Download The Present and Future of Insulin Therapy in the Era of

The Present and Future of Insulin
Therapy in the Era of Pathophysiologic
Treatment of T2DM:
Marked Reduction of Insulin Use
Outline
• Value of Glycemic Control
• But do without Hypo Weight Gain
• Hypo topics
– In general, SU, Insulin
Lecture Based on Evidence -Based PRACTICE
EBM=Evidence
=
Based Medicine
Has Led to Students/MDs who don’t ThinkEg: if no evidence, continue doing same old dangerous
therapy (SU);
Specialists are abrogating their responsibility to evaluate
and lead in use of new medications, processes of care
+
EBM=Evidence
Based Medicine
Research Evidence
Randomized,
Prospective
Publication Trials
Critical Appraisal
+
Patient-Based
Experience
Clinical expertise
Expert Opinions
Guidelines
= Evidence
Based
Practice
Duggal, Evidence-Based Medicine in Practice,, Int’l j. Clinical Practice,65:639-644,2011
Allan D. Sniderman, MD; Kevin J. LaChapelle, MD; Nikodem A. Rachon, MA;
and Curt D. Furberg, MD, PhDMayo Clin Proc The Necessity for Clinical Reasoning in the
Era of Evidence-Based Medicine October 2013;88(10):1108-1114
Trisha Greenhalgh et al, Evidence based medicine: a movement in crisis? BMJ 2014; 348
Why Bother to Treat
Agressively?
There’s
Your
‘Market
EPIDEMIC
From: Trends in Prevalence and Control of Diabetes in the United States,
1988–1994 and 1999–2010Trends in Prevalence and Control of
Diabetes in the United States
Figure Legend:
Prevalence of total confirmed diabetes and obesity.
Data from U.S. adults aged ≥20 y in NHANES 1988–1994, 1999–2004, and 2005–2010. Total confirmed diabetes was defined as
diagnosed diabetes or undiagnosed diabetes with diagnostic levels of both hemoglobin A1c (≥6.5%) and fasting glucose (7.0 mmol/L
[≥126 mg/dL]). Obesity was defined as body mass index ≥30 kg/m 2; 601 persons were missing body mass index data. Prevalence
estimates for total confirmed diabetes and obesity were obtained using only the subsample of participants who attended the
morning fasting session (7385 participants for 1988–1994, 5680 participants for 1999–2004, and 6719 participants for 2005–2010).
The midpoint for obesity prevalence between 1988–1994 and 1999–2004 was calculated as the average of the prevalence of the 2
Ann Intern Med. 2014;160(8):517-525. doi:10.7326/M13-2411
periods. NHANES = National Health and Nutrition Examination Survey.
Date of download: 4/17/2014
One third of adults with diabetes
are undiagnosed
• ~10% of US adults have diabetes/~20
million persons in 2005
• Nearly one third don’t know they have
diabetes
• 26% of US adults have impaired fasting
Total:
35%
of
US
adults
with
diabetes
or
IFG
glucose (IFG)*
~73.3 million persons
*100–125 mg/dL
Cowie CC et al. Diabetes Care. 2006;29:1263-8.
NIDDK. National Diabetes Statistics. www.diabetes.niddk.nih.gov.
Considering the Epidemic of Metabolic Syndrome,
Prediabetes, Prevention Data, Undiagnosed Diabetes-
ER Office and Pre-Admission
IDENTIFICATION IS CRITICAL!
• Family history: whether parents or siblings have had
diabetes
• Obesity: especially with an increase in abdominal girth
• High-risk ethnic group: African Americans, Hispanics,
Native Americans, Asians, and Pacific Islanders
• Age: we’re looking at all ages, if patient seems at risk
• Impaired fasting glucose or impaired glucose tolerance
• Hypertension: blood pressure ≥ 140/90 mm Hg in adults
• High density lipoproteins < 35 mg/dL or triglyceride
levels ≥ 250 mg/dL
• Gestational diabetes or given birth to an infant
weighing > 9 pounds
• Pre-adm , pre-cath, pre-op , pre-CABG
FBS >100, ppg >140, POC HgA1c >6.0
Hyperglycemia Leads to Complications
Hyperglycemia
Spike
(variability
Continuous
) PPG BROWNLEE’s Unified Theory
A1C
Chronic
toxicity
Acute toxicity
Tissue lesion
Diabetic complications
Microvascular
Retinopathy
Macrovascular
NephropathyNeuropathy
PVD
MI
Stroke
Often Present at Diagnosis
American Diabetes Association. At: http://www.diabetes.org/diabetes-statistics/complications.jsp.
