When considering hormonal weight gain, most people’s thoughts turn to insulin. Insulin is a hormone produced by the pancreas that has gotten a lot of negative press as the “fat storage hormone.” However this is not necessarily the case. In healthy, non – diabetic individuals, insulin works in partnership with another hormone called glucagon to keep blood sugar levels steady. Insulin allows blood sugar into body cells when blood sugar gets high, and glucagon takes sugar out of the cells and back into the blood stream when blood sugar gets low. This happens mostly in response to consuming or not consuming food, but is also influenced by other factors such as sleep and stress. If there is an excess of blood sugar after insulin has successfully transferred enough sugar into cells, the excess gets stored as fat in the liver or turned into adipose tissue (fat cells), contributing to weight gain. However in this case, insulin is not to blame. Insulin has performed its role efficiently by moving appropriate amounts of sugar into cells. Therefore the real cause of weight gain is not insulin but the excess calories and/or sugar consumed. An excess of energy that is not used up by the body gets stored as fat. Insulin itself is not to blame for weight gain, however a resistance of insulin, where body cells become resistant to the effects of insulin, can contribute to weight gain and more noticeably, make it significantly harder to lose weight.
When cells first become resistant to insulin, the pancreas responds by increasing insulin production in order to get more sugar out of the blood and into the cells. This is why high insulin levels or hyperinsulemia, and not high blood sugar levels, can often be one of the first signs of insulin resistance. Over time, cells become increasingly resistant to insulin and the pancreas can no longer produce enough insulin to compensate, this leads to chronically elevated blood sugar levels, potential weight gain and/or difficulty losing weight (1). Insulin resistance can also manifest as unexplained fatigue (as cells are not receiving adequate energy), frequent urination, increased thirst and more frequent infections such as UTI’s (1). Insulin resistance and the associated blood sugar imbalances also increases cravings for sugary foods and snacks which increases caloric load and contributes to weight gain. Over time, if not managed, insulin resistance develops into metabolic syndrome and diabetes (1).
The exact cause of insulin resistance is poorly understood. Perhaps the most well understood cause of insulin resistance is excess body weight caused by caloric excess. Insulin resistance has a bi-directional relationship with increased body fat. Weight gain from excessive calorie consumption leads to insulin resistance and insulin resistance further aggravates weight gain. However, in many cases, insulin resistance occurs first and exists in otherwise healthy weight individuals. In these cases, the cause of insulin resistance is unknown. There are many underlying factors that can contribute to the development of insulin resistance such as genetics, thyroid dysfunction, PCOS, diets high in unhealthy fats and excess sugar, lack of exercise, age (over 45 years), nutrient deficiencies or electrolyte imbalances, various medications, chronic stress, inflammation or trauma (1).
For women, insulin resistance and associated weight gain is most evident in cases of PCOS, thyroid dysfunction or perimenopause.
PCOS:
PCOS (polycystic ovarian syndrome) is a complex endocrine and metabolic condition affecting the reproductive cycle of reproductive aged women. It commonly manifests as irregular or absent menstrual periods, acne, hirituism (presence of unwanted body and facial hair), mental health issues and increased odds of infertility and obesity. Insulin resistance and PCOS also have a bi-directional relationship with each other. High insulin is both a symptom of PCOS and also an underlying causal mechanism of PCOS. Insulin resistance occurs in 70-95% of people with obese PCOS phenotypes and 30-75% of people with lean PCOS phenotypes (3,4). In most cases, PCOS is characterised by elevated androgenic or male hormones such as testosterone and/or DHEA. With PCOS, high ovarian androgens can cause high insulin in some individuals (8). High testosterone changes body composition, favouring an increase of fat accumulation around the midline which then indirectly also increases insulin resistance (8), especially in the overweight or obese PCOS phenotype. High insulin can then stimulate ovarian cells to make more testosterone, creating a vicious cycle (5). These cycles become very difficult to break and often require a change in the metabolic environment either through weight loss, dietary and lifestyle changes and/or insulin sensitising medications or herbal medicines/supplements. The degree of intervention required to shift the internal metabolic environment and correct underlying insulin resistance is variable and highly dependant on the unique case of the PCOS patient.
