Lantus (Glargine)/ Levemir (Detemir) ?

[Kumar]

Hello,

Many benefits are indicated specific/uniquue to Lantus
(Glargine)/ Levemir (Detemir) insulins;

"http://medweb.bham.ac.uk/easdec/prevention/lantusnotes.htm"

"Insulin glargine, sold under the name Lantus, is a
long-acting basal insulin analogue, usually given once or
twice daily to help control the blood sugar level of those
with diabetes. Its theoretical advantage is that it has a 24
hour duration of action, with a "peakless" profile. Thus, it
more closely resembles the basal insulin secretion of the
normal pancreatic beta cells.. The peakless profile of Lantus
also enables the dose to be relatively higher than standard
NPH insulin. Because standard NPH is normally administered at
night, its peak of action tends to coincide with the lower
serum glucose levels associated with nocturnal metabolism.
This can induce nocturnal hypoglycaemia. Lantus offers the
benefit of a more consistent pharmacological dynamic without
nocturnal hypoglycaemia.

Lantus is formulated at pH4, whereby it is completely soluble.
Upon injection, it is neutralized leading to the release small
precipitates. This ensures that small amount of Lantus is
released into the body continuously, giving a peakless profile
http://en.wikipedia.org/wiki/Lantus "

"Key Benefits

No pronounced peak.

Only insulin analog used once a day, proven to lower basal
glucose levels for a full 24 hours.

Can be used with oral diabetes medications and/or short-acting
insulin to control diabetes. http://chinese-school.netfirms.c-
om/diabetes-insulin-lantus.html "

In view of above quotes, I want to unerstand:-

1. How lantus is different/unique in its availabilty in view
of that it precipitate and crystalize after injected due
changes in its low pH=4 to 7 whereas other long acting may
be injected in already precipitated/crystalized state due
to higher pH (7.0)?

2. How it is diffetrent from other long acting insulins which
may also be having 24hrs effects?

3. How lantus can be claimed to have "no pronounced peak"?

4. With claimed "no pronounced peak and steady availability
during 24 hrs.", will it be better suited to diabetics2
with persisting chronic hyperglycemia (persistance of this
take care persistance of higher glucose levels)?

5. In view of claimed "no pronounced peak and steady
availability during 24 hrs", can it result lesser hunger
(if insulin is a cause to getting hunger) hat other
insulins with pronounced peaks?

6. How lantus's considerable low pH=4 than body's injected
sites pH(I think 7 appx.) can damage/effect locally and
systemically?

I think, above questions are need to be looked into seriously,
so pls contribute?

Best wishes.

[Kumar]

On Mar 9, 9:25 am, "Kumar" <lordshiva5...@gmail.com> wrote:
> Hello,
>
> Many benefits are indicated specific/uniquue to Lantus
> (Glargine)/ Levemir (Detemir) insulins;
>
> "http://medweb.bham.ac.uk/easdec/prevention/lantusnotes.htm"
>
> "Insulin glargine, sold under the name Lantus, is a
> long-acting basal insulin analogue, usually given once or
> twice daily to help control the blood sugar level of those
> with diabetes. Its theoretical advantage is that it has a 24
> hour duration of action, with a "peakless" profile. Thus, it
> more closely resembles the basal insulin secretion of the
> normal pancreatic beta cells.. The peakless profile of
> Lantus also enables the dose to be relatively higher than
> standard NPH insulin. Because standard NPH is normally
> administered at night, its peak of action tends to coincide
> with the lower serum glucose levels associated with
> nocturnal metabolism. This can induce nocturnal
> hypoglycaemia. Lantus offers the benefit of a more
> consistent pharmacological dynamic without nocturnal
> hypoglycaemia.
>
> Lantus is formulated at pH4, whereby it is completely
> soluble. Upon injection, it is neutralized leading to the
> release small precipitates. This ensures that small amount
> of Lantus is released into the body continuously, giving a
> peakless profilehttp://en.wikipedia.org/wiki/Lantus"
>
> "Key Benefits
>
> No pronounced peak.
>
> Only insulin analog used once a day, proven to lower basal
> glucose levels for a full 24 hours.
>
> Can be used with oral diabetes medications and/or
> short-acting insulin to control diabetes.http://chinese-sch-
> ool.netfirms.com/diabetes-insulin-lantus.html"
>
> In view of above quotes, I want to unerstand:-
>
> 1. How lantus is different/unique in its availabilty in view
> of that it precipitate and crystalize after injected due
> changes in its low pH=4 to 7 whereas other long acting
> may be injected in already precipitated/crystalized state
> due to higher pH (7.0)?
>
> 2. How it is diffetrent from other long acting insulins
> which may also be having 24hrs effects?
>
> 3. How lantus can be claimed to have "no pronounced peak"?
>
> 4. With claimed "no pronounced peak and steady availability
> during 24 hrs.", will it be better suited to diabetics2
> with persisting chronic hyperglycemia (persistance of
> this take care persistance of higher glucose levels)?
>
> 5. In view of claimed "no pronounced peak and steady
> availability during 24 hrs", can it result lesser hunger
> (if insulin is a cause to getting hunger) hat other
> insulins with pronounced peaks?
>
> 6. How lantus's considerable low pH=4 than body's injected
> sites pH(I think 7 appx.) can damage/effect locally and
> systemically?
>
> I think, above questions are need to be looked into
> seriously, so pls contribute?
>
> Best wishes.

