Diabetes mellitus type 1 medical therapy: Difference between revisions

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{{Diabetes mellitus}}
{{Diabetes mellitus}}


{{CMG}}; {{AE}} [[Priyamvada Singh|Priyamvada Singh, M.B.B.S.]] [mailto:psingh13579@gmail.com]; {{CZ}}
{{CMG}}; {{AE}} [[Priyamvada Singh|Priyamvada Singh, M.B.B.S.]] [mailto:psingh13579@gmail.com]; {{CZ}}{{VD}}
 
==Overview==
See also: [[Blood glucose monitoring]].
 
The goals of [[therapy]] for [[diabetes mellitus type 1|type 1]] or [[diabetes mellitus type 2|type 2 diabetes mellitus]] ([[diabetes mellitus|DM]]) are to eliminate [[symptom|symptoms]] related to [[hyperglycemia]], reduce or eliminate the long-term microvascular and macrovascular [[Complication (medicine)|complications]] of [[diabetes mellitus|DM]], and allow the [[patient]] to achieve as normal lifestyle as possible. [[diabetes mellitus type 1|Type 1 diabetes]] is characterized by an absolute [[insulin]] deficiency. For these [[patient|patients]], a basal-bolus regimen with a long-acting [[Analog (chemistry)|analog]] and a short- or rapid-acting [[insulin]] [[Analog (chemistry)|analog]] is the most physiologic [[insulin]] regimen and the best option for optimal [[blood sugar|glycemic]] control.


==Medical Therapy==
==Medical Therapy==


==Overview==
[[diabetes mellitus type 1|Type 1 diabetes]] is characterized by an absolute [[insulin]] deficiency. For these [[patient|patients]], a basal-bolus regimen with a long-acting [[Analog (chemistry)|analog]] and a short- or rapid-acting [[insulin]] [[Analog (chemistry)|analog]] is the most physiologic [[insulin]] regimen and the best option for optimal [[blood sugar|glycemic]] control. The medical [[therapy]] for [[diabetes mellitus type 1|type 1 DM]]:<ref>Type 1 Diabetes mellitus "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 27th,2016</ref><ref name="pmid27974167">{{cite journal| author=Strich D, Balagour L, Shenker J, Gillis D| title=Lower Basal Insulin Dose is Associated with Better Control in Type 1 Diabetes. | journal=J Pediatr | year= 2016 | volume=  | issue=  | pages=  | pmid=27974167 | doi=10.1016/j.jpeds.2016.11.029 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27974167  }}</ref><ref>{{Cite web|url=http://www.tdctoolkit.org/wp-content/themes/tdc/algorithms/13_InsulinAlgorithmType1.pdf|title=Insulin treatment algorithms|last=|first=|date=|website=|publisher=|access-date=}}</ref>
The goals of therapy for type 1 or type 2 diabetes mellitus (DM) are to
{| class="wikitable"
* Eliminate symptoms related to hyperglycemia
! colspan="4" |Duration of Action of Standard [[Insulin]] and [[Insulin]] [[Analog (chemistry)|Analogues]].*
* Reduce or eliminate the long-term microvascular and macrovascular complications of DM
|-
* Allow the patient to achieve as normal a lifestyle as possible
|'''[[Insulin]]'''
|'''Onset of Action'''
|'''Peak Action'''
|'''Effective Duration'''
|-
| colspan="4" |'''Standard'''
|-
|[[insulin|Regular]]
|30-60 min
|2-3 hr
|8-10 hr
|-
|[[insulin|NPH]]
|2-4 hr
|4-10 hr
|12-18 hr
|-
|[[insulin|Zinc insulin(Lente)]]
|2-4 hr
|4-12 hr
|12-20 hr
|-
|[[insulin|Extended Zinc insulin]]
|6-10 hr
|10-16 hr
|18-24 hr
|-
| colspan="4" |'''Analogues'''
|-
|[[Insulin lispro|Lispro]]
|5-15 min
|30-90 min
|4-6 hr
|-
|[[Insulin aspart|Aspart]]
|5-15 min
|30-90 min
|4-6 hr
|-
|[[Insulin glargine|Glargine]]
|2-4 hr
|None
|20-24 hr
|-
| colspan="4" |* Serum [[insulin]] profiles are based on a [[Subcutaneous tissue|subcutaneous]] [[Injection (medicine)|injection]] of 0.1 to 0.2 unit per kilogram of body weight; large variation within and between persons may be noted. Data are from DeWitt and Hirsch.6
|}


