Metabolic syndrome and the menopausal woman.
Subject: Insulin resistance (Diagnosis)
Insulin resistance (Care and treatment)
Insulin resistance (Patient outcomes)
Insulin resistance (Risk factors)
Menopause (Care and treatment)
Menopause (Patient outcomes)
Author: Morstein, Mona
Pub Date: 02/01/2012
Publication: Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464
Issue: Date: Feb-March, 2012 Source Issue: 343-344
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 282825224
Full Text: Weight gain is an epidemic in the US today, with up to 66% of all Americans being either overweight or obese. Increased central fat in the abdominal (a.k.a. visceral) fat initiates numerous hormonal and biological abnormalities in humans, including "insulin resistance," whereby cells, mostly adipose, lose their sensitivity to react to insulin and absorb glucose from the bloodstream. This is a growing problem throughout our society, including our aging women.

Insulin Resistance Biochemistry

Insulin is a hormone secreted by pancreatic beta cells in the islets of Langerhans. It attaches to receptors on cells, mostly the fat and liver cells, but a little bit on muscle cells as well, although insulin like glucose-1 has more muscle receptor cells than insulin. Insulin initiates chemical signals for a glucose transporter -Glut-4 - to absorb glucose into the cells.

Insulin is called "the fat-building hormone" and is designed to store glucose as fat in fat, liver, and muscle cells; promote abdominal fat; increase protein absorption into cells; reduce metabolic burning; and increase glycogen, fatty acids, and protein synthesis.

Insulin resistance (IR) occurs when the body's cells do not recognize insulin. As a result, glucose levels in the serum stay elevated and the pancreas secretes increased insulin levels. Glucose that does enter cells is transformed to metabolically active fat, which produces cytokines which further decreases the cells' capacity to recognize insulin. Insulin resistance also reduces appetite control so people are prone to overeat, thus badly increasing glucose levels and fat development (see Table 1).

There are many IR etiological factors and it is beyond this article's scope to expand on all of them. Here is a list of the main factors:

* Obesity: abdominal/visceral fat leads to IR via the cytokines that it produces which reduce cellular insulin response and to the fat dumping which causes liver IR.

* Lack of exercise: regular, continuous exercise can burn off calories and fat, not only during exercise sessions but even between them. The growth of lean muscle mass is vital to prevent IR.

* Refined carbohydrates: a metaanalysis showed that high-fructose corn syrup was the No. 1 food ingredient for the rise in obesity in our country in the last 30 years. Refined sugars and white flours, high in calories, very low in nutrients, and devoid of fiber, play havoc with the biochemistry and hormonal regulation of our bodies, promoting IR.

* Saturated fats: increased ingestion of saturated fats due to eating agriindustry grain-fed meats (vs. grass-fed/grass-finished meats), as well as fast foods and processed foods, indeed cause cells to become insulin resistant.

* Gluttony: excess caloric intake, especially in sugar and saturated fat, leads to obesity, and IR.

* Hormonal imbalances: alternatively oriented physicians will study the thyroid, adrenal, and sexual reproductive hormones in patients, as those hormones, if not in healthy balanced states, can decrease metabolism, increase glucose production from the liver, decrease the capacity for muscle/bone building, and lead to abdominal weight gain.

* Environmental toxicities: WHO has clearly stated that arsenic and lead can lead to IR, as can many chemicals prevalent in our world, such as bisphenol A, ammonium perfluorooctanoate (in Teflon), phthalates. Mercury in high-fructose corn syrup is also very damaging to body cells.

When IR develops further in the patient, it can turn into metabolic syndrome (MetSyn).

Features of MetSyn:

* central obesity

* insulin resistance

* dyslipidemia: elevated TG, small dense LDL particles, reduced HDL

* high blood pressure

* hypercoagulable state

* pro-inflammatory state

ATP III Diagnostic Criteria For MetSyn

Three Or More Positive Can Diagnose Metabolic Syndrome

Waist circumference

Women: >35 inches/88 cm

Men: >40 inches/102 cm

Elevated triglycerides: > 150 mg/dl

Low HDL: Women < 40 mg/dl

Men: < 50 mg/dl

Hypertension: > /= 130/85 mmHG

Fasting glucose:

>/= 100 mg/dl (< 126 mg/dl)

These features lead to the complications of the condition, including increased risk of cardiovascular disease, and if it is not reversed and continues or worsens, it leads to the likely eventual diagnosis of type 2 diabetes.

