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1.
Org Biomol Chem ; 21(34): 6940-6948, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37581278

ABSTRACT

A common protocol for enantioselective alkynylation of isatins and isatin-derived ketimines using terminal alkynes and Me2Zn in the presence of a catalytic amount of a chiral perhydro-1,3-benzoxazine with moderate to excellent enantioselectivity under mild reaction conditions is described. The additions to ketimines present a novel approach to chiral amines being derivatives of oxindoles. The reaction is broad in scope with respect to aryl- and alkyl-substituted terminal alkynes and isatin derivatives. In isatins, the alkynylation occurs at the Si face of the carbonyl group, whereas in the ketimine derivatives it occurs at the Re face of the imine.

2.
Endocr Pract ; 26(6): 604-611, 2020 Jun 02.
Article in English | MEDLINE | ID: mdl-32160049

ABSTRACT

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN. Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN. Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia. Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition. Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition.


Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Blood Glucose , Humans , Hypoglycemic Agents , Inpatients , Insulin , Insulin Glargine , Parenteral Nutrition, Total , Prospective Studies , Risk Factors
3.
Clin Nutr ; 39(2): 388-394, 2020 02.
Article in English | MEDLINE | ID: mdl-30930133

ABSTRACT

BACKGROUND: There is no established insulin regimen in T2DM patients receiving parenteral nutrition. AIMS: To compare the effectiveness (metabolic control) and safety of two insulin regimens in patients with diabetes receiving TPN. DESIGN: Prospective, open-label, multicenter, clinical trial on adult inpatients with type 2 diabetes on a non-critical setting with indication for TPN. Patients were randomized on one of these two regimens: 100% of RI on TPN or 50% of Regular insulin added to TPN bag and 50% subcutaneous GI. Data were analyzed according to intention-to-treat principle. RESULTS: 81 patients were on RI and 80 on GI. No differences were observed in neither average total daily dose of insulin, programmed or correction, nor in capillary mean blood glucose during TPN infusion (165.3 ± 35.4 in RI vs 172.5 ± 43.6 mg/dL in GI; p = 0.25). Mean capillary glucose was significantly lower in the GI group within two days after TPN interruption (160.3 ± 45.1 in RI vs 141.7 ± 43.8 mg/dL in GI; p = 0.024). The percentage of capillary glucose above 180 mg/dL was similar in both groups. The rate of capillary glucose ≤70 mg/dL, the number of hypoglycemic episodes per 100 days of TPN, and the percentage of patients with non-severe hypoglycemia were significantly higher on GI group. No severe hypoglycemia was detected. No differences were observed in length of stay, infectious complications, or hospital mortality. CONCLUSION: Effectiveness of both regimens was similar. GI group achieved better metabolic control after TPN interruption but non-severe hypoglycemia rate was higher in the GI group. CLINICAL TRIAL REGISTRY: This trial is registered at clinicaltrials.gov as NCT02706119.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin Glargine/therapeutic use , Insulin/therapeutic use , Parenteral Nutrition, Total/methods , Aged , Combined Modality Therapy , Female , Humans , Hypoglycemic Agents/administration & dosage , Injections, Subcutaneous , Insulin Glargine/administration & dosage , Male , Prospective Studies , Spain , Treatment Outcome
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