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RELIEF FROM PERIMENOPAUSE

RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

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Page 1: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

RELIEF FROM PERIMENOPAUSE

Page 2: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

CONTENTSWhat is Perimenopause? 4

Hormonal Fluctuations During Perimenopause 5

Common Symptoms of Perimenopause 6

Simple Tips for Supporting Natural Hormone Balance 7

Targeted Strategies for Symptom Relief in Perimenopause 12

Cycle Irregularities 12

Hot Flashes & Night Sweats 13

Vaginal Dryness 14

Low Sex Drive 16

Insomnia 17

Stress & Anxiety 18

Brain Fog 19

Weight Gain 21

What About Hormone Therapy? 22

Action Plan 23

Honor Your Body 24

Page 3: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

Menopause. A word that often evokes feelings of dread, fear, anticipation, or even relief.

The time surrounding menopause, called perimenopause, often gets a bad rap because of the multitude of uncomfortable symptoms commonly associated with it: hot flashes, insomnia, weight gain, mood swings, and low-sex drive.

But, here’s the good news: you don’t have to live with these symptoms. While you can’t avoid Mother Nature, and you will inevitably age, (like fine wine, of course), the symptoms associated with perimenopause are often controllable with diet, lifestyle, and targeted supplementation. For more about balancing your hormones and over 500+ healthy recipes, visit 131Method.com

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WHAT IS PERIMENOPAUSE?

WHAT IS PERIMENOPAUSE?

4

HORMONES

Menopause refers to the permanent end of menstruation, i e “the final bleed ” The average age when a woman gets her last menstruation is around 51 True menopause is defined as the consecutive absence of a period for 12 months Perimenopause, however, refers to the years immediately leading up to menopause and the first year after menopause

Perimenopause can last for several years starting in your mid-40s; although some women may experience these symptoms starting in their early 40s and may last for a decade Studies show that women can expect to go through menopause and perimenopause at around the same age as their mother During perimenopause, your ovaries gradually become less efficient until they eventually stop responding to hormones that trigger ovulation

Page 5: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

HORMONAL FLUCTUATIONS DURING PERIMENOPAUSE

WHAT IS PERIMENOPAUSE?

5

HORMONES

HORMONAL FLUCTUATIONS DURING PERIMENOPAUSEThe main sex hormones affected during perimenopause include estrogen, progesterone, and testosterone This leaves us wondering, what is actually going on in our bodies during perimenopause?

You are born with two ovaries, and inside each of those ovaries are millions of follicles (tiny fluid-filled sacs that contain an egg) From the start of your very first period, your body releases one follicle/egg per month in a process known as ovulation These follicles are responsible for producing estrogen, testosterone, and progesterone During your reproductive years, your ovaries naturally lose thousands of follicles due to ovulation and other natural processes

As your follicle number declines, your body enters perimenopause This lower follicle count causes drops, or irregularities, in estrogen, progesterone, and testosterone, causing the annoying perimenopause symptoms

Page 6: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

COMMON SYMPTOMS OF PERIMENOPAUSE

WHAT IS PERIMENOPAUSE?

6

HORMONES

COMMON SYMPTOMS OF PERIMENOPAUSEDespite the variation in the age a woman begins to experience perimenopause, the symptoms associated with this natural process are relatively consistent Some of the most common symptoms resulting from this hormonal shift, which we discuss in detail in this guide, include:

• Menstrual Cycle Irregularities

• Hot Flashes

• Vaginal Dryness

• Low Sex Drive

• Insomnia

• Stress & Anxiety

• Brain Fog

• Weight Gain

Page 7: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

7

HORMONES

Before we discuss targeted strategies for easing perimenopause symptoms, let’s review the solid foundation of nourishing foods and lifestyle modifications that are key to promoting hormonal balance

You can’t build a house on a faulty foundation Similarly, you cannot promote hormonal balance without a solid foundation of nourishing foods, proper exercise, and a balanced lifestyle

Before paying hundreds of dollars to treat your perimenopause symptoms, establish your own personal healthy foundation That sought after solution may be found in simple diet, exercise, or lifestyle modifications

