A case study
A moderately overweight, sedentary, 17-year-old female consults with her parents for weight loss. During your consultation, which is immediately after lunch, you notice she is drowsy, and upon questioning her mother, she says this is a common occurrence. Prior records from other clinicians show a history of a single ovarian cyst, and she reports inconsistent menstrual cycling. Her academic performance has declined in the last year due to several factors; she reports brain fog, especially after meals, daytime sleepiness (in class), and poor memory and learning. She tried a low calorie weight loss plan, didn’t lose any weight and experienced mild to moderate anxiety for the first time in her life.
Lab analysis and possible causes:
- Fasting glucose: 105-elevated. Optimal levels are 75-86 mg/dL, Reference is 65-99. This client is above reference range. Possible causes include:
- Insulin resistance
- Metabolic syndrome
- Vitamin B1 deficiency
- Fatty liver/congested liver
- HPA axis dysfunction
- HbA1c:7-elevated. Optimal is 4.5-5.2%, reference range is less than 5.6%. Possible causes include and physician referral recommended:
- Metabolic Syndrome
- Triglycerides: Lab high-Possible causes
- Early stage hyperglycemia
- Metabolic syndrome
- Fatty liver/liver congestion
- Insulin resistance
- Low bile acids
- Transvaginal Ultrasound: Single ovarian cyst. Can be associated with insulin resistance and metabolic syndrome.
Insulin can interact with gonadotropins, mediated by the insulin receptor and luteinizing hormone (LH), that can contribute to premature arrest of follicle growth (Franks, Gilling-Smith, Watson, & Willis, 1999).
Based on the dysglycemic pattern, dyslipidemia, and elevated HbA1c, as well as her presentation of being overweight and inactive, and her main complaints and symptoms (post meal fatigue, cravings, brain fog), I would classify this client as having mild cognitive impairment caused by metabolic syndrome/ insulin resistance and is at risk of diabetes (type 1). Further evaluation with her PCP will be needed for an exact diagnosis of diabetes, since it is beyond my scope as a clinical nutritionist. Recommended tests include fasting insulin, hs-CRP, homocysteine and possibly a full iron and thyroid panel. A saliva or urine 24 -hour cortisol test is also helpful for further evaluation. Other functional tests can be recommended if required. Regardless, the problem is most likely created by poor lifestyle choices such as overeating and sedentary lifestyle and exposure to toxins such as phthalates that can disrupt insulin signaling. This pattern can lead to low intracellular or neuronal glucose that can affect brain function and contribute to neuroinflammation.
Her brain-based complaints are a clear sign that the hyperglycemia and hyperinsulinemia are degenerating the brain and promoting inflammation. HbA1C, which is a glycated hemoglobin molecule, can break down the blood brain barrier and lead to neuroinflammation. Long term, this can lead to decreased amyloid plaque clearance, increase in tau phosphorylation and Alzheimer’s disease (type 3 diabetes). Although she has not been officially diagnosed as T2D, I will be speaking to her with the assumption that she will be diagnosed as either pre-diabetic or diabetic by her PCP. Although she is only 17, she should be aware of the consequences of her health with potential cognitive impairment, especially with advanced age. T2D is associated with lower total gray matter volume (GMV) and this loss is associated with cognitive dysfunction (Climie et al., 2015). Low levels of physical activity or cardiovascular fitness have also been associated with lower GMV. Obesity and lack of physical activity are commonly seen in T2D and have been associated with brain atrophy and dementia with advanced age (Climie et al., 2015). In addition, abdominal adiposity can lead to chronic inflammation and insulin resistance, both factors in impairing neuronal function. Abdominal fat differs in metabolic activity compared to peripheral fat, and is strongly associated with production of the pro-inflammatory cytokines that generate insulin resistance. “Chronic low-grade inflammation, insulin resistance, advanced glycation end products (AGEs), hormonal effects and vascular disease may all be mechanisms that could explain the associations between T2D, abdominal obesity and brain atrophy” (Climie et al., 2015).
Another thing to bring to her attention is the ovarian cyst and irregular menstrual cycle. Functional ovarian cysts are a common gynecological problem of women of reproductive age worldwide. Nutrition and diet can affect sex hormones and their binding proteins, and insulin resistance can also affect ovarian function (Tafazoli, Fazeli, Dadgar, & Nematy, 2016). A high fat and high sugar diet can lead to adiposity. Insulin resistance is associated with a dysregulation of the insulin growth factor IGF-1 (Aguirre, De Ita, de la Garza, & Castilla-Cortazar, 2016). This is important because IGF-1 can influence the production of estrogen from the dominant follicle and plasma estrogen levels which can also influence ovulation and follicular development. “Mice with high fat and high energy diet were insulin resistant, glucose tolerant, and had dyslipidemia; these factors can be due to oxidative stress, cytokines inflammatory effect, and other factors which may affect the function of the ovaries” (Tafazoli et al., 2016). Insulin resistance and obesity are implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis (Chitme et al, 2017).
Excessive dietary fat can affect the metabolism of prostaglandins, that can impact ovarian function. High levels of dietary fat are associated with insulin signaling and ovarian function. Insulin resistance can also affect ovarian function (Tafazoli et al., 2016).
Although only one cyst was identified, this client should be aware that she is at a higher risk of PCOS. Insulin resistance is one of the root causes of PCOS because insulin can lead to abdominal fat, which can change the hormonal signaling in the body that leads to cysts. “Development of insulin resistance in PCOS is proven to involve decreased glucose transport of adipocytes, decreased insulin receptor stimulation and hepatic clearance of insulin, increased pancreatic sensitivity, steroidogenesis, and reduced muscular glucose transport” (Chitme et al, 2017). Other symptoms to look out for are androgen type symptoms such as dark hair on the face, acne and mood swings (Hutchins, n.d.). The anxiety may be a clue that the metabolic condition is affecting her brain. If the problem continues, it can lead to infertility, further cognitive impairment and neurodegeneration.
Aguirre, G. A., De Ita, J. R., de la Garza, R. G., & Castilla-Cortazar, I. (2016). Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med, 14, 3. doi:10.1186/s12967-015-0762-z
Climie, R. E., Moran, C., Callisaya, M., Blizzard, L., Sharman, J. E., Venn, A., . . . Srikanth, V. (2015). Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus. PLoS ONE, 10(11), e0142589. doi:10.1371/journal.pone.0142589
Davis, M. (2018). Dysglycemias and the Brain. Retrieved (2018m September 19) from http://coursecontent.muih.edu//NUTR834/NUTR%20834%20Module%201%20Week%204%20Dysglycemias%20and%20Brain%20Function/
Franks, S., Gilling-Smith, C., Watson, H., & Willis, D. (1999). Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am, 28(2), 361-378.
Hutching, J. (n.d.) Your Blood Sugar May Be the Key to Your Hormone Imbalance. Retrieved (2018, September 19) from https://health.clevelandclinic.org/polycystic-ovary-syndrome-pill-not-remedy/
Rakel, D. (2018). Integrative Mecidine (Vol. 4): Elsevier Inc.
Tafazoli, M., Fazeli, E., Dadgar, S., & Nematy, M. (2016). The Association of the Dietary Fat and Functional Ovarian Cysts in Women of Reproductive Age Referring to Three Hospitals in Mashhad, Iran, 2014. Int J Community Based Nurs Midwifery, 4(2), 148-156.