Menopause can be unbearable for women, bringing hot flashes, brain fog, insomnia and other life-invading symptoms. Local doctors say there is hope, and better ways to cope, for women today thanwhat was available to their mothers.

"People ask me when they will be done with menopause," said Dr. Sarah Hanson, an OB/GYN at York Hospital. "I answer, 'When you're dead.' Menopause encompasses the last half of a woman's life, the part where they are not reproductive anymore."

Hanson points out that what women think of when they say "menopause"are those symptoms ofhot flashes, night sweats, difficulty sleeping. For most women, thosesymptoms have a shelf life. They usually do not last more than a few years.

"What women think of as menopause is usually pre-menopause, or peri-menopause," Hanson said. "That's where the symptoms are happening. That can last three to seven years. The ovaries are no longer preparing to reproduce and hormones get thrown out of whack. But, it is a normal part of a woman's life cycle."

Some women pass through this phase easily, and menopause is like a lamb, often requiring zero medical intervention. Hanson said for others, it is a lion, fraught with symptoms and women seek any relief available to them.

"I spend a lot of my day talking about menopause," said Dr. Caroline Scoones of Harbor Women's Health, who also practices at Portsmouth Regional Hospital. "Here on the Seacoast, we have a wonderful population of women, teens, moms, menopausal women and much older women. At any time, a good 20% of them are chatting with me about menopause."

Scoones said menopause occurs when a woman has not had a period in 12 months.

"It is a transition and women go through transitions their entire lives," she said. "From the time they begin adolescence, when their reproductive systems are ramping up, to the time we enter menopause and our reproductive systems are ramping down, we are experiencing hormonal changes. It's not the same for men. We get the short end of the stick, but it's the wonderful system we are stuck with."

The average age of a woman entering menopause is 51, but Dr. Kristin Yates of Garrison Women's Heath and Wentworth-Douglass Hospital said it can range several years on either side of that age. It's rare but some women begin entering this phase of life as early as their 40s.

"When you are born, you have a certain amount of eggs in your ovaries," Yates said. "That number goes down every month when you ovulate and have a period. Eventually they run out and you no longer ovulate. You stop having periods and the amount of estrogen your body secretes gets lower."

"My first advice is to do nothing," said Hanson. "If you can handle the symptoms, this is normal and there is nothing you have to do. For other women, of course, that's not the option they choose because the symptoms are interfering with their daily life. Our grandmothers just endured it. You can, but you don't have to."

Scoones said the question of what to do relates to how many of the symptoms a woman gets, how they are interrupting every day living, and herpersonal views.

"Are you a super natural type and you do not want to take anything?" said Scoones. "Are you the oppositeand want to go full hog?Or are you somewhere in between? We can help you, or you can choose to tough it out."

Hanson said women who maintain a more healthy lifestyle, with a lot of physical activity, a healthy diet, and who maintain a good body weight generally handle menopause more easily. And, she said, it's good for our overall health anyway, so why not do it?

"People who are overweight or who smoke may have a more difficult time," Hanson said.

Hanson said women in pre-menopausecan experience hot flashes, difficulty sleeping, mood changes and shifts, and a feeling of cloudiness or fogginess, and still perform equally well every day. But, they are uncomfortable.

"These are neurological symptoms, all of them," said Hanson. "We know moods affect hormones,and hormones affect moods. For some women, low-dose birth control pills will be enough to handle the hormonal change."

Scoones said over-the-counter products, like black cohosh or evening primrose work for some women, but not all. Some natural products like Estrovera canhelp some women mitigate symptoms.

"They can be taken daily, with little side effects," said Scoones. "I think about 50% respond to these non-pharmaceutical methods."

Scoones said those with severe symptoms, like thosewho cannot sleep, who drip sweat and who are miserable in general, might consider prescription relief.

Yates said hormone replacement therapies have gone through several schools of thought.

"Women were worried about the risk of blood clotsor strokes," said Yates. "We now know that relatively small doses have low risk, and can be safe and effective. There are some women who are not good candidates, women who have a history of clots, strokes or who have had breast cancer."

"We all did it, then no one did it," she said. "Now we are better able to use low-dose hormone therapymore successfully."

Scoones agreed, saying hormonal therapies are more nuanced now.

"We can tailor hormonal treatments to deal with your particular symptoms," said Scoones. "There are transdermal estrogen treatments. There is an IUD that can be used to treat the heavy flow that usually precedes peri-menopause. We have choices that can help with sleep, anxiety, hot flashes and weight gain."

