Nutritional Management of Athletes with Type 1 Diabetes: A Narrative Review.

Type 1 diabetes mellitus (T1DM) represents a complex clinical challenge for health systems. The autoimmune destruction of pancreatic beta cells leads to a complete lack of insulin production, exposing people to a lifelong risk of acute (DKA, coma) and chronic complications (macro and microvascular). Physical activity (PA) has widely demonstrated its efficacy in helping diabetes treatment. Nutritional management of people living with T1DM is particularly difficult. Balancing macronutrients, their effects on glycemic control, and insulin treatment represents a complex clinical challenge for the diabetologist. The effects of PA on glycemic control are largely unpredictable depending on many individual factors, such as intensity, nutrient co-ingestion, and many others. Due to this clinical complexity, we have reviewed the actual scientific literature in depth to help diabetologists, sport medicine doctors, nutritionists, and all the health figures involved in diabetes care to ameliorate both glycemic control and the nutritional status of T1DM people engaging in PA. Two electronic databases (PubMed and Scopus) were searched from their inception to January 2024. The main recommendations for carbohydrate and protein ingestion before, during, and immediately after PA are explained. Glycemic management during such activity is widely reviewed. Micronutrient needs and nutritional supplement effects are also highlighted in this paper.

The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime?

Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine. A bidirectional relationship between GE and glycemia has been established: GE may explain the up to 30-40 % variance in glycemic response following a carbohydrate-rich meal. In addition, acute and chronic hyperglycemia induce deceleration of GE after meals. Hypoglycemia accelerates GE, but its role in counterregulation has been poorly investigated. The role of GE as a counterregulatory mechanism has been confirmed in pathophysiological conditions, such as gastroparesis or following recurrent hypoglycemia. Therefore, it could represent an "ancestral" mechanism, highly conservative and effective in all individuals, conditions and clinical contexts. Recent guidelines recommend GLP-1 receptor agonists (GLP-1RAs) either as the first injectable therapy for type 2 diabetes mellitus or in combination with insulin. Considering the potential impact on GE, it would be important to study subjects on GLP-1 RAs during hypoglycemia, to establish whether a possible deceleration of GE impairs glucose counterregulation.

Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways.

Late-onset Alzheimer's disease (LOAD) is the most frequent cause of dementia in older persons. Subjects affected by type 2 diabetes mellitus (T2DM) are at higher risk of vascular disease, cognitive decline, and dementia. LOAD has many characteristics shared with impaired insulin signaling pathways, and substantial evidence has demonstrated a pivotal role in dysregulated glucose metabolism in its pathogenesis. Recent studies have shown that some anti-diabetic drugs, other than regulating the metabolism of peripheral tissues, can also modulate the brain's metabolism, reduce inflammation, and have a direct neuroprotective effect. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class with many pleiotropic effects that may have strong neuroprotective potential. After a summary of the principal "anti-diabetic" drugs acting as suitable candidates in treating LOAD, this narrative review explored the potential role of SGLT2i on cognition from pre-clinical to clinical studies.

Diurnal Cycling of Insulin Sensitivity in Type 2 Diabetes: Evidence for Deviation From Physiology at an Early Stage.

The aim of this study was to establish the contribution of insulin resistance to the morning (a.m.) versus afternoon (p.m.) lower glucose tolerance of people with type 2 diabetes (T2D). Eleven subjects with T2D (mean [SD] diabetes duration 0.79 [0.23] years, BMI 28.3 [1.8] kg/m2, A1C 6.6% [0.26%] [48.9 (2.9) mmol/mol]), treatment lifestyle modification only) and 11 matched control subjects without diabetes were monitored between 5:00 and 8:00 a.m. and p.m. (in random order) on one occasion (study 1), and on a subsequent occasion, they underwent an isoglycemic clamp (a.m. and p.m., both between 5:00 and 8:00, insulin infusion rate 10 mU/m2/min) (study 2). In study 1, plasma glucose, insulin, C-peptide, and glucagon were higher and insulin clearance lower in subjects with T2D a.m. versus p.m. and versus control subjects (P < 0.05), whereas free fatty acid, glycerol, and ß-hydroxybutyrate were lower a.m. versus p.m. However, in study 2 at identical hyperinsulinemia a.m. and p.m. (∼150 pmol/L), glucose Ra and glycerol Ra were both less suppressed a.m. versus p.m. (P < 0.05) in subjects with T2D. In contrast, in control subjects, glucose Ra was more suppressed a.m. versus p.m. Leucine turnover was no different a.m. versus p.m. In conclusion, in subjects with T2D, insulin sensitivity for glucose (liver) and lipid metabolism has diurnal cycles (nadir a.m.) opposite that of control subjects without diabetes already at an early stage, suggesting a marker of T2D. ARTICLE HIGHLIGHTS: In people with type 2 diabetes (T2D), fasting hyperglycemia is greater in the morning (a.m.) versus the afternoon (p.m.), and insulin sensitivity for glucose and lipid metabolism is lower a.m. versus p.m. This pattern is the reverse of the physiological diurnal cycle of people without diabetes who are more insulin sensitive a.m. versus p.m. These new findings have been observed in the present study in people without obesity but with recent-onset T2D, with good glycemic control, and in the absence of confounding pharmacological treatment. It is likely that the findings represent a specific marker of T2D, possibly present even in prediabetes before biochemical and clinical manifestations.

