Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) e waist body mass index (wBMI): Which is better?

Obesity and overfat are most commonly assessed using the body mass index (BMI), which evaluates "total obesity", without accounting for body fat distribution. Therefore, several indexes of obesity have been proposed, combining BMI with other measures or singular parameters. The aim of the study was to evaluate the accuracy of a new, simple index that takes into account both BMI and Waist Circumference (WC), Waist Body Mass Index (wBMI) in comparison to BMI, WC e Waist-to-Height Ratio (WHtR) for the identification of overfat and obese patients identified by fat mass percentage (FM%). 2400 non diabetic patients were enrolled. From the analysis carried out it emerges that wBMI, BMI, WC and WHtR all have a statistically significant positive correlation (p-Value < 0.001) with FM%. The multivariate analysis showed the positive relationship between these four indexes and the FM. To assess the accuracy of these indices in diagnosing the condition of overfat and obesity we used the statistical analysis Receiver Operating Characteristic (ROC). The Area Under the Curve (AUC) derived from the ROC showed that for the male gender the indicator with the greatest discriminating capacity of the conditions of overfat and obesity was the WHtR and the wBMI for the female gender. The wBMI is therefore configured as an additional tool at the disposal of the healthcare professional aimed at framing the overfat and obese patient and monitoring him during the course of treatment. Moreover wBMI is an indicator able to provide information about the FM% constituting an accurate tool for the evaluation of the overfat and obese patient.

Different distribution of phenotypes and glucose tolerance categories associated with two alternative proposed cutoffs of insulin resistance.

We investigated whether two alternative HOMA-IR thresholds recently proposed identify similar phenotype and have the same impact on gluco-metabolic risk. The two IR cutoffs, IR1 and IR2 (IR1: HOMA-IR >5.9 and IR2: HOMA-IR between 2.8 and 5.9 with HDL-C <51 mg/dl), were applied to a database of 2,360 outpatients, and their association with phenotypes, glucose tolerance, lipids and metabolic syndrome (MetS) was examined. IR1 group showed 5.5% of overweight versus 27.8% of IR2 subjects, and obesity was present in 92.3 versus 68.4%, respectively. We observed the major prevalence of pathological waist in IR1 compared to IR2 subjects: 96.0 versus 80.5% (p < 0.001). After OGTT, IR1 patients presented higher prevalence of impaired glucose tolerance (IGT: 25.8 vs. 20.2%, p < 0.001) and DM2 was diagnosed in 39.7% of IR1 versus 11.3% of IR2 patients (p < 0.001) with odds ratio (OR) 8.3 (95% CI 6.1-11.6) versus 0.8 (0.6-1.2), respectively. IR1 versus IR2 cutpoint showed higher significant (mean ± SEM) total cholesterol (224.8 ± 2.6 vs. 213.1 ± 1.7 mg/dl, p < 0.001) and triglyceride (208.1 ± 12.3 vs. 177.4 ± 4.8 mg/dl, p < 0.001) levels. MetS prevalence was significantly higher in IR1 than IR2 (89.0 vs. 78.3%, p < 0.001). The IR1 cutpoint was associated with a higher OR of MetS 7.3 (5.3-10.2) versus 5.2 (2.8-9.5) of IR2. In summary, the two alternative HOMA-IR cutoffs identify subjects with different distribution of phenotypes and gluco-metabolic risk. The IR1 patients are characterized by higher prevalence of obesity, pathological waist, MetS, dyslipidemia and IGT/DM2.

The role of DPP4 activity in cardiovascular districts: in vivo and in vitro evidence.

The introduction of incretin hormone-based therapies represents a novel therapeutic strategy, since these drugs not only improve glycemia with minimal risk of hypoglycemia, but also have other extraglycemic beneficial effects. These agents, which are effective in improving glucose control, could also have positive effects on the incidence of cardiovascular events. The aim of this review is to summarize the present literature about the role of dipeptidyl peptidase 4 (DPP4) in cardiovascular districts, not only strictly correlated to its effect on glucagon-like peptide-1 (GLP-1) circulating levels, but also to what is known about possible cardiovascular actions. Actually, DPP4 is known to be present in many cells and tissues and its effects go beyond purely metabolic aspects. Almost always the inhibition of DPP4 activity is associated with improved cardiovascular profile, but it has shown to possess antithrombotic properties and these different effects could be connected with a site and/or species specificity of DPP4. Certainly, DPP4 seems to exert many functions, both directly and indirectly, on cardiovascular districts, opening new possibilities of prevention and treatment of complications at this level, not only in patients affected by diabetes mellitus.

