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AIMS: This study aimed to investigate whether the response to adding metformin to insulin in young adults with type 1 diabetes (T1D) differs according to weight phenotype and insulin sensitivity index. METHODS: A prospective pilot study was conducted over 26 weeks in which insulin plus metformin (2 g/day) was administered to 35 individuals, ranging from normal weight (NW) to overweight (OW) to obese (OB) T1D individuals, to correlate insulin sensitivity indices and other clinical variables. RESULTS: At the end of the follow-up period, all groups showed an increase in the eGDR (NW: 7.37 vs 8.16, p = 0.002; OW: 7.28 vs 8.24, p < 0.001; OB: 6.33 vs 7.52 p < 0.001). KITT and SEARCH SCORE improved only in the OB group (2.15 vs 3.14, p < 0.001 and 5.26 vs 5.72, p = 0.007, respectively). Furthermore, HbA1c and BMI were significantly greater in the OB group (- 0.62%, p < 0.001; - 1.12 kg/m2, p = 0.031, respectively). Regression analysis revealed that the serum levels of triglycerides and uric acid were significantly (0.059, p = 0.013; 0.076, p = 0.001) associated with insulin sensitivity indices. CONCLUSIONS: The study showed that eGDR improved independently of basal weight after metformin treatment. However, the KITT and SEARCH indices improved only in the obese group. Triglycerides and uric acid are associated with insulin sensitivity indices. These results highlight the heterogeneity of the mechanisms underlying insulin resistance and its response to metformin in individuals with T1D.
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BACKGROUND: Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes. METHODS: Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2-5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D). RESULTS: During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death. CONCLUSIONS: Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.