EAT A VARIETY OF ANTI-INFLAMMATORY FATS

Your body needs a variety of fats to create hormones, including saturated fat and cholesterol For in-depth lessons on inflammation, and over 300 anti-inflammatory recipes, visit 131 Method These foods contain fats that are the building blocks of hormone production:

• Avocados

• Wild-caught salmon

• Pasture-raised eggs

Page 8: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

8

HORMONES

• Coconut oil

• Nuts (especially those high in omega-3 like walnuts and macadamia nuts)

• Seeds (especially flax and chia seeds)

• Grass-fed butter

• Olive oil

LIMIT PROCESSED FOODS AND ADDED SUGAR

Processed food and/or foods high in added sugar can increase levels of inflammation, disrupt hormonal balance, worsen weight gain, and fuel mood swings Try to eat a diet rich in whole foods that are minimally processed and contain little to no added sugars

EAT AT LEAST FIVE CUPS OF NON-STARCHY VEGETABLES PER DAY

Non-starchy vegetables are low in carbohydrates, but high in fiber The fiber, vitamins, and nutrients in these vegetables help support hormonal balance

Page 9: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

9

HORMONES

Examples of non-starchy vegetables include:

• Dark leafy greens

• Crucifers - broccoli, cauliflower, cabbage, kale

• Tomatoes

• Bell peppers

• Asparagus

• Eggplant

• Zucchini

• Cucumbers

• Radishes

• Green beans

DON’T EAT NAKED CARBS

Blood sugar control is key to hormonal balance To keep blood sugar in check, always pair a carbohydrate source—like fruit, beans, or quinoa—with a protein and/or fat containing food For example, instead of only eating an apple for a snack, pair it with 1-2 tablespoons of nut butter for added protein and fat

Page 10: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

10

HORMONES

MAKE STRESS MANAGEMENT A PRIORITY

Elevated stress levels cause our hormones to go haywire Given the erratic hormonal fluctuations already occurring in perimenopause, this is the last thing we need! Find a stress reducing activity and commit to it daily, if possible Even five minutes of deep breathing or meditation can have a huge benefit on hormonal balance

GET ENOUGH SLEEP

Aim to get seven to eight hours of high quality sleep per night Poor sleep negatively affects your hormones Engage in healthy sleep hygiene such as:

• Avoid caffeine after 1 p m

• Limit technology within an hour of bedtime

• Establish a regular night time routine

• Sleep in a dark, cool room

We will discuss further strategies for insomnia later!

MOVE YOUR BODY

Exercise can reduce stress levels, increase blood flow, and promote hormonal balance Try to incorporate

Page 11: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

SIMPLE TIPS FOR SUPPORTING NATURAL HORMONE BALANCE

11

HORMONES

natural movement, like walking, into your daily routine Additionally, find a type of exercise that you enjoy and can realistically maintain Like zumba class? Great! Love lifting weights? Excellent! The best form of exercise is the one that makes you happy and keeps you motivated

REDUCE XENOESTROGEN EXPOSURE

Xenoestrogens are a group of hormone-disrupting compounds that mimic natural estrogen found in the body (1) During perimenopause, your estrogen levels are often erratic or reduced Xenoestrogens can block or bind to your estrogen receptors and further complicate the already scattered production and reception of estrogen during perimenopause Although xenoestrogens are not completely unavoidable, there are some ways to reduce exposure:

• Choose glass over plastic when storing and reheating food

• Use makeup and skincare products that are free from parabens, phthalates, and triclosan

• Avoid pesticides by choosing organic produce whenever possible For more on organic vs conventional produce, read this

Page 12: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

CYCLE IRREGULARITIES

TARGETED STRATEGIES FOR SYMPTOM RELIEF IN PERIMENOPAUSE

TARGETED STRATEGIES FOR SYMPTOM RELIEF

12

HORMONES

Creating a solid foundation of nourishing foods, movement, and stress management is key to finding relief from perimenopause However, many women still experience symptoms despite their best efforts Here are some additional strategies you can use to find relief from these frustrating symptoms:

Disclaimer: Please check with your doctor before starting any new supplements.