Postmenopausal Women

How does IR specifically affect postmenopausal women (PMW)? Statistics show that 40% to 50% of PMW have MetSyn, so all physicians who see this category of patients need to investigate and treat this situation. PMW have been shown to gain up to on average a pound a year; also, as women age, they may devote less time to exercising. (Carr)

Multiple studies have been done regarding IR and PMW; some showed that increased IR developed, some did not. One in particular showed that in women over 60 years old with visceral fat, IR clearly developed. (DeNino) Another study showed that up to 14 years postmenopause, developing MetSyn was an increased risk, along with its complications of hypertension, hypertriglyceridemia, and obesity. (Menopause)

Postmenopausal women, especial ly those struggling with MetSyn, tend to have higher cholesterol, and higher LDL cholesterol numbers, at least 10% to 20% higher than premenopausal women. PMW tend to gain 16% more triglycerides after the transition, have elevation in their lipoprotein(a) faction, and decrease their protective HDL levels. PMW have higher levels of PA 1-1 and tPA, as well as increased interleukin-6 levels. All three of those increase the risk of CVD.

In PMW with MetSyn, hormone levels have shown high testosterone and free androgen index, high estradiol, low thyroid function, high Cortisol, and increased inflammatory markers. Please note that elevation in Cortisol is usually from active biochemical changes in adipose fat cells, which produce excessive Cortisol, and is not necessarily associated with adrenal activity.

PMW have also been shown to be low in vitamin D, which is associated with MetSyn and an increased effect of IR.

The lack of estrogen production, normal in PMW, is also potentially a risk factor because when a woman loses the production of that hormone, it is easier for her to gain central obesity, have higher fibrinogen levels, reduce HDL, and increase LDL and TG. In one rat study, estrogen inhibited fat storage in the liver, muscle, and fat tissue; activated pathways that promote burning the fat in muscles; broke down stored fats for energy; and was in general "anti-insulin." (Greenberg) Also, it seems that natural menopause is a bit more protective than surgical menopause in developing MetSyn - in 263 women who had a bilateral oophorectomy before natural menopause, 47% of the surgical women developed MetSyn vs. only 36% of women who went through natural menopause. (Endocrine Today) In MetSyn women with elevated BMI, testosterone tends to be elevated and sex hormone binding globulin tends to be decreased.

CVD is rare in women under 50 years old, but equals the occurrence in men by age 71, and there is a higher risk of CVD in MetSyn PMW. In one study, MetSyn in PMW increased heart sensitive-C-reactive protein. (Lewis) Women with elevated HS-CRP greater than 3 had a higher risk of CVD event. PMW with MetSyn also had a 66% increased risk in developing cognitive impairment, 40% increased risk of gallbladder surgery. In terms of MetSyn developing into frank type 2 diabetes mellitus, of the around 40% of PMW with MetSyn, 80% of those patients develop type 2 diabetes mellitus, 9 out of 10 have serious complications within 6 years (CVD, retinal damage, renal failure, skin ulceration), and one-third die within 6 years of diagnosis.

So, physicians seeing menopausal women have to take great care in analyzing them for IR, and doing a comprehensive laboratory analysis and physical exam.

