Aims: Hypoglycemia is a potential risk in the management of patients suffering from type 2 diabetes (T2DM) and hospitalized in internal medicine units (IMUs). The aim of this analysis was to evaluate incidence of hypoglycemia and related risk factors in a group of patients admitted to IMUs.Methods: We used the FADOI-DIAMOND study carried out in 53 Italian IMUs. The DIAMOND design included two cross-sectional surveys interspersed with an educational program. In both phases each center reviewed the charts of the last 30 hospitalized patients with known T2DM (n = 3167), including information about hypoglycemia during hospital stay. The association between occurrence of hypoglycemia and potential predictors was evaluated by means of a multivariable logistic regression analysis.Results: A total of 385 symptomatic hypoglycemic events were observed (rate = 12%). Advanced age, cognitive dysfunction, and nephropathy were associated with hypoglycemia. Hypoglycemia occurred in 19.4% of patients treated according to the insulin sliding-scale method versus 11.4% of patients treated with basal bolus (p < 0.01). More patients with hypoglycemia received sulfonylureas versus the no-hypoglycemia group (28.3% versus 20.6%, p < 0.001). Significantly longer length of hospital stay and increased in-hospital mortality were found in the group with hypoglycemia compared with the no-hypoglycemia group (12.7 +/- 10.9 versus 9.6 +/- 6.5 days; 8.8% versus 4.8%, p < 0.01).Conclusions: Hypoglycemia in hospitalized patients with diabetes is associated with increased length of hospitalization and in-hospital mortality. Identification of patients at increased risk of hypoglycemia may be important for optimally adapting treatment and patient management. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Hypoglycemia is a very common problem, mostly in frail, severely ill, older hospitalized patients. Hypoglycemia has been implicated in the development of adverse clinical outcomes, including an increased mortality. Fear of iatrogenic hypoglycemia remains an obstacle to adequate inpatient glycemic control. It may be considered as a marker of disease, rather than cause in itself of undesirable events. Several factors, such as treatment with exogenous insulin, mismatch between insulin administration and meal intake with the loss of normal counter regulatory responses, place patients with diabetes at higher risk for hypoglycemia than the ones without diabetes. In this review we discuss the causes and predictors of hypoglycemia in non-critically ill hospitalized patients and how to prevent them. Subcutaneous insulin with basal-bolus regimen rather than sliding scale and the use of analogues may minimize hypoglycemic events. In-patient glycemic management should be patient-centered, following the current guidelines, and aimed to prevent hypoglycemic events.

Appropriate management of hyperglycemia is crucial for patients with type 2 diabetes. Aim of the FADOI-DIAMOND study was to evaluate real-world management of type 2 diabetic patients hospitalized in Internal Medicine wards (IMW) and the effects of a standardized educational intervention for IMW staff. DIAMOND has been carried out in 53 Italian IMW, with two cross-sectional surveys interspersed with an educational program (PRE phase and POST phase). In PRE phase, each center reviewed the charts of the last 30 hospitalized patients with known type 2 diabetes. An educational program was conducted in each center by means of the “outreach visit,” a face-to-face meeting between IMW staff and a trained external expert. Six months after, each center repeated the data collection (POST phase), specular to the PRE. A total of 3,167 patients were enrolled (1,588 PRE and 1,579 POST). From PRE phase to POST, patients with registered anthropometric data (54.1 vs. 74.9 %, p < 0.001) and in-hospital/recent measurement of glycated hemoglobin (48.2 vs. 61.4 %, p < 0.005) increased significantly. After educational program, more patients received insulin during hospitalization (68.3 vs. 63.6 %, p = 0.005). A more relevant variation in glycemia during hospitalization was observed in POST phase than PRE (−22.2 vs. −15.5 mg/dL, p < 0.001), without differences as for occurrence of hypoglycemia (12.3 vs. 11.9 %). A one-shot educational intervention led to persistent improvement in the management of hospitalized patients with type 2 diabetes and to significant better glycemic control. Further studies might evaluate the effectiveness of a more aggressive educational program, on both management and outcomes.

