The serum profile of adipokines in naïve patients with diabetes mellitus type 2 and obesity

Background: The aim of this study was to explore the relationship of serum profile of adipokines with cardiovascular risk factors and anthropometric parameters in patients with diabetes mellitus type 2. Subjects: A population of 108 obese patients with DM2 was analyzed. A complete biochemical anthropometric and nutritional evaluation was performed. Results: In the analysis with leptin as a dependent variable, the IL‐6 and glucose levels remained in the model (F = 6.2; P<0.05), with an increase of 5.8 (CI 95%:2.7–7.6) ng/ml with each 1 pg/ml of IL‐6 and of 5.2 (CI95%:2.5–5.8) ng/ml with each 1 mg/dl of glucose. In a second model with adiponectin as a dependent variable, the BMI remained in the model (F = 3.77;P<0.05), with an decrease of ?3.77 (CI 95%:0.53–7.1) ng/ml with each 1 point of BMI. In the third multivariate analysis with IL‐6 as a dependent variable, the glucose level remained in the model (F = 10.1; P<0.01), with an increase of 0.09 (CI95%:0.06–0.12) pg/ml with each 1 mg/dl of glucose. In the fourth multivariate analysis with resistin as a dependent variable, the CRP remained in the model (F = 2.51; P<0.05), with an increase of 0.28 (CI 95%:0.08–0.48) pg/ml with each 1 mg/dl of CRP. Conclusion: Serum profile of adipokines is associated with different risk factors in diabetic obese patients. J. Clin. Lab. Anal. 25:409–413, 2011. © 2011 Wiley Periodicals, Inc.     

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-na?ve 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.     

Insulin detemir improves glycaemic control without weight gain in insulin-naïve patients with type 2 diabetes: subgroup analysis from the PREDICTIVE study

Objective:  Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVE^TM) is a multi‐national, open‐label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. This post hoc subanalysis evaluates insulin‐naïve patients on oral antidiabetic drugs (OADs) who were initiated on insulin detemir as basal therapy (± OADs). Methods:  The European cohort of the PREDICTIVE study currently includes 20,531 patients (12,981 with type 2 diabetes) who were prescribed insulin detemir and followed up for 12, 26 or 52 weeks. Here, we report data from a subgroup of 2377 OAD‐treated, insulin‐naïve type 2 diabetes patients for a mean follow‐up of 14.4 weeks. Patients were prescribed insulin detemir as basal therapy (± OADs) by their physician, as part of routine clinical care. Results were reported in comparison with baseline observations. Results:  One serious adverse drug reaction was reported, which was a major hypoglycaemic episode. Treatment with insulin detemir (± OADs) significantly reduced mean haemoglobin A_1c (HbA_1c) (?1.3%; p < 0.0001), fasting glucose (?3.7 mmol/l; p < 0.0001), and within‐patient fasting glucose variability (?0.5 mmol/l; p < 0.0001). In the majority of patients (82%), these improvements in glycaemic control were achieved with once daily administration of insulin detemir. There was a small reduction in mean body weight (?0.7 kg; p < 0.0001), which was most apparent in patients with a higher body mass index (BMI) at baseline. A significant negative relationship between weight change and baseline BMI was observed (greater the BMI, greater the weight reduction). Multiple regression analysis showed that BMI and HbA_1c at baseline, and change in HbA_1c, were all predictors for weight change (p < 0.0001 for all), with BMI being the strongest predictor. Conclusions:  Patients with type 2 diabetes naïve to insulin can be effectively treated with once‐daily insulin detemir (± OADs) to achieve improved glycaemic control with no adverse effect on weight and a low risk of hypoglycaemia. These short‐term results are consistent with the findings of clinical trials.     

