Menopause Int 2008;14:21-25
doi:10.1258/mi.2007.007032
© 2008 British Menopause Society
Metabolic syndrome and the menopause
Risto J Kaaja
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland
Correspondence: Risto J Kaaja, Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland. Email: risto.kaaja{at}huch.fi
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Summary
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The metabolic syndrome consists of a combination of risk factors
that include abdominal obesity, atherogenic dyslipidaemia, hypertension
and insulin resistance. It increases the risk of cardiovascular
disease and type 2 diabetes. The increased risk of cardiovascular
disease is higher in women than in men. The first manifestation
of metabolic syndrome may occur in pregnancy presenting as gestational
diabetes or preeclampsia. Both conditions are associated with
increased insulin resistance. Also metabolic syndrome is more
common in polycystic ovarian syndrome. It has been suggested
that there is a metabolic syndrome resulting from the menopause
due to estrogen deficiency, as many of the risk factors are
more prevalent in postmenopausal women. Also estrogen replacement
improves insulin sensitivity and reduces the risk of diabetes.
The key elements in managing the metabolic syndrome are weight
reduction, increasing physical activity and diet modification.
If blood pressure, lipid and glycaemic control are not achieved
through these interventions then pharmacological therapy will
be required.
Key Words: Cardiovascular disease • diabetes • insulin resistance • metabolic syndrome • obesity
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Introduction
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The metabolic syndrome is a combination of risk factors including
abdominal obesity, dyslipidaemia (elevated triglycerides (TG),
decreased high-density lipoprotein (HDL) cholesterol), glucose
intolerance and hypertension. As the concept of the syndrome
was proposed by Gerald Reaven in 1988,
1 these factors had been
investigated in various combinations for several decades. The
pathogenesis of the syndrome is complex and so far incompletely
understood, but obesity, sedentary lifestyle, dietary factors
and genetic factors are known to contribute and interact in
its development.
1–3 It is uncertain whether the starting
point is insulin resistance leading to obesity or vice versa.
Of note relatively small reductions in body weight may significantly
reduce abdominal adipose tissue and increase insulin sensitivity.
The most important effect of the metabolic syndrome is the increased
risk of cardiovascular disease and type 2 diabetes.
4–14
The following changes occur at or after the menopause: increased total cholesterol and TG, decreased HDL and HDL subfraction 2, increased low density lipoprotein, particularly in the small, dense subfraction, increased lipoprotein (Lp [a]), increased insulin resistance, decreased insulin secretion, decreased insulin elimination, increased android fat distribution, impaired vascular function, increased factor VII and fibrinogen and reduced sex-hormone binding globulin. Many of these changes will themselves have adverse effects on other metabolic risk factors. These changes have led to the concept of a distinct menopausal metabolic syndrome, which originates in estrogen deficiency.15 Estrogen replacement can diminish the expression of this syndrome. Studies undertaken in Europe and the USA show that metabolic syndrome is common, affecting 20–40% of women after the menopause depending on the various diagnostic criteria.16–18 This review will discuss the various different diagnostic criteria for metabolic syndrome, prevalence, risk of cardiovascular disease, effect of the menopause and estrogen replacement, and therapeutic interventions.
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Different diagnostic criteria of the metabolic syndrome
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In the past few years, several expert groups have developed
simple diagnostic criteria to be used in clinical practice to
identify people with the metabolic syndrome (
Box 1). These include
the World Health Organization,
19 the European Group for Study
of Insulin Resistance,
20 the Adult Treatment Panel III (ATP
III),
21 the American Association of Clinical Endocrinologists,
22 the International Diabetes Federation (IDF)
23 and the 2005 American
Heart Association and National Heart, Lung, Blood Institute
update of the ATP III criteria.
24 The various definitions exist
because of differing opinions on the thresholds that should
be used for specific criteria. Furthermore, there is a lack
of consensus on which components are fundamentally necessary
and most clinically relevant for diagnosis. For example, International
Diabetes Federation (IDF), and ATP III criteria differ on whether
an increased waist circumference is an essential criterion.
The IDF clinical definition thus makes the presence of abdominal
obesity necessary for diagnosis.
23 When this is present, two
additional factors are sufficient for diagnosis. IDF recognizes
and emphasizes ethnic differences in the correlation between
abdominal obesity and other metabolic syndrome risk factors.
