Year: 2020
Type: dissertation
Study design: Observational Study
Abstract: Background: Inflammation is implicated in the development, progression and long-term complications of type 2 diabetes (T2DM). Hyperglycemia and visceral adipose tissue, which are common in people at risk or diagnosed with T2DM, promote inflammation. Hyperinsulinemia, a compensatory mechanism in response to insulin resistance and a result of some pharmacologic treatments for T2DM, may also be proinflammatory, which has important implications for treatment strategies. Purpose: To further understand the effect that diet and its associated relationship with insulin, has on inflammation and T2DM outcomes. Aim 1: Examines the association between fasting insulin and high sensitivity C-reactive protein (hs-CRP), a marker of inflammation, in adults without diabetes, assessing the potential mediating role of visceral adipose tissue, operationalized as waist circumference. Using a multinomial logistic regression, with hs-CRP divided into three levels of risk and average-risk as the base group, in the reduced adjusted model we found that fasting insulin was associated with high-risk (RRR = 1.07, p < .001) and low-risk (RRR = 0.91, p < .001) hs-CRP. In the full adjusted model also controlling for waist circumference, the low-risk RRR was 0.97 (p < .001) and high-risk RRR was 1.02 (p = .002), reflecting the attenuation of 69% and 68% for each group respectively, indicating this relationship may be partially mediated by visceral adipose tissue. Aim 2: Examines the association between diet (net carbohydrates and total sugar) and white blood cell count (WBC), a marker of inflammation, as well as glucose control (glycated hemoglobin [HbA1c]). We found a significant association between net carbohydrate intake and WBC (β = 0.001, p = .047) but not between total sugar intake and WBC (β = 0.000, p = .838), after adjusting for potential confounders. We did not find a significant association between HbA1c and either net carbohydrate (β = 0.001, p = .311) or total sugar (β = -0.000, p = .815), after adjusting for potential confounders. Aim 3: Examines the effect of a very low-carbohydrate diet (VLC) compared to a Dietary Approaches to Stop Hypertension diet (DASH) on fasting insulin, insulin resistance, and inflammation in overweight or obese adults with prediabetes or T2DM and hypertension over 4 months. Overall, the VLC group experienced greater reductions in fasting insulin compared to the DASH group (-3.86 µU/mL, p = .027) and Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR; -0.51, p = .029). However, these effects were no longer significant after a Bonferroni adjustment for multiple comparisons. The VLC group experienced greater reductions in WBC (-0.72 K/uL, p = .004), which was maintained after a Bonferroni adjustment. Reductions in IL-6 approached significance in the DASH vs. VLC group (0.77 pg/mL, p = .070), although this was not significant after the Bonferroni adjustment. Statistically significant differences between diet groups were not observed for the other tested inflammatory markers. Conclusions: This dissertation adds to the evidence that prevention and treatment efforts for T2DM may be improved if inflammation is addressed. These results suggest that treatment approaches that simultaneously decrease insulin levels while achieving glycemic control may provide additional anti-inflammatory effects.
Author: Amanda L. Missel
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3160372455