Biomedical subjects

Massimo Massi-Benedetti

Publications and source records attributed to Massimo Massi-Benedetti.

8 recordsLinked to original sources

PubMed2006

Changing targets in the treatment of type 2 diabetes.

BACKGROUND: While correction of hyperglycemia remains central to the management of type 2 diabetes, current management approaches address an integrated constellation of disorders that predispose patients to the risk of microvascular and macrovascular complications. SCOPE: This paper reviews glycemic control targets and associated cardiovascular disease risk management in type 2 diabetes, as recommended by the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the UK National Institute for Clinical Excellence (NICE). It is based upon MEDLINE literature searches from January 1995 to April 2006. FINDINGS: Current guidelines recommend glycated hemoglobin (HbA1c) target levels of approximately 6.0-7.5%. However, European and US data suggest that HbA1c targets are achieved by only approximately one-third of patients with type 2 diabetes. Progression from pre-diabetic impaired glucose tolerance to type 2 diabetes has recently become a target for early intervention with pharmacological agents. The aggressive treatment of dyslipidemia towards defined target levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol is recommended. The ADA and IDF recommend blood pressure targets of 130/80 mmHg in type 2 diabetes, and the use of aspirin for secondary cardiovascular disease prevention and primary prevention in patients at increased risk. Although inflammatory biomarkers, such as C-reactive protein, may predict type 2 diabetes risk, their role remains unclear. CONCLUSIONS: Concerted efforts are necessary to increase the proportion of patients achieving current treatment targets. Such measures must aim to educate patients and physicians, remove barriers due to health care organization and access, and improve the monitoring of cardiovascular disease risk indicators. The poly-pharmacy 'pill burden' may be alleviated through the use of drugs that are effective against multiple aspects of the metabolic syndrome, and by co-formulation of agents with established efficacy.

Blood Glucose↗

PubMed2005

Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.

BACKGROUND: Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes. METHODS: We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993. FINDINGS: Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups. INTERPRETATION: Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events.

Adult↗

PubMed2005

Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes.

OBJECTIVE: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS: Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively. CONCLUSIONS: These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.

Blood Glucose↗

PubMed2004

Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes.

A nonlinear model predictive controller has been developed to maintain normoglycemia in subjects with type 1 diabetes during fasting conditions such as during overnight fast. The controller employs a compartment model, which represents the glucoregulatory system and includes submodels representing absorption of subcutaneously administered short-acting insulin Lispro and gut absorption. The controller uses Bayesian parameter estimation to determine time-varying model parameters. Moving target trajectory facilitates slow, controlled normalization of elevated glucose levels and faster normalization of low glucose values. The predictive capabilities of the model have been evaluated using data from 15 clinical experiments in subjects with type 1 diabetes. The experiments employed intravenous glucose sampling (every 15 min) and subcutaneous infusion of insulin Lispro by insulin pump (modified also every 15 min). The model gave glucose predictions with a mean square error proportionally related to the prediction horizon with the value of 0.2 mmol L(-1) per 15 min. The assessment of clinical utility of model-based glucose predictions using Clarke error grid analysis gave 95% of values in zone A and the remaining 5% of values in zone B for glucose predictions up to 60 min (n = 1674). In conclusion, adaptive nonlinear model predictive control is promising for the control of glucose concentration during fasting conditions in subjects with type 1 diabetes.

Blood Glucose↗

PubMed2004

Closing the loop: the adicol experience.

The objective of the project Advanced Insulin Infusion using a Control Loop (ADICOL) was to develop a treatment system that continuously measures and controls the glucose concentration in subjects with type 1 diabetes. The modular concept of the ADICOL's extracorporeal artificial pancreas consisted of a minimally invasive subcutaneous glucose system, a handheld PocketPC computer, and an insulin pump (D-Tron, Disetronic, Burgdorf, Switzerland) delivering subcutaneously insulin lispro. The present paper describes a subset of ADICOL activities focusing on the development of a glucose controller for semi-closed-loop control, an in silico testing environment, clinical testing, and system integration. An incremental approach was adopted to evaluate experimentally a model predictive glucose controller. A feasibility study was followed by efficacy studies of increasing complexity. The ADICOL project demonstrated feasibility of a semi-closed-loop glucose control during fasting and fed conditions with a wearable, modular extracorporeal artificial pancreas.

Blood Glucose↗

PubMed2004

The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients.