For this reason, criteria of abdominal obesity are specified
by nationality or ethnicity based on best available population
estimates. For women of European origin (Europid), the IDF specified
threshold for abdominal obesity is a waist circumference
80
cm. These thresholds apply to Europids living in the USA as
well as Europe. For Asian populations, except for Japan, the
threshold is
80 cm and for Japanese women
90 cm. In contrast,
in ATP III, any three of the five criteria constitutes the diagnosis.
24 Thus, a joint statement by American Diabetes Association and
the European Association for the Study of Diabetes concluded
that ‘too much critically important information is missing
to warrant its designation as a "syndrome."’
25 All the
definitions, however, include a measure of central obesity,
glucose level, dyslipidaemia and hypertension and the thresholds
for some of the components vary by gender and ethnic group.
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Prevalence of the metabolic syndrome
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Estimates of the prevalence of the metabolic syndrome vary mainly
because the studies have been undertaken in different populations
using different diagnostic criteria.
26–32 The prevalence
of the metabolic syndrome increases with age especially after
the menopause.
18 In the Finnish population-based Health 2000
Survey, the prevalence of the metabolic syndrome in women aged
45 years and older was 40% with the ATP III criteria and 44%
with IDF definitions.
16 In another European population-based
cohort study including younger subjects (>30 years of age),
the prevalence of the metabolic syndrome was 19.7, 23.4, 28.5
and 34.1% according to WHO, ATP III 2001, ATP III 2005 and IDF
definitions, respectively.
17
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The metabolic syndrome and cardiovascular disease
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It has been estimated that 48% of coronary events in women can
be attributed to the metabolic syndrome.
33 The metabolic syndrome
is an important risk factor for cardiovascular disease incidence
and mortality, as well as all-cause mortality.
34 Analysis of
21 prospective studies found that individuals with the metabolic
syndrome, compared with those without, had an increased mortality
from all causes (relative risk [RR] 1.35; 95% confidence interval
[CI], 1.17–1.56) and cardiovascular disease (RR, 1.74;
95% CI, 1.29–2.35); as well as an increased incidence
of cardiovascular disease (RR, 1.53; 95% CI, 1.26–1.87),
coronary heart disease (RR, 1.52; 95% CI, 1.37–1.69) and
stroke (RR, 1.76; 95% CI, 1.37–2.25). The RR of cardiovascular
disease associated with the metabolic syndrome was higher in
women compared with men and higher in studies that used the
World Health Organization definition compared with studies that
used the ATP III definition. A meta-analysis of 43 cohorts (inception
1971–1997) and 172,573 individuals found that the metabolic
syndrome had a RR of cardiovascular events and death of 1.78
(95% CI, 1.58–2.00). The association was stronger in women
(RR, 2.63 versus 1.98,
P = 0.09).
11 However, in the DECODE study
of nine European population-based cohorts, cardiovascular disease
mortality was lower in women than in men.
17
Visceral adipose tissue (VAT) compartments may confer increased metabolic risk compared with subcutaneous abdominal adipose tissue (SAT). Participants (n = 3001) drawn from the Framingham Heart Study (48% women; mean age, 50 years), underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005.35 In both sexes, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, TG and HDL cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus and metabolic syndrome. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. Furthermore in women, the relationship between VAT and risk factors were consistently stronger than in men.
Both leptin and C-reactive protein (CRP) have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. A study of 1000 healthy volunteers (48 men and 52 women) found that leptin and CRP levels were significantly higher in women.36 Furthermore, the Minoh study revealed that CRP concentration was more strongly related to metabolic syndrome in women than in men.37
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Insulin sensitivity after the menopause
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After the menopause systolic blood pressure continues to rise
and diastolic blood pressure decreases, leading to widening
pulse pressure.
38 At the same time, women gain approximately
0.55 kg per year
39 with an increase in abdominal obesity.
40 At the same time, lean body mass (muscle) is reduced.
41 The
literature on the effect of the menopause on insulin resistance
is conflicting. Most investigators have used mathematical models
or indirect estimates of insulin resistance, and data from direct
measurements of insulin sensitivity by means of the reference
method (i.e. the euglycaemic-hyperinsulinaemic clamp) are scarce.
42–44 It seems that an increase in body weight may have a greater
influence on an increase in insulin sensitivity than menopausal
status.
45 However, Walton
et al.
44 found that the menopause
is associated with significant changes in insulin metabolism,
with a decline in insulin sensitivity thereafter. De Nino
et al.
