Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

OBJECTIVES: The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. METHODS: The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. RESULTS: Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. CONCLUSIONS: Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Does C-reactive protein identify a subclinical metabolic disease in healthy subjects?

BACKGROUND: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects. DESIGN: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia. RESULTS: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile. CONCLUSIONS: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.

Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes.

BACKGROUND AND DESIGN: Conflicting data exist about uric acid levels in type 2 diabetes mellitus, as low levels were found in diabetic patients, while elevated serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance. The present study was addressed to evaluate the relation between uric acid and metabolic parameters, creatinine clearance and albumin excretion rate in a cohort of type 2 diabetic patients. RESULTS: Hyperuricemic patients were older and had higher values of body mass index (BMI), systolic and diastolic blood pressure, triglycerides, albumin excretion rate, C-peptide and prevalence of hypertension, metabolic syndrome and macroalbuminuria and lower values of high-density lipoprotein (HDL)-cholesterol, creatinine clearance and glycated haemoglobin (HbA1c). The correlations between uric acid levels and triglycerides, BMI, systolic blood pressure, albumin excretion rate, C-peptide, creatinine clearance, HDL-cholesterol and HbA1c remained significant in a multiple regression analysis after adjustment for age, sex and duration of diabetes. After performing multiple logistic regression analyses, uric acid levels were independently associated with hypertension [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.6--2], after adjustment for age, sex, duration of diabetes and macroalbuminuria (OR = 1.5; 95% CI 1.1--2.0), after adjustment for age, sex, HbA1c levels, creatinine clearance, duration of diabetes and blood pressure levels and the metabolic syndrome (OR = 1.6; 95% CI 1.5--1.8), after adjustment for age, sex and creatinine clearance. CONCLUSIONS: In type 2 diabetes, hyperuricemia seems to be associated with the insulin-resistant syndrome and with early onset or increased progression to overt nephropathy, while hypouricemia is associated with worse metabolic control, hyperfiltration and a late onset or decreased progression to overt nephropathy.

Low HDL-cholesterol: a component of the metabolic syndrome only in the presence of fasting hypertriglyceridemia in type 2 diabetic patients.

The relation between isolated low HDL-cholesterol and the components of the metabolic syndrome is poorly known in type 2 diabetes. We evaluated cardiovascular risk parameters in type 2 diabetic patients with low HDL-cholesterol, compared to those with low HDL-cholesterol and hypertriglyceridemia, isolated hypertriglyceridemia and normal lipid parameters. Patients with low HDL-cholesterol/high triglycerides had higher BMI (29.6 +/- 5.7 vs 27.9 +/- 4.4 or vs 28.1 +/- 5.2 kg/m(2) ), prevalence of obesity (69% vs 55% or vs 54%), higher levels of uric acid (339.0 +/- 83.3 vs 303.3 +/- 95.2 or vs 303.3 +/- 89.2 micromol/l) and C-peptide (0.76 +/- 0.40 vs 0.63 +/- 0.33 or vs 0.63 +/- 0.36 nmol/l) and number of components of the metabolic syndrome (27% patients with all the components) compared to patients with isolated low HDL-cholesterol or normal subjects, respectively. A similar pattern of values was evident in patients with isolated hypertriglyceridemia. With logistic regression analysis, BMI and uric acid levels were significantly associated with the presence of hypertriglyceridemia (both isolated or associated with low HDL-cholesterol), while patients with isolated low HDL-cholesterol and those without dyslipidemia displayed a similar more favourable metabolic pattern. These results indicate that low HDL-cholesterol is a component of the metabolic syndrome only in the presence of fasting hypertriglyceridemia in type 2 diabetic patients.

Influence of a familial history of diabetes on the clinical characteristics of patients with Type 2 diabetes mellitus.

AIMS: To evaluate the roles of maternal and paternal diabetes and diabetes in relatives other than parents on the clinical characteristics in Type 2 diabetes mellitus. METHODS: A total of 2,113 Type 2 diabetic patients were recruited, and those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately. RESULTS: The prevalence of diabetes in the mother, father and other relatives was 25.5, 6.5 and 21.2%, respectively. No difference in the clinical characteristics was found in patients with diabetes in the mother or father. Patients with parental diabetes were significantly younger, with higher LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis than those without familial diabetes; on multiple logistic regression, only age (P = 0.0003), age at diabetes diagnosis (P = 0.0014) (inverse association), and LDL-cholesterol (P = 0.030) remained significantly associated with parental diabetes. Patients with diabetic relatives other than parents displayed significantly higher total and LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis that those with no known diabetic relatives; on multiple logistic regression, only age at diabetes diagnosis was inversely associated with diabetes in relatives other than parents (P = 0.013). CONCLUSIONS: The data do not indicate a different influence of maternal and paternal diabetes on the clinical characteristics of Type 2 diabetic patients, while there is evidence that parental diabetes brings to an earlier onset of the disease and higher LDL-cholesterol values; the presence of diabetes in relatives other than parents constituted a small risk for earlier manifestation of the disease.

Relationship of residual beta-cell function, metabolic control and chronic complications in type 2 diabetes mellitus.

As the relationships between C-peptide levels and metabolic control and chronic complications are poorly known in type 2 diabetes, due to the slow decline of beta-cell function, we evaluated these associations in a cohort of type 2 diabetic patients. After excluding insulin-treated subjects, 1,533 patients were divided according to their C-peptide fasting levels in quartiles. Patients within the lowest C-peptide quartile showed significantly higher duration of diabetes, prevalence of retinopathy and values of HDL-cholesterol, albumin excretion rate and HbA1c, while BMI, diastolic blood pressure, percentages of hypertension and metabolic syndrome, and values of triglycerides and uric acid were significantly higher in the highest C-peptide quartile. The associations between C-peptide and duration of diabetes, AER, HbA1c, retinopathy and the components of the metabolic syndrome remained significant, after multiple adjustments. In conclusion, these data support the hypothesis that a reduced insulin secretion is associated with a longer duration of diabetes and a greater prevalence of microvascular complications, while higher insulin levels are associated with the components of the metabolic syndrome.

Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy.

Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors in poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (> 20 micrograms/min) or normal albumin excretion rate (< 20 micrograms/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7 +/- 1.2 vs 3.4 +/- 0.6 micrograms/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.