Background:Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.Methods:The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA(1c) <7% (<53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.Results:The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA1c of <= 8% (<= 64 mmol/mol), shorter duration of diabetes at baseline (<5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.Conclusion:Lower baseline HbA(1c), shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA(1c) <7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.

Objectives: Optimal glucose levels in hospitalized patients with type 2 diabetes (T2D) are not well defined, especially in Internal Medicine Units (IMU), whose patients are frequently complex. An appropriate management of hyperglycemia is however known to improve clinical outcome of patients with T2D. Aim of the FADOI-DIAMOND study was to collect information about the management of T2D patients hospitalized in IMU, before and after a standardized educational intervention on health professionals. Methods: DIAMOND is a three-step study, carried-out in 53 Italian IMU. In step A each center retrospectively reviewed the hospital charts of the last 30 patients hospitalized for any cause and with known T2D (excluding patients with acute stroke or myocardial infarction). An educational program (step B) was conducted in each center by means of the "outreach visit", a face-to-face meeting between health personnel (physicians and nurses) and a trained external expert. Contents of the intervention had been pre-defined by a Scientific Committee according to international guidelines, and major deviations from best medical practice detected in step A. Six months after, each center repeated the retrospective data collection, specular to step A (step C). Results: A total of 3167 patients were enrolled in the study (1588 step A, 1579 step C). Patient populations in steps A and C, as described in Table 1, were similar. From steps A to C, patients with missing registered anthropometric data decreased significantly (54.1% vs 74.9%, p < 0.001), while a higher percentage had in-hospital measurement of HbA1c (61.4% vs 48.2%, p < 0.005). After educational program, more patients received insulin during hospitalization (68.3% vs 63.6%, p = 0.005), with a slight decrease of IMU using the sliding-scale method (47.2% vs 52.8%). A more relevant variation of glycemia during hospitalization was observed in step C than A (−22.2 vs −15.5 mg/dl, p < 0.001). Rates of occurrence of hypoglycaemia were superimposable between the two steps (12.3% vs 11.9%), and these episodes were more frequent in patients using the sliding-scale method (19.4% vs 11.4%, p < 0.01). Mean length of hospital stay (step C) was higher in patients with episodes of hypoglycaemia (12.4 ± 11.1 vs 9.7 ± 6.6 days, p < 0.01). Conclusions: A one-shot educational intervention led to significant and persistent changes in the management of hospitalized patients with T2D. Further studies might evaluate the effectiveness of a more aggressive educational program, on both management and outcomes. Our study design allows to measure the impact on clinical practice of an educational interventional, a modality adapt to real life and generally requiring limited financial resources. Acknowledgments: The study was supported by an unrestricted grant by Novo Nordisk SpA . Table 1Characteristics of patients enrolled in the FADOI-DIAMOND study. Step A Step C Age (mean ± SD) 75.0 ± 11.5 75.4 ± 11.0 Female gender (%) 53.0 48.5 BMI (kg/m2 — mean ± SD) 28.7 ± 6.8 28.8 ± 5.7 ≥3 diseases other than T2D (%) 62.9 56.6 ≥4 drug other than those for T2D (%) 66.0 67.1 Therapy on admission (%) Oral hypoglicemic agents only 28.7 23.4 Insulin only 34.7 43.4 Combination therapy 25.0 21.8 Diet only 8.8 8.7 Fasting glycemia on admission (mg/dL — mean ± SD) 162.4 ± 80.54 164.4 ± 75.22 Open table in a new tab

Biphasic insulin aspart 30 (BIAsp 30) has been shown in randomised controlled trials and the IMPROVE™ observational study to reduce postprandial blood glucose (PPBG) – thought to be an independent risk factor for cardiovascular disease. We used multivariate regression analysis to identify predictors of PPBG reduction in the IMPROVE™ study. A total of 52,419 type 2 diabetes patients were enrolled in the IMPROVE™ study (pre-study therapy subgroups: no pharmaceutical therapy, n = 8966; oral antidiabetic drugs [OADs] only, n = 33,797; insulin ± OADs, n = 9568; missing information on pre-study therapy, n = 88). Mean change from baseline in PPBG (mean of three meals) in the global cohort was −6.3 mmol/L; reductions in subgroups were: no pharmaceutical therapy, −8.8 mmol/L; OADs only, −6.0 mmol/L; insulin ± OADs, −5.1 mmol/L. High baseline PPBG was consistently and strongly predictive of PPBG response; lower baseline HbA1c and body mass index, greater age and shorter diabetes duration were also significant predictors of PPBG change. The novel findings from this study indicate that most patients can be expected to achieve a PPBG response with BIAsp 30 irrespective of baseline characteristics or previous therapy with an expected larger PPBG reduction when baseline PPBG is higher.

