486443.pdf (17.21 MB)
Outcomes and Phenotype of Screen-Detected Diabetes and New and Emerging Therapies for Type 1 and Type 2 Diabetes Mellitus
thesis
posted on 2009-10-06, 11:20 authored by Sudesna ChatterjeePrincipal aims were to investigate long-term outcomes from T2DM and IGT screening,
examine morphological and biochemical phenotypes of screened subjects, comparing White
Europeans (WE) with South Asians (SA), and emerging therapies including basal insulin
analogues in T1DM and meglitinides in T2DM and their place in management.
Following adjustment for age, sex and ethnicity, no significant difference in mortality,
microvascular or macrovascular outcomes were detected between known and screened
T2DM after ten years. Findings were limited by few events and relatively short follow-up.
These data may be useful in power calculations for longer randomised controlled trials.
Body fat is higher in SA than WE for given BMI and increases with worsening glucose
tolerance. Bioelectrical impedance analysis and skinfold thickness are less sensitive and
specific with increasing body fat regardless of ethnicity, and gender. Ethnicity and BMI, but
not age, predict total and abdominal fat using DEXA scanning.
After adjustment for age, BMI, WHR, gender, smoking and drug history, no differences
between SA and WE for adiponectin and resistin were detected. Leptin is predicted by age,
gender and smoking in WE but only gender in SA. BMI predicts hsCRP in both groups
while age and smoking predicts TNFa in SA. Longitudinal cohort studies are needed to
determine impact of interventions on risk markers in different ethnic groups.
Insulin glargine results in a small but significant glycaemic improvement without
significantly increased hypoglycaemia, weight gain or reduced patient satisfaction when
used in a basal bolus regimen with aspart compared with NPH insulin in T1DM.
In a six-month randomised study, four different dual oral combinations including
nateglinide, pioglitazone, metformin and gliclazide, in early T2DM result in significant
glycaemic improvement without increasing hypoglycaemia or patient dissatisfaction with no
significant differences between groups. Longer RCT are required to determine how duration
of glycaemic improvement with each combination.
History
Date of award
2007-01-01Awarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- PhD