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Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus

Antonino Catalano, Basilio Pintaudi, Nancy Morabito, Giacoma Di Vieste, Loretta Giunta, Maria Lucia Bruno, Domenico Cucinotta, Antonino Lasco, and Antonino Di Benedetto

Background

Sclerostin is an osteocyte-derived inhibitor of the Wnt/β-catenin signaling pathway, which acts as a negative regulator of bone formation. Published data on sclerostin levels in type 1 diabetes mellitus (T1DM) are few.

Objective

To evaluate gender differences in sclerostin serum levels and the association among sclerostin, bone mass, bone metabolism, and the main clinical characteristics of subjects with T1DM.

Design and methods

A total of 69 patients with T1DM (mean age, 33.7±8.1; 49% males) were enrolled in this cross-sectional study in a clinical research center. Bone mineral density was measured by phalangeal quantitative ultrasound (QUS); bone turnover markers (urinary pyridinoline, deoxypyridinoline (D-PYR), and urine hydroxyproline (OH-PRO) to evaluate bone resorption; serum bone alkaline phosphatase and BGP to evaluate bone formation) and sclerostin were assessed.

Results

D-PYR and sclerostin were significantly higher in women when compared with men (P=0.04). A disease duration >15 years was associated with higher sclerostin levels (P=0.03). Bone turnover markers and QUS parameters were not correlated with sclerostin. A significant negative correlation was observed among QUS parameters, BMI, and OH-PRO. Sclerostin serum levels were correlated with homocysteine (r=−0.34, P=0.005) and vitamin B12 (r=−0.31, P=0.02). Generalized linear model showed that macroangiopathy was the only predictor of sclerostin serum levels (β=−11.8, 95% CI from −21.9 to −1.7; P=0.02).

Conclusions

Our data demonstrate that women with T1DM exhibit higher sclerostin levels than men and that circulating sclerostin is not associated with bone turnover markers and phalangeal QUS measurements. Macroangiopathy was associated with sclerostin levels.

Restricted access

No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study

Domenico Cucinotta, Filippo De Luca, Alfonso Gigante, Teresa Arrigo, Antonino Di Benedetto, Antonino Tedeschi, Fortunato Lombardo, Giacomo Romano, and Concetta Sferlazzas

Cucinotta D, De Luca F, Gigante A, Arrigo T, Di Benedetto A, Tedeschi A, Lombardo F, Romano G, Sferlazzas C. No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study. Eur J Endocrinol 1994;130:253–8. ISSN 0804–4643

Plasma glucose and insulin responses to oral glucose and insulin sensitivity by the euglycemic hyperinsulinemic clamp technique were investigated in 30 cystic fibrosis patients with normal fasting blood glucose levels and normal (N = 12), impaired (N = 12) or diabetic (N = 6) glucose tolerance, and in 12 control subjects. In a subgroup of 10 cystic fibrosis patients with non-diabetic glucose tolerance both oral glucose tolerance test and clamp were performed again 48–52 months later. Following oral glucose, glycemic responses were higher in cystic fibrosis patients than in controls, whereas insulin responses were reduced significantly only in the patients with diabetic glucose tolerance. Insulin sensitivity did not differ significantly in the patient subgroups with different degrees of glucose tolerance and in controls. In the 10 patients who underwent a 4-year follow-up, insulin responses to oral glucose decreased significantly, whilst insulin sensitivity did not change substantially. Insulin sensitivity persisted unmodified even in the patients with deteriorating glucose tolerance. No correlations were observed between metabolic data and clinical status of patients. In conclusion, in cystic fibrosis subjects with fasting euglycemia and different degrees of glucose tolerance: (i) insulin sensitivity is not impaired; (ii) eventual changes of glucose tolerance over time are not associated with modifications of insulin sensitivity; (iii) insulin secretion deteriorates over time even in the patients with stable glucose tolerance; (iv) eventual deterioration of both glucose tolerance and insulin secretion is not linked to a worsening of either nutritional or clinical parameters.

