Is moderate-intensity interval training more tolerable than high-intensity interval training in adults with obesity?

Interval training (IT) has been shown to be a time-effective alternative to traditional training programmes in the management of obesity. Nevertheless, studies comparing the effects of different IT intensities on inflammation, muscle and liver damage, and perceptual responses in people with obesity are relatively scarce. This study aimed to compare the acute effects of two different IT protocols matched by the mean load and duration on biochemical and perceptual responses in sedentary adults with obesity. Twenty-two volunteers (age = 33.40 ± 10.01 years, BMI = 38.29 ± 7.09 kg/m²) were randomized to perform two conditions: moderate-intensity IT (MIIT) 5 × 3 min (70% of peak power output (PPO))/2 min (45%PPO) and high-intensity IT (HIIT) 8 × 1 min (90%PPO)/2 min (45%PPO). Blood samples were drawn before and after exercise for biochemical and haematological measurements. Rating of perceived exertion (RPE) was assessed during and after exercise. Perceptual pain was evaluated before, throughout and after exercise. C-reactive protein, white blood cells and neutrophils increased only after HIIT (p < 0.001, for all). Aspartate aminotransferase, alanine aminotransferase, creatine kinase and lactate dehydrogenase increased in both HIIT and MIIT (p < 0.001, for all), without any difference between sessions. HIIT induced a greater increase of blood lactate compared to MIIT (p < 0.05). Pain and RPE scores were higher during HIIT vs. MIIT (p < 0.001 and p < 0.01, respectively). MIIT induced fewer immune system perturbations and less muscle pain and was perceived as more tolerable compared to HIIT session. Therefore, MIIT could be used as a first step to promote body adaptations before starting a HIIT programme in sedentary people with obesity.

Correction: Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity.

[This corrects the article DOI: 10.1371/journal.pone.0301369.].

Impact of Time of Day on Glycemia in Response to Postprandial Supramaximal Sprints in Adults With Type 1 Diabetes.

OBJECTIVES: In this study we explore the impact of postprandial exercise timing (morning vs evening) on glycemia in individuals with type 1 diabetes (T1D) during short all-out sprints on a cycle ergometer. METHODS: Ten healthy physically sedentary male (n=7) and female (n=3) volunteers with type 1 diabetes, 22.8±2.8 years of age, and with a diabetes duration of 9.7±5.5 years and glycated hemoglobin level of 8.6±1.2%, underwent comprehensive screening and assessment of their physical health and fitness status before study participation, under the guidance of a physician. Each participant underwent 2 postprandial exercise sessions on separate days: the first in the morning at 8:00 AM and second in the evening at 8:00 PM, both conducted 60 minutes after a standardized meal. RESULTS: Morning exercise showed a less pronounced reduction in plasma glucose (PG) levels compared with evening exercise (-2.01±1.24 vs -3.56±1.6 mmol/L, p=0.03). In addition, higher cortisol levels were observed in the morning vs evening (128.59±34 vs 67.79±26 ng/mL, p<0.001). CONCLUSIONS: Morning repeated sprint exercise conducted in the postprandial state consistent with the protective effect of higher cortisol levels resulted in a smaller reduction in PG levels compared with evening exercise. This highlights the potential influence of exercise timing on glycemic responses and cortisol secretion in the management of T1D.

Molecular mechanisms underlying the defects of two novel mutations in the HSD17B3 gene found in the Tunisian population.

17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) converts Δ4-androstene-3,17-dione (androstenedione) to testosterone. It is expressed almost exclusively in the testes and is essential for appropriate male sexual development. More than 70 mutations in the HSD17B3 gene that cause 17ß-HSD3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD) have been reported. This study describes three novel Tunisian cases with mutations in HSD17B3. The first patient is homozygous for the previously reported mutation p.C206X. The inheritance of this mutation seemed to be independent of consanguineous marriage, which can be explained by its high frequency in the Tunisian population. The second patient has a novel splice site mutation in intron 6 at position c.490 -6 T > C. A splicing assay revealed a complete omission of exon 7 in the resulting HSD17B3 mRNA transcript. Skipping of exon 7 in HSD17B3 is predicted to cause a frame shift in exon 8 that affects the catalytic site and results in a truncation in exon 9, leading to an inactive enzyme. The third patient is homozygous for the novel missense mutation p.K202M, representing the first mutation identified in the catalytic tetrad of 17ß-HSD3. Site-directed mutagenesis and enzyme activity measurements revealed a completely abolished 17ß-HSD3 activity of the p.K202M mutant, despite unaffected protein expression, compared to the wild-type enzyme. Furthermore, the present study emphasizes the importance of genetic counselling, detabooization of 46,XY DSD, and a sensitization of the Tunisian population for the risks of consanguineous marriage.

