Michela Petrizzo

The Effects of a Mediterranean Diet on the Need for Diabetes Drugs and Remission of Newly Diagnosed Type 2 Diabetes: Follow-up of a Randomized Trial

OBJECTIVE To assess the long-term effects of dietary interventions on glycemic control, need for diabetes medications, and remission of type 2 diabetes. RESEARCH DESIGN AND METHODS Originally, in a two-arm trial design, overweight, middle-aged men and women with newly diagnosed type 2 diabetes were randomized to a low-carbohydrate Mediterranean diet (LCMD; n = 108) or a low-fat diet (n = 107). After 4 years, participants who were still free of diabetes medications were further followed up until the primary end point (need of a diabetic drug); remission of diabetes (partial or complete) and changes in weight, glycemic control, and cardiovascular risk factors were also evaluated. RESULTS The primary end point was reached in all participants after a total follow-up of 6.1 years in the low-fat group and 8.1 years in the LCMD group; median survival time was 2.8 years (95% CI 2.4–3.2) and 4.8 years (4.3–5.2), respectively. The unadjusted hazard ratio for the overall follow-up was 0.68 (0.50–0.89; P < 0.001). LCMD participants were more likely to experience any remission (partial or complete), with a prevalence of 14.7% (13.0–16.5%) during the first year and 5.0% (4.4–5.6%) during year 6 compared with 4.1% (3.1–5.0%) at year 1 and 0% at year 6 in the low-fat diet group. CONCLUSIONS In patients with newly diagnosed type 2 diabetes, an LCMD resulted in a greater reduction of HbA1c levels, higher rate of diabetes remission, and delayed need for diabetes medication compared with a low-fat diet.

Long-term effect of mediterranean-style diet and calorie restriction on biomarkers of longevity and oxidative stress in overweight men.

We report the effects of a Mediterranean-style diet, with or without calorie restriction, on biomarkers of aging and oxidative stress in overweight men. 192 men were randomly assigned to either a Mediterranean-style diet or a conventional diet. The intervention program was based on implementation of a Mediterranean dietary pattern in the overweight group (MED diet group), associated with calorie restriction and increased physical activity in the obese group (lifestyle group). Both groups were compared with participants in two matched control groups (advice groups). After 2 years, there was a significant difference in weight loss between groups, which was −14 kg (95% CI −20 to −8) in lifestyle groups and −2.0 kg (−4.4 to 0) in the advice groups, with a difference of −11.9 kg (CI −19 to −4.7 kg, P < .001); moreover, there was a significant difference between groups at 2 years for insulin (P = .04), 8-iso-PGF2α (P = .037), glucose (P = .04), and adiponectin (P = .01). Prolonged adherence to a Mediterranean-style diet, with or without caloric restriction, in overweight or obese men is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress, and improved insulin sensitivity.

Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes—a randomized controlled trial

Aim: Endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are markers of endothelial injury and repair. We compared the effects of pioglitazone versus metformin on the circulating numbers of EMPs and EPCs in patients with newly diagnosed type 2 diabetes.

A nomogram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients

Objectives To develop a nomogram for estimating the glycated haemoglobin (HbA1c) response to different dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. Design A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted. Electronic searches were carried out up to December 2013. Trials were included if they were carried out on participants with type 2 diabetes, lasted at least 12 weeks, included at least 30 participants and had a final assessment of HbA1c. A random effect model was used to pool data. A nomogram was used to represent results of the metaregression model. Participants Adults with type 2 diabetes. Interventions Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin). Outcome measures The HbA1c response to each DPP-4 inhibitor within 1 year of therapy. Results We screened 928 citations and reviewed 98 articles reporting 98 RCTs with 100 arms in 24 163 participants. There were 26 arms with vildagliptin, 37 with sitagliptin, 13 with saxagliptin, 13 with linagliptin and 11 with alogliptin. For all 100 arms, the mean baseline HbA1c value was 8.05% (64 mmol/mol); the decrease of HbA1c from baseline was −0.77% (95% CI −0.82 to −0.72%), with high heterogeneity (I2=96%). Multivariable metaregression model that included baseline HbA1c, type of DPP-4 inhibitor and fasting glucose explained 58% of variance between studies, with no significant interaction between them. Other factors, including age, previous diabetes drugs and duration of treatment added low predictive power (<1%). The nomogram estimates the absolute HbA1c reduction from baseline using the type of DPP-4 inhibitor, baseline values of HbA1c and fasting glucose. Conclusions Baseline HbA1c level and fasting glucose explain most of the variance in HbA1c change in response to DPP-4 inhibitors: each increase of 1.0% units HbA1c provides a 0.4–0.5% units greater fall.

The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes?

