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BackgroundSevere and sustained emotional stress creates a physiological burden through increased sympathetic activity and higher energy demand. This may lead to increased oxidative stress and development of the metabolic syndrome. Emotional stress has been shown to contribute to the onset, progression, and control of type 2 diabetes (T2D). Stress management and biofeedback assisted relaxation have been shown to improve glycemic control. Use of a mobile app for stress management may enhance the scalability of such an approach. ObjectiveThe aim of this study was to assess the effect of using a mobile app of biofeedback-assisted relaxation on weight, blood pressure (BP), and glycemic measures of patients with T2D. MethodsAdult patients with T2D and inadequate glycemic control (hemoglobin A1c [HbA1c]>7.5%) were recruited from the outpatient diabetes clinic. Baseline weight, BP, HbA1c, fasting plasma glucose (FPG), triglycerides (TG), and 7-point self-monitoring of blood glucose were measured. Patients were provided with a stress reducing biofeedback mobile app and instructed to use it 3 times a day. The mobile app—Serenita—is an interactive relaxation app based on acquiring a photoplethysmography signal from the mobile phone’s camera lens, where the user places his finger. The app collects information regarding the user’s blood flow, heart rate, and heart rate variability and provides real-time feedback and individualized breathing instructions in order to modulate the stress level. All clinical and biochemical measures were repeated at 8 and 16 weeks of the study. The primary outcome was changes in measures at 8 weeks. ResultsSeven patients completed 8 weeks of the study and 4 completed 16 weeks. At week 8, weight dropped by an average of 4.0 Kg (SD 4.3), systolic BP by 8.6 mmHg (SD 18.6), HbA1c by 1.3% (SD 1.6), FPG by 4.3 mmol/l (4.2), and serum TG were unchanged. ConclusionsStress reduction using a mobile app based on biofeedback may improve glycemic control, weight, and BP.

Diabetes mellitus (DM) is more common among people living with human immunodeficiency virus (PLWH) compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%), and diabetic (6.9%) PLWH. Glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher body mass index, Ethiopian origin, HIV duration, lower integrase inhibitor exposure, and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1c likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation. [ABSTRACT FROM AUTHOR]

In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well‐established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) and Glucagon‐like peptide‐receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage. [ABSTRACT FROM AUTHOR]

Background Diabetic foot infections (DFIs) are frequently polymicrobial, yet the relevance of each isolated pathogen, remains ill-defined. Specifically, the prevalence and pathogenicity of enterococcal DFIs and the impact of targeted antienterococcal treatment remain elusive. Methods We collected demographic, clinical, and outcome-related data on patients admitted with DFIs to the Hadassah Medical Center diabetic foot unit between 2014 and 2019. The primary outcome was a composite of in-hospital death or major amputation. Secondary outcomes included any amputation, major amputation, length of stay (LOS), and 1-year major amputation or mortality rate. Results Enterococci were isolated in 35% of 537 eligible DFI case patients, who were notable for a higher prevalence of peripheral vascular disease, increased levels of C-reactive protein, and higher Wagner scores. Infection in enterococci-positive individuals was mostly polymicrobial (96.8% vs 61.0% in non–enterococci-infected patients; P <.001). Enterococci-infected patients were more likely to undergo amputation (72.3% vs 50.1%; P <.001) and had longer hospital stays (median LOS, 22.5 vs 17 days; P <.001), but the primary end point of major amputation or in-hospital death did not differ between groups (25.5% vs 21.0%; P =.26). Appropriate antienterococcal antibiotics were used in 78.1% of enterococci-infected patients and, compared with results in untreated patients, were associated with a trend toward a lower rate of major amputations (20.4% vs 34.1%; P =.06) but longer hospitalization (median LOS, 24 vs 18 days; P =.07). Conclusions Enterococci are common in DFIs and associated with higher rates of amputation and longer hospitalization. A reduction in major amputation rates with appropriate enterococci treatment is suggested retrospectively, meriting validation by future prospective studies. [ABSTRACT FROM AUTHOR]

