Type 1 diabetes mellitus (T1DM), an autoimmune disease in which the insulin-producing pancreatic ?-cells are destroyed, results in the inability of the pancreas to produce insulin to regulate blood glucose levels, an accumulation of glucose in the blood and cell starvation. Elevated glycated haemoglobin (HbA1c) levels, a metabolic marker of glucose control, are characteristic of T1DM. Chronic exposure to high blood glucose levels leads to microvascular and macrovascular complications. Disease management requires regular blood glucose monitoring and daily exogenous insulin administration to maintain fasting and post-prandial blood glucose levels within near to the normal range of 3.9 to 5.6 mmol/L. However, T1DM patients on daily insulin replacement therapy have been observed to experience weight-gain over time, regardless of the level of glycaemic control achieved. The study aimed to determine the effects of quarterly adjusted total daily doses of twice-daily biphasic insulin and basal NPH plus prandial regular insulin to achieve optimum glycaemic control, on body mass index (BMI) in T1DM patients. Secondarily, dosage regimens that achieved optimum glycaemic control, without increasing BMI, as well as gender differences in BMI and HbA1c outcomes, were also explored.
All available clinic records of T1DM patients who attended the Kalafong Hospital Diabetes clinic between 2009 and 2014, and not on metformin and/or acarbose, were reviewed (n=493) and all eligible patients included in the study (n=211, mean±SD=43±14.4 years, 51% female, duration of T1DM ?2 years). Baseline and quarterly BMI levels were calculated from initial and quarterly height and weight measurements obtained from clinic records, respectively. Prescribed total daily insulin dosage and regimen at each visit and measurements of other clinically important covariates of interest were also recorded.
Baseline characteristics stratified by gender indicated no significant differences in the mean age distribution, number of years with T1DM, number of years of observation in the study, proportions on the basal NPH plus prandial regular insulin regimen and number of clinic visits. However, females had a statistically significant higher baseline BMI than males and more males were current smokers than females. Although females had a statistically and clinically significant higher baseline HbA1c level than males, they were prescribed similar average twice-daily biphasic insulin doses.
On multivariate multilevel mixed-effects linear regression analysis, time-varying BMI was significantly increased by exposure to any insulin regimen. Higher baseline HbA1c and BMI levels were predictive of an increase in BMI. However, males experienced significant comparative reductions in BMI on exposure to the adjusted twice-daily biphasic regimen, the regimen prescribed for 85% of patients and equally spread by gender. Poor glycaemic control during insulin therapy was associated with a reduction in BMI, and vice versa, regardless of regimen.
The study concluded that exposure to adjusted doses of insulin to achieve optimum glycaemic control in T1DM patients resulted in a statistically significant increase in BMI. However, this relationship seemed to be more prominent in female patients and in patients at higher baseline HbA1c levels and BMI categories, respectively. In addition, increasing BMI was consistent with improvements in blood glucose control.