===Cures for Type 1 Diabetes===
{| class="wikitable"
There is no practical cure now for type 1 diabetes. The fact that type 1 diabetes is due to the failure of one of the cell types of a single organ with a relatively simple function (i.e. the failure of the islets of Langerhans) has led to the study of several possible schemes to cure this form diabetes mostly by replacing the pancreas or just the beta cells.<ref name=Vinik>{{cite journal |author=Vinik AI, Fishwick DT, Pittenger G |title=Advances in diabetes for the millennium: toward a cure for diabetes |journal=MedGenMed : Medscape general medicine |volume=6 |issue=3 Suppl |pages=12 |year=2004 |pmid=15647717 |doi=}}</ref> Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (when they have developed diabetic nephropathy) and become insulin-independent may now be considered "cured" from their diabetes. A simultaneous pancreas-kidney transplant is a promising solution, showing similar or improved survival rates over a kidney transplant alone. <ref name=Stratta>
! colspan="3" |[[Insulin]] Algorithm for [[diabetes mellitus type 1|Type 1 Diabetes Mellitus]] in Children and Adults
|-
! colspan="3" |ABBREVIATIONS BASAL: [[Insulin glargine|Glargine]] or [[Insulin detemir|Detemir]] BOLUS (Prandial): Reg: [[insulin|Regular Insulin]] (peak action 3-4 hrs) RAI: Rapid Acting [[Insulin]] = [[Insulin aspart|Aspart]], [[Insulin glulisine|Glulisine]], or [[Insulin lispro|Lispro]] (peak action 1-1 ½ hrs) PPG: Post-Prandial [[Glucose]] SMBG: Self-monitored [[blood sugar|blood glucose]] TDI: Total daily [[insulin]] dosage in units
|-
|Split-Mix [[Insulin]] [[therapy|Therapies]]
|1. Two shots: [[insulin|NPH]] + [[insulin|Reg]] or RAI 2:1 ratio AM; 1:1 ratio PM
2. Three shots: AM: NPH + Reg or RAI


{{cite journal
PM: [[insulin|Reg]] or RAI
| author=Stratta RJ, Alloway RR.| title=Pancreas transplantation for diabetes mellitus: a guide to recipient selection and optimum immunosuppression.| journal=BioDrugs. | year=1998 | pages=347-357 | volume=10 | issue=5 | id=PMID 18020607 


}}</ref>Still, they generally remain on long-term [[immunosuppressive drug]]s and there is a possibility that the immune system will mount a [[host versus graft]] response against the transplanted organ.<ref name=Vinik/>
HS: [[insulin|NPH]]


Transplants of exogenous beta cells have been performed experimentally in both mice and humans, but this measure is not yet practical in regular clinical practice. Thus far, like any such transplant, it has provoked an immune reaction and long-term immunosuppressive drugs will be needed to protect the transplanted tissue.<ref>{{cite journal |author=Shapiro AM, Ricordi C, Hering BJ, ''et al'' |title=International trial of the Edmonton protocol for islet transplantation |journal=N. Engl. J. Med. |volume=355 |issue=13 |pages=1318-30 |year=2006 |pmid=17005949 |doi=10.1056/NEJMoa061267}}</ref> An alternative technique has been proposed to place transplanted beta cells in a semi-permeable container, isolating and protecting them from the immune system. [[Stem cell research]] has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.<ref name=Vinik/> A 2007 trial of 15 newly diagnosed patients with type 1 diabetes treated with [[stem cell]]s raised from their own [[bone marrow]] after [[immune suppression]] showed that the majority did not require any insulin treatment for prolonged periods of time.<ref>{{cite journal |last= Voltarelli |first=JC |coauthors=Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. |year = 2007 |title=Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. |journal=JAMA |volume=297 |issue=14 |pages=1568-76 |id=PMID 17426276 |url=http://jama.ama-assn.org/cgi/content/full/297/14/1568}}</ref>
2/3 TDI ÷ as 2/3 AM [[insulin|NPH]] + 1/3 as [[insulin|Reg]] or RAI


Microscopic or nanotechnological approaches are under investigation as well, in one proposed case with implanted stores of insulin metered out by a rapid response valve sensitive to blood glucose levels. At least two approaches have been demonstrated ''in vitro''. These are, in some sense, closed-loop insulin pumps.
1/3 TDI ÷ as ½ PM [[insulin|Reg]] or RAI + ½ [[insulin|NPH]] at HS


Type 1 is treated with insulin replacement therapy &mdash; usually by injection or [[insulin pump]], dietary control, typically including carbohydrate tracking, and careful monitoring of [[blood glucose]] levels using [[Glucose meter]]s.
3. Two shots Premix 2/3 AM + 1/3 PM


Untreated Type 1 diabetes can lead to one form of diabetic coma, diabetic ketoacidosis, which can be fatal. At present, insulin treatment must be continued for a lifetime; this will change if better treatment, or a cure, is discovered. Continuous glucose monitors have been developed which alert to the presence of dangerously high or low blood sugar levels.
Total Daily [[Insulin]] : 0.3-0.5 units/kg/day, and titrate to glycemic targets
|Follow [[Glycosylated hemoglobin|A1c]] Every 3-6 months and Adjust Regimen to Maintain [[blood sugar|Glycemic]] Targets
|-
| colspan="3" |OR
|-
|Intensive [[Insulin]] [[Therapy]] (IIT)
|Physiologic [[Insulin]]-1:1 basal:bolus ratio SQ
Basal: [[insulin glargine|Glargine]] QD or [[insulin detemir|Detemir]] QD-BID


In some extreme cases, a pancreas transplant can help restore proper glucose regulation. However, the surgery and accompanying immunosuppression required is considered by many physicians to be more dangerous than continued insulin replacement therapy and is therefore often used only as a last resort (such as when a kidney must also be transplanted or in cases where the patient's blood glucose levels are extremely control resistant). Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs and may become clinically available in the future. Thus far, beta cell replacement has only been performed on patients over age 18, and with tantalizing successes amidst nearly universal failure.
Bolus: RAI (or Reg) before each meal: If meal skipped, skip dose


. '''Premeal [[insulin]] dose include'''s:


====Contraindicated medications====
1. [[Insulin]] to cover [[carbohydrate]] ingested; 1 unit RAI covers 500/TDI grams [[carbohydrate]] from meal