Sorry, other related groups also to contrinute to this
topic, so added.

[shoppa]

On Mar 8, 11:25 pm, "Kumar" <lordshiva5...@gmail.com> wrote:
> 2. How it is diffetrent from other long acting insulins
> which may also be having 24hrs effects?
>
> 3. How lantus can be claimed to have "no pronounced peak"?
>
> 4. With claimed "no pronounced peak and steady availability
> during 24 hrs.", will it be better suited to diabetics2
> with persisting chronic hyperglycemia (persistance of
> this take care persistance of higher glucose levels)?
>
> 5. In view of claimed "no pronounced peak and steady
> availability during 24 hrs", can it result lesser hunger
> (if insulin is a cause to getting hunger) hat other
> insulins with pronounced peaks?

In the perfect world it wouldn't have any peak and would be
good for 24 hours, but in the real world it doesn't always
work that way for everybody. Some of us take two shots 12
hours apart to smooth it out.

There is a broad peak at about 6 hours and many of us time our
shots to position that peak where it's most useful.

Tim.

[Tseverson]

My 94-year-old Mother is a Type 2 diabetic (over 30 years).
Her blood glucose readings have a long history of being in the
"out of control" range. She is currently using "insulin N"
(NPH). Could she consider switching to Lantus or Levemir?

[Kumar]

Andrew B. Chung, MD/PhD wrote:
> Lantus is really not indicated in someone with the usual
> type-2 diabetes.
>
> Indeed, type-2 diabetics using Lantus will likely run a
> higher risk of becoming hypoglycemic when trying to eat
> less to lose the visceral adipose tissue (VAT) that is
> killing them.
Thanks and welcome. How Lantus is specific to above effect?

Pls also tell about other questions.
> Andrew <><
> --
> Andrew B. Chung, MD/PhD http://EmoryCardiology.com
>
> convicted neighbor Kumar wrote:
> > On Mar 9, 9:25 am, "Kumar" <lordshiva5...@gmail.com>
> > wrote:
> > > Hello,
> > >
> > > Many benefits are indicated specific/uniquue to Lantus
> > > (Glargine)/ Levemir (Detemir) insulins;
> > >
> > > "http://medweb.bham.ac.uk/easdec/prevention/lantusnotes-
> > > .htm"
> > >
> > > "Insulin glargine, sold under the name Lantus, is a
> > > long-acting basal insulin analogue, usually given once
> > > or twice daily to help control the blood sugar level of
> > > those with diabetes. Its theoretical advantage is that
> > > it has a 24 hour duration of action, with a "peakless"
> > > profile. Thus, it more closely resembles the basal
> > > insulin secretion of the normal pancreatic beta cells..
> > > The peakless profile of Lantus also enables the dose to
> > > be relatively higher than standard NPH insulin. Because
> > > standard NPH is normally administered at night, its peak
> > > of action tends to coincide with the lower serum glucose
> > > levels associated with nocturnal metabolism. This can
> > > induce nocturnal hypoglycaemia. Lantus offers the
> > > benefit of a more consistent pharmacological dynamic
> > > without nocturnal hypoglycaemia.
> > >
> > > Lantus is formulated at pH4, whereby it is completely
> > > soluble. Upon injection, it is neutralized leading to
> > > the release small precipitates. This ensures that small
> > > amount of Lantus is released into the body continuously,
> > > giving a peakless
> > > profilehttp://en.wikipedia.org/wiki/Lantus"
> > >
> > > "Key Benefits
> > >
> > > No pronounced peak.
> > >
> > > Only insulin analog used once a day, proven to lower
> > > basal glucose levels for a full 24 hours.
> > >
> > > Can be used with oral diabetes medications and/or
> > > short-acting insulin to control diabetes.http://chinese-
> > > -school.netfirms.com/diabetes-insulin-lantus.html"
> > >
> > > In view of above quotes, I want to unerstand:-
> > >
> > > 1. How lantus is different/unique in its availabilty in
> > > view of that it precipitate and crystalize after
> > > injected due changes in its low pH=4 to 7 whereas
> > > other long acting may be injected in already
> > > precipitated/crystalized state due to higher pH
> > > (7.0)?
> > >
> > > 2. How it is diffetrent from other long acting insulins
> > > which may also be having 24hrs effects?
> > >
> > > 3. How lantus can be claimed to have "no pronounced
> > > peak"?
> > >
> > > 4. With claimed "no pronounced peak and steady
> > > availability during 24 hrs.", will it be better
> > > suited to diabetics2 with persisting chronic
> > > hyperglycemia (persistance of this take care
> > > persistance of higher glucose levels)?
> > >
> > > 5. In view of claimed "no pronounced peak and steady
> > > availability during 24 hrs", can it result lesser
> > > hunger (if insulin is a cause to getting hunger) hat
> > > other insulins with pronounced peaks?
> > >
> > > 6. How lantus's considerable low pH=4 than body's
> > > injected sites pH(I think 7 appx.) can damage/effect
> > > locally and systemically?
> > >
> > > I think, above questions are need to be looked into
> > > seriously, so pls contribute?
> > >
> > > Best wishes.
> >
> > Sorry, other related groups also to contrinute to this
> > topic, so added.

