Diabetes: What is on the Horizon...Banting\ഠLecture. From the triumvirate to the ominous octet: a...
Transcript of Diabetes: What is on the Horizon...Banting\ഠLecture. From the triumvirate to the ominous octet: a...
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Diabetes: What is on the Horizon
Ajay Chaudhuri, MBBS, MRCP (UK) Clinical Professor, Department of Medicine Program Director, Endocrinology Fellowship UB|MD Internal Medicine – Endocrinology, Diabetes & Metabolism Director, Kaleida’s Diabetes & Endocrinology Center of WNY, President WNY ADA, Buffalo
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
HOPE AND OPTIMISM
• Prediabetes- We can Prevent Diabetes !!
• Diabetes
– Get more patients with type 1 and type 2 diabetes to goal without increasing the risk of hypoglycemia
– Prevent complications – Reverse Complications
HOPE AND OPTIMISM
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Prediabetes
Screening For Diabetes
Testing at least every 3 yrs starting at age 45
American Diabetes Association. Diabetes Care. 2014:37, S14-80
Test Prediabetes Diabetes
FPG 100-125 mg/dL ≥126 mg/dL OGTT 140-199 mg/dL ≥200 mg/dL A1C 5.7-6.4% ≥6.5%
A1C ≥ 6.0% IFG and IGT
+ Other Features
Lifestyle intervention and/or metformin, follow-up @6 mo
Intervention and Follow-Up Screen for Diabetes:
A1C - or - FPG – or -
2-hour, 75-g OGTT
Normal
Re-evaluate in 3 years if risk
factors remain
METFORMIN IS NOT FDA APPROVED FOR PREVENTION
American Diabetes Association. Diabetes Care. 2014:37, S14-80
Lifestyle intervention,
follow-up @1 year
A1C ≥ 5.7% IFG or IGT DIABETES
Lifestyle intervention plus metformin, follow-up @3 mo
Cum
ulat
ive
Inci
denc
e of
Dia
bete
s (%
)
Years
40
30
20
10
0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Placebo
Metformin
Lifestyle
Knowler WC, et al. NEJM. 2002;346:393-403
Diabetes Prevention Program
Older Adults (Cases/100 person-yrs)
Placebo 10.8 Metformin 9.6 Lifestyle 3.1
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Preventing Complications
Management of diabetes
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
1993-1997 2005-2010
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
SUMMARY OF THE LANDMARK CLINICAL TRIALS
• Intensive glycemic control reduces microvascular complications
• Intensive glycemic control reduces macrovascular complications • without established CVD • In long term follow up studies
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
STENO-2
•Intensive Treatment Goals: Hemoglobin A1c, <6.5% cholesterol, <175 mg/dL triglycerides, <150 mg/dL systolic blood pressure, <130 mm Hg diastolic blood pressure, <80 mm Hg
0
10
20
30
40
50
60
COMPOSITE ENDPOINT OF DEATH FROM CV CAUSES, NONFATAL MI, CABG, PCI, NONFATAL STROKE, AMPUTATION, OR SURGERY FOR PAD: STENO-2
Prim
ary
Com
posi
te
Endp
oint
(%
)
Months of Follow-up 0 24 48 60 96 36 84 72 12
Conventional Therapy
Intensive Therapy
P=0.007
Hazard ratio = 0.47 (95% CI, 0.24–0.73; P=0.008)
Gæde P et al. N Engl J Med 2003;348:383-393. Copyright 2003 Massachusetts Medical Society. All rights reserved.
