# Results of a cohort study on incidence of complications

**URL:** <https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479>\
**Category:** Complications & More\
**Tags:** research, a1c\
**Created:** [October 9, 2019, 3:25pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479 "2019-10-09T15:25:41Z")\
**Posts on this page:** 14\
**Page:** 1

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**Author:** ![CatLady](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/catlady/32/36_2.png) [@CatLady](https://forum.fudiabetes.org/u/CatLady)\
**Post date:** [October 9, 2019, 3:25pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/1 "2019-10-09T15:25:41Z")

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[https://www.bmj.com/content/bmj/366/bmj.l4894.full.pdf](https://www.bmj.com/content/bmj/366/bmj.l4894.full.pdf)

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**Author:** ![docslotnick](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/docslotnick/32/75_2.png) [@docslotnick](https://forum.fudiabetes.org/u/docslotnick)\
**Post date:** [October 10, 2019, 4:27pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/2 "2019-10-10T16:27:38Z")

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Just skimmed the article, but some takeaways:

1. Why is A1c of 6.5 regarded as the magic low end? Why not 5.5 or 6.0?

2. I noted on one of the charts that SD averaged in each cohort level to be \>70 (I think). I don’t think this would result in a very good Time in Range.

3. In the conclusions, it is recommended to have clinicians be focused on hypoglycemia with an A1c as low as 6.5. Perhaps a CGM with appropriate alarms would be indicated?

It seems that these studies are focused on poorly controlled T1 diabetics.

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**Author:** ![Eric](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/eric/32/9209_2.png) [@Eric](https://forum.fudiabetes.org/u/Eric)\
**Post date:** [October 10, 2019, 4:57pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/3 "2019-10-10T16:57:15Z")

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Am I missing something here?

> RESULTS  
> Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years

> Study cohort  
> …  
> We included children and adults with a diagnosis of diabetes for five or less years when first recorded in the registries.

Complications are a concern years down the road. Seems like an odd group to be studying.

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**Author:** ![Jen](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/jen/32/4777_2.png) [@Jen](https://forum.fudiabetes.org/u/Jen)\
**Post date:** [October 10, 2019, 5:35pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/4 "2019-10-10T17:35:49Z")

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> [@docslotnick](#):
>
> Why is A1c of 6.5 regarded as the magic low end? Why not 5.5 or 6.0?

A 6.5% was just the upper end of the low range, so it would have included those with an A1c of 6.0% or 5.5%. My guess is that the number of people who hit an A1c of 6.5% is already pretty low, so narrowing it even further would result in even fewer participants to compare to.

Having said that, I do agree it would be interesting to look at lower A1c levels. But the reality is that actually achieving lower A1c levels is very difficult for most people even with pumps and CGMs and all the other tools available. So I’m not sure there’s much motivation (or funding) to look at an A1c of, say, 5.5% when most people may never be able to achieve that. I read somewhere that the lower target for the DCCT was actually supposed to be 6.0%, but 7.0% was what that cohort actually achieved (on average).

> [@Eric](#):
>
> Complications are a concern years down the road. Seems like an odd group to be studying.

I’m pretty sure these were just the characteristics of the participants at the start of the study. The study followed them for up to 20 years.

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**Author:** ![EdD](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/edd/32/6286_2.png) [@EdD](https://forum.fudiabetes.org/u/EdD)\
**Post date:** [October 10, 2019, 6:29pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/5 "2019-10-10T18:29:26Z")

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Thanks for posting - I find it very interesting.

Ed

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**Author:** ![Eric](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/eric/32/9209_2.png) [@Eric](https://forum.fudiabetes.org/u/Eric)\
**Post date:** [October 10, 2019, 6:34pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/6 "2019-10-10T18:34:06Z")

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> [@Jen](#):
>
> I’m pretty sure these were just the characteristics of the participants at the start of the study. The study followed them for up to 20 years.

That makes more sense, thanks.