Bone Health Care Pathway for Non-metastatic Prostate Cancer Patients on Radiation and Androgen Deprivation Therapy.

BACKGROUND/AIM: Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength. Therefore, we decided to develop an interdisciplinary pathway of care (IPC) dedicated to non-metastatic PCa patients on long-term ADT and RT. PATIENTS AND METHODS: An interdisciplinary team allocated resources to support an IPC to manage patients' CTIBL and prevent fragility fractures. The team provided a diagnostic and therapeutic workflow according to patients' and professional perspectives, consistent with recommendations and healthcare policies. The hospital's quality department certified the IPC, the Ethical Committee approved procedures over the workflow. The Fracture Liaison Service (FLS) standards inspired services and professionals' activities and interactions. RESULTS: Preliminary data support the feasibility of the IPC from professionals' and patients' perspectives. Median age of the enrolled patients was 75 years, more than a half (58.9%) had low grade osteopenia or normal BMD (T-score ≥-1.5 standard deviation, SD), while 23.5% and 17.6% had osteoporosis and osteopenia, respectively. The IPC meets the requirements of a FLS concerning crucial indicators. CONCLUSION: Our IPC was a suitable approach to assure timely identification, assessment, initiation, and monitoring of adherence to anti-fracture treatments among non-metastatic PCa patients on long-term ADT and RT. Further data are required to show its effectiveness on fragility fracture prevention.

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.

Sudden Cardiac Death in Hypertensive Patients.

In patients with hypertension, but without established cardiovascular disease, predictive factors for sudden cardiac death (SCD) remain undefined. We followed for an average of 10.3 years a cohort of 3242 initially untreated hypertensive patients without evidence of coronary or cerebrovascular heart disease at entry. All patients underwent a complete clinical examination which included ECG and 24-hour ambulatory blood pressure monitoring. At entry, the mean age of patients was 50.0 years, 45% were women, and 6.1% had type 2 diabetes mellitus. Average office blood pressure was 154/96 mm Hg, and average 24-hour ambulatory blood pressure was 136/86 mm Hg. Prevalence of left ventricular hypertrophy at ECG was 13.9%. During follow-up, SCD occurred in 33 patients at a rate of 0.10 per 100 patient-years (95% CI, 0.07-0.14). The rate of SCD was 0.07 and 0.30 per 100 patient-years, respectively, in the cohort of patients without and with ECG left ventricular hypertrophy ( P<0.01). In a multivariable Cox model with Firth penalized maximum bias reduction method for rare outcome events, left ventricular hypertrophy almost tripled the risk of SCD (adjusted hazard ratio, 2.99; 95% CI, 1.47-6.09; P=0.002) after adjustment for age ( P<0.0001), sex ( P=0.019), diabetes mellitus ( P<0.0001), and 24-hour ambulatory pulse pressure ( P=0.036). For each 10 mm Hg increase in 24-hour ambulatory pulse pressure, the risk of SCD increased by 35%. The time-dependent area under the receiver operating characteristic curve was 0.85 (95% CI, 0.74-0.96). We conclude that in patients with hypertension without established cardiovascular disease, age, diabetes mellitus, ECG left ventricular hypertrophy, and 24-hour ambulatory pulse pressure are independent prognostic markers for SCD in the long-term.

Electrocardiography for diagnosis of left ventricular hypertrophy in hypertensive patients with atrial fibrillation.

Left ventricular (LV) hypertrophy at electrocardiography (ECG) predicts incident atrial fibrillation (AF). However, the diagnostic performance of ECG for diagnosis of LV hypertrophy in patients with AF is still not well characterized. We analyzed 563 hypertensive patients enrolled in the Umbria-Atrial Fibrillation (Umbria-FA) registry, an ongoing prospective observational registry in patients with AF. All patients underwent ECG and standard echocardiography at their entry in the Register. Mean age was 74 years and 43% of patients were women. Prevalence of ECG-LV hypertrophy, defined by Perugia criterion corrected for body mass index, was 23%. Echocardiographic LV mass was the reference standard. Sensitivity, specificity and diagnostic accuracy of ECG-LV hypertrophy were 37.4% (95% confidence interval [CI]: 31.6-43.4), 90.0% (95% CI: 86.0-93.2) and 64.5% (95% CI: 60.4-68.3), respectively. Performance was comparable in patients with AF or sinus rhythm at ECG recording. The area under the receiver-operating characteristic (ROC) curve was 0.622 (95% CI: 0.580-0.664) in the group with AF and 0.662 (95% CI: 0.605-0.720) in that with sinus rhythm (p â€‹= â€‹0.266 for comparison). These data suggest that standard ECG is reliable for diagnosis of LV hypertrophy in patients with a history of AF, regardless of the presence of AF or sinus rhythm at the time of ECG recording.