Francesco Gallo

Influence of environment on insulin sensitivity.

Genetic and environmental factors influence insulin sensitivity (IS) during ones lifetime. Actually, uterine environment may affect IS at birth and later in life. In particular, various exogenous toxic substances, coupled to a genetic predisposition, may remarkably influence the regulation of the hypothalamus-hypophysis-adrenal gland axis, and the production or the activity of insulin, cerebral incretins, pro-inflammatory cytokines, and placental hormones. Owing to this reaction against environmental injuries, fetal growth and endocrine system development may be impaired, leading to low or large birth weight, or prematurity. Reduced growth in early life has been related to insulin resistance, which can be silent for years and evident in predisposed adults. The incidence of type 2 diabetes mellitus and obesity associated with sedentary lifestyle patterns and inadequate dieting behaviors in children and adolescents has rapidly increased during the last decade. Recent evidences suggest that the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor- (PPAR-) gene and the angiotensin converting enzyme (ACE) I/D gene polymorphism combined with environmental factors, such as phthalates interfering with the post receptorial action of insulin, alter insulin-sensible tissues. Therefore, IS, deriving from a complex interaction between genotype and environment, may change during life and depends on previous metabolic control, which is a sort of metabolicmemory. The goal for the future is preventing the complications associated with impaired IS through the control of exogenous factors and the use of drugs selectively effective on its pathogenesis.

Toxic environment and obesity pandemia: Is there a relationship?

Obesity is a multi-factorial disease, resulting from genes, environment and behaviour interactions, and represents the most common metabolic disorder in the Western Hemisphere. Its prevalence has dramatically risen during the last three decades, reaching worldwide epidemic proportions. Recent cumulating evidence suggests that obesity may represent an adverse health consequence of exposure during the critical developmental windows to environmental chemicals disrupting endocrine function. Moreover, exposure to these chemicals seems to play a key role in the development of obesity-related metabolic and cardiovascular diseases. Further research is needed to elucidate the relationship between this exposure and the obesity pandemia and the involved mechanisms as well as to refine hazard identification.

A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records (n = 2453) of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n = 1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.

Geographic variation in the frequency of abdominal adiposity and metabolic syndrome in Italian adolescents with type 1 diabetes.

In line with the global obesity epidemic, a raised weight gain has been described in children and adolescents with type 1 diabetes mellitus (T1DM) [1, 2]. The waist-to-height ratio (W/h), a proxy measure of central fat distribution, has been proposed as a simple and useful tool to detecting, among overweight children, those with a higher likelihood of having cardiometabolic risk [3]. Since the distribution of overweight in the general population in Italy varies among different geographic areas and shows the highest prevalence in the south [4], we explored whether the frequency of abdominal adiposity and consequently of metabolic syndrome (MetSy) also varied across the different geographic areas in Italian adolescents with T1DM. This cross-sectional study included a total of 412 Italian adolescents of Caucasian origin (219 males) with T1DM, aged 16–19 years, with a duration of diabetes of 8.4 ± 3.9 years. They were recruited from 18 care referral centers for diabetes in childhood affiliated to the Study Group on Diabetes of the Italian Society of Paediatric Endocrinology and Diabetology. Anthropometry, blood pressure, and venous fasting blood samples tested for triglycerides and HDL cholesterol were measured; HbA1c values (mean of four determinations during the previous year) were mathematically standardized to the DCCT normal range. All patients were on multi-injection or pump insulin treatment; the daily insulin dose (ID) per body surface area was calculated. MetSy was defined according to the IDF criteria; all patients were considered to fulfill the criterion of hyperglycemia. Communicated by Renato Lauro.

High frequency of diabetic ketoacidosis at diagnosis of type 1 diabetes in Italian children: a nationwide longitudinal study, 2004–2013

This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004–2013. DKA was defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH < 7.30) and severe (pH < 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3–41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003–1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.