Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Pharmaceutical Sciences


Biomedical and Pharmaceutical Sciences

First Advisor

Brian J. Quilliam


Over the recent years, the incidence of diabetes has significantly increased. Use of preventive services and treatment with oral antidiabetic drugs (OAD) has remained cornerstone in the management of type 2 diabetes (T2DM). Despite strong evidence that treating diabetes using these disease management strategies decreases morbidity, mortality and complications, glycemic control as well as other diabetes related outcomes remain unsatisfactory. The prevalence of diabetes in the United States has grown vastly in proportion over the last few years with the American Diabetes Association estimating that 9.3% of the population suffered from diabetes in the year 2012. These estimates are expected to increase in the future with the World Health Organization (WHO) estimating that 366 billion people (4.4%) will have diabetes. Diabetes places a greater clinical as well as economic burden on the patients as well as the health care system.

The presence of comorbid depression is frequent in people suffering from diabetes and can cause health outcomes in patients with diabetes. Poor adherence and persistence to diabetic medications resulting from the occurrence of adverse events is a cause of poor health as well as economic outcomes. There is a continuing need to evaluate the associations between comorbidities as well as common complications of medication treatment in persons with diabetes and examine how they influence health behavior. Evidence regarding differences in the utilization of preventive care services in diabetic patients with and without comorbid depression is scant. Similarly, the factors that predispose an individual to hypoglycemia as well as the association between hypoglycemic episodes and persistence to OAD therapy, specifically sulfonylureas, has rarely been quantified retrospectively. This dissertation utilizes the manuscript format and has four fold objectives:

  1. To review the current literature regarding the role of hypoglycemia and comorbid depression in the diabetes and examine their impact on clinical and economic aspects of diabetes management;
  2. To quantify the effect of comorbid depression on the rates of preventive care service use in a nationally representative population of US adults;
  3. To identify significant predictors and estimate the costs associated with the occurrence of hypoglycemia in the inpatient and outpatient settings.
  4. To evaluate the association between the development of hypoglycemia and persistence to oral sulfonylurea therapy in patients newly initiated on this class of OAD medications.

In order to review the literature regarding the effect of hypoglycemia and comorbid depression and diabetes, we utilized various biomedical and psychological databases. We analyzed the effect of comorbid depression as a principal risk factor associated with use of ADA recommended preventive services in patients with diabetes using the Medical Expenditure Panels Survey Data. A logistic regression was performed to achieve this objective and all the relevant confounders were controlled for in order to achieve the results. Claims data provided by the Blue Cross and Blue Shield of Rhode Island was utilized to assess the relationship between hypoglycemia and persistence to sulfonylurea medication as well as outline the predictors and costs of hypoglycemia. A time-varying Cox proportional hazards regression model was utilized to compare the hazard rate of medication discontinuation in diabetic patients that were exposed to hypoglycemic events, compared to those that were unexposed. A predictive modelling approach was utilized to highlight the factors associated with hypoglycemia

While the impact of comorbid depression and diabetes was significant both clinically and economically, it was seen that the extent of preventive care service use was comparable for diabetic patients with and without comorbid depression but suboptimal in general thus indicating major gaps in the implementation of ADA recommended preventive care practices. While depression was not significantly associated with increased use of the recommended diabetes preventive care services, other sociodemographic factors were seen to contribute. Moreover, though no significant association between events of hypoglycemia and subsequent discontinuation sulfonylurea medication was illustrated, we demonstrated several clinical factors to have a profound impact on the risk of developing hypoglycemic episodes.



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