In Trinidad, screening for T2DM is opportunistic: in clinical settings, individuals are assessed for identifiable risk factors and those subjectively deemed high-risk are recommended for formal screening . Currently, however, more than 50% of diabetic patients remain undiagnosed  and among those within reach of opportunistic screening, a major contributor to non-detection is the non-exhaustive collection of risk factors used to determine risk – it can exclude diabetic patients in whom traditional risk assessment is less convincing.
To address this issue, adjuncts to the current set of risk factors are needed but they must be carefully selected. New adjuncts should be not only sensitive, but should improve the sensitivity of the already-in-use pool of risk factors – they should broaden and strengthen the definition of a high-risk individual. Since timely risk assessment is vital in busy clinical settings, adjuncts must be efficiently and safely implementable. Lastly, a specific adjunct will limit the number of individuals wrongly classified as high-risk. Here, we will explore the potential of AN as an adjunct to T2DM risk assessment prior to formal T2DM screening in the Trinidadian population. We will explore the prevalence of AN among diabetic patients, the potential of AN to improve detection of T2DM and the innate qualities of the test that make it suitable.
AN is “a symmetric eruption characterized by hyperpigmented, velvety cutaneous thickening that can occur on any part of the body” . It is considered a cutaneous marker of hyperinsulinemia and insulin resistance [7, 19] and has been established as a risk factor for T2DM [6, 20, 21]. AN has been formally recommended by the ADA as part of the T2DM risk assessment criteria for children and adolescents . However, among adults, the implementation of AN in this capacity has been limited by infrequent manifestation in some populations .
In this Trinidad-based study, a relatively high manifestation of AN among diabetic patients was found - as many as 1 in 2 diabetic patients had AN. Of note, AN was 20% more likely to manifest in diabetic patients of East Indian than African or mixed origin – possibly due to a higher prevalence of ectopic fat and associated insulin resistance in the former . However, the prevalence in all of these dominant ethnic groups was quite high: 2 in 5 diabetic patients of either African or mixed origin and 3 in 5 of East Indian origin demonstrated AN. This high prevalence of AN - both overall and among the major Trinidadian ethnic groups - strongly supports its implementation as a sensitive marker of T2DM in the unique ethnic population of Trinidad.
We also found the prevalence of AN to be high across age groups although we did observe a steady decrease in the prevalence of AN with increasing age. Formal recommendations of the American Diabetes Association (ADA) have recognised AN as a risk factor for T2DM in children and adolescents and have incorporated it into formal risk assessment protocols since 2000 . Studies have found that approximately 60% to 92% of Black and Hispanic children with T2DM have AN  making it a highly sensitive marker in this age group. Indeed, in a recent survey among asymptomatic school-aged children screened for and confirmed with T2DM in Trinidad, all had AN . The current study provides additional evidence of the value of AN as a valuable marker of T2DM risk in younger age groups. However, despite decreasing prevalence with age, more than one in three diabetic patients in this study over 70 years had AN: AN was still relatively prevalent in older age groups.
It is worth mentioning that this higher prevalence of AN in younger diabetic patients was partially explained by a higher prevalence of obesity in younger patients. However, even after adjusting for BMI and other factors, this trend of decreasing prevalence of AN with increasing age was still clearly observed. Litonjua et al. observed that newly diagnosed T2DM patients with AN “required markedly higher insulin doses to achieve euglycaemia” . More severe insulin resistance in diabetic patients with AN may explain this decreasing prevalence of AN with age - a survivor effect.
The prevalence of AN was also high in both males (46%) and females (58%). Polycystic ovary syndrome (PCOS) is a well-established as an insulin-resistant state [25, 26] and may have accounted for some or all of the higher prevalence of AN among women with T2DM.
To be a valuable adjunct to the T2DM screening process, AN should improve risk assessment by traditional risk factors. As recommended by the ADA, “the decision to test for diabetes should ultimately be based on clinical judgment and patient preference” . Thus as an established risk factor for T2DM that is highly prevalent among diabetic patients in the Trinidadian population, the observation of AN alongside other risk factor(s) for T2DM should increase clinical suspicion of T2DM. Additionally, the incidental or intentional observation of this well-established skin marker of insulin resistance should prompt further risk assessment for T2DM.
For example, in this study approximately 60% of diabetic patients were found to be obese or overweight, and of these patients, 70% demonstrated AN. AN and obesity are associated with greater insulin resistance than obesity alone  and the finding of AN in an obese individual strengthens clinical suspicion of T2DM. Conversely, approximately 40% of diabetic patients were found to be of normal weight and as many as 30% of these demonstrated AN i.e. 12% of all diabetic patients were of normal weight yet manifested AN. AN in traditionally low-risk groups may be a valuable indicator of T2DM. However, in the absence of a control group in this study, we were unable to quantify this effect.
The interaction between BMI and ethnicity revealed interesting findings. Among obese diabetic patients, AN was most prevalent among East Indians. Among diabetic patients of normal weight however, Africans had a 1.7 times greater odds of demonstrating AN than East Indians of the same age, sex and waist circumference. Although the study was insufficiently powerful to show that this OR was different from one, this unexpected finding suggests that AN could be more prevalent among African than East Indian diabetic patients of normal weight, and this finding is worthy of further exploration in appropriately-powered studies.
AN can be rapidly assessed at the neck making it an extremely practical risk assessment tool. Examination for AN at other sites of the body can also marginally improve detection of T2DM. Among diabetic patients in this study, 52.7% had AN at the neck with or without AN at other sites, and a further 4.8% (approximately 1 in 20 diabetic patients) had AN only at other sites. Similar findings of neck involvement in 93% to 99% of AN was noted in the literature [13, 21]. The low sensitivity of this further examination for AN at other sites, together with the additional time demands that it incurs, may render it impractical in routine practice. AN at other sites has also been less extensively described and quantified than AN at the neck and this may affect the validity of its routine assessment . Potentially, the presence of AN at other sites may still provide useful evidence of T2DM risk in uncertain situations.
So far, we have discussed AN as a tool for improving the detection of undiagnosed T2DM. However, AN is also an important predictor of future T2DM. Stuart et al. described it as “a readily visible marker of endogenous hyperinsulinemia and thus, a marker for risk of developing non-insulin-dependent diabetes” . Therefore, like other established risk factors for T2DM, the presence of AN is a valuable tool for recommendation of early lifestyle change for the prevention of T2DM and its complications, especially in a population where it is so readily manifest.
Apart from exploring AN as a valuable adjunct to T2DM screening, its link to other cardiovascular risk factors was explored. In this study, AN was found to have a demographic-adjusted association with each of obesity, hypertension and hypercholesterolemia. However, in our further multivariable analysis with all three variables (as well as demographic variables), only obesity remained associated with AN while the latter two did not. Consistent with this, a strong association between obesity, its accompanying insulin resistance, and AN is widely documented [8, 19], and these findings emphasize that the presence of AN is more closely aligned with obesity than other cardiovascular risk factors.
One limitation of this study was that it did not allow for formal quantification of improvement in sensitivity of T2DM risk assessment attributable to the addition of AN to the pool of current risk factors. Such an assessment would provide valuable evidence to support health policy decision making. The promising results presented here favour further research into quantifying the benefit of AN in preparation for formal policy recommendation.
Another important limitation was that the study was conducted in a population of diabetic patients only. Therefore, the specificity of AN as a marker of T2DM could not be assessed. Study findings suggest that AN is a prevalent risk factor that can support clinical decision making. However, lack of information on the specificity of AN limits our ability to draw conclusions on whether the presence of AN alone or in traditionally low-risk groups is enough on its own to warrant screening for T2DM. If AN were found to be relatively non-specific, then its stand-alone value would be limited. Importantly, however, AN also predicts future T2DM making any measure of specificity difficult to interpret: while low specificity may mean that fewer cases will truly have T2DM, detection of AN provides an opportunity for preventing or delaying future T2DM. Schwartz reported that “it now appears that most, if not all, obesity-related AN, as well as syndromic AN, is related to insulin-resistant states” .
We also recognise that diabetic patients in our study were sampled only from tertiary hospitals and our findings may therefore be more representative of diabetic patients with more severe disease. Since AN is associated with more severe disease , our estimate of the prevalence of AN may be an over-estimation and should be extrapolated to the general population of diabetic patients with caution. Additionally, our inferences concerning the usefulness of AN in detecting undiagnosed T2DM, are based on the assumption that the distribution of risk factors for T2DM in already-diagnosed diabetic patients will be reflective of that seen in undiagnosed patients, and this assumption may not necessarily be true.