Diabetes Update

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Diabetes Update

• Matt Bouchonville, MD
• Endocrinology Division
• University of New Mexico
• ACP New Mexico Chapter Scientific Meeting
• November 7, 2014
• mbouchonville_at_salud.unm.edu

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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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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 2014311(17)1778. Increase in prevalence
  in youth between 2001 and 2009 of T1D (20) and
  T2D (30)

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Diabetes prevalence in the US leveling off?
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Lower rates of diabetes-related complications in
the US
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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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Surgery group gt6Xs more likely to be in
remission of T2D at 15 yrs
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Remission less likely with longer duration of
diabetes
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Surgery associated with gt50 reduction in
microvascular complications
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Surgery associated with 30 reduction in
macrovascular complications
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Impact of bariatric surgery on diabetes-related
complications attenuated by longer duration of
diabetes
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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

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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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SGLT2-inhibitors
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Similar A1c reduction (-0.52) by end of study
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Weight loss (-3.22 kg) vs gain (1.44 kg) with
SGLT2I versus SU treatment
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Less hypoglycemia with SGLT2I vs SU treatment
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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

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Inhaled insulin
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Afrezza (Technosphere insulin)
Technosphere insulin particles made up of
diketopiperazine derivatives and insulin, which
self-organize into a lattice array, and form
particles of 24 µm diameter.
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Rapid absorption of Technosphere insulin
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• Cough 30
• No clinically meaningful changes in PFTs
  (short-term)

Modest A1c reduction at 12 weeks
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Affrezza FDA Approval June 2014

• Prandial insulin in T1D or T2D
• Baseline PFTs required
• Post-market studies in progress
• Subjects with baseline lung disease
• Lung cancer risk?

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U-300 Insulin glargine (Lantus)
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Similar reduction in A1c compared to U-100
glargine
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Similar reduction in FPG compared to U-100
glargine
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Similar doses of basal and mealtime insulin
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Less nocturnal hypoglycemia with U-300 glargine
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Similar glycemic control and dosing with U-300
glargine insulin but less nocturnal hypoglycemia
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Insulin peglispro (LY2605541)
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PEG
(20 kDa)
Insulin
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Insulin peglispro (LY2605541)
Patent application US 12/481,111, 2009.
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Insulin peglispro (LY2605541)

• Compared to insulin glargine
• Less glycemic variability
• Less hypoglycemia
• No weight gain
• Preferential hepatic (vs peripheral action)

Diabetes Care 201437659-665.
Diabetes Care 2014372609-2615.
Diabetes 201463390-392.
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Glimins
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Imeglimin

• Targets mitochondria (oxidative phosphorylation
  blocker) decreased hepatic gluconeogenesis
• Increases skeletal muscle glucose uptake
• Enhanced insulin secretion in response to glucose

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A1c reduction of 0.7 compared to addition of
placebo
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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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Continuous subcutaneous insulin infusion (CSII)
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Basal insulin rates
CSII allows for delivery of variable rates of
basal insulin infusion throughout the day
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Does insulin pump therapy eradicate the dawn
phenomenon?
Diabetes 201463Supplement 1 A212-A343.
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Diabetes 201463Supplement 1 A212-A343.
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Unpredictability of the dawn phenomenon
Roughly a 50 chance of the dawn phenomenon
occurring on any given night
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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
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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

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FDA Approves Threshold Suspend Feature
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Mean glucose values in 1,438 threshold suspend
events
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Less nocturnal hypoglycemia (38 reduction) with
threshold suspend feature
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No increase in hemoglobin A1c
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No difference in rare occurrence of ketosis
between control group and threshold suspend users
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Bionic Pancreas
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• 5-day outpatient study in 20 adults and 32
  adolescents with T1D
• Bionic pancreas vs conventional insulin pump

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• Adults average glucose 133 mg/dL (bionic) vs 159
  mg/dL (pump) Plt0.001
• Adolescents average glucose 138 mg/dL (bionic)
  vs 157 mg/dL (pump) P0.004

• Adults Percent of time hypoglycemic 4.1
  (bionic) vs 7.3 (pump) P0.01
• Adolescents Percent of time hypoglycemic 6.1
  (bionic) vs 7.6 (pump) P0.23

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(almost)
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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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Type 1 diabetic patient
Islet cell transplantation
Y
Y
Immune recognition of transplanted islet cells
requires immunosuppression
Y
Encapsulation of islet cells in a PFTE device
shields them from immune attack (polytetrafluoroet
hylene)
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• Human islet cells subcutaneously implanted into
  rodents
• After 5 months
• Stable islet cell mass
• Sufficient insulin secretion to ameliorate
  experimental diabetes

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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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• 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

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New Mexico
Counties with Endocrinologists
Type 1 diabetes referrals
Type 2 diabetes referrals
Data derived from NM DOH, UNM Quality Dept
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• 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

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Endo ECHO Specialist Panel
Pediatric Endocrinologist
Nephrologist
Adult Endocrinologist
Behavioral Health specialist
Social worker
Pharmacist
Community Health Worker
RN/CDE/ nutritionist
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Endo ECHO Community Partners
Endo ECHO COEs
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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

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Diabetes Update

• The stats revisited
• Bariatric surgery long-term effects on DM
• Newer drugs for diabetes
• Technology update
• A cure for type 1 diabetes?
• Endo ECHO Meeting the needs of underserved
  communities

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Questions?