Effects of antihypertensive treatments on incidence of diabetes: a case-control study.

AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.

Hypertriglyceridaemic waist phenotype and ß-cell function in subjects with normal and impaired glucose tolerance.

AIM: To determine the association between the hypertriglyceridaemic waist phenotype, a combination of enlarged waist circumference and increased triglyceride levels, and ß-cell function in subjects with normal glucose tolerance and those with impaired glucose tolerance. METHODS: We studied 1344 outpatients clinic without diabetes. Overnight fasting blood samples were obtained to measure plasma glucose, insulin and lipids. An oral glucose tolerance test was performed in all subjects. All patients were divided in four groups, two groups with normal glucose tolerance and two with impaired glucose tolerance, with or without the hypertriglyceridaemic waist phenotype. Insulin resistance and ß-cell function were calculated by homeostatsis model assessment 2 indices. RESULTS: Twenty per cent of subjects showed the hypertriglyceridaemic waist phenotype and 23.8% had impaired glucose tolerance. We found a progressive significant increase (P < 0.001) of insulin resistance from subjects with normal glucose tolerance without the hypertriglyceridaemic waist phenotype with respect to patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype. In subjects with normal glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with a mild, but not significant, increase of homeostatsis model assessment 2-ß levels; but, in patients with impaired glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with significantly lower homeostatsis model assessment 2-ß levels [127.0 (103.0-162.7) vs. 123.0 (96.0-147.0); P < 0.05]. The hypertriglyceridaemic waist phenotype displayed a higher (odds ratio 95% CI) ß-cell dysfunction of 1.8 (1.3-2.6) and insulin resistance of 5.0 (2.7-8.5) compared with 1.3 (0.9-1.9) and 2.4 (1.8-3.2), respectively, of waist circumference alone. CONCLUSION: In this study, the hypertriglyceridaemic waist phenotype is associated with increased insulin resistance and an overstimulation of ß-cell function in subjects with normal glucose tolerance, while patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype showed a reduction in ß-cell function. These data suggest the importance of the identification of patients with impaired glucose tolerance combined with the hypertriglyceridaemic waist phenotype for an early intervention in relation to the high risk of developing Type 2 diabetes.

Motivational readiness for treatment in weight control programs: the TREatment MOtivation and REadiness (TRE-MORE) test.

BACKGROUND AND AIMS: The degree of motivation before starting the treatment represents a pre-treatment predictor of successful weight management. The aim of this study is to develop and validate a new self-reported questionnaire of motivation and readiness to change before starting a lifestyle modification program (the TREatment MOtivation and REadiness test) (TRE-MORE) for overweight patients. METHODS AND RESULTS: TRE-MORE was evaluated in a consecutive series of 129 obese patients attending our Outpatient Clinic. Validation of the questionnaire was performed through test-retest reliability, internal consistency, psychopathological correlates, and concurrent validity. Subjects have been evaluated by means of a clinical interview, and different self-reported questionnaires, assessing the eating specific and general psychopathology, and quality of life. TRE-MORE total and subscales scores showed good test-retest reliability and internal consistency. We identified 10 items grouped in 3 areas (obstacles and desire to overcome, taking care of themselves, and sharing the problems, current lifestyle). TREMORE scores were significantly correlated with eating specific psychopathology and quality of life measures. Univariate and Receiver Operating Characteristic curve analysis showed that TRE-MORE total and subscales scores represent a good model for predicting a weight loss >5% of the initial weight after 6 months of treatment. CONCLUSION: TRE-MORE represents a validated and easy-to-use questionnaire assessing at the meantime the treatment motivation and readiness with good predictive capacity for weight loss.

Relationship between GLP-1 levels and dipeptidyl peptidase-4 activity in different glucose tolerance conditions.

