Rachael  R. Irving1, James L. Mills1, Eric G. Choo-Kang2 , Anthony Mullings3,  Errol Y Morrison1, Rosemarie Wright-Pascoe4, Wayne Mclaughlin1 .
1  Department of  Basic Medical  Sciences, University  of the West Indies,   
  Kingston, Jamaica.
2 Department of Pathology, University of the West Indies, Kingston, Jamaica.
3  Department of Gynaecology, Obstetrics and Child Health, University  of 
   the West  Indies, Kingston, Jamaica.
4  Department of Medicine, University  of the West Indies, Kingston, Jamaica.
Abstract
Background  : Many studies support a correlation between glycemic control and  diabetes complications in patients with type 2 diabetes.   Epidemiological analysis showed a continuum between risk of  cardiovascular complications and glycemia, so that for each percentage  point decrease in HbA1c there was a twenty five percent reduction in  diabetes related death.  Studies showed that persons affected by  diabetes who understand the risk for, and implications of the  complications of the disease are more likely to have better glycemic  control and outcome.
Aim : To determine the levels of glycemic control in persons with early 
 onset autosomal dominant type 2 diabetes.
Methods  : Eighty nine affected individuals from families with early onset  autosomal dominant type 2 diabetes were assessed for levels of glycemic  control.  Glycemic control each three months, for a period of twelve  months was monitored by HbA1c. Patient’s  demographic and anthropometric  data, adherence to treatment plan and attendance  patterns at clinics  were also assessed.
Results:   The significant changes in mean HbA1c in the 89 affected individuals  from baseline to 12 months followed a linear pattern ( 12.3± 1.2% at 0  month , 12.3±1.6% at 3 months, 12.0±1.0% at 6 months, 11.7±0.9% at 9  months, 11.4±1.7% at 12 months, p <0.005).  There was no  statistically significant difference in HbA1c from baseline to 12  months  for the different patterns of adherence to treatment plan  however those with  excellent adherence to treatment  had a steeper  decreased in HbA1c from baseline to 12 months (excellent adherence:  HbA1c decreased 1.9% over 12 months, poor adherence : HbA1c decreased  1.08 % over 12 months).  There was no statistically significant  difference in HbA1c between those with poor or moderate patterns of  attendance at clinics however when the comparison was made between those  with poor and excellent attendance, the statistical difference was  significant (p<0.05).  Patients with excellence attendance had the  greatest decreased in HbA1c from baseline to 12 months (12.2±4.4% at  baseline to 8.9±3.0% at 12 months, p <0.05). 
Conclusion
Adherence to treatment plan and attendance at clinics enhance reduction in HbA1c.
Introduction
Early onset autosomal dominant type 2 is increasingly occurring in families of African descent (1). This type of diabetes is characterized by insulin resistance, dyslipidemia, and a high risk of long term complications (1-2). Early onset autosomal dominant type 2 is usually diagnosed in persons aged < 35 years(2) as compared to classical type 2 diabetes diagnosed in persons ≥ 45 years(3).   Development of the disease at an earlier age increases the risk of  duration dependent complications such as cardiovascular disease. In the  United States of America  type 2 diabetes contributes to more cases of  adult-onset loss of vision, renal failure, and amputation than any other  disease(4). 
     Glycemia, can be measured most reliably with the glycosylated  hemoglobin assay (HbA1c). HbA1C value indicates glycemic control over a 2  to 3 months period; values less than 7% are considered optimal (7).There is substantial evidence that improving glycemic control decreases the risk of microvascular complications (5-6).  Epidemiological  analysis showed a continuous association between the risk of  cardiovascular complications and glycemia, such that for every  percentage point decrease in HbAlc (e.g., 9 to 8%), there was a 25%  reduction in diabetes-related deaths, a 7% reduction in mortality rate,  and an 18% reduction in combined fatal and non-fatal myocardial  infarction (5,8). Tight glycemic  control has been shown to prevent the onset or progression of diabetic  nephropathy in type 2 diabetic patients (5-6 ). 
     Adherence to treatment plan which include dietary intake, proper blood  pressure, lipid and glucose monitoring are fundamentals for proper  glycemic control and reduction in risks of complications related to  diabetes(8). In this study  demographic and anthropometric data, treatment adherence and attendance  patterns at clinics in relations to glycemic control over 12 months of  89 individuals with early onset autosomal dominant type 2 diabetes are  presented. 