Hanson said in cases where blood flow is extreme, a procedure called endometrial ablation, an outpatient surgery, can alleviate the situation.

"Some women opt for hysterectomy," she said. "We can do that usinglaparoscopy in many cases, or with the more traditional vaginal application."

If the choice is hormone therapy, Scoones said the North American Menopause Society recommends the lowest effective dose, for the shortest duration of time, usually two to threeyears.

"You are not broken," said Scoones. "This is a natural course of a woman's life and you will not need hormone replacement therapy forever, just until you feel good again."

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Menopause is dreadful. But there's hope for how to cope with it better - Foster's Daily Democrat

The novel hormone irisin has the ability to drive the cognitive benefits of exercise, and therefore holds great promise for treating cognitive decline in Alzheimers disease, researchers atMassachusettsGeneralHospital (MGH) have found. In a study published inNatureMetabolism, the team reported that irisin, secreted by the muscles during exercise, could be an effective therapeutic for addressing deficits of the brain that result from Alzheimers disease.

Preserving cognitive function is a major challenge in an increasingly aging population, saysChristiane Wrann, DVM, PhD,leaderof the Program in Neuroprotection in Exercise at MGHand senior author of the study. Exercise is known to have positive effects on brain health, which is why identifying key mediators of those neuroprotective benefits, like irisin, has become such a critical goal of research.

Using mouse models, the team showed that genetic deletion of irisin impairs cognitive function in exercise, aging and Alzheimers disease, which was in part caused by alterations of newborn neurons in the hippocampus. The hippocampus is the compartment of the brain that stores memories and is the first to show signs of Alzheimers disease.At the same time, the MGH study found that elevating irisin levels in the bloodstream improved cognitive function and neuroinflammation in mouse models for Alzheimers disease.

For the first time, we showed that soluble irisin, and not its full-length parent protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function, explains Wrann, who is also an assistant professor of Medicine at Harvard Medical School. These effects can possibly go well beyond what exercise itself can bring. This is particularly important inasmuch as irisin, a small natural peptide, would be much easier to develop into a therapeutic than the much larger membrane-bound protein FNDC5. While previous research used the parent protein FNDC5, she adds, scientists this time delivered only the irisin portion through an adeno-associated viral vector approach to the liver, similar to gene replacement therapy, and discovered irisin was able to cross the blood-brain barrier and directly affect the brain.

What makes this study particularly strong is that we show irisins effect on cognitive function in not one but four different mouse models, states Bruce Spiegelman of Dana-Farber Cancer Institute and Harvard Medical School, who discovered irisin in 2012 and is a co-author of the current paper. Researchers were further encouraged by the fact that irisin treatment was effective in Alzheimers disease mouse models even after the development of significant pathology. This could have implications for intervention in humans with Alzheimers disease where therapy typically starts after patients have become symptomatic, Wrann says.

Another important finding of the study is that irisin protects against neuroinflammation by acting directly on glia cells in the brain. Co-author Rudy Tanzi, co-director of the McCance Center for Brain Health at MGH, explains: Its hard to imagine anything better for brain health than daily exercise, and our findings shed new light on the mechanism involved: protecting against neuroinflammation, perhaps the biggest killer of brain neurons as we age. Adds Wrann: Since irisin does not specifically target amyloid plaques, but rather neuroinflammation directly, were optimistic it could have beneficial effects on neurodegenerative diseases beyond just Alzheimers.

Reference: Islam MR, Valaris S, Young MF, et al. Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab. 2021;3(8):1058-1070. doi:10.1038/s42255-021-00438-z

This article has been republished from materials provided by Massachusetts General Hospital. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cognitive Benefits of Exercise Are Driven by the Hormone Irisin - Technology Networks

Introduction

Type 2 diabetes mellitus (T2DM) and osteoporosis are common chronic diseases, and the relationship between the two is becoming a hot research topic.1,2 Previous studies have shown that although bone mineral density (BMD) is normal or elevated,3 T2DM patients increase the risk of fractures compared with non-diabetic patients.46 T2DM can influence bone metabolism by affecting osteoblasts and osteoclasts, and the imbalance between the two may lead to osteoporosis.7 It has been confirmed that there are insulin receptors on the surface of both cells,8 and insulin signaling can regulate the bone formation of osteoblasts and bone resorption of osteoclasts.9 In vitro, it has been shown that the physiological concentration of insulin can increase the proliferation rate of osteoblasts, collagen synthesis, alkaline phosphatase production, and glucose uptake and inhibit osteoclast activity.10 Thus, insulin is an anabolic agent for bone formation, and elevated insulin levels may increase bone density.11,12 It has been widely accepted that insulin resistance is the main problem of T2DM metabolic disorders. It is caused by the defect in the insulin signaling pathway that reduces the cellular insulin response; pancreatic cells overcome the reduced sensitivity by enhancing insulin secretion, thereby developing hyperinsulinemia.9,13 Hyperinsulinemia can also negatively affect sex hormone-binding globulin to increase free sex hormone levels, preventing bone loss.11,14

