Epidemiological Investigation of Type 2 Diabetes and Alzheimer’s Disease in a Pakistani Population

Abstract

The epidemic of type 2 diabetes mellitus (T2DM) and the possibility of it contributing to the risk of Alzheimer’s disease (AD) have become important health concerns worldwide and in Pakistan, where the co-occurrence of T2DM and AD is becoming more frequent. To gain insights on this phenomenon, a cross-sectional study was initiated. We recruited and interviewed 820 research participants from four cities in Pakistan: 250 controls, 450 T2DM, 100 AD, and 20 with both diseases. Significant differences between groups were observed for age (p < 0.0001), urban vs. rural locality (p = 0.0472) and residing near industrial areas. The average HbA1c (%) level was 10.68 ± 2.34 in the T2DM group, and females had a lower level than males (p = 0.003). In the AD group, significant relationships existed between education and family history. Overall, the results suggest that T2DM and AD were associated with both socio-demographic and environmental factors in Pakistani participants. Detailed molecular investigations are underway in our laboratory to decipher the differential genetic pathways of the two diseases to address their increasing prevalence in this developing nation.

Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

“…Our team recently published the results of a descriptive study of Pakistani patients with T2DM, which confirmed gender differences and suggested possible associations with environmental factors [1]. The present study extends those observations to investigate a pilot study of global gene expression patterns in the same patients, using microarrays coupled with Ingenuity Pathway Analysis (IPA) and followed by selective gene validation.…”

“…We randomly selected our study subjects from our previously reported cohort recruited from the out-patient departments of four different regional hospitals of Pakistan, i.e., Islamabad, Rawalpindi, Lahore, and Abbottabad (see details in [1]). The study was undertaken with the prior approval by the Howard University Institutional Review Board (IRB-17-MED-43), and the informed consent was obtained from volunteers as per the approval of the Institutional Review Board (IRB) of Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) (28/IRB; dated.…”

“…We have retrieved the detailed background information of our participants from our earlier cohort report [1], where besides age and gender, their HbA1C, plasma glucose (mg/dl), BMI, locality, literacy, history of T2DM, medication use, and smoking history were also captured (see additional information in supplemental Table S2). This review of the records established that the study subjects in the present report were free of obesity (high BMI) and had abstained from use of alcohol (due to cultural practice) The subjects were 2 adults from the T2DM group and 2 from the control group (one male and female from each group): they were gender-and weight-matched, with average age of 68 ± 14.1 years.…”

“…This study has some strengths, notably, being among the first in Pakistan to investigate altered gene expression in T2DM versus non-diabetic subjects, where we mapped those genes to their affected pathways. It builds upon our prior establishment of a cohort of T2DM patients from different regions of Pakistan [1]. Obesity is one of the major drivers in developing T2DM and is becoming increasingly prevalent in the developing world, including southeast Asian countries like Pakistan and India.…”

“…Type 2 Diabetes Mellitus (T2DM), the predominant form of diabetes, is a chronic, multifactorial, metabolic disorder characterized by hyperglycemia and has become a public health challenge worldwide [1][2][3]. T2DM accounts for 90% to 95% of all diabetes cases with the heritability ranging between 40% and 70% [4,5].…”