Measurement of bone mineral density in patients with type 2 diabetes mellitus

AIM：To investigate into the changes in bone mineral density (BMD) in patients with Type 2 diabetes mellitus.METHODS:BMD of lumbar vertebrae 2-4 and femur in 63 cases of patients with type 2 diabetes mellitus were measured with dual energy X-ray absorptiometry (DEXA) and were compared with age, sex and BMI-matched normal control group. RESULTS:No significant differences were found in BMD of lumbar vertebrae 2-4 in female of menopause with Type 2 diabetes mellitus(P&;gt;0.05), but BMD of total were lower than that of the controls (P&;lt;0.05), BMD of neck were significantly lower than that of the controls (P&;lt;0.01); No significant differences were found in BMD of L2-4 and femur in male of 50 years old above with Type 2 diabetes mellitus (P&;gt;0.05). CONCLUSION:BMD of Type 2 diabetes mellitus is different according to different sex,BMD of female of menopause with type 2 diabetes mellitus were descended easily,especially in areas of neck BMD, it should couse to pay attention to in order to prevent pathologic bone fracture;BMD of male of 50 years old above with Type 2 diabetes mellitus have no the obvious changes than that of the controls.     

Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes

Aim: The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate‐to‐severe hyperglycaemia (A1C = 7.5–12.0%). Methods: In an initial 12‐week phase (Phase A), 492 patients were randomised 1 : 1 in a double‐blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up‐titrated to 30 mg after 6 weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up‐titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up‐titrated to 45 mg qd Results: At the end of Phase A, mean changes from baseline were ?1.0% and ?0.9% for A1C; ?26.6 mg/dl and ?28.0 mg/dl for fasting plasma glucose; and ?52.8 mg/dl and ?50.1 mg/dl for 2‐h post‐meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycaemic parameters were greater with SITA/MET vs. PIO: ?1.7% vs. ?1.4% for A1C (p = 0.002); ?45.8 mg/dl vs. ?37.6 mg/dl for fasting plasma glucose (p = 0.03); ?90.3 mg/dl vs. ?69.1 mg/dl for 2‐h postmeal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO. The incidence of hypoglycaemia was similarly low in both groups. Body weight decreased with SITA/MET and increased with PIO (?1.1 kg vs. 3.4 kg; p < 0.001). Conclusion: Improvements in glycaemic control were greater with SITA/MET vs. PIO, with weight loss vs. weight gain. Both treatments were generally well tolerated.     

Variants of GCKR affect both β-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2

OBJECTIVE

In genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-related phenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2 diabetes.

RESEARCH DESIGN AND METHODS

In 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and β-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula.

RESULTS

The major alleles of rs6717980 and rs2384628 were associated with reduced β-cell function (P < 0.05), with mutual additive effects of each variant (P < 0.01). The minor alleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated with reduced eGFR according to a recessive model (P < 0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose (P < 0.05) and rs8731 and insulin sensitivity (P < 0.05) and triglycerides (P < 0.05).

CONCLUSIONS

Our findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients with newly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD.Glucokinase regulatory protein (GCKR) is expressed in liver and, to a lesser extent, in β-cells and exerts an inhibitory effect on glucokinase (GCK) by decreasing the affinity of the latter for glucose (1). Thus, it is in a key position to regulate liver glucose balance and, perhaps, glucose-stimulated insulin secretion.Allelic variability of two GCKR single nucleotide polymorphisms (SNPs), rs780094 and rs1260326, in strong linkage disequilibrium (LD) with each other, is associated with a number of human traits, including serum triglyceride (2–5), fasting glucose (2,5), C-reactive protein (6), coagulation protein C (7), uric acid (8), insulin levels (4), and susceptibility to type 2 diabetes (2,4,5,9,10). Moreover, the missense variant P446 L of rs1260326 is associated with reduced glomerular filtration rate (estimated glomerular filtration rate [eGFR]) and increased risk of chronic kidney disease (CKD) (11). On the whole, the major rs1260326 allele is associated with higher fasting glucose and insulin, lower eGFR, and increased CKD risk, but lower triglycerides. Thus, this single allele seems to be a multifaceted risk indicator of chronic diseases.Most studies reporting that GCKR variation is associated with diabetes-related intermediate phenotypes were performed in nondiabetic individuals, and surrogate markers, not state-of-art methods, were used to assess β-cell function or insulin sensitivity (2,4,5,9,10). Because both traits display a significant spread in patients with type 2 diabetes, the question arises whether GCKR variants may affect β-cell function in diabetic patients, thereby potentially being a determinant of type 2 diabetes heterogeneity, a marker of the metabolic phenotype, or a tool to select optimal therapy and to better define prognosis. Moreover, because GCKR is involved in the susceptibility to CKD, it might help to select subgroups of patients with higher risk of renal complications.We therefore undertook the present investigation to test whether the genetic variability of GCKR affects renal or β-cell function in patients with newly diagnosed type 2 diabetes. We used the database of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), an ongoing investigation of patients with newly diagnosed type 2 diabetes. This cohort was deemed useful for our purposes because of the absence of the potentially confounding effects of long-lasting antidiabetic treatments and of the limited impact of duration and severity of hyperglycemia per se on the metabolic phenotypes.     

