# Should diabetes treatment optimize glycemic variability?

**URL:** <https://forum.fudiabetes.org/t/should-diabetes-treatment-optimize-glycemic-variability/5225>\
**Category:** Treatment\
**Tags:** glycemic-variability\
**Created:** [October 9, 2018, 10:09am UTC](https://forum.fudiabetes.org/t/should-diabetes-treatment-optimize-glycemic-variability/5225 "2018-10-09T10:09:09Z")\
**Posts on this page:** 1\
**Showing post:** 10

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**Author:** ![oni](https://yyz2.discourse-cdn.com/flex030/user_avatar/forum.fudiabetes.org/oni/32/4872_2.png) [@oni](https://forum.fudiabetes.org/u/oni)\
**Post date:** [October 13, 2018, 4:44pm UTC](https://forum.fudiabetes.org/t/should-diabetes-treatment-optimize-glycemic-variability/5225/10 "2018-10-13T16:44:34Z")

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How high is high? Is 90 high? Is 110 high? How long at 120 causes complications? How much extra risk for 3 hours at 130? Is it the same as 260 for 1 minute? The official recommendations for GCK MODY (avg 5.5-7.5% A1c) is no treatment necessary and no known extra mortality risk.

For me, there is quite a bit I think isn’t known about that subject. Not for certain.

I hope the dozen articles I have shared from my collection are sufficient facts to satisfy readers over our opinions 🙂

Since I already covered that the GV oxidative stress theory has been disproven (so far) for T1Ds and T2Ds, let’s do the last theory, glycation: **High GV has no significant effect on T2Ds**. For T1Ds, its effect on Glycated Hemoglobin (HbA1c) is extremely minor the lower your mean glucose is. If your average glucose is 140mg/dL, then the difference between low and high variability on A1c is only 0.27%.

 ![InShot_20181013_085012280](https://canada1.discourse-cdn.com/flex030/uploads/fudiabetes/original/2X/a/a375f7b72ec72f5fb92c4bf970f1c5c8f240a26a.jpeg)

High GV has significant effects on glycation only at mean glucose levels far higher than most would find reasonable or properly managed:

> **[Does Glucose Variability Influence the Relationship Between Mean Plasma...](http://care.diabetesjournals.org/content/34/8/1843)**
>
> OBJECTIVE The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA1c and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability...

Here’s an article showing variability has no effect on quality of life: [https://www.ncbi.nlm.nih.gov/pubmed/26285951](https://www.ncbi.nlm.nih.gov/pubmed/26285951)

And here is one showing hypoglycemia is a much greater concern than glucose variability:

> <https://www.ncbi.nlm.nih.gov/pubmed/22313018>
>
> Chronic sustained hyperglycemia unequivocally predicts vascular disease in diabetes. However, the vascular risk of glucose variability, including hypoglycemia, is uncertain. Vascular dysfunction is present in children with type 1 diabetes and is a critical precursor of atherosclerosis. We aimed to evaluate the relationship between glucose variability and vascular function in children with type 1 diabetes.Fifty-two type 1 diabetes subjects (14 \[SD 2.7\] years old, 25 males) had continuous glucose monitoring that included 48 h of data used to evaluate glucose variability (mean amplitude of glycemic excursions \[MAGE\] and other measurements) and hypoglycemia indices (glycemic risk assessment diabetes equation \[GRADE\] hypoglycemia, Low Blood Glucose Index \[LBGI\], and observed duration of hypoglycemia). Children with type 1 diabetes and 50 age- and gender-matched controls had assessments of vascular function (flow-mediated dilatation \[FMD\] and glyceryl trinitrate-mediated dilatation \[GTN\]).Children with type 1 diabetes had lower FMD and GTN than controls (P=0.02 and P\<0.001, respectively). GRADE hypoglycemia and LBGI were inversely related to FMD (r=-0.36, P=0.009 and r=-0.302, P=0.03, respectively) but did not relate to GTN. GRADE hypoglycemia was independently related to FMD (regression coefficient=-0.25±0.09, P=0.006). MAGE and other measurements of glucose variability measurements did not relate to FMD or GTN.Hypoglycemia, but not glucose variability, during continuous glucose monitoring relates to impaired vascular endothelial function in children with type 1 diabetes. Hypoglycemia may be an additional risk factor for early cardiovascular disease, but the effect of glucose variability, independent of glycosylated hemoglobin, on vascular function remains uncertain.

There is one good study from this year that shows _fasting_ GV predicts cardiovascular, mortality, and hypoglycemic risk.  
They blame the cardiovascular & mortality risk on increased hypoglycemia, however. For those who think more hypos “do not automatically lead to negative consequences”, such a claim should be surprising.

> **[Day-to-day fasting glycaemic variability in DEVOTE: associations with severe...](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002963/)**
>
> The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) was a double-blind, randomised, event-driven, treat-to-target prospective trial...

The most up-to-date review of all this research was published in The Lancet in August. I’d upload it but doesn’t seem I can attach PDFs.  
It is not free, but here is the link: [https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30136-0/fulltext](https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30136-0/fulltext)

There are some other minor studies, like one showing how children with variability in the normoglycemic range (but not persistent hyperglycemia) lose cognitive function. Because of more hypos? 🤔…

But I hope I have been thorough enough already with the major research 🙂  
Happy Reading!

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