AIM: The reduced levels of glucagon-like peptide 1 (GLP-1) after an oral glucose load in Type 2 diabetic patients could be dependent either on a reduced synthesis or an increased degradation; but GLP-1 and dipeptidyl peptidase IV (DPP-IV) levels during an oral glucose tolerance test (OGTT) have not been studied together. The aim of the present study was to investigate GLP-1 and DPP-IV levels during an OGTT in patients with different degrees of glucose tolerance. METHODS: Fifty six subjects (34 female, 22 male) matched for sex, age, body mass index (BMI) and waist circumference underwent a 75 g oral glucose tolerance test. Twenty-eight had normal glucose tolerance, 15 had impaired glucose tolerance and 13 had Type 2 diabetes mellitus. GLP-1 assay was performed with an ELISA kit, and DPP-IV assay using a colorimetric method. RESULTS: At 30 min GLP-1 levels were significantly lower in subjects with impaired glucose tolerance and type 2 diabetes mellitus compared to those with normal glucose tolerance. The area under the GLP-1 curve was significantly different among the three groups; there was a significant decrease between subjects with normal and impaired glucose tolerance(P = 0.004) and between those with normal glucose tolerance and type 2 diabetes mellitus. (P < 0.001), while the area under the curve for DPP-IV showed no significant difference between the groups. CONCLUSIONS: These results suggest that an increase of GLP-1 degradation does not play a role in the early stages of diabetes mellitus.

Glucagon-like peptide-1 response to meals and post-prandial hyperglycemia in Type 2 diabetic patients.

BACKGROUND: The impaired response of glucagonlike peptide-1 (GLP-1) to meals in diabetic patients can contribute to the pathogenesis of impaired insulin secretion and post-prandial hyperglycemia. This study is aimed at the assessment of the relationship between meal-induced GLP-1 and post-prandial hyperglycemia in Type 2 diabetic patients. METHODS: Twenty-one drug-naïve Type 2 diabetic patients were studied. Blood glucose and active GLP-1 levels were measured 0, 30, 60, 90, and 120 min after a standard test meal. A continuous glucose monitoring (CGM) system was applied for the following 3 days. Nutrient intake at each meal was calculated on the basis of patients' food records. For each patient, post-prandial 120-min glucose incremental area under the curve (iAUC) was included in linear regression model exploring its relationship with total energy and carbohydrate intake, and the angular coefficient for total energy (EAC) and carbohydrate (CAC) was calculated. RESULTS: GLP-1 levels peaked 30 min after the test meal. Logarithmically transformed 60-min GLP-1 iAUC showed a significant inverse correlation with glycated hemoglobin (HbA1c) (p<0.01). A significant inverse correlation of 60-min GLP-1 iAUC was also observed with EAC and CAC (both p<0.01), meaning that patients with a lower GLP-1 response to the test meal had a higher increment of post-prandial glucose for each additional unit of total energy or carbohydrate intake. CONCLUSIONS: In Type 2 diabetic patients, a lower GLP-1 response to meals is associated with a higher HbA1c, and with a greater degree of meal-induced hyperglycemia, both in a meal test and during CGM in "real-life" conditions.

Motivational readiness to change in lifestyle modification programs.

Weight management programs still remain a great challenge as drop out rates represent a growing problem. It is essential to try and identify the predictors of success, in order to make a proposal really custom-tailored to the patients. Among the most valuable applications of valid weight loss prediction models is the early identification of individuals with the least estimated probability of success, who should be directed to alternative therapies. Equally important are improvements in the matching between treatments and participants, which are dependent on the measurement of relevant pre-treatment variables. In the treatment of obesity and in many other pathologies and dependencies, the motivation to change has an important role both in the period of the weight loss and in the phase of the maintenance of the result. Therefore, if the patient is considered to be ready to lose weight, weight loss therapy should be initiated, if not, the immediate goal will be to prevent further weight gain and explore barriers to weight reduction. Many papers have been published regarding the measurement of the degree/level of motivation of the patient towards a specific treatment. Unfortunately, most of these questionnaires have been created and then applied to different areas; in particular they have been used before starting specific therapies for addiction. Unfortunately, a validated and easy-to-use questionnaire assessing at the meantime treatment motivation and readiness with adequate predictive capacity for weight loss actually is not available in most languages, so that empiric non-objective methods continue to be used.

Lipoperoxidation and antioxidant capacity in patients with poorly controlled type 2 diabetes.

Type 2 diabetes is a heterogeneous disease resulting from insulin resistance and/or from a beta-cell secretory defect. Hyperglycemia, which occurs during type 2 diabetes, causes disorders of oxidative-antioxidative balance in the cells, leading to increased free-radical formation. Reduced antioxidant capacity is supposed to be one of the causes of the occurrence of complications in type 2 diabetes. The aim of this study was to evaluate lipoperoxidation and plasma antioxidant status in patients with poorly controlled type 2 diabetes with or without complications. In this study, 15 patients with type 2 diabetes without complications and 11 patients with type 2 diabetes with complications were enrolled. The 'ferric-reducing ability of plasma' showed no differences between the two experimental groups. A small, nonsignificant, Superoxide dismutase (SOD) activity reduction was observed in patients with diabetes with complications when compared to those patients with diabetes without complications; on the contrary, we found increased lipoperoxidation in patients with diabetes with complications compared with those patients with diabetes without complications. We also observed a positive correlation between malondialdehyde levels and high density lipoprotein or vitamin E in all analyzed patients with type 2 diabetes. Data obtained from our study show that patients with poorly controlled type 2 diabetes with complications have higher lipoperoxidation than patients with complication-free diabetes, although a residual compensatory response to hyperglycemia-induced oxidative stress occurs.

Exenatide: a review from pharmacology to clinical practice.

BACKGROUND: Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying. METHODS: In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c

Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk.

AIMS: Glucagon-like peptide-1 (GLP-1), a gastrointestinal hormone mainly produced in the post-prandial state, reduces blood glucose through the stimulation of insulin secretion and the inhibition of glucagon release. Long-acting GLP-1 receptor agonists, and dipeptidyl-peptidase-4 (DPP-4) inhibitors which increase GLP-1 levels, are used as hypoglycemic treatments in type 2 diabetes. This paper aims at reviewing the potential benefit of those treatments in the prevention of cardiovascular risk in type 2 diabetic patients. DATA SYNTHESIS: Experimental studies have shown that GLP-1 has several potentially beneficial actions on cardiovascular risk. Some of those, such as protection from myocardial ischemic damage and improvement of cardiac function, have also been demonstrated in humans. However, the equivalence of GLP-1 agonists and DPP-4 inhibitors with GLP-1, with respect to cardiovascular risk profile, cannot be assumed or taken for granted. Drugs of those two classes have been shown to effectively reduce glycated hemoglobin and to have a specific effect on post-prandial glucose; furthermore, they seem to reduce blood pressure and to have some favorable effects on lipid profiles. Additionally, GLP-1 agonists induce weight loss in diabetic patients. CONCLUSION: The profile of action of GLP-1 receptor agonists and DPP-4 inhibitors suggests the possibility of an actual reduction in cardiovascular risk, which needs to be confirmed by large long-term clinical trials.

Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1).

The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy, whereas members of the IGF system are neurotropic factors. Here, we investigated the effects of constant and intermittent high glucose concentrations on IGF1 and IGF-binding proteins (IGFBPs) in human neuroblast long-term cell cultures fetal neuroepithelial cells (FNC). These cells express the IGF1 receptor, and express and release in the culture medium IGFBP2, IGFBP4, and IGF1. The release of IGF1 was significantly increased by 17beta-estradiol (10 nM). IGF1 (100 nM) treatment determined a significant increase of IGFBP2 and a decrease of IGFBP4 release. In addition, IGF1 (1-100 nM) stimulated FNC cell proliferation in a dose-dependent manner. We hypothesized that this effect may be, at least partially, due to IGF1-induced up-regulation of the expression of the Alzheimer's disease related gene SELADIN-1 (now known as DHCR24 ), which acts as a pro-survival factor for neuronal cells. Conversely, the exposure to intermittent (20/10 mM), but not stable (20 mM), high glucose concentrations decreased the release of IGF1 and IGFBP2 in the culture medium and inhibited FNC growth by inducing apoptosis. The latter was prevented by the addition of IGF1 to the culture medium. Furthermore, high glucose concentrations reduced the expression of DHCR24. In conclusion, our results indicate for the first time that intermittent high glucose concentrations, similar to those observed in poorly controlled diabetic patients, may contribute to the development of diabetic neuropathy by interfering with the tropic effects exerted by the IGF system, and suggest the involvement of the neuroprotective factor DHCR24.

Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study.