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes

Objective: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia.

Methods: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites.

Conclusion: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT02451137.     

Almotriptan in triptan-naïve patients: new evidence of benefits

Although triptans represent the standard of care for migraine that is severe, disabling and/or suboptimally responsive to migraine non-specific analgesia, they are often underused in clinical practice. Simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) may provide effective treatment in some patients, but it is an inadequate response to these drugs that drives the therapeutic progression to triptans at the end of the traditional 'step-care' approach. However, there are several disadvantages to this approach. It may cause patients to lose confidence in their physician during this hierarchical 'trial-and-error' search for optimal treatment when prescribed medications are ineffective, leading them to cease consulting before triptans are tried. It may also result in a protracted time interval of suboptimal treatment, with unnecessary suffering in patients who are triptan candidates. The alternative approach of 'stratified care', in which medication is prescribed according to the severity of symptoms, enables triptans to be used earlier in the treatment plan, especially when triptan candidates are given a choice between simple analgesic/NSAID and triptan medication from the start. This raises the question about the efficacy of triptans in triptan-na?ve (TN) patients. A recent exploratory post-hoc analysis compared the effect of almotriptan 12.5 mg in TN patients (n = 342) with that in triptan-experienced patients (n = 237). Almotriptan was effective in both cohorts with a consistent trend in favour of the efficacy of almotriptan in TN patients, notably for sustained pain freedom (SPF) and SPF plus no adverse events. Moreover, both headache recurrence at 24 h and the use of rescue medication was lower in the TN patients, whereas tolerability was equally good in both cohorts. These findings indicate that TN patients can expect excellent symptom control when they progress from non-specific analgesia to treatment with almotriptan and support the earlier use of triptans in line with the stratified care paradigm.     

Are spouses of patients with type 2 diabetes at increased risk of developing diabetes?

OBJECTIVE: To determine whether spouses of patients with type 2 diabetes have an increased risk of diabetes compared with spouses of subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS: A random sample of spouses of patients with type 2 diabetes (group 1S) attending a general practice diabetes clinic was compared with spouses of nondiabetic subjects (as determined by oral glucose tolerance test [OGTT]) (group 2S). Spouses in both groups underwent OGTT, fasting lipid profile, and blood pressure (BP) measurements. RESULTS: A total of 245 subjects in group 1S and 234 subjects in group 2S underwent OGTT. Group 1S had a significantly higher incidence of fasting glucose, impaired glucose tolerance, or type 2 diabetes (19.1 vs. 9.4%). Group 1S also had higher fasting glucose and triglyceride levels, higher BMI, and a trend toward higher BP. Multivariate logistic regression analysis, adjusted for BMI and age, showed the risk of diabetes in the spouse of a patient with diabetes was 2.11 (95% CI 1.74-5.1), as compared with the spouse of a subject with normal glucose tolerance. Similarly, the risk of any degree of glucose intolerance in a spouse of a patient with type 2 diabetes was 2.32 (1.87-3.98), as compared with a spouse of a subject with normal glucose tolerance. CONCLUSIONS: Spouses of patients with type 2 diabetes have a significantly increased risk of glucose intolerance and type 2 diabetes, and they should be classified as high risk for diabetes. This finding has implications for screening programs, which should include spouses of subjects with diabetes.     