{{MedCondContrAbs
2. Additional [[insulin]] to correct for high SMBG; 1 unit RAI lowers PG by approximately 1800/TDI mg/dL. (Reg lowers [[blood sugar|PG]] by ~1500/TDI)


|MedCond = Type I diabetes mellitus|Glipizide|Glyburide|Repaglinide}}
3. Consider adjustment for exercise


==Research Foundations==
'''Total Daily [[Insulin]]'''5 : 0.3-0.5 units/kg/day and titrate to [[blood sugar|glycemic]] targets
The major charitable organization in the USA devoted to type 1 diabetes research is the [[Juvenile Diabetes Research Foundation]] (JDRF), whose mission is to cure type 1 diabetes and its complications through the support of research. Since its founding in 1970, JDRF has contributed more than $1 billion to diabetes research, including more than $137 million in FY 2007. In FY2007, the Foundation funded 700 centers, grants and fellowships in 20 countries.
|Follow [[Glycosylated hemoglobin|A1c]] Every 3-6 months and Adjust Regimen to Maintain [[blood sugar|glycemic]] Targets
|-
| colspan="2" |Pramlintide Consider as adjunct [[therapy]] to [[insulin]] in [[patient|patients]] unable to stabilize PPG.
|
|-
| colspan="3" |'''Footnotes'''
1 Consider referring all [[diabetes mellitus type 1|type 1]] [[patient|patients]] to pediatric/adult endocrinologist/comprehensive diabetes specialty team, and consider continuous [[glucose]] monitoring. If [[insulin pump]] [[therapy]] is considered-refer to Certified Pump Trainer.


The [[International Diabetes Federation]] is a worldwide alliance of over 160 countries to address diabetes research and treatment.
2 Modern [[glucose]] meters give values corrected to [[blood sugar|plasma glucose]].  


The [[American Diabetes Association]] funds some work on type 1 but devotes much of its resources to [[type 2 diabetes]] due to the increasing prevalence of the latter type.
3 Most [[diabetes mellitus type 1|type 1]] [[patient|patients]] need IIT to attain [[blood sugar|glycemic]] targets; IIT may be by SQ multiple [[Injection (medicine)|injection]] or by SQ continuous [[insulin pump]].  


Diabetes Australia is involved in promoting research and education in Australia on both type 1 and type 2 diabetes.
4 Dosages may differ in children and adolescents.


The [[Canadian Diabetes Association]] is also involved in educating, researching, and sustaining sufferers of Type 1 Diabetics in Canada.
5 Dosage does not depend on [[patient]]'s race.<ref name="ChalewKamps2020">{{cite journal|last1=Chalew|first1=Stuart|last2=Kamps|first2=Jodi|last3=Jurgen|first3=Brittney|last4=Gomez|first4=Ricardo|last5=Hempe|first5=James|title=The relationship of glycemic control, insulin dose, and race with hypoglycemia in youth with type 1 diabetes|journal=Journal of Diabetes and its Complications|volume=34|issue=6|year=2020|pages=107519|issn=10568727|doi=10.1016/j.jdiacomp.2019.107519}}</ref>


==Cure==
6 Twice daily dosing may be required at low basal [[insulin]] doses.  
As of 2008, there is no known cure for diabetes mellitus type 1 used by modern medical insitutes or hospitals.<ref>Without the use of large doses of [[immunosuppressant]]s, that causes a multitude of other medical issues.</ref> There is ongoing [[biomedical research|research]] on various approaches to curing diabetes type 1.


Diabetes type 1 is caused by the non-existence of a sufficient number of [[beta cell]]s in the body; these cells, which are found in the [[Langerhans islets]] in the [[pancreas]], produce and secrete [[insulin]], the single hormone responsible for allowing [[glucose]] to enter from the [[blood]] into [[cell (biology)|cell]]s. Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the [[endogenous]] ability of the body to produce insulin in response to the level of blood glucose". This section does not deal with approaches other than that (for instance, closed-loop integrated glucometer/insulin pump products), which may also greatly increase quality of life for those who have diabetes type 1, and may by some be termed "artificial pancreas". Instead, it only deals with such approaches for thoroughly curing the underlying condition of diabetes type 1, by enabling the body to endogenously, ''in vivo'', produce insulin in response to the level of blood glucose.
7 Strongly recommend referral to Registered/Licensed Dietitian or Certified [[Diabetes]] Educator with experience in [[diabetes]] [[diet (nutrition)|nutrition]] counseling.  


===Reversion===
8 Consider decreasing 1 unit for every 30 minute s of vigorous [[Physical exercise|physical activity]].
====Encapsulation Approach====
|}
[[Image:Bio-artificial pancreas with Islet Sheet technology.JPG|thumb|left|300px|'''The Bio-artificial pancreas''': this diagram shows a cross section of [[tissue engineering|bio-engineered tissue]] with encapsulated [[islets of Langerhans|islet cells]] which deliver [[endocrine]] [[pancreas#function|hormones]] in response to [[glucose]].]]


