1/18
Saturday Morning Class #11 Lp(a) and DM
First some definitions:
There are several types of diabetes mellitus- type 1, type 2 and some in between. The fundamental problem is that there is not enough insulin to regulate blood glucose, either because it is missing (type 1) .
Saturday Morning Class #11 Lp(a) and DM
First some definitions:
There are several types of diabetes mellitus- type 1, type 2 and some in between. The fundamental problem is that there is not enough insulin to regulate blood glucose, either because it is missing (type 1) .
2/18 or because there is "insulin resistance” (type 2), in which case insulin levels are high but ineffective, primarily due to resistance at the muscle level. There are other kinds of diabetes, such as diabetes insipidus, which can be due to pituitary or renal disorders.
3/18 Both types of diabetes cause thirst and paradoxical increased urine flow, but one has glucose in the urine and the other does not. For this reason, it was thought in 19th century that diabetes was due to kidney abnormalities, which in fact it is primary pancreas/liver/muscle
4/18 Fun facts:
1-Diabetes was first described in ancient Egypt in the Ebers Papyrus- "to eliminate urine which is too often/plentiful". Almost all ancient cultures had some form of description for it.
1-Diabetes was first described in ancient Egypt in the Ebers Papyrus- "to eliminate urine which is too often/plentiful". Almost all ancient cultures had some form of description for it.
5/18
2-The term was coined by Demetrius of Apamea in 1 BCE B.C and it means siphon- "whatever one drinks is passed through a pipe"
3-Banting and MacLeod received the Nobel prize in 1923 for discovering insulin and prize money shared w/their students- Best and Banting in photo
2-The term was coined by Demetrius of Apamea in 1 BCE B.C and it means siphon- "whatever one drinks is passed through a pipe"
3-Banting and MacLeod received the Nobel prize in 1923 for discovering insulin and prize money shared w/their students- Best and Banting in photo
6/18 So, how is Lp(a) related to this?
1-What we have learned in last 20 years is that epidemiologically, there is an inverse association of Lp(a) and prevalence of Type 2 DM – meaning those with high Lp(a) have lower rates of T2DM
1-What we have learned in last 20 years is that epidemiologically, there is an inverse association of Lp(a) and prevalence of Type 2 DM – meaning those with high Lp(a) have lower rates of T2DM
7/18 2-There is an inverse association of triglyceride levels, which are elevated in T2DM, with correlation r-value of -0.15-0.2
3-There are several studies that show those with extremely low Lp(a), <5 mg/dL or <12.5 nmol/L, are at higher risk of developing new onset T2DM.
3-There are several studies that show those with extremely low Lp(a), <5 mg/dL or <12.5 nmol/L, are at higher risk of developing new onset T2DM.
8/18 4-What is not known is if this is casual- i.e. chicken or egg- what comes first, insulin resistance causing low Lp(a) or low Lp(a)/LPA gene affecting ability to manage glucose
9/18 Some hints:
1-Insulin affects the LPA gene by suppressing apo(a) production- so if one has rising insulin levels it may reduce Lp(a) (i.e. reverse causality)- in cell culture and humans. ncbi.nlm.nih.gov/pubmed/10027576 ncbi.nlm.nih.gov/pubmed/25649924
1-Insulin affects the LPA gene by suppressing apo(a) production- so if one has rising insulin levels it may reduce Lp(a) (i.e. reverse causality)- in cell culture and humans. ncbi.nlm.nih.gov/pubmed/10027576 ncbi.nlm.nih.gov/pubmed/25649924
10/18
2-Weight loss raise Lp(a) but low carbs/high fat diets can lower Lp(a)- but insulin levels go down in both, so more complex
3-Apo(a) makes Lp(a) with LDL-sized particles. Pts w/ T2DM make large VLDL, its possible they are too big to make Lp(a), thus lower Lp(a)
2-Weight loss raise Lp(a) but low carbs/high fat diets can lower Lp(a)- but insulin levels go down in both, so more complex
3-Apo(a) makes Lp(a) with LDL-sized particles. Pts w/ T2DM make large VLDL, its possible they are too big to make Lp(a), thus lower Lp(a)
11/18 1-There may be a sweet spot for Lp(a) levels, maybe 5-10 mgdL, and maybe it does have some effect on how liver handles glucose- see paper on risk for CVD and seemingly J-curve. @OxPL_apoB ncbi.nlm.nih.gov/pubmed/17541022
12/18 1-This seems to be true in many studies albeit non-significant, where there is a bit of a dip HR <1.0 in risk at Lp(a)- Bruneck, Lp(a) studies collaboration, FOURIER- all hypothesis generating
13/18 Practical Implications:
1-There is not much you can do for your Lp(a) if your Lp(a) is <5 mg/dL, or <12.5 mg/dL, so if you have high risk of DM, need to lose weight, eat healthy and exercise
1-There is not much you can do for your Lp(a) if your Lp(a) is <5 mg/dL, or <12.5 mg/dL, so if you have high risk of DM, need to lose weight, eat healthy and exercise
14/18 2-In ongoing clinical trials, there is a theoretical risk if one lowers Lp(a) to <5 mg/L, there could be higher risk of DM, this will be monitored. Think statins, niacin, etc
15/18 3-It does seem like LDL-Lp(a) and glucose are weakly linked in opposite directions
4-For anyone with Lp(a) >10 mg/dL, I would not worry about this association.
4-For anyone with Lp(a) >10 mg/dL, I would not worry about this association.
16/18 3-this is a nice study we published where you can see the relationship of Lp(a) to both CVD and DM on same graph- instructive. ncbi.nlm.nih.gov/pubmed/24089516
17/18 Quiz- 5 points
The relationship of Lp(a) levels to new onset T2DM can be best characterized as (chose best answer)
1-Occurs in obese patients only
2-Is present inversely at all levels of Lp(a)
3-Is present in all types of DM
4-Is noted only in very low Lp(a)
The relationship of Lp(a) levels to new onset T2DM can be best characterized as (chose best answer)
1-Occurs in obese patients only
2-Is present inversely at all levels of Lp(a)
3-Is present in all types of DM
4-Is noted only in very low Lp(a)
18/18 Bonus question – 1 point
True False:
The Nobel prize for the discovery of insulin was awarded to Sir Frederick Banting and his student Charles Best
True False:
The Nobel prize for the discovery of insulin was awarded to Sir Frederick Banting and his student Charles Best
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