However, more and more studies have shown a negative association between insulin resistance and bone mineral density,11,15,16 indicating that insulin resistance in T2DM patients may weaken the physiological effects of insulin on bones.1 Therefore, the relationship between insulin resistance and osteoporosis is still controversial. To address this question, in this study, we used a C peptide to evaluate insulin resistance based on the modified insulin resistance homeostasis model (HOMA-IR) and explored the relationship between HOMA-IR (CP) and the risk of osteoporosis in different gender groups of T2DM patients.

This was a cross-sectional study. We selected 575 T2DM patients from the outpatient department of Endocrinology and Metabolism at our hospital from February 2016 to August 2018. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of the Third Affiliated Hospital of Soochow University for retrospective analysis (ethics number: 2014-KD-79). The sample size calculation used the method of computer simulation inspection efficiency (see Supplementary Material-Computer simulation inspection efficiency). Since the patients were anonymous, informed consent was not required. Inclusion criteria: T2DM was defined as: fasting blood glucose level 7.0 mmol/l, 2 hours postprandial or random blood glucose level 11.1 mmol/l, glycosylated hemoglobin (HbA1c) 6.5%. Record the patients use of T2DM treatment drugs. The following patient populations were excluded: (1) patients using hormone replacement therapy, bisphosphonates, glucocorticoids, proton pump inhibitors, etc. (14 cases); (2) patients with missing bone density results (311 cases); (3) patients under 18 years old (1 case); (4) patients with missing HOMA-IR (CP) (15 cases). The research flow chart is shown in Figure 1. Among the 250 patients with available BMD data and the 311 patients with missing BMD data, almost all clinical factors were similar (all P > 0.05) (see Supplementary Table S1).

Figure 1 Flowchart of the study.

The general data of the patient was recorded, including menopause information. The height, weight, waist circumference, and hip circumference of patients were measured, and the body mass index (BMI) and waist-to-hip ratio were calculated. The fasting venous blood was collected, and the fasting blood glucose, uric acid, and blood lipid levels were measured using an automatic biochemical analyzer (Beckman Coulter AU5800, Brea, CA, USA). Fasting C peptide was determined by electrochemiluminescence immunoassay (Roche Cobas8000, Indianapolis, IN, USA). HbA1c was measured by high-performance liquid chromatography (D-10 system, Bio-Rad, USA).

Instead of insulin, fasting C-peptide was used to evaluate insulin resistance and islet function according to a modified formula. The modified HOMA-IR [HOMA-IR (CP)] formula = 1.5 + fasting blood glucose (mmol/L) fasting C-peptide (pmol/L)/2800. The modified HOMA-islet [HOMA-islet (CP-DM)] formula = 0.27 fasting C-peptide (pmol/L)/[fasting blood glucose (mmol/L) 3.5].17

The dual-energy X-ray absorptiometry (DXA, Hologic, Discovery-WI, USA) was used to determine the bone density of the lumbar spine (L1-L4) (unit: g/cm2). Trained and certified technicians performed all DXA scans. The diagnosis of osteopenia and osteoporosis was based on the T score of the World Health Organization (the T value was the standard deviation between the patient BMD and the BMD of the young adult reference population). 2.5 < T value < 1.0 was defined as osteopenia, T value 2.5 was defined as osteoporosis.18

Data were expressed as mean standard deviation (SD) (Gaussian distribution) or median (Q1-Q3) (Skewed distribution) for continuous variables and as numbers or percentages for categorical variables. To examine the association between HOMA-IR (CP) and osteoporosis risk, we constructed three distinct models using univariate and multivariable binary logistic regression models, including non-adjusted model, minimally-adjusted model (Adjust I), and fully-adjusted model (Adjust II). Covariates were included as potential confounders in the final models if they changed the estimation of HOMA-IR (CP) on osteoporosis by more than 10% or significantly associated with osteoporosis (P < 0.10). The subgroup analyses were performed using a stratified binary logistic regression model. The effect sizes with 95% confidence intervals were recorded. To investigate the nonlinear relationship between HOMA-IR (CP) and osteoporosis risk, we used a generalized additive model and smooth curve fitting (penalized spline method) to address nonlinearity. Moreover, the two-piecewise binary logistic regression model was used to explain the nonlinearity further.

