CHAPTER FIVE
5.0 DISCUSSION
Type 2 diabetes mellitus, formerly known as non-insulin dependent diabetes mellitus or adult onset diabetes, is a metabolic disorder that is characterized by hyperglycemia in the context of insulin resistance and relative insulin deficiency (Vinay et al., 2008). Sex differences and the role of gonadal hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance because of the increasing prevalence of type 2 diabetes mellitus and the metabolic abnormalities associated with aging. Body composition is closely associated with insulin sensitivity, and increased body fat, particularly in the visceral compartment, is a risk factor for developing type 2 diabetes mellitus. Sex differences in body composition and/or insulin sensitivity are evident in humans throughout the lifespan.
In this study female sex hormone was assayed in patients on antidiabetic drugs (metformin and diabinese), observable data shows the mean age of the diabetic patients and the control to be 57.43±1.31 and 43.30±2.67 respectively and this was different and statistically significant (p˂0.05). The educational status of the diabetic patients and non-diabetic control subjects were tertiary 27 (45%); secondary 3(5%); Primary 9 (15%) and none 21 (35%) and non-diabetic control subjects were tertiary 31 (77.5%); primary 1 (2.5%); none education 8 (20%) and none has secondary education and this was statistically significant. The significant differences recorded in the mean age, marital status and educational status of the diabetic patients compare with the control may be attributed to a product of chance. However Campagnoli et al. (2012) reported no significant difference in the mean age and other demographic indices of patients treated with metformin and other antidiabetic agents.
Also, the anthropometric indices between diabetic patients using antidiabetic drugs (Metformin and Diabinese) and non-diabetic patients (control) depicts a significantly (p˂0.05) increased mean height in the diabetic patients (170.78±0.62) compare to control (168.4±0.816). The mean weight and BMI of the diabetic patients compare with the control were however not statistically significant (p>0.05). This finding was consistent with the previous work of Shahghebi et al. (2013) that recorded a higher BMI in diabetic patients compare with that of the control. Also, another author documented the treatment with metformin to be associated with less hypoglycaemic events and less or no weight gain when compared to insulin and sulfonylurea treatment (Eriksson1 and Nystrom, 2015). Also studies by Onalan et al. indicated that treatment with metformin increases insulin sensitivity and reduce weight and body mass index (BMI), blood pressure, and cholesterol levels (Onalan et al., 2005). However Campagnoli et al. (2012) reported no significant difference in the mean height, weight and BMI of patients treated with metformin and other antidiabetic agents.
In this study the comparison of biochemical parameters (estrogen, progesterone and fasting blood sugar)in diabetes patient using antidiabetic drugs (metformin and diabinese) and non-diabetic control patients shows a significantly (p˂0.05) reduced level of Estrogen (35.5 ±3.988) and Progesterone (0.78 ±0.0 06) in the diabetic patients using antidiabetic drugs compared with the non-diabetic control patients (58.72 ±12.31 and 2.49 ±0.64 respectively). However, the diabetic patients on antidiabetic drugs recorded a significantly (p˂0.05) elevated fasting blood sugar level (9.11 ±0.39) compared with the non-diabetic control patients (5.07 ±0.85). The decrease in estrogen and progesterone recorded in the diabetic patients may be associated with the effects of antidiabetic drugs on these hormones levels. Metformin has been documented to reduce sex hormone (Hankinson and Eliassen, 2007; Farhat et al., 2011). This findings correlates with the report of Campagnoli et al. (2012) in which metformin was reported to decrease circulating androgen and estrogen levels in non-diabetic women with breast cancer. Estrogen and progesterone are hormones produces and released by the ovaries, adrenal gland and the placental during pregnancy. They are also kept in reserve in the adipose tissue and have been documented to affect how cells respond to insulin. A fluctuation in progesterone, estrogen and other hormones has been documented to exacerbate diabetic symptoms. With the aforementioned, the lowering effects of antidiabetic drugs may directly reduce the level of these hormones as demonstrated by this present study.
Also, estrogen and progesterone has been implicated in the activation of the constitutive androstane receptor (CAR) is an orphan nuclear receptor. It was originally characterized as a nuclear receptor that can activate an empirical set of retinoic acid response elements without retinoic acid (Baes et al. 1994, Choi et al. 1997), and can be activated in response to xenochemical exposure, including phenobarbital (PB)-stimulated activation of a response element, NR1, found in the human cytochrome p450 2B (CYP2B) genes (Honkakoski et al. 2008, Sueyoshi et al. 2009). Metformin on the other hand act in an antagonistic manner, this mechanism may equally explain the lower level of estrogen and progesterone recorded in this study. Although to the best of our knowledge, till date there is no documentation on the direct effect of metformin on estrogen and progesterone.
