15 research outputs found
Metabolic effects of pioglitazone and sodium-glucose cotransporter 2 inhibitors in familial partial lipodystrophy
No full textObjective: We aimed to evaluate the potential metabolic benefits of pioglitazone, a PPARG agonist, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with familial partial lipodystrophy (FPLD). Methods: This retrospective medical chart study included 38 adult patients with FPLD (18 treated with pioglitazone and 20 with SGLT2 inhibitors). Results: Treatment with pioglitazone reduced HbA1c from 8.6% (6.2–9.2) to 7.0% (5.9–8.8) at month 6 (p = 0.004) and 7.0% (6.1–8.7) at month 12 (p = 0.107). Triglycerides decreased by 25% (6–55%) at month 6 (p = 0.001) and 16% (4–44%) at month 12 (p = 0.008). A modest reduction in ALT was observed at month 12 (p= 0.046). Treatment with SGLT2 inhibitors reduced HbA1c from 8.7% (7.9–10.2) at baseline to 8.1% (7.4–9.4) at month 6 (p = 0.003) and 7.9% (7.3–8.9) at month 12 (p = 0.003). Median triglyceride levels decreased by 11% (0–33%) at month 6 (p = 0.013), while changes at month 12 were not significant. No meaningful changes were observed in weight, ALT, or AST. Conclusions: We observed modest metabolic improvements following treatment with pioglitazone and SGLT2 inhibitors in patients with FPLD
Insulin Resistance in Brain and Possible Therapeutic Approaches
No full textAlthough the brain has long been considered an insulin-independent organ, recent research has shown that insulin has significant effects on the brain, where it plays a role in maintaining glucose and energy homeostasis. To avoid peripheral insulin resistance, the brain may act via hypoinsulinemic responses, maintaining glucose metabolism and insulin sensitivity within its own confines; however, brain insulin resistance may develop due to environmental factors. Insulin has two important functions in the brain: controlling food intake and regulating cognitive functions, particularly memory. Notably, defects in insulin signaling in the brain may contribute to neurodegenerative disorders. Insulin resistance may damage the cognitive system and lead to dementia states. Furthermore, inflammatory processes in the hypothalamus, where insulin receptors are expressed at high density, impair local signaling systems and cause glucose and energy metabolism disorders. Excessive caloric intake and high-fat diets initiate insulin and leptin resistance by inducing mitochondrial dysfunction and endoplasmic reticulum stress in the hypothalamus. This may lead to obesity and diabetes mellitus (DM). Exercise can enhance brain and hypothalamic insulin sensitivity, but it is the option least preferred and/or continuously practiced by the general population. Pharmacological treatments that increase brain and hypothalamic insulin sensitivity may provide new insights into the prevention of dementia disorders, obesity, and type 2 DM in the future
Gait Variability and Kinematic Alterations in People with Diabetes Mellitus and Peripheral Neuropathy
No full textBackground: People with diabetes and peripheral neuropathy have been reported to show alterations in lower limb joint function compared to healthy non-diabetic people. Specifically the maximum angular movement available at certain joints can be reduced during static, non-weight bearing tasks. Limited joint range of motion has the potential to compromise balance and stability thereby increasing the risk of falling. It is unclear whether a reduction in the extent of movement available at the joints is reflected by a reduction in the amount of angular movement actually utilised during a functional task such as stair negotiation. The aim of this study was to determine if people with diabetes show reduced dynamic range of motion at the ankle, knee and hip joints during stair ascent and descent in comparison to controls. Falls risk during stair negotiation was calculated by measuring the degree of variability in dynamic joint range of motion. Methods: Data were generated from three groups: subjects with diabetes and peripheral neuropathy (DPN), diabetes without peripheral neuropathy (DM), and healthy controls (Ctl). The study was conducted in a gait laboratory using motion capture and related 3D software for analysis. Joint range of motion for the ankle, knee, and hip were captured during level walking, stair ascent, and descent. A seven step, bespoke staircase was fabricated for this purpose. Analysis of Variance (ANOVA) and Newman-Keuls tests were used to analyse the data. Results: Significantly reduced ankle range of motion, in the sagittal plane, was observed in the DPN group during stair ascent when compared to the controls. For stair descent, the DPN group demonstrated a significant increase in knee and hip ROM in the frontal plane, and also hip ROM in the transverse plane. No significant differences between the groups were identified for joint variability. Conclusions: People with DPN demonstrate alterations in dynamic range of motion at the lower limb joints during stair ascent and descent. The degree of angular movement utilised for both stair tasks was decreased at the ankle joint and this has the potential to undermine balance and stability. In contrast, angular movement at the knee and hip joints was increased in the frontal and transverse planes. This may compensate for impaired balance and stability by increasing the base of support to maintain balance and assist in foot clearance and placement. The specific combination of increased angular movement at the knee and hip may represent a compensatory stair gait strategy in response to reduced angular movement at the ankle joint
A cohort analysis of familial partial lipodystrophy from two Mediterranean countries
No full textAim: To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications. Materials and methods: An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 +/- 17 years, 70% women; FPLD3: 18 patients, mean age: 44 +/- 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted. Results: Patients were diagnosed at a mean age of 39 +/- 19 years, 20 +/- 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 +/- 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 +/- 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 +/- 3 years, which was shorter in the Turkish cohort (68 +/- 2 vs. 83 +/- 4 years, P = .01). Cardiovascular events were a major cause of death. Conclusions: Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances.Secretaria Xeral de Investigacion e Desenvolvemento, Xunta de Galicia [ED431B 2020/37]; Asociacion Espanola de Familiares y Afectadosde Lipodistrofias; Instituto de Salud Carlos III [PI22/00514]; Fundacion Alfonso Martin Escudero; Juan Rodes research contract [JR23/00042]; ERDFSecretaria Xeral de Investigacion e Desenvolvemento, Xunta de Galicia,Grant/Award Number: ED431B 2020/37; Asociacion Espanola de Familiares y Afectadosde Lipodistrofias; Instituto de Salud Carlos III,Grant/Award Number: PI22/00514;Fundacion Alfonso Martin Escudero; Juan Rodes research contract, Grant/Award Number: JR23/00042; ERD
Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy
No full textAbstract
Background
Classical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause autosomal dominant familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss.
