects with type 2 diabetes: results from the RAED2 Randomized Trial.

OBJECTIVE: Both aerobic (AER) and resistance (RES) training, if maintained over a period of several months, reduce HbA1c levels in type 2 diabetes subjects. However, it is still unknown whether the short-term effects of these types of exercise on blood glucose are similar. Our objective was to assess whether there may be a difference in acute blood glucose changes after a single bout of AER or RES exercise. STUDY DESIGN: Twenty-five patients participating in the RAED2 Study, a RCT comparing AER and RES training in diabetic subjects, were submitted to continuous glucose monitoring during a 60-min exercise session and over the following 47 h. These measurements were performed after 10.9+0.4 weeks of training. Glucose concentration areas under the curve (AUC) during exercise, the subsequent night, and the 24-h period following exercise, as well as the corresponding periods of the non-exercise day, were assessed. Moreover, the low (LBGI) and high (HBGI) blood glucose indices, which summarize the duration and extent of hypoglycaemia or hyperglycaemia, respectively, were measured. RESULTS: AER and RES training similarly reduced HbA1c. Forty-eight hour glucose AUC was similar in both groups. However, a comparison of glucose AUC during the 60-min exercise period and the corresponding period of the non-exercise day showed that glucose levels were lower during exercise in the AER but not in the RES group (time-by-group interaction p = 0.04). Similar differences were observed in the nocturnal periods (time-by-group interaction p = 0.02). Accordingly, nocturnal LBGI was higher in the exercise day than in the non-exercise day in the AER (p = 0.012) but not in the RES group (p = 0.62). CONCLUSIONS: Although AER and RES training have similar long-term metabolic effects in diabetic subjects, the acute effects of single bouts of these exercise types differ, with a potential increase in late-onset hypoglycaemia risk after AER exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT01182948.

Comparison of two creatinine-based estimating equations in predicting all-cause and cardiovascular mortality in patients with type 2 diabetes.

OBJECTIVE: To compare the performance of two glomerular filtration rate (GFR)-estimating equations in predicting the risk of all-cause and cardiovascular mortality in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We followed 2,823 type 2 diabetic outpatients for a period of 6 years for the occurrence of all-cause and cardiovascular mortality. GFR was estimated using the four-variable Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: At baseline, an estimated GFR (eGFR) <60 mL/min/1.73 m(2) was present in 22.0 and 20.2% of patients using the MDRD study equation and the CKD-EPI equation, respectively. A total of 309 patients died during the follow-up (152 patients from cardiovascular causes). Both creatinine-based equations were associated with an increased risk of all-cause and cardiovascular mortality. However, the CKD-EPI equation provided a more accurate risk prediction of mortality than the MDRD study equation. Receiving operating characteristic curves showed that the areas under the curve (AUCs) for all-cause mortality (AUC 0.712 [95% CI 0.682-0.741]) and cardiovascular mortality (0.771 [0.734-0.808]) using eGFR(CKD-EPI) were significantly greater (P < 0.0001 by the z statistic) than those obtained by using eGFR(MDRD) (0.679 [0.647-0.711] for all-cause mortality and 0.739 [0.698-0.783] for cardiovascular mortality). CONCLUSIONS: Our findings suggest that the estimation of GFR using the CKD-EPI equation more appropriately stratifies patients with type 2 diabetes according to the risk of all-cause and cardiovascular mortality compared with the MDRD study equation.

Aortic and mitral annular calcifications are predictive of all-cause and cardiovascular mortality in patients with type 2 diabetes.

OBJECTIVE: To examine the association of aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) with all-cause and cardiovascular mortality in type 2 diabetic individuals. RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data from 902 type 2 diabetic outpatients, who had undergone a transthoracic echocardiography for clinical reasons during the years 1992-2007. AVS and MAC were diagnosed by echocardiography, and a heart valve calcium (HVC) score was calculated by summing up the AVS and MAC variables. The study outcomes were all-cause and cardiovascular mortality. RESULTS: At baseline, 477 (52.9%) patients had no heart valves affected (HVC-0), 304 (33.7%) had one valve affected (HVC-1), and 121 (13.4%) had both valves affected (HVC-2). During a mean follow-up of 9 years, 137 (15.2%) patients died, 78 of them from cardiovascular causes. Compared with patients with HVC-0, those with HVC-2 had the highest risk of all-cause and cardiovascular mortality, whereas those with HVC-1 had an intermediate risk (P < 0.0001 by the log-rank test). After adjustment for sex, age, BMI, systolic blood pressure, diabetes duration, A1C, LDL cholesterol, estimated glomerular filtration rate, smoking, history of myocardial infarction, and use of antihypertensive and lipid-lowering drugs, the hazard ratio of all-cause mortality was 2.3 (95% CI 1.1-4.9; P < 0.01) for patients with HVC-1 and 9.3 (3.9-17.4; P < 0.001) for those with HVC-2. Similar results were found for cardiovascular mortality. CONCLUSIONS: Our findings indicate that AVS and MAC, singly or in combination, are independently associated with all-cause and cardiovascular mortality in type 2 diabetic patients.