A typical PMW analysis could include:

1. fasting glucose and insulin followed by high-sugar, high-white flour, high-saturated fat meal (e.g., from fast-food restaurant - one pancake, one syrup, one serving hash browns, water) and then repeat glucose and insulin 1.5 hours after the meal. Postprandial glucose can at times diagnose IR more effectively than fasting glucose;

2. CBC with differential;

3. comprehensive CMP, including hepatic panel with GCT (elevation can be first indicator of fatty liver), kidney panel, lipids, electrolytes;

4. ferritin (elevation is most common first sign of fatty liver);

5. TSH, free t3, free T4;

6. estradiol, free/total testosterone, sex hormone binding globulin;

7. homocysteine, HS-CRP, fibrinogen;

8. vitamin D3;

9. salivary Cortisol x4 and DHEA;

10. weight, waist circumference, BMI and/or waist/hip ratio;

11. vitals;

12. general physical exam;

13. environmental toxicity urine challenge

Treatment of Postmenopausal Women with MetSyn or IR

There are several key goals to treatment of PMW with IR/MetSyn:

* weight loss

* appropriate diet

* exercise

* lifestyle: stress relaxation, sleep, detox

* drugs

* supplementation

* hormones

Weight Loss

Many studies show that losing just 7% to 10% of weight in the first year can have a massive benefit in eradicating MetSyn and reducing the risk of developing diabetes and other medical complications. If a 5'3" woman weighs 200 lbs, it means that if she just loses up to 20 pounds, while still being clearly overweight, that weight loss alone can have a major impact on her health. Most alternatively minded physicians can easily enable that little weight loss with any cooperative and motivated patient. One can figure out the patient's BMR, via this classic methodology:

Diet

The first thing to discuss with the patient about how to lose the weight is combining an effective diet with an exercise protocol. Many studies have been done, but the lower-carbohydrate diet is recommended by the Nutrition and Metabolism Society, and has been shown to be advantageous in innumerable studies. Tangential diets along those lines also include a raw-foods diet, or an "alkaline diet/,"both vegan with high amounts and quality of vegetables, and nuts and seeds and oils as a dietary focus.

The standard lower-carbohydrate diet removes all refined grains and sugars, and most whole-grain products, except perhaps for some crackers, which are very high in fiber, and lower in carbs. Also, patients can get shirataki noodles (from konjak or tofu), and some kelp noodles are very low in carbs.

Patients should also consume:

1. organic as much as possible;

* good proteins: variety of nuts/ seeds, non-GMO organic non-soy-protein isolate soy, nontoxic fish, legumes, animal flesh (organic, grass-fed, grass-finished), omega-3 organic eggs, cow/goat/sheep cheese or nondairy cheese; plain yogurts; unsweetened nondairy milks;

* beverages: water (half body size in ounces to a lucid amount); green tea, herbal teas; coffee or coffee substitutes; unsweetened alternative milks; fresh vegetable juices; one serving of alcohol (if no fatty liver, and patient can handle alcohol - this lowers serum glucose); alternative "soda pops" sweetened with any of the allowed sweeteners listed below (e.g., Zevia);

* 2 to 5 cups of vegetables a day (not allowed: potatoes, yams, sweet potatoes).

* one fruit serving a day (in addition to avocadoes and tomatoes) -preferably berries;

* good oils: unrefined organic extra-virgin olive oil, organic coconut oil, walnut oil (contains omega-3), sesame oil, flaxseed oil (uncooked; contains omega-3), organic butter (cow or goat), butter substitutes;

* alternative sugars: stevia, erythritol, xylitol. No artificial sweeteners, no agave, coconut nectar, honey, etc.

The good news is that as soon as patients start eating this way, their IR drops severely and their appetite control comes back into use, so they often notice that within a week, they are less hungry, require less food, and enjoy what they are eating. This is obviously win-win for doctors and patients and immediately helps reverse MetSyn.

Exercise

A study done by the University of Pittsburgh on weight loss showed that physical activity with that goal should include one hour of exercise a day for five days a week, split between aerobic and resistance exercise. Johns Hopkins did a study showing that patients 55 to 75 years old who exercised 60 minutes 3 times a week with a mixture of aerobic and anaerobic had a 20% loss in abdominal fat, and weight loss. In the MetSyn patients in the study, 9 completely resolved their MetSyn and there were no new cases. Last, a Northwestern Memorial Hospital study looked at 6000 women who in 1992 had no evidence of CVD. Over the next 9 years, women with MetSyn were 57% more likely to die than those without MetSyn. Women who worked out and had higher cardiovascular fitness, however, lost ad the elevated risk and became equal to women without MetSyn.