Modeling was performed with the statistical software R (http://www.R-project.org, The R Foundation) and EmpowerStats (http://www. empowerstats.com, X&Y Solutions, Inc, Boston, MA). P < 0.05 (two-sided) was considered statistically significant.

A total of 234 T2DM patients were included in the study, with 139 males and 95 females, aged 57.5 10.8 years old (range: 2383 years old). Among them, 112 cases were first diagnosed (no hypoglycemic drugs were used), 122 cases were controlled by drugs (including 55 metformin, 37 acarbose, 24 sulfonylureas, 12 insulin, and 5 thiazolidinediones, new hypoglycemic drugs [including glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors] 2 cases, some patients have combined medication). The results of BMD measurement showed that there were 82 cases (35.0%) with normal bone mass, 118 cases (50.4%) with osteopenia, and 34 cases (14.5%) with osteoporosis. The general information and blood indicators of different gender groups are shown in Table 1.

Table 1 Comparison of General Information and Blood Indicators of Different Gender Groups

Compared with male T2DM patients, female patients were older (P = 0.047) and had longer disease course (P = 0.013), and have a higher proportion of drug control (P = 0.012); but their BMI, waist-to-hip ratio, fasting blood glucose, fasting C-peptide, HOMA-IR (CP), HOMA-islet (CP-DM), and HbA1c were not significantly different (all P > 0.05). The osteoporosis percentage in female patients was slightly higher than that in male patients (15.8% vs 13.7%), but the difference was insignificant (P = 0.651).

The univariate logistic regression analysis was performed by taking osteoporosis as the dependent variable (Y = 1) and using the clinical data and blood indicators from different gender groups as independent variables (see Table 2). The results showed that age, uric acid, and HOMA-IR (CP) were all possible related factors for osteoporosis in female patients (P < 0.10), while in male patients, the association between the above indicators and osteoporosis was not significant (P > 0.10).

Table 2 Univariate Analysis of Clinical Data, Blood Indicators, and Osteoporosis of Different Gender Groups

Multivariable logistic regression analysis was used to evaluate the association between HOMA-IR (CP) and osteoporosis by adjusting the covariates. The model with non-adjusted covariates equaled to univariate logistic regression analysis. The minimally-adjusted covariates (Adjust I) included age and uric acid, and the fully-adjusted covariates (Adjust II) included age, BMI, waist-to-hip ratio, disease course, HOMA-islet (CP-DM), uric acid, triacylglycerol, and high-density lipoprotein (see Table 3). For female patients, the increase in HOMA-IR (CP) elevated the risk of osteoporosis in all regression models with non-adjusted, minimally-adjusted, and fully-adjusted covariates, and the association was significant in the fully-adjusted model, with OR = 2.63 (95% CI: 1.155.99, P = 0.022). For male patients, the association between HOMA-IR (CP) and osteoporosis was not significant in all three models (all P > 0.05). The interaction effect between different genders was significant (P for interaction all < 0.05), indicating that the relationship between HOMA-IR (CP) and osteoporosis was affected by gender.

Table 3 Multivariable Logistic Regression Analysis of the Effect of HOMA-IR (CP) on Osteoporosis

GAM was used to test the relationship between HOMA-IR (CP) and osteoporosis risk in female patients. The results showed a nonlinear relationship between the two after correcting for age, BMI, waist-to-hip ratio, disease course, HOMA-islet (CP-DM), uric acid, triacylglycerol, and high-density lipoprotein (degree of freedom was 1.862, P = 0.024). Figure 2 showed the changes of osteoporosis risk with HOMA-IR (CP) in female patients: at first, the changes were very little; after a certain HOMA-IR (CP) value, the osteoporosis risk significantly increased, showing a piecewise linear relationship. By observing the fitted curve, we set the inflection point as 4.00.

Figure 2 The relationship between HOMA-IR (CP) and osteoporosis risk. Adjust for: age, BMI, waist-to-hip ratio, disease course, HOMA-islet (CP-DM), uric acid, triacylglycerol, and high-density lipoprotein.

