A prediction model to assess the risk of egfr loss in patients with type 2 diabetes and preserved kidney function: The amd annals initiative.

OBJECTIVE: To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline. RESEARCH DESIGN AND METHODS: A cohort of 504.532 T2DM outpatients participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score. RESULTS: A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96-14.01) in the Learning and a HR of 13.45 (12.93-13.99) in the Validation cohort. The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8. CONCLUSIONS: In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame.

COVID-19 in people living with diabetes: An international consensus.

The COVID-19 pandemic has added an enormous toll to the existing challenge of diabetes care world-wide. A large proportion of patients with COVID-19 requiring hospitalization and/or succumbing to the disease have had diabetes and other chronic conditions as underlying risk factors. In particular, individuals belonging to racial/ethnic minorities in the U.S. and other countries have been significantly and disproportionately impacted. Multiple and complex socioeconomic factors have long played a role in increasing the risk for diabetes and now for COVID-19. Since the pandemic began, the global healthcare community has accumulated invaluable clinical experience on providing diabetes care in the setting of COVID-19. In addition, understanding of the pathophysiological mechanisms that link these two diseases is being developed. The current clinical management of diabetes is a work in progress, requiring a shift in patient-provider interaction beyond the walls of clinics and hospitals: the use of tele-medicine when feasible, innovative patient education programs, strategies to ensure medication and glucose testing availability and affordability, as well as numerous ideas on how to improve meal plans and physical activity. Notably, this worldwide experience offers us the possibility to not only prepare better for future disasters but also transform diabetes care beyond the COVID-19 era.

Triple-layer Mesh Plasty for Re-recurrent Ventral Hernia in a Liver Transplant Patient: A Case Report.

Ventral hernias often occur in transplanted patients because of weakness of the abdominal wall, poor muscle mass, and ascitis. In this report we describe the case of a re-recurrent ventral hernia seen emergently in a liver transplant recipient, who was treated using a singular 3-layer approach by placement of an intraperitoneal mesh, stressing technical aspects of the plasty as well as the importance of a sublay technique in the reinforcement of a previous prosthetic plasty.

Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus.

Many people with type 2 diabetes mellitus (T2DM) fail to achieve glycaemic control promptly after diagnosis and do not receive timely treatment intensification. This may be in part due to 'clinical inertia', defined as the failure of healthcare providers to initiate or intensify therapy when indicated. Physician-, patient- and healthcare-system-related factors all contribute to clinical inertia. However, decisions that appear to be clinical inertia may, in fact, be only 'apparent' clinical inertia and may reflect good clinical practice on behalf of the physician for a specific patient. Delay in treatment intensification can happen at all stages of treatment for people with T2DM, including prescription of lifestyle changes after diagnosis, introduction of pharmacological therapy, use of combination therapy where needed and initiation of insulin. Clinical inertia may contribute to people with T2DM living with suboptimal glycaemic control for many years, with dramatic consequences for the patient in terms of quality of life, morbidity and mortality, and for public health because of the huge costs associated with uncontrolled T2DM. Because multiple factors can lead to clinical inertia, potential solutions most likely require a combination of approaches involving fundamental changes in medical care. These could include the adoption of a person-centred model of care to account for the complex considerations influencing treatment decisions by patients and physicians. Better patient education about the progressive nature of T2DM and the risks inherent in long-term poor glycaemic control may also reinforce the need for regular treatment reviews, with intensification when required.

Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients.

BACKGROUND AND AIMS: Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION: To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER: ACTRN12609000255280 (https://www.anzctr.org.au/).

Clinical use of the co-formulation of insulin degludec and insulin aspart.

AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.

Risk factors for hypoglycemia in patients with type 2 diabetes, hospitalized in internal medicine wards: Findings from the FADOI-DIAMOND study.

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.

Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?