CYCLE IRREGULARITIESAbout 80 percent of women experience some type of change in their cycle even as early as seven years before their last period At first, you may experience heavier and more frequent periods This is likely due to the erratic bursts of estrogen coming from your ovaries, or an imbalanced estrogen to progesterone ratio

Oppositely, as your body begins to make less estrogen nearing menopause, your period may become much lighter and less frequent due to longer cycles and sporadic ovulation

Page 13: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

HOT FLASHES & NIGHT SWEATS

TARGETED STRATEGIES FOR SYMPTOM RELIEF

13

HORMONES

What You Can Do

• If experiencing heavy periods, avoid excessively hot showers and baths whenever you’re bleeding

• Avoid alcohol during heavy periods as this limits blood clotting and can make bleeding worse

• Eat more cruciferous vegetables (kale, broccoli, cauliflower, arugula, and cabbage) as these contain a compound that supports healthy estrogen metabolism

• Consider a supplement called DIM (diindolylmethane), which contains high amounts of the above estrogen regulating compound

• Increase iron-rich foods to replace losses from heavy periods, like red meat, chicken, turkey, liver, shrimp, eggs, and sardines

HOT FLASHES & NIGHT SWEATSHot flashes are sudden feelings of heat that spread throughout the upper body Most women experience hot flashes at some point during perimenopause Likewise,

Page 14: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

VAGINAL DRYNESS

TARGETED STRATEGIES FOR SYMPTOM RELIEF

14

HORMONES

night sweats often follow hot flashes and feel similar to heavy sweating These symptoms can start before you notice any cycle irregularities and may continue one to two years after your last period (menopause)

What You Can Do

• Wear breathable fabrics like cotton or wicking fabrics often found in athletic clothes

• Limit spicy foods, excessive caffeine, and alcohol as these may trigger hot flashes

• Quit smoking

• Try acupuncture; although results are mixed, some women have found relief from hot flashes with acupuncture (2)

• Try black cohosh, an herb that has been shown to reduce hot flashes by up to 26 percent (3), (4)

VAGINAL DRYNESSThe third most common symptom during perimenopause is vaginal dryness Like the other symptoms, this occurs due to progressively dropping estrogen levels

Page 15: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

TARGETED STRATEGIES FOR SYMPTOM RELIEF

15

HORMONES

As menopause approaches, most women find that their vaginas take longer to become sexually lubricated, and they may even experience vaginal irritation during sex

What You Can Do

• Take more time for foreplay! Even before perimenopause, women typically take longer to become sexually aroused than men Be open and honest with your partner, so you can discuss strategies to increase the effectiveness of foreplay

• Avoid body washes and personal hygiene products that contain fragrances or dyes that can dry out the sensitive vaginal area

• Choose cotton-based panties that allow the vagina to “breathe ” We know this may not seem sexy, but clothing companies are getting pretty creative nowadays!

• Use water-based lubricants

• Avoid vaginal douches These will only make vaginal dryness worse

Page 16: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

LOW SEX DRIVE

TARGETED STRATEGIES FOR SYMPTOM RELIEF

16

HORMONES

LOW SEX DRIVEIf vaginal dryness isn’t sexy enough, perimenopause may cause your sex drive to plummet

Testosterone is the main hormone responsible for giving you a healthy sex drive As you enter perimenopause, your ovaries produce less testosterone and begin to rely more on your adrenal glands, especially if you are overly stressed This causes the adrenal glands to produce less testosterone and more cortisol (your main stress hormone) As a result: bye-bye sex drive!

But, it’s not the end for you girlfriend! Here are a few strategies to help you get your groove back

What You Can Do

• Use adaptogenic herbs, like ashwagandha, to help balance cortisol levels This herb may even enhance arousal, lubrication, and orgasm scores (5) The most common way to take this herb is through capsule form

• Prioritize stress management - treat the root cause! Make things like meditation, yoga, deep breathing, walking, reading, or journaling a priority to reduce stress and boost testosterone As you reduce stress levels,

Page 17: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

INSOMNIA

TARGETED STRATEGIES FOR SYMPTOM RELIEF

17

HORMONES

your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win!

