Jesús Reviriego

A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus.

OBJECTIVE The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia. METHODS Patients with type 2 diabetes mellitus (HbA(1c) >/=6.5% and </=9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16 weeks at 41 centers in Canada and Spain. RESULTS A total of 297 patients were randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was 58.4 (10.9) years (range, 24-85 years), mean (SD) body mass index was 31.4 (4.8) kg/m(2), mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months, and 30.6% of patients were receiving medication for dyslipidemia. Treatment with pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA(1c) by 0.8% and 0.9% from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction in HbA(1c) of 0.2% was observed in the placebo group (P = 0.025). In patients with medium (>/=7% to <8%) or high (>/=8% to </=9.8%) baseline HbA(1c), both doses of pioglitazone significantly reduced HbA(1c) (both P < 0.001 vs placebo). Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001, respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P < 0.001, respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P < 0.001, respectively). Pioglitazone 45 mg also significantly reduced serum triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg were associated with a significant reduction in serum alanine aminotransferase relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone appeared to be safe and was well tolerated. CONCLUSIONS In the present study, pioglitazone 30 and 45 mg produced significant improvements in HbA(1c), insulin sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia.

Effects of a short-acting insulin analog (insulin Lispro) versus regular insulin on lipid metabolism in insulin-dependent diabetes mellitus

Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the physiological postprandial insulin profile. The aim of this study was to compare the effects of intensive insulin therapy on lipid metabolism using preprandial IL and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM) subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did not change after both treatments. In IDDM patients, total cholesterol and triglyceride levels appeared lower after RI than after IL. The low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P < .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities were observed at baseline, the protein content was lower (P < .05) after IL (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05). LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both treatments and did not normalize. IDDM and control subjects showed similar LDL subfraction distribution at baseline and after both treatments. Two-hour postprandial VLDL composition alterations, although improved after RI, completely normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) activities were similar to the control group and did not change after both treatments. Hepatic lipase (HL) activity was lower in diabetic patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after both treatments. In conclusion, in IDDM patients, IL (injected immediately before the meal) may offer small different effects on lipoprotein metabolism versus RI (injected 30 minutes before the meal) that, taken together, do not seem relevant.

Healthcare Costs Associated with Change in Body Mass Index in Patients with Type 2 Diabetes Mellitus in Spain

AbstractBackground: Weight management is considered a key therapeutic strategy in type 2 diabetes mellitus. However, little is known about the impact of weight loss or body mass index (BMI) reduction on type 2 diabetes-related healthcare costs. Objective: The aim of this study was to estimate the economic impact of change in BMI among patients with type 2 diabetes mellitus from the Spanish healthcare system perspective. Methods: The ECOBIM study is an observational, non-interventional study in which data on BMI change and costs incurred by patients with type 2 diabetes were collected cross-sectionally and retrospectively for a 12-month period. Generalized linear mixed models were applied to estimate the effects of (i) BMI change in general (one-slope model); (ii) BMI gain and no BMI gain (two-slope model); and (iii) BMI gain and no BMI gain among obese and non-obese patients (four-slope model). Results: We studied 738 patients with a mean (SD) age of 66 (11) years and BMI of 30.6 (5.2) kg/m2. During the 12-month study period, 41.2% of patients gained BMI (BMI gainers) and 58.8% experienced either loss (52.2%) or no change (6.6%) in BMI (non-BMI gainers). One-unit gain (or loss) in BMI was significantly (p<0.001) associated with a 2.4% cost increase (or decrease) [one-slope model]. Every unit gain in BMI was associated with a 20.0% increase in costs among BMI gainers while losing one unit was associated with an 8.0% decrease in costs among non-BMI gainers (two-slope model, p<0.01). The economic benefit associated with reducing one BMI unit was 9.4% cost decrease in obese and 2.7% in non-obese patients (4-slope model). Conclusion: An increase in BMI among patients with type 2 diabetes was associated with increased 1-year direct healthcare costs. A reduction in BMI was associated with appreciable short-term economic benefits, especially in obese patients.

Clinical evaluation of combined therapy for type 2 diabetes.