46 also found that insulin sensitivity decreased slowly after
menopause, but this insulin resistance became significant only
when women were older than 60 years of age. They also found
that age-related differences in visceral fat explain only a
modest part of the decline in insulin sensitivity in non-obese
women and men.
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The effects of hormone replacement therapy on the metabolic syndrome
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Results of the effects of hormone replacement therapy (HRT)
on the metabolic syndrome are contradictory. Different regimens
(estrogen alone or combined with a progestogen) and routes of
administration have varying effects. A meta-analysis pooled
results of 107 randomized controlled trials on the effect of
HRT on metabolic, inflammatory or thrombotic components.
47 Insulin
resistance was calculated by homeostasis model assessment (HOMA-IR).
It showed that HRT reduced abdominal fat (–6.8% [CI, –11.8
to –1.9%]), HOMA-IR (–12.9% [CI, –17.1 to
–8.6%]) and new-onset diabetes (RR, 0.7 [CI, 0.6–0.9])
in women without diabetes. In women with diabetes, HRT reduced
fasting glucose (–11.5% [CI, –18.0 to –5.1%])
and HOMA-IR (–35.8% [CI, –51.7 to –19.8%]).
HRT also reduced low-density lipoprotein/HDL cholesterol ratio
(–15.7% [CI, –18.0 to –13.5%]), Lp(a) (–25.0%
[CI, –32.9 to –17.1%]), mean blood pressure (–1.7%
[CI, –2.9 to –0.5%]), E-selectin (–17.3% [CI,
–22.4 to –12.1%]), fibrinogen (–5.5% [CI,
–7.8 to –3.2%]) and plasminogen activator inhibitor-1
(–25.1% [CI, –33.6 to –15.5%]). Oral agents
produced larger beneficial effects than transdermal agents,
but increased CRP (37.6% [CI, 17.4 to 61.3%]) and decreased
protein S (–8.6% [CI, –13.1 to –4.1%]), while
transdermal agents had no effect. The Women's health Initiative
randomized trial found that postmenopausal therapy with conjugated
equine estrogens alone may reduce the incidence of treated diabetes.
48 The effect was smaller than that seen with the addition of the
progestogen medroxyprogesterone acetate.
Other regimes have been studied illustrating the metabolic differences of individual regimens. For example, dydrogesterone has no adverse effect on the beneficial effects of estrogen alone on glucose tolerance.49 Comparison of oral and transdermal estradiol with addition of oral norethisterone showed that insulin sensitivity was increased by oral estradiol but this was reversed by the addition of norethisterone. Transdermal estradiol did not affect insulin sensitivity.50
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Early markers of the metabolic syndrome: polycystic ovary syndrome, preeclampsia, gestational diabetes mellitus
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Polycystic ovary syndrome (PCOS) is one of the most common hormonal
disorders in women, with a prevalence estimated between 5 and
10%.
51 PCOS is a syndrome of ovarian dysfunction. Its clinical
manifestations may include: menstrual irregularities, signs
of androgen excess and obesity. Insulin resistance is also common.
PCOS is associated with an increased risk of type 2 diabetes
and cardiovascular events.
52 PCOS and the metabolic syndrome
have many features in common. For example, one study found that
6.6% women with PCOS had diabetes; among the 368 non-diabetics,
the prevalence for individual components comprising the metabolic
syndrome were: waist circumference >88 cm in 80%, HDL cholesterol
<50 mg/dL in 66%, TG
150 mg/dL in 32%, blood pressure
130/85
mmHg in 21% and fasting glucose concentrations
110 mg/dL in
5%.
53 Also a history of PCOS may be associated with an increased
risk of atherosclerotic cardiovascular disease in older postmenopausal
women as evidenced by the Rancho Bernado Study.
54
Preeclampsia complicates 
5% of pregnancies in the USA.55 Increased pre-pregnancy body mass index (BMI) is an important risk factor for preeclampsia. Women with high glucose, insulin and triglyceride levels are more likely to develop preeclampsia. There are data suggesting an increased CVD risk and hyperinsulinaemia in women with a history of preeclampsia.55,56
A pregnancy complicated by gestational diabetes mellitus presents an increased risk for subsequent glucose intolerance and type 2 diabetes, as well as the metabolic syndrome.57,58 A review of the literature between 1965 and 2001 revealed progression from gestational diabetes to postpartum type II diabetes as high as 70%.57
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Sympathetic overactivity and insulin resistance
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Sympathetic overactivity is closely related to insulin resistance.