Poor self-rated health in adult patients with type 2 diabetes in the town of S?dert?lje: A cross-sectional study

Objective

Several studies indicate that ethnicity may be a strong predictor of poor self-rated health (SRH). The aims of the present study were to investigate whether there was an association between ethnicity and poor SRH in subjects with type 2 diabetes and to determine if the association remained after adjusting for possible confounders such as age, gender employment, marital status, and education.

Design

A cross-sectional study based on a patient population in the town of Södertälje. An unconditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs).

Setting

Four primary health care centers.

Subjects

A total of 354 individuals were included: Assyrian/Syrian-born (n = 173) and Swedish-born (n = 181).

Results

The odds ratio for rating poor SRH for Assyrian/Syrian subjects with type 2 diabetes was 4.5 times higher (95% CI = 2.7–7.5) than for Swedish patients in a crude model. After adjusting for possible confounders, unemployed/retired people had 5.4 times higher odds for reporting poor SRH than employees (OR = 5.4; 95% CI = 2.3–12.5). Women had 1.8 times higher odds (95% CI = 1.0–3.0) for reporting poor SRH than men. In the final model poor SRH among Assyrians/Syrians decreased but still remained significant (OR=3.7; 95% CI = 2.5–6.6).

Conclusions

The findings in this study are important for planning primary health care services. They highlight the crucial importance of being aware of the subjective health status of immigrants fleeing from war in the Middle East and resettling in Sweden.Key Words: Assyrians/Syrians, ethnicity, self-rated health, type 2 diabetesThis study highlights the relationship between self-rated health and ethnicity in subjects with type 2 diabetes.

• Socioeconomic factors did not explain the ethnic differences in rating poor general health.
• Unemployed/retired patients with type 2 diabetes, regardless of ethnicity, had the highest odds ratio for reporting poor general health.

Self-rated health (SRH) is a powerful and independent predictor of long-standing chronic diseases; although its biological basis is unknown some studies have shown an association with circulating cytokines in women [1]. It has been documented that SRH is a major predictor of morbidity, mortality, and health services utilization [2]. Furthermore, SRH is an important indicator of the quality of life as well as a good predictor of future health [6] and mortality in persons with diabetes [7]. In addition, age and gender [8], life satisfaction [9], and heritability [10] are factors related to SRH.Several studies indicate that SRH is poorer among immigrants than in native populations in Western countries, and belonging to a particular ethnic group has been shown to be a strong predictor of poor mental health and poor subjective health [11–13]. However, there are some studies showing that immigrants in general have a higher prevalence of poor SRH [14,15] and that Swedes report the highest prevalence of good health compared to ten European countries [16].The novelty of this primary health care study is the analysis of SRH in a group of foreign-born patients, i.e. Assyrians/Syrians with type 2 diabetes, and their controls in Södertälje, south of Stockholm.The aims of the study were to investigate whether there was an association between ethnicity and poor self-rated health in subjects with type 2 diabetes and to analyze whether the association remained after adjusting for possible confounders such as gender, age, employment, marital status, and educational level.     

A prospective study investigating the impact of multiparametric MRI in biopsy-naïve patients with clinically suspected prostate cancer: The PROKOMB study

BackgroundIn patients with suspected prostate cancer (PCa) according to current guidelines systematic transrectal ultrasound (TRUS)-guided biopsy of the prostate is performed to verify or rule out PCa. However, TRUS-guided biopsy can result in underdetection of clinically significant cancers as well as diagnosis of clinically insignificant cancers. Multiparametric MRI (mpMRI) might improve the diagnostic pathway and help to avoid unnecessary biopsies.Design and methodsThe PROKOMB (Prostata – Kooperatives MRT-Projekt Berlin) study is a prospective two-arm multicentre study designed to evaluate the potential role of mpMRI as a triage test before biopsy. Up to 600 biopsy-naïve men with suspicion for PCa undergo mpMRI at two dedicated imaging centers. Only patients with equivocal or suspicious lesions on mpMRI undergo prostate biopsy including systematic as well as MRI-guided targeted biopsies at several different community-based urologists or hospitals. The PROKOMB study is designed to evaluate how many biopsies can be avoided, how many clinically insignificant cancers are diagnosed on prostate biopsy in patients with positive findings on mpMRI, and how many clinically significant cancers are missed using this alternative diagnostic pathway. For the purpose of this study clinically significant PCa is defined as Gleason ≥ 3 + 4 cancer. In addition, the detection rates of different techniques for MRI-guided biopsy are evaluated as well as psychological distress before mpMRI and after the diagnosis of PCa.ConclusionThe PROKOMB study might help in defining the role of mpMRI in biopsy-naïve patients with suspected PCa in an ambulatory care setting.     

Efficacy of eletriptan in triptan-naïve patients: results of a combined analysis

OBJECTIVE: To compare the efficacy and tolerability of eletriptan 20 mg, 40 mg, and 80 mg in triptan-na?ve patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-na?ve and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-na?ve patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of eletriptan were well tolerated. CONCLUSIONS: These data suggest that eletriptan has comparable efficacy versus placebo among both triptan-na?ve and triptan-experienced patients.     

Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type‐2 diabetes mellitus

Objective. Low density lipoprotein cholesterol (LDL‐C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL‐C profile in patients with type‐2 diabetes (T2DM). We aimed to study the postprandial levels of LDL‐C in T2DM patients. Material and methods. After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat‐rich meal of 3,515 kJ containing 54?% fat, 13?% protein and 33?% carbohydrates. Only drinking water was allowed postprandially. Blood samples were drawn at times 0 (fasting), 1.5, 3.0, 4.5 and 6.0?h (postprandial). In all samples, LDL‐C was measured with modified beta quantification (separation by ultracentrifugation followed by measurement of infranate high density lipoprotein cholesterol (HLD‐C) using a homogeneous assay). Results. At all postprandial times, levels of LDL‐C showed highly significant (p<0.005) decreases compared to time 0 (mean [95?% CI] maximum change in LDL‐C levels at 3.0?h: ?0.16?mmol/L [?0.12; ?0.20]; p<0.001). Independently of fasting LDL‐C levels and ongoing statin therapy, LDL‐C decreased significantly more in female compared to male patients postprandially (mean [95?% CI] maximum unadjusted change versus time 0 in LDL‐C for men [n = 56] at 3.0?h: ?0.14?mmol/L [?0.19; ?0.10], p<0.001; for women [n = 18] at 4.5?h: ?0.26?mmol/L [?0.35; ?0.18], p<0.001; ?0.14?mmol/L [?0.24; ?0.05], p = 0.005 between genders for the mean [95?% CI] fasting adjusted difference at 4.5?h in the change versus time 0 in LDL‐C; gender by time interaction: p = 0.007 (repeated measures mixed model)). Conclusions. In T2DM patients served a fat‐rich meal, levels of LDL‐C decreased significantly more in women compared to men postprandially, irrespective of fasting levels or ongoing statin therapy. This might have implications in the atherosclerotic process and on any difference in the risk of CVD between genders.     

Liraglutide: can it make a difference in the treatment of type 2 diabetes?