A biological approach to the artificial pancreas is to implant [[tissue engineering|bioengineered tissue]] containing [[islets of Langerhans|islet cells]], which would secrete the amounts of insulin, [[amylin]] and [[glucagon]] needed in response to sensed glucose.
* [[Insulin]] receiving [[patient|patients]] who took Sotagliflozin had better [[blood sugar|glycemic]] control compared to [[Scientific control|control group]] with [[Glycosylated hemoglobin|glycated hemoglobin]] level ([[Glycosylated hemoglobin|HbA1c]]) lower than 7.0% and lower risk of sever [[hypoglycemia]]. Although chance of [[diabetic ketoacidosis]] is higher with Sotagliflozin.<ref name="GargHenry2017">{{cite journal|last1=Garg|first1=Satish K.|last2=Henry|first2=Robert R.|last3=Banks|first3=Phillip|last4=Buse|first4=John B.|last5=Davies|first5=Melanie J.|last6=Fulcher|first6=Gregory R.|last7=Pozzilli|first7=Paolo|last8=Gesty-Palmer|first8=Diane|last9=Lapuerta|first9=Pablo|last10=Simó|first10=Rafael|last11=Danne|first11=Thomas|last12=McGuire|first12=Darren K.|last13=Kushner|first13=Jake A.|last14=Peters|first14=Anne|last15=Strumph|first15=Paul|title=Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes|journal=New England Journal of Medicine|volume=377|issue=24|year=2017|pages=2337–2348|issn=0028-4793|doi=10.1056/NEJMoa1708337}}</ref>


When islet cells have been transplanted via the [[Edmonton protocol]], insulin production (and glycemic control) was restored, but at the expense of [[immunosuppression]]. [[Micro-encapsulation|Encapsulation]] of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.<ref>[http://www.isletmedical.com/pages/define_methods.htm Cerco Medical: Science: Methods<!-- Bot generated title -->]</ref>
{| class="wikitable"
! colspan="4" |[[blood sugar|Glycemic]] Goals
|-
| colspan="4" |Individualize goal based on [[patient]] [[risk factor|risk factors]]
|-
|[[Glycosylated hemoglobin|HbA1c]]
|≤6%
|≤7%
|≤8%
|-
|[[blood sugar|FPG]]
|≤110
|120
|140 mg/dl
|-
|2h PP
|≤130
|180
|180 mg/dl
|-
| colspan="4" |Intensify management if: Absent/stable [[cardiovascular disease]], mild-moderate microvascular [[Complication (medicine)|complications]], intact [[hypoglycemia]] awareness, infrequent [[hypoglycemia|hypoglycemic]] episodes, recently diagnosed [[diabetes]]. Less intensive management if: Evidence of advanced or poorly controlled [[cardiovascular disease|cardiovascular]] and/or microvascular [[Complication (medicine)|complications]], [[hypoglycemia]] awareness, vulnerable [[patient]] (ie, impaired cognition, [[dementia]], fall history). See “[[Glycosylated hemoglobin|A1c]] Goal” [[treatment]] strategy for further explanation. [[Glycosylated hemoglobin|A1c]] is referenced to a non-diabetic range of 4-6% using a DCCT-based assay. ADA Clinical Practice Recommendations. [[Diabetes]] Care 2009;32(suppl 1):S19-20.
|}
[[File:Insulin basal bolus.png|center|thumb|498x498px|Diagram explaining the basal-bolus insulin schedule. The long acting insulin is given once (usually glargine, Lantus) or twice (usually detemir, Levemir) daily to provide a base, or basal insulin level. Rapid acting (RA) insulin is given before meals and snacks. A similar profile can be provided using an insulin pump where rapid acting insulin is given as the basal and premeal bolus insulin.]]
{| class="wikitable"
! colspan="2" |[[Insulin]] Delivery
|-
!Modes of [[Insulin]] delivery
!
|-
|'''Syringe'''
|'''Syringe''' is a device with a hollow center, plunger, needle, and removable needle guard.
|-
|'''[[Insulin]] pens''' 
|'''[[Insulin]] pens''' provide a convenient, easy-to-use way of [[injection (medicine)|injecting]] [[insulin]] and may be less painful than a standard needle and syringe. An [[insulin]] pen looks like a pen with a cartridge. Some of these devices use replaceable cartridges of [[insulin]]. Other pens are prefilled with [[insulin]] and are totally disposable after the [[insulin]] is injected. [[Insulin]] pen users screw a short, fine, disposable needle on the tip of the pen before an [[injection (medicine)|injection]]. Then users turn a dial to select the desired dose of [[insulin]], inject the needle, and press a plunger on the end to deliver the [[insulin]] just under the [[skin]]. [[Insulin]] pens are less widely used in the United States than in many other countries.
|-
|'''External [[insulin pump]]'''
|'''External [[insulin pumps]]''' are typically about the size of a deck of cards or cell phone, weigh about 3 ounces, and can be worn on a belt or carried in a pocket. Most pumps use a disposable plastic cartridge as an [[insulin]] reservoir. A needle and plunger are temporarily attached to the cartridge to allow the user to fill the cartridge with [[insulin]] from a vial. The user then removes the needle and plunger and loads the filled cartridge into the pump. Disposable [[Intravenous therapy|infusion]] sets are used with [[insulin pump]]s to deliver [[insulin]] to an [[Intravenous therapy|infusion]] site on the body, such as the abdomen. Infusion sets include a cannula—a needle or a small, soft tube—that the user inserts into the [[tissue]] beneath the [[skin]]. Devices are available to help insert the cannula. Narrow, flexible plastic tubing carries [[insulin]] from the pump to the [[Intravenous therapy|infusion]] site. On the [[skin]]'s surface, an adhesive patch or dressing holds the [[Intravenous therapy|infusion]] set in place until the user replaces it after a few days. Users set the pumps to give a steady trickle or "basal" amount of [[insulin]] continuously throughout the day. Pumps can also give "bolus" doses—one-time larger doses—of [[insulin]] at meals and at times when [[blood sugar|blood glucose]] is too high based on the programming set by the user. Frequent [[blood sugar|blood glucose]] monitoring is essential to determine [[insulin]] dosages and to ensure that [[insulin]] is delivered.
|-
|'''[[Injection (medicine)|Injection]] ports'''
|'''[[Injection (medicine)|Injection]] ports''' provide an alternative to daily [[Injection (medicine)|injections]]. [[Injection (medicine)|Injection]] ports look like [[Intravenous therapy|infusion]] sets without the long tubing. Like [[Intravenous therapy|infusion]] sets, [[Injection (medicine)|injections]] ports have a cannula that is inserted into the [[tissue]] beneath the [[skin]]. On the [[skin]]'s surface, an adhesive patch or dressing holds the port in place. The user injects [[insulin]] through the port with a needle and syringe or an [[insulin]] pen. The port remains in place for several days and is then replaced. Use of an [[Injection (medicine)|injection]] port allows a person to reduce the number of [[skin]] punctures to one every few days to apply a new port.
|-
|'''[[Injection (medicine)|Injection]] aids'''
|'''[[Injection (medicine)|Injection]] aids''' are devices that help users give [[Injection (medicine)|injections]] with needles and syringes through the use of spring-loaded syringe holders or stabilizing guides. Many [[Injection (medicine)|injection]] aids have a button the user pushes to inject the [[insulin]].
|-
|'''[[Insulin]] jet injectors'''
|'''[[Insulin]] jet injectors''' send a fine spray of [[insulin]] into the [[skin]] at high pressure instead of using a needle to deliver the [[insulin]].
|-
|'''Hybrid Closed-Loop [[Insulin]] Delivery System'''
|A sensor monitors the [[Blood sugar|blood glucose]] constantly and automated algorithmic adjust the basal [[insulin]] [[Intravenous therapy|infusion]] rate. Same as the prior forms, it has a [[Intravenous therapy|infusion]] set which provide [[insulin]]. This method has been linked to few device related [[Adverse effect (medicine)|side effects]].<ref name="BergenstalGarg2016">{{cite journal|last1=Bergenstal|first1=Richard M.|last2=Garg|first2=Satish|last3=Weinzimer|first3=Stuart A.|last4=Buckingham|first4=Bruce A.|last5=Bode|first5=Bruce W.|last6=Tamborlane|first6=William V.|last7=Kaufman|first7=Francine R.|title=Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes|journal=JAMA|volume=316|issue=13|year=2016|pages=1407|issn=0098-7484|doi=10.1001/jama.2016.11708}}</ref>
|}