To our  knowledge this is one of the first investigations that evaluates  glycemic control as it relates to adherence to treatment plan and clinic  attendance in a homogenous population of persons with early onset  autosomal type 2 diabetes
Statistics :
    Data was analyzed by  using SPSS 12.2 (SPSS Inc. in Chicago). Demographic variables were  analyzed using Spearman’s correlation coefficient. Correlation  regression was used to access multiple relationships. The associated t  and ANOVA tests were done to test the statistical significance of the  correlation coefficient and regression models reported.
Methods
     Patients with early onset autosomal dominant type 2 diabetes were  recruited for the study on glycemic control.  General practitioners were  asked to refer affected patients with a family history of early onset  type 2 diabetes to the testing centre: the Department of Basic Medical  Sciences, University of the West Indies, Mona, Jamaica.  A total of 105  persons were recruited as they met the study's entry criteria (diagnosis  of diabetes and 2 family members with early onset autosomal dominant  type 2 diabetes (2)).  Exclusion criteria were: ambulatory individual, current heart or kidney  failure, blindness, a severe concurrent illness likely to limit life or  require extensive systemic treatment, inadequate understanding or  unwillingness to participate in the study. 
    A  total of 105 patients attending public and private clinics in the  Kingston Metropolitan area of Jamaica were recruited. The study was a  longitudinal/cross-sectional one and was conducted at the Department of  Basic Medical Sciences, Mona which forms part of the University of the  West Indies Faculty of Medical Sciences. The study received ethical  approval from the University of the West Indies Faculty of Medical  Sciences/ University Hospital of the West Indies Ethics Committee (IRB).
    At initial  interview the study requirements were explained to the participant. A  consulting physician ensured that the patient was well enough to  participate in the study. After initial interviews 89 patients were  selected for further participation in the study. Informed consent was  obtained from each participant. Patients were asked from the first day  of study to strictly adhere to all treatment plans recommended by their  doctors and to keep all clinic appointments.  Demographic data were  obtained by interviews. Adherence to treatment plan and attendance at  clinics were self reported and monitored by reviewing of the docket by a  consulting physician. Adherence to treatment plan was defined as poor  if patient adhered to ≤ 49% of treatment recommendations, moderate if  patient adhered to 50-79% of treatment recommendations and excellent if  patients adhered to 80% or more of treatment recommendation. Poor  attendance at clinic was defined as attending clinic less than 50% of  recommended time, moderate 50% to 79% of recommended time and excellent  80% or more of recommended time.  Glycemic control starting at baseline was monitored by checking HbA1c  at 3 months intervals up to 12 months.  Body Mass Index (BMI) utilizing  weight and height (weight/height – kg/m2 ) was measured by a standard  stadiometer. Waist/hip circumference was done by measuring waist at the  maximal circumference between the lower ribs and hip and measuring hip  at the level of the maximal protrusion of the buttocks with a steel  tape. Systolic and diastolic blood pressure measurements were obtained  using a standard sphygmomanometer whilst the patient was seated.  Hypertension was defined as a history of hypertension treatment or  systolic pressure ≥ 140mmHg or diastolic pressure ≥ 90mmHg (9)
Results
    Eighty nine  patients were assessed for glycemic control at 3 months intervals  starting at baseline for a period of 12 months. According to demographic  data from table 1: The patients involved in the study were of African  descent. Mean age of participants at time of study was 42± 15.6 years.  Mean age at time of diagnosis was 31.9 ± 5.9 years. The duration of  diabetes in the cohort at the time of the study ranged from 0 to 57  years. Sixty point seven percent of the study cohort was taking oral  agents only, and the other 39.3% were taking insulin.  Forty point four  percent had known diabetes related complications (on diuretics for  kidney problems/ lost some sensation in feet-neuropathy) and high blood  pressure (systolic >130±6.5, diastolic > 90±4.8 mmHg). Total (5.4±  0.9mol/l) and LDL (3.4± 0.5 mmol/l)) cholesterol levels were elevated.  BMI of these patients was 26.7±3.5kg/m2 
    Thirty six persons or  40.4% of the study cohort had household income of < $(US) 5000.00  yearly.  Thirty six or 40.4% of the study cohort had < 5 years of  formal education.  Approximately 60% of the study cohort moderately or  poorly adhered to their treatment regimens whilst 73.1% had moderate or  poor attendance at clinics.  Mean daily caloric intake of the study  participants was 2500±45.0 k/cal.