OBJECTIVE: The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) assesses the effect of pioglitazone, a peroxisome proliferator-activated receptor agonist, with anti-inflammatory and vascular properties, on the secondary prevention of macrovascular events in type 2 diabetes. RESEARCH DESIGN AND METHODS: PROactive is an on-going randomized, double-blind outcome study in patients with type 2 diabetes managed with diet and/or oral blood glucose-lowering drugs (combination of oral agents with insulin is permitted) who have a history of macrovascular disease. Patients are randomized to receive pioglitazone (forced titration from 15 to 30 to 45 mg, depending on tolerability) or placebo in addition to existing therapy. The primary end point is the time from randomization to occurrence of a new macrovascular event or death. Follow-up is estimated to span 4 years. RESULTS: A total of 5238 patients have been randomized from 19 countries. At entry into the study, patients enrolled are a mean age of 61.8 years, with type 2 diabetes for a mean of 9.5 years; 60.9 and 61.5% are taking metformin or a sulfonylurea, respectively; and 33.6% are using insulin in addition to oral glucose-lowering drugs. The majority of patients are men (66.1%). Patients are required to meet one or more of entry criteria, as follows: >6 months' history of myocardial infarction (46.7%); coronary artery revascularization (30.8%), stroke (18.8%), or acute coronary syndrome for >3 months (13.7%); other evidence of coronary artery disease (48.1%); or peripheral arterial occlusive disease (19.9%). One-half (48.5%) of the patients have two or more of these risk factors. Three-quarters (75.4%) have hypertension, and 58.8% are current or previous smokers. CONCLUSIONS: The cohort of patients enrolled in PROactive is a typical type 2 diabetic population at high risk of further macrovascular events. The characteristics of this population are ideal for assessing the ability of pioglitazone to reduce the cardiovascular risk of patients with type 2 diabetes.

Adult↗

PubMed2003

Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.

BACKGROUND: Sulfonylureas (SUs) have been used for many years as first-line therapy for patients with type 2 diabetes mellitus whose blood glucose levels have not been effectively controlled by diet and exercise alone. Glimepiride is a once-daily SU that was introduced in 1995. Since then, a considerable body of evidence has been amassed regarding its use in type 2 diabetes. OBJECTIVE: This review provides a comprehensive summary of available data on the pharmacology, pharmacokinetics, efficacy, and safety profile of glimepiride in the treatment of type 2 diabetes. It also examines the use of glimepiride to achieve and maintain good glycemic control in patients with type 2 diabetes in current clinical practice. METHODS: Relevant articles were identified through a search of MEDLINE for English-language studies published from 1990 to 2002. The search terms used were glimepiride, sulfonylureas, and type 2 diabetes mellitus. The manufacturer of glimepiride provided additional information. RESULTS: Glimepiride differs from other SUs in a number of respects. In clinical studies, glimepiride was generally associated with a lower risk of hypoglycemia and less weight gain than other SUs. Results of other studies suggest that glimepiride can be used in older patients and those with renal compromise. There is evidence that glimepiride preserves myocardial preconditioning, a protective mechanism that limits damage in the event of an ischemic event. Glimepiride can be used in combination with other oral antidiabetic agents or insulin to optimize glycemic control. CONCLUSION: Based on the evidence to date, glimepiride is an effective and well-tolerated once-daily antidiabetic drug and provides an important treatment option for the management of type 2 diabetes.

Blood Glucose↗

PubMed2003

The costs of type 2 diabetes mellitus in Italy: a CODE-2 sub-study.

AIM: To estimate the direct, indirect, and intangible costs associated with type 2 diabetes mellitus in Italy in 1998. To evaluate the economic impact of diabetic complications, and to investigate drug treatment patterns and associated costs in patients with type 2 diabetes. METHODS: The Italian arm of an international study (COsts of Diabetes in Europe--Type 2 [CODE-2], a descriptive, cross-sectional survey) was set up to collect information retrospectively by means of questionnaires from a sample of 1263 patients. Resource use was measured in monetary terms using a set of costs and tariffs. Intangible costs were estimated using the EuroQol questionnaire. RESULTS: The average yearly cost for medical resources for a patient with type 2 diabetes was 2991 Euro, whereas the estimated cost for the whole population with type 2 diabetes was about 5170 million Euro. This corresponds to 6.65% of the total healthcare expenditure (public and private) in Italy. Of direct costs, 29% was spent for the treatment of diabetes and 39% for the treatment of diabetic complications; while the remaining 32% was spent for healthcare not related to diabetes. Quality of life score in patients with type 2 diabetes (EuroQoL overall average score) was 0.68. CONCLUSIONS: Type 2 diabetes has a high cost to society. The major cost component is due to the care of diabetic complications, not to the treatment of the illness itself; in particular, drug costs represent a relatively small proportion of such treatment cost.

Cost of Illness↗