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Diabetes Update
Matt Bouchonville, MD
Endocrinology Division
University of New Mexico
ACP New Mexico Chapter Scientific Meeting
November 7, 2014
[email protected]
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
Diabetes: Current rates and
projections
• CDC Press Release 2010: 1 in 3 adults with
DM by 2050
• ADA Report: health care costs for DM
increased by 40% to $245 billion between
2007 and 2012
• JAMA 2014;311(17):1778.: Increase in
prevalence in youth between 2001 and
2009 of T1D (20%) and T2D (30%)
Diabetes prevalence in the US leveling off?
Lower rates
of diabetesrelated
complications
in the US
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
Surgery group
>6X’s more
likely to be in
remission of
T2D at 15 yrs
Remission
less likely
with longer
duration of
diabetes
Surgery
associated with
>50% reduction
in microvascular
complications
Surgery
associated with
30% reduction in
macrovascular
complications
Impact of bariatric
surgery on diabetesrelated complications
attenuated by longer
duration of diabetes
Conclusions
• Compared to usual care, bariatric surgery
was associated with:
• Higher diabetic remission rates
• Fewer diabetic complications
• Bariatric surgery may have less influence on
diabetic remission and complication rates in
patients with longer duration of disease
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
SGLT2inhibitors
Similar A1c
reduction
(-0.52%) by end
of study
Weight loss
(-3.22 kg) vs
gain (+1.44 kg)
with SGLT2I
versus SU
treatment
Less hypoglycemia with
SGLT2I vs SU treatment
FDA Approval
March 2013 – Canagliflozin (Invokana)
January 2014 – Dapagliflozin (Farxiga)
August 2014 – Empagliflozin (Jardiance)
Contraindications: Severe renal impairment
Adverse effects: Hypotension/dehydration, genital
mycotic infections
Inhaled insulin
Afrezza (Technosphere insulin)
Technosphere insulin particles
made up of diketopiperazine
derivatives and insulin, which
self-organize into a lattice
array, and form particles of 2–4
µm diameter.
Rapid absorption of Technosphere insulin
• Cough ~30%
A1c
• No clinically meaningful changesModest
in PFT’s
reduction at 12
(short-term)
weeks
Affrezza: FDA Approval
June 2014
• Prandial insulin in T1D or T2D
• Baseline PFT’s required
• Post-market studies in progress:
– Subjects with baseline lung disease
– Lung cancer risk?
U-300 Insulin
glargine (Lantus)
Similar reduction in
A1c compared to
U-100 glargine
Similar reduction in
FPG compared to
U-100 glargine
Similar doses
of basal and
mealtime
insulin
Less nocturnal
hypoglycemia
with U-300
glargine
Similar glycemic control and dosing with U300 glargine insulin but less nocturnal
hypoglycemia
Insulin peglispro (LY2605541)
PEG
(20 kDa)
Insulin
Insulin peglispro (LY2605541)
Patent application US 12/481,111, 2009.
Insulin peglispro (LY2605541)
Compared to insulin glargine:
•
•
•
•
Less glycemic variability
Less hypoglycemia
No weight gain
Preferential hepatic (vs peripheral action)
Diabetes Care 2014;37:659-665.
Diabetes Care 2014;37:2609-2615.
Diabetes 2014;63:390-392.
Glimins
Imeglimin
• Targets mitochondria
(oxidative phosphorylation
blocker) = decreased hepatic
gluconeogenesis
• Increases skeletal muscle
glucose uptake
• Enhanced insulin secretion in
response to glucose
A1c reduction of 0.7% compared to addition of placebo
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
Continuous
subcutaneous
insulin infusion
(CSII)
Basal insulin rates
CSII allows for delivery of variable rates of basal
insulin infusion throughout the day
Does insulin pump therapy
eradicate the dawn
phenomenon?
Diabetes 2014;63:Supplement 1 A212-A343.
Diabetes 2014;63:Supplement 1 A212-A343.
Unpredictability
of the dawn
phenomenon
Roughly a 50%
chance of the
dawn
phenomenon
occurring on any
given night
No impact on frequency of the dawn
phenomenon (A) but increased hypoglycemia
(B) in dawn programmers vs non-programmers
*, P = 0.47 compared with dawn programmers. †, P = 0.001 compared with
dawn programmers
Conclusions
• The dawn phenomenon does not occur predictably
in patients with type 1 diabetes
• CSII programming for a fixed increase in early
morning insulin to counteract the dawn
phenomenon was associated with:
• No effect on the occurrence of the dawn phenomenon
• Increased rates of hypoglycemia
• The prevailing strategy for countering the dawn
phenomenon is not effective and may be
hazardous to the patient
FDA Approves Threshold
Suspend Feature
Mean
glucose
values in
1,438
threshold
suspend
events
Less nocturnal
hypoglycemia
(38% reduction)
with threshold
suspend feature
No increase in
hemoglobin
A1c
No difference in rare occurrence of
ketosis between control group and
threshold suspend users
Bionic Pancreas
• 5-day outpatient study in 20 adults and
32 adolescents with T1D
• Bionic pancreas vs conventional insulin
pump
• Adults: Percent
average of
glucose
time hypoglycemic
133 mg/dL 4.1%
(bionic) vs 7.3%
159 mg/dL
(pump);
(pump);
P=0.01
P<0.001
• Adolescents: Percent
average of
glucose
time hypoglycemic
138 mg/dL
(bionic)
6.1%
(bionic)
vs 157vsmg/dL
7.6% (pump);
(pump); P=0.004
P=0.23
(almost)
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
Type 1 diabetic patient
Islet cell transplantation
Immune recognition
of transplanted islet
cells requires
immunosuppression
Encapsulation of islet
cells in a PFTE device
shields them from
immune attack
(polytetrafluoroethylene)
• Human islet cells subcutaneously implanted
into rodents
• After 5 months:
– Stable islet cell mass
– Sufficient insulin secretion to ameliorate
experimental diabetes
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
• No difference in sustained viral response to
treatment in patients treated via ECHO model
vs those treated in UNM HCV clinic
• ECHO model is an effective way to treat HCV
infection in underserved communities
New Mexico
Counties with
Endocrinologists
Type 1 diabetes
referrals
Type 2 diabetes
referrals
Data derived from NM DOH, UNM Quality Dept
• Leona M. and Harry B. Helmsley Charitable Trust
• 3-year pilot program
• 8 Endo ECHO Centers of Excellence (COE) in New
Mexico
• Evaluation conducted by New York University
Endo ECHO: Specialist Panel
Pediatric
Endocrinologist
Adult
Endocrinologist
Nephrologist
Behavioral
Health
specialist
Social worker
Pharmacist
Community
Health Worker
RN/CDE/
nutritionist
Endo ECHO
Community
Partners
= Endo
ECHO COE’s
Evaluation (NYU)
• Utilization measures
– Hospitalizations
• Disease-specific outcomes
– HbA1c, BP, LDL
• Patient-specific outcomes
– Patient satisfaction, medication adherence, behavioral change
• Provider-specific outcomes
– Provider satisfaction, self-efficacy, knowledge
Diabetes Update
1. The “stats” revisited
2. Bariatric surgery – long-term effects on DM
3. Newer drugs for diabetes
4. Technology update
5. A “cure” for type 1 diabetes?
6. Endo ECHO: Meeting the needs of underserved
communities
Questions?