Case presentation
Here, we report a patient with a lamin A specific pathogenic variant in exon 11, denoted LMNA (c.1745G > A; p.R582H), present in the homozygous state. Fat distribution was compared radiographically to an unrelated heterozygote LMNA p.R582H patient from another pedigree, a healthy female control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9), and typical FPLD2 (n = 8). The whole-body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, the p.R582H LMNA variant in homozygous fashion was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, the heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482.
Conclusions
Our observations and radiological comparisons demonstrate an additive effect of LMNA pathogenic variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy.http://deepblue.lib.umich.edu/bitstream/2027.42/174029/1/40842_2020_Article_100.pd
Cedrus libani iğne yapraklarındaki terpenik ve yağ asitlerinin incelenmesi
No full textBu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.ÂBSTRAKT Bu çalışmada materyal olarak en fazla 1 cm. çapm- daki ince daliarıda içeren sedir (Cedrus libani) iğne yap rakları kullanıldı. Materyalin hegzan ekstraksiyonu yapıla rak reçine asitleri, terpen asitleri ve karboksilli asitler belirlendi. E una ek olarak aynı materyalden hidrodistilasyonla elde edilen uçucu yağ G.C. yöntemi ile incelendi. ASTRACT Cedar (Cedrus libani) needles and twigs on branches with maximum diameter 1 cm. (technical foliage) were the material for this study. The resin acids, terpene acids and carboxylic acids of the hexan extract of this material were identified. In addition to this the essential of the same material obtained from hydrodistillation was studied by G.C. methodÂBSTRAKT Bu çalışmada materyal olarak en fazla 1 cm. çapm- daki ince daliarıda içeren sedir (Cedrus libani) iğne yap rakları kullanıldı. Materyalin hegzan ekstraksiyonu yapıla rak reçine asitleri, terpen asitleri ve karboksilli asitler belirlendi. E una ek olarak aynı materyalden hidrodistilasyonla elde edilen uçucu yağ G.C. yöntemi ile incelendi. ASTRACT Cedar (Cedrus libani) needles and twigs on branches with maximum diameter 1 cm. (technical foliage) were the material for this study. The resin acids, terpene acids and carboxylic acids of the hexan extract of this material were identified. In addition to this the essential of the same material obtained from hydrodistillation was studied by G.C. method
Risk factors for amputation in patients with diabetic foot infection: a prospective study
No full textThere is a variety of diagnostic and therapeutic algorithms for diabetic foot infections (DFIs). Some of them are too difficult to be applied in routine clinical approach. In the routine clinical approach, it is necessary to find new risk factors and end up with a quick and easy assessment of DFIs. In this study, we aimed to evaluate the independent risk factors for osteomyelitis, amputation and major amputation in patients with DFI using standard scoring procedures. We prospectively studied 379 patients with DFI. The variables were analysed using logistic analysis. A total of 126 cases (332%) underwent amputation. The odds ratios in the amputation model were 309 for osteomyelitis (P 60 days (P = 0001), 310 for ulcer depth > 15 mm (P < 0001) and 1028 for fungal DFI (P = 0015). In this study, the unusual result of well-known literature was fungal DFI as an independent risk factor for amputation in patients with DFI
Burden of Diabetic Foot Patients' Caregivers and Affecting Factors: A Cross-Sectional Study
No full textWith the increase in the diabetic foot patients in recent decades, the caregivers of diabetic foot patients increase too. Most of these caregivers are informal caregivers. However, the studies examining the burden of the caregivers and affecting factors are limited. This study was conducted to determine the burden of the caregivers of diabetic foot patients and affecting factors. This cross-sectional study was conducted between the January and October 2020 in a diabetic foot council of a university hospital. Zarit Caregiver Burden Scale and a participant identification form were used for data collection. Most of the caregivers were female (75.2%) and the mean age was 51.27 +/- 11.48 years. The burden of the caregivers was at moderate level in the current study. Factors affecting the caregivers' burden were caregivers' age, patients' family structure, caregivers' education level, caregivers' income level, hours per week spending for the care of the patients, and lack of choice
Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy
No full textContext: Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective: Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design: An 8-domain LDS was developed by eight disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at two different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in two cohorts of patients with lipodystrophy treated with metreleptin. Results: LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by one or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility, and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R=0.79-0.99, P<0.001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P<0.001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P=0.04). Conclusions: The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions
