The prediction of Metabolic Syndrome alterations is improved by combining waist circumference and handgrip strength measurements compared to either alone.

BACKGROUND: Adiposity is a major component of the metabolic syndrome (MetS), low muscle strength has also been identified as a risk factor for MetS and for cardiovascular disease. We describe the prevalence of MetS and evaluate the relationship between muscle strength, anthropometric measures of adiposity, and associations with the cluster of the components of MetS, in a middle-income country. METHODS: MetS was defined by the International Diabetes Federation criteria. To assess the association between anthropometric variables (waist circumference (WC), waist-to-hip ratio (W/H), body mass index (BMI)), strength (handgrip/kg bodyweight (HGS/BW)) and the cluster of MetS, we created a MetS score. For each alteration (high triglycerides, low HDLc, dysglycemia, or high blood pressure) one point was conferred. To evaluate the association an index of fat:muscle and MetS score, participants were divided into 9 groups based on combinations of sex-specific tertiles of WC and HGS/BW. RESULTS: The overall prevalence of MetS in the 5,026 participants (64% women; mean age 51.2 years) was 42%. Lower HGS/BW, and higher WC, BMI, and W/H were associated with a higher MetS score. Amongst the 9 HGS/BW:WC groups, participants in the lowest tertile of HGS/BW and the highest tertile of WC had a higher MetS score (OR = 4.69 in women and OR = 8.25 in men;p < 0.01) compared to those in the highest tertile of HGS/BW and in the lowest tertile of WC. CONCLUSION: WC was the principal risk factor for a high MetS score and an inverse association between HGS/BW and MetS score was found. Combining these anthropometric measures improved the prediction of metabolic alterations over either alone.

Self-Reported Prevalence of Chronic Non-Communicable Diseases in Relation to Socioeconomic and Educational Factors in Colombia: A Community-Based Study in 11 Departments.

Background: Chronic non-communicable diseases are prevalent conditions in developing countries, such as Colombia. Several socioeconomic and educational factors have been associated with these pathologies. However, there is little country-specific information regarding the self-reported prevalence of chronic diseases and their association with the aforementioned factors in Colombia. Objectives: To evaluate the current situation of chronic non-transmissible diseases in Colombia by self-report and to analyze its potential relationship with sociodemographic, economic and educational factors. Methods: This is a cross-sectional baseline sub-analysis from the prospective, standardized collaborative PURE study in Colombia. Participants were recruited between 2005 to 2009, in 11 departments of the country, and included 7,485 subjects of 35 to 70 years old. Questionnaires of self-reported chronic non-communicable diseases, and demographic, socioeconomic and educational variables were applied. Results: Hypertension was the most prevalent chronic condition reported with a prevalence of 22.2% (21.2%-23.1%, 95% CI), followed by diabetes with a prevalence of 5.7% (5.1%-6.2%, 95% CI), asthma 2.7% (2.2%-3.0%, 95% CI), coronary heart disease 2.4% (2.0%-2.7%, 95% CI), stroke and heart failure 1.5% (1.2%-1.8%, 95% CI) each, chronic obstructive pulmonary disease 1.2% (0.6%-1.5%, 95% CI), and cancer 1.2% (1.0%-1.5%, 95% CI). Among the study sample, 23.3% (22.4%-24.3%, 95% CI) reported having one chronic NCDs, and 6.4% (5.9%-7.0%, 95% CI) reported having multiple chronic NCDs. The prevalence of multiple NCDs increased significantly with age, was more common in those from households with higher income, whereas it was significantly lower in persons with high education.The central and central-east regions of the country are those with the higher prevalence of self-reported NCDs. Conclusion: The results of the current study indicate the presence of socioeconomic and educational inequalities in the distribution of chronic NCDs in the Colombian population.

Lixisenatide reduces glycaemic variability in insulin-treated patients with type 2 diabetes.

