Does the diabetes presentations and treatment differs in the different stages of women's life. What is the interplay between diabetes and both puberty and menopause
2. Estrogen and insulin interaction on Blood
sugar and the menstrual cycle
• Every hormone influences the others
• Sex hormones influence glucose metabolism
• Estrogen improves insulin sensitivity and enhances glucose-stimulated
insulin secretion.
• Estrogen augments insulin sensitivity at low concentrations but diminishes
insulin sensitivity at high concentrations
• This helps to explain the high incidence of diabetes in pregnant women
3. Women may be more sensitive to insulin during the follicular phase, and less sensitive during the
luteal phase).
This may explain the fluctuation in insulin needs and appetite changes along with the cycle
Insulin and growth hormone levels have an effect on oogenesis.
Diabetes is associated with delayed oocyte maturation and less frequent ovulation. There is also
impaired meiotic maturation of the follicle and potential impaired follicular development.
5. The interplay between diabetes mellitus and
Menarche and puberty
• T1DM girls have an older age at menarche (13.5y vs 12.6y)
and an increased rate of menstrual irregularities compared
with others without diabetes.
6. Menarche and puberty
Other difficulties encountered in girls with T1DM (compared with boys)
• Growth spurt is stunted that this is closely associated with diabetes control.
• Excessive weight gain, and weight loss difficulties during puberty
• More difficult glucose control
• Menstrual disturbances due to dysfunction of the HPO axis
• Too vigorous treatment with supraphysiological doses of insulin may
contribute to the etiology of menstrual disorders by causing
hypedandrogenism and PCOS.
7. Menarche and puberty
• Early menarche is a predictor of late development of T2DM
• An inverse correlation between age at menarche and type 2 diabetes
(adjustment for BMI may attenuate this correlation, because earlier
menarche was linked to increased BMI
9. The interplay between diabetes mellitus and
menopause
• The menopausal transition is characterized by a substantial decline in
estrogen production, while androgen production declines at a lower rate,
resulting in relative androgen excess.
• These subsequent hormonal alterations are linked with IR, central adipose
tissue deposition and a decrease in lean mass
• The incidence of diabetes dramatically increased when women came to the
postmenopausal period
10. Early menopause and premature ovarian
insufficiency
• The risk of subsequent T2DM development after menopause could be
influenced by the duration of exposure to sex hormones.
• A shorter reproductive lifespan increased the risk of incident T2DM
• Premature ovarian insufficiency and early menopause are associated with an
increased risk of T2DM later in life
• Women with premature ovarian insufficiency showed an increased risk of
T2DM by 32%
• Surgical menopause could also result in a higher risk of incident T2DM.
11. Menopause:
Metabolic changes
Changes related to insulin action
• Altered sex hormone concentrations (relative hyperandrogenaemia and
decreasing SHBG
• Reduced insulin signaling through reduced activation of oestrogen
receptor-α
• Increased visceral adiposity
• Increased production of FFA, which are converted to triglycerides in
the muscles and liver
• Chronic inflammation
Changes in insulin secretion and degradation:
• Apoptosis of pancreatic β-cells
• Augmented hepatic insulin degradation
12. Menopausal symptoms and diabetes
mellitus
• A large body of evidence suggests that women experiencing
vasomotor symptoms at midlife have a higher risk of developing
incident diabetes mellitus than women who do not experience such
symptoms.
• The link between diabetes mellitus and vasomotor symptoms is
complex, as the direction of the cause-and-effect association has not
been clarified
13. Diabetes and age at menopause
Equally, diabetes mellitus can affect ovarian ageing
• Women with T1DM experience menopause at an earlier age
• Women with T1DM onset before menarche experienced delayed menarche
and earlier natural menopause
• Women with T1DM and early-onset T2DM can experience menopause at
an earlier age than women without diabetes mellitus.
Possible causes include
• Autoimmune destruction of ovarian follicles, microvascular complications and
• Poor glycaemic control contributing to ovarian aging
15. Diabetes and fertility
• Fecundability (ability to conceive) has been reported to be lower
for women with diabetes, with odds ratios for conception within a
given menstrual cycle, of 0.76 for type 1 diabetes, and 0.64 for
type 2 diabetes in comparison to women without diabetes (after
adjustment for maternal age and pre-pregnancy BMI)
16. Menstrual abnormalities and infertility
• T1DM & T2DM should be considered in the DD of menstrual
abnormalities and infertility.