Abstract Objective: Therapeutic guidelines recommend the combination of drugs as necessary to control type 2 diabetes (T2D). This research assessed the effectiveness of pioglitazone (Pio), metformin (Met) and sulfonylurea (SU) combinations in the routine clinical practice. Research design and methods: A nationwide, 12-month prospective, observational cohort study was performed in 2294 patients with T2D (50.3% females, mean age: 61.1 years, mean body mass index: 30.2 kg/m2, mean time since diagnosis: 8.5 years) who started, at the discretion of treating physician, oral antihyperglycaemic treatment with either Pio + SU, Pio + Met or SU + Met because of inadequate control with previous therapy. Fasting plasma glucose (FPG), glycohaemoglobin (HbA1c), lipids, blood pressure, and anthropometric parameters were measured, and 10-year cardiovascular risk was estimated. Results: FPG, HbA1c and total cholesterol at baseline had mean values (184.6 mg/dl, 8.5% and 246.0 mg/dl, respectively) associated with an excess of micro- and macrovascular risk. The mean changes from baseline in the Pio + SU, Pio + Met and SU + Met cohorts were, respectively, −37.9, −32.7 and −25.8 mg/dl for FPG; −1.1, −1.0 and −0.7% for HbA1c; −30.7, −38.7 and −17.1 mg/dl for triglycerides; and +2.3, +2.5 and +0.6 mg/dl for HDL cholesterol. In consequence, the estimated 10-year cardiovascular risk decreased more in the Pio cohorts, particularly with Pio + Met (1.7% versus 1.4% Pio + SU and 1.0% SU + Met –Framingham equation– and 0.6% versus 0.4% SU + Met – Systematic Coronary Risk Evaluation model–). Related adverse events were significantly (p = 0.016) more frequent in Pio cohorts (4.7% with Pio + SU, 5.1% with Pio + Met) than in the SU + Met cohort (2.4%). Conclusions: In patients with T2D failing therapy, mostly SU or Met monotherapy, pioglitazone add-on treatment was associated with a significant improvement of micro- and macrovascular risk estimations. These results from real-life clinical conditions support the findings of prior randomised trials, although they should be interpreted with caution because of the observational, nonrandomised design.

Impacto de las herramientas «Mapas de Conversaciones™» sobre el conocimiento de la diabetes en pacientes españoles con diabetes mellitus tipo 2: un estudio aleatorizado y comparativo

BACKGROUND AND AIM This paper presents results from the Spanish subpopulation of a study comparing Conversation Maps™ (CM)-based education with regular care (RC) in type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS Adult patients with T2DM who were considered as not demonstrating ideal disease management were randomly assigned to CM or RC with assessments following (Visit 2), and at follow-up 6 months after (Visit 3), the final CM session. The primary endpoint was diabetes knowledge at Visit 3. RESULTS 310 patients were randomised to receive CM education (n=148) or RC (n=162). Median knowledge scores were ranked significantly higher in the CM group than the RC group at Visit 2 and Visit 3 (p<0.001). No significant differences in clinical and other outcomes were identified between the interventions, except satisfaction with care (p<0.001, Visit 2; p=0.055, Visit 3) and perception of goal attainment (p<0.001 and p = 0.046, respectively) that were both higher in the CM group. CONCLUSIONS In these patients from Spain, CM was superior to RC in terms of diabetes knowledge 6 months after education was completed, suggesting that CM should be considered for use in patients requiring diabetes education.

Alta prevalencia de obesidad en una población laboral en España

BACKGROUND AND OBJECTIVES To report the prevalence of obesity in a Spanish working population and its changes in recent years. MATERIAL AND METHODS Data were collected from routine medical examinations performed on workers by a national mutual insurance society for occupational accidents and diseases (Ibermutuamur). A structured questionnaire was completed and physical examinations were performed. Overweight was defined as BMI ranging from 25 and 29.9, obesity as BMI of 30-39.9, and morbid obesity as BMI ≥ 40 kg/m(2). RESULTS Data from 1,336,055 medical examinations performed from May 2004 to November 2007 were collected. Prevalence rates in the population examined in 2004 (n=230,684; 73% males; average age, 36.4 years) were: morbid obesity, 0.5% (0.6% males, 0.5% females); obesity, 14.5% (17.0% males, 7.7% females); overweight, 38.4% (44.8% males, 21.3% females). Prevalence rates of obesity and overweight were higher in blue-collar workers (16.4% and 40.5% respectively) as compared to white-collar workers (10.9% and 34.4% respectively). There was a progressive increase in prevalence of obesity during the 4-year study (2004-2007) in both males (17.0%, 17.6%, 17.9%, 18.2%) and females (7.6%, 8.0%, 8.4%, 8.7%). CONCLUSIONS Prevalence of obesity and overweight in the Spanish working population is high, especially in male blue-collar workers, and is increasing. There is a need to promote early prevention programs and specific treatments for obesity.

Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study

BackgroundType 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy.MethodsOver a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed.ResultsAll study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported.ConclusionsIn patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia.

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Insulin pharmacokinetics following subcutaneous administration were modeled, simulated, and displayed through an interactive and user‐friendly interface to illustrate the time course of administered insulins frequently prescribed, providing a simple tool for clinicians through a straightforward visualization of insulin regimens. Pharmacokinetic data of insulin formulations with different onset and duration of action from several clinical studies, including insulin glargine, regular insulin, neutral protamine Hagedorn (NPH), insulin lispro, and premixed preparations of NPH with regular insulin (Mix 70/30), and insulin lispro protamine suspension with insulin lispro (Mix 50/50, Mix 75/25), were used to develop a predictive population pharmacokinetic model of insulins with consideration of factors such as insulin formulation, weight‐based dosing, body‐weight effect on volume of distribution, and administration time relative to meals, on the insulin time‐action profile. The model‐predicted insulin profile of each insulin was validated and confirmed to be comparable to observed data via an external validation method. Model‐based simulations of clinically relevant insulin‐dosing scenarios to cater to specific initial patient and prescribing conditions were then implemented with differential equations using the R statistical program (version 3.2.2). The R package Shiny was subsequently applied to build a web browser interface to execute and visualize the model simulation outputs. The application of insulin pharmacokinetic modeling enabled informative visualization of insulin time‐action profiles and provided an efficient and intuitive educational tool to quickly convey and interactively explore many insulin time‐action profiles to ease the understanding of insulin formulations in clinical practice.

Prevalence of impaired fasting glucose and type 1 and 2 diabetes mellitus in a large nationwide working population in Spain

INTRODUCTION To report the prevalence of impaired fasting glucose (IFG), undiagnosed and diagnosed diabetes, and their association to occupational categories in a representative sample of working population in Spain. MATERIALS AND METHODS A cross-sectional study of workers who attended routine medical check-ups from January 2007 to December 2007. A structured questionnaire was completed, and physical examinations and routine serum biochemical tests were performed. IFG was defined as fasting glucose levels ranging from 100 to 125 mg/dl with no diagnosis of T1DM or T2DM; T1DM was defined as previous diagnosis of T1DM; and T2DM as previous diagnosis of T2DM, treatment with oral antidiabetic drugs or insulin or fasting glucose levels ≥126 mg/dl, according to ADA criteria. RESULTS Of the 371,997 participants (median age 35 [interquartile range 29-44] years), 72.4% were male. Raw prevalence rates (95% CI) of IFG, undiagnosed (UKDM), and previously known type 2 (KDM2) and type 1 (KDM1) diabetes were 10.4% (10.3-10.5%), 1.3% (1.2-1.3%), 1.1% (1.1-1.2%), and 0.3% (0.3-0.3%), respectively. With the exception of KDM1, prevalence of these conditions increased with age and was greater among manual/blue-collar workers (12.1%, 1.5%, 1.3% and 0.3%, respectively) as compared to non-manual/white-collar workers (7.3%, 0.8%, 0.8% and 0.3%, respectively). Age- and sex-adjusted prevalence rates of IFG, UKDM and KDM2 were 13.1%, 2.0% and 2.4%, respectively. DISCUSSION In this sample of Spanish working population, impaired glycemic profiles were common. Prevalence rates of IFG and T2DM were high among blue-collar workers (except for T1DM). These data emphasize the need for earlier structured preventive schemes.

Impact of frailty in older patients with diabetes mellitus: An overview

Diabetes and frailty are two conditions that frequently occur concurrently and are increasingly prevalent in the older patient. We review the concept, epidemiology and consequences of frailty, and the implications of the presence of frailty in the management of diabetes. Frailty is associated with decreased quality of life, a risk of falls, new or increased disability, hospitalization, and increased mortality. All of these factors affect the management of diabetes in older patients. It is important to rule out frailty in all diabetic patients aged >70 years; if frailty is suspected, a comprehensive and multidisciplinary medical and functional assessment of the patient should be conducted to develop an individualized treatment plan. This plan should include nutritional measures, physical activity, and education on self-care and diabetes; drugs should not be used without a clear indication. Antihyperglycemic drugs that may cause excessive weight loss and/or are associated with a high risk of hypoglycemia should be avoided.