Glycemic control :
General glycemic control (Table 1: All study participants)
  At 3 months mean HbA1c was 12.3±1.6%, at 6 months  12.0 ±1.0%, 9 months 11.7±0.9% and the end of 12 months 11.4±1.7%.   Mean fasting blood sugar was 11.1±2.8 mmmol/l at the beginning of the  study.  At the end of 12 months fasting blood sugar was 8.9 ±0.9 mmol/l.
Sub-groups based on attendance patterns at clinics (Table 2)
  Patients with poor attendance at clinics had baseline HbA1c of 12.2±5.0, their
HbA1c decreased to 12.00 ±  3.9 at 3 months then remained at that level for 6 months, then  decreased to 11.2 ±3.4 at 9 months and further decreased to 10.6±2.7 at  12 months.  There was no statistically significant difference in HbA1c  between any of the periods. Patients with moderate attendance at clinics  had HbA1c of 11.8±4.5 at baseline then a decrease to 11.0±4.2 at 3  months, an increase to 11.1±3.6 at 6 months, a decrease to 10.8±3.8 at 9  months then  a further reduction to 10.5±3.9 at 12 months. No  statistically significant difference was noted between periods of  assessment.  Patients with excellent attendance at clinics had a  constant decrease in HbA1 over 12 months moving from 12.2±4.4 at  baseline to 8.9±2.9. A statistically significant difference was noted  between baseline and 12 months (p<0.05)
Sub-groups based on adherence to treatment plan (Table 3)
    Baseline and 3  months HbA1c were the same in patients with poor adherence to treatment  plan. HbA1c then decreased steadily from 3 to 12 months. No statistical  difference in HbA1c was noted between any three months period. Those  patients with moderate adherence to treatment plan had an increase in  HbA1c   from baseline to 6 months then a decrease below baseline value  at 9 and 12 months. Patients with excellent adherence to treatment plan  had a linear decrease in HbA1c
over 12 months moving from  11.3± 4.7 at baseline to 10.2± 4.0 at 3 months to 10.0 ± 2.7 at 6  months then to 9.4± 3.7 at 9 months and finally to 9.4 ±3.8 at 12  months.
Glycemic control in specific subgroups based on years of formal education (Figure 1)
 Figure 1. Measurements of Glycosylated Hemoglobin over 12 months
in early onset autosomal dominant type 2 diabetes patients with
different levels of education
HbA1c decreased  significantly (9.0 ±1.0 % to 8.2 ± 0.8 %, p<0.05) during the first  three months, then decreased non-significantly to 8.1 ±1.1% (p>0.05)  by six months, remained steady at 8.1±1.1% between 6 and 9 months then  decreased significantly  (from 8.1±1.1 to 7.7±1.0 %(p<0.05) between 9  and 12 months  in probands with ≥10 years of formal education.
    In  probands with 5 to 9 years of formal education HbA1c decreased  non-significantly from 10±2.1% to 9.9±1.8% (p>0.05) during the first  three months, then decreased non-significantly from 9.9±1.8 to 9.7±1.8%  (p>0.05) during three to six months then further decreased  non-significantly from 9.7±1.8 to 9.6±1.7% from six to nine months then  decreased significantly from 9.6±1.7 to 9.3±1.0% (P<0.05) from nine  to twelve months.
     HbA1c decreased  non-significantly from 12.5±1.1 to 12.4±2.4% (p>0.05) during the  first three months, then increased non-significantly to 12.6±2.1%  (p>0.05) by six months, decreased non-significantly from 12.6±2.1 to  12.5±1.9% (p>0.05) between 6 and 9 months then decreased  significantly from 12.5±1.9% to 12.0 ±1.2% (p<0.05) between 9 and 12  months in probands with <5 years of formal education.
Glycemic control based on age (Figure 2)
     In persons  ≥ 50  years  HbA1c  non-significantly decreased from 12.2±3.1% at 0 month to  12.0±2.4 (p>0.05) at 3 months then rose significantly from 12.0±2.4%  at 3 months to 12.9±3.9%  (p<0.05)at the end of 12 months. In persons  < 50 years HbA1c decreased significantly from 11.4±1.0% at 0 months  to 10.9±1.9% (p<0.05) at three months then further decreased  significantly to 10.2±1.4% (p<0.05) by 12 months.
 Table 1:   Baseline- characteristics of the study cohort 
                 (n=89)
--------------------------------------------------------------------------------------------------- 
-------------------------------------------------------------------------------------------------
Mean age at time of study (years)                      42± 15.6
Mean age at diagnosis (years)                            31.9 ± 5.9
Duration range of diabetes (years)                     0-57 years
On OHA                                                             54 (60.7%)                           
On Insulin                                                           35 (39.3%)
Known diabetes related complications              18 (20.2%)
High Blood Pressure (>130/90 mmHg)             18 (20.2%)
BMI (kg/m2 )                                                      26.7±3.5
Total Cholesterol (mmol/l)                                5.4±0.9
HDL (mmol/l)                                                   1.4±0.2
Triglyceride (mmol/l)                                        1.3±0.2
LDL (mmol/l)                                                    3.4±0.5
FBS  mmol/l                                                      11.1±0.8
Insulin mU/l                                                       16.2±4.9
Total kcal/day                                                     2500±45.0
Hospitalization profile
  Age ≥≥50 years                                                10 (11.2%)
   Age < 50 years                                                3(3.3%)
HbA1c (%)
0 month (beginning of study)                             12.3 ±1.2
3 months                                                             12.3± 1.6
6 months                                                             12.0 ±1.0
9 months                                                             11.7 ±0.9
12 months                                                           11.4±1.7
 Ethnicity
Afro-Jamaican                                                    89 (100%)  
Annual Household income ($US)
    <5000.00                                                        36 (40.4%)
      5-10000.00                                                   36(40.4%)
    $10,000.00                                                      17(19.1%)
Education level of Subjects
  < 5 years of formal education                           36(40.4%)                    
    5-9 years formal schooling                              36(40.4%)   
  ≥ 10 years formal schooling                             17 (19.1%) 
 Adherence to treatment regimen
   Excellent    (80-100% compliance)                 36(40.4%)
    Moderate (79-50% compliance)                     17(19.1%)
    Poor          (<50% compliance)                       36(40.4%)
  Scheduled attendance at clinics
    Excellent  (80-100% of time)                             24( 26.7%)                 
    Moderate (79-50% of time)                               48 (53.3 %)
    Poor          (<50% of time)                                 17 (19.1%)
     Table 2: Attendance at Clinics and 12 months  Glycemic profile
Appointment keeping  |           Time ( Months)  |        ||||
0  |          3  |          6  |          9  |          12  |        |
                       HbA1c  |        |||||
Poor   |          12.2± 5.0  |          12.0±3.9  |          12.0±2.9  |          11.2±3.4  |          10.6±2.7  |        
Moderate  |          11.8±4.5  |          11.0±4.2  |          11. 0±3.6  |          10.8±3.8  |          10.5±3.9  |        
Excellent  |          12.2±4.4  |          10.6±3.9  |          10.5±3.1  |          9.7±3.3  |          8.9±2.9  |        
 Glycemic profile over 12 months of patients’ appointment keeping 
   pattern
Table 3 : Adherence to Treatment Plan and HBA1c over 12 months
Adherence to Treatment Plan  |            Time (months)  |        ||||
0  |          3  |          6  |          9  |          12  |        |
                         HbA1c  |        |||||
Poor   |          10.2±4.8  |          10.2±3.9  |          10.1±3.4  |          9.4±3.9  |          9.2±3.1  |        
Moderate  |          10.2±4.7  |          10.4±4.7  |          10.8±4.1  |          9.5±2.9  |          9.3±3.6  |        
Excellent  |          11.3±4.7  |          10.2±4.0  |          10.0±2.7  |          9.4±3.7  |          9.4±3.8  |        
Patient’s adherence to their treatment plan and glycemic levels 
from baseline to 12 months
 Figure 2: Measurements of Glycosylated Hemoglobin over 12 months
in early onset autosomal dominant type 2 diabetes patients based
on age 
Discussion
In  terms of demographic data of the entire cohort dyslipidemia (elevated  total and LDL cholesterol), BMI above normal range, high blood pressure,  long duration of disease and diabetes related complications were  general features.  These features complicate and prevent tight control  of glycemia . In the studied population (n=89) there was a less than 1%  point drop in  HbA1c  at the end of twelve months. At the beginning of  12 months HbA1c was 12.3% and at the end of 12 months 11.4%.  When the  cohort was divided into different subgroups, persons with ≥10 years of  education had better glycemic control than persons with less education.  Many studies have shown that, there are no correlation between  educational level and glycemic control however Zgibor et al (10)  has shown that specialist care was associated with a higher level of  participation in diabetes self care practices and a lower HbA1c level.  Care delivered by specialist has been associated with better glycemic  control and delivery of practices measures that are more consistent with  established practices guidelines (9,10).  Zgibor and collegeues(10)  have also shown that patients receiving specialist care are more likely  to have an educational level beyond high school and annual income >   (US) $20,000.00. The 20% of the cohort with ≥10 years of formal  education had a greater than 1% drop in HbA1c level over a 12 months  period, moving from 9.0% at baseline to 7.7% by the end of twelve  months.