I typically have patients do 30 to 40 minutes of aerobic and then 20 to 30 minutes of resistance ideally five days a week. For resistance, anything can be used, from sit-ups/chin-ups, to free weights or weight machines; resistance bands are easy for patients to use. Anaerobic combined with aerobic exercise enhanced glucose disposal in postmenopausal women with type 2 diabetes.18 Some I train to do "burst exercise," which rotates between regular pace with maximum pace to enhance weight loss. If patients can motivate themselves to embark on this type of schedule, the rewards are consistent and limitless.

Exercise can lower IR, decrease triglycerides, decrease hypertension, promote weight loss, improve body image, and decrease depression.

Lifestyle: Stress Relaxation, Sleep, Detox

Stress relaxation is also vital for those patients who more easily lose their sense of peace in day-to-day life. Perimenopausal women with abdominal fat had elevated Cortisol, negative moods, and life stress, so physicians need to address this aspect of health. Yoga was found to reduce blood pressure and increase energy and sense of well-being in MetSyn adults aged 30 to 65 years.

The NHANES study showed that if patients sleep less than 6 hours a night, they had a 235% increase risk of becoming obese compared with those who slept 7 hours a night. Lack of sleep increases ghrelin, a hormone that drives people to eat more and especially carbs; lowers leptin, a hormone that controls appetite; and raises Cortisol, which increases glucose production from the liver.

Sleep apnea needs to be investigated and treated as well if signs and symptoms seem to indicate that it may be a problem.

If a patient was found to be toxic in IR-inducing minerals or chemicals, undergoing an appropriate detoxification protocol would be meaningful.

Drugs

In a classic study mentioned frequently at alternative conferences, a study comparing metformin and lifestyle changes clearly showed that lifestyle invention for three years was more effective at reducing the prevalence and onset of MetSyn than metformin. In fact, as a rule, metformin did not prevent MetSyn in women as it may have in men. In the metformin group, 23% were no longer MetSyn patients; in the lifestyle group, 38% eradicated their MetSyn. Exenatide is a twice-a-day injection and is very expensive, so not all patients wish or are able to begin its off-label protocol of reducing the appetite.

Drugs for IR tend to include off-label metformin to reduce glucose levels or Byetta (Exenatide) to reduce appetite, and also medications to control high blood pressure or elevated lipids. Most alternatively minded doctors are aware that diet, exercise, and supplements can have marked effects on those signs and oftentimes do not feel compelled to use them unless hypertension is fully established.

Supplementation

There are many benefits to using nutritional and botanical supplementation with MetSyn menopausal patients.

Benefits to nutritional/botanical supplementation:

* fix nutrient deficiencies and enable cells to function maximally

* enhance insulin sensitivity and lower glucose levels

* antioxidant and anti-inflammatory protection

* appetite control

* antihypertensive and antihyperlipidemic action

* increase mood: antidepression/-anxiety

A study done in Iran showed that postmenopausal urban women had higher BMI and lower DRI intakes of calcium, B2, B6, folate, zinc, selenium, and fruits and vegetables.

However, it is important to give patients at least some of the below. Physicians of course change supplements around to their own individual requirements for patients:

* good multiple: not a one a day. Most alternative physicians use companies that require 6 capsules a day. This replenishes nutrients that may be low due to poor diet, or the body may need extra to support a return to health;

* fish oils; at least 1000 mg EPA/750 mg DHA a day. Benefits to essential fatty acids include lower lipids, lowering high blood sugar, promoting insulin sensitivity, being anti-inflammatory, treating essential fatty acid deficiency, promoting good mood;

* IR formula containing nutrients and botanicals that reduce IR: extra chromium, zinc, vanadium, Gymnema sylvestre, Momordica charantia, ginseng, holy basil, cassia cinnamon;

* antioxidants to protect the body from damage from elevated glucose levels and proinflammatory cytokines:

* R-alpha-lipoic acid

* green tea extract

* N-acetylcysteine

* other botanicals, flavonoids, proantbrocyanidins: cuvcumin, resveratrol, bilberry or blueberry, hawthorn, gingko, Silybum marianum;

* lecithin: for weight loss, prevention of cholelithiasis due to weight loss, and as a gentle antihyperlipidemia;

* vitamin D3 and calcium: correct if hypovitaminosis: there are many studies showing that vitamin D3 can lower glucose levels in IFG patients, reduce IR, and reduce risk of metabolic syndrome in older men and women.