Aims:  The international IMPROVE™ observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30.

The IMPROVE (TM) observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries.Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients' diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data.A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA(1c) 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA(1c) 9.2%) and insulin +/- OADs (n = 9568, diabetes duration 10.4 years, baseline HbA(1c) 9.3%). At final visit, HbA(1c), fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: -3.1%, -5.9 and -9.0 mmol/l, respectively; OADs-only: -2.1%, -4.1 and -6.1 mmol/l; insulin +/- OADs: -2.0%, -3.3 and -5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naive groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy.Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.

Objective:The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs).Methods:IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naive patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA(1c) <7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire.Results:A total of 29 160 insulin-naive patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%. Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline.Conclusions:This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naive patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

IMPROVE (TM) is an open-label, multinational, non-randomised, 26-week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin.Patients (n = 3856) with type 2 diabetes previously receiving human premixed insulin with or without oral antidiabetic drugs were eligible for inclusion. Demographic data, efficacy end-points (HbA(1c), fasting blood glucose and postprandial blood glucose) and safety end-points (serious adverse drug reactions, hypoglycaemia and adverse events) were collected at baseline and final visit. A subgroup analysis of mean dose change was also undertaken.Switching patients to BIAsp 30 resulted in significant improvements in glycaemic control combined with a reduced risk of hypoglycaemia. Patients who reached the HbA(1c) target (< 7%) had shorter diabetes duration, lower HbA(1c) at baseline and needed less insulin. Over 30% of patients were able to reach this target without experiencing hypoglycaemia over the 26-week period. Compared with asymmetric dose switching, unit-for-unit switching resulted in the highest proportion of patients reaching HbA(1c) target and incurred the least amount of dose titration.A unit-for-unit switch is the most effective as well as the simplest approach when transferring patients from biphasic human insulin 30 to BIAsp 30.

The IMPROVE (TM) study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions. Methods: Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen. Results: Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients. Conclusions: The IMPROVE (TM) baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

BACKGROUND:In this era of evidence-based medicine, clinicians require a comprehensive range of well-designed studies to support prescribing decisions and patient management. In recent years, data from observational studies have become an increasingly important source of evidence because of improvements in observational-study methods and advances in statistical analysis.OBJECTIVE:This article reviews the current literature and reports some of the key studies indicating that observational studies can both complement and build on the evidence base established by randomized controlled trials (RCTs).METHODS:A literature search using the MEDLINE/PubMed database (years: 1966-present) was carried out using the search terms observational or observational study(ies), historical control, nonrandomized, and postmarketing surveillance. All references comparing observational studies with randomized controlled trials were obtained and reviewed and were also hand-checked for studies not identified in the database searches.RESULTS:Observational studies play an important role in investigating treatment outcomes. Data from large observational studies can clarify the tolerability profile of marketed medicines. In particular, observational studies can be of benefit in the study of large, heterogeneous patient populations with complex, chronic diseases such as diabetes mellitus. Observational studies have played a key role in supporting the results of Phase III studies of insulin analogues for the treatment of patients with type 1 and type 2 diabetes. Future observational studies in the field of diabetes such as PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation) and IMPROVE will further our understanding of this global pandemic.CONCLUSIONS:Well-designed observational studies can play a key role in supporting the evidence base for drugs and therapies. Current evidence suggests that observational studies can be conducted using the same exacting and rigorous standards as are used for RCTs. The observational study design should be considered as a complementary rather than a rival analytic technique.