Abbreviations: HOMA-IR (CP), homeostasis model assessment for insulin resistance based on C-peptide; BMI, body mass index; HOMA-islet (CP-DM), homeostasis model assessment islet beta-cell function based on C-peptide.

The two-piecewise logistic regression model method was used further to evaluate the threshold effect of the fitted curve. The log-likelihood ratio test of HOMA-IR (CP) at the inflection point 4.00 was statistically significant (P = 0.005), suggesting that the two-piecewise regression model was appropriate for describing the relationship between HOMA-IR (CP) and osteoporosis (see Table 4). When HOMA-IR (CP) < 4.00, the risk of osteoporosis in female patients did not change much with HOMA-IR (CP), (P = 0.474); when HOMA-IR (CP) > 4.00, the increase in HOMA-IR (CP) significantly elevated the risk of osteoporosis in female patients, with OR = 26.88 (95% CI: 2.75262.69, P = 0.005).

Table 4 Nonlinear Relationship Between HOMA-IR (CP) and Osteoporosis

The relationship between insulin resistance and the risk of osteoporosis in T2DM patients is still controversial. Our study found that this relationship was significantly affected by gender. In female patients, the higher the degree of insulin resistance, the greater the risk of osteoporosis. However, the relationship was not a simple linear relationship, and there was a threshold effect. When HOMA-IR (CP) > 4.00, the risk of osteoporosis increased significantly.

The incidence of osteoporosis is gradually increasing in recent years, which affects the patients life quality and causes serious social health problems.19,20 Many factors are related to osteoporosis, including age, gender, endocrine, and metabolic diseases.21 The age-related reduction of sex hormones is one reason for osteoporosis, as sex hormones play an important role in maintaining bone health.22 Compared with older males, hormone deficiency is more pronounced in older females.23 Diabetes is also an important cause of osteoporosis. Many studies2,24 have shown that people with T2DM have a higher risk of bone fractures than non-diabetic patients. Our study showed that the proportion of osteoporosis in female T2DM patients was higher than that of male patients, consistent with the previous studies.

T2DM is the most common endocrine system disease in the clinic, with insulin resistance as the basic pathological feature, accompanied by internal environmental disorders and abnormal synthesis and secretion of various cytokines. These effects influence bone metabolism and then cause bone loss and destruction of bone ultrastructure.25 In recent years, studies have shown that insulin directly affects bone cells,14 but the relationship between insulin resistance and osteoporosis is still unclear. Bilic-Curcic et al26 proposed that abdominal obesity and hyperinsulinemia played a protective role in postmenopausal women with T2DM, leading to an increase in the total femoral bone density. A cohort study of the elderly27 showed that insulin resistance was associated with increased bone density. The synergistic effect of excess insulin and other anabolic hormones, such as pancreatic amylin, insulin-like growth factors, and parathyroid hormone, can increase bone density.28 However, our results were different, which might be due to the heterogeneity of the study population, such as age, gender, race, and menopause. In addition, we used a modified HOMA-IR model to evaluate insulin resistance, in which C-peptide replaced insulin. C-peptide is more stable and is considered an effective substitute for insulin.29 Moreover, the bone density we measured was based on the lumbar spine, which might also cause inconsistent results. It has been reported30 that significant insulin resistance in T2DM patients is associated with low bone density. T2DM patients are often accompanied by mild inflammation, and chronic inflammation can lead to the development of osteoporosis through oxidative stress.31 Weber et al (31) speculated that the relationship between insulin resistance and osteoporosis might not be linear, and there was a threshold effect. Our results confirmed this perspective. When HOMA-IR (CP) > 4.00, the higher the insulin resistance of female T2DM patients, the greater the risk of osteoporosis. In our study, the proportion of female patients who had menopause accounted for 85.3%. The sharp decline in estrogen after menopause led to the loss of bone mass. This gender difference may affect the relationship between insulin resistance and osteoporosis.32 In addition, with the increase of insulin resistance, other related factors, such as pro-inflammatory cytokines, have also increased, which exerts an adverse effect on bone health, exceeding the anabolic effect of insulin on bone and leading to decreased bone density.11,33

Our study has some limitations. Firstly, this is a single-center retrospective study. There were only 34 patients with osteoporosis, and there was a high proportion of missing BMD results. The sample size needs to be expanded to obtain a more accurate HOMA-IR (CP) threshold. Secondly, there might be unknown confounding factors that affected our results. For example, serum 25-hydroxyvitaminD27,34 and diabetes medications35 are important factors that affect bone health. Finally, this study only found a significant association between HOMA-IR (CP) and osteoporosis in female patients, and more male patients should be collected for further research. The relationship between insulin resistance and osteoporosis is complex and has not been fully understood. Further research is needed to clarify the relationship between the two.

