2.3 Demographic and Phenotypic Factors Affecting HbA1c
Literature review reveals that age and gender are demographic and phenotypic factors that influence HbA1c concentrations among individuals17,18. Moreover, clinical conditions such as cardiovascular disease, retinopathy, and nephropathy, influence the concentration of HbA1c18. Literature also shows that there is a positive relationship between average concentration of blood glucose and HbA1c among individuals19.
2.4 HbA1c and Age
A significant positive correlation is found between age and HbA1c levels. Based on a cross-sectional study performed on 1972 subjects in India, HbA1c levels increased 0.01% with each year above the age of twenty. Patients above the age of fifty were found to have levels of HbA1c exceeding 6.5% in comparison to patients below the age of fifty20. In another study measuring the mortality rate in patients and their HbA1c values, it was found that low and high HbA1c values were correlated with patients aged fifty-five to seventy-four21. Across-sectional study done among 1573 adults revealed that HbA1c concentrations increase with age of individuals17. This shows that the instability in glycemic values causing hyperglycemia and hypoglycemia in older patients. In this view, age it a factor that requires consideration in the diagnosis and management of diabetes among the populations.
Furthermore, HbA1c has been found to increase with age. In a cross-sectional research project performed on adults with diabetes, it was found that their HbA1c levels increased with age22.In patients aged seventy and older, a cross sectional analysis found A1c levels were positively correlated with age. The level of A1c increased each year with age23. Another study using serial cross-sectional surveys, concluded that patients aged sixty-five and above maintained relatively lowerglycemicvalues, while poor glycemiclevelswere most widely prevalent in patients between eighteen years old to thirty-nine years old. Patients above the age of sixty-five are less likely to exhibit poor glycemicvalues compared to young and middle-aged groups24.
A Zimbabwean study concluded age has no significant influence on HbA1c values25.On the other hand; a study in Singapore stated younger patients had poor glycemic results. It went on to say further research they have done also portrayed that studies performed in Germany, The Netherlands and The United States also determined younger patients have higher glycemic outcomes. However, some studies contradict this and state HbA1c results are lower in younger patients. The evidence for association between age and HbA1c levels varies from study to study for younger patients26.
A study researched the influence of age on HbA1c levels. It sampled patients aged 50-89 years old. The glycemic values were found to be significantly lower in the youngest group (50-69 year olds), with an HbA1c of 6.9%, and the highest in the eldest group (80-89 year olds), with an HbA1c of 8.62%27. As age increases, the HbA1c levels increase which might mean older patients are more insulin resistant than younger patients. They cannot maintain normal glycemic levels.
A research project performed on more than 2,400 nondiabetic patients measured their HbA1c levels to conclude whether glycemic levels increase with age. It found a positive association between A1c levels and age. Patients less 40 years old had an average HbA1c value of 6.0%, while patients aged over 70 had an average 6.6%28. This depicts older patients tend to have higher glycemic levels than younger patients which means their insulin sensitivity is decreasing.
Glycemic Control Algorithm
In a Hong Kong Chinese population, over 15,500 patients were studied. The aim was to analyze the relationship between age and glucose levels. It concluded there was a progressive increase in glycemic levels as the age increased29. There is a directionally proportional relationship between HbA1c and age. This might be because as age progresses, it gets harder to maintain the body’s tendency to absorb certain foods and control glucose levels.
A study conducted in the United States with urban African American patients witnessed a trend in younger patients (less than 30 years old) to have higher levels of HbA1c than older patients did. The initial HbA1c values were 9.9% in younger patients compared to 8.8% (greater than 69 years old) 30. Although other studies have found higher glycemic values in older patients, younger patients will also have higher values if they have uncontrolled diabetes.
A research product conducted in the United States from 2007-2010 found that glycemic control was most common in the younger aged patients (18-39 years old), and least common in older patients (over 65 years old). Poor glycemia was prevalent in the younger and middle-aged patients compared to the older patients. The study concludes stating the reasoning behind this might be adherence of younger patients to the healthcare system and to perform routine check-ups with healthcare providers31. Because older patients tend to go to doctors more often for check-ups, their results would be closely monitored which might lead to stable controlled glycemic values.
In the Latino population, low-income families were studied for glycemic control. It was found younger adult patients in the communities had poorer HbA1c levels than the older patients32. The reasoning behind this was an association made between younger patients and having a high fat diet, which leads them to obesity and its complications.
HbA1c and Gender
Many differences correlated to gender can be found in humans. A study performed on Caucasian patients reviewed gender equality in HbA1c management. The results of the research project depicted no difference between female and male patients’ results for glycemiclevels33. The conclusion was surprising because women tend to have lowerglycemicoutcomes. This might be due to pregnancy, hormonal changes, social factors and lifestyle wayse.g. dieting.
In a second research study conducted, an analysis featuring how women and men differ in HbA1c levels was explored. It concluded, men have lower glycemic values than women. A speculation was made that this was because the counter response to hypoglycemic levels is naturally low in women compared to men and thus females have a reduced ability to reach desired glycated hemoglobin results34. Depending on the gender, lifestyles change. Women go through pregnancy and hormonal changes more than men which can affect their lifestyles and behavioral aspects.
In Saudi Arabia, a study was aimed to assess glycemic outcomes in Saudi diabetic patients and furthermore compare it between males and females. The cross sectional study analyzing one-thousand patients was performed. It observed the female diabetic patients had increased HbA1c values than the male patients. The study concluded Saudi diabetic women have alower HbA1c when compared to Saudi men35. The reasoning behind this might be because of cultural differences. Men are more active than women in Saudi Arabia because of the way their society is shaped. Women tend to go to gatherings with food and desserts more than men do and they experience pregnancy, which typically means hormonal changes and affects their diet. Another factor, which might weigh in to this conclusion is the weather. It is typically hot in Saudi Arabia, which also means less outdoor activities thus leading to poorer diets.
According to a study conducted in Zimbabwe, it found age and gender played no significant role in influencing the results of HbA1c25. It concluded gender has no significant influence on HbA1c values in patients.
A gender-based study performed to determine the impact of gender on glycemic control concluded significantly fewer women than men received the target HbA1c value of <7.0%. Women were found to have a higher incident rate of severe hypoglycemia than men36. Because women tend to focus on appearance more than men do, hormones and diets can impact the HbA1c results in the long run.
In Taiwan, a research project was conducted to calculate glycemic control outcomes based on gender. It found no significant change of HbA1c in males, but a 0.10% decrease in females37. This again may be due to the hormonal changes in women, which can cause slight fluctuations in the test results.
A study looking at how gender affects insulin resistance states that women are more insulin resistant than men because of the composition of their bodies. Hormones including sex hormones in females have a positive effect on insulin sensitivity. Because women go through menopause, they are more prone to be given estrogen replacement which has shown to play a role in insulin sensitivity. Estrogen has been found to protect β-cell functions, which in return may protect against developing insulin resistivity and diabetes38. This might be why males might have higher glycemic values than females.
Mixed results were found describing the correlation between glycemia according to gender. These mixed results may be due to the culture and lifestyle of the patients. Some cultures and lifestyles restrict patients from having much outdoor activities because of weather for example. This might be why there is an inconsistency as to which gender has better glycemic values.
How to Diagnose Diabetes
HbA1c is measured in all patients, diabetic and non-diabetic patients alike. This is because some patients are not known diabetics and doctors use HbA1c to diagnose diabetes. Some clinics might do full check-ups for patients which requires them to perform this test as well. Patients who come to Kuwait as first time residents might have this test performed as a routine examination.
A cross-sectional study conducted at the King Abdul-Aziz University Hospital in Jeddah, Saudi Arabia reported diabetic patients had the highestglycemicvalues. It concluded patients with hypertension and hyperlipidemia have accelerated diabetes mellitus complications. Improved glycemicresultsare associated with reduced retinopathy, nephropathy, and neuropathy39.
Certain conditions have either a positive or a negative effect on HbA1c concentrations. It is found that iron deficiency anemia increases HbA1c values because of the structure of the hemoglobin molecule being altered. According to a cross sectional study, there is a positive correlation between HbA1c concentrations and Hb values40.
Hemoglobin A1c is an important indicator for diagnosis and assessment of certain diseases and conditions such as severe hyper or hypoglycemia. It can be used to identify states of continuous hyperglycemia and do not seem to alter with short hypoglycemic episodes or hyperglycemic spikes41.
In a similar cross-sectional study, one hundred and ten participants were recruited to take part in a research project to examine how stable HbA1c levels are fortype one diabetic patients. It was found that type one diabetic patients influence HbA1c levels depending on their self-efficacy42.