• Try maca root in powder or supplement form This plant may increase sexual desire in menopausal women (6)

INSOMNIAHot flashes and night sweats often lead to another common perimenopausal symptom: insomnia On top of that, reduced estrogen levels can lower melatonin levels, which is your main sleep hormone that rises at night to induce sleep

Unfortunately, insomnia can worsen other perimenopause symptoms, like weight gain, and anxiety, so ignoring this symptom may lead to a vicious cycle of unpleasant side effects

What You Can Do

• Practice good sleep hygiene, like limiting technology before bed, avoiding alcohol at night, and limiting caffeine after 1 p m

• Keep your room dark and at a cool temperature

Page 18: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

STRESS & ANXIETY

TARGETED STRATEGIES FOR SYMPTOM RELIEF

18

HORMONES

• Drink a cup of valerian root tea before bed, which may reduce hot flashes and insomnia (7)

• Add a magnesium supplement We prefer magnesium glycinate, as it is well absorbed and tolerated Try starting with 150-200 milligrams 1-2 hours before bed

• Consider Calmful Sleep powder by Natural Vitality This supplement powder contains a combination of magnesium glycinate and melatonin It also provides GABA and L-Theanine, which are two compounds that promote feelings of calm and may promote better sleep as well

STRESS & ANXIETYAs you enter perimenopause, you may notice that you feel more anxious and don’t cope as well with stress This happens because of a natural decline in progesterone levels, a hormone that promotes feelings of calm and stability The drop in progesterone is a natural and inevitable process, though temporary Your ability to cope with stress will eventually return! In the meantime, there are a few strategies you can implement to reduce the overall effect of stress and anxiety experienced during perimenopause

Page 19: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

BRAIN FOG

TARGETED STRATEGIES FOR SYMPTOM RELIEF

19

HORMONES

What You Can Do

• Slow down and rest Instead of fighting against your body, work in harmony with it You have permission to take care of yourself Rest and engage in calming activities that you enjoy It’s okay to ask for help, and it is okay to say “no” in order to prioritize your own health

• Boost magnesium-rich foods and/or consider a magnesium supplement This mineral is a natural stress-reliever Unfortunately, more than half of Americans do not get enough magnesium Magnesium rich foods include: nuts, seeds, and leafy green vegetables

• Take ashwagandha As mentioned earlier, this herb helps to naturally balance stress hormones and has shown to significantly reduce anxiety (8), (9)

• Talk with your doctor about trying a natural progesterone cream

BRAIN FOGAre you losing your keys more often? Do you struggle to remember dates or specific details? You can thank perimenopause for that

Page 20: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

TARGETED STRATEGIES FOR SYMPTOM RELIEF

20

HORMONES

Estrogen helps with memory and increases a compound called BDNF in your brain (10) BDNF keeps brain cells healthy and regulates your mood, among other things When estrogen levels are low or sporadic, as in perimenopause, you can experience brain fog, forgetfulness, and trouble concentrating

What You Can Do

• Try to exercise several times per week Exercise can increase BDNF and improve memory

• Eat low-mercury fish that is rich in nourishing omega-3 fats for the brain (primarily salmon, sardines, anchovies, mackerel, and herring)

• Consider practicing meditation, which can improve focus, reduce brain fog, and enhance memory (11)

• Eat probiotic rich foods like yogurt, kefir, kombucha, raw sauerkraut, kimchi, and fermented vegetables The health of your gut affects many aspects of your brain function as well

Page 21: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

WEIGHT GAIN

TARGETED STRATEGIES FOR SYMPTOM RELIEF

21

HORMONES

WEIGHT GAINAs you age, you may find that maintaining or losing weight is more difficult This may be especially true once you enter perimenopause due to fluctuating levels of estrogen and reduced testosterone levels

Despite what you may hear, weight gain during menopause is not inevitable

What You Can Do

• Incorporate strength training As your testosterone levels drop, so will your lean body mass Lifting weights can help build muscle and boost your metabolism (12)

• Consider dietary phasing As a key component to the 131 Method, dietary phasing prevents your metabolism from adapting to one way of eating With this formula, you can burn through menopausal weight struggles

• Limit refined carbohydrates or high-carb diets Perimenopause can reduce your body’s ability to metabolize carbs effectively, which may lead to further weight gain (13)

Page 22: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

WHAT ABOUT HORMONE THERAPY?