[Kumar]

Andrew B. Chung, MD/PhD wrote:
> convicted neighbor Kumar wrote:
> > Andrew, in the Holy Spirit, boldly wrote:
> >
> > > Lantus is really not indicated in someone with the usual
> > > type-2 diabetes.
> > >
> > > Indeed, type-2 diabetics using Lantus will likely run a
> > > higher risk of becoming hypoglycemic when trying to eat
> > > less to lose the visceral adipose tissue (VAT) that is
> > > killing them.
> >
> > Thanks and welcome. How Lantus is specific to above
> > effect?
>
> Lantus has an extremely long duration of action which will
> make it less forgiving for someone who has chosen to eat
> considerably less.
But it is claimed to has steady and lesser hypoglycemic giving
effects. Is it better suited to diabetics who have persisting
hyperglycemia and need continual/occasional insulin's exposure
during 24hrs?

In view of its claimed "peakless effect", can it cause lesser
cravings due to steady(not peak) exposure?

Can there be some adversities due to its low pH and its
continual and prolonged exposure on increased synthesis and
decreased breakdown of energy stores due to indicated actions
of insulin?
> > Pls also tell about other questions.
> > > Andrew <><
> > > --
> > > Andrew B. Chung, MD/PhD http://EmoryCardiology.com
> > >
> > > convicted neighbor Kumar wrote:
> >
> > > > > Hello,
> > > > >
> > > > > Many benefits are indicated specific/uniquue to
> > > > > Lantus (Glargine)/ Levemir (Detemir) insulins;
> > > > >
> > > > > "http://medweb.bham.ac.uk/easdec/prevention/lantusn-
> > > > > otes.htm"
> > > > >
> > > > > "Insulin glargine, sold under the name Lantus, is a
> > > > > long-acting basal insulin analogue, usually given
> > > > > once or twice daily to help control the blood sugar
> > > > > level of those with diabetes. Its theoretical
> > > > > advantage is that it has a 24 hour duration of
> > > > > action, with a "peakless" profile. Thus, it more
> > > > > closely resembles the basal insulin secretion of the
> > > > > normal pancreatic beta cells.. The peakless profile
> > > > > of Lantus also enables the dose to be relatively
> > > > > higher than standard NPH insulin. Because standard
> > > > > NPH is normally administered at night, its peak of
> > > > > action tends to coincide with the lower serum
> > > > > glucose levels associated with nocturnal metabolism.
> > > > > This can induce nocturnal hypoglycaemia. Lantus
> > > > > offers the benefit of a more consistent
> > > > > pharmacological dynamic without nocturnal
> > > > > hypoglycaemia.
> > > > >
> > > > > Lantus is formulated at pH4, whereby it is
> > > > > completely soluble. Upon injection, it is
> > > > > neutralized leading to the release small
> > > > > precipitates. This ensures that small amount of
> > > > > Lantus is released into the body continuously,
> > > > > giving a peakless
> > > > > profilehttp://en.wikipedia.org/wiki/Lantus"
> > > > >
> > > > > "Key Benefits
> > > > >
> > > > > No pronounced peak.
> > > > >
> > > > > Only insulin analog used once a day, proven to lower
> > > > > basal glucose levels for a full 24 hours.
> > > > >
> > > > > Can be used with oral diabetes medications and/or
> > > > > short-acting insulin to control diabetes.http://chi-
> > > > > nese-school.netfirms.com/diabetes-insulin-lantus.ht-
> > > > > ml"
> > > > >
> > > > > In view of above quotes, I want to unerstand:-
> > > > >
> > > > > 1. How lantus is different/unique in its availabilty
> > > > > in view of that it precipitate and crystalize
> > > > > after injected due changes in its low pH=4 to 7
> > > > > whereas other long acting may be injected in
> > > > > already precipitated/crystalized state due to
> > > > > higher pH (7.0)?
>
> It is a different insulin analogue.
>
> > > > > 2. How it is diffetrent from other long acting
> > > > > insulins which may also be having 24hrs effects?
>
> Again, it is a different insulin analogue.
>
> > > > > 3. How lantus can be claimed to have "no pronounced
> > > > > peak"?
>
> That is what is observed.
>
> > > > > 4. With claimed "no pronounced peak and steady
> > > > > availability during 24 hrs.", will it be better
> > > > > suited to diabetics2 with persisting chronic
> > > > > hyperglycemia (persistance of this take care
> > > > > persistance of higher glucose levels)?
>
> It is for lowering the basal glucose level.
>
> > > > > 5. In view of claimed "no pronounced peak and steady
> > > > > availability during 24 hrs", can it result lesser
> > > > > hunger (if insulin is a cause to getting hunger)
> > > > > hat other insulins with pronounced peaks?
>
> When beneficial, it will increase hunger.
>
> > > > > 6. How lantus's considerable low pH=4 than body's
> > > > > injected sites pH(I think 7 appx.) can
> > > > > damage/effect locally and systemically?
>
> The pH is brought up by the body's buffering system at the
> site of injection.
>
> Andrew <><
> --
> Andrew B. Chung, MD/PhD http://EmoryCardiology.com