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**Author:** ![EdD](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/edd/32/6286_2.png) [@EdD](https://forum.fudiabetes.org/u/EdD)\
**Post date:** [October 10, 2019, 6:39pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/7 "2019-10-10T18:39:33Z")

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> [@docslotnick](#):
>
> Why is A1c of 6.5 regarded as the magic low end? Why not 5.5 or 6.0?

I would say it is related to this statement half way down pg6  
Moreover, we observed an increased risk of severe hypoglycaemia with HbA1c levels \<6.5% (\<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol).

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**Author:** ![Katers87](https://avatars.discourse-cdn.com/v4/letter/k/a9adbd/32.png) [@Katers87](https://forum.fudiabetes.org/u/Katers87)\
**Post date:** [October 10, 2019, 7:09pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/8 "2019-10-10T19:09:42Z")

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I’m confused about the results. Based on the chart (Table 1) below, it looks like .6% of those with 16-20 years duration with an A1c of \<6.5 have Albuminuria whereas 4.9% of those with 16-20 years duration with an A1c of between 6.5 & 6.9 have Albuminuria.

Is this an accurate interpretation? I understand the difference may not be statistically significant, but the difference in % seems consistent across duration categories. [Edit: these percentages are merely the percentage of people with retinopathy/albuminuria that have that A1c- not the percentage I thought it was. They don’t give the N value for each duration which I find annoying because by the time 20 years have passed, we might only have 10 people left in the \<6.5 group]

![image](https://canada1.discourse-cdn.com/flex030/uploads/fudiabetes/original/2X/d/d9e49cf82e625cf07c5323d7a65ee1182857fc8f.png)

“Participants were categorised by glycaemic control  
based on area under the curve, a weighted mean  
value calculated using the trapezoidal method that  
takes into consideration the interval between HbA1c  
measurements.”

Are they saying that participants were kept in the same A1c cohort throughout time and they’ve sort of averaged the A1c values with the trapezoidal method?

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<div class="post-metadata">

**Author:** ![Katers87](https://avatars.discourse-cdn.com/v4/letter/k/a9adbd/32.png) [@Katers87](https://forum.fudiabetes.org/u/Katers87)\
**Post date:** [October 10, 2019, 7:28pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/9 "2019-10-10T19:28:44Z")

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Also, the odds ratios in the chart below (table 2) are confusing:

![image](https://canada1.discourse-cdn.com/flex030/uploads/fudiabetes/original/2X/3/30d66dc349900af415b317f28a7bede42705ec85.png)

The unadjusted and adjusted odds ratios of any retinopathy vs none for someone with an A1c \<6.5% are well under 1.0 (though the p-value shows this difference isn’t necessarily meaningful)

However, somehow the odds ratios increase significantly when each form of retinopathy is evaluated individually. That doesn’t really make any sense.

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**Author:** ![bkh](https://avatars.discourse-cdn.com/v4/letter/b/da6949/32.png) [@bkh](https://forum.fudiabetes.org/u/bkh)\
**Post date:** [October 10, 2019, 8:24pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/10 "2019-10-10T20:24:21Z")

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> [@Katers87](#):
>
> However, somehow the odds ratios increase significantly when each form of retinopathy is evaluated individually. That doesn’t really make any sense.

Look at the n-values. The total N for \<6.5% is 75. The N for the two specific kinds of retinopathy shown in your example are 7 + 6. So that says the other 62 folks had a much lower incidence of retinopathy to get an overall odds ratio less than 1.

> Are they saying that participants were kept in the same A1c cohort throughout time and they’ve sort of averaged the A1c values with the trapezoidal method?

Looks to me like they calculate each subject’s “average” A1C over the 20 year period, and put them into that group, so their results don’t distinguish between those who improved their A1C from those who didn’t.

