This document discusses timely insulin initiation and overcoming clinical inertia in the management of type 2 diabetes (T2D). It notes that the global prevalence of diabetes is increasing rapidly and is projected to affect 700 million people by 2045. In Africa, it is estimated that the number of adults with diabetes will rise from 19 million currently to 47 million by 2045. The document summarizes studies from Uganda finding low rates of recommended screening and care processes among diabetic patients. It emphasizes the benefits of early intensive glycemic control, as shown in studies like the UKPDS, and indications for insulin therapy in T2D. The document outlines the physiological insulin secretion pattern and roles of basal and bolus insulin in mimicking this pattern.
Final Presentation for Block 6
Objectives:
Describe the mechanism of action, side-effects and counseling points for GLP-1 RA
Compare and contrast GLP-1 RA studies
Discuss the PIONEER-6 study and its implications to clinical practice
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Final Presentation for Block 6
Objectives:
Describe the mechanism of action, side-effects and counseling points for GLP-1 RA
Compare and contrast GLP-1 RA studies
Discuss the PIONEER-6 study and its implications to clinical practice
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Dr. John Buse prepared useful practice aids pertaining to type 2 diabetes for this CME activity titled "An Update on SGLT2 Inhibition for the Prevention and Treatment of Kidney Disease in Patients With Type 2 Diabetes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Wm2VJw. CME credit will be available until June 12, 2020.
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Dr. John Buse prepared useful practice aids pertaining to type 2 diabetes for this CME activity titled "An Update on SGLT2 Inhibition for the Prevention and Treatment of Kidney Disease in Patients With Type 2 Diabetes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Wm2VJw. CME credit will be available until June 12, 2020.
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
Ponencia realizada por el Dr. Eduard Montanya Mias del Hospital Universitari de Bellvitge (Barcelona). Director Científico CIBERDEM en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of ...Dayu Agung Dewi Sawitri
Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner.
Diselenggarakan oleh Perkeni, Kementerian Kesehatan RI dan STENO Diabetes Center
Achieving Hba1c targets: Strategies For Initiating and Intensifying Diabetes ...Nemencio Jr
This module highlights the appropriate HbA1c targets that reduce microvascular and macrovascular complications in appropriate populations and how to safely achieve them with current anti-hyperglycemic agents
The use of vildagliptin in patients with type 2 diabetes with renal impairmentUsama Ragab
The use of vildagliptin in patients with type 2 diabetes with renal impairment
By Dr. Usama Ragab Youssif
Agenda
----------
Case presentation
Diabetes and CKD: What is the problem
Drug treatment in patient with CKD: choice of treatment
Vildagliptin in mild renal impairment
Vildagliptin in moderate and severe renal impairment
Vildagliptin in ESRD (patients on HD)
Vildagliptin in kidney transplant patients with NODAT
Final bottom-line
Learn more about the 2022 NICE guideline NG28 update using the self-guided CPD-accredited Cardiorenal Protection module, which gives you all the data you need to help contextualise the changes and build a strong understanding of how these changes will impact your day-to-day practice and improve outcomes for your patients with T2D. (Approx. 10 mins)
Is your approach to T2D management up to date?CogoraLtd
Learn more about the 2022 NICE guideline NG28 update using the self-guided CPD-accredited Cardiorenal Protection module, which gives you all the data you need to help contextualise the changes and build a strong understanding of how these changes will impact your day-to-day practice and improve outcomes for your patients with T2D. (Approx. 10 mins)
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
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1. Timely insulin initiation and
overcoming clinical inertia in T2D
management
26TH MAY 2021
DR LUMU WILLIAM(MBcHB, MMED,MScDm,PhD
fellow) Physician/Diabetologist Mengo Hospital, President
Uganda Diabetes Association
2. Novo Nordisk®
Diabetes is a rapidly growing
social challenge worldwide
1. International Diabetes Federation. IDF Diabetes Atlas, 5th edn. Brussels, Belgium: International Diabetes Federation. 2011.
2. International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation. 2019.
The increasing global
prevalence of diabetes 1,2
285 million
adults with diabetes1
2010
2019
2045
463 million
adults with diabetes2
51%
increase in number
of adults with diabetes
700 million
adults with diabetes2
3. 700 MILLION
TODAY, 463 MILLION PEOPLE HAVE DIABETES.
BY 2045, IT’S ESTIMATED THAT
PEOPLE WILL HAVE DIABETES GLOBALLY
1 IN 2
PEOPLE WITH DIABETES DO
NOT KNOW THEY HAVE IT
ONLY HALF
OF THE PEOPLE IN TREATMENT FOR DIABETES
ACHIEVE THE PLANNED TREATMENT TARGETS
4.2 MILLION
PEOPLE DIED OF DIABETES IN
2019
References: 1 IDF. Diabetes Atlas, 9th Edition, 2019. Available at https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.html
4. Novo Nordisk®
The diabetes challenge in Africa*
19 MILLION
ADULTS HAVE DIABETES
BY 2045 THIS FIGURE
COULD RISE TO
47 MILLION 2
366,200
PEOPLE DIED OF DIABETES-
RELATED CAUSES IN 20191
19 MILLION PEOPLE4
29 MILLION PEOPLE1
47 MILLION PEOPLE2
2019 2030 2045
IDF. Diabetes Atlas, 9th Edition, 2019. Available at https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.html
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Processes of care among diabetic patients in
Uganda ( Kibirige et al 2016)
Glycosylated Haemoglobin performed at least once in previous year 9.6 %
Assessment of lipid profile 14.0 %
Screening for diabetic nephropathy 12.4%
Screening for diabetic retinopathy
14.0 %
5
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Processes of care cont’d
Screening for cardiac complications 5.6%
Screening for diabetic foot disease 21.2%
Screening for peripheral vascular disease 18.0%
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Outcome Measures for diabetic patients in
Uganda (Kibirige et al 2016)
Parameter Frequency(%)
Fasting Blood Sugar < 7.2mmol 42.8
Glycated Hemoglobin <7% 20.8
Optimal Blood Pressure control< 140/80mmHg
56.0
Optimal Lipid control (LDL< 100mg/dl) 20.0
7
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IDF. Diabetes Atlas, 9th Edition, 2019. Available at https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.html
Total health expenditure on diabetes per adult with
diabetes (20 – 79 years) in 2019
9. Novo Nordisk®
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Patients remain on multiple OAD therapy
too long
Prior to insulin initiation, patients had received OAD therapy for 8.7 ± 6.7 years
Clinical inertia exists despite:
• The benefits of timely glycaemic control
• Guidelines encouraging earlier use of insulin
At insulin initiation in SOLVE:
Distribution of HbA1c at time of
insulin initiation
41% had HbA1c ≥9.0%
22% had HbA1c ≥10.0%
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
4 5 6 7 8 9 10 11 12 13 14 15 16
Patients
(%)
41% ≥9.0%
22% ≥10.0%
8.9%
Average HbA1c was 8.9%
OAD, oral antidiabetic drug
Khunti et al. Diabetes Obes Metab 2012;14:654–61
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Often there is a failure to advance therapy when
required
At insulin initiation, the average
patient had:
5 years with HbA1c >8%
(11.6 mmol/L)
10 years with HbA1c >7%
(9.6 mmol/L)
66.6
35.3
44.6
18.6
0
20
40
60
80
100
Diet Sulfonylurea Metformin Combination
Subjects
(%)
Percentage of subjects intensifying therapy
when HbA1C >8%
Brown et al. Diabetes Care 2004;75:1535-40
11. Novo Nordisk®
T2D management considerations for individualized treatment:
ADA/EASD Position Statement 2015
T2D, type 2 diabetes; AE, adverse event; CV, cardiovascular
Adapted from Inzucchi SE et al. Diabetes Care 2015;38:140−149
Hyperglycaemia management approach
More stringent Less stringent
Long Short
Hypoglycaemia and
AE risks
Absent Severe
Important comorbidities
Highly motivated Less motivated
Resources and support
system Readily available Limited
HbA1c
7%
Life expectancy
Disease duration
Established vascular
complications
Patient attitude and
expectations
Few/mild
Absent Severe
Few/mild
Newly diagnosed Long-standing
Low High
Usually
not
modifiable
Potentially
modifiable
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Even after initiation, there are still
challenges to achieve glycaemic goals
6.5
7.0
7.5
8.0
8.5
9.0
2001 2002 2003 2004 2005 2006 2007
3.5
4.0
4.5
5.0
5.5
6.0
2001 2003 2005 2007
Type 1 diabetes
Type 2 diabetes
+ insulin
Year
Year
Mean
HbA1c
(%)
Mean
Tchol
(mmol/l)
In patients with type 1 diabetes or type 2 diabetes on insulin, there was a 0.1%
relative improvement in HbA1c vs. improvements in total cholesterol of 15% and
29%, respectively between 2001 and 2007
Currie et al. Diabetic Medicine 2010; 27:938-948
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Progression of type 2 diabetes
Adapted from Kendall et al. Am J Med 2009:122(Suppl. 6):S37–50
Insulin resistance
Insulin level
FPG
Postprandial glucose
β-cell function
Progression of type 2 diabetes
Diabetes
4–7 years
Development of macrovascular complications
Development of microvascular complications
Diabetes diagnosis
Impaired glucose tolerance
Incretin effect
FPG, fasting plasma glucose
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Beta-cell function progressively declines
Beta-cell
function
(%,
HOMA)
Extrapolation of
beta-cell function
prior to diagnosis
0
20
40
100
–4 6
–10 –8 –6 –2 0 2 4
80
60
–12 8
Diabetes diagnosis
Time from diagnosis (years)
UKPDS: at 6 years, more than 50% of
patients need insulin to reach target
(FPG ≤108 mg/dL [≤6.0 mmol/L])
FPG, fasting plasma glucose; HOMA, homeostasis model assessment; UKPDS, United Kingdom Prospective Diabetes Study
Lebovitz. Diabetes Rev 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58); Wright et al. Diabetes Care 2002;25:330–6
15. Novo Nordisk®
Metabolic memory is a term used to describe beneficial effects
of immediate intensive treatment of hyperglycemia and the
observation that they are maintained for many years,
regardless of glycemia in the later course of diabetes.
What is Legacy Effect or Metabolic Memory?
Drzewoski J, Kasznicki J, Trojanowski Z. The role of “metabolic memory” in the natural history of diabetes mellitus. Pol Arch Med Wewn. 2009 Jul 1;119(7-8):493-500.
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The benefits of early tight control in T2DM: UKPDS
Any diabetes-related endpoint
Myocardial infarction
Microvascular disease
1977–1991
Randomisation
2007
(30 years)
10 years post-trial follow-up period
(non-interventional)
UKPDS original results:
Intensive vs. conventional treatment
12%*
25%*
16%**
1997
(20 years)
9%*
24%*
15%*
Improvements in glycaemic control reduce
the risk of complications
T2DM
UKPDS – macrovascular complications1,2
*p<0.05, **p=0.052 – intensive vs. conventional treatment
DCCT, Diabetes Control and Complications Trial; EDIC, European Diploma in Intensive Care Medicine; T2D, type 2 diabetes mellitus; UKPDS, United Kingdom Prospective Diabetes Study
1. UKPDS Study Group. Lancet 1998;352:837–53; 2. Holman et al. N Engl J Med 2008;359:1577–89
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Why use insulin?
• Reduction of diabetes complications:
• Effective treatment choice
• Cardiovascular disease
• Retinopathy
• Neuropathy
• Nephropathy
• When beta cells in the pancreas fail and they
can no longer secrete insulin
• Most efficacious glucose lowering agent
Nathan et al. Diabetes Care. 2009;32:193-203
Lebovitz. Diabetes Rev 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58); Wright et al.
Diabetes Care 2002;25:330–6
18. Novo Nordisk®
Better HbA1c control is associated with reductions in long-
term health complications
MI, myocardial infarction; UKPDS, UK Prospective Diabetes Study
UKPDS 35: Stratton et al. BMJ 2000;321:405–11
43%
Lower extremity
amputation or fatal
peripheral vascular
disease
37%
Microvascular
disease
19%
Cataract
extraction
14%
MI
16%
Heart failure
12%
Stroke
Every 1% drop in HbA1c can reduce long-term diabetes complications
• UKPDS: Prospective observational
study in 23 hospital-based clinics in
England, Scotland and Northern Ireland
• n=4,585 patients; 3,642 included in analysis
of relative risk
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Indications of insulin in type 2 diabetes
Patients meeting any of the following criteria may require insulin therapy:
• Symptoms of hyperglycaemia
• Polyuria, thirst, fungal infections, painful neuropathy, foot ulceration/infection and bacterial infections
• Presence of complications
• Systemic infection, sepsis, acute MI, unstable angina, diabetic ketoacidosis
• Scheduled for surgery
• High values at diagnosis
• FPG >250 mg/Dl(13.8mmol/l), PPG >300 mg/dL(16.7mmol/l), HbA1C >9%
• Unsatisfactory glycaemic control on optimal dose of 2-3 OADs
• Pregnant women with gestational diabetes / diabetes in pregnancy
RCN 2006. Starting Insulin Treatment in Adults with T2DM
Das et al. JAPI 2009 http://www.japi.org/february_2009/premix_insulin.html
20. Novo Nordisk®
What is Insulin?
Peptide hormone that is exclusively
secreted by the beta-cells of the
pancreas and responsible for
carbohydrate, fat and protein
metabolism
Gough S, Narendran P. Insulin and insulin treatment. In: Textbook of Diabetes, Fourth Edition. Holt RIG, Cockram CS,
Flyvbjerg A, Goldstein BJ (Eds). Blackwell Publishing Ltd, 2010
21. Novo Nordisk®
Structure of Human Insulin
Glu
Thr
Lys
Thr
Tyr Phe Phe Gly Arg
Glu
Gly
Cys
Val
Leu
Tyr
Leu
Ala
Val
Leu
His
Ser
Gly
Cys
Leu
His
Gln
Asn
Val
Phe
B1
Asn Cys
Tyr
Asn
Glu
Leu
Gln
Tyr
Leu
Ser
Cys
Ile
Ser
Thr
Cys
Cys
Gln
Glu
Val
Ile
Gly
A21
B28
B30
Asp
B23
Pro
B7
B19
A20
A7
Gough S, Narendran P. Insulin and insulin treatment. In: Textbook of Diabetes, Fourth Edition. Holt RIG, Cockram CS,
Flyvbjerg A, Goldstein BJ (Eds). Blackwell Publishing Ltd, 2010
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• Insulin is secreted continuously by beta cells in a glucose
dependent manner and this constitutes the basal insulin
secretion.
• Basal insulin secretion constitutes 50% of the total daily
insulin.
• Basal insulin suppresses lipolysis and glycogenolysis.
• Remainder(50%) of insulin secretion is post prandial and
this is constituted by the first and second phases of insulin
secretion.
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• During the first phase of insulin secretion, there is a sizable
release of preformed insulin from storage granules within
the beta cell in response to a meal
• The first phase of insulin secretion promotes peripheral
utilization of the prandial nutrient, suppresses hepatic
glucose production and limits post prandial glucose
elevation
• The first phase of insulin secretion begins within 2 min of
nutrient ingestion and continues for 10-15min giving way
to second phase of insulin secretion
.
24. Novo Nordisk®
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• The second phase of prandial insulin secretion is sustained until
normoglycemia is restored.
• Average daily insulin secretion by non diabetic pancreas is 30 Units.
26. Novo Nordisk®
Physiologic Insulin Secretion : Basal/Bolus Concept
Breakfast Lunch Supper
Insulin
(µU/mL)
Glucose
(mg/dL)
Basal Glucose
150
100
50
0
7 8 9 1011121 2 3 4 5 6 7 8 9
A.M. P.M.
Time of Day
Basal Insulin
50
25
0
Nutritional Glucose
Nutritional (Prandial)
Insulin
Suppresses Glucose
Production Between
Meals & Overnight
The 50/50 Rule
27. Novo Nordisk®
What are human insulin ?
• Structure and molecular pharmacology of human
insulin is retained
• Manufactured by recombinant DNA technology
(rDNA)
28. Novo Nordisk®
What are insulin analogues ?
• Structure of insulin is modified
• Molecular pharmacology of human insulin is retained
Designed to:
• More closely mimic normal physiologic insulin secretion
patterns (basal, bolus)
• Match the time-action profile of SC-delivered insulin to
physiological requirements
29. Novo Nordisk®
Insulin secretion is delayed and blunted in type 2 diabetes
Adapted from: Polonsky KS, et al. N Engl J Med. 1996 Mar 21;334(12):777-783.
Normal
Type 2 diabetes
Time (24 hours)
800
600
400
200
0
Insulin
Secretion
(pmol/min)
Meal Meal Meal
The goal of insulin therapy is to restore normal insulin secretion
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Insulin Kinetics-Human insulin
Trade Name Composition Type of insulin Onset of
action
Peak action Duration of
action
Actrapid
(Uganda)
Soluble insulin Short acting 30min 1-3hrs 8hrs
Humulin-R Soluble insulin Short acting 30min 1-3hrs 5-7hrs
Protophane/Ins
ulatard(Uganda)
Isophane Intermediate acting 1-5hours 4-12 hours 24 hours
Humulin N Isophane Intermediate acting 1hr 2-8hrs 18-20hrs
Mixtard
30/70,Humulin
30/70(Uganda)
Pre-mixed soluble
insulin +NPH
Short+ intermediate 30mins 2-10 hrs 24hrs
32. Novo Nordisk®
Insulin replacement therapy aims to recreate the normal blood insulin
profile
Mealtime (prandial) insulin excursions
Rapid rise; short duration
0800 1200 1600 2000 2400
0
10
20
30
40
50
0400
Time (h)
Serum
insulin
(mU/L)
0800
Flat basal insulin profile
Breakfast Lunch Dinner
Kruszynska 1987
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GUIDE TO CHOICE OF INSULIN
Type of insulin Type of sugar controlled
Rapid acting insulin analogues e.g
aspart,lispro,gluisine
Post prandial blood sugar
Short acting insulin e.g soluble (actrapid) Post prandial blood sugar
Intermediate acting insulin e.g NPH(
Insulatard)
Fasting hyperglycemia
Long acting insulin analogues e.g Glargine,
Determir
Fasting hyperglycemia
Pre-mix e.g Mixtard, Novo mix Both Fasting and Post prandial hyperglycemia
34. Novo Nordisk®
50% 55% 60% 70%
50% 45% 40% 30%
30%
70%
<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2
PPG
FPG
0
20
40
60
80
100
HbA1c range (%)
%
contribution
to
HbA
1c
Most insulin is
initiated when
HbA1c >8.5%
Adapted from Monnier et al. Diabetes Care 2003;26:881-5
Guidance threshold for insulin initiation
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Glucose Triad of Diabetes Management:-
Address the FPG and PPG requirements in T2DM
HbA1c
PPG
FPG
PPG is the predominant contributor in
patients with satisfactory to good control of
diabetes, whereas the contribution of FPG
increases with worsening diabetes1
PPG and FPG increase with HbA1c
2
FPG, fasting plasma glucose; PPG, postprandial plasma glucose
1. Monnier et al. Endocr Pract 2006;12:S1:42–6; 2. Monnier et al. Diabetes Care 2007;30:263–9; 3. Ketema et al. Arch Public Health 2015;73:43
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• Modification of the insulin regimen, e.g.
adding to or changing the therapy in
order to maintain glycaemic control
INTENSIFICATION
Principles of insulin therapy
• Dose titration to ensure that the patient
receives the maximum benefit from the
prescribed treatment
OPTIMISATIOM
INITIATION
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Insulin optimization and intensification should
follow disease progression
Beta-cell
function
(%)
Treatment optimisation and intensification
Lifestyle + OADs
Basal and 1–4 bolus or premix
Basal insulin/Premix* + OADs
Schematic diagram adapted from Kahn. Diabetologia 2003;46:3–19; Inzucchi et al. Diabetologia 2012;55(6):1577–96; IDF Clinical Guidelines Task Force.
Global guideline for type 2 diabetes, 2012
Titrate dose to reach/maintain glycaemic targets
Intensify for mealtime insulin coverage
Initiate
Optimise
Intensify
OAD, oral antidiabetic drug; * IDF 2012
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What are the strategies for intensification of
insulin therapy in type 2 diabetes?
IDF Clinical Guidelines Task Force. Global guideline for type 2 diabetes, 2012. www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf; 2. General practice management of type 2
diabetes, 2016–18. Melbourne: The Royal Australian College of General Practitioners and Diabetes Australia, 2016. https://www.diabetesaustralia.com.au/best-practice-guidelines; 3. Harper et
al. Can J Diabetes 2013;37(Suppl. 1):S61–8 (Appendix 3); 4. NICE. The management of type 2 diabetes. NICE Clinical Guideline 87 (modified December 2015).
https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493; 5. Garber et al. Endocr Pract 2016;22:1–113
Basal–bolus
therapy
Premix
BID or TID
Premix insulin
OD or BID
Prandial insulin
Basal insulin
+ OADs
Starting regimens: Intensification regimens:
39. Guideline Initiation Intensification
IDF1 • Basal OD
• Premixed OD/BID
• Basal-plus or basal−bolus
Diabetes Australia2 • Basal OD
• Premixed OD
• Add GLP-1 RA
• Basal-plus or basal−bolus
• Premixed BID or TID
Canadian Diabetes
Association3
• Basal OD
• Premixed OD/BID
• Basal-plus or basal−bolus
• Premixed BID
NICE4 • Basal OD/BID
• Premixed OD/BID
• Basal-plus or basal−bolus
• Premixed BID
AACE5 • Basal • Add GLP-1 RA or prandial insulin
• (Premixed among other options)
Initiation and intensification in T2D: Summary of international
guidelines
AACE, American Association of Clinical Endocrinologists; BID, twice daily; EASD, European Association for the Study of Diabetes; GLP-1 RA, glucagon-like peptide-1 receptor agonist; IDF, International
Diabetes Federation; NICE, UK National Institute for Health and Care Excellence; OD, once daily; TID, three-times daily; T2D, type 2 diabetes
1. IDF Clinical Guidelines Task Force. Global guideline for type 2 diabetes, 2012. www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf; 2. General practice management of type 2
diabetes, 2016–18. Melbourne: The Royal Australian College of General Practitioners and Diabetes Australia, 2016. https://www.diabetesaustralia.com.au/best-practice-guidelines; 3. Harper et al. Can J
Diabetes 2013;37(Suppl. 1):S61–8 (Appendix 3); 4. NICE. The management of type 2 diabetes. NICE Clinical Guideline 87 (modified December 2015).
https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-1837338615493; 5. Garber et al. Endocr Pract 2016;22:1–113
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Insulin regimens
• Choice of the insulin regimen will depend on the HbA1C
• If HBAIC is 7% to 10% or its 1% to 2% above the
individualized target-Basal insulin initiated together with metformin
• If HBA1C is >10% or it is 2% above the individualized target
initiate basal- bolus insulin or biphasic premixed insulin therapy
initiated with metformin
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1.Basal insulin regimen
• If patient is lean initiate with 5 to 10units at bedtime and if patient is obese
initiate with 10 to 15U or initiate with 0.1-0.2U/kg
• Bedtime insulin is used together with oral agents
• Monitor fasting blood glucose every morning and calculate average fasting
glucose every three to seven days and increase bed time insulin by 2 to 5 units
until fasting sugar has reached the individualized target.
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2.Pre-mixed regimen( e.g Mixtard, Novomix)
• Indicated when patient is very hyperglycaemic
• The total dose is then divided into 2 with 2/3 of the dose given
30minutes(Mixtard) or 15minutes(Novomix) before break fast and 1/3 of the total
daily dose is given 30 minutes(Mixtard) or 15 minutes(Novomix) before supper.
• NB Before injection food must be already on the table.
• TDD=0.5-1 UNIT/KG/Day
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• For Example if patient has weight of 90Kg
• His TDD will be 0.5x90=45units
• Dose at breakfast will be 2/3x45=30 units
• Dose at supper will be 1/3x45=15 units
• All patients on Mixtard and any other insulin MUST have a
GLUCOMETER and a personal blood sugar log where they record their
blood sugar values when they measure.
• Stop Sulphonyl ureas, Glitazones
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• They should measure TWICE a day i.e before breakfast and supper and then
RECORD
• The blood sugar log must always be checked by the doctor or clinician to get
the breakfast and supper averages
• Recommended targets before meals are 4.5-7mmol/l
• Adjust insulin doses by 2-3 units every after 3 days till the above target is
achieved.
• For Pre breakfast when not on target adjust pre supper dose and for pre supper
sugar adjust pre breakfast dose
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Physiological insulin
profile:
• Basal component
• Meal-related peaks
Short/Rapid-acting insulin
together with a basal insulin
provide physiological insulin
replacement
Premix insulins such as
BHI 30 /BIAsp 30 replace
both
meal-related and
basal insulin
1 insulin, 1 device
Advantage of premix insulin – 1 & 1
Garber et al. Diabetes Obes Metab 2006;8:58–66
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3.Basal-Bolus Regimen
If patient has been on pre mix insulin such as Mixtard and
his blood sugars are not well controlled he/she can be
changed to a basal-bolus regimen.
The Basal-Bolus Regimen
Estimate TDD of insulin
-Weigh patient
-Multiply Wgt by 0.5-1 unit=TDD
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Basal bolus…..
-Divide TDD into 2 halves i.e 50%-BASAL and 50% Prandial
-For the Basal Half,3/4 of it should be given at break fast and ¼ given at 10.30pm
-For the Prandial half ,divide by 3 to give the doses at meals
E.g for a 60Kg man
The TDD of insulin will be 0.5x60=30 units
50% of 30=15 units basal insulin such as NPH (Insulatard)
50% of 30=15 units prandial insulin such as soluble insulin(Actrapid)
These will be given as follows
Insulatard
10 units at break fast
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Basal bolus………
5 units at 10.30pm
Actrapid (soluble)
5 units at break fast,5units at lunch ,5 units at Supper
This can be presented in the table as shown
51. Barriers to optimal insulin therapy
Fear of hypoglycaemia
Reluctance to inject
in public
Fear of reduced
quality of life
Fear of needles/injection pain
Perception that disease
is becoming more
severe
Inability to fully tailor
treatment to patients’
needs
Korytkowski. Int J Obes Relat Metab Disord 2002;26:S18–S24; Polonsky et al. Diabetes Care 2005;28:2543–5;
Rubin and Peyrot. J Clin Psychol 2001;57:457–78
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Patient-centred insulin initiation
Patient
Needs
Preferences Tolerances
Age
Disease
progression
Inzucchi et al. Diabetologia 2012;55:1577–96
• There is a call for a move toward more
patient-centered care
• Treatment for type 2 diabetes should
consider the needs, preferences and
tolerances, as well as age and disease
progression, of each patient
• These factors make it difficult to
prescribe a single treatment
regimen designed for everyone
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Injection sites
• Insulin is injected through the skin into the fatty tissue
known as the subcutaneous layer.
• You do not give it into muscle or directly into the blood.
• Absorption of insulin varies depending on the part of the
body into which you inject. The abdomen absorbs insulin
the fastest and is the site used by most people. The upper
arms, buttocks and thighs are also used by some people.
• It is essential to give each injection in a slightly different
spot within the one site (such as the abdomen)
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Storage
• Keep your unopened insulin FlexPen® on their side in the fridge. Do
not allow to freeze (2oc – 8oc).
• Once opened, insulin may be kept at room temperature (less than
30 degrees) for one month (28 days)
• Insulin may be damaged by extreme temperatures. It must not be
left where temperatures are over 30 degrees (remember it can get
this hot in the glove box of your car) or in direct sunlight.
• Insulin FlexPen® can be safely carried in your handbag or pocket.
• May be damaged by vigorous shaking
• If refrigeration not available store in clay pot
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Conclusion
• Insulin should be initiated early and timely in type 2 diabetes
• Clinical inertia should be overcome in insulin initiation
• Insulin therapy should be individualized
• Principles of insulin therapy ;initiation, optimization and
intensification must be followed for effective insulin therapy
56