[Andrew B.]

convicted neighbor Kumar wrote:
> Andrew, in the Holy Spirit, boldly wrote:
> > convicted neighbor Kumar wrote:
> > > Andrew, in the Holy Spirit, boldly wrote:
> > >
> > > > Lantus is really not indicated in someone with the
> > > > usual type-2 diabetes.
> > > >
> > > > Indeed, type-2 diabetics using Lantus will likely run
> > > > a higher risk of becoming hypoglycemic when trying to
> > > > eat less to lose the visceral adipose tissue (VAT)
> > > > that is killing them.
> > >
> > > Thanks and welcome. How Lantus is specific to above
> > > effect?
> >
> > Lantus has an extremely long duration of action which will
> > make it less forgiving for someone who has chosen to eat
> > considerably less.
>
> But it is claimed to has steady and lesser hypoglycemic
> giving effects.

For someone who is not purposefully eating less to lose
his/her visceral adipose tissue (VAT).

> Is it better suited to diabetics who have persisting
> hyperglycemia and need continual/occasional insulin's
> exposure during 24hrs?

This would not describe someone who is purposefully eating
less and is thus consequently losing his/her VAT and
overcoming his/her insulin resistance.

> In view of its claimed "peakless effect", can it cause
> lesser cravings due to steady(not peak) exposure?

If it is beneficial, a person will be hungrier.

> Can there be some adversities due to its low pH and its
> continual and prolonged exposure on increased synthesis and
> decreased breakdown of energy stores due to indicated
> actions of insulin?

Local irritation at the site of injection.

Andrew <><
--
Andrew B. Chung, MD/PhD http://EmoryCardiology.com

[Kumar]

On Mar 17, 12:56 pm, "Andrew B. Chung, MD/PhD"
<lov...@thetruth.com> wrote:
> convicted neighbor Kumar wrote:
> > Andrew, in the Holy Spirit, boldly wrote:
> > > convicted neighbor Kumar wrote:
> > > > Andrew, in the Holy Spirit, boldly wrote:
>
> > > > > Lantus is really not indicated in someone with the
> > > > > usual type-2 diabetes.
>
> > > > > Indeed, type-2 diabetics using Lantus will likely
> > > > > run a higher risk of becoming hypoglycemic when
> > > > > trying to eat less to lose the visceral adipose
> > > > > tissue (VAT) that is killing them.
>
> > > > Thanks and welcome. How Lantus is specific to above
> > > > effect?
>
> > > Lantus has an extremely long duration of action which
> > > will make it less forgiving for someone who has chosen
> > > to eat considerably less.
>
> > But it is claimed to has steady and lesser hypoglycemic
> > giving effects.
>
> For someone who is not purposefully eating less to lose
> his/her visceral adipose tissue (VAT).

How such steady any additional long term effect become
possible? Is it different in polymerization into
crystals/precipitation after injection than other long
acting insulin?
> > Is it better suited to diabetics who have persisting
> > hyperglycemia and need continual/occasional insulin's
> > exposure during 24hrs?
>
> This would not describe someone who is purposefully eating
> less and is thus consequently losing his/her VAT and
> overcoming his/her insulin resistance.
Yes, but what about to them who are not overcoming his/her
insulin resistance and having persisting hyperglycemia?

> > In view of its claimed "peakless effect", can it cause
> > lesser cravings due to steady(not peak) exposure?
>
> If it is beneficial, a person will be hungrier.
How steady and peakless insulin's exposure can effect
irregular eating habits?
> > Can there be some adversities due to its low pH and its
> > continual and prolonged exposure on increased synthesis
> > and decreased breakdown of energy stores due to indicated
> > actions of insulin?
>
> Local irritation at the site of injection.
Can it cause comparetively more and irreversible tissue damges
due to its lower pH than other insulins with higher pH?
> Andrew <><
> --
> Andrew B. Chung, MD/PhDhttp://EmoryCardiology.com- Hide
> quoted text -
>
> - Show quoted text -

[Kumar]