One concept of the bio-artificial pancreas uses encapsulated islet cells to build an ''islet sheet'' which can be surgically implanted to function as an artificial pancreas.<ref>[http://www.isletmedical.com/pages/company_research.htm Cerco Medical: Company: Islet Sheet Research<!-- Bot generated title -->]</ref>
[[File:Insulin needle.jpg|left|thumb|Most people who take insulin use a needle and syringe to inject insulin just under the skin.]]
[[File:Insulin Port.jpg|center|thumb|Using an injection port reduces the number of skin punctures to one every few days to apply a new port. The user injects insulin through the port.]]


This islet sheet design consists of:
[[File:Insulin Pump.jpg|left|thumb|Insulin pumps contain enough insulin for several days. An infusion set carries insulin from the pump to the body through flexible plastic tubing and a soft tube or needle inserted under the skin.]]
*an inner mesh of fibers to provide strength for the islet sheet;
*islet cells, encapsulated to avoid triggering a proliferating immune response, adhered to the mesh fibers;
*a [[semi-permeable membrane|semi-permeable]] protective layer around the sheet, to allow the [[diffusion]] of nutrients and secreted hormones;
*a protective coating, to prevent a foreign body response resulting in a fibrotic reaction which walls off the sheet and causes failure of the islet cells.


Islet sheet with encapsulation research is pressing forward with large animal studies at the present, with plans for human clinical trials within a few years.
[[File:Insulin Pens.jpg|center|thumb|Insulin pens are a convenient alternative to a needle and syringe for insulin injections]]


====Islet Cell Transplantation Approach====
{{main|Islet cell transplantation}}
Less invasive than a pancreas transplant, islet cell transplantation is considered a very promising approach to curing type 1 diabetes.


In one variant of this procedure, islet cells are injected into the patient's [[liver]], where they take up residence and begin to produce insulin. The liver is expected to be the most reasonable choice because it is more accessible than the pancreas, and the islet cells seem to produce insulin well in that environment. The patient's body, however, will treat the new cells just as it would any other introduction of foreign tissue. The [[immune system]] will attack the cells as it would a bacterial infection or a skin graft. Thus, the patient also needs to undergo treatment involving [[immunosuppressants]], which reduce immune system activity.


Recent studies have shown that islet cell transplants have progressed to the point that 58% of the patients in one study were insulin independent one year after the operation.<ref>{{cite web|url=http://www.mayoclinic.com/health/islet-cell-transplant/DA00046|title=Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com|accessdate=2007-06-04|format= |work=}}</ref> It would be best to use islet cells which will not provoke this immune reaction.


