Loss of early insulin secretion leads to postprandial hyperglycaemia

AIMS/HYPOTHESIS: A loss of early-phase insulin response is common in Type II diabetic patients and in people with impaired glucose metabolism. It is hypothesized that this alteration is not simply a marker for the risk of developing diabetes, rather it is a an important pathogenetic mechanism causing excessive postprandial hyperglycaemia. METHODS: Relevant literature on the epidemiology, physiopathology, and therapeutic intervention related to loss of early insulin secretion and postprandial hyperglycaemia has been analysed. RESULTS: In response to intravenous glucose, insulin secretion is biphasic. This behaviour translates as a rapid release of insulin into the blood stream in response to the ingestion of carbohydrates or a mixed meal. The rapid increase in portal insulin concentration and the avid binding of the hormone to its receptor on liver cell membranes, account for a prompt suppression of endogenous glucose production and reduction of the rate of increase in plasma glucose concentrations. This has been supported by experimental studies carried out in both animals and humans: the selective abolition of early insulin secretion in healthy subjects results in impaired glucose tolerance, excessive glucose excursions, and possible hampering of the thermic effects of ingested carbohydrates. In non-diabetic subjects, the loss of early insulin secretion is a determinant for developing diabetes. The critical role of the early-phase insulin response in determining postprandial hyperglycaemia, is supported by an amelioration of glucose tolerance by restoring the acute rise in plasma insulin concentrations after the ingestion of both glucose and a mixed meal. This amelioration in plasma glucose profile can prevent late hyperglycaemia and hyperinsulinaemia. CONCLUSION/INTERPRETATION: Therapeutic approaches aimed at restoring a physiological pattern of insulin secretion could prove effective in reducing postprandial glucose excursions particularly in the early stage of Type II diabete

Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials

AbstractBackground and aimsWe aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM).Methods and resultsData were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (−0.42% [±0.11] to −0.79% [0.08]; all p 7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05).ConclusionThis post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS

EARLIER INTERVENTION IN TYPE 2 DIABETES

In type 2 diabetes, the onset and progression of complications is significantly delayed by improving glycaemic control. However, the proportion of patients reaching and sustaining guideline recommendations for glycaemic targets remains unacceptably low. Recent clinical trials and predictive physiologically based mathematical simulations (Archimedes model) indicate that benefits can be enhanced with earlier intervention and timely achievement of glycaemic targets. This article reviews the evidence for early intervention, showing that intensive approaches, including earlier introduction of combination therapy, allow more patients to achieve glycaemic targets and hence reduce complications and delay disease progression

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials *

AbstractBackground and aimsBasal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar).Methods and resultsData were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy.ConclusionThis analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D

a consensus statement for the clinical use of the renal sodium glucose co transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

ABSTRACTIntroduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus.Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin .Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inh..

Gender effect on the Relation between Diabetes and Hospitalization for Heart Failure

Aims: Cardiovascular risk among diabetic patients is at least twice as much the one for nondiabetic individuals and even greater when diabetic women are considered. Heart failure (HF) is a common unfavorable outcome of cardiovascular disease in diabetes. However, since the comparison among sexes of heart failure prevalence in diabetic patients remains limited, this study is aimed at expanding the information about this point. Methods: We have evaluated the association between diabetes and HF by reviewing the medical records of all subjects discharged from the Internal Medicine and Cardiology Units of all hospitals in the Tuscany region, Italy, during the period January 2002 through December 2008. In particular we sought concomitance of ICD-9-CM codes for diabetes and HF. Results: Patients discharged by Internal Medicine were on average older, more represented by women, and had a lesser number of individuals coded as diabetic (p &lt; 0.05 for all). Relative risk for HF (95 % CI) was signifi cantly higher in patients with diabetes, irrespective of gender 1.39 (1.36– 1.41) in males; 1.40 (1.37–1.42) in females. When the diabetes-HF association was analyzed according to decades of age, a “horse-shoe” pattern was apparent with an increased risk in 40–59 years old in female patients discharged by Internal Medicine. Conclusions: Although there is not a diff erence in the overall HF risk between hospitalized male and female diabetic patients, women have an excess risk at perimenopausal ag

Diabetes and acute bacterial skin and skin structure infections.

Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical needs in this area. Pathogenetic mechanisms underlying the increased risk of ABSSSIs in diabetes mellitus are multifactorial: high glucose levels play a crucial pathogenetic role in the tissue damage and delayed clinical cure. Moreover, the presence of diabetes complications (neuropathy, vasculopathy) further complicates the management of ABSSSIs in patients with diabetes. Multidrug resistance organisms should be considered in this population based on patient risk factors and local epidemiology and etiological diagnosis should be obtained whenever possible. Moreover, drug-drug interactions and drug-related adverse events (such as nephrotoxicity) should be considered in the choice of antibiotic therapy. Reducing unnecessary hospitalizations and prolonged length of hospital stay is of primary importance now, more than ever. To achieve these objectives, a better knowledge of the interplay between acute and chronic hyperglycemia, multidrug resistant etiology, and short and long-term outcome is needed. Of importance, a multidisciplinary approach is crucial to achieve full recovery of these patients

Tailoring treatment to the individual in type 2 diabetes practical guidance from the Global Partnership for Effective Diabetes Management

Good glycaemic control continues to be the most effective therapeutic manoeuvre to reduce the risk of development and/or progression of microvascular disease, and therefore remains the cornerstone of diabetes management despite recent scepticism about tight glucose control strategies. The impact on macrovascular complications is still a matter of debate, and so glycaemic control strategies should be placed in the context of multifactorial intervention to address all cardiovascular risk factors. Approaches to achieve glycaemic targets should always ensure patient safety, and results from recent landmark outcome studies support the need for appropriate individualisation of glycaemic targets and of the means to achieve these targets, with the ultimate aim to optimise outcomes and minimise adverse events, such as hypoglycaemia and marked weight gain. The primary goal of the Global Partnership for Effective Diabetes Management is the provision of practical guidance to improve patient outcomes and, in this article, we aim to support healthcare professionals in appropriately tailoring type 2 diabetes treatment to the individual. Patient groups requiring special consideration are identified, including newly diagnosed individuals with type 2 diabetes but no complications, individuals with a history of inadequate glycaemic control, those with a history of cardiovascular disease, children and individuals at risk of hypoglycaemia. Practical guidance specific to each group is provided

Changing the Treatment Paradigm for Type 2 Diabetes

Based on the results of the U.K. Prospective Diabetes Study (UKPDS), “… treatment of type 2 diabetes [should] include aggressive efforts to lower blood glucose levels as close to normal as possible. …” This was the recommendation the American Diabetes Association promulgated based on the results of the UKPDS when published (1). The suggestion was soon adopted by official guidelines in every region of the world (2). They are generally consistent in recommending an A1C goal of <7.0%. However, the results of the UKPDS remained inconclusive with respect to cardiovascular (CV) complications because of a risk reduction that was only close to statistical significance (−16%, P = 0.052). In support of the UKPDS results, however, a recent meta-analysis of randomized trials in type 2 diabetes (3) calculated a 19% reduction in the incidence of any type of macrovascular event associated with improved long-term glycemic control. Moreover, a strong association between glycemic control and micro- and macrovascular disease has been highlighted in type 1 diabetic patients (4,5)

Incidence of complications in bronchoscopy. Multicentre prospective study of 20,986 bronchoscopies.

Aim. To evaluate the frequency of complications in bronchoscopy from data compiled between 1/2/2002 to 1/2/2003. Materials and methods. Nineteen Italian centres of thoracic endoscopy participated in the study, for a total of 20,986 bronchoscopies (FBS), including 10,658 explorative bronchoscopies (EB) (50.79%), 5,520 bronchial biopsies (BB) (26.30%), 1,660 transbronchial biopsies (TBB) (7.91%), 1,127 broncho-alveolar lavages (BAL) (5.37%), 930 transbronchial needle-aspirates (TBNA) (4.43%), 1.091 therapeutic bronchoscopies (TB), comprising NDYAG Laser, argon-plasma, electrocautery knife, stent insertion (5.20%). 82.4% of the procedures involved the use of a flexible bronchoscope, 16.3% were carried out using a rigid bronchoscope and 1.3% using the mixed technique. Results. The total number of complications recorded was 227 (1.08% of the cases examined), including 20 (0.09%) during local anesthesia and pre-medication, 195 (0.92%) during the endoscopic procedures and 12 (0.05%) in the two hours following FBS. The total number of deaths was 4 (0.02%), due to cardiac arrest, pulmonary edema, delayed respiratory failure and shock in pre-medication, respectively. 68.28% of the complications were treated medically, 25.99% by means of endoscopy and 5.72% with surgery. The healing percentage was 98.2%. Conclusions. This study has shown that bronchoscopy is a safe method with low incidence of mortality and complications. The preparation, experience and continuous training of the operators of the medical and nursing team seem to play a fundamental role in reducing the incidence of complications at least in certain procedures such as BB and TBB