Management of newly diagnosed patients with type 2 diabetes: What are the attitudes of physicians? A SUBITO!AMD survey on the early diabetes treatment in Italy

Early intensive therapy in type 2 diabetes can prevent complications. Nevertheless, metabolic control is often sub-optimal in newly diagnosed patients. This webbased survey aimed to evaluate opinions of physicians about treatment, priorities, and barriers in the care of patients first referred to diabetes clinics. Data on physician attitudes toward therapeutic preferences for two clinical case models (same clinical profile, except HbA1c levels of 8.6 and 7.3% at the first access, respectively) were collected. Participants were asked to rank from 1 (most important) to 6 (least important) a list of priorities and barriers associated with the care of new patients. Overall, 593 physicians participated. In both case models, metformin and education were primary options, although their combination with other classes of drugs varied substantially. Main priorities were ‘‘to teach the patient how to cope with the disease’’ and ‘‘to achieve HbA1c target’’; main barriers were ‘‘lack of time’’ and ‘‘long waiting list’’. At multivariate analyses, physicians from the South of Italy had a twofold higher likelihood to attribute a rank 1–2 to organizational barriers than those operating in the North (South vs. North: OR: 2.4; 95% CI 1.4–4.1; Center vs. North: OR: 2.4; 95% CI 0.9–3.2). In the absence of a widely accepted evidence-based therapeutic algorithm driving the therapeutic choices according to the patient characteristics, prescriptions vary according to physician preferences. Education is perceived as a key-strategy, but organizational barriers and geographic disparities are an obstacle. These findings can drive new strategies to reduce clinical inertia, attitudes variability, and geographic disparities

The Impact of Adherence to Screening Guidelines and of Diabetes Clinics Referral on Morbidity and Mortality in Diabetes

Despite the heightened awareness of diabetes as a major health problem, evidence on the impact of assistance and organizational factors, as well as of adherence to recommended care guidelines, on morbidity and mortality in diabetes is scanty. We identified diabetic residents in Torino, Italy, as of 1st January 2002, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations to compare primary versus specialty care management of diabetes and the fulfillment of a quality-of-care indicator based on existing screening guidelines (GCI). Then, we performed regression analyses to identify associations of these factors with mortality and cardiovascular morbidity over a 4 year- follow-up. Patients with the lowest degree of quality of care (i.e. only cared for by primary care and with no fulfillment of GCI) had worse RRs for all-cause (1.72 [95% CI 1.57–1.89]), cardiovascular (1.74 [95% CI 1.50–2.01]) and cancer (1.35 [95% CI 1.14–1.61]) mortality, compared with those with the highest quality of care. They also showed increased RRs for incidence of major cardiovascular events up to 2.03 (95% CI 1.26–3.28) for lower extremity amputations. Receiving specialist care itself increased survival, but was far more effective when combined with the fulfillment of GCI. Throughout the whole set of analysis, implementation of guidelines emerged as a strong modifier of prognosis. We conclude that management of diabetic patients with a pathway based on both primary and specialist care is associated with a favorable impact on all-cause mortality and CV incidence, provided that guidelines are implemented

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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Factors Associated with Beta-Cell Dysfunction in Type 2 Diabetes: The BETADECLINE Study

<div><p>Aims</p><p>Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes.</p><p>Materials and Methods</p><p>Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I).</p><p>Results</p><p>At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA_1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P<0.05 for all). At multivariate analysis, the risk of having a P/I ratio in the upper quartile was higher in the subjects on secretagogue drugs (odds ratio [OR] 4.2; 95% confidence interval [CI], 2.6–6.9) and in the males (OR 1.8; 95% CI, 1.1–2.9).</p><p>Conclusions</p><p>In the BetaDecline study population, baseline higher PI/I values, a marker of beta-cell dysfunction, were more frequent in men and in patients on secretagogues drugs. Follow-up of this cohort will allow the identification of clinical predictors of beta-cell failure in type 2 diabetic outpatients.</p></div