====Islet Cell Regeneration Approach====
[[File:Closed-Loop Insulin Delivery System.jpg|alt=Closed-Loop Insulin Delivery System |thumb|Hybrid Closed-Loop Insulin Delivery System is one the Insulin delivery systems. <ref>{{Cite web|url=https://www.wjgnet.com/1948-9358/full/v5/i5/WJD-5-689-g004.htm|title=Principle of closed loop system|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>|center|432.986x432.986px]]
Research undertaken at the Massachusetts General Hospital in Boston Masschusetts from 2001 and 2003 demonstrated a protocol to reverse type 1 diabetes in mice.<ref>{{cite web |url=http://www.massgeneral.org/news/releases/111303faustman.htm|title=November 13, 2003 Regeneration of insulin-producing islets may lead to diabetes cure|accessdate=2007-06-04|format= |work=}}</ref> Three other institutions have had similar results, published in the March 24, 2006 issue of [[Science (journal)|''Science'']]. A fourth study by the [[National Institutes of Health]] further confirmed the approach, and also sheds light on the biological mechanisms involved.<ref name="pmid17124308">{{cite journal |author=Faustman DL, Tran SD, Kodama S, ''et al'' |title=Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice |journal=Science |volume=314 |issue=5803 |pages=1243; author reply 1243 |year=2006 |pmid=17124308 |doi=10.1126/science.1129811}}</ref>


====Stem Cells Approach====
Research is being done at several locations in which islet cells are developed from [[stem cell]]s.


In January 2006, a team of South Korean scientists has grown pancreatic beta cells, which can help treat diabetes, from stem cells taken from the umbilical cord blood of newborn babies.


In April 2007, it was reported by the ''Times Online'' that 15 young Brazilian patients diagnosed with Type 1 diabetes were able to naturally produce insulin once again after undergoing mild chemotherapy to temporarily weaken their immune systems and then injection of their own stem cells. This allowed the pancreatic beta cells to produce insulin. Since white blood cells were blocking the pancreas from producing insulin, Dr. Voltarelli and colleagues killed the immune cells, allowing the pancreas to secrete insulin once more.


However, there were no control subjects, which means that all of the processes could have been completely or partially natural. Secondly, no theory for the mechanism of cure has been promoted. It is too early to say whether the results will be positive or negative in the long run.<ref name="pmid17426276">{{cite journal |author=Voltarelli JC, Couri CE, Stracieri AB, ''et al'' |title=Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus |journal=JAMA |volume=297 |issue=14 |pages=1568-76 |year=2007 |pmid=17426276 |doi=10.1001/jama.297.14.1568}}</ref>


====Gene Therapy Approach====
[[Image:Gene therapy.jpg|left|thumb|300px|[[Gene therapy]]: Designing a [[viral vector]] to deliberately infect cells with [[DNA]] to carry on the viral production of [[insulin]] in response to the blood sugar level.]]
Technology for [[gene therapy]] is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.<ref>[http://www.niddk.nih.gov/fund/reports/gene_therapy_summ.htm Gene Therapy Approaches to Diabetes<!-- Bot generated title -->]</ref>
*Gene therapy can be used to manufacture insulin directly:  an oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines. Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein. The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days. Therefore by varying the amount of oral medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin producing intestinal cells die off, they are boosted by additional oral medications.<ref>[http://www.liebertonline.com/doi/pdf/10.1089/dia.2005.7.549?cookieSet=1 Mary Ann Liebert, Inc. - Cookie absent<!-- Bot generated title -->]</ref>
*Gene therapy might eventually be used to cure the cause of beta cell destruction, thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible.<ref>http://www.hopkinsbayview.org/healthcarenews06/060605diabetes.html</ref>
*Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells, and subsequently adult stem cells will develop into beta cells. This makes the supply of beta cells in the duodenum self replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed.<ref>[http://www.engeneinc.com/ Engene Inc<!-- Bot generated title -->]</ref>


=====Yonsei University study=====
Scientists in the South Korean university of Yonsei have, in 2000, succeeded in reversing diabetes in mice and rats. Using a viral vector, a DNA encoding the production of an insulin analog was injected to the animals, which remained non-diabetic for at least the eight months duration of the study.<ref>[http://www.sciam.com/article.cfm?articleID=00042B27-190C-1C68-B882809EC588ED9F Gene Therapy for Diabetes: Scientific American<!-- Bot generated title -->]</ref>


====Nanotechnology Approach====
Under the nanotechnological approach to curing diabetes type 1, many "nanobots" would be injected into the patient's [[bloodstream]]. These nanobots would be able to synthesize insulin, and to secrete it according to the level of glucose they would sense.<ref>http://ieeexplore.ieee.org/iel5/6/29742/1353792/13537927.html</ref>


=====Nano Mist=====
An American body called "Nano Mist" claims to be involved in a diabetes cure-related nanotechnology project. Their product is at least 10 years behind FDA approval.<ref>[http://dev.nsta.org/evwebs/1150/futuretech.htm The Nano Mist - Curing Diabetes<!-- Bot generated title -->]</ref>


==References==
==References==
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[[Category:Endocrinology]]
[[Category:Endocrinology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Primary care]]
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Latest revision as of 19:56, 20 September 2020

Diabetes mellitus main page

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, M.B.B.S. [2]; Cafer Zorkun, M.D., Ph.D. [3]Vishal Devarkonda, M.B.B.S[4]

Overview

See also: Blood glucose monitoring.

