Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia.

OBJECTIVE: Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. DESIGN: Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes. METHODS: Clinical, biochemical, radiological and treatment data were collected. We established a prediction model for the identification of FHH-positive cases by logistic regression analysis and area under the ROC curve (AUROC) was estimated. RESULTS: We included 66 index cases, of which 30 (45.5%) had a pathogenic variant. FHH-positive cases were younger (p = 0.029), reported more frequently a positive family history (p < 0.001), presented higher magnesium (p < 0.001) and lower parathormone levels (p < 0.001) and were less often treated for hypercalcemia (p = 0.017) in comparison to FHH-negative cases. Magnesium levels showed the highest AUROC (0.825, 95%CI: 0.709-0.941). The multivariate analysis revealed that family history and magnesium levels were independent predictors of a positive genetic result. The predictive model showed an AUROC of 0.909 (95%CI: 0.826-0.991). CONCLUSIONS: The combination of magnesium and a positive family history offered a good diagnostic accuracy to predict a positive genetic result. Therefore, the inclusion of magnesium measurement in the routine evaluation of patients with suspected FHH might provide insight into the identification of a positive genetic result of any of the CaSR-related genes.

Glucocorticoid-induced hyperglycemia.

Corticosteroid-induced hyperglycemia is a common medical problem that can lead to frequent emergency room visits, hospital admissions and prolonged hospital stay, in addition to the well known morbidity associated with hyperglycemia. However, the diagnosis and treatment of corticosteroid-induced hyperglycemia is surprisingly undervalued by most professionals, probably because of the lack of quality studies to determine specific strategies of action. In the present review, we discuss the pathophysiology of corticosteroid-induced hyperglycemia, focusing on diverse patterns of hyperglycemia induced by the different formulations, and provide clues for diagnosis based on the duration of treatment and the administration schedule of corticosteroids. We propose a treatment strategy based on both the pathophysiology of the process and the mechanism of action of different corticosteroids, and take into account dosing and administration timing to predict the duration of therapy. Finally, we propose treatment goals that differ slightly between the transient and continuous use of corticosteroids based on evidence from clinical practice guidelines of diabetes care both in ambulatory and hospital settings.

Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin Infusion (CSII) Until Optimization of Glycemic Control.

The aim was to evaluate changes in insulin requirements from onset of continuous subcutaneous insulin infusion (CSII) until glucose optimization in type 1 diabetes and to determine patient characteristics to be considered when CSII is implemented. We retrospectively analyzed 74 type 1 diabetic patients over a follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c levels at the end of follow-up were excluded. We compared total daily doses (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI), diabetes duration, and indication for CSII. At follow-up, HbA1c decreased by 0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate was 60% of total basal rate. Insulin requirements were higher in males and in obese patients. Female patients and patients with longer diabetes duration showed a higher percentage of basal insulin. The number of basal segments was 4.9 ± 2.9. Basal requirements were higher in the second half of the nocturnal period. The dawn phenomenon was more relevant in men. Improvements in glycemic control were more marked in younger patients, in patients with higher HbA1c, in patients using more basal segments, and in patients initiating CSII for glucose control before pregnancy. Sex, diabetes duration, and BMI should be considered when initiating CSII. Our findings may help clinicians in clinical decision making regarding CSII therapy.

Glycemic control and perinatal outcomes of pregnancies complicated by type 1 diabetes: influence of continuous subcutaneous insulin infusion and lispro insulin.

AIMS: This study compared glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes mellitus (T1DM) treated with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) using regular (RI) or lispro (LP) insulin. METHODS: Three hundred fifteen consecutive singleton pregnancies of T1DM women using the same insulin program since before pregnancy (196 MDI with NPH + RI, 16 MDI with NPH + LP, 44 CSII with RI, 59 CSII with LP) were studied. Variables of glycemic control assessed included glycated hemoglobin, mean blood glucose (MBG), and insulin doses in each trimester, diabetic ketoacidosis, and hypoglycemic comas. Variables of pregnancy outcome included miscarriage, preterm birth, large or small for gestational age (LGA or SGA, respectively) newborns, and perinatal mortality. Multiple linear regression and logistic regression analysis were used. RESULTS: Groups differed in baseline and glycemic control but not in maternal or fetal outcomes. In multivariate analysis, LP was associated with higher second trimester MBG and lower rate of hypoglycemic coma, CSII with higher third trimester MBG, and CSII + LP with lower insulin requirements and lower rate of hypoglycemic coma. As to pregnancy outcomes, LP was associated with lower risk of preterm birth and higher risk of SGA, CSII with lower risk of SGA and higher risk of LGA and perinatal mortality, and CSII + LP with higher risk of miscarriage. CONCLUSIONS: Pregnant women with T1DM using LP and/or CSII had different characteristics. LP with or without CSII was independently associated with fewer hypoglycemic comas, whereas impact of LP/CSII on the fetus had a favorable or an unfavorable influence depending on the specific outcome.