53%
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ABC OF DIABETES CARE A A1C
B Blood pressure C Cholesterol
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Prevention of Complications with ABC of diabetes
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
DIABETES ENDOCRINOLOGY CENTER OF WESTERN NEW YORK OUTCOMES
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
OUTCOMES OF PATIENTS FROM DIABETES ENDOCRINOLOGY CENTER OF WNY • Mean Hba1c: 6.8% • Mean LDL-C: 75mg/dl • Mean HDL-C: males: 38mg/dl; females: 45mg/dl • Mean Systolic BP: 125mm Hg • Mean Diastolic BP: 78mm Hg • 85% on statins • 90% on ACE inhibitors/ARBs • 85% on aspirin • 65% on insulin
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
CLINICAL OUTCOMES OF PATIENTS FROM DIABETES ENDOCRINOLOGY CENTER OF WNY
• No foot ulcers, gangrene or amputations for 11 years
• No endstage renal failure, dialysis or transplantation for 7 years
• Mean microalbuminuria diminished • Cessation of laser therapy within two
years of attending
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Achieve Glycemic goals without hypoglycemia
Management of diabetes
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
PATHOPHYSIOLOGY OF TYPE 2 DIABETES
Slide Source: Lipids Online Slide Library www.lipidsonline.org
Reprinted with permission from DeFronzo R et al. Diabetes. 2009;58:773-795. Copyright © 2009 American Diabetes Association. All rights reserved.
Ominous Octet
IncreasedHGP
Hyperglycemia
ETIOLOGY OF T2DM
Decreased GlucoseUptake
Impaired InsulinSecretion Increased Lipolysis
Decreased Incretin Effect
Decreased Insulin Secretion
Increased Hepatic Glucose
Production
Islet–Α cell
Increased Glucagon Secretion
Decreased Glucose Uptake
Increased Lipolysis
Increased Glucose
Reabsorption
HYPERGLYCEMIA
Neurotransmitter Dysfunction
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Targeting the Core Defects of Type 2 Diabetes
Slide Source: Lipids Online Slide Library www.lipidsonline.org
Reprinted with permission from DeFronzo R et al. Diabetes. 2009;58:773-795. Copyright © 2009 American Diabetes Association. All rights reserved.
Ominous Octet
IncreasedHGP
Hyperglycemia
ETIOLOGY OF T2DM
Decreased GlucoseUptake
Impaired InsulinSecretion Increased Lipolysis
Decreased Incretin Effect
Decreased Insulin Secretion
Increased Hepatic Glucose
Production
Islet–Α cell
Increased Glucagon Secretion
Decreased Glucose Uptake
Increased Lipolysis
Increased Glucose
Reabsorption
HYPERGLYCEMIA
Neurotransmitter Dysfunction
SGLT2 inhibitor
Incretins
BromSR
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
ANTIDIABETES THERAPY: TREATMENT EFFECTS1,2
Class Expected
Decrease in A1C (%)
Biguanides 1 – 2
Sulfonylureas 1 – 2
Glinides 0.5 – 1.5 Alpha glucosidase inhibitors
0.5 – 0.8
Thiazolidinediones 0.5 – 1.4
DPP-IV inhibitors 0.5 – 0.8
GLP-1 receptor agonists 0.5 – 1.5
Insulin 1.5 – 3.5 1. Nathan DM et al. Diabetes Care. 2009;32(1):193-203. 2. American Association of Clinical Endocrinologists. Endocrine Practice. 2007;13:3-68.
SGLT2 inhibitor 0.6 to 1.1%
Copyright © 2015 AACE. May not be reprinted in any form without express written permission from AACE.
Copyright © 2015 AACE. May not be reprinted in any form without express written permission from AACE.