The goals of therapy for type 1 or type 2 diabetes mellitus (DM) are to eliminate symptoms related to hyperglycemia, reduce or eliminate the long-term microvascular and macrovascular complications of DM, and allow the patient to achieve as normal lifestyle as possible. Type 1 diabetes is characterized by an absolute insulin deficiency. For these patients, a basal-bolus regimen with a long-acting analog and a short- or rapid-acting insulin analog is the most physiologic insulin regimen and the best option for optimal glycemic control.

Medical Therapy

Type 1 diabetes is characterized by an absolute insulin deficiency. For these patients, a basal-bolus regimen with a long-acting analog and a short- or rapid-acting insulin analog is the most physiologic insulin regimen and the best option for optimal glycemic control. The medical therapy for type 1 DM:[1][2][3]

Duration of Action of Standard Insulin and Insulin Analogues.*
Insulin Onset of Action Peak Action Effective Duration
Standard
Regular 30-60 min 2-3 hr 8-10 hr
NPH 2-4 hr 4-10 hr 12-18 hr
Zinc insulin(Lente) 2-4 hr 4-12 hr 12-20 hr
Extended Zinc insulin 6-10 hr 10-16 hr 18-24 hr
Analogues
Lispro 5-15 min 30-90 min 4-6 hr
Aspart 5-15 min 30-90 min 4-6 hr
Glargine 2-4 hr None 20-24 hr
* Serum insulin profiles are based on a subcutaneous injection of 0.1 to 0.2 unit per kilogram of body weight; large variation within and between persons may be noted. Data are from DeWitt and Hirsch.6
Insulin Algorithm for Type 1 Diabetes Mellitus in Children and Adults
ABBREVIATIONS BASAL: Glargine or Detemir BOLUS (Prandial): Reg: Regular Insulin (peak action 3-4 hrs) RAI: Rapid Acting Insulin = Aspart, Glulisine, or Lispro (peak action 1-1 ½ hrs) PPG: Post-Prandial Glucose SMBG: Self-monitored blood glucose TDI: Total daily insulin dosage in units
Split-Mix Insulin Therapies 1. Two shots: NPH + Reg or RAI 2:1 ratio AM; 1:1 ratio PM

2. Three shots: AM: NPH + Reg or RAI

PM: Reg or RAI

HS: NPH

2/3 TDI ÷ as 2/3 AM NPH + 1/3 as Reg or RAI

1/3 TDI ÷ as ½ PM Reg or RAI + ½ NPH at HS

3. Two shots Premix 2/3 AM + 1/3 PM

Total Daily Insulin : 0.3-0.5 units/kg/day, and titrate to glycemic targets

Follow A1c Every 3-6 months and Adjust Regimen to Maintain Glycemic Targets
OR
Intensive Insulin Therapy (IIT) Physiologic Insulin-1:1 basal:bolus ratio SQ

Basal: Glargine QD or Detemir QD-BID

Bolus: RAI (or Reg) before each meal: If meal skipped, skip dose

. Premeal insulin dose includes:

1. Insulin to cover carbohydrate ingested; 1 unit RAI covers 500/TDI grams carbohydrate from meal

2. Additional insulin to correct for high SMBG; 1 unit RAI lowers PG by approximately 1800/TDI mg/dL. (Reg lowers PG by ~1500/TDI)

3. Consider adjustment for exercise

Total Daily Insulin5 : 0.3-0.5 units/kg/day and titrate to glycemic targets

Follow A1c Every 3-6 months and Adjust Regimen to Maintain glycemic Targets
Pramlintide Consider as adjunct therapy to insulin in patients unable to stabilize PPG.
Footnotes

1 Consider referring all type 1 patients to pediatric/adult endocrinologist/comprehensive diabetes specialty team, and consider continuous glucose monitoring. If insulin pump therapy is considered-refer to Certified Pump Trainer.

2 Modern glucose meters give values corrected to plasma glucose.

3 Most type 1 patients need IIT to attain glycemic targets; IIT may be by SQ multiple injection or by SQ continuous insulin pump.

4 Dosages may differ in children and adolescents.

5 Dosage does not depend on patient's race.[4]

6 Twice daily dosing may be required at low basal insulin doses.

7 Strongly recommend referral to Registered/Licensed Dietitian or Certified Diabetes Educator with experience in diabetes nutrition counseling.

