Pablo Aschner

Multifaceted Determinants for Achieving Glycemic Control: The International Diabetes Management Practice Study (IDMPS)

OBJECTIVE—The International Diabetes Mellitus Practice Study is a 5-year survey documenting changes in diabetes treatment practice in developing regions. RESEARCH DESIGN AND METHODS—Logistic regression analysis was used to identify factors for achieving A1C <7% in 11,799 patients (1,898 type 1 diabetic and 9,901 type 2 diabetic) recruited by 937 physicians from 17 countries in Eastern Europe (n = 3,519), Asia (n = 5,888), Latin America (n = 2,116), and Africa (n = 276). RESULTS—Twenty-two percent of type 1 diabetic and 36% of type 2 diabetic patients never had A1C measurements. In those with values for A1C, blood pressure, and LDL cholesterol, 7.5% of type 1 diabetic (n = 696) and 3.6% of type 2 diabetic (n = 3,896) patients attained all three recommended targets (blood pressure <130/80 mmHg, LDL cholesterol <100 mg/dl, and A1C <7%). Self-monitoring of blood glucose was the only predictor for achieving the A1C goal in type 1 diabetes (odds ratios: Asia 2.24, Latin America 3.55, and Eastern Europe 2.42). In type 2 diabetes, short disease duration (Asia 0.97, Latin America 0.97, and Eastern Europe 0.82) and treatment with few oral glucose–lowering drugs (Asia 0.64, Latin America 0.76, and Eastern Europe 0.62) were predictors. Other region-specific factors included lack of microvascular complications and old age in Latin America and Asia; health insurance coverage and specialist care in Latin America; lack of obesity and self-adjustment of insulin dosages in Asia; and training by a diabetes educator, self-monitoring of blood glucose in patients who self-adjusted insulin, and lack of macrovascular complications in Eastern Europe. CONCLUSIONS—In developing countries, factors pertinent to patients, doctors, and health care systems all impact on glycemic control.

Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes

Aim: To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment‐naïve patients with type 2 diabetes.

Diabetes trends in Latin America.

The incidence of type 1 diabetes in Latin America ranges from 0.4 to 8.3 cases per 100 000 children under 15 years of age, and the prevalence of type 2 diabetes ranges from 1.2% to 8%, with higher prevalence rates in urban areas. The frequency of diabetes in Latin America is expected to increase by 38% over the next 10 years, compared with an estimated 14% increase in the total population. The total number of cases of diabetes is expected to more than double and to exceed the number of cases in the US, Canada, and Europe by 2025. Factors underlying this increase include aging and increased life expectancy of the population, increased urbanization, and lifestyle changes among Native American populations. In many places, only a minority of individuals currently receives treatment for diabetes. Furthermore, the diagnosis of type 2 diabetes often occurs late in the course of the disease, with the result that 10–40% of patients have chronic complications at the time of diagnosis. Hospital costs account for most direct expenditures associated with treatment, and mortality associated with diabetes has increased markedly in some areas over the past 2 decades. Copyright

Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial

BACKGROUND In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin. METHODS In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0-5·5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114. FINDINGS 732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1·72%, SE 0·06) than for those on sitagliptin (n=253; -1·13%, SE 0·06) with a mean difference of -0·59% (95% CI -0·77 to -0·42, p<0·0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4·21 [SE 0·54] vs 0·50 [SE 0·09] events per patient-year; p<0·0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event. INTERPRETATION Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease. FUNDING Sanofi.

Determination of the cutoff point for waist circumference that establishes the presence of abdominal obesity in Latin American men and women

AIMS The recent definitions of the metabolic syndrome (MS) recognize the need for ethnic and region-specific waist circumference (WC) cut-offs that identify people with abdominal obesity. We tested WC as a diagnostic tool to identify people with visceral adiposity in Hispanics from the Latin America region. METHODS We used the area of visceral adipose tissue (VAT) ≥ 100 cm² at the level between the 4th and 5th lumbar vertebrae in abdominal CT scans as a marker of visceral adiposity and established the optimal WC threshold for men and women by means of receiver operating characteristic (ROC) curves. RESULTS 179 men and 278 women from Mexico, El Salvador, Venezuela, Colombia and Paraguay were included. The ROC curves were highly discriminative of excess VAT for men and women (area under the curve 0.9 and 0.8 respectively) and the WC threshold was identified at 94 cm for men and between 90 and 92 cm for women. CONCLUSION In men the WC cutoff was equal to that proposed for europids and suggested for US adults who may have strong genetic contribution to insulin resistance such as Hispanics. In women the threshold was significantly higher than previously proposed for South and Central Americans.