Introduction: The basal insulin products currently on market do not optimally mimic endogenous insulin secretion. These unmet clinical needs have fueled the development of new basal insulin analogues for improving their pharmacokinetics/pharmacodynamics profile. Areas covered: We review the recent literature investigating the efficacy and safety of new basal insulin analogues in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of treatment visits for these patients in 2012. Insulin degludec is a desB30 insulin acylated at the LysB29 residue with a glutamate linker and 16-carbon fatty diacyl side chain. Insulin lispro has been PEGylated at lysine B28, via a urethane bond, which increases the hydrodynamic size of the molecule and reduces its absorption and clearance following subcutaneous administration. Glargine U300 represents a new high-strength glargine formulation (300 U/ml): once injected, U300 forms a compact subcutaneous depot with a smaller surface area to produce a more gradual and prolonged release. Both PEG-lispro and glargine U300 are not yet on the market. Expert opinion: Ultra-long acting and high-strength formulations of new basal analogues have the potential for less glycemic variability, less (nocturnal) hypoglycemia and weight-loss advantage for PEG-lispro. However, these new basal insulin analogues need to be monitored closely for adverse signals.

Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: Follow-up of a randomized trial

Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108) or a low-fat diet (n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34+KDR+ and CD34+KDR+CD133+ counts had increased with the Mediterranean diet compared with the low-fat diet (p < 0.05 for both). At the EOT evaluation, there was a significant (p = 0.024) difference of −0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) (p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34+KDR+, r = −0.24, p = 0.020; CD34+KDR+CD133+, r = −0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

Anti-inflammatory Effect of Mediterranean Diet in Type 2 Diabetes Is Durable: 8-Year Follow-up of a Controlled Trial

There is increasing evidence that plasma markers of low-grade inflammation modulate the risk of developing type 2 diabetes: for each 1 log mg/L increment in C-reactive protein (CRP) levels, there is a 26% increased risk (1), and for each 1 log μg/mL increment in adiponectin levels, there is a 28% decreased risk (2). However, the Mediterranean diet is able to reduce the incidence of future diabetes by 19–23% (3). Using the data of a randomized trial (MEditerranean DIet and Type 2 diAbetes [MEDITA]) (4), we investigated 1 ) whether the Mediterranean diet has a durable effect on circulating levels of CRP and adiponectin in subjects with newly diagnosed type 2 diabetes and 2 ) whether the changes in these inflammatory markers influenced the development of diet failure. In a two-arm, single-center trial, 215 men and women with newly diagnosed type 2 diabetes were randomized to …

Basal Supplementation of Insulin Lispro Protamine Suspension Versus Insulin Glargine and Detemir for Type 2 Diabetes Meta-analysis of randomized controlled trials

OBJECTIVE We compared the effect of insulin lispro protamine suspension (ILPS) with that of insulin glargine and insulin detemir, all given as basal supplementation, in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search until February 2012, including online registries of ongoing trials and abstract books. All randomized controlled trials comparing ILPS with insulin glargine or detemir with a duration of ≥12 weeks were included. RESULTS We found four trials lasting 24–36 weeks involving 1,336 persons: three studies compared ILPS with glargine, and one trial compared ILPS with detemir. There was no significant difference in change in HbA1c level between ILPS and comparators, in the proportion of patients achieving the HbA1c goals of ≤6.5 or <7%, in weight change, or in daily insulin doses. There was no difference in overall hypoglycemia, but nocturnal hypoglycemia occurred significantly more with ILPS than with comparator insulins (mean difference 0.099 events/patient/30 days [95% CI 0.03–0.17]). In a prespecified sensitivity analysis comparing data obtained in patients who remained on their once-daily insulin regimen, not significantly different event rates for nocturnal hypoglycemia were observed between ILPS and comparator insulins (0.063 [−0.007 to 0.13]), and ILPS was associated with lower insulin dose (0.07 units/kg/day [0.05–0.09]). CONCLUSIONS There is no difference between ILPS and insulin glargine or detemir for targeting hyperglycemia, but nocturnal hypoglycemia occurred more frequently with ILPS than with comparator insulins. Nocturnal hypoglycemia was not significantly different in people who injected insulin once daily.

Gender-differences in glycemic control and diabetes related factors in young adults with type 1 diabetes: results from the METRO study

PurposeTo describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes.MethodsWe collected data from 300 consecutively patients (168 males and 132 females), aged 18–30 years, among those admitted at Diabetes Unit of University of Campania “Luigi Vanvitelli” (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry.ResultsAs compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women.ConclusionsYoung adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

Continuous glucose monitoring for patients with type 1 diabetes on multiple daily injections of insulin: pros and cons

Continuous glucose monitoring associated with intensive insulin regimens represents a useful tool to lower HbA1c in selected adults with type 1 diabetes. Recent randomized controlled trials demonstrated greater glycemic benefits in type 1 diabetic patients treated with multiple daily injections of insulin and continuous glucose monitoring over usual care. These positive outcomes, however, are counter-balanced by several limitations that restrict the use of continuous glucose monitoring in the real life, including the apparent lack of benefits in children and pregnant diabetic women, the high cost, the stringent patients’ selection, and the presence of a multi-disciplinary team with specific expertise. Pros and Cons of using continuous glucose monitoring in type 1 diabetic patients with multiple daily injections of insulin are here discussed.