Type 2 diabetes mellitus (T2DM) is a major cause of cardiovascular (CV) disease. Several large clinical trials have shown that the risk for patients with diabetes of developing CV complications is only partially reduced by early, intensive glycaemic control and lifestyle interventions, and that such complications result from changes in complex, not fully explored networks that contribute to the maintenance of endothelial function. The accumulation of senescent cells and the low-grade, systemic, inflammatory status that accompanies aging (inflammaging) are involved in the development of endothelial dysfunction. Such phenomena are modulated by epigenetic mechanisms, including microRNAs (miRNAs). MiRNAs can modulate virtually all gene transcripts. They can be secreted by living cells and taken up in active form by recipient cells, providing a new communication tool between tissues and organs. MiRNA deregulation has been associated with the development and progression of a number of age-related diseases, including the enduring gene expression changes seen in patients with diabetes. We review recent evidence on miRNA changes in T2DM, focusing on the ability of diabetes-associated miRNAs to modulate endothelial function, inflammaging and cellular senescence. We also discuss the hypothesis that miRNA-containing extracellular vesicles (i.e. exosomes and microvesicles) could be harnessed to restore a 'physiological' signature capable of preventing or delaying the harmful systemic effects of T2DM.

Clinical implications of oxidative stress and potential role of natural antioxidants in diabetic vascular complications.

AIMS: The possible link between hyperglycaemia-induced oxidative stress (OxS) and diabetic complications is suggested by many in vitro studies. However, not much attention has been paid to the clinical evidence supporting this hypothesis, as well as to their possible therapeutic implications. DATA SYNTHESIS: Some prospective studies show a direct correlation between an increase in OxS biomarkers and the appearance of diabetes complications. This is consistent with the evidence that any acute increase of glycaemia, particularly post-prandial, and hypoglycaemia causes endothelial dysfunction and inflammation, through the generation of an OxS. However, the detection of free radicals is difficult as they are highly reactive molecules with a short half-life. Instead, the metabolites of OxS are measured. Interventional trials with supplemented antioxidants have failed to show any beneficial effects. Conversely, natural foods show very promising results. CONCLUSIONS: The "new antioxidant" approach includes the possibility of controlling free radical production and increasing intracellular antioxidant defence, a concept different from the old one, when antioxidant activities implied scavenging the free radicals already produced. A synergistic action in this respect could convincingly be obtained with a balanced 'Mediterranean Diet' (MedD) type. Early intensive glucose control is still the best strategy to avoid OxS and its associated diabetes complications.

Lispro insulin in people with non-alcoholic liver cirrhosis and type 2 diabetes mellitus.

AIMS: To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). METHODS: 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead. RESULTS: CGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post-absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (ΔAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05

Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC).

BACKGROUND AND AIMS: The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. METHODS: International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). RESULTS: The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. CONCLUSIONS: Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels.

Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls.

BACKGROUND AND AIMS: Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation. METHODS AND RESULTS: In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production. CONCLUSION: This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.

Oxidative stress after a carbohydrate meal contributes to the deterioration of diastolic cardiac function in nonhypertensive insulin-treated patients with moderately well controlled type 2 diabetes.

The prevalence and prognostic importance of diastolic dysfunction in type 2 diabetes has only recently been appreciated. We tested the hypothesis that in insulin treated type 2 diabetes (D), carbohydrate consumption induces oxidative stress resulting in further impairment of diastolic function beyond structural myocardial stiffness. The effects of a pure carbohydrate breakfast (48 g) on oxidative stress and cardiac function were studied in the fasting and postmeal states in subjects without hypertension or overt cardiac disease (moderately well controlled D, n=21 and controls without D, n=20). Studied variables included systolic and early diastolic (E') myocardial velocities, traditional metabolic and hemodynamic parameters, serum nitrotyrosine, and sVCAM-1. In D compared to control subjects, the postmeal increase (∆) in glucose (1.44±2.78 vs. 0.11±0.72 mmol/l, p=0.04) and ∆nitrotyrosine (0.34±0.37 vs. -0.23±0.47 nM/l, p<0.001) were significantly higher. sVCAM-1 was higher in fasting and postmeal (p=0.02). E' was significantly lower in postmeal (7.3±1.3 vs. 9.6±1.3 cm/s, p<0.001) and fasting (p<0.001) whereas the rate pressure product was significantly higher (9 420±1 118 vs. 7 705±1 871 mm Hg/min, p<0.001). Multivariable regression models of the pooled data demonstrated that independent predictors for postmeal E' were ∆nitrotyrosine and septal thickness (R² 0.466) and for fasting E' age, ∆nitrotyrosine, and septal thickness (R² 0.400). In insulin requiring type 2 diabetes, carbohydrate consumption may induce oxidative stress that is associated with worsening diastolic function, indicating that this metabolic factor is an important determinant of diastolic dysfunction in the diabetic heart beyond the increase in structural myocardial stiffness.

