Preventing misdiagnosis of diabetes in the elderly

[PGW]

Should the NICE guidelines be updated because of this research.

Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts - BMC Endocrine Disorders

Background Measurement of gylcated hemoglobin A1c (HbA1c) plays a central role in monitoring quality of antidiabetic therapy and in the diagnosis of diabetes. Several studies report increased levels of HbA1c in nondiabetic elderly. However, this observation did not reach incorporation into daily...

bmcendocrdisord.biomedcentral.com

What do you all think?

 

[trophywench]

Well frankly, no, IMHO. Just cos they've studied something for shedloads of people in a particular region of the Baltic States does not necessarily mean it will be the same for either the people of Britain or the population of somewhere else.

Take Polish people, generally. Visit one - eg if you happened to be an agent for someone like Pearl Assurance years ago, as my husband was - where part of his Area had more than a few Polish customers that he needed to collect money from every so often, so he was visiting them for a pre-arranged reason, not knocking on their doors hawking his wares, so to speak. No way would they ever conduct business on their doorstep, you must be invited inside. Hence he would be offered hospitality from every such household he needed to call at - and fortunately he was aware of this, otherwise with the amount of tots of vodka and accompanying snacks he could have consumed, he'd have never got home, and looked like Colonel Blimp, let alone driven back to the office. But if you don't ever accept something in the way of food or drink - you are deeply insulting them!

They're also built of sturdier stock than the feeble individuals we are generally, not at all unusual even today to see em lasting well into their 90s and older with all their faculties intact - whereas it's unusual for us lot now.

 

[PGW]

Well frankly, no, IMHO. Just cos they've studied something for shedloads of people in a particular region of the Baltic States does not necessarily mean it will be the same for either the people of Britain or the population of somewhere else.

Take Polish people, generally. Visit one - eg if you happened to be an agent for someone like Pearl Assurance years ago, as my husband was - where part of his Area had more than a few Polish customers that he needed to collect money from every so often, so he was visiting them for a pre-arranged reason, not knocking on their doors hawking his wares, so to speak. No way would they ever conduct business on their doorstep, you must be invited inside. Hence he would be offered hospitality from every such household he needed to call at - and fortunately he was aware of this, otherwise with the amount of tots of vodka and accompanying snacks he could have consumed, he'd have never got home, and looked like Colonel Blimp, let alone driven back to the office. But if you don't ever accept something in the way of food or drink - you are deeply insulting them!

They're also built of sturdier stock than the feeble individuals we are generally, not at all unusual even today to see em lasting well into their 90s and older with all their faculties intact - whereas it's unusual for us lot now.

So are you saying that the current NICE pre-diabetes hba1c of 42mmol should apply to everone irrespective of age?

 

[helli]

I think anything based on age is going to be very variable as we age so differently.
I do think it is reasonable to "loosen constraints" for "biological elderly".
However, the age indicators for one 75 year old woman may be very different from the markers for another.
Take my mother and mother-in-law. My MIL is 76, had both hips replaced, has type 2 diabetes, overweight and does no exercise. My mother is 81, a regular gym attendee, not overweight, no diabetes and still has her full set of joints.
It does not feel right to treat them both the same because they are "over 75".

I think it is about treating the patient rather than the number.

 

[childofthesea43]

The bottom line with the standard thresholds of 42 and 48 is that they were derived from a single study decades ago of a tiny cohort none of whose ages exceeded 39, so their incorporation into guidelines applied to all ages has been simply imbecilic. Especially for a measure crucially dependent upon red cell turnover which varies with age in all ethnic groups.

 

[Robin]

Especially for a measure crucially dependent upon red cell turnover which varies with age in all ethnic groups.

Good point, I’m sure I read recently that the reason people's HbA1cs tend to increase with age is because their red cell turnover slows, rather than them having more glucose sloshing around in their blood. I can’t remember where I saw it, unfortunately.

 

[Eddy Edson]

They define "healthy" subgroups and show that in these, mean HbA1c rises with age, and conclude that diagnostic thresholds should also increase with age.

But how do they know that the "healthy" people are in fact healthy? Maybe some of them are in fact diabetic, and the conclusion should rather be that diabetic prevalence tends to increase with age.

The issue depends crucially on how they define "healthy". If there were some objective criteria independent of HbA1c then the thing would be easy. But there aren't, and the criteria they use are "no self-reported diabetes or diabetes medication". There are two problems with that: the obvious self-reporting aspect, but also: even a perfectly accurate self-reporter will have to base his/her report on measured HbA1c. So it just seems to me that there's a fundamental circularity to the logic of the argument.

I'd be happy to believe that discordance between HbA1c and actual BG levels increases with age due to RBC changes or whatever; but I'd also be happy to believe that people's glucose regulation deteriorates with age. I just don't think this study has enough oomph to distinguish between the two.