Hormone Formulas

Bioidentical-type hormones are used most commonly by alternative physicians. Hormones that may be imbalanced in postmenopausal women with MetSyn include:

A study reported that women with low estrogen who were not treated with hormone replacement therapy had higher levels of Cortisol, which is associated with abdominal fat development. When those women were given HRT, their Cortisol numbers diminished and they decreased their abdominal fat. Studies show that HRT seems to be safest used via transdermal application vs. oral.

Each physician has to evaluate if bioidentical hormone replacement therapy is safe and appropriate for each female patient. If a woman's IR is combined with frequent or severe hot flashes or osteoporosis, then BHRT seems more indicated. If the patient refuses to engage in dietary, exercise, sleep, or stress/lifestyle changes, then BHRT may be the lesser of two evils given the risks of the her having damage from elevated glucose levels and becoming a type 2 diabetic patient.

Summary

Postmenopausal women require a comprehensive work-up to analyze if they presently have or are at risk of developing IR and/or MetSyn. Discussions with patients who have those conditions is vital, so that they understand the increasing risks of serious complications. Helping patients become motivated to make changes, and clearly presenting areas that they need to address, while supporting their efforts, is an incredibly effective method of reversing this condition and having women go through their menopausal years in a much healthier way.

References

Postmenopausal Women and MetSyn

Carr MC The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 88(6):2404-2411.

DeNino WF, Tchernof A, Dionne I), et al. Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care. 2001;24:925-932.

Kaaja RJ. Metabolic Syndrome and the menopause. Menopause Int. March 2008; 14:121-125.

Bliss RM. Estrogen and exercise promote leanness in similar ways [online article]. USDA. Oct. 21, 2005.

Weinberg ME et at. Low sex hormone binding globulin is associated with the metabolic syndrome in postmenopausal women. Metabolism. 2006 Nov; 55(1l):1473-1480.

Postmenopausal status may increase risk for the metabolic syndrome. Menopause. 2008; 15:524-529

Lewis SJ. After menopause: novel marker helps to identify women at risk for heart disease. J Fam Prac. July 2004.

Santoro N. Bilateral oophorectomy before menopause associated with increased risk for metabolic syndrome. Endocr Today. August 2008.

Exercise

Diabetes Care. 2000; 22(4). (IR)

J Cardiopulm Rehab. 2002; 22. (TC) JAMA. 2002; 288(13). (HTN)

Physician Sports Med. 1999; 27(10). (depression)

Physician Sports Med. 1999; 27(10). (anaerobic type 2)

Stress Relaxation

Cohen BE, Chang AA. Restorative yoga in adults with metabolic syndrome.

Metab Syndr Relat Disord. Sept 2008; 6(3); 223-229.

Epel E, Brownell KD. Stress may cause excess abdominal fat in otherwise slender women. Psychosom Med. Sept/Oct 2000,

Gangwisch JE et al. Inadequate sleep as a risk factor for obesity: analyses of the NHANES 1. Sleep. 2005 Oct: 28(10):1289-1296.

IR Testing

Rao SS. Impaired glucose tolerance and impaired fasting glucose. Am Fam Physician, 2004 Apr 15;69(8):1961-1968

IR Etiology

A survey of bisphenol A in US canned foods [online article]. Environmental Working Group. March 5, 2007. EWG. org

Tseng CH. The potential biological mechanisms of arsenic-induced diabetes mellitus. Toxicol Appl Pharmacol. 2004 Jun 1; 197(2):67-83. http://www.ncbi.nlm.nih.gov/pubmed/15163543.

Low Carb Diet

Nutrition & Metabolism Society. Fighting the mainstream misinformation on diabetes and obesity [Web page], http://tinyurl.com/d48m7j.