Objective: The cardiorenal benefits of adding sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy for patients on insulin, particularly those on intensive regimens that include short-acting (SA) insulin, have not been explored.Research Design and Methods: In Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular (CV), renal, metabolic, and safety outcomes with dapagliflozin versus placebo by insulin dose and regimen were studied with Cox regression models.Results: The study included 7,013 insulin users at baseline, with 4,650 (66.3%) patients on regimens including SA insulin. Insulin doses varied, with 2,443 (34.8%) patients receiving <0.5 IU/kg, 2,795 (39.9%) 0.5 to ≤1 IU/kg, and 1,339 (19.1%) >1 IU/kg. Dapagliflozin reduced CV death/hospitalization for heart failure among overall insulin users (hazard ratio [HR] 0.82 [95% CI 0.69-0.97]) and consistently in patients on insulin regimens with or without SA insulin (0.83 [0.67-1.03] and 0.78 [0.57-1.07], respectively, Pinteraction = 0.75). No heterogeneity was observed by insulin dose (Pinteraction = 0.43). The HR for major adverse CV events with dapagliflozin among insulin users (0.84 [0.74-0.97]) was similar irrespective of regimen or dose (Pinteraction = 0.75 and 0.07). Dapagliflozin reduced the rate of adverse renal outcomes overall and consistently across subgroups of insulin users. Decreases in HbA1c, weight, and systolic blood pressure with dapagliflozin were seen regardless of insulin dose or regimen. The known safety profile of dapagliflozin was unchanged in patients on intensive insulin regimens.Conclusions: The benefits and safety of dapagliflozin were maintained in high-risk patients receiving high-dose or intensive insulin regimens including SA insulin.Article Highlights: Limited data exist regarding the cardiorenal, metabolic, and safety outcomes of SGLT2 inhibitors in patients on high-dose or intensive insulin regimens including short-acting insulin. In DECLARE-TIMI 58, 17,160 patients including 7,013 baseline insulin users were randomized to dapagliflozin versus placebo. Outcomes among insulin users by insulin dose and regimen were studied. Our results suggest that use of dapagliflozin by patients with type 2 diabetes managed with insulin, including high-dose or intensive insulin regimens, provided significant cardiovascular, renal, and metabolic benefits, in line with overall trial results. Adverse events associated with dapagliflozin, including hypoglycemia and diabetic ketoacidosis, were rare in this cohort. [ABSTRACT FROM AUTHOR]

Aims: Data regarding diabetic foot ulcers in patients after solid organ transplantation, particularly kidney transplantation, are limited. Chronic immunosuppression may be associated with impaired wound healing and a higher risk of amputations. In this study, we characterised the clinical presentation and outcomes of patients after kidney transplantation admitted to the diabetic foot unit, compared to non-kidney-transplant patients.Materials and Methods: Data on the baseline characteristics, clinical presentation, and outcomes of all patients admitted to the diabetic foot unit of a large tertiary centre between the years 2014 and 2019 were collected. The most recent admission of each patient was considered. Primary outcomes were major amputations and 1 year mortality rate.Results: During the study period, 537 patients were hospitalised, 18 of them were receiving immunosuppressive therapy due to kidney transplantation. Baseline characteristics of the patients were broadly similar, except that smoking was reported by 22.0% of the non-transplant patients and by none of the post-transplant patients (p = 0.01). Post-transplant patients tended to be younger (59.4 ± 11.1 vs. 65.3 ± 12.2; p = 0.07), were more likely to have type-1 diabetes (16.7% vs. 5.2%; p = 0.07) and had lower glucose levels upon admission (9.4 ± 4.3 vs. 12.0 ± 6.4 mmol/L; p = 0.07). Overall, 30% of the patients underwent major amputation, in-patient mortality rate was 9.3%, and 1 year mortality rate was 27.2%. Rates were similar in the post-transplant versus the non-post-transplant patients (p = 0.83, 1.00, 0.59, respectively).Conclusions: Post-transplant patients did not incur worse outcomes in spite of immunosuppressive therapy. Limb salvage efforts should be pursued in these patients similar to the overall population. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 57-year-old man with intractable non-islet-cell tumor hypoglycemia (NICTH) caused by ectopic secretion of prohormone insulin-like growth factor II (proIGF-II). It mentions that the patient underwent treatment with alpelisib, a phosphatidylinositol 3-kinase inhibitor, which resulted in the restoration of normoglycemia and improved well-being, highlighting the potential of alpelisib as a treatment option for NICTH.