• Better glycemic control and prevention of diabetic complications
improves these irregularities and increases fertility rates
• Women with persistent menstrual abnormalities despite adequate
treatment need to be approached by broader evaluation (examination of
the hypothalamic-pituitary-ovarian axis, presence of AITD and
antiovarian autoantibodies, or hyperandrogenism)
17. Infertility risk factors related to diabetes
mellitus
• Shortening of reproductive period (late menarche and premature menopause)
• Menstrual abnormalities (such as oligomenorrhea )
• Poor glycemic control and presence of diabetes complications
• Hyperandrogenism and polycystic ovary syndrome
• Autoimmunity (Hashimoto's thyroiditis and antiovarian autoantibodies)
• Sexual dysfunction
18. Type 2 diabetes & infertility
• Obese women experience longer times to conception, even if they are young and cycling
regularly
• T2DM is associated with infertility, alterations in the length of menstrual cycle, and the
age of onset of menopause.
• This may be explained by the correlation of T2DM to PCOS
• Poor glycemic control and the presence of diabetic complications are associated with
menstrual irregularities and lower fertility by 20%
• Increase in fertility was evident in the past 20 years and could be attributed to stricter
metabolic control.
19. Diabetes and Polycystic Ovary Syndrome
(PCOS)
• Diabetes and PCOS are related diseases.
• Women with either disease should keep an eye out for any
symptoms of the other.
People with diabetes might pay special attention to any excess hair
growth on the body or face (hirsutism) .
People with PCOS may benefit from regular screenings for diabetes or
prediabetes.
20. Autoimmunity
• Hashimoto's thyroiditis is highly prevalent among patients with Type 1
diabetes (some studies reported >40% prevalence).
• Menstrual cycle changes observed in patients with Hashimoto's thyroiditis
include menorrhagia, more frequent and longer periods, and dysmenorrhea.
• Antiovarian autoantibodies were found in girls with Type 1 diabetes in higher
frequency compared with healthy controls.
21. Gestational diabetes
• Gestational diabetes occurs in about 7 in 100 pregnancies in the USA but can be as
common as 14 in 100 pregnancies in some populations.
• Women are more likely to develop it if they have a family history of it or if they are
overweight or obese.
• Furthermore, during pregnancy and after childbirth, not only change of hormone
balance, but also lifestyle changes including increased energy intake, change in food
choice and physical inactivity might contribute to the development of type 2 diabetes
• Early periods are associated with risk of gestational diabetes
• People with gestational diabetes have a higher risk of developing type 2 diabetes after
their pregnancy and should be regularly screened for diabetes throughout their adult
lives.
23. Management
• The aim should be a holistic approach that includes the treatment
of menopausal and genitourinary symptoms, while ensuring
metabolic, cardiovascular and bone health
24. Diabetes mellitus management
The interventions in women with diabetes mellitus have multiple goals:
Glycaemic control
Weight reduction
After menopause: decrease of cardiovascular risk, osteoporosis and
sarcopenia
25. • Women with diabetes mellitus after menopause should follow the same
guidelines that apply to all patients with diabetes mellitus concerning
lifestyle modifications (controlling body weight, adopting a healthy diet,
exercising regularly
26. Effects of HRT on glucose tolerance in women
without diabetes
• HRT consists of estrogen monotherapy in women with a history of hysterectomy or
oestrogen combined with a progestogen in women with an intact uterus, to counteract
the proliferative effect of estrogens on the endometrium.
• HRT use is associated with a lower risk of T2DM later in life
• Non-diabetic users had significantly lower abdominal adiposity and waist
circumference and more positive lipid profiles than non-users.
• HRT reduced the incidence of T2DM by 30%, decreasing insulin resistance by 13%
• In women with pre-existing diabetes mellitus, HRT improves glycaemic control and
HbA1c concentrations
27. • The protective effect of HRT against T2DM observed in the WHI trial dissipated after
treatment discontinuation.
• The available studies were not designed to investigate the effect of HRT on the
prevention of T2DM in women without T2DM or the effect on glucose homeostasis in
women with pre-existing diabetes mellitus as a primary end point. Therefore, HRT
should not be administered for T2DM prevention or control.
• Disadvantages include the increased risk of venous thromboembolism, stroke,
endometrial cancer, breast cancer, cholecystitis… etc
28. • Therefore, patients should weigh the benefits against risks prior to
undergoing HRT.
• HRT is indicated as hormone replacement therapy in women with premature
ovarian insufficiency until the age of natural menopause
• Otherwise, the advice is to use the minimum effective dose for the shortest
possible duration.