Low carb diet reversed MetSyn in 50% of participants. J Nutr. Aug 2007.

Low carb reduces saturated fats and markers of inflammation in MetSyn patients. Lipids. Dec 2007.

Drugs

Metformin and lifestyle prevention may help prevent the metabolic syndrome. Ann Intern Med. 2005; 142:611-619.

Supplements

Nemati A, Baghi AN. Assessment of nutritional status in postmenopausal women of Ardebil, Iran. J Biol Sci. 2008:(1):196-200. Available at: http://www.scialert.neL/qredirect.php?doi=Jbs.2008.196.200&linkid=pdf.

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007; 30:980-986.

Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am I Clin Nutr. 2004; 79:820-825.

Vitamin D (lower MetSyn): Diabetes. Oct 2008.

Curcumin/Resveratrol: Nutr Metab. 2008; 5:17.

[ILLUSTRATION OMITTED]

English BMR Formula

Women: BMR = 655 + (4.35 x weight in pounds) + (4.7 x height in inches) - (4.7 x age in years)

Men: BMR = 66 + (6.23 x weight in pounds) + (12.7 x height in inches) - (6.8 x age in years)

Adding in the daily activity of the patient allows one to specify true caloric needs.

Harris Benedict Formula

To determine your total daily calorie needs, multiply your BMR by the appropriate activity factor, as follows:

* If you are sedentary (little or no exercise): Calorie-Calculation = BMR x 1.2

* If you are lightly active (light exercise/sports 1-3 days/week): Calorie-Calculation = BMR x 1.375

* If you are moderately active (moderate exercise/sports 3-5 days/week): Calorie-Calculation = BMR x 1.55

* If you are very active (hard exercise/sports 6-7 days a week) *. Calorie-Calculation = BMR x 1.725

* If you are extra active (very hard exercise/sports & physical job or 2 x training): Calorie-Calculation = BMR x 1.9

Total Calorie Needs Example: If you are sedentary, multiply your BMR (1 745) by 1.2 = 2094. This is the total number of calories that you need to maintain your current weight.

To encourage weight loss, one can deduct 500 to 1000 kcal/day from one's total calorie needs equation; however, one does not lower caloric needs to less than 1000 kcal/day total.

Dr. Mona Morstein is a naturopathic physician. She is chair of nutrition, gastroenterology professor, and clinical supervisor at Southwest College of Naturopathic Medicine, Tempe, Arizona. Dr. Morstein has a generalized practice seeing all ages, both genders, and acute and chronic disease, but she does focus on prediabetes and diabetes, gastroenterological conditions, and women's health. Dr. Morstein frequently lectures on diabetes and gastroenterological conditions in North America. She has created the Insulin Intensive Seminar, a two-day conference wherein medical professionals and students learn a comprehensive program of using insulin with all types of diabetic patients in all situations.

m.morstein@scnm.edu
Table 1
Increases Insulin Production   Causes Insulin Inhibition

Eating                         Low serum glucose

Elevation in serum glucose     Insulin sensitivity

Insulin mimetics:              In-between meals
Glucagon-like
peptide-1 and gastric
inhibitory peptide

Sulphonylurea drugs            Damaged pancreatic beta cells

Insulin resistance


Hormones              Action

Estrogen              May be low or high (in women with high
                      BMI)

Testosterone          Anabolic: aids lean muscle development
                      (but can be high in MetSyn women due to
                      IR)

DHEA                  Anabolic: aids lean muscle development
                      and fat loss at 50 mg/day (may also be
                      high due to IR)

Cortisol              Signals liver production of glucose (may
                      be high due to abdominal fat)

Thyroid (Free T4 and  Maximizes metabolism Free T3)


Transdermal            Oral

No increased           Increases HS-CRP
inflammatory markers

Lowers fibrinogen and  Lowers fibrinogen and PAI-1 but worsens
PAI-1                  pro-coagulation factors

Reduces IR             May worsen IR
Increase adiponectin   Increase leptin (and thus appetite)
(lowers appetite)

LDL-C lowers           LDL-C lowers and increases HDL and TG
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