 

[childofthesea43]

They define "healthy" subgroups and show that in these, mean HbA1c rises with age, and conclude that diagnostic thresholds should also increase with age.

But how do they know that the "healthy" people are in fact healthy? Maybe some of them are in fact diabetic, and the conclusion should rather be that diabetic prevalence tends to increase with age.

The issue depends crucially on how they define "healthy". If there were some objective criteria independent of HbA1c then the thing would be easy. But there aren't, and the criteria they use are "no self-reported diabetes or diabetes medication". There are two problems with that: the obvious self-reporting aspect, but also: even a perfectly accurate self-reporter will have to base his/her report on measured HbA1c. So it just seems to me that there's a fundamental circularity to the logic of the argument.

I'd be happy to believe that discordance between HbA1c and actual BG levels increases with age due to RBC changes or whatever; but I'd also be happy to believe that people's glucose regulation deteriorates with age. I just don't think this study has enough oomph to distinguish between the two.

I broadly agree with the comments on the study. Irrespective of that I think we also agree that any thresholds for T2 diagnosis based upon A1c should be sensitive to the age-dependent rate of rbc turnover.

 

[Eddy Edson]

I broadly agree with the comments on the study. Irrespective of that I think we also agree that any thresholds for T2 diagnosis based upon A1c should be sensitive to the age-dependent rate of rbc turnover.

You can make a case that individual average RBC life should be incorporated in diabetes diagnosis, regardless of patient age. See eg https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714656/pdf/nihms916510.pdf from some of the same MassGen/Harvard people who worked on the standard empirical regression relating HbA1c and average BG.

The glycated hemoglobin assay (HbA1c) is essential for the diagnosis and management ofdiabetes because it provides the best estimate of a patient’s average blood glucose (AG) over the preceding 2–3 months and is the best predictor of disease complications.

However, there is substantial unexplained glucose-independent variation in HbA1c that makes AG estimation inaccurate and limits the precision of medical care for diabetics.

The true AG of a non-diabetic and a poorly-controlled diabetic may differ by less than 15 mg/dL, but patients with identical HbA1c and thus identical HbA1c-based estimates of AG may have true AG that differs by more than 60mg/dl.

We combine a mechanistic mathematical model of hemoglobin glycation and red blood cell flux with large sets of intra-patient glucose measurements to derive patient-specific estimates of non-glycemic determinants of HbA1c including mean red blood cell age (MRBC). We find that interpatient variation in derived MRBC explains all glucose-independent variation in HbA1c.

We then use our model to personalize prospective estimates of AG and reduce errors by more than50% in four independent sets of more than 200 patients. The current standard of care provided AG estimates with errors > 15 mg/dL for 1 in 3 patients. Our patient-specific method reduced this error rate to 1 in 10. This personalized approach to estimating AG from HbA1c should improve medical care for diabetes using existing clinical measurements.

I know that studies generally show HbA1c increasing with age, but I haven't seen robust studies looking at whether this is due to deteriorating glucose regulation (for whatever reason); or to increasing discordance between HbA1c and BG, perhaps because of changes to RBC life-spans. Do you know of any?

 

[childofthesea43]

You can make a case that individual average RBC life should be incorporated in diabetes diagnosis, regardless of patient age. See eg https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714656/pdf/nihms916510.pdf from some of the same MassGen/Harvard people who worked on the standard empirical regression relating HbA1c and average BG.

The glycated hemoglobin assay (HbA1c) is essential for the diagnosis and management ofdiabetes because it provides the best estimate of a patient’s average blood glucose (AG) over the preceding 2–3 months and is the best predictor of disease complications.

However, there is substantial unexplained glucose-independent variation in HbA1c that makes AG estimation inaccurate and limits the precision of medical care for diabetics.

The true AG of a non-diabetic and a poorly-controlled diabetic may differ by less than 15 mg/dL, but patients with identical HbA1c and thus identical HbA1c-based estimates of AG may have true AG that differs by more than 60mg/dl.

We combine a mechanistic mathematical model of hemoglobin glycation and red blood cell flux with large sets of intra-patient glucose measurements to derive patient-specific estimates of non-glycemic determinants of HbA1c including mean red blood cell age (MRBC). We find that interpatient variation in derived MRBC explains all glucose-independent variation in HbA1c.

We then use our model to personalize prospective estimates of AG and reduce errors by more than50% in four independent sets of more than 200 patients. The current standard of care provided AG estimates with errors > 15 mg/dL for 1 in 3 patients. Our patient-specific method reduced this error rate to 1 in 10. This personalized approach to estimating AG from HbA1c should improve medical care for diabetes using existing clinical measurements.

I know that studies generally show HbA1c increasing with age, but I haven't seen robust studies looking at whether this is due to deteriorating glucose regulation (for whatever reason); or to increasing discordance between HbA1c and BG, perhaps because of changes to RBC life-spans. Do you know of any?

Interesting - but no, I have not yet seen such a study. Thank you for your incisive views on this topic.