Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Non alcoholic fatty liver disease is positively associated with increased glycated haemoglobin levels in subjects without diabetes

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study

A family history of type 2 diabetes as a predictor of fatty liver disease in diabetes-free individuals with excessive body weight

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes

Preliminary trajectories in dietary behaviors during the COVID-19 pandemic: A public health call to action to face obesity

The world is currently struggling to face the coronavirus pandemic (COVID-19), and many countries have imposed lockdowns and recommended quarantine to limit both the spread of the virus and overwhelming demands for medical care. Direct implications include the disruption of work routines, boredom, depression, increased calorie consumption, and other similar harmful effects. The present narrative review article briefly analyzes the preliminary effects of the quarantine lifestyle from the standpoint of dietary habits. In six different databases, we searched for original articles up to 10 August 2020, assessing eating habits among populations during the COVID-19 pandemic, and recorded any change in the intake of major food categories, as well as changes in body weight. The research strategy yielded 364 articles, from which we selected 12 articles that fitted our goal. Our preliminary findings revealed a sharp rise of carbohydrates sources consumption, especially those with a high glycemic index (i.e., homemade pizza, bread, cake, and pastries), as well as more frequent snacks. A high consumption of fruits and vegetables, and protein sources, particularly pulses, was also recorded, although there was no clear peak of increase in the latter. Data concerning the consumption of junk foods lacked consistency, while there was a decreased alcohol intake and fresh fish/seafood consumption. As a possible connection, people gained body weight. Therefore, in the realistic perspective of a continuing global health emergency situation, timely preventive measures are needed to counteract obesity-related behaviors in the long-term, so as to prevent further health complications

Trends in coffee and tea consumption during the covid-19 pandemic

Over the last two years, many countries have enforced confinement to limit both the spread of COVID-19 and the demand for medical care. Confinement has resulted in a disruption of work routines, boredom, depression, and changes in eating habits, among them consumption of coffee and tea. Following six databases, we examined articles tracking consumption of these beverages. Out of 472 articles, including 23 beverage entries, 13 matched our criteria. While no clear trend in coffee consumption during the coronavirus pandemic emerged (7 of 13 studies indicated an increase, accounting for 53.8%), tea consumption clearly increased (70% versus 30%). Considering the global health emergency continuum, more research is needed to better understand the paths underlying food choices and the ways those changes may influence health outcomes, including those related to COVID-19 disease

Higher Muscle Mass Implies Increased Free-Thyroxine to Free-Triiodothyronine Ratio in Subjects With Overweight and Obesity

Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS “S. de Bellis” (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04327375

The association between dysphagia and OSA Disfagia e OSA

Objective. The aim of our study was to investigate the presence of dysphagia in patients with Obstructive Sleep Apnoea (OSA) and to correlate swallowing impairment with hypnologic and anatomic parameters. Methods. The study population includes 36 patients suffering from OSA. Patients were divided into two groups using the presence of dysphagia as a distinctive parameter. Group 1 included 27 OSA patients without signs of dysphagia and Group 2 included 9 OSA patients with signs of dysphagia. Results. The age of patients in Group 2 was higher compared with the age of patients in Group 1. Analysis of Continuous Positive Airway Pressure (CPAP), obtained in the titration phase, showed that OSA patients with signs of dysphagia required a higher level of CPAP pressure than those who were not affected by swallowing abnormalities (12.6 ± 1 vs 10.5 ± 1.9 p = 0.003). No other differences in anthropometric, hypnologic, or arterial blood gas values were found between the two groups. Conclusions. In clinical practice, all OSA patients should undergo a complete ENT exam, including assessment of swallowing, before CPAP therapy is started. This may predict the need for higher CPAP pressure settings to resolve apnoea episodes in the presence of dysphagia as well as guide the choice of CPAP interfaces (orofacial vs. nasal) in these patients

Cross-sectional relationship among different anthropometric parameters and cardiometabolic risk factors in a cohort of patients with overweight or obesity