9
Brownlee M. Diabetes mellitus: theory and practice. Elsevier Science Publishing Co., Inc; 1990:279-291.
Ceriello A. Diabetes. 2005;54:1-7.
Trends in Age-Standardized Rates of Diabetes-Related
Complications among U.S. Adults with and without Diagnosed
Diabetes, 1990–2010.
Gregg EW et al. N Engl J Med 2014;370:1514-1523
Impact of Intensive Therapy in Type 2 Diabetes
Summary of Major Clinical Trials:
BUT Subset Evaluations Show Reduced CV Outcomes if shorter
duration of DM, without significant pre-existing complications
Initial Trial
Long Term Follow-up
Study
Microvascular
Macrovascular
Mortality
UGDP
↔
↔
↔
UKPDS
DCCT/EDIC*
ACCORD
ADVANCE
VADT
↓
↓
↓
↓
↓
↓
↔
↔
↔
↓
↓
↔
↔
↔
↔
↔
↓
↔
↑(unadj.), ↔ (adj.)
↔
↔
↑- likely due to hypoglycemia and weight
gain
Hypoglycemia Outcomes VADT, ACCORD, ADVANCE
Consequences of Hypoglycemia
• Prolonged QT- intervals– Can be of pronged duration
– Greater with higher catecholamine levels
Diabetologia 52:42,2009
IJCP Sup 129, 7/02
• Associated with Angina
Diabetes Care 26, 1485, 2003
Europace 10,860
/ Ischemic EKG changes
Porcellati, ADA2010
• Associated with Arrhythmias
• Associated with Sudden Death
• Increased Variabiltyincreases inflammation, ICU mortality
Endocrine Practice 16,¾ 2010
Hirsch ADA2010
CV Risk of SU and Insulin
So benefit of both
SU/Insulin in
research studies –UKPDS,
DCCT/EDIC
But adverse risk in ‘real
world’ usewould not pass current
FDA
guidelines for CV risk
with a new agent
Pharmacoepidemiology and Drug Safety. 2008;(17):753759.
Increased Mortality with SU
Endo 2012, abstract
Fits FDA criteria for
market withdrawal
DOI: 10.1177/1479164112465442
Diabetes and Vascular Disease Research published online 4 January 2013
Thomas Forst, Markolf Hanefeld, Stephan Jacob, Guido Moeser, Gero Schwenk, Andreas Pfützner and Axel Haupt
review and meta-analysis of observational studies
Acute coronary syndrome in
patients with diabetes mellitus:
perspectives of an interventional
cardiologist.
Sanon S, Patel R, Eshelbrenner C,
Sanon VP, Alhaddad M, Oliveros R,
Pham SV, Chilton R.
Am J Cardiol. 2012 Nov 6;110(9
Suppl):13B-23B
Complications CAN Be Reduced;
MUST Avoid Hypoglycemia, Weight Gain
1. DCCT/EDIC and UKPDS- decreased Micro, Macrovascular disease
2. Confusion with VADT, ADVANCE, ACCORD Trials
a. Older, longer duration DM, one third with CV disease
b. Decreased micro, no benefit CV reduction, ACCORD increased Mortality
c. we believe because undue hypoglycemia, weight gain
3. ADA says adjust HgA1c goal Higher if Older, longer duration DM, CV disease
4. I DISAGREE
5. We have 8 classes of drugs that have no undue risk hypoglycemia, weight gain
a. so I’m Older, longer duration DM, CV disease
-on 3 meds with no undue risk hypoglycemia, weight gain
b. my HgA1c 5.4 !!c. so I still aim for lowest without no undue risk hypoglycemia,
weight gain