3: Preventing complications of diabetes

Bate, Katherine; Jerums, George

doi:10.5694/j.1326-5377.2003.tb05655.x

Cited by 71 publications

(46 citation statements)

References 27 publications

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“…The drop in blood pressure and the rise in HDL cholesterol level with SGLT2 inhibitor therapy could even make SGLT2 inhibitors more promising. This is because; in patients with type 2 diabetes the major cause of morbidity and mortality is attributed to cardiovascular diseases [4,37]. But SGLT2 inhibitors long term effects on cardiovascular outcomes is uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Microvascular complications like diabetic retinopathy, nephropathy, and neuropathy are major causes of new cases of blindness and renal insufficiency [3]. Moreover, in type 2 diabetes macrovascular complications, including coronary heart disease and stroke, are major causes of morbidity and mortality [4]. According to a prospective study, in patients with type 2 diabetes, a 1% increase in HbA1c was associated with 20% to 30% increase in mortality or cardiovascular events [5].…”

Section: Introductionmentioning

confidence: 99%

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Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Berhan

Barker

2013

BMC Endocr Disord

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BackgroundThe discovery of sodium-glucose co-transporter 2 (SGLT2) inhibitors, with a novel mechanism independent of insulin secretion or sensitization, bring about a new therapeutic approach to the management of type 2 diabetes mellitus. The aim of this meta-analysis was to evaluate the safety and efficacy of SGLT2 inhibitors at different doses in randomized double blind clinical trials.MethodsThis meta-analysis was conducted by including randomized double-blind controlled trials of SGLT2 inhibitors in patients with type 2 diabetes irrespective of their antidiabetic drug exposure history but with an inadequate glycemic control. All the effect sizes were computed using the random effects model. Standardized mean differences (SMDs) and odds ratios (OR) were computed for continuous and dichotomous variables, respectively. Additional analyses like sensitivity analysis, subgroup analysis and meta-regression were also performed.ResultsThe pooled analyses demonstrated a significant reduction in mean changes in Hemoglobin A1c (HbA1c) (SMD = −0.78%, 95% CI, -0.87 to −0.69), fasting plasma glucose (FPG) (SMD = −0.70 mg/dl, 95% CI, -0.79 to −0.61), body weight (overall SMD = −0.59 kg, 95% CI, -0.65 to −0.52) and blood pressure from baseline with SGLT2 inhibitors based therapy. Consistently a significant number of patients treated with SGLT2 inhibitors achieved HbA1c < 7% (OR = 2.09, 95% CI, 1.77 to 2.46). SGLT2 inhibitors based therapy was associated with adverse events like genital and urinary tract infections.ConclusionAll studied doses of SGLT2 inhibitors, either as monotherapy or in combination with other antidiabetic agents, consistently improved glycemic control in patients with type 2 diabetes. However, a small percentage of patients suffer from genital and urinary tract infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Berhan

Barker

2013

BMC Endocr Disord

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“…Cardiovascular disease (CVD) is a major complication and the leading cause of premature death among patients with diabetes (Centers for Disease Control and Prevention, 1999). The primary risk factor for CVD among patients with type 1 diabetes is hyperglycemia, although other risk factors, such as hypertension and dyslipidemia, may occur secondary to uncontrolled hyperglycemia (Bate & Jerums, 2003). In contrast, the pathophysiology of cardiovascular complications of type 2 diabetes involves elements of hyperglycemia, dyslipidemia, hypertension, and obesity.…”

Section: Introductionmentioning

confidence: 99%

Hypolipidemic effect of Salicornia herbacea in animal model of type 2 diabetes mellitus

Hwang

Lee

et al. 2007

Nutr Res Pract

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To control blood glucose level as close to normal is a major goal of treatment of diabetes mellitus. Hyperglycemia and hyperlipidemia are the major risk factors for cardiovascular complications, the major cause of immature death among the patients with type 2 diabetes. The purpose of this study is to determine the hypoglycemic and hypolipidemic effects of Salicornia herbacea in animal model of type 2 diabetes and to investigate the possible mechanisms for the beneficial effects of S. herbacea. S. herbacea was extracted with 70% ethanol and desalted with 100% ethanol. Three week-old db/db mice (C57BL/KsJ, n=16) were fed AIN-93G semipurified diet or diet containing 1% desalted ethanol extract of S. herbacea for 6 weeks after 1 week of adaptation. Fasting plasma glucose, triglyceride, and total cholesterol were measured by enzymatic methods and blood glycated hemoglobin (HbA1C) by the chromatographic method. Body weight and food intake of S. herbacea group were not significantly different from those of the control group. Fasting plasma glucose and blood glycated hemoglobin levels tended to be lowered by S. herbacea treatment. Consumption of S. herbacea extract significantly decreased plasma triglyceride and cholesterol levels (p<0.05). The inhibition of S. herbacea extract against yeast α-glucosidase was 31.9% of that of acarbose at the concentration of 0.5 mg/mL in vitro. The inhibitory activity of ethanol extract of S. herbacea against porcine pancreatic lipase was 59.0% of that of orlistat at the concentration of 0.25 mg/mL in vitro. Thus, these results suggest that S. herbacea could be effective in controlling hyperlipidemia by inhibition of pancreatic lipase in animal model of type 2 diabetes.

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“…Likewise, we have shown that Tst (in adrenal) and Trak2 (skeletal muscle) transcript levels correlate with traits associated with fat metabolism and colocalize with pQTLs for lipid level and body weight, while Hpx (adrenal) and Pex11b (fat) represent c3-eQTLs relating to blood sugar regulation and traits recognized as downstream consequences of abnormal blood sugar regulation (4, 10, 55, 64) (Supplementary Table S6). These c3-eQTLs are particularly striking given that they also occur in tissues that are physiologically relevant for the control of these traits, suggesting that they represent strong candidate genes underlying these phenotypes in the SHR.…”

Section: Discussionmentioning

confidence: 83%

Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat

Morrissey

Grieve

Heinig

et al. 2011

Physiological Genomics

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The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. Quantitative trait transcript (QTT) analysis in the RI strains showed highly significant correlation between cis-eQTL transcript abundance and clinically relevant traits such as systolic blood pressure and blood glucose, with the physical location of a subset of the cis-eQTLs colocalizing with “physiological” QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain. These findings provide a basis for the functional testing and ultimate elucidation of the molecular basis of these metabolic and cardiovascular phenotypes.

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3: Preventing complications of diabetes

Cited by 71 publications

References 27 publications

Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Hypolipidemic effect of Salicornia herbacea in animal model of type 2 diabetes mellitus

Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat

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