Background Body fat distribution influences the risk of cardio-metabolic disease in people with overweight. This study was aimed at identifying the anthropometric parameters more strongly associated with the majority of cardio-metabolic risk factors. Methods This study included 1214 subjects (840 women), with a body-mass-index (BMI) = 25 Kg/ m2, aged 39.2 ± 13 years. Fasting blood glucose (FBG), triglycerides (TG), total, HDL- and LDL-cholesterol, uric acid, vitamin D, high-sensitive C-reactive protein (hs-CRP), white blood cells (WBC), platelets, insulin and insulin resistance (HOMA-IR), systolic (SBP) and diastolic blood pressure (DBP), smoking habit and snoring were evaluated as cardio-metabolic risk factors.We also included the Systematic COronary Risk Evaluation (SCORE) to estimate cardiovascular risk in our study population. BMI, waist circumference (WC), waistto- height-ratio (WHtR) and neck circumference (NC) were evaluated as anthropometric parameters. Results All four anthropometric parameters were positively associated to SBP, DBP, TG, FBG, insulin, HOMA-IR, WBC, and snoring (p<0.001), and negatively associated with HDL-cholesterol (p<0.001). NC showed a positive association with LDL-cholesterol (ß = 0.76; p = 0.01; 95% C.I. 0.19 to 1.32), while vitamin D was negatively associated to WC (ß = -0.16; p<0.001; 95% C.I. -0.24 to -0.09), BMI (ß = 0.42); p<0.001; 95% C.I. -0.56 to -0.28) and WHtR (ß = -24.46; p<0.001; 95% C.I. -37 to -11.9). Hs-CRP was positively correlated with WC (ß = 0.003; p = 0.003; 95% C.I. 0.001 to 0.006), BMI (ß = 0.01; p = 0.02; 95% C.I. 0.001 to 0.012) and WHtR (ß = 0.55; p = 0.01; 95% C.I. 0.14 to 0.96). SCORE was associated to NC (ß = 0.15; 95% CI 0.12 to 0.18; p<0.001), BMI (ß = -0.18; 95% CI -0.22 to 0.14; p<0.001) and WHtR (ß = 7.56; 95% CI 5.30 to 9.82; p<0.001). Conclusions NC, combined with BMI and WC or WHtR could represent an essential tool for use in clinical practice to define the cardio-metabolic risk in individuals with excess body weight

Adherence to a mediterranean diet and thyroid function in obesity: A cross-sectional Apulian survey

BackgroundMuch research suggests that Mediterranean eating habits and lifestyle contribute to counteract the risk of chronic diseases while promoting longevity, but little information is available on the effects of the Mediterranean diet (Med-Diet) on thyroid function, particularly among overweight/obese subjects. Nevertheless, consistent data reported a slight increase in serum levels of the thyroid-stimulating hormone (TSH) and a higher rate of conversion of thyroxine (T4) to triiodothyronine (T3) in obesity. This cross-sectional study was aimed at investigating the relationship between adherence to the Med-Diet and circulating thyroid hormones in a cohort of overweight/obese subjects from Apulia (Southern Italy). Methods: We studied 324 consecutive outpatient subjects (228 women and 96 men, age range 14–72 years) taking no drug therapy and showing normal levels of thyroid hormones, but complicated by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m2). The PREDIMED (PREvención con DIeta MEDiterránea) questionnaire was cross-sectionally administered to assess the adherence to the Med-Diet, and hormonal, metabolic, and routine laboratory parameters were collected. Results: Higher adherence to Med-Diet was found to be inversely related to free T3 (p < 0.01) and T4 (p < 0.01) serum levels. Considering each item in the PREDIMED questionnaire, people consuming at least four spoonfuls of extra-virgin olive oil (EVOO) per day, as well as those consuming at least two servings of vegetables per day, had lower free T3 levels (p 0.033 and p 0.021, respectively). Furthermore, consuming at least four spoonfuls of EVOO per day was found to be associated to lower free T4 serum concentrations (p 0.011). Multinomial logistic regression models, performed on tertiles of thyroid hormones to further investigate the relationship with Med-Diet, corroborated the significance only for free T4. Conclusion: Increased adherence to the Med-Diet was independently associated to a slightly reduced thyroid function, but still within the reference range for free T3 and T4 serum levels. This first finding in this field opens up a research line on any underlying biological interplay