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
• Individualize glycemic goals based on patient characteristics and avoid hypoglycemia
• Promptly intensify antihyperglycemic therapy to maintain blood glucose at individual targets • Combination therapy necessary for most patients • Base choice of agent(s) on individual patient medical
history, behaviors and risk factors, ethno-cultural background, and environment
• Insulin eventually necessary for many patients • SMBG vital for day-to-day management of blood sugar
• All patients using insulin • Many patients not using insulin
Common Principles in AACE/ACE and ADA/EASD T2DM Treatment Algorithms
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Type 1 Diabetes- Closed Loop systems
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SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Use of Liraglutide with insulin in Type1 diabetes
• Addition of Liraglutide to Insulin in patients with well controlled type 1 diabetes results in the reduction of mean fasting & weekly glucose concentrations, a reduction in glycemic excursions and HbA1c
• Decrease in insulin requirements with no increase in hypoglycemia
Background
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Reversing complications
Management of diabetes
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Reversal of Complications with ABC
GLP-1 RECEPTOR AGONISTS REVERSE ALBUMINURIA
Akshata Desai, MD Mentor: Paresh Dandona, MD, Phd
Department of Endocrinology, SUNY at Buffalo
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
EVOLUTION OF ALBUMINURIA
89%
10%
1%
Baseline Microalbuminuria
48%
47%
5%
normoalbuminuria microalbuminuria macroalbuminuria
4%
50%
46%
Baseline Normoalbuminuria
Baseline Macroalbuminuria
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
GLP users non GLPusers
GLP users non GLPusers
GLP users non GLPusers
Baseline Normoalbuminuria Baseline Microlabuminuria Baselinemacroalbuminuria
97.3 95.24
25.1
6.9 2.86 0
2.3 4.4
74.9
88.5
23.1
12.3
0.4 0.36 0 4.6
74 87.7
Per annum comparison of evolution of albuminuria between GLP users and non users Normal Microalbuminuria Macroalbuminuria
p 0.0005 p<0.0001
p 0.0005
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
ALBUMINURIA IN THE TWO GROUPS
0
5000
10000
15000
20000
25000
30000
1 2
Series250Series249Series248Series247Series246Series245Series244Series243Series242Series241Series240Series239Series238Series237Series236
0
2000
4000
6000
8000
10000
12000
14000
16000
1 2
Series108
Series107
Series106
Series105
Series104
Series103
Series102
Series101
Series100
Series99
GLP-1RA users
Non-GLP users
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Reduction in Macrovascular and Microvascular complications: IRIS/LEADER/EMPA-REG
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
Sharing Best Practices to Improve Care
CDE-Ambassador A Novel Approach To Comprehensive
Diabetes Care At The Primary Care Level Fida Al-Atrash, MD Margaret Mersereau, RN, BSN, CDE Mary Bierbrauer, RN, BSN, CDE Nasir M. Khan, MD, FACP Nitesh D Kuhadiya, MD, MPH Husam Ghanim, PHD Ajay Chaudhuri, MBBS, MRCP CP
Patients &Methods This is a Retrospective review of patients with type 2 diabetes who were managed by their primary care provider and whose treatment was further organized/modified by a CDE-A These patients were not seen by an endocrinologist during that period and for at least 3 years prior to inclusion in this management plan A CDE-A was attached to this primary care group to advise/guide the management of diabetic patients in collaboration with the primary care physicians (PCP’s)
Patients &Methods
The initial training of the CDE-A’s was for a period of 3 months by the endocrinologists
Following the initial training period, the CDE-A continued to be in regular consultation with the endocrinologists in case further advice was needed
Any changes to the anti-diabetic regimen that was suggested by the CDE-A had to be authorized by the PCP
The first consecutive 100 subjects who were referred and seen by CDE-A were included in this analysis The start date was the first visit with the CDE-A (i.e. intervention visit) The follow up visit date was the first scheduled visit with their physician following the intervention The last set of HbA1c and labs done prior to intervention was used as baseline data for the purpose of the analysis
Patients & Methods
Most patients met with the CDE-A twice during that period Follow up data (weight, BP) was documented on the date of follow up with PCP in 6 months then again at one year mark. Follow up laboratory values were collected around the dates of follow up Another group of 45 patients who had not been referred to the CDE-A and were managed by the PCP’s alone over the same period were used as the controls
Patients & Methods
In the CDE-A intervention group, HbA1c fell by 1.6±2.1% with a fall in HbA1c was 1.9±2.0% in those in whom anti-diabetic treatment was altered and by 1.1±2.1% in whom drug therapy was not changed six months post intervention. The reduction in all the parameters were significantly greater in the intervention group when compared to controls
HIGHLIGHTS OF RESULTS
Our data clearly show that the participation of the CDE-A, under the guidance of an endocrinologist at the primary care level led to a marked reduction in HbA1c, LDLc, triglycerides, blood pressure and body weight within 5 months These changes were dependent on changes in dietary habits and drug therapy including the addition or optimization in the doses of anti-diabetic drugs and insulin therapy
HIGHLIGHTS OF RESULTS
SCHOOL OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF MEDICINE
HOPE AND OPTIMISM • Diabetes can be prevented- Take advantage
of the Diabetes Prevention Program
• Control the ABC’s- To prevent and reverse complications
• Understand the pathophysiology and utilize approaches to improve glycemic control without increasing the risk of hypoglycemia