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Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance).
Morales-Oyarvide, V, Yuan, C, Babic, A, Zhang, S, Niedzwiecki, D, Brand-Miller, JC, Sampson-Kent, L, Ye, X, Li, Y, Saltz, LB, et al
Journal of the National Cancer Institute. 2019;(2):170-179
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Abstract
BACKGROUND Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. METHODS We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.
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No disparity of the efficacy and all-cause mortality between Asian and non-Asian type 2 diabetes patients with sodium-glucose cotransporter 2 inhibitors treatment: A meta-analysis.
Cai, X, Gao, X, Yang, W, Chen, Y, Zhang, S, Zhou, L, Han, X, Ji, L
Journal of diabetes investigation. 2018;(4):850-861
Abstract
AIMS/INTRODUCTION To evaluate whether there is disparity of the efficacy and all-cause mortality and other adverse effects between Asian and non-Asian patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors treatment. MATERIALS AND METHODS Randomized clinical trials publicly available before January 2017, comparing SGLT2 inhibitors treatment with a placebo in type 2 diabetes patients were identified. The association between treatment and outcomes was estimated by computing the weighted mean difference for glycated hemoglobin level, blood pressure level, lipid profile levels and bodyweight, and the odds ratios for adverse events. RESULTS A total of 17 trials with Asian patients were included and 39 trials with non-Asian patients were included. Comparison of the glycated hemoglobin decreases corrected by a placebo between Asian and non-Asian patients showed that there was a non-significant difference of 0.05% between groups (P > 0.05). Comparisons of the bodyweight changes and blood pressure changes corrected by a placebo between Asian and non-Asian patients did not show a significant difference between groups (P > 0.05). The risk of all-cause mortality was not increased when compared with a placebo both in Asian and non-Asian populations, and the risk of genital infection in Asian and non-Asian populations were both significant increased. CONCLUSIONS Overall, according to the present meta-analysis, comparison of the efficacy in SGLT2 inhibitors treatment between Asian and non-Asian type 2 diabetes patients showed no significant difference in glycated hemoglobin reduction and bodyweight reduction. Furthermore, no disparity was found in the risk of all-cause mortality or hypoglycemia in SGLT2 inhibitors treatment between Asian and non-Asian patients.
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Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes.
Cusi, K, Sanyal, AJ, Zhang, S, Hoogwerf, BJ, Chang, AM, Jacober, SJ, Bue-Valleskey, JM, Higdon, AN, Bastyr, EJ, Haupt, A, et al
Diabetes, obesity & metabolism. 2016;:50-58
Abstract
AIMS: To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D). MATERIALS AND METHODS Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naïve T2D patients and 163 T2D patients previously treated with basal insulin. RESULTS Alanine aminotransferase (ALT) increased in patients treated with BIL, was higher than in glargine-treated patients at 4-78 weeks (difference at 52 weeks in both T1D and T2D: 7 international units/litre (IU/L), P < .001), and decreased after discontinuation of BIL. More BIL patients had ALT ≥3× upper limit of normal (ULN) than glargine. No patient had ALT ≥3× ULN with bilirubin ≥2× ULN that was considered causally related to BIL. In insulin-naїve T2D patients, LFC decreased with glargine but was unchanged with BIL. In T1D and T2D patients previously treated with basal insulin, LFC was unchanged with glargine but increased with BIL. In all three populations, LFC was higher after treatment with BIL vs glargine (difference at 52 weeks: 2.2% to 5.3%, all P < .01). CONCLUSIONS Compared to glargine, patients treated with BIL had higher ALT and LFC at 52-78 weeks. No severe drug-induced liver injury was apparent with BIL treatment for up to 78 weeks.
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Empagliflozin/metformin fixed-dose combination: a review in patients with type 2 diabetes.
Hu, J, Zou, P, Zhang, S, Zhou, M, Tan, X
Expert opinion on pharmacotherapy. 2016;(18):2471-2477
Abstract
Most patients with type 2 diabetes, who receive monotherapy, are unable to maintain glucose levels with the progress of disease. Therefore, combination therapy with two or more anti-diabetic agents of different classes is highly desired. Sodium glucose co-transporter 2 (SGLT2) inhibitors improve glycemic control through increasing urinary glucose excretion, which is independent of β-cell function. In addition, they are generally well tolerated and associated with a low risk of hypoglycaemia. SGLT2 inhibitors as add-on therapy to metformin have an additive effect on glycemic control in patients with type 2 diabetes, and fixed-dose tablet is likely to reduce pill burden and then improve patients' adherence. Areas covered: This article reviews empagliflozin/metformin combination therapy for the treatment of type 2 diabetes. The clinical efficacy and tolerability of empagliflozin/metformin in patients with type 2 diabetes are discussed based on the available literature. Expert opinion: It was found that empagliflozin/metformin combination therapy could significantly improve glycemic control, body weight and blood pressure with a low risk of hypoglycaemia. In addition, the empagliflozin/metformin fixed-dose tablets, supported by bioequivalence studies, could reduce pill burden to further achieve the improved patients' adherence, better glycemic control and optimized cost-effectiveness.
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Metformin and carbohydrate-modified diet: a novel obesity treatment protocol: preliminary findings from a case series of nondiabetic women with midlife weight gain and hyperinsulinemia.
Mogul, HR, Peterson, SJ, Weinstein, BI, Zhang, S, Southren, AL
Heart disease (Hagerstown, Md.). 2001;(5):285-92
Abstract
The authors conducted a retrospective analysis of a new obesity treatment protocol, metformin and hypocaloric, carbohydrate-modified diet, in high-risk, nondiabetic hyperinsulinemic women with progressive midlife weight gain (refractory to diet and exercise). Thirty consecutive nondiabetic women with glucose-mediated area-under-the-curve (AUC) insulin elevations (>or=100 microU/mL) in two body mass index (BMI) categories (group I: 25 to 32.9 kg/m(2) and group II: 33 to 41.7 kg/m(2)) participated in a 1-year treatment program of metformin (mean daily doses of 1,500 mg/day [group I] and 2,000 mg/day [group II]) and carbohydrate-modified dietary regimens. Follow-up body weight (at 3, 6, and 12 months), percentage of patients meeting goal weight attainment (10% reduction in body weight or BMI normalization), and fasting insulin levels (as available) are reported in 26 women (18/18 in group I and 8/12 in group II) who returned for one or more follow-up visits. Significant weight loss was observed at 3, 6, and 12 months in both group I (3.47 [SE 0.68], 6.41 [0.72], and 8.06 [0.96] kg, P < 0.0001) and group II (4.4 [0.8], 9.7 [2.3], 15.1 [3.3], P = 0.001, 0.004, 0.011). Twenty-five of 26 (96%) patients lost >or=5% of their body weight at 6 months and 21/26 (81%) patients lost >or=10% of their body weight at 12 months. Posttreatment fasting insulin decrement (-35.5 [8.2]%) was the most significant predictor of 1-year weight loss (R(2)=0.656, regression coefficient = 0.810, P = 0.005). Following completion of the 1-year intervention study, weight stabilization (within 1 kg) was observed at a 6-month surveillance in 8/9 patients who attained goal weight and continued metformin without additional nutritional counseling, in contrast to weight gain (>or=4 kg or 50% of lost weight) in 5/6 patients who discontinued metformin. The authors concluded that metformin and carbohydrate-modified hypocaloric diet could be an effective novel treatment for long-term weight management in nondiabetic, hyperinsulinemic women.