Characteristics of adult-onset auto-immune type 1 diabetes.

BACKGROUND: Classically described as a disease of childhood and adolescence, diabetes mellitus type 1 (T1DM) can occur in adulthood. Adult-onset T1DM is poorly documented and is often misdiagnosed. This study aims to describe the epidemiological aspect of T1DM with adult-onset and detail its clinical, paraclinical, and therapeutic characteristics. MATERIALS AND METHODS: A 9-year retrospective longitudinal study (2011-2019) was conducted including adult patients (age >20 years) with confirmed diabetes and at least one of the auto-antibodies (auto-Abs) to glutamic-acid-decarboxylase (GAD), to islet-tyrosine-phosphatase 2 (IA2) or islet-cell-antibodies (ICA) positive. RESULTS: A total of 166 patients were included (sex-ratio M/F: 1.34; mean age: 28.6 years [20-56 years]). At the onset, 50.6% of patients presented with diabetic ketosis and 13.3% with diabetic ketoacidosis. Cardinal symptoms of diabetes were present in 30.7% of patients only at diagnosis, while the discovery was fortuitous in 5.4% of cases. 27.7% of patients developed an additional auto-immune disease mainly autoimmune thyroid disease. The risk of developing another AUTO-IMMUNE DISEASE was highest in females (p = 0.010) and increased with age (p = 0.011). GAD-Abs, IA2-Abs, and ICA were positive in 98.2%, 13.3%, and 17.4% of cases respectively. Only GAD-Abs were found positive in 73.1%. Upon diagnosis, 75.9% of patients were treated with insulin, while 24.1% of patients were initially put on oral anti-diabetic drugs before requiring insulin within an average of 7.42 months. CONCLUSIONS: Adult-onset T1DM has a different clinical course (slower onset, less abrupt symptoms, more insidious presentation, and more prolonged progression to insulin) that has to be known. Misdiagnosis of adult-onset T1DM can have serious consequences.

The Use of Digital Technology to Assess Cognitive Function in Tunisian Adults.

BACKGROUND: There has been increasing evidence and support for the use of digital technology in the cognitive health field. Despite the growing use of innovative digital technology to assess cognitive function, such technology remains scarce in Arabic countries, particularly in Tunisia. OBJECTIVE: To investigate the effectiveness of a digitally delivered cognitive assessment battery in differentiating varying degrees of cognitive function in older Tunisian adults. METHODS: One hundred fifty-five Tunisian older adults (age: 62.24±7.52 years) were assigned to one of four groups: healthy controls (HC), at-risk (AR), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Participants completed a translated version of the Neurotrack digital cognitive battery. RESULTS: The AD group performed significantly lower on the associative learning (p = 0.01) and associative memory assessments (p = 0.002), than the HC and AR groups. The AD group also performed worse on the inhibition measure (p = 0.008) than the HC, AR, and MCI groups. For recognition memory, the was a significant difference between all four groups (p < 0.0005), with AD having the lowest scores followed by the MCI, AR, and HC groups, respectively. There were no significant differences observed on attention, executive function and processing speed performance between the four groups (p > 0.05). CONCLUSION: The use of digital technology appears to be a viable solution to current cognitive assessment challenges for assessing cognitive function in a Tunisian population. These findings provide further support for the use of digital technology in cognitive assessment, particularly in understudied populations.

A novel thymidine phosphorylase mutation in a family with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Molecular docking, dynamic simulation and computational investigations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; OMIM 603041) is a rare inherited metabolic disorder mostly caused by mutations in TYMP gene encoding thymidine phosphorylase (TP) protein that affects the mitochondrial nucleotide metabolism. TP, functionally active as a homodimer, is involved in the salvage pathway of pyrimidine nucleosides. MNGIE-like syndrome having an overlapping phenotype of MNGIE was also described and has been associated with mutations in POLG and RRM2B genes. In the present study, we report the molecular investigation of a consanguineous family including two patients with clinical features suggestive of MNGIE syndrome. Bioinformatics analyses were carried out in addition to mtDNA deletion screening and copy number quantification in the blood of the two patients. Whole exome sequencing and Sanger sequencing analyses revealed the segregation in the affected family a novel mutation c.1205T>A (p.L402Q) within the exon 9 of the TYMP gene. In addition, mtDNA analysis revealed the absence of mtDNA deletions and a decrease of the copy number in the blood of the two patients of the studied family. The p.Leu402Gln mutation was located in a conserved amino acid within the α/ß domain of the TP protein and several software supported its pathogenicity. In addition, and based on docking and molecular dynamic simulation analyses, results revealed that L402Q caused a conformational change in TP mutated structure and could therefore alter its flexibility and stability. These changes prevent also the formation of stable homodimer leading to non-functional protein with partial or complete loss of its catalytic activity.

[Cardiovascular and metabolic impact of glucocorticoid substitution therapy in patients with Addison's disease]. / Répercussions métaboliques et cardiovasculaires de la substitution glucocorticoïde au cours de la maladie d'Addison.

Recent studies conducted in patients with Addison's disease (AD) highlighted that this disease, even after treatment, is a significant cause of morbi-mortality. This study aims to determine the cardiovascular and metabolic deleterious impact of long-course glucocorticoid substitution therapy. We conducted a retrospective study of 28 patients with treated Addison's disease evolving for more than 15 years. The average age of patients was 58, 53 years, with a female predominance (65%). The average follow-up period was 17, 87 years. Initial dose of hydrocortisone was 32, 5 mg/day (20.52 mg/m2) and 27, 9 mg/day (16,41mg/m2) at the time of the study. The prevalence of the metabolic syndrome (MS) in patients with AM was 35.71% after a period of treatment longer than 15 years. At the end of the follow-up period, 28.57% of patients were obese; 25% of patients had developed AH (arterial hypertension) and type 2 diabetes. The prevalence of dyslipidemia went from 3.57% to 42.85%. Only one patient had myocardial infarction at 25-year follow-up. Factors favoring the onset of MS in our study were history of disease and weight loss at the moment of diagnosis. Adjustment of substitution therapy is a challenge in patients with Addison's disease due to morbi-mortality associated with overdose. A regular follow-up and a personalized therapeutic approach are necessary to improve patients' prognosis.

Potential Predictive Role of Lipid Peroxidation Markers for Type 2 Diabetes in the Adult Tunisian Population.

OBJECTIVES: We evaluated the potential clinical relevance of malondialdehyde (MDA) and autoantibodies to copper oxidized low-density lipoprotein (CuOx-LDL) in type 2 diabetes occurrence. METHODS: This cross-sectional study enrolled 69 normoglycemic subjects, 18 prediabetic patients and 108 type 2 diabetes patients. MDA concentration was assessed spectrophotometrically. Plasma IgG, IgA and IgM levels to CuOx-LDL were determined by ELISA. RESULTS: Plasma MDA levels were considerably higher in obese, prediabetic and type 2 diabetes subjects compared to controls. In multiple linear regression analysis, both MDA and IgA to CuOx-LDL were significantly associated with glucose metabolism markers (p<0.05). Multiple logistic regression analyses showed that high plasma MDA and IgA to CuOx-LDL were independent risk factors for type 2 diabetes (OR 1.196, 95% CI: 1.058 to 1.353; p=0.004; OR 1.626, 95% CI: 1.066 to 2.481; p=0.024; respectively). Importantly, elevated IgA to CuOx-LDL predicted incident diabetes in patients with prediabetes (OR 2.321, 95% CI:1.063 to 5.066; p=0.035). From stratified analyses by body mass index (BMI), both MDA and IgA to CuOx-LDL remained independent predictors of type 2 diabetes occurrence in non-obese subjects (p<0.05). More interesting, elevated IgA to CuOx-LDL levels could be predictors of type 2 diabetes in obese prediabetic subjects (p=0.044). Conversely, neither IgG nor IgM to CuOx-LDL was associated with glucose metabolism markers, obesity or type 2 diabetes. CONCLUSIONS: Plasma MDA and IgA to CuOx-LDL were significantly associated with blood markers of glucose metabolism. High levels of MDA and IgA to CuOx-LDL could independently predict type 2 diabetes development in normoglycemia and prediabetic subjects.

[Guillain Barré syndrome and diabetic acido-ketotic decompensation during pregnancy: a case report and review of the literature]. / Syndrome de Guillain Barré et décompensation acidocétosique du diabète au cours de la grossesse: a propos d'un cas et revue de la littérature.

A 27-year-old pregnant woman was admitted to the resuscitation department with severe spontaneous acute ketoacidosis as early symptom of type 1 diabetes. The patient underwent resuscitation and insulin treatment with good clinical and biological evolution. On day 4, the patient had polyradiculoneuritis characterised by acute onset. Additional emergency examinations were negative. Lumbar cytopunction showed albuminocytologic dissociation. Electromyogram confirmed the diagnosis of Guillain Barré syndrome (GBS). The patient was treated with veinoglobulin and underwent physical rehabilitation. A dramatic improvement in neurological signs was noted. With regard to pregnancy, the patient aborted a week after being diagnosed with GBS. The association of GBS with ketotic decompensation is rare. Indeed, a few cases have been reported in the literature. This association during pregnancy was never described, hence the originality of this case study.

Reproductive outcomes of female patients with congenital adrenal hyperplasia due to 21-hydroxylase defi ciency.

Fertility in women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) appears to be reduced, especially in women with the classic salt-wasting type. Several factors have been suggested to contribute to this subfertility such as androgen excess, adrenal progesterone hypersecretion, consequences of genital reconstructive surgery, secondary polycystic ovaries syndrome, and psychosexual factors. In contrast to this subfertility, pregnancies are commonly normal and uneventful. Adequate glucocorticoid therapy and improvement of surgical and psychological management could contribute to optimize fertility in CAH female patients, even among women with the classic variant. This review provides current information regarding the reproductive outcomes of women with CAH due to 21-OHD and the fertility and pregnancy issues in this population.

Complicated urinary tract infections associated with diabetes mellitus: Pathogenesis, diagnosis and management.

Diabetes mellitus has a number of long-term effects on the genitourinary system. These effects predispose to bacterial urinary tract infections (UTIs) in the patient with diabetes mellitus. Complicated UTIs are also common and potentially life-threatening conditions. They include emphysematous pyelonephritis, emphysematous pyelitis/cystitis, xanthogranulomatous pyelonephritis, renal/perirenal abscess, and renal papillary necrosis. Improved outcomes of these entities may be achieved by early diagnosis, knowledge of common predisposing factors, appropriate clinical and radiological assessment, and prompt management. Herein we review complicated UTIs associated with diabetes mellitus in terms of pathogenesis, clinical manifestations, radiological features, and current management options.

Isolated adrenocorticotropic hormone deficiency due to probable lymphocytic hypophysitis in a woman.

We report a 22-year-old woman who presented with asthenia, weight loss and hypotension in which extensive pituitary and adrenal investigations were diagnostic of isolated adrenocorticotropic hormone deficiency (IAD) of pituitary origin. Magnetic resonance imaging of the hypothalamus and pituitary showed a normal-sized pituitary, with no mass lesion. The diagnosis of IAD probably secondary to lymphocytic hypophysitis (LYH) was made. IAD is able to be the way of presentation of LYH, although the disease could or could not turn into a panhypopituitarism. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment. Indeed, regular endocrine and imaging follow up is important for patients with IAD and normal initial pituitary imaging results to detect early new-onset pituitary hormones deficiencies or imaging abnormalities.

Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser Syndrome in a girl with a 46, XX karyotype: A case report and review of literature.

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a characteristic syndrome in which the Mullerian structures are absent or rudimentary. It is also associated with anomalies of the genitourinary and skeletal systems. Its association with gonadal dysgenesis is extremely rare and appears to be fortuitous, independent of chromosomal anomalies. We report such a case in a 21-year-old girl who presented primary amenorrhea and impuberism. The endocrine study revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46, XX. No chromosome Y was detected at the fluorescence in situ hybridization (FISH) analysis. Internal genitalia could not be identified on the pelvic ultrasound and pelvic magnetic resonance imaging. Laparoscopy disclosed concomitant ovarian dysgenesis and MRKH syndrome. There were no other associated malformations. Hormonal substitution therapy with oral conjugated estrogens was begun. The patient has been under regular follow-up for the last two years and is doing well.