GLP-1 receptor agonists and HBA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists are available for the treatment of type 2 diabetes. We assessed the efficacy of exenatide and liraglutide to reach the HbA(1c) target of <7% in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search for randomized controlled trials (RCTs) involving GLP-1 agonists through September 2010. RCTs were included if they lasted at least 12 weeks, included 30 patients or more, and reported the proportion of patients reaching the HbA(1c) target of <7%. RESULTS: A total of 25 RCTs reporting 28 comparisons met the selection criteria, which included 9771 study participants evaluated for the primary endpoint, 5083 treated with a GLP-1 agonist and 4688 treated with placebo or a comparator drug. GLP-1 agonists showed a statistically significant reduction in HbA(1c) compared to placebo and the proportion of participants achieving the HbA(1c) goal <7% was 46% for exenatide, 47% for liraglutide, and 63% for exenatide LAR (long-acting release). Moreover, the reduction of the HbA(1c) level and the rate of HbA(1c) goal attainment were higher for both exenatide LAR and liraglutide, as compared to comparator drugs. Higher rates of hypoglycemia with exenatide b.i.d. and liraglutide compared to placebo were associated with the concomitant use of a sulfonylurea. Exenatide b.i.d. and liraglutide were associated with weight loss compared to placebo or other antidiabetic drugs. Baseline HbA(1c) was the best predictor for achievement of A1c target (overall weighted R(2) value = 0.513, p < 0.001). CONCLUSIONS: A greater proportion of patients with type 2 diabetes can achieve the HbA(1c) goal <7% with GLP-1 agonists compared to placebo or other antidiabetic drugs; in absolute terms, exenatide LAR was best for the attainment of the HbA(1c) goal.

Leukocyte telomere length is associated with complications of type 2 diabetes mellitus.

OBJECTIVE: The key goal of diabetes management is to prevent complications. While the patho-physiological mechanisms responsible for diabetes complications have been extensively studied, at present it is impossible to predict which patient with diabetes could develop complications. In recent years, the role of leukocyte telomere length in the pathogenesis of cardiovascular disease and Type 2 diabetes has been investigated. However, studies aiming to investigate the role of telomeres in the development and progression of Type 2 diabetes, as well as diabetic complications, are still lacking. As a consequence, this study aimed to verify whether leukocyte telomere length is associated with the presence and the number of diabetic complications in a sample of patients with Type 2 diabetes. METHODS: This is a cross-sectional study. Nine hundred and one subjects were enrolled, including 501 patients with Type 2 diabetes, of whom 284 had at least one complication and 217 were without complications, and 400 control subjects. Leukocyte telomere length was measured by quantitative real-time PCR. RESULTS: Patients with diabetes complications had significantly shorter leukocyte telomere length than both patients without diabetes complications and healthy control subjects. Moreover, among patients with diabetes complications, leukocyte telomere length became significantly and gradually shorter with the increasing number of diabetes complications. The magnitude of the effect of the decrease of the abundance of telomeric template vs. a single-copy gene length (T/S ratio) on complications is described by the estimated odds ratio OR=5.44 (95%CI 3.52-8.42). CONCLUSIONS: The results of the study support the hypothesis that telomere attrition may be a marker associated with the presence and the number of diabetic complications.