Glucose Intolerance in Colombia: A population-based survey in an urban community

Objective— To determine the prevalence of diabetes and its relationship to age and obesity in an urban community in Colombia. Research Design and Methods— A cluster sample of 670 adults ≥ 30 yr of age was selected from the city of Santafè de Bogotá. Classification of diabetes and IGT was according to WHO criteria. Results— Response to the survey, conducted in 1988–1989, was 71% for men and 84% for women. Prevalence of diabetes was 7% in both sexes. Prevalence of IGT was 5% in men and 7% in women. Age-standardized prevalence of diabetes in the 30- to 64-yr age range was comparable with that reported in urban Brazilians and rural Hispanics in the U.S.. Prevalence was higher than in the white population of the U.S. but lower than in several urban U.S. Hispanic communities. Some 40% of men and 30% of women with diabetes were unaware of their condition before the survey, but all those <50 yr of age were diagnosed previously. Glucose intolerance was associated with high BMI in men and with advancing age in both sexes. Conclusions— Glucose intolerance is common in this community and will likely increase in frequency in Colombians with further urbanization and population aging.

Diabetes in South and Central America: An update

The estimated population of the South and Central America (SACA) Region is 467.6 million and 64% is in the age range of 20-79 years but the population pyramid and age distribution are changing. The average prevalence of diabetes in the Region is 8.0% and is expected to reach 9.8% by the year 2035. Prevalence is much lower in rural settings than in urban and the differences attributed to lifestyle changes may be a target for intervention. The indigenous population is a particularly vulnerable group needing special attention. On average, 24% of the adult cases with diabetes are undiagnosed but in some countries this is still as high as 50%. Health expenditure due to diabetes in the Region is around 9% of the global total. Inadequate glycemic control, defined as HbA1c >7%, is a strong predictor of chronic complications which increase resource use in the Region and less than half of the patients enrolled in diabetes care programmes are at target. Fifty percent or more of the adult population is overweight/obese and around one third of the adult population has metabolic syndrome using regional cutoffs for waist circumference. The number of people with IGT is almost equal to those with diabetes presenting an additional challenge for prevention. Children with type 1 diabetes represent only 0.2% of the total population with diabetes but the incidence may be increasing. In many places they have limited access to insulin, and even when available, it is not used appropriately. The available epidemiological data provide the background to act in developing national diabetes programmes which integrate diabetes care with cardiovascular prevention and promote diabetes prevention as well.

Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo‐controlled 54‐week trial in patients with type 2 diabetes (一项为期54周的对持续使用二甲双胍与罗格列酮联合治疗的2型糖尿病患者加用西格列汀治疗的有效性与安全性的随机安慰剂对照研究)

Background:  New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes (T2D), a progressive disorder that often requires combination therapy. The present study assessed the efficacy and safety of sitagliptin as add‐on therapy to metformin and rosiglitazone in patients with T2D.

Pancreatic Safety of Sitagliptin in the TECOS Study

OBJECTIVE We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i). RESEARCH DESIGN AND METHODS In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly. RESULTS Baseline differences were minimal between participants confirmed to have no pancreatic events, acute pancreatitis, or pancreatic cancer. Among those participants randomized to receive sitagliptin, 23 (0.3%) (vs. 12 randomized to receive placebo [0.2%]) had pancreatitis (hazard ratio 1.93 [95% CI 0.96–3.88], P = 0.065; 0.107 vs. 0.056/100 patient-years), with 25 versus 17 events, respectively. Severe pancreatitis (two fatal) occurred in four individuals allocated to receive sitagliptin. Cases of pancreatic cancer were numerically fewer with sitagliptin (9 [0.1%]) versus placebo (14 [0.2%]) (hazard ratio 0.66 [95% CI 0.28–1.51], P = 0.32; 0.042 vs. 0.066 events/100 patient-years). Meta-analysis with two other DPP-4i cardiovascular outcome studies showed an increased risk for acute pancreatitis (risk ratio 1.78 [95% CI 1.13–2.81], P = 0.01) and no significant effect for pancreatic cancer (risk ratio 0.54 [95% CI 0.28–1.04], P = 0.07). CONCLUSIONS Pancreatitis and pancreatic cancer were uncommon events with rates that were not statistically significantly different between the sitagliptin and placebo groups, although numerically more sitagliptin participants developed pancreatitis and fewer developed pancreatic cancer. Meta-analysis suggests a small absolute increased risk for pancreatitis with DPP-4i therapy.

Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance.

Objectives:To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D).Design:Multicenter, international observational study: cross-sectional analysis.Subjects:Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation.Results:Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15–1.74), women: OR 1.62 (1.29–2.04)), iIGT (men: OR 1.59 (1.15–2.01), women: OR 1.30 (0.96–1.76)), IFG+IGT (men: OR 1.64 (1.27–2.13), women: OR 1.83 (1.36–2.48)) and nT2D (men: OR 1.80 (1.35–2.42), women: OR 1.73 (1.25–2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12–1.90), women: OR 1.81 (1.41–2.35)), IFG+IGT (men: OR 1.42 (1.14–1.77), women: OR 1.74 (1.35–2.26)) and nT2D (men: OR 1.77 (1.40–2.27), women: OR 2.38 (1.81–3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45–0.88)).Conclusions:Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women.