On Mar 18, 11:51 pm, "Andrew B. Chung, MD/PhD"
<lov...@thetruth.com> wrote:
> convicted neighbor Kumar wrote:
> > Andrew, in the Holy Spirit, boldly wrote:
> > > convicted neighbor Kumar wrote:
> > > > Andrew, in the Holy Spirit, boldly wrote:
> > > > > convicted neighbor Kumar wrote:
> > > > > > Andrew, in the Holy Spirit, boldly wrote:
>
> > > > > > > Lantus is really not indicated in someone with
> > > > > > > the usual type-2 diabetes.
>
> > > > > > > Indeed, type-2 diabetics using Lantus will
> > > > > > > likely run a higher risk of becoming
> > > > > > > hypoglycemic when trying to eat less to lose the
> > > > > > > visceral adipose tissue (VAT) that is killing
> > > > > > > them.
>
> > > > > > Thanks and welcome. How Lantus is specific to
> > > > > > above effect?
>
> > > > > Lantus has an extremely long duration of action
> > > > > which will make it less forgiving for someone who
> > > > > has chosen to eat considerably less.
>
> > > > But it is claimed to has steady and lesser
> > > > hypoglycemic giving effects.
>
> > > For someone who is not purposefully eating less to lose
> > > his/her visceral adipose tissue (VAT).
>
> > How such steady any additional long term effect become
> > possible? Is it different in polymerization into
> > crystals/precipitation after injection than other long
> > acting insulin?
>
> It is precipitation from decreased solubility at neutral pH
> compared to other insulin analogues.

Whether other long acting are not injected in already
precipitated/ crystalize form due to higher/neutral pH? If
yes, how these can be different from lantus in effect?
> > > > Is it better suited to diabetics who have persisting
> > > > hyperglycemia and need continual/occasional insulin's
> > > > exposure during 24hrs?
>
> > > This would not describe someone who is purposefully
> > > eating less and is thus consequently losing his/her VAT
> > > and overcoming his/her insulin resistance.
>
> > Yes, but what about to them who are not overcoming his/her
> > insulin resistance and having persisting hyperglycemia?
>
> All can overcome their insulin resistance by eating less.
Still who are experiancing persisting hyperglycemia, whether
lantus is better for its claimed steady and continual efect?
> > > > In view of its claimed "peakless effect", can it cause
> > > > lesser cravings due to steady(not peak) exposure?
>
> > > If it is beneficial, a person will be hungrier.
>
> > How steady and peakless insulin's exposure can effect
> > irregular eating habits?
>
> Insulin does not affect irregular eating habits.
Previously, I think insulin was related to stimulating hunger?
> > > > Can there be some adversities due to its low pH and
> > > > its continual and prolonged exposure on increased
> > > > synthesis and decreased breakdown of energy stores due
> > > > to indicated actions of insulin?
>
> > > Local irritation at the site of injection.
>
> > Can it cause comparetively more and irreversible tissue
> > damges due to its lower pH than other insulins with
> > higher pH?
>
> Not clinically seen.
Means, if we inject a solution having pH=4 (equal to insulin),
it will not effect and damage?
> Andrew <><
> --
> Andrew B. Chung, MD/PhDhttp://EmoryCardiology.com- Hide
> quoted text -
>
> - Show quoted text -

[Matt Weber]

On 19 Mar 2007 01:47:37 -0700, "Kumar"
<lordshiva5753@gmail.com> wrote:

>> > How such steady any additional long term effect become
>> > possible? Is it different in polymerization into
>> > crystals/precipitation after injection than other long
>> > acting insulin?
The Solubility product of the chemical determines how long and
how flat the curve is. Lantus has a reputation for having a
very low solubility, so it takes a number of doses to reach
steady state, i.e. it takes much longer than 24 hours for all
of a single injection to dissolve.

By contrast NPH is much more soluble at body pH than Lantus,
The more soluble the insulin, the more 'peaky' it becomes.
>>
>> It is precipitation from decreased solubility at neutral pH
>> compared to other insulin analogues.
>
>Whether other long acting are not injected in already
>precipitated/ crystalize form due to higher/neutral pH? If
>yes, how these can be different from lantus in effect?
>> > > > Is it better suited to diabetics who have persisting
>> > > > hyperglycemia and need continual/occasional insulin's
>> > > > exposure during 24hrs?

[Matt Weber]

On 20 Mar 2007 00:16:15 -0700, "Kumar"
<lordshiva5753@gmail.com> wrote:

>
>matt weber wrote:
>> On 19 Mar 2007 01:47:37 -0700, "Kumar"
>> <lordshiva5753@gmail.com> wrote:
>>
>> >> > How such steady any additional long term effect become
>> >> > possible? Is it different in polymerization into
>> >> > crystals/precipitation after injection than other long
>> >> > acting insulin?
>> The Solubility product of the chemical determines how long
>> and how flat the curve is. Lantus has a reputation for
>> having a very low solubility, so it takes a number of doses
>> to reach steady state, i.e. it takes much longer than 24
>> hours for all of a single injection to dissolve.
>>
>> By contrast NPH is much more soluble at body pH than
>> Lantus, The more soluble the insulin, the more 'peaky' it
>> becomes.
>
>Thanks. As such, will lantus be lesser available insulin than
>NPH resulting lesser but prolonged steady effect? Will lantus
>be required more units to be injected than NPH to control
>blood glucose levels, considering its slower/lesser but
>steady effect?
Ultimately total Lantus dose and NPH/Ultralente daily doses
will be the same, i.e. at some point you reach equilibirium,
but that takes many days, and until that happens you are
either going to live with high BG numbers, or use a faster
acting insulin like NPH or
R/Humalog/Novolog to provide cover until the Lantus reaches
steady state.
>
>Btw, in healthy people, how endogenous insulin behave--with
>peaks or peakless?
In circulation, Insulin has a pretty short half life.. on the
order of 10-15 minutes. Insuliin is produced as Proinsulin,
which is not active, Proinsulin is broken down into insulin
and Peptide C.