In summary, the relationship between insulin resistance and osteoporosis risk in T2DM patients is significantly affected by gender. The higher the degree of insulin resistance in female T2DM patients, the greater the risk of osteoporosis. Moreover, this relationship is not simply linear, and there is a threshold effect. This study will help clinicians assess the risk of osteoporosis in T2DM female patients and make appropriate early interventions.

All data generated or analyzed during this study are available from the corresponding author upon reasonable request.

The study was approved by the Institutional Ethics Committee of the Third Affiliated Hospital of Soochow University for retrospective analysis (ethics number: 2014-KD-79).

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

There is no funding to report.

The authors report no conflicts of interest in this work.

1. Ahmad OS, Leong A, Miller JA, et al. A mendelian randomization study of the effect of type-2 diabetes and glycemic traits on bone mineral density. J Bone Miner Res. 2017;32(5):10721081. doi:10.1002/jbmr.3063

2. Xu Y, Wu Q. Trends in osteoporosis and mean bone density among type 2 diabetes patients in the US from 2005 to 2014. Sci Rep. 2021;11(1):3693. doi:10.1038/s41598-021-83263-4

3. Zhu L, Xu Z, Li G, et al. Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes - an investigation by chemical shift-encoded water-fat MRI. Eur J Radiol. 2019;113:158164. doi:10.1016/j.ejrad.2019.02.020

4. Looker AC, Eberhardt MS, Saydah SH. Diabetes and fracture risk in older U.S. adults. Bone. 2016;82:915. doi:10.1016/j.bone.2014.12.008

5. Napoli N, Strotmeyer ES, Ensrud KE, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014;57(10):20572065. doi:10.1007/s00125-014-3289-6

6. Jia P, Bao L, Chen H, et al. Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies. Osteoporos Int. 2017;28(11):31133121. doi:10.1007/s00198-017-4183-0

7. Sassi F, Buondonno I, Luppi C, et al. Type 2 diabetes affects bone cells precursors and bone turnover. BMC Endocr Disord. 2018;18(1):55. doi:10.1186/s12902-018-0283-x

8. Fulzele K, Riddle RC, DiGirolamo DJ, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142(2):309319. doi:10.1016/j.cell.2010.06.002

9. Conte C, Epstein S, Napoli N. Insulin resistance and bone: a biological partnership. Acta Diabetol. 2018;55(4):305314. doi:10.1007/s00592-018-1101-7

10. Thrailkill KM, Lumpkin CK, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab. 2005;289(5):E735745. doi:10.1152/ajpendo.00159.2005

11. Shin D, Kim S, Kim KH, Lee K, Park SM. Association between insulin resistance and bone mass in men. J Clin Endocrinol Metab. 2014;99(3):988995. doi:10.1210/jc.2013-3338

12. Nyman JS, Kalaitzoglou E, Clay bunn R, Uppuganti S, Thrailkill KM, Fowlkes JL. Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes. Bone Rep. 2017;7:18. doi:10.1016/j.bonr.2017.07.001

13. Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care. 2008;31(Suppl 2):S262268. doi:10.2337/dc08-s264

14. Shanbhogue VV, Finkelstein JS, Bouxsein ML, Yu EW. Association between insulin resistance and bone structure in nondiabetic postmenopausal women. J Clin Endocrinol Metab. 2016;101(8):31143122. doi:10.1210/jc.2016-1726

15. Ahn SH, Kim H, Kim BJ, Lee SH, Koh JM. Insulin resistance and composite indices of femoral neck strength in Asians: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV). Clin Endocrinol (Oxf). 2016;84(2):185193. doi:10.1111/cen.12958

16. Shah VN, Sippl R, Joshee P, et al. Trabecular bone quality is lower in adults with type 1 diabetes and is negatively associated with insulin resistance. Osteoporos Int. 2018;29(3):733739. doi:10.1007/s00198-017-4353-0

17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412419. doi:10.1007/BF00280883

18. Golob AL, Laya MB. Osteoporosis: screening, prevention, and management. Med Clin North Am. 2015;99(3):587606. doi:10.1016/j.mcna.2015.01.010

19. Ma C, Tonks KT, Center JR, Samocha-Bonet D, Greenfield JR. Complex interplay among adiposity, insulin resistance and bone health. Clin Obes. 2018;8(2):131139. doi:10.1111/cob.12240

