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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


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


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

Presenter

Presentation Notes

IFG: fasting (8 hours) plasma glucose 100-125 mg/dL IGT: 2-hour value in 75-g OGTT 140-199 mg/dL Follow-up here refers to formal reassesment of glycemic status. Follow-up should be individualized with respect to venue, frequency and goals. Other features: <60 years old BMI ≥ 30 kg/m2 and either A1C > 6.0%, hypertension, low HDL, high triglycerides or family history of diabetes in first-degree relative Diabetes: A1C ≥6.5%, fasting ≥126 mg/dl, 2-hour ≥200 mg/dl; should be confirmed on a separate day unless unequivocally elevated and/or symptomatic

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


Preventing Complications

Management of diabetes


1993-1997 2005-2010


Presenter

Presentation Notes

UKPDS 10-Year Follow-Up: Benefits of Intensive Glucose Control Sustained for up to 10 Years Despite Early Loss of A1C Level Advantage


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


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%

Presenter

Presentation Notes

Composite endpoint of death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for PAD: Steno-2 In Steno-2, the intensive therapy group had a 53% reduction in macrovascular disease, relative to the conventional therapy group. This 53% reduction in macrovascular disease is much higher than the percent reduction reported in single intervention trials of blood pressure, lipids, or ACE inhibitors, suggesting that multiple risk factor interventions are critical in high-risk subjects. Reference: Gæde P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-393.


ABC OF DIABETES CARE A A1C

B Blood pressure C Cholesterol


Prevention of Complications with ABC of diabetes


DIABETES ENDOCRINOLOGY CENTER OF WESTERN NEW YORK OUTCOMES


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


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


Achieve Glycemic goals without hypoglycemia


PATHOPHYSIOLOGY OF TYPE 2 DIABETES

Presenter

Presentation Notes

Hyperglycemia and Acute Myocardial Infarction

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

Presenter

Presentation Notes

Ominous Octet The pathogenesis of type 2 diabetes includes eight identified pathophysiological defects: Decreased insulin secretion Decreased incretin effect Decreased glucose uptake in the muscle Increased glucagon secretion Increased hepatic glucose production Increased lipolysis Increased glucose reabsorption Neurotransmitter dysfunction Reference: Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773-795. http://www.ncbi.nlm.nih.gov/pubmed/19336687


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

Presenter

Presentation Notes

Ominous Octet The pathogenesis of type 2 diabetes includes eight identified pathophysiological defects: Decreased insulin secretion Decreased incretin effect Decreased glucose uptake in the muscle Increased glucagon secretion Increased hepatic glucose production Increased lipolysis Increased glucose reabsorption Neurotransmitter dysfunction Reference: Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773-795. http://www.ncbi.nlm.nih.gov/pubmed/19336687


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%

Presenter

Presentation Notes

Antidiabetes Therapy: Treatment Effects Read slide as is


• 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


Type 1 Diabetes- Closed Loop systems

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


Reversing complications



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


EVOLUTION OF ALBUMINURIA

89%

10%

1%

Baseline Microalbuminuria

48%

47%

5%

normoalbuminuria microalbuminuria macroalbuminuria

4%

50%

46%

Baseline Normoalbuminuria

Baseline Macroalbuminuria


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


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


Reduction in Macrovascular and Microvascular complications: IRIS/LEADER/EMPA-REG


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


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

diabetes: what is on the horizon...banting\ഠlecture. from the triumvirate to the ominous octet: a...

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