Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA1
Smoldering Insulin Resistance: Strategies to Optimize
Cardiometabolic Health
Smoldering Insulin Resistance: Strategies to Optimize
Cardiometabolic Health
Thomas Dayspring, MD, FACP, FNLA, NCMP
Chief Academic OfficerTrue Health Diagnostics
Richmond, VA
Thomas Dayspring, MD, FACP, FNLA, NCMP
Chief Academic OfficerTrue Health Diagnostics
Richmond, VA
Disclosures (Last 12 months)
► Employment► True Health Diagnostics
► Lecture Bureau Sanofi Regeneron
As diabetes develops, we currently waste the first ∼10 years of the natural history
If we found prediabetes and early diabetes when they first presented and treated them more effectively, we
could prevent or delay the progression of hyperglycemia and the development of complications
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA2
► The earliest stage of type 2 diabetes is prediabetes(impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]), where glucose levels are higher than normal but not in the diabetes range
► Prediabetes tends to progress to diabetes, and over time, persistent hyperglycemia leads to the complications that are the major source of morbidity, mortality, and cost
► This natural history reflects underlying loss of β-cell function due in part to factors such as elevated glucose and lipid levels, inflammation, amyloid, and oxidative and endoplasmic reticulum stress
Natural History of Type 2 Diabetes
Philips LS et al. Diabetes Care 2014;37:2668–2676
► Unfortunately, we waste the first 10 years of the n atural history when the disorder is easiest to treat
► There are 79 million Americans with prediabetes and 7 million with early T2DM who are largely unrecognized because we do not screen to find these states of dysglycemia
► Moreover, when we do make the diagnosis, we do not treatin a way that lowers glucose levels to normal and as a consequence, the disease tends to progress, and patients need more and more medications
Natural History of Type 2 Diabetes
Philips LS et al. Diabetes Care 2014;37:2668–2676
Natural History of Type 2 Diabetes
Philips LS et al. Diabetes Care 2014;37:2668–2676
Prediabetes Diabetes Complications
Dev
elop
men
t of
Dia
bete
s,
Dia
bete
s C
ompl
icat
ions
Years
Prediabetes is glucose > normal but not as high as diabetes
Underlying loss of β-cell function and mass (apoptosis) due to high glucose and lipids, inflammation and oxidative and ER stress
Diagram illustrating the natural history of
diabetes from progression from
prediabetes to diabetes and development of
diabetes complications over time without
interventions
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA3
Natural History of Type 2 Diabetes
Diagram illustrating the natural history of diabetes
from progression from prediabetes to diabetes
and development of diabetes complications
with interventions such as lifestyle change or a
glucose-lowering medication that are
successful in decreasing progression from
prediabetes to diabetes, but then are stopped
Philips LS et al. Diabetes Care 2014;37:2668–2676
Prediabetes Diabetes Complications
Dev
elop
men
t of
Dia
bete
s,
Dia
bete
s C
ompl
icat
ions
Start
Prediabetes is glucose > normal but not as high as diabetes
↓ progression with interventions that ↓ glucose
Benefit persists