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<div class="post-metadata">

**Author:** ![Katers87](https://avatars.discourse-cdn.com/v4/letter/k/a9adbd/32.png) [@Katers87](https://forum.fudiabetes.org/u/Katers87)\
**Post date:** [October 10, 2019, 8:29pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/11 "2019-10-10T20:29:59Z")

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> [@bkh](#):
>
> Look at the n-values. The total N for \<6.5% is 75. The N for the two specific kinds of retinopathy shown in your example are 7 + 6. So that says the other 62 folks had a much lower incidence of retinopathy to get an overall odds ratio less than 1.

Yes, but there is no reason the odds ratio should increase dramatically when each form of retinopathy is evaluated individually versus any form of retinopathy at all.

I don’t think 75 represents the number of people in that category. I think it represents the number of people with “Any retinopathy” in that group (\<6.5%) since that value falls under the “No. of participants with events” column.

> [@bkh](#):
>
> Looks to me like they calculate each subject’s “average” A1C over the 20 year period, and put them into that group, so their results don’t distinguish between those who improved their A1C from those who didn’t.

Yes, that was my understanding as well.

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<div class="post-metadata">

**Author:** ![Katers87](https://avatars.discourse-cdn.com/v4/letter/k/a9adbd/32.png) [@Katers87](https://forum.fudiabetes.org/u/Katers87)\
**Post date:** [October 10, 2019, 8:41pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/12 "2019-10-10T20:41:51Z")

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"The risk of any retinopathy (simplex or worse)  
for participants with an HbA1c level \<6.5% (\<48 mmol/  
mol) compared with 6.5-6.9% (48-52 mmol/mol) did  
not differ: unadjusted odds ratio 0.85 (95% confidence  
interval 0.63 to 1.13, P=0.25) and adjusted odds ratio  
0.77 (0.56 to 1.05, P=0.10)…

A different pattern was observed for preproliferative  
diabetic retinopathy or worse, with risk increases in  
participants with low HbA1c levels (\<6.5%, \<48 mmol/  
mol) in unadjusted analysis (odds ratio 3.74, 1.19 to  
11.76, P=0.02) and in adjusted analysis (3.29, 0.99 to  
10.96, P=0.05)…

For the most advanced  
stage (proliferative diabetic retinopathy or earlier  
laser photocoagulation), risk increases were observed  
for participants with low HbA1c levels (\<6.5%, \<48  
mmol/mol): odds ratio 4.18 (1.17 to 14.90, P=0.03) in  
unadjusted analysis and 2.48 (0.71 to 8.62, P=0.15)  
in adjusted analysis."

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<div class="post-metadata">

**Author:** ![bkh](https://avatars.discourse-cdn.com/v4/letter/b/da6949/32.png) [@bkh](https://forum.fudiabetes.org/u/bkh)\
**Post date:** [October 10, 2019, 8:45pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/13 "2019-10-10T20:45:28Z")

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> [@Katers87](#):
>
> Yes, but there is no reason the odds ratio should increase dramatically when each form of retinopathy is evaluated individually versus any form of retinopathy at all.

I didn’t look at the original paper, and just guessed that the two categories of retinopathy that they showed were “optical” outliers. With small numbers in the subgroups it seems reasonable to expect lots of spread, so some subgroups will look extra bad or extra good just because of the spread, even if that doesn’t accurately reflect the underlying reality that we’d find in a large population.

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<div class="post-metadata">

**Author:** ![Katers87](https://avatars.discourse-cdn.com/v4/letter/k/a9adbd/32.png) [@Katers87](https://forum.fudiabetes.org/u/Katers87)\
**Post date:** [October 10, 2019, 8:50pm UTC](https://forum.fudiabetes.org/t/results-of-a-cohort-study-on-incidence-of-complications/8479/14 "2019-10-10T20:50:08Z")

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I guess they’re saying the odds of simplex are better (not necessarily significantly) in the \<6.5 group, but that the odds of the worse retinopathies are higher? The only three categories of retinopathy are simplex, PPDR, or PDR.

Still seems like a strange conclusion.