59 Insulin plays an important role in linking dietary intake with
the sympathetic nervous system. It is hypothesized that during
fasting, insulin resistance, sympathetic activity and activation
of the renin–angiotensin system are decreased. Sympathetic
outflow is suppressed via an inhibitory pathway between the
hypothalamus and brain-stem sympathetic centres. Conversely,
in the presence of insulin resistance or increased carbohydrate
intake, a small increase in glucose and a greater rise in insulin
increases insulin-mediated glucose metabolism in these hypothalamic
neurons, resulting in suppression of the inhibitory pathway
with a resultant increase in sympathetic outflow. Insulin may
enhance central nervous system activity, although the exact
mechanisms through which insulin resistance and hyperinsulinaemia
predispose individuals to sympathetic hyperactivity are not
well established. Also ageing is accompanied by a greater increase
in sympathetic traffic in women than in men.
60 It is thus of
interest that the centrally acting sympatholytic agent moxonidine
improved metabolic profile in terms of decreased insulin resistance.
61
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A therapeutic approach to metabolic syndrome
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Results from clinical trials conducted in China, Finland and
USA have demonstrated that lifestyle-interventions (reduction
of obesity, increased physical activity and dietary changes)
reduce the risk of progression from impaired glucose tolerance
to type 2 diabetes and also improves several CVD risk factors
and the metabolic syndrome.
62–64 An American/National
Heart, Lung and Blood Institute Scientific Statement has provided
a summary of clinical management for the metabolic syndrome.
24 The prime emphasis in management of the metabolic syndrome is
to reduce underlying modifiable risk factors (obesity, physical
inactivity and atherogenic diet) through lifestyle changes.
There are specific recommendations for diet, exercise and weight
loss of initially 7–10% of baseline weight in the first
year with continued weight loss thereafter with the goal to
ultimately achieve desirable weight (BMI <25 kg/m
2).
If blood pressure, lipid and glycaemic control are not achieved through these interventions then pharmacological therapy will be required. While antihypertensives lower blood pressure some such as beta blockers and diuretics, but not all (ACE inhibitors, calcium channel blockers, angiotensin II antagonists), may worsen cardiovascular risk factors such as insulin resistance. Those at risk of developing metabolic syndrome (history of preeclampsia, gestational diabetes, central obesity, glucose intolerance) should avoid the use of high dose beta-blockers and/or diuretics because of their diabetogenic effects.65
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Conclusion
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It has been suggested that there is a metabolic syndrome resulting
from the menopause due to estrogen deficiency, as many of the
risk factors are more prevalent in postmenopausal women. It
increases the risk of cardiovascular disease and type 2 diabetes.
The increased risk of cardiovascular disease is higher in women
than in men. The metabolic syndrome is of importance in women
as cardiovascular disease is the leading cause of death.
Competing interests: None declared.
Accepted: November 6, 2007.
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References
|
|---|
- Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–607[Medline]
- Hu G, Qiao Q, Tuomilehto J. The metabolic syndrome and cardiovascular risk. Curr Diab Rev 2005;1:137–43
- Liese AD, Mayer-Davis EJ, Haffner SM. Development of the multiple metabolic syndrome: an epidemiologic perspective. Epidemiol Rev 1998;20:157–72[Free Full Text]
- Laaksonen DE, Lakka HM, Niskanen LK, et al Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 2002;156:1070–7[Abstract/Free Full Text]
- Lorenzo C, Okoloise M, Williams K, et al The metabolic syndrome as predictor of type 2 diabetes: the San Antonio Heart Study. Diabetes Care 2003;26:3153–9[Abstract/Free Full Text]
- Wang JJ, Hu G, Miettinen ME, Tuomilehto J. The metabolic syndrome and incident diabetes: assessment of four suggested definitions of the metabolic syndrome in a Chinese population with high post-prandial glucose. Horm Metab Res 2004;36:708–15[Medline]
