Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Burden of Diabetic Foot Patients' Caregivers and Affecting Factors: A Cross-Sectional Study.

With 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.

Risk factors for amputation in patients with diabetic foot infection: a prospective study.

There 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 (33·2%) underwent amputation. The odds ratios in the amputation model were 3·09 for osteomyelitis (P < 0·001), 4·90 for arterial stenosis (AS) (P < 0·001), 3·67 for the history of DFI (P = 0·001), 2·47 for ulcer duration >60 days (P = 0·001), 3·10 for ulcer depth > 15 mm (P < 0·001) and 10·28 for fungal DFI (P = 0·015). In this study, the unusual result of well-known literature was fungal DFI as an independent risk factor for amputation in patients with DFI.

Insulin resistance in brain and possible therapeutic approaches.

Although 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.