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Skin autofluorescence based decision tree in detection of impaired glucose tolerance and diabetes.

Smit AJ, Smit JM, Botterblom GJ, Mulder DJ - PLoS ONE (2013)

Bottom Line: With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%).Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%).SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University Medical Center Groningen, and University of Groningen, Groningen, The Netherlands. a.j.smit@umcg.nl

ABSTRACT

Aim: Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire±FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.

Methods: Participants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).

Results: 218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).

Conclusion: SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM's value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.

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Summary design of skin AF based IGT/diabetes detection decision model (SAF-DM), using SAF level age-dependent cutoff levels (shown here for age >50 years, different cut-off levels at lower age), using age percentiles.Effects of low reflectance have not been included.
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pone-0065592-g001: Summary design of skin AF based IGT/diabetes detection decision model (SAF-DM), using SAF level age-dependent cutoff levels (shown here for age >50 years, different cut-off levels at lower age), using age percentiles.Effects of low reflectance have not been included.

Mentions: The summary design of this model is shown in Figure 1. The model adds, depending on the measured skin AF age percentile, question-based information which may be obtained readily in a screening setting. In case of elevated skin AF age percentile, maximally three questions are asked about conditions possibly leading to increased skin AF levels: questions ask for a recent history of serious (leading to hospital admission) infections (<1 year) or CVE (<2 years), or a history of renal or autoimmune disease. In case of documented and ongoing peripheral arterial or coronary disease (stable angina pectoris) a recent admission was not required. Further, in case skin AF is below age percentile cut-off levels questions are asked on classical IGT/diabetes risk factors apart from age: questions on weight/BMI, on 1st degree family history of diabetes (and if so, the number), and on use of antihypertensives. These questions were formulated and asked for in the same manner as in the FINDRISC questionnaire [8]. Scoring in the developed decision model first depends on a >70th (<50 years) or >80th (≥50 years) age percentile cut-off level of skin AF, plus information on the questions described above, and on BMI with different cut-off levels: at >35 kg/m2, >32 kg/m2, and >29 kg/m2, respectively. Persons with a BMI>35 kg/m2 were assumed to have diabetes/IGT, independent of other information. For the latter two BMI groups, a combined weighing of BMI, skin AF percentile and information on number of first degree relatives with diabetes and on antihypertensive use determined whether the decision tree outcome gave a positive score for IGT/diabetes. This combined risk weighing was based on the risk assumptions for the three variables BMI, family history and skin AF derived from data of questionnaire-based risk estimates (FINDRISC and Cambridge Diabetes Risk Score, CDRS). In the persons with an elevated skin AF above the defined age percentile cutoff, the then asked questions described above, are accounted for as follows. If one of the questions on an alternative condition in the last year was positively answered, the decision tree result states that diabetes/IGT may be present, but alternative explanations for the abnormal results are available. In the decision tree performance analysis below such a response was scored as negative for IGT/diabetes.


Skin autofluorescence based decision tree in detection of impaired glucose tolerance and diabetes.

Smit AJ, Smit JM, Botterblom GJ, Mulder DJ - PLoS ONE (2013)

Summary design of skin AF based IGT/diabetes detection decision model (SAF-DM), using SAF level age-dependent cutoff levels (shown here for age >50 years, different cut-off levels at lower age), using age percentiles.Effects of low reflectance have not been included.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672176&req=5

pone-0065592-g001: Summary design of skin AF based IGT/diabetes detection decision model (SAF-DM), using SAF level age-dependent cutoff levels (shown here for age >50 years, different cut-off levels at lower age), using age percentiles.Effects of low reflectance have not been included.
Mentions: The summary design of this model is shown in Figure 1. The model adds, depending on the measured skin AF age percentile, question-based information which may be obtained readily in a screening setting. In case of elevated skin AF age percentile, maximally three questions are asked about conditions possibly leading to increased skin AF levels: questions ask for a recent history of serious (leading to hospital admission) infections (<1 year) or CVE (<2 years), or a history of renal or autoimmune disease. In case of documented and ongoing peripheral arterial or coronary disease (stable angina pectoris) a recent admission was not required. Further, in case skin AF is below age percentile cut-off levels questions are asked on classical IGT/diabetes risk factors apart from age: questions on weight/BMI, on 1st degree family history of diabetes (and if so, the number), and on use of antihypertensives. These questions were formulated and asked for in the same manner as in the FINDRISC questionnaire [8]. Scoring in the developed decision model first depends on a >70th (<50 years) or >80th (≥50 years) age percentile cut-off level of skin AF, plus information on the questions described above, and on BMI with different cut-off levels: at >35 kg/m2, >32 kg/m2, and >29 kg/m2, respectively. Persons with a BMI>35 kg/m2 were assumed to have diabetes/IGT, independent of other information. For the latter two BMI groups, a combined weighing of BMI, skin AF percentile and information on number of first degree relatives with diabetes and on antihypertensive use determined whether the decision tree outcome gave a positive score for IGT/diabetes. This combined risk weighing was based on the risk assumptions for the three variables BMI, family history and skin AF derived from data of questionnaire-based risk estimates (FINDRISC and Cambridge Diabetes Risk Score, CDRS). In the persons with an elevated skin AF above the defined age percentile cutoff, the then asked questions described above, are accounted for as follows. If one of the questions on an alternative condition in the last year was positively answered, the decision tree result states that diabetes/IGT may be present, but alternative explanations for the abnormal results are available. In the decision tree performance analysis below such a response was scored as negative for IGT/diabetes.

Bottom Line: With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%).Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%).SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University Medical Center Groningen, and University of Groningen, Groningen, The Netherlands. a.j.smit@umcg.nl

ABSTRACT

Aim: Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire±FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.

Methods: Participants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).

Results: 218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).

Conclusion: SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM's value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.

Show MeSH
Related in: MedlinePlus