We inject insulin under the skin and let it diffuse into the
circulator system. It acts much more rapidly if given by IV.
Injected R insulin is also slowed down because in storage it
bonds with itself toward the back of the B chain, making a
dimer (2 molecules tied together). The Dimer in inactive, and
has a half life on the order of 30 minutes, which is why there
is a lag in effect when R type insulin is given, even by IV.

Humalog was designed not to have that problem. By re-arranging
the back end of the B chain (Which Humalog, Novolog/Novorapid
and Apidra all do) you can prevent the dimer from forming, so
the injected insulin is immediately active.
>
>Pls also tell about other questions...as possible tissue
>damges due to low pH, positive and negative impacts on
>continual exposure's specific to lantus and lantus impact on
>overeatings (if promoted by more and continual insulin's
>exposures?
compared to 'real' acids, Lantus pH is pretty high. It takes
very little to counter the acidity of Lantus. a Ph of 4 means
you only need
1/1000th as much base to counter it as you would need from an
equal volume of a real acid (like HCl or H2SO4)....

>> >> It is precipitation from decreased solubility at neutral
>> >> pH compared to other insulin analogues.
>> >
>> >Whether other long acting are not injected in already
>> >precipitated/ crystalize form due to higher/neutral pH? If
>> >yes, how these can be different from lantus in effect?
>> >> > > > Is it better suited to diabetics who have
>> >> > > > persisting hyperglycemia and need
>> >> > > > continual/occasional insulin's exposure during
>> >> > > > 24hrs?
>

[Kumar]

On Mar 22, 8:57 am, matt weber <matth...@qwest.net> wrote:
> On 21 Mar 2007 02:21:56 -0700, "Kumar"
> <lordshiva5...@gmail.com> wrote:
>
>
>
>
>
>
>
> >matt weber wrote:
> >> On 20 Mar 2007 00:16:15 -0700, "Kumar"
> >> <lordshiva5...@gmail.com> wrote:
>
> >> >matt weber wrote:
> >> >> On 19 Mar 2007 01:47:37 -0700, "Kumar"
> >> >> <lordshiva5...@gmail.com> wrote:
>
> >> >> >> > How such steady any additional long term effect
> >> >> >> > become possible? Is it different in
> >> >> >> > polymerization into crystals/precipitation after
> >> >> >> > injection than other long acting insulin?
> >> >> The Solubility product of the chemical determines how
> >> >> long and how flat the curve is. Lantus has a
> >> >> reputation for having a very low solubility, so it
> >> >> takes a number of doses to reach steady state, i.e. it
> >> >> takes much longer than 24 hours for all of a single
> >> >> injection to dissolve.
>
> >> >> By contrast NPH is much more soluble at body pH than
> >> >> Lantus, The more soluble the insulin, the more 'peaky'
> >> >> it becomes.
>
> >> >Thanks. As such, will lantus be lesser available insulin
> >> >than NPH resulting lesser but prolonged steady effect?
> >> >Will lantus be required more units to be injected than
> >> >NPH to control blood glucose levels, considering its
> >> >slower/lesser but steady effect?
>
> >> Ultimately total Lantus dose and NPH/Ultralente daily
> >> doses will be the same, i.e. at some point you reach
> >> equilibirium, but that takes many days, and until that
> >> happens you are either going to live with high BG
> >> numbers, or use a faster acting insulin like NPH or
> >> R/Humalog/Novolog to provide cover until the Lantus
> >> reaches steady state.
> >Does it also indicates, injecting more lantus units than
> >other long acting?
> >> >Btw, in healthy people, how endogenous insulin
> >> >behave--with peaks or peakless?
> >> In circulation, Insulin has a pretty short half life.. on
> >> the order of 10-15 minutes. Insuliin is produced as
> >> Proinsulin, which is not active, Proinsulin is broken
> >> down into insulin and Peptide C.
> >Ultimate effect of any insulin is in monomerization. How
> >peak effect by any insulin is calculated?
>
> perhaps in the short term, but long term, once you have
> reached equilibirium, a unit of insulin injected is a unit
> of insulin injected.....
Can imbalance/instability in any ICF prminient constitutent
as Potassium caused by added/reduced injected insulin be a
reason to show acute effects of instablities of that
constituent? Whether Hypoglycemia's symptoms resembles with
some symptoms of potassium, Mg, Phosphate instabilities?
> >Btw, in what polymer sized chain, other long acting
> >insulins and lantus are there--pre/post injected?
> >> We inject insulin under the skin and let it diffuse into
> >> the circulator system. It acts much more rapidly if given
> >> by IV. Injected R insulin is also slowed down because in
> >> storage it bonds with itself toward the back of the B
> >> chain, making a dimer (2 molecules tied together). The
> >> Dimer in inactive, and has a half life on the order of 30
> >> minutes, which is why there is a lag in effect when R
> >> type insulin is given, even by IV.
> >In body, is it either monomer or dimer of any insulin's
> >molecules?
>
> When R insulin is injected it is a dimer. NPH, S,L and U
> are cystalline structures built around 6 insulin moleculre
> wrapped around a protamine core. The insulin dissociateds
> from a Hexamer to a Dimer to a monomer. Only the Monomer
> is active.