TARGETED STRATEGIES FOR SYMPTOM RELIEF

22

HORMONES

• Prioritize sleep Getting enough sleep is key to reducing sugar cravings, regulating your appetite hormones, and boosting your metabolism

WHAT ABOUT HORMONE THERAPY?Hormone therapy is perhaps one of the most confusing and contradictory topics in women’s health

When hormone therapy was first prescribed, not much was known about the long-term effects Years later, it was discovered that certain types of estrogen therapy could increase a woman’s risk of uterine and breast cancer However, many doctors stress that the hormone therapy used today is much different and safer than before

Often considered the more natural alternative, bioidentical hormones are compounds that have the same molecular structure as the hormones produced in your body Many functional medicine or naturopathic doctors use forms of bioidentical hormones to reduce perimenopausal symptoms There are conflicting opinions whether bioidentical hormones are safer than synthetic hormones

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ACTION PLAN

ACTION PLAN

23

HORMONES

Hormone therapy will not cure all perimenopausal symptoms, but it may provide relief from some of the common complaints, like hot flashes and vaginal dryness The bottom line is that there is no ideal answer to whether or not you should use hormone therapy Each woman’s situation and body is unique, so the question of hormone therapy should be thoughtfully discussed with a doctor who is experienced in this field

ACTION PLAN• Decide which lifestyle tips you’re ready to start

changing today:

• Eat a variety of anti-inflammatory fats

• Limit processed foods and added sugar

• Eat at least five cups of non-starchy veggies

• Don’t eat naked carbs

• Make stress management a priority

• Get enough sleep

• Move your body

• Reduce xenoestrogen exposure

Page 24: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

HONOR YOUR BODY

HONOR YOUR BODY

24

HORMONES

• Depending on your symptoms, review the strategies given above

• Consult with your doctor, or find an integrative healthcare provider for a more natural approach to discuss different options or hormone replacement therapy

HONOR YOUR BODY There are many inevitable changes that we cannot control during perimenopause And let’s be honest, the symptoms suck But, at the risk of sounding super cheesy, we encourage you to look back at all of the amazing things your body has done for you so far Whether this be birthing your babies, supporting your family, and/or being a boss babe who is totally rocking her career, we’re positive that your body has done amazing things

We know you may feel frustrated with your body right now, so focus on the factors that you can control

You can control the types of foods you eat, so make sure to eat a nourishing diet rich in anti-inflammatory fats,

Page 25: RELIEF FROM PERIMENOPAUSE€¦ · your sex drive will increase Plus, sex is a natural stress reducer So, it’s a win-win! • Try maca root in powder or supplement form This plant

HONOR YOUR BODY

25

HORMONES

non-starchy vegetables, and lots of fiber Limit refined carbohydrates and sugar as much as possible Make sleep and stress management a priority in your life Ask for help Laugh, meditate, and take a vacation because GIRL, you deserve one Find a method of exercise that works best for you Listen to your body and honor it It’s the only one you have!

The 131 Method can help you stop dieting and finally understand how your unique body works Our proven system can help you balance your hormones, ignite your metabolism, and break through stubborn weight loss resistance Plus, our team of 131 Registered Dietitians are here to help you along the way Join us today!

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RESOURCES

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HORMONES

RESOURCES1 https://www sciencedirect com/science/article/abs/pii/S0960076011000288

2 https://www mayoclinic org/diseases-conditions/hot-flashes/diagnosis-treatment/drc-20352795

3 https://www ncbi nlm nih gov/books/NBK79338/

4 https://www tandfonline com/doi/ /10 3109/09513590 2013 831836?scroll=top&needAccess=true

5 https://www naturalmedicinejournal com/journal/2016-04/ashwagandha-root-extract-and-sexual-function-women

6 https://www ncbi nlm nih gov/pubmed/20691074

7 https://www ncbi nlm nih gov/pmc/articles/PMC3813196/

8 http://www ijpm info/article asp?issn=0253-7176;year=2012;volume=34;issue=3;spage=255;epage=262;aulast=Chandrasekhar

9 https://www liebertpub com/doi/full/10 1089/acm 2014 0177

10 https://www ncbi nlm nih gov/pubmed/27602095

11 https://www ncbi nlm nih gov/pubmed/22496570

12 https://www ncbi nlm nih gov/pmc/articles/PMC3296386/

13 http://care diabetesjournals org/content/diacare/23/12/1731 full pdf