20. Cosman F, de Beur SJ, LeBoff MS, et al. Clinicians Guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):23592381. doi:10.1007/s00198-014-2794-2

21. Rubin MR, Schwartz AV, Kanis JA, Leslie WD. Osteoporosis risk in Type 2 diabetes patients. Expert Rev Endocrinol Metab. 2013;8(5):423425. doi:10.1586/17446651.2013.835567

22. Riggs BL, Khosla S, Melton LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23(3):279302. doi:10.1210/edrv.23.3.0465

23. Sawicki P, Talalaj M, Zycinska K, Zgliczynski WS, Wierzba W. A cross-sectional comparison of selected anthropometric, laboratory and densitometric parameters in postmenopausal osteoporotic women with and without vertebral compression fractures. Endokrynol Pol. 2021;72(3):191197. doi:10.5603/EP.a2021.0011

24. Fan Y, Wei F, Lang Y, Liu Y. Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporos Int. 2016;27(1):219228. doi:10.1007/s00198-015-3279-7

25. Heilmeier U, Patsch JM. Diabetes and Bone. Semin Musculoskelet Radiol. 2016;20(3):300304. doi:10.1055/s-0036-1592366

26. Bilic-Curcic I, Makarovic S, Mihaljevic I, Franceschi M, Jukic T. Bone mineral density in relation to metabolic syndrome components in postmenopausal women with diabetes mellitus type 2. Acta Clin Croat. 2017;56(1):5863. doi:10.20471/acc.2017.56.01.09

27. Napoli N, Conte C, Pedone C, et al. Effect of Insulin resistance on BMD and fracture risk in older adults. J Clin Endocrinol Metab. 2019;104(8):33033310. doi:10.1210/jc.2018-02539

28. Fornari R, Marocco C, Francomano D, et al. Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects. Eat Weight Disord. 2018;23(3):375381. doi:10.1007/s40519-017-0362-4

29. Fasipe OJ, Ayoade OG, Enikuomehin AC. Severity grade assessment classifications for both insulin resistance syndrome and status of pancreatic beta cell function in clinical practice using homeostasis model assessment method indices. Can J Diabetes. 2020;44(7):663669. doi:10.1016/j.jcjd.2020.02.003

30. Arikan S, Tuzcu A, Bahceci M, Ozmen S, Gokalp D. Insulin resistance in type 2 diabetes mellitus may be related to bone mineral density. J Clin Densitom. 2012;15(2):186190. doi:10.1016/j.jocd.2011.11.005

31. Tonks KT, White CP, Center JR, Samocha-Bonet D, Greenfield JR. Bone Turnover is suppressed in insulin resistance, independent of adiposity. J Clin Endocrinol Metab. 2017;102(4):11121121. doi:10.1210/jc.2016-3282

32. Mesinovic J, McMillan LB, Shore-Lorenti C, et al. Sex-specific associations between insulin resistance and bone parameters in overweight and obese older adults. Clin Endocrinol (Oxf). 2019;90(5):680689. doi:10.1111/cen.13947

33. Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg Res. 2011;6:30. doi:10.1186/1749-799X-6-30

34. Gagnon C, Lu ZX, Magliano DJ, et al. Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: ausDiab). J Clin Endocrinol Metab. 2012;97(6):19531961. doi:10.1210/jc.2011-3187

35. Lee HS, Hwang JS. Impact of type 2 diabetes mellitus and antidiabetic medications on bone metabolism. Curr Diab Rep. 2020;20(12):78. doi:10.1007/s11892-020-01361-5

Read the original:
Association Analysis of Insulin Resistance and Osteoporosis Risk in Ch | TCRM - Dove Medical Press

Posted on 31 August, 2021

What follows is an extract from Yves Rees new book, titled All About Yves: Notes from a transition. Its published here with full permission.

I sink onto the red couch, clutching myself tight. I cross my legs, instinctive self-protection, then think better of it. Too feminine. Better to manspread a little. Before me, a coffee table houses a water jug, two glasses and a box of tissues. Typical shrink set-up.

Would you like some water?

Um, yes please.

The gender psychologist bends his lanky frame to pour from the jug. After handing over a glass, he settles into the armchair opposite. He crosses his legs, I note, but in that loose male wayone foot resting on the opposite thigh, crotch wide open. Still taking up space.

I look down at my own legs, spread them a little further apart. It feels insolent, to be so cavalier with my limbs.

