Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women

Crespo, Carlos; Smit, Ellen; Snelling, Anastasia; Sempos, Christopher T.; Andersen, Ross E.

doi:10.2337/diacare.25.10.1675

Cited by 83 publications

(50 citation statements)

References 30 publications

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“…Similar to our results, previous studies of postmenopausal women with diabetes have shown that hormone use is associated with better glycemic control (22,(52)(53)(54)(55)(56). Although this could be a direct effect of hormone therapy on glucose metabolism (57,58), it could also reflect a "healthy user" effect because previous studies have shown that women taking hormone replacement therapy are more likely to have a higher education level, have better health status, and engage in health-promoting behaviors compared with women not taking hormones (59 -61).…”

Section: Multivariable Analysessupporting

confidence: 82%

Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes

et al. 2005

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OBJECTIVE -Glycemic control (HbA 1c [A1C]) is strongly associated with microvascular disease in individuals with diabetes, but its relation to macrovascular disease and atherosclerosis is less clear. This study examines the relationship between A1C, carotid intima-media thickness (IMT), and traditional cardiovascular risk factors in individuals with diabetes. RESEARCH DESIGN AND METHODS-A cross-sectional study of 2,060 people with diagnosed and undiagnosed (unrecognized) diabetes in the Atherosclerosis Risk in Communities study was performed.RESULTS -LDL and HDL cholesterol, plasma triglycerides, and waist-to-hip ratio were significantly associated with A1C after multivariable adjustment. African Americans with undiagnosed and diagnosed diabetes had significantly elevated A1C values compared with whites, even after adjustment for potentially confounding factors. There was a graded association between A1C and carotid IMT. In a fully adjusted model in individuals with undiagnosed diabetes, the odds ratio (OR) of being in the highest quartile of IMT versus the lowest was 2.46 (95% CI 1.16 -5.03, comparing the highest quartile of A1C to the lowest). In people with diagnosed diabetes, the comparable OR was 2.62 (1.36 -5.06).CONCLUSIONS -This study identified several important associations between A1C and known risk factors for cardiovascular disease and suggested that A1C is independently related to carotid IMT. Chronically elevated glucose levels may contribute to the development of atherosclerosis in people with diabetes, independent of other risk factors. Diabetes Care 28:1965-1973, 2005R ecent estimates suggest that there are ϳ18 million individuals with diabetes in the U.S., affecting ϳ9% of the total adult population (1). Glycemic control is a focus of clinical treatment of diabetes. HbA 1c (A1C), a measure of long-term glycemic control, is used to monitor and guide clinical treatment in individuals with diabetes. Elevated A1C levels are strongly associated with diabetes-related microvascular disease (2-4), but whether A1C is independently associated with the progression of atherosclerosis (5) and cardiovascular events (6) in individuals with diabetes remains controversial.The U.K. Prospective Diabetes Study (UKPDS) showed an overall 25% reduction (P ϭ 0.0099) in the risk of microvascular disease end points in the intensively treated group (median A1C ϭ 7.0%) compared with the conventionally treated group (7.9%) after 10 years of follow-up (2). There is some evidence from epidemiologic studies that similar reductions in A1C may also reduce the risk of cardiovascular disease in people with diabetes (6,7). In the UKPDS trial, there was a 16% reduction (P ϭ 0.052) in myocardial infarction observed for the intensively treated group compared with the conventionally treated group. Although the findings were only of borderline statistical significance, the UKPDS provided intriguing evidence of glycemic control as a possible modifiable risk factor for coronary heart disease.Few studies have explicitly examined the asso...

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Section: Multivariable Analysessupporting

confidence: 82%

Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes

et al. 2005

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“…In small trials of postmenopausal women with diabetes, estrogen has been associated with lower levels of HbA 1c (27,28), fasting glucose, and insulin (23); improved insulin sensitivity (27); and decreased hyperandrogenicity (23). In large observational cohort studies of women with diabetes, estrogen with or without progestin has been associated with lower HbA 1c concentrations (29,30) and lower fasting glucose levels (30). However, one small crossover study found no effects of either transdermal or oral estrogen on these parameters among women with type 2 diabetes (31).…”

Section: Discussionmentioning

confidence: 99%

Estrogen Therapy and Risk of Cardiovascular Events Among Women With Type 2 Diabetes

et al. 2003

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OBJECTIVE -To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes. RESEARCH DESIGN AND METHODS-A retrospective, case-cohort study was conducted among 6,017 women aged 45-80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n ϭ 215), coronary revascularization (n ϭ 253), and cardiovascular deaths (n ϭ 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a timedependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses.RESULTS -Current use of estrogen with (RR 0.43, 95% CI 0.22-0.85) or without (0.48, 0.30 -0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of Ͻ25 months' duration (1.12, 0.49 -2.54), first episode of use Ն25 months' duration (0.32, 0.06 -1.70), and current use that was not the first episode of use (0.42, 0.42-0.67) indicated that recent initiation was not associated with an increase or decrease in risk.CONCLUSIONS -These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.

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“…Changes in environment and lifestyle have escalated the rates of type 2 diabetes and obesity (Zimmet et al 2005). Estrogen deficiency in postmenopausal women contributes to the development of visceral obesity, insulin resistance and the risk of developing type 2 diabetes (Louet et al 2004), while treatment with 17b-estradiol (E 2 ) or conjugated equine estrogens improves insulin sensitivity and lowers blood glucose levels (Espeland et al 1998, Crespo et al 2002, Saglam et al 2002. Results from the Women's Health Initiative study showed a reduced incidence of diabetes in postmenopausal women on hormone replacement therapy or after estrogen treatment alone (Margolis et al 2004, Bonds et al 2006.…”

Section: Introductionmentioning

confidence: 99%

The estrogen receptor α-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms

Lundholm

Bryzgalova

Gao

et al. 2008

Journal of Endocrinology

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The aim of this study was to validate the role of estrogen receptor a (ERa) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERa-selective agonist propyl pyrazole triol (PPT) or 17b-estradiol (E 2 ) in ob/ob mice. Female ob/ob mice were treated with PPT, E 2 or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPTand E 2 treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E 2 treatment. However, PPT and E 2 had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E 2 treatment. In the liver, treatment with E 2 and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPTexerts anti-diabetic effects, and these effects are mediated via ERa.

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Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women

Cited by 83 publications

References 30 publications

Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes

Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes

Estrogen Therapy and Risk of Cardiovascular Events Among Women With Type 2 Diabetes

The estrogen receptor α-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms

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