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Objective: Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites.Research Design and Methods: We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer.Results: We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001).Conclusions: Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective: Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion. However, GLP-1 also improves endothelial function in diabetes.Research Design and Methods: Sixteen type 2 diabetic patients and 12 control subjects received a meal, an oral glucose tolerance test (OGTT), and two hyperglycemic clamps, with or without GLP-1. The clamps were repeated in diabetic patients after 2 months of strict glycemic control.Results: During the meal, glycemia, nitrotyrosine, and plasma 8-iso prostaglandin F2α (8-iso-PGF2a) remained unchanged in the control subjects, whereas they increased in diabetic patients. Flow-mediated vasodilation (FMD) decreased in diabetes, whereas GLP-1 increased in both groups. During the OGTT, an increase in glycemia, nitrotyrosine, and 8-iso-PGF2a and a decrease in FMD were observed at 1 h in the control subjects and at 1 and 2 h in the diabetic patients. In the same way, GLP-1 increased in both groups at the same levels of the meal. During the clamps, in both the control subjects and the diabetic patients, a significant increase in nitrotyrosine and 8-iso-PGF2a and a decrease in FMD were observed, effects that were significantly reduced by GLP-1. After improved glycemic control, hyperglycemia during the clamps was less effective in producing oxidative stress and endothelial dysfunction and the GLP-1 administration was most effective in reducing these effects.Conclusions: Our data suggest that during the meal GLP-1 can simultaneously exert an incretin effect on insulin secretion and a protective effect on endothelial function, reasonably controlling oxidative stress generation. The ability of GLP-1 in protecting endothelial function seems to depend on the level of glycemia, a phenomenon already described for insulin secretion. [ABSTRACT FROM AUTHOR]

Objective: Insulin analogs are increasingly used in patients with type 2 diabetes. We compared the effect of basal, biphasic, prandial, and basal-bolus insulin regimens with insulin analogs to reach the hemoglobin A(1c) (HbA(1c)) target of <7% in people with type 2 diabetes.Research Design and Methods: We conducted an electronic search for randomized controlled trials (RCTs) involving insulin analogs. RCTs were included if they lasted at least 12 weeks, reported the proportion of diabetic patients reaching the HbA(1c) target of <7% (primary outcome), and the number of patients in any arm was >30.Results: We found 16 RCTs, with 20 comparisons and 7,759 patients. A greater proportion of patients achieved the HbA(1c) goal of <7% with both biphasic (odds ratio 1.88 [95% CI 1.38-2.55]) and prandial (2.07 [1.16-3.69]) insulin compared with basal insulin; this was associated for biphasic insulin with greater hypoglycemia (event/patient/30 days, mean difference, 0.34 [range 0-0.69]) and weight gain in kg (1.0 kg [0.28-1.73]). Compared with biphasic insulin, the basal-bolus regimen was associated with a greater chance to reach the HbA(1c) goal (odds ratio 1.75 [95% CI 1.11-2.77]), with no greater hypoglycemia or weight gain. The effect of insulin analogs on long-term diabetes complications is still lacking.Conclusions: A greater proportion of type 2 diabetic patients can achieve the HbA(1c) goal <7% with biphasic or prandial insulin compared with basal insulin; in absolute terms, the basal-bolus regimen was best for the attainment of the HbA(1c) goal. [ABSTRACT FROM AUTHOR]

Objective: BEYOND trial evaluated the feasibility of either basal insulin plus glucagon-like peptide 1 receptor agonist (GLP-1RA) or basal insulin plus sodium-glucose cotransporter 2 inhibitor (SGLT2i) to replace a full basal-bolus insulin (BBI) regimen in participants with type 2 diabetes and inadequate glycemic control., Research Design and Methods: Participants were randomized (1:1:1) to: 1 ) intensification of the BBI regimen ( n = 101), 2 ) fixed ratio of basal insulin plus GLP-1RA (fixed-combo group; n = 102), and 3 ) combination of basal insulin plus SGLT2i (gliflo-combo group; n = 102). The primary efficacy outcome was change from baseline in HbA 1c at 6 months., Results: Baseline characteristics were similar among the three groups (mean HbA 1c was 8.6% [70 mmol/mol]). At 6 months, patients experienced similar reduction in HbA 1c level (-0.6 ± 0.8, -0.6 ± 0.8, and -0.7 ± 0.9%, mean ± SD, respectively; noninferiority P < 0.001 vs. BBI), and the proportion of patients with HbA 1c ≤7.5% was also similar (34%, 28%, and 27%, respectively; P = 0.489). Total insulin dose increased in the BBI group (62 units/day) and decreased both in the fixed-combo and gliflo-combo groups (27 units/day and 21 units/day, respectively; P < 0.01). The proportion of patients with hypoglycemia was 17.8%, 7.8%, and 5.9%, respectively ( P = 0.015). There were 12 dropouts in the fixed-combo group, 9 in the gliflo-combo group, and none in the BBI group., Conclusions: BEYOND provides evidence that it is possible and safe to switch from a BBI regimen to either a once-daily fixed-combo injection or once-daily gliflozin added to basal insulin, with similar glucose control, fewer insulin doses, fewer injections daily, and less hypoglycemia., (© 2021 by the American Diabetes Association.)

Background: Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes., Purpose: We performed a meta-analysis of randomized controlled trials (RCTs) comparing CGM with usual care for parameters of glycemic control in both type 1 and type 2 diabetes., Data Sources: Many electronic databases were searched for articles published from inception until 30 June 2019., Study Selection: We selected RCTs that assessed both changes in HbA 1c and time in target range (TIR), together with time below range (TBR), time above range (TAR), and glucose variability expressed as coefficient of variation (CV)., Data Extraction: Data were extracted from each trial by two investigators., Data Synthesis: All results were analyzed by a random effects model to calculate the weighted mean difference (WMD) with the 95% CI. We identified 15 RCTs, lasting 12-36 weeks and involving 2,461 patients. Compared with the usual care (overall data), CGM was associated with modest reduction in HbA 1c (WMD -0.17%, 95% CI -0.29 to -0.06, I 2 = 96.2%), increase in TIR (WMD 70.74 min, 95% CI 46.73-94.76, I 2 = 66.3%), and lower TAR, TBR, and CV, with heterogeneity between studies. The increase in TIR was significant and robust independently of diabetes type, method of insulin delivery, and reason for CGM use. In preplanned subgroup analyses, real-time CGM led to the higher improvement in mean HbA 1c (WMD -0.23%, 95% CI -0.36 to -0.10, P < 0.001), TIR (WMD 83.49 min, 95% CI 52.68-114.30, P < 0.001), and TAR, whereas both intermittently scanned CGM and sensor-augmented pump were associated with the greater decline in TBR., Limitations: Heterogeneity was high for most of the study outcomes; all studies were sponsored by industry, had short duration, and used an open-label design., Conclusions: CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes., (© 2020 by the American Diabetes Association.)

Objective: The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes., Research Design and Methods: We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA 1c , proportion of patients at HbA 1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI., Results: We identified 26 RCTs, lasting 12-52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA 1c (WMD = -0.47%, 95% CI -0.59 to -0.35), more patients at HbA 1c target (RR = 1.65, 95% CI 1.44-1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93-1.39) and a reduction in weight (WMD = -2.5 kg, 95% CI -3.3 to -1.7), with high heterogeneity ( I 2 > 89%, P < 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46-0.93) and reduced weight (WMD = -4.7 kg, 95% CI -6.9 to -2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA 1c WMD = -0.56%, 95% CI -0.72 to -0.40)., Conclusions: GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability., (© 2017 by the American Diabetes Association.)