Hypothyroidism and Insulin Resistance
Hypothyroidism, characterised by an under-active thyroid, has a profound impact on glucose metabolism and is closely linked to insulin resistance. Thyroid hormones—T3 and T4—play a critical role in regulating the body’s energy expenditure and glucose metabolism. In hypothyroidism, the reduced levels of thyroid hormones lead to a decrease in basal metabolic rate, which can impair the body’s ability to utilise glucose efficiently (6). This impaired glucose response, increases the demand for insulin, contributing to elevated insulin levels and progression towards insulin resistance (6). The presence of insulin resistance further exacerbates the metabolic dysfunction associated with hypothyroidism, creating a vicious cycle where elevated insulin levels promotes fat storage and prevents fat loss. Hypothyroidism-related insulin resistance is particularly concerning in women, as women are at higher risk for thyroid dysfunction due to the increased energy demands of pregnancy and post-partum as well as perimenopause.
Perimenopause and Insulin Resistance
Perimenopause, the transition leading up to menopause, increases the risk of developing insulin resistance. During perimenopause and menopause, a decline in both oestrogen and progesterone can interfere with insulin sensitivity. Oestrogen and progesterone play a protective metabolic role, increasing metabolic rate and sensitising cells to insulin. As these hormones decline, body wide changes occur, including changes in the functioning of many organs like the liver, gall bladder and pancreas. This leads to a marked increase in abdominal fat which further exacerbates insulin resistance. Testosterone, which is strongly associated and weight gain in women (7), is the last hormone to drop in the perimenopausal transition, making the late perimenopausal and menopausal years (characterised by low oestrogen, low progesterone and higher relative testosterone) a particularly sensitive time for developing insulin resistance. Additionally, perimenopausal women often experience an increase in cortisol levels due to stress, sleep disturbances and a loss of muscle mass, further disrupting metabolic function and increasing the risk of developing insulin resistance. To read more about perimenopausal weight gain, please read my article here
Even though it is known that insulin resistance makes it significantly harder to lose weight, there is far more evidence suggesting that insulin resistance is a result of weight gain and not necessarily the other way around. The degree to which insulin resistance actually promotes weight gain is debatable and not universal to all women. This is why many people with insulin resistance, PCOS and even diabetes are lean. It is thought that the onset of insulin resistance can promote a modest increase in weight which generally plateaus unless accompanied by caloric excess. It is also true that most people underestimate the amount of calories they consume and can therefore unnecessary blame insulin resistance for weight gain. In all cases, following a diet and lifestyle that helps to sensitise the body to insulin can be beneficial in managing insulin resistance, stopping the progression of insulin resistance towards diabetes and metabolic syndrome and over time may help make weight loss easier. Read my article on blood sugar management here https://talidavoinea.au/12-tips-for-blood-sugar-management/
References:
Brenta G. (2011). Why can insulin resistance be a natural consequence of thyroid dysfunction?. Journal of thyroid research, 2011, 152850. https://doi.org/10.4061/2011/152850
Stepto, N.K., et al., Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemichyperinsulaemic clamp. Hum Reprod, 2013. 28(3): p. 777-84.
Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, Lehnert H. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev. 2012 Oct;33(5):812-41.
Diamanti-Kandarakis, E. and A. Papavassiliou, Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends in Molecular Medicine, 2006. 12(7): p. 324-32.
Volpi, E., Lieberman, S. A., Ferrer, D. M., Gilkison, C. R., Rasmussen, B. B., Nagamani, M., & Urban, R. J. (2005). The relationships between testosterone, body composition, and insulin resistance: a lesson from a case of extreme hyperandrogenism. Diabetes care, 28(2), 429–432. https://doi.org/10.2337/diacare.28.2.429