    Glycemic control is the only measure proven to prevent diabetic microvascular and neuropathic complications (5,6).  Unfortunately, 40.0 % of the study cohort had higher HbA1c levels at  the end of 12 months than at the beginning of the study.  The poor  glycemic control may have been due to disease duration and poor self  care. The disease duration of diabetes ranged from 0 to 57 years. Older  people in the study tended to have the disease for longer periods. Of  the cohort, the subgroup aged ≥ 50 years were the only group in which  HbA1c was higher at the end of the study than at the beginning. HbA1c  moved from 12.2% at baseline  to12.9% at the end of 12 months.  Blaum et  al (11) found that disease  duration and poor self-care were related to glycemic control. The  patients ≥ 50 years had greater incidences of hospitalization (10 older  persons versus 3 younger persons) due to diabetes related complications.   The Kumamoto study (2000) confirmed that improved glucose control  reduces the microvascular complications such as retinopathy,  nephropathy, and neuropathy in type 2 diabetes (6).  The poor glycemic control in these patients may have precipitated  microvasular complications and lead to the increase incidences of  hospitalization.  In patients with type 2 diabetes prospective studies  have shown an association between the degree of hyperglycaemia and  increased risk of microvascular complications, sensory neuropathy,  myocardial infarction stroke , macrovascular mortality, and all cause  mortality(5-6,11)
     Regression analysis done in this study identified five variables  associated with poor glycemic control : education, use of insulin,  duration of diabetes, age and attendance at clinics. Persons ≥50 years  based on demographic data  in this study tend to use insulin, had  diabetes for a longer time, attended clinics less and were more likely  to have <5 years of formal education. At the end of 12 months persons  aged ≥ 50 years had poorer glycemic control with an increase in HbA1c
At 12 months.
    While the race/ethnic population was homogeneous, the socioeconomic  status of the population was not. Most of the patients had very low  income, a few patients however had ≥ 10 years of formal education and  earned > $10,000.00 per year which limits the generalization of the  study results. 
     Finally, multiple factors affect glycemic control. The study did not  incorporated disease severity, access/quality of care, self-care skills,  exercise, psychological  status, behavioral pattern and knowledge of  the disease which might have had effect on glycemic control (4-7,10,11-12)
     This study  identified patients with early onset autosomal dominant type 2 diabetes  that have poor glycemic control.  The study also identified patients  with this form of atypical diabetes that might be able to have optimal  control. The findings should not be generalized to all patients with  early onset Type 2 diabetes but can be applied to racial/ethnically  homogeneous populations.  In this study those who were older, had  diabetes for a longer period of time, used insulin and had < 5 years  of formal education had poorer glycemic control. The younger, better  educated had better glycemic control and was closer to the optimal of  < 7.0% (5,11). This study  provides a useful methodology to assess disease management systems using  longitudinal data. It does not provide answers to why patients are not  optimally controlled but provides a beginning from which to investigate  and address obstacles that might prevent patients with diabetes from  having optimal glycemic control.
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 Corresponding author:   Rachael Irving, Department of Basic Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.

 
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