BACKGROUND: Recent evidence suggests that some hypoglycemic treatments could affect the incidence of malignancies. This study was aimed at the assessment of cancer-related mortality in type 2 diabetic patients treated with different hypoglycemic drugs. METHODS: A retrospective observational cohort study was performed on a consecutive series of 3002 type 2 diabetic outpatients. Cancer-related death was identified through the City Registry Office. For patients visited for the first time after January 1 (st), 2000, information on incidence of cancer was also available. RESULTS: During a mean follow-up of 4.3+/-2.5 years, 87 cases of cancer-related death were recorded, with a yearly incidence rate of 0.70%. Patients receiving secretagogues showed a significantly higher mortality than the rest of the sample (unadjusted OR [95%CI] 1.76 [1.15-2.69], p=0.009), which was maintained after adjustment for confounders (HR 2.29 [1.21-4.02], p=0.003). Conversely, no significant association of cancer-related mortality was observed with insulin sensitizers or exogenous insulin. In comparison with patients receiving no hypoglycemic treatment, those on secretagogue or insulin monotherapy showed a higher cancer-related mortality (HR 2.25 [1.10-4.78], p=0.034 and HR 2.11 [1.01-4.50], p=0.048, respectively). The effect of treatments on incidence of malignancies was similar to that observed on cancer-related death. CONCLUSIONS: Insulin secretagogues and, to a lesser extent, exogenous insulin, appear to be associated with increased mortality for cancer, even after adjustment for multiple confounders. This issue deserves further investigation through epidemiological studies on larger samples of patients.

National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the FIrenze-Bagno A Ripoli study.

BACKGROUND: The International Diabetes Federation (IDF) proposed to modify the diagnostic criteria for metabolic syndrome (MS) previously issued by the National Cholesterol Education Program (NCEP). Aim of the present investigation is to compare the predictive value for diabetes of NCEP and IDF definitions of MS in a large sample of predominantly Caucasian subjects. METHODS: A prospective observational study was performed on a cohort study (n = 3096) enrolled in a diabetes-screening programme, the FIrenze-Bagno A Ripoli study. All subjects with fasting glucose >126 mg/dl and/or post-load glucose > or =200 mg/dl (5.7%) were excluded from the present analysis. Follow-up of each subject was continued until diagnosis of diabetes, death or until 31 December 2005. Mean follow-up was 27.7 +/- 11.3 months. RESULTS: Among subjects enrolled, 13.7 and 25.2% were affected by MS using NCEP and IDF criteria respectively. During follow-up, 38 new cases of diabetes were diagnosed, with a yearly incidence rate of 0.5%. The relative risk for diabetes in subjects with MS was 10.10 [5.13; 20.00] and 7.87 [3.70; 16.7] using NCEP and IDF definitions respectively. After adjustment for age, sex, fasting glucose and waist circumference, NCEP-defined MS, but not IDF-, was significantly associated with incident diabetes (hazard ratio, 95% CI: 2.41 [1.01; 5.95] and 2.05 [0.80; 5.29] respectively). CONCLUSIONS: Although the reasons for the proposed changes in diagnostic criteria for MS are easily understandable, the newer IDF definition, while increasing estimates of prevalence of the syndrome, reduces the effectiveness of MS in identifying subjects at risk for diabetes. Further research is needed before the previous NCEP criteria are abandoned.

Metabolic syndrome and pulse pressure.

AIM: Pulse pressure (PP) has been reported to be increased in patients with abdominal adiposity and insulin resistance. Aim of the present study is to verify the association of high PP with metabolic syndrome (MS) and with its individual components. METHODS: The relationship between PP and MS was studied in a sample of 1724 subjects aged (mean +/- s.d.) 52.8 +/- 1.3 years, enrolled in a screening programme for diabetes FIrenze-Bango A Ripoli (FIBAR) study, and in a consecutive series of 1775 patients with type 2 diabetes aged 64.3 +/- 9.1 years; only subjects not treated with antihypertensive medication were included in the analysis. RESULTS: In the FIBAR sample, PP was significantly higher in subjects with MS. A significant correlation of PP was found in women with waist circumference, fasting glucose and triglyceride (r = 0.14, 0.15, and 0.09 respectively), and in men with fasting glucose only (r = 0.09); the correlation was no longer significant after adjustment for age and mean blood pressure. Similar results were obtained in the series of patients with type 2 diabetes. DISCUSSION: High PP is associated with MS and its components, but this association seems to disappear after adjustment for age and mean blood pressure. On the basis of the present data, high PP cannot be considered as one of the alterations associated with MS.