Despite advances in the management of type 2 diabetes, glycaemic control remains suboptimal for many patients because of the complexities of disease progression and the need to balance improved glycaemic control against adverse treatment effects, particularly weight gain and hypoglycaemia. Thus, the development of new antidiabetes therapies continues in earnest. Incretin hormones have been the recent focus of research, as they account for up to 70% of the insulin response following a meal. There is also a high concordance between the physiological actions of one hormone, glucagon-like peptide-1 (GLP-1), and the therapeutic needs of patients. As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). Liraglutide, a human GLP-1 analogue sharing 97% of its amino acid sequence identity with native GLP-1, has been approved for use as monotherapy (not in Europe) and in combination with selected oral agents. In this supplement, we summarise key liraglutide data, offer practical insight into what we might expect of liraglutide in clinical use and examine selected case studies. For reasons of the safety and efficacy of GLP-1 receptor agonists, many thought leaders believe that these will become background therapy for majority of patients in the coming years. This supplement will serve as a resource from which readers can extract information concerning the potential benefits for patients who are overweight, losing pancreatic beta-cell function and drifting towards the ravaging effects of chronic hyperglycaemia.     

Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes

BACKGROUND. Previous efforts to preserve β cell function in individuals with type 1 diabetes (T1D) have focused largely on the use of single immunomodulatory agents administered within 100 days of diagnosis. Based on human and preclinical studies, we hypothesized that a combination of low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte CSF (G-CSF) would preserve β cell function in patients with established T1D (duration of T1D >4 months and <2 years).METHODS. A randomized, single-blinded, placebo-controlled trial was performed on 25 subjects: 17 subjects received ATG (2.5 mg/kg intravenously) followed by pegylated G-CSF (6 mg subcutaneously every 2 weeks for 6 doses) and 8 subjects received placebo. The primary outcome was the 1-year change in AUC C-peptide following a 2-hour mixed-meal tolerance test (MMTT). At baseline, the age (mean ± SD) was 24.6 ± 10 years; mean BMI was 25.4 ± 5.2 kg/m²; mean A1c was 6.5% ± 1.1%; insulin use was 0.31 ± 0.22 units/kg/d; and length of diagnosis was 1 ± 0.5 years.RESULTS. Combination ATG/G-CSF treatment tended to preserve β cell function in patients with established T1D. The mean difference in MMTT-stimulated AUC C-peptide between treated and placebo subjects was 0.28 nmol/l/min (95% CI 0.001–0.552, P = 0.050). A1c was lower in ATG/G-CSF–treated subjects at the 6-month study visit. ATG/G-CSF therapy was associated with relative preservation of Tregs.CONCLUSIONS. Patients with established T1D may benefit from combination immunotherapy approaches to preserve β cell function. Further studies are needed to determine whether such approaches may prevent or delay the onset of the disease.TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01106157","term_id":"NCT01106157"}}NCT01106157.FUNDING. The Leona M. and Harry B. Helmsley Charitable Trust and Sanofi.     

Characteristics of patients with type 2 diabetes in México: Results from a large population-based nationwide survey

OBJECTIVE: To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México. RESEARCH DESIGN AND METHODS: In 2000, information was obtained from 42,886 subjects aged > or =20 years using a multistage sampling procedure. Standardized questionnaires were used. Anthropometric measurements, blood pressure, and capillary glucose concentrations were taken. RESULTS: Type 2 diabetes was found in 3,597 subjects (age-adjusted prevalence 8.18%), of which 2,878 (80%) had previously been diagnosed. The average age of the diabetic participants was 55.2 +/- 13.5 years; 13% were <40 years of age. Nine percent had been diagnosed for >10 years. The average BMI was 29.2 +/- 5.7 kg/m(2); three-quarters of the cases had BMI >25 kg/m(2). The average waist circumference was 102 +/- 13.4 cm, and increased waist circumference was more common among women. Arterial hypertension was found in half of the cases and, of those on treatment, only one-third had a blood pressure <140/90 mmHg. Smoking was reported in 34% of the diabetic group, a higher rate than in the nondiabetic subjects. There was at least one modifiable coronary risk factor in 67.6% of the cases. Very few followed an exercise or dietary regimen and a small percentage used insulin. CONCLUSIONS: Diabetes affects a large proportion of Mexican adults (8.18%). This figure may be underestimated. The majority of the subjects had modifiable risk factors for the chronic complications of diabetes. Only a few achieved adequate blood pressure control and other treatment goals.