F De Luca, Istituto di Clinica Pediatrica, Policlinico Universitario, 98100 Messina, Italy

Free access

Improvement of selective screening strategy for gestational diabetes through a more accurate definition of high-risk groups

Basilio Pintaudi, Giacoma Di Vieste, Francesco Corrado, Giuseppe Lucisano, Fabio Pellegrini, Loretta Giunta, Antonio Nicolucci, Rosario D'Anna, and Antonino Di Benedetto

Objective

This study aimed to assess the predictive value of risk factors (RFs) for gestational diabetes mellitus (GDM) established by selective screening (SS) and to identify subgroups of women at a higher risk of developing GDM.

Design

A retrospective, single-center study design was employed.

Methods

Data of 1015 women screened for GDM at 24–28 weeks of gestation and diagnosed according to the International Association of Diabetes and Pregnancy Study Groups criteria were evaluated. Information on RFs established by SS was also collected and their association with GDM was determined. To identify distinct and homogeneous subgroups of patients at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used.

Results

Overall, 113 (11.1%) women were diagnosed as having GDM. The application of the SS criteria would result in the execution of an oral glucose tolerance test (OGTT) in 58.3% of women and 26 (23.0%) cases of GDM would not be detected due to the absence of any RF. The RECPAM analysis identified high-risk subgroups characterized by fasting plasma glucose values >5.1 mmol/l (odds ratio (OR)=26.5; 95% CI 14.3–49.0) and pre-pregnancy BMI (OR=7.0; 95% CI 3.9–12.8 for overweight women). In a final logistic model including RECPAM classes, previous macrosomia (OR=3.6; 95% CI 1.1–11.6), and family history of diabetes (OR=1.8; 95% CI 1.1–2.8), but not maternal age, were also found to be associated with an increased risk of developing GDM. A screening approach based on the RECPAM model would reduce by over 50% (23.0 vs 10.6%) the number of undiagnosed GDM cases when compared with the current SS approach, at the expense of 50 additional OGTTs required.

Conclusions

A screening approach based on our RECPAM model results in a significant reduction in the number of undetected GDM cases compared with the current SS procedure.

Restricted access

Metabolic and clinical events preceding diabetes mellitus onset in cystic fibrosis

Domenico Cucinotta, Teresa Arrigo, Filippo De Luca, Antonino Di Benedetto, Fortunato Lombardo, Riccardo Scoglio, Concetta Sferlazzas, and Giuseppe Magazzú

Cucinotta D, Arrigo T, De Luca F, Di Benedetto A, Lombardo F, Scoglio R, Sferlazzas C, Magazzú G. Metabolic and clinical events preceding diabetes mellitus onset in cystic fibrosis. Eur J Endocrinol 1996;134:731–6. ISSN 0804–4643

Serial assessments of glucose tolerance, of glucose and insulin areas during an oral glucose tolerance test (OGTT) and of clinical parameters as well were evaluated retrospectively in seven diabetic cystic fibrosis patients (study group) during the 4–6.3 years that preceded diabetes mellitus diagnosis. The same metabolic and clinical parameters were also evaluated in seven age-matched patients who did not develop diabetes during a similar observation period (control group). In the study group, glucose tolerance was impaired in all patients but one since the first OGTT and glucose areas progressively increased over time, whereas in the control group glucose tolerance remained stable during the whole observation period. A significant and progressive blunting of insulin secretion occurred over time in both groups. Insulin secretion, however, was reduced but not exhausted at diabetes diagnosis. Neither modification of glycosylated haemoglobin levels over time nor serum islet cell antibodies at diabetes onset were observed in the study group. The overall clinical course of the disease was not different in either group and remained stable during the observation period. These results indicate that in cystic fibrosis diabetes mellitus onset is preceded by a long-standing deterioration of glucose tolerance, whilst insulin secretion progressively declines over time, irrespectively of glucose tolerance status. The prediabetic worsening of glucose tolerance is not necessarily linked to a worsening of overall clinical status.

Filippo De Luca, Istituto di Clinica Pediatrica, Policlinico Universitario, 98100 Messina, Italy