The psychologist studies me over the rim of his glasses. He sports a white shirt and dark jeans, business casual, the slim-cut fabric flattering his elegant lines. No matter what happens, Ill never achieve that lissom shape. Ill remain forever stuck at 57, with a pelvis built to accommodate a human skull.

The psychologist watches me and I squirm under his gaze. I dont know what to do with my hands. Without thinking, I re-cross my legs.

So, he begins. What brings you here?

The psychologist was accredited with the World Professional Association for Transgender Health (WPATH), the global body that oversees trans medicine. Since 1979, WPATH has published Standards of Care to guide the treatment of trans and gender-nonconforming people. By using WPATH Standards, the psych would determine whether I was suffering from gender dysphoria, the medical term for the discomfort or distress that is caused by a discrepancy between a persons gender identity and that persons sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics).

In other words, gender dysphoria was the wrongness associated with my assigned role of woman. Id been born with female genitals, the world pronounced me woman, and now I was convinced thered been a terrible mistake. That was dysphoria.

The psychologists role was to shine the light of science on my distress. If I was found to have sufficient gender dysphoria, I would be officially transgender. With that diagnosis, I could get the green light for hormone replacement therapy and gender-affirmation surgery. I could carry my transness around like certified document, awash with red wax seals and weighty signatures. The world would have to believe me. Id be a legit member of Club Trans. Without the gender dysphoria diagnosis, I could get nothing. No surgery, no legitimacy. No hormones, unless I could find someone who prescribed testosterone via informed consent. Without the diagnosis, Id be just a fucked-up woman, a lady with issuesdisturbed, perhaps, but not trans. Or not, at least, according to the medical profession.

All About Yves is a timely and thought-provoking memoir about the trans experience.

So, what do you remember of early childhood? the psych asks in our second session. What kind of toys did you like to play with?

Hes in a blue shirt today, a lanyard draped around his neck. I feel like an insect under a magnifying glass, a strange specimen ripe for classification.

Um . . . well, I liked playing with my older brother, I begin. I idolised him. I always admired his clothes and wanted to look like him.

Hmmm, okay. The psych scribbles a few notes. And what were your favourite toys? What games did you play with your friends?

I make some quick calculations. The true answer is that I played with Barbies. Dolls houses. Dress-ups. I read fairytales. All the classic girl stuff. But thats not answer the psychs looking for. Im supposed to say that I rolled around in the dirt with trucks and climbed trees with my catapult and always, always refused to wear pink. Thats what female-to-male gender dysphoria is meant to look like. Thats the trans script Im meant to follow.

Only why is this new script as dull and narrow as the one I left behind?

Well, I played with a mix of toys, I guess. I had Barbies but also played heaps of cricket. We had Lego. I loved doing Warhammer with my brother.

Im spinning a story, telling neat tales of a tomboy childhood, once again inhabiting the character Ive been assigned: the trans person, born in the wrong body, a sick person looking for a cure. This is todays role. I must pull off the performance to get the diagnosis I need.

None of its a lie, not exactlyjust a question of emphasis. I mention the skateboard; omit the pink T-shirts and fairy wings. The full truth is so messy, too messy to fit inside this antiseptic office. The full truth is not woman, but not man either. Rather its something else altogether, something outside the stale binary that limits our imagination.

The psych pauses to take notes, re-crosses his legs. I sip water to fill the space.

And how did you feel about your body during childhood?

Well, I had an eating disorder as a teenager.

An eating disorder? Really? Tell me about that. Hes excited now, pen flying, on the trail of some solid dysphoria points. I can see my tally rising.

This is all a game, I realise, not a quest for truth. The rules are obvious: love everything masculine, disdain everything feminine. Hate your body. Share trauma. Be a fuck-up, but not too muchpsychosis is a disqualification. If you tick all the boxes, accumulate enough points, youll win the grand prize: gender dysphoria diagnosis, the golden ticket that opens all the doors.

The whole farce would be amusing if the stakes werent so high.

Simply put, diagnosis wields immense power, writes trans and disability activist Eli Clare. It can provide us access to vital medical technology or shame us, reveal a path toward less pain or get us locked up. It opens doors and slams them shut.

I would play along with the diagnosis game because I needed doors to open.

All About Yves: Notes from a transition is released today by Allen and Unwin (August 31, 2021). Buy it from all good bookshops or find itonline.

Read the rest here:
Notes from a transition: The Diagnosis Game - HerCanberra