29. Conclusions
• Low level of estrogen may promote nutrient storage in adipose tissue
• Most reports indicated that high doses of estrogen are associated with
insulin resistance
• Early menarche, early menopause, long or irregular menstrual cycle, severe
menopausal symptoms and postmenopausal status have been linked to a
higher risk of type 2 diabetes.
• Whereas hormone-replacement therapy in postmenopausal women was
linked to a reduced risk.
30. Conclusions
• Type I diabetes may be associated with a higher incidence of premature menopause.
• Postmenopausal women with diabetes mellitus have a higher risk of CVD and fracture
than women without diabetes mellitus, independently of BMD.
• Postmenopausal women with diabetes mellitus should follow the holistic approach,
aiming for quality of life and optimal metabolic, cardiovascular and bone health.
• Individual women need to weigh the risks and benefits of HRT
Notas do Editor
In fact, some, but not all studies suggest that early menopause (shorter duration of exposure to estrogen) is correlated with a higher risk of type 2 diabetes.
However, this finding may be influenced by the higher BMI in non-diabetic women
menstrual disturbances due to dysfunction of the HPO axis:
Disruption in pulsatile secretion of GnRH
Lower basal level of LH
Different reactions of LH to exogenous GnRH
Furthermore, during pregnancy and after childbirth, not only change of hormone balance, but also lifestyle changes including increased energy intake, change in food choice and physical inactivity might contribute to the development of type 2 diabetes.
It was reported that the prevalence of diabetes among women aged 50 years and older was at least 15% in the United States [11
The exact biological mechanism is not fully understood, but there are several factors that may help to explain the relationship, including increasing antioxidative stress and anti-inflammation ability, modulating cholesterol metabolism [12], or increasing insulin sensitivity [13] by estrogen
The pathophysiological mechanisms and the clinical results of the interaction between diabetes mellitus and menopause are different for T1DM and T2DM9
Sexual dysfunction & diabetes
Higher prevalence of impaired sexual arousal and inadequate lubrication was found to be significantly higher in women with Type 1 diabetes compared with healthy controls.
In some cases, this could be due to body weight, but many other factors may play a role, such as genetics (16-18).
Most glucose-lowering medications do not affect bone metabolism, except thiazolidinediones and canagliflozin, which can decrease BMD and increase bone resorption and fracture risk132,153
Newer HRT regimens might not affect glucose metabolism as seen with the older regimens113,114,115. Progestogens have traditionally been associated with the development of insulin resistance116
Management of women with diabetes mellitus after menopause should start with cardiovascular disease (CVD) risk stratification, based on CVD risk factors, duration of diabetes mellitus and the presence of target organ damage. Lifestyle modifications are the first intervention, which consists of body weight control, a healthy diet, intake of calcium and vitamin D, moderation in alcohol consumption, cessation of smoking and regular physical activity of 150 min per week including both aerobic and muscle-strengthening exercise. Therapeutic targets are the control of menopausal symptoms and diabetes mellitus, as well as weight management and reduction of the risk of CVD and osteoporosis. Concerning type 2 diabetes mellitus, metformin, glucagon-like peptide 1 (GLP1) receptor agonists, sodium–glucose cotransporter 2 inhibitors (SGLT2) are preferred regimens owing to their favourable effect on body weight and insulin sensitivity. Agents to be avoided as first-line options include thiazolidinediones and canagliflozin in those with an increased risk of osteoporosis. In women with menopausal symptoms or women with premature ovarian insufficiency, menopausal hormone therapy (HRT) can be considered after careful CVD risk stratification. Transdermal oestradiol is typically preferred over oral preparations as it is associated with a lower risk or no risk of thrombosis. In women with an intact uterus, a progestogen should be used to oppose the hyperplastic effects of oestrogens on the endometrium. Progestogens that do not counteract the beneficial effects of oestrogens on carbohydrate metabolism include micronized progesterone, dydrogesterone, low-dose oral or transdermal norethisterone acetate (NETA). Women with prevalent CVD or target organ damage or three or more CVD risk factors or type 1 diabetes mellitus (T1DM) for >20 years should be advised to avoid HRT. CKD, chronic kidney disease; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids
In women with diabetes mellitus and indications to receive HRT, such as bothersome menopausal symptoms, vulvovaginal atrophy or a diagnosis of premature ovarian insufficiency, HRT should be considered after CVD risk stratification. The transdermal route is preferred in women with long-standing diabetes mellitus, obesity or other cardiovascular risk factors.