Chronic hyperglycaemia and glucose variability are associated with the development of chronic diabetes-related complications. We conducted a pooled analysis of patient-level data from three 24-week, randomized, phase III clinical trials to evaluate the impact of lixisenatide (LIXI) on glycaemic variability (GV) vs placebo as add-on to basal insulin. The main outcome GV measures were standard deviation (s.d.), mean amplitude of glycaemic excursions (MAGE), mean absolute glucose (MAG) level, area under the curve for fasting glucose (AUC-F), and high (HBGI) and low blood glucose index (LBGI). The change in GV metrics over 24 weeks and relationships among baseline GV, patient characteristics and outcomes were assessed. Data were pooled from 1198 patients (665 LIXI, 533 placebo). Values for s.d., MAG level, MAGE, HBGI, and AUC-F significantly decreased with LIXI vs placebo, while LBGI values were unchanged. Higher baseline GV measures correlated with older age, longer type 2 diabetes duration, lower body mass index, higher baseline glycated/haemogobin, greater reduction in postprandial glucose (PPG) level, and higher rates of symptomatic hypoglycaemia. These data show that LIXI added to basal insulin significantly reduced GV and PPG excursions vs placebo, without increasing the risk of hypoglycaemia (LBGI).

Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia.

BACKGROUND: A randomised, double-blind, placebo-controlled study evaluated lipid- and glucose-lowering effects of colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients. METHODS: Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥2.6 mmol/L) and triglycerides < 500 mg/dL (<5.6 mmol/L) were randomised to colesevelam 3.75 g/day or placebo for 16 weeks. The intent-to-treat population comprised 103 colesevelam and 106 placebo recipients. RESULTS: At the end of the study, mean reduction from baseline in total LDL particle concentration was significantly greater with colesevelam versus placebo (mean treatment difference: -113 nmol/L; p = 0.02). Increases in total very low-density lipoprotein particle concentration (VLDL-P) and high-density lipoprotein particle concentration (HDL-P) did not differ significantly between the groups; however, with colesevelam versus placebo, there were significantly (p < 0.05) greater increases in large and medium VLDL-P and large HDL-P and reductions in small VLDL-P. Mean size increases were significantly greater with colesevelam for VLDL (mean treatment difference: 5.3 nm; p < 0.0001) and HDL (0.1 nm; p = 0.002). CONCLUSIONS: Colesevelam improved the overall atherogenic lipoprotein profile in adults with prediabetes and primary hyperlipidaemia, despite potentially less favourable changes in VLDL particles.

Initial combination therapy with metformin plus colesevelam in drug-naïve Hispanic patients with early type 2 diabetes.

OBJECTIVE: To evaluate initial combination therapy with metformin plus colesevelam in drug-naïve Hispanic patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Patients self-identified as Hispanic from a previous study were included in this exploratory post hoc analysis. Patients were randomized to metformin plus colesevelam or metformin plus placebo. The primary efficacy parameter was the mean change in glycated hemoglobin (HbA1c) levels from baseline. RESULTS: Metformin plus colesevelam had a greater mean HbA1c reduction (-1.2 ± 0.1%) than metformin plus placebo (-0.8 ± 0.1%; P = 0.001) from mean baselines of 7.7% and 7.6%, respectively. Low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein (apo) B levels were also reduced (P < 0.0001 for all), while triglyceride (P < 0.0001) and apoA-I (P < 0.05) levels were increased with metformin plus colesevelam treatment compared with metformin plus placebo. With metformin plus colesevelam versus metformin plus placebo, more patients achieved an HbA1c of < 7.0% (75% vs 56%) and LDL-C of < 100 mg/dL (49% vs 14%; both P < 0.05). CONCLUSION: Metformin plus colesevelam may be an effective initial treatment option for Hispanic patients with early type 2 diabetes mellitus.

Clinical effects of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes.

OBJECTIVE: To evaluate the efficacy and safety of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes. MATERIALS AND METHODS: A 16-week, randomized, double-blind, placebo-controlled, multinational study evaluating colesevelam in participants with primary hyperlipidemia (low-density lipoprotein cholesterol [LDL-C] level ≥ 100 mg/dL) and prediabetes (fasting plasma glucose level ≥ 110 to ≤ 125 mg/dL, or 2-hour postload glucose level ≥ 140 to < 200 mg/dL during an oral glucose tolerance test) was conducted between January 14, 2008 and April 3, 2009. Participants were randomized 1:1 to colesevelam 3.75 g/day or placebo. The primary efficacy endpoint was mean change from baseline in LDL-C level with colesevelam compared with placebo. Participants who self-identified as Hispanic during enrollment were included in this exploratory analysis evaluating the efficacy of colesevelam in Hispanics with primary hyperlipidemia and prediabetes. RESULTS: From a total of 216 subjects with primary hyperlipidemia and prediabetes, 153 Hispanics were included in this post hoc analysis; 77 subjects were randomized to colesevelam and 76 subjects were randomized to placebo. At week 16, LDL-C levels were significantly reduced with colesevelam compared with placebo (mean treatment difference, -19.4%; P < 0.0001). Achievement of LDL-C level < 100 mg/dL was more frequent with colesevelam than with placebo (27% vs 11%; P = 0.002). In addition, significant mean reductions in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B levels (P ≤ 0.0002 for all), and a significant median increase in triglyceride levels (P = 0.003), were seen with colesevelam compared with placebo. At study end, there was a significant mean reduction in glycated hemoglobin levels and median reduction in fasting plasma glucose levels with colesevelam compared with placebo (P ≤ 0.02 for both). A fasting plasma glucose level < 100 mg/dL was achieved in 44% of colesevelam recipients compared with 23% of placebo recipients (P < 0.05). Overall, colesevelam was well tolerated. CONCLUSION: Colesevelam may be a treatment option for Hispanic subjects with primary hyperlipidemia and prediabetes, mainly to reduce LDL-C levels, with added beneficial effect on glucose levels. TRIAL REGISTRATION: www.ClinicalTrials.gov identifier NCT00570739.

Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus.

BACKGROUND: The bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM). OBJECTIVE: To assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables). METHODS: This 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.5%-10.0%, low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo. RESULTS: In total, 286 patients were randomized (metformin plus colesevelam [n = 145]; metformin plus placebo [n = 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: -16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), and apolipoprotein (apo) B (-8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 µmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo. CONCLUSION: Initial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739.

Rationale and design of a clinical trial to evaluate metformin and colesevelam HCl as first-line therapy in type 2 diabetes and colesevelam HCl in prediabetes.

OBJECTIVE: The complications of type 2 diabetes mellitus (DM) can begin early in the progression from impaired glucose tolerance to type 2 DM. Metformin is recommended as initial drug therapy for managing hyperglycemia in type 2 DM. The bile acid sequestrant colesevelam hydrochloride (HCl) is approved in the United States for glycemic control in adults with type 2 DM. Colesevelam HCl improves glycemic control and reduces low-density lipoprotein-cholesterol in patients inadequately controlled on metformin-, sulfonylurea-, or insulin-based therapy. This trial is designed to evaluate whether initial therapy with metformin + colesevelam HCl provides greater glucose control and additional lipid and lipoprotein benefits, as compared to metformin alone in drug-naïve patients with type 2 DM, and whether treatment with colesevelam HCl has a beneficial effect on lipid and glucose levels in drug-naïve patients with impaired glucose tolerance and/or impaired fasting glucose (prediabetes). RESEARCH DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, drug-naïve patients with type 2 DM will be randomized 1 : 1 to metformin + colesevelam HCl or metformin + matching placebo, while those with prediabetes will be randomized 1 : 1 to colesevelam HCl or placebo, for 16 weeks of treatment. The primary efficacy endpoint will be change in glycosylated hemoglobin (HbA(1c)) in patients with type 2 DM and change in low-density lipoprotein-cholesterol levels in patients with prediabetes. CONCLUSION: A potential limitation is that there is no direct comparator for the dual glucose- and lipid-lowering effect of colesevelam HCl in the prediabetes cohort. However, results of this trial will help to define the extent to which colesevelam HCl can help improve cardiometabolic risk factors for complications of type 2 DM in the first-line environment, and will also indicate the extent to which early intervention with colesevelam HCl can help to correct metabolic abnormalities associated with prediabetes.