8 Consider decreasing 1 unit for every 30 minute s of vigorous physical activity.

Glycemic Goals
Individualize goal based on patient risk factors
HbA1c ≤6% ≤7% ≤8%
FPG ≤110 120 140 mg/dl
2h PP ≤130 180 180 mg/dl
Intensify management if: Absent/stable cardiovascular disease, mild-moderate microvascular complications, intact hypoglycemia awareness, infrequent hypoglycemic episodes, recently diagnosed diabetes. Less intensive management if: Evidence of advanced or poorly controlled cardiovascular and/or microvascular complications, hypoglycemia awareness, vulnerable patient (ie, impaired cognition, dementia, fall history). See “A1c Goal” treatment strategy for further explanation. A1c is referenced to a non-diabetic range of 4-6% using a DCCT-based assay. ADA Clinical Practice Recommendations. Diabetes Care 2009;32(suppl 1):S19-20.
Diagram explaining the basal-bolus insulin schedule. The long acting insulin is given once (usually glargine, Lantus) or twice (usually detemir, Levemir) daily to provide a base, or basal insulin level. Rapid acting (RA) insulin is given before meals and snacks. A similar profile can be provided using an insulin pump where rapid acting insulin is given as the basal and premeal bolus insulin.
Insulin Delivery
Modes of Insulin delivery
Syringe Syringe is a device with a hollow center, plunger, needle, and removable needle guard.
Insulin pens  Insulin pens provide a convenient, easy-to-use way of injecting insulin and may be less painful than a standard needle and syringe. An insulin pen looks like a pen with a cartridge. Some of these devices use replaceable cartridges of insulin. Other pens are prefilled with insulin and are totally disposable after the insulin is injected. Insulin pen users screw a short, fine, disposable needle on the tip of the pen before an injection. Then users turn a dial to select the desired dose of insulin, inject the needle, and press a plunger on the end to deliver the insulin just under the skin. Insulin pens are less widely used in the United States than in many other countries.
External insulin pump External insulin pumps are typically about the size of a deck of cards or cell phone, weigh about 3 ounces, and can be worn on a belt or carried in a pocket. Most pumps use a disposable plastic cartridge as an insulin reservoir. A needle and plunger are temporarily attached to the cartridge to allow the user to fill the cartridge with insulin from a vial. The user then removes the needle and plunger and loads the filled cartridge into the pump. Disposable infusion sets are used with insulin pumps to deliver insulin to an infusion site on the body, such as the abdomen. Infusion sets include a cannula—a needle or a small, soft tube—that the user inserts into the tissue beneath the skin. Devices are available to help insert the cannula. Narrow, flexible plastic tubing carries insulin from the pump to the infusion site. On the skin's surface, an adhesive patch or dressing holds the infusion set in place until the user replaces it after a few days. Users set the pumps to give a steady trickle or "basal" amount of insulin continuously throughout the day. Pumps can also give "bolus" doses—one-time larger doses—of insulin at meals and at times when blood glucose is too high based on the programming set by the user. Frequent blood glucose monitoring is essential to determine insulin dosages and to ensure that insulin is delivered.
Injection ports Injection ports provide an alternative to daily injections. Injection ports look like infusion sets without the long tubing. Like infusion sets, injections ports have a cannula that is inserted into the tissue beneath the skin. On the skin's surface, an adhesive patch or dressing holds the port in place. The user injects insulin through the port with a needle and syringe or an insulin pen. The port remains in place for several days and is then replaced. Use of an injection port allows a person to reduce the number of skin punctures to one every few days to apply a new port.
Injection aids Injection aids are devices that help users give injections with needles and syringes through the use of spring-loaded syringe holders or stabilizing guides. Many injection aids have a button the user pushes to inject the insulin.
Insulin jet injectors Insulin jet injectors send a fine spray of insulin into the skin at high pressure instead of using a needle to deliver the insulin.
Hybrid Closed-Loop Insulin Delivery System A sensor monitors the blood glucose constantly and automated algorithmic adjust the basal insulin infusion rate. Same as the prior forms, it has a infusion set which provide insulin. This method has been linked to few device related side effects.[6]
Most people who take insulin use a needle and syringe to inject insulin just under the skin.
Using an injection port reduces the number of skin punctures to one every few days to apply a new port. The user injects insulin through the port.
Insulin pumps contain enough insulin for several days. An infusion set carries insulin from the pump to the body through flexible plastic tubing and a soft tube or needle inserted under the skin.
Insulin pens are a convenient alternative to a needle and syringe for insulin injections



Closed-Loop Insulin Delivery System
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References

  1. ↑ Type 1 Diabetes mellitus "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 27th,2016
  2. ↑ Strich D, Balagour L, Shenker J, Gillis D (2016). "Lower Basal Insulin Dose is Associated with Better Control in Type 1 Diabetes". J Pediatr. doi:10.1016/j.jpeds.2016.11.029. PMID 27974167.
  3. ↑ "Insulin treatment algorithms" (PDF).
  4. ↑ Chalew, Stuart; Kamps, Jodi; Jurgen, Brittney; Gomez, Ricardo; Hempe, James (2020). "The relationship of glycemic control, insulin dose, and race with hypoglycemia in youth with type 1 diabetes". Journal of Diabetes and its Complications. 34 (6): 107519. doi:10.1016/j.jdiacomp.2019.107519. ISSN 1056-8727.
  5. ↑ Garg, Satish K.; Henry, Robert R.; Banks, Phillip; Buse, John B.; Davies, Melanie J.; Fulcher, Gregory R.; Pozzilli, Paolo; Gesty-Palmer, Diane; Lapuerta, Pablo; Simó, Rafael; Danne, Thomas; McGuire, Darren K.; Kushner, Jake A.; Peters, Anne; Strumph, Paul (2017). "Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes". New England Journal of Medicine. 377 (24): 2337–2348. doi:10.1056/NEJMoa1708337. ISSN 0028-4793.
  6. ↑ Bergenstal, Richard M.; Garg, Satish; Weinzimer, Stuart A.; Buckingham, Bruce A.; Bode, Bruce W.; Tamborlane, William V.; Kaufman, Francine R. (2016). "Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes". JAMA. 316 (13): 1407. doi:10.1001/jama.2016.11708. ISSN 0098-7484.
  7. ↑ "Principle of closed loop system".

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