Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Serum ionized magnesium levels in relation to metabolic syndrome in type 2 diabetic patients.

Objective: To evaluate circulating serum ionized magnesium (i-Mg) concentrations in patients with type 2 diabetes mellitus, and to investigate its relationship with the components of the metabolic syndrome. Design: cross-sectional study. Setting: Outpatients' service for diabetic patients at the University Hospital of Messina, Italy. Subjects: 290 patients with type 2 diabetes mellitus. Measures of Outcome: Serum i-Mg was measured by ion selective electrode. Age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, HbA1c, HDL cholesterol, triglycerides, and urinary albumin excretion rate (UAER) were considered in the analyses. Patients with hypomagnesemia, defined as serum i-Mg < 0.46 mmol/l, were compared with those having normal serum i-Mg levels, and variables proven to be associated with low i-Mg levels in the univariate analysis were entered in a multivariable logistic regression model to obtain a deconfounded estimate of the association between metabolic parameters and hypomagnesemia. Results: In univariate analysis, serum i-Mg levels were significantly reduced in patients with low HDL cholesterol, high triglycerides values, high waist circumference, high blood pressure, microalbuminuria and clinical proteinuria. Hypomagnesemia was highly prevalent in our study population (N = 143, 49.3%). After adjusting for potential confounders, plasma triglycerides (OR = 4.71; 95% CI = 2.56-8.67), waist circumference (OR = 2.21; 95% Cl = 1.21-4.04), microalbuminuria (OR = 2.43; 95% CI = 1.16-5.08) and clinical proteinuria (OR = 2.04; 95% Cl = 1.02-5.68) were independently associated with hypomagnesemia. Conclusions: Hypomagnesemia is highly prevalent in diabetic outpatients. High plasma triglycerides, waist circumference and albuminuria are independent correlates of hypomagnesemi

Genistein in the metabolic syndrome: Results of a randomized clinical trial

Context: This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS). Objective: Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease. Design and Setting: This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy. Patients: Patients included 120 postmenopausal women with MetS according to modified Third Report of the National Cholesterol Education Program (NCEP), Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Intervention: After a 4-week stabilization period, postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein daily (n = 60) for 1 year. Main Outcome Measures: The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR) at 1 year. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, visfatin, adiponectin, and homocysteine levels. Data on adverse events were also recorded. Results: At 1 year in genistein recipients, fasting glucose, fasting insulin, and HOMA-IR (mean from 4.5 to 2.7; P < .001) decreased and were unchanged in placebo recipients. Genistein statistically increased HDL-C (mean from 46.4 to 56.8 mg/dL) and adiponectin and decreased total cholesterol, LDL-C (mean from 108.8 to 78.7 mg/dL), triglycerides, visfatin, and homocysteine (mean from 14.3 to 11.7 mu mol/L) blood levels. Systolic and diastolic blood pressure was also reduced in genistein recipients. Genistein recipients neither experienced more side adverse effects than placebo nor discontinued the study. Conclusion: One year of treatment with genistein improves surrogate endpoints associated with risk for diabetes and cardiovascular disease in postmenopausal women with MetS.Context: This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS). Objective: Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease. Design and Setting: This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy. Patients: Patients included 120 postmenopausal women with MetS according to modified Third Report of the National Cholesterol Education Program (NCEP), Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Intervention: After a 4-week stabilization period, postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein daily (n = 60) for 1 year. Main Outcome Measures: The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR) at 1 year. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, visfatin, adiponectin, and homocysteine levels. Data on adverse events were also recorded. Results: At 1 year in genistein recipients, fasting glucose, fasting insulin, and HOMA-IR (mean from 4.5 to 2.7; P<.001) decreased and were unchanged in placebo recipients. Genistein statistically increased HDL-C (mean from 46.4 to 56.8 mg/dL) and adiponectin and decreased total cholesterol, LDL-C (mean from 108.8 to 78.7 mg/dL), triglycerides, visfatin, and homocysteine (mean from 14.3 to 11.7 μmol/L) blood levels. Systolic and diastolic blood pressure was also reduced in genistein recipients. Genistein recipients neither experienced more side adverse effects than placebo nor discontinued the study. Conclusion: One year of treatment with genistein improves surrogate endpoints associated with risk for diabetes and cardiovascular disease in postmenopausal women with MetS. Copyright © 2013 by The Endocrine Society

High GADA titer increases the risk of insulin requirement in LADA patients: A 7-year follow-up (NIRAD study 7)

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes ( P2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (PIC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).

OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P&lt;0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P&lt;0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P&lt;0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P&lt;0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p&lt;0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes. © 2016 Springer-Verlag Berlin Heidelber

[AMD Annals: a model of continuous monitoring and improvement of the quality of diabetes care].

OBJECTIVE: in recent years, several initiatives have been launched by the Associazione medici diabetologi (AMD) in the context of a national quality improvement program.These activities include: identification of specific indicators of quality of diabetes care, development of a software to calculate such indicators by using routine clinical data, creation of a network of diabetes clinics and analysis and publication of the results in ad hoc reports (AMD Annals). Through the best performer approach, each centre could compare its own performance not only with the theoretical targets suggested by existing guidelines, but also with the results achieved by the best centres operating within the same healthcare system.We evaluated whether the involvement of diabetes clinics into the AMD Annals initiative improved the quality of care over 4 years. DESIGN: a controlled before and after study was performed to compare data collected from 2004 to 2007 by two groups of centres: group A included centres that had been involved in the project since the first edition of AMD Annals; group B included centres only involved in the last edition. SETTING AND PARTICIPANTS: overall, 124 diabetes clinics provided data on over 100,000 type 2 diabetes patients/year seen from 2004 to 2007. MAIN OUTCOME MEASURES: process indicators included the proportion of patients with at least one measurement of HbA1c, blood pressure and lipid profile during the previous 12 months. Intermediate outcomes included percentages of patients with levels of HbA1c ≤ 7%, blood pressure ≤ 130/85 mmHg and LDL-cholesterol <100 mg/dl (favourable indicators), and the percentages of patients with levels of HbA1c ≥ 9%, blood pressure ≥ 140/90 mmHg and LDL-cholesterol ≥ 130 mg/dl (unfavourable indicators). Percentages of patients treated with insulin, two or more antihypertensive agents, and statins were also evaluated. A multilevel analysis adjusted for age, gender, diabetes duration, and clustering effect was applied to investigate the changes in the indicators between the two groups of centres during 4 years. RESULTS: lipid profile monitoring increased more in group A (+6.2% from 2004 to 2007) than in group B (+2.4%), while HbA1c and blood pressure monitoring did not change over time in both groups. As for the outcomes considered, the percentage of patients with HbA1c ≤ 7% increased by 6% in group A and by 1.3%in group B, while the proportion of patients achieving the blood pressure target increased in group A (+6.4%), but not in group B (-1.4%). A reduction in the percentage of patients with blood pressure ≥ 140/90 mmHg was found in group A (-7.3%) but not in group B (-0.9%). Marked improvements in the proportion of patients with LDL-cholesterol at target were documented in both groups (group A: +10.5%; group B: +12.2%.) The proportion of patients treated with insulin increased in group A only (+5.8%), while the use of statins grew by 20%in both groups.The proportion of individuals treated with two or more antihypertensive drugs increased by 3.6% in group A and by 1.6% in group B. CONCLUSION: the AMD Annals approach can be considered as a case model for quality improvement activities in chronic diseases and a tool to evaluate the level of adoption/acceptance of guidelines in clinical practice. The considerable success documented was obtained without allocation of extra resources or financial incentives but simply through a physician-led effort made possible by the commitment of the specialists involved

AMD Annals: a model of continuous monitoring and improvement of the quality of diabetes care

OBJECTIVE: in recent years, several initiatives have been launched by the Associazione medici diabetologi (AMD) in the context of a national quality improvement program.These activities include: identification of specific indicators of quality of diabetes care, development of a software to calculate such indicators by using routine clinical data, creation of a network of diabetes clinics and analysis and publication of the results in ad hoc reports (AMD Annals). Through the best performer approach, each centre could compare its own performance not only with the theoretical targets suggested by existing guidelines, but also with the results achieved by the best centres operating within the same healthcare system.We evaluated whether the involvement of diabetes clinics into the AMD Annals initiative improved the quality of care over 4 years. DESIGN: a controlled before and after study was performed to compare data collected from 2004 to 2007 by two groups of centres: group A included centres that had been involved in the project since the first edition of AMD Annals; group B included centres only involved in the last edition. SETTING AND PARTICIPANTS: overall, 124 diabetes clinics provided data on over 100,000 type 2 diabetes patients/year seen from 2004 to 2007. MAIN OUTCOME MEASURES: process indicators included the proportion of patients with at least one measurement of HbA1c, blood pressure and lipid profile during the previous 12 months. Intermediate outcomes included percentages of patients with levels of HbA1c ≤ 7%, blood pressure ≤ 130/85 mmHg and LDL-cholesterol <100 mg/dl (favourable indicators), and the percentages of patients with levels of HbA1c ≥ 9%, blood pressure ≥ 140/90 mmHg and LDL-cholesterol ≥ 130 mg/dl (unfavourable indicators). Percentages of patients treated with insulin, two or more antihypertensive agents, and statins were also evaluated. A multilevel analysis adjusted for age, gender, diabetes duration, and clustering effect was applied to investigate the changes in the indicators between the two groups of centres during 4 years. RESULTS: lipid profile monitoring increased more in group A (+6.2% from 2004 to 2007) than in group B (+2.4%), while HbA1c and blood pressure monitoring did not change over time in both groups. As for the outcomes considered, the percentage of patients with HbA1c ≤ 7% increased by 6% in group A and by 1.3%in group B, while the proportion of patients achieving the blood pressure target increased in group A (+6.4%), but not in group B (-1.4%). A reduction in the percentage of patients with blood pressure ≥ 140/90 mmHg was found in group A (-7.3%) but not in group B (-0.9%). Marked improvements in the proportion of patients with LDL-cholesterol at target were documented in both groups (group A: +10.5%; group B: +12.2%.) The proportion of patients treated with insulin increased in group A only (+5.8%), while the use of statins grew by 20%in both groups.The proportion of individuals treated with two or more antihypertensive drugs increased by 3.6% in group A and by 1.6% in group B. CONCLUSION: the AMD Annals approach can be considered as a case model for quality improvement activities in chronic diseases and a tool to evaluate the level of adoption/acceptance of guidelines in clinical practice. The considerable success documented was obtained without allocation of extra resources or financial incentives but simply through a physician-led effort made possible by the commitment of the specialists involved