Whether lantus is in monomerized form before injected?

Is it possible that solubility/availability of polymerized
insulin is different in different people? If yes how?
>
>
>
>
> >> Humalog was designed not to have that problem. By
> >> re-arranging the back end of the B chain (Which Humalog,
> >> Novolog/Novorapid and Apidra all do) you can prevent the
> >> dimer from forming, so the injected insulin is
> >> immediately active.
>
> >> >Pls also tell about other questions...as possible tissue
> >> >damges due to low pH, positive and negative impacts on
> >> >continual exposure's specific to lantus and lantus
> >> >impact on overeatings (if promoted by more and continual
> >> >insulin's exposures?
> >> compared to 'real' acids, Lantus pH is pretty high. It
> >> takes very little to counter the acidity of Lantus. a Ph
> >> of 4 means you only need
> >> 1/1000th as much base to counter it as you would need
> >> from an equal volume of a real acid (like HCl or
> >> H2SO4)....
> >Means, lantus due to its low pH, not specifically damaging
> >to tissues in any way?
>
> It has a relatively low pH, but we are talking about tiny
> amounts (fractions of a cc) of what is at best, only weakly
> acidic. The injection will cause a few milligrams to
> bicarbonate to be neutralized, and compared to overall
> bicarbonate stores, insignificant..... The pH is not low
> enough to cause any significant tissue damage. It isn't
> like you are injecting concentrated Sulfuric or
> Hydrochloric acid.-

Thanks for much information.

Hide quoted text -
>
> - Show quoted text -- Hide quoted text -
>
> - Show quoted text -

[Matt Weber]

On 21 Mar 2007 02:21:56 -0700, "Kumar"
<lordshiva5753@gmail.com> wrote:

>
>matt weber wrote:
>> On 20 Mar 2007 00:16:15 -0700, "Kumar"
>> <lordshiva5753@gmail.com> wrote:
>>
>> >
>> >matt weber wrote:
>> >> On 19 Mar 2007 01:47:37 -0700, "Kumar"
>> >> <lordshiva5753@gmail.com> wrote:
>> >>
>> >> >> > How such steady any additional long term effect
>> >> >> > become possible? Is it different in polymerization
>> >> >> > into crystals/precipitation after injection than
>> >> >> > other long acting insulin?
>> >> The Solubility product of the chemical determines how
>> >> long and how flat the curve is. Lantus has a reputation
>> >> for having a very low solubility, so it takes a number
>> >> of doses to reach steady state, i.e. it takes much
>> >> longer than 24 hours for all of a single injection to
>> >> dissolve.
>> >>
>> >> By contrast NPH is much more soluble at body pH than
>> >> Lantus, The more soluble the insulin, the more 'peaky'
>> >> it becomes.
>> >
>> >Thanks. As such, will lantus be lesser available insulin
>> >than NPH resulting lesser but prolonged steady effect?
>> >Will lantus be required more units to be injected than NPH
>> >to control blood glucose levels, considering its
>> >slower/lesser but steady effect?
>
>> Ultimately total Lantus dose and NPH/Ultralente daily doses
>> will be the same, i.e. at some point you reach
>> equilibirium, but that takes many days, and until that
>> happens you are either going to live with high BG numbers,
>> or use a faster acting insulin like NPH or
>> R/Humalog/Novolog to provide cover until the Lantus reaches
>> steady state.
>Does it also indicates, injecting more lantus units than
>other long acting?
>> >Btw, in healthy people, how endogenous insulin
>> >behave--with peaks or peakless?
>> In circulation, Insulin has a pretty short half life.. on
>> the order of 10-15 minutes. Insuliin is produced as
>> Proinsulin, which is not active, Proinsulin is broken down
>> into insulin and Peptide C.
>Ultimate effect of any insulin is in monomerization. How peak
>effect by any insulin is calculated?
perhaps in the short term, but long term, once you have
reached equilibirium, a unit of insulin injected is a unit of
insulin injected.....
>
>Btw, in what polymer sized chain, other long acting insulins
>and lantus are there--pre/post injected?
>> We inject insulin under the skin and let it diffuse into
>> the circulator system. It acts much more rapidly if given
>> by IV. Injected R insulin is also slowed down because in
>> storage it bonds with itself toward the back of the B
>> chain, making a dimer (2 molecules tied together). The
>> Dimer in inactive, and has a half life on the order of 30
>> minutes, which is why there is a lag in effect when R type
>> insulin is given, even by IV.
>In body, is it either monomer or dimer of any insulin's
>molecules?
When R insulin is injected it is a dimer. NPH, S,L and U are
cystalline structures built around 6 insulin moleculre wrapped
around a protamine core. The insulin dissociateds from a
Hexamer to a Dimer to a monomer. Only the Monomer is active.
>>
>> Humalog was designed not to have that problem. By
>> re-arranging the back end of the B chain (Which Humalog,
>> Novolog/Novorapid and Apidra all do) you can prevent the
>> dimer from forming, so the injected insulin is immediately
>> active.
>> >
>> >Pls also tell about other questions...as possible tissue
>> >damges due to low pH, positive and negative impacts on
>> >continual exposure's specific to lantus and lantus impact
>> >on overeatings (if promoted by more and continual
>> >insulin's exposures?
>> compared to 'real' acids, Lantus pH is pretty high. It
>> takes very little to counter the acidity of Lantus. a Ph of
>> 4 means you only need
>> 1/1000th as much base to counter it as you would need from
>> an equal volume of a real acid (like HCl or H2SO4)....
>Means, lantus due to its low pH, not specifically damaging to
>tissues in any way?
It has a relatively low pH, but we are talking about tiny
amounts (fractions of a cc) of what is at best, only weakly
acidic. The injection will cause a few milligrams to
bicarbonate to be neutralized, and compared to overall
bicarbonate stores, insignificant..... The pH is not low
enough to cause any significant tissue damage. It isn't like
you are injecting concentrated Sulfuric or Hydrochloric acid.