- Wang JJ, Li HB, Kinnunen L, et al How well does the metabolic syndrome defined by five definitions predict incident diabetes and incident coronary heart disease in a Chinese population? Atherosclerosis 2007;192:161–8[Medline]
- Lakka HM, Laaksonen DE, Lakka TA, et al The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709–16[Abstract/Free Full Text]
- Hu G, Qiao Q, Tuomilehto J, et al Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004;164:1066–76[Abstract/Free Full Text]
- Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005;28:1769–78[Abstract/Free Full Text]
- Gami AS, Witt BJ, Howard DE, et al Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403–14[Abstract/Free Full Text]
- Qiao Q, Gao W, Zhang L, et al Metabolic syndrome and cardiovascular disease. Ann Clin Biochem 2007;44:232–63[Abstract/Free Full Text]
- WHO Consultation. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva: World Health Organisation, 1999
- National Institute of Health. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285:2486–97[Free Full Text]
- Spencer CP, Godsland IF, Stevenson JC. Is there a menopausal metabolic syndrome? Gynecol Endocrinol 1997;11:341–55[Medline]
- Sipilä K, Koivistoinen T, Moilanen L, et al Metabolic syndrome and arterial stiffness. The health 2000 survey. Metabolism 2007;56:320–6[Medline]
- Qiao Q. The DECODE study group. Comparison of different definitions of the metabolic syndrome in relation to cardiovascular mortality in European men and women. Diabetologia 2006;49:2837–46[Medline]
- Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third national health and nutrition examination survey. JAMA 2002;287:356–9[Abstract/Free Full Text]
- Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539–53[Medline]
- Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16:442–3[Medline]
- National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285:2486–97[Free Full Text]
- Einhorn D, Reaven GM, Cobin RH, et al American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003;9:237–52[Medline]
- Alberti KG, Zimmet P, Shaw J. IDF Epidemiology task force consensus group. The metabolic syndrome: a new worldwide definition. Lancet 2005;366:1059–62[Medline]
- Grundy SM, Cleeman JI, Daniels SR, et al American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005;112:2735–52[Medline]
- Kahn R, Buse J, Ferranini E, Stern M, American Diabetes Association, European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005;28:2289–304[Abstract/Free Full Text]
- Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care 2004;27:2444–9[Abstract/Free Full Text]
- Lorenzo C, Williams K, Gonzalez-Villalpando C, Haffner SM. The prevalence of the metabolic syndrome did not increase in Mexico City between 1990–1992 and 1997–1999 despite more central obesity. Diabetes Care 2005;28:2480–5[Abstract/Free Full Text]
- Lorenzo C, Williams K, Hunt KJ, Haffner SM. Trend in the prevalence of the metabolic syndrome and its impact on cardiovascular disease incidence: the San Antonio Heart Study. Diabetes Care 2006;29:625–30[Abstract/Free Full Text]
- Park HS, Kim SM, Lee JS, et al Prevalence and trends of metabolic syndrome in Korea: Korean National Health and Nutrition Survey 1998–2001. Diabetes Obes Metab 2007;9:50–8[Medline]
- Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski. Geographical variation in the major risk factors of coronary heart disease in men and women aged 35–64 years. The WHO MONICA Project. World Health Stat Quarterly 1988;41:115–40
- Hu G, Qiao Q, Silventoinen K, et al Occupational, commuting, and leisure-time physical activity in relation to risk for type 2 diabetes in middle-aged Finnish men and women. Diabetologia 2003;46:322–9[Medline]
- Hu G, Tuomilehto J, Borodulin K, Jousilahti P. The joint associations of occupational, commuting, and leisure-time physical activity, and the Framingham risk score on the 10-year risk of coronary heart disease. Eur Heart J 2007;28:492–8[Abstract/Free Full Text]
- Wilson PW, Kannel WB, Silbershatz H, D‘Agostino RB. Clustering of metabolic factors and coronary artery disease. Arch Intern Med 1999;159:1104–9[Abstract/Free Full Text]
- Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006;119:812–9[Medline]
- Fox CS, Massaro JM, Hoffman U, et al Abdominal visceral adipose tissue compartments, association with metabolic risk factors in the Framingham Heart Study. Circulation 2007;116:39–48[Abstract/Free Full Text]
- Shamsuzzaman A, Winnicki M, Wolk R, et al Independent asoociation between plasma leptin and C-reactive protein in healthy humans. Circulation 2004;109:2181–5[Medline]