Objective: In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk.Research Design and Methods: In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes.Results: Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001).Conclusions: Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Aims  We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM). Methods and results  DECLARE–TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m2): normal (18.5 to <25), overweight (25 to <30), moderately obese (30 to <35), severely obese (35 to <40), and very-severely obese (≥40). Outcomes analysed were CV death, hospitalization for heart failure (HHF), renal-specific composite outcome, and atrial fibrillation or flutter (AF/AFL). Of 17 134 patients, 9.0% had a normal BMI, 31.5% were overweight, 32.4% were moderately, 17.2% severely, and 9.8% were very-severely obese. Higher BMI was associated with a higher adjusted risk of HHF and AF/AFL (hazard ratio 1.30 and 1.28, respectively, per 5 kg/m2; P  < 0.001 for all). Dapagliflozin reduced body weight by similar relative amounts consistently across BMI categories (percent difference: −1.9 to −2.4%). Although relative risk reductions in CV and renal-specific composite outcomes with dapagliflozin did not significantly differ across the range of BMI (P for interaction ≥0.20 for all outcomes), obese patients (BMI ≥ 30 kg/m2) tended to derive greater absolute risk reduction in HHF and AF/AFL (P for interaction 0.02 and 0.09, respectively) than non-obese patients. Conclusions  In DECLARE–TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534. [ABSTRACT FROM AUTHOR]

Objective: Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c.Research Design and Methods: In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models.Results: In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06-1.19], 1.08 [1.04-1.13], and 1.17 [1.11-1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction > 0.05).Conclusions: Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c <7%. [ABSTRACT FROM AUTHOR]

Objective: The association of long‐term HbA1c variability with mortality has been previously suggested. However, the significance of HbA1c variability and trends in different age and HbA1c categories is unclear. Research Design and Methods: Data on patients with diabetes listed in the Israeli National Diabetes Registry during years 2012–2016 (observation period) were collected. Patients with >4 HbA1c measurements, type 1 diabetes, eGFR < 30mg/ml/min, persistent HbA1c < 6% or malignancy were excluded. Utilizing machine learning methods, patients were classified into clusters according to their HbA1c trend (increasing, stable, decreasing). Mortality risk during 2017–2019 was calculated in subgroups defined by age (35–54, 55–69, 70–89 years) and last HbA1c (≤7% and >7%) at end of observation period. Models were adjusted for demographic, clinical and laboratory measurements including HbA1c, standard deviation (SD) of HbA1c and HbA1c trend. Results: This historical cohort study included 293,314 patients. Increased HbA1c variability (high SD) during the observation period was an independent predictor of mortality in patients aged more than 55 years (p < 0.01). The HbA1c trend was another independent predictor of mortality. Patients with a decreasing versus stable HbA1c trend had a greater mortality risk; this association persisted in all age groups in patients with HbA1c > 7% at the end of the observation period (p = 0.02 in age 35–54; p < 0.01 in aged >55). Patients with an increasing versus stable HbA1c trend had a greater mortality risk only in the elderly group (>70), yet in both HbA1c categories (p < 0.01). Conclusions: HbA1c variability and trend are important determinants of mortality risk and should be considered when adjusting glycaemic targets. [ABSTRACT FROM AUTHOR]