[Kumar]

On Mar 22, 8:57=C2=A0am, matt weber <matth...@qwest.net>
wrote:
> On 21 Mar 2007 02:21:56 -0700, "Kumar"
> <lordshiva5...@gmail.com> wrote:
>
>
>
>
>
>
>
> >matt weber wrote:
> >> On 20 Mar 2007 00:16:15 -0700, "Kumar"
> >> <lordshiva5...@gmail.com> wrote:
>
> >> >matt weber wrote:
> >> >> On 19 Mar 2007 01:47:37 -0700, "Kumar"
> >> >> <lordshiva5...@gmail.com> wrote: Followings are the
> >> >> indicated actions of insulin:-

"Actions on cellular and metabolic level

Effect of insulin on glucose uptake and metabolism. Insulin
binds to its receptor (1) which in turn starts many protein
activation cascades
(2). These include: translocation of Glut-4 transporter to the
plasma membrane and influx of glucose (3), glycogen
synthesis (4), glycolysis
(3) and fatty acid synthesis (6).The actions of insulin on the
global human metabolism level include:

Control of cellular intake of certain substances, most
prominently glucose in muscle and adipose tissue (about
=E2=85=94 of body cells). Increase of DNA replication and
protein synthesis via control of amino acid uptake.
Modification of the activity of numerous enzymes (allosteric
effect). The actions of insulin on cells include:

Increased glycogen synthesis =E2=80=93 insulin forces storage
of glucose in liver (and muscle) cells in the form of
glycogen; lowered levels of insulin cause liver cells to
convert glycogen to glucose and excrete it into the blood.
This is the clinical action of insulin which is directly
useful in reducing high blood glucose levels as in diabetes.
Increased fatty acid synthesis =E2=80=93 insulin forces fat
cells to take in blood lipids which are converted to
triglycerides; lack of insulin causes the reverse. Increased
esterification of fatty acids =E2=80=93 forces adipose tissue
to make fats (ie, triglycerides) from fatty acid esters; lack
of insulin causes the reverse. Decreased proteinolysis
=E2=80=93 forces reduction of protein degradation; lack of
insulin increases protein degradation. Decreased lipolysis
=E2=80=93 forces reduction in conversion of fat cell li= pid
stores into blood fatty acids; lack of insulin causes the
reverse. Decreased gluconeogenesis =E2=80=93 decreases
production of glucose from various substrates in liver; lack
of insulin causes glucose production from assorted substrates
in the liver and elsewhere. Increased amino acid uptake
=E2=80=93 forces cells to absorb circulating am= ino acids;
lack of insulin inhibits absorption. Increased potassium
uptake =E2=80=93 forces cells to absorb serum potassium[some
other mineral also dependant on K homeostatis]; lack of
insulin inhibits absorption. Arterial muscle tone =E2=80=93
forces arterial wall muscle to relax, increasing blood flow,
especially in micro arteries; lack of insulin reduces flow by
allowing these muscles to contract.
http://en.wikipedia.org/wiki/Insulin "

In nature, in normal person, insulin may not be exposed
continually and more. As such and in view of above indicated
actions of insulin, how more and continual exposure of insulin
can effect adversely?