- Nakanishi N, Shiraishi T, Wada M. C-reactive protein concentration is more strongly related to metabolic syndrome in women than in men: the Minoh study. Circ J 2005;69:386–91[Medline]
- Staessen J, Bulpitt CJ, Fagard R, Lijnen P, Amery A. The influence of menopause on blood pressure. J Hum Hypertens 1989;3:427–33[Medline]
- Crawford SL, Casey VA, Avis NE, McKinlay SM. A longitudinal study of weight and the menopause transition: results from the Massachusetts Women's Health Study. Menopause 2000;7:96–104[Medline]
- Toth MJ, Tchernof A, Sites CK, Poehlman ET. Effects of menopausal status on body composition and abdominal fat distribution. Int J Obes Relat Metab Disor 2000;24:226–31[Medline]
- Kongnyyuy E, Norman RJ, Flight IHK, Rees MCP. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database Syst Rev 2007;(2):CD001018
- Toth MJ, Sites CK, Eltabbakh GH, Poehlman ET. Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women. Diabetes 2000;23:801–6
- Lasco A, Alvaro S, Frisina N, Di Benedetto A, Denzzo G, Cucinotta D. Long-term transdermal estrogen therapy improves lipid profile but not insulin resistance in healthy postmenopausal women. Diabetes Care 2000;23:422–4[Medline]
- Walton C, Godsland IF, Proudler AJ, Wynn V, Stevenson JC. The effect of the menopause on insulin sensitivity, secretion and elimination in non-obese healthy women. Eur J Clin Invest 1993;23:466–73[Medline]
- Guthrie JR, Ball M, Dudley EC, et al Impaired fasting glycaemia in middle-aged women: a prospective study. Int J Obes Relat Metab Disord 2001;25:646–51[Medline]
- DeNino WF, Tchernof A, Dionne IJ, et al Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care 2001;24:925–32[Abstract/Free Full Text]
- Salpeter SR, Walsh JME, Ormiston TM, et al Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 2006;8:538–54[Medline]
- Bonds DE, Lasser N, Qi L, et al The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial. Diabetologia 2006;49:459–68[Medline]
- Crook D, Godsland IF, Hull J, Stevenson JC. Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up. Br J Obstet Gynaecol 1997;104:298–304[Medline]
- Spencer CP, Godsland IF, Cooper AJ, Ross D, Whitehead MI, Stevenson JC. Effects of oral and transdermal 17 beta-estradiol with cyclical oral norethindrone acetate on insulin sensitivity, secretion, and elimination in postmenopausal women. Metabolism 2000;49:742–7[Medline]
- Ehrmann DA. Medical progress: polycystic ovary syndrome. New Engl J Med 2005;352:1223–36[Free Full Text]
- The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Hum Reprod 2004;19:41–7[Abstract/Free Full Text]
- Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN; PCOS/Troglitazone Study Group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:48–53[Abstract/Free Full Text]
- Krentz AJ, von Muhlen D, Barrett-Connor E. Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease. Menopause 2007;14:284–92[Medline]
- Bentley-Lewis R, Koruda K, Seely EW. The metabolic syndrome in women. Nat Clin Pract Endocrinol Metab 2007;3:696–704[Medline]
- Laivuori H, Tikkanen MJ, Ylikorkala O. Hyperinsulinemia 17 years after preeclamptic first pregnancy. J Clin Endocrinol Metab 1996;81:2908–11[Abstract]
- Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002;25:1862–8[Abstract/Free Full Text]
- Di Cianni G, Lencioni C, Volpe L, et al C-reactive protein and metabolic syndrome in women with previous gestational diabetes. Diabetes Metab Res Rev 2007;23:135–40[Medline]
- Kaaja R, Pöyhönen-Alho MK. Insulin resistance and sympathetic overactivity. J Hypertens 2006;24:131–41[Medline]
- Narkiewicz K, Phillips BG, Kato M, et al Gender-selective interaction between aging, blood pressure, and sympathetic nerve activity. Hypertension. 2005;45:522–5[Abstract/Free Full Text]
- Kaaja R, Kujala S, Manhem K, et al Effects of sympatholytic therapy on insulin indices in hypertensive postmenopausal women. In J Clin Pharm Ther 2007;45:394–401
- Pan X, Li G, Hu Y, et al Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20:537–44[Abstract]
- Tuomilehto J, Lindstrom J, Eriksson JG, et al Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50[Abstract/Free Full Text]
- Knowler WC, Barrett-Connor E, Fowler SE, et al Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403[Abstract/Free Full Text]
- Messerli FH, Grossman E, Leonetti G. Antihypertensive therapy and new onset diabetes. J Hypertens 2004;22:1845–7[Medline]
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1.0 mmol/L