BackgroundFamilial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis, but little is known about its activity in FPL.MethodsPatients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone).ResultsSix patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed.ConclusionsOur findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.

Low-level laser therapy (LLLT) has been shown to increase the proliferation of several cell types. We evaluated the effects of LLLT on adhesion, proliferation, and gene expression of vascular endothelial growth factor (VEGF) and type 2 receptor of VEGF (VEGFR2) at mesenchymal stem cells (MSCs) from human (hMSCs) and rat (rMSCs) adipose tissues on nutritional deficiencies. A dose-response curve was performed with cells treated with laser Ga-Al-As (660 nm, 30 mW) at energy of 0.7 to 9 J. Cell adhesion and proliferation were quantified 20, 40, and 60 min after LLLT and 24, 72, and 120 h after cultivation. Gene expression was verified by RT-PCR after 2 h of LLLT. A minor nutritional support caused a significant decrease in proliferation and adhesion of hMSCs and rMSCs. However, at the lowest LLLT dose (0.7 J), we observed a higher proliferation in hMSCs at standard condition shortly after irradiation (24 h). Adhesion was higher in hMSCs cultivated in controlled conditions at higher LLLT doses (3 and 9 J), and rMSCs show a reduction in the adhesion on 1.5 to 9 J. On nutritional deprivation, a 9 J dose was shown to reduce proliferation with 24 h and adhesion to all culture times in rMSCs. VEGF and VEGFR2 were increased after LLLT in both cell types. However, hMSCs under nutritional deprivation showed higher expression of VEGF and its receptor after irradiation with other laser doses. In conclusion, LLLT on human and rat MSCs might upregulate VEGF messenger RNA (mRNA) expression and modulate cell adhesion and proliferation distinctively.

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

SUMMARY INTRODUCTION: Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management. CASE: RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression. DISCUSSION: We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications. CONCLUSION: Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

ObjectiveTo compare the effects of different aerobic training protocols on cardiometabolic variables in patients with type 2 diabetes mellitus (T2DM).MethodsThis study was a parallel clinical trial. Fifty-two men and women with T2DM (&gt;40 years) were randomly allocated into three groups, and 44 (22 males/22 females) were included in the final analysis. Exercise intensity was based on the speed corresponding to the maximum oxygen consumption (vV˙O2max). Moderate intensity continuous training (MICT) involved 14 minutes at 70% of vV˙O2max; short interval high-intensity interval training (S-HIIT) consisted of 20 bouts of 30 seconds at 100% of V˙O2max with 30 seconds passive recovery; long interval high-intensity training (L-HIIT) consisted of 5 bouts of 2 minutes at 100% of vV˙O2max with 2 minutes passive recovery. Training protocols were performed on a motorized treadmill two times per week for eight weeks. Glycated hemoglobin (Hb1Ac), total cholesterol, triglycerides, resting systolic blood pressure (SBP), resting diastolic blood pressure (DBP), resting heart rate (resting HR) and maximum oxygen consumption (V˙O2max) were measured before and after the exercise intervention. The study was registered on the Brazilian clinical trial records (ID: RBR45 4RJGC3).ResultsThere was a significant difference between groups for changes on V˙O2max. Greater increases on V˙O2max were achieved for L-HIIT (p = 0.04) and S-HIIT (p = 0.01) in comparison to MICT group, with no significant difference between L-HIIT and S-HIIT (p = 0.9). Regarding comparison within groups, there were significant reductions on HbA1c and triglycerides levels only for L-HIIT (p&lt; 0.05). V˙O2max significantly increased for both L-HIIT (MD = 3.2 ± 1.7 ml/kg/min, p&lt; 0.001) and S-HIIT (MD = 3.4 ± 1.7, p&lt; 0.001). There was a significant reduction on resting SBP for L-HIIT group (MD = -12.07 ± 15.3 mmHg, p&lt; 0.01), but not for S-HIIT and MICT. There were no significant changes from pre- to post-training on fasting glycemia, total cholesterol, HDL, LDL, resting HR and resting DBP for any group (p &gt; 0.05).ConclusionLow-volume HIIT promoted greater improvements in cardiorespiratory capacity in comparison with low-volume MICT, independent of the protocols used. There were no other differences between groups. All protocols improved at least one of the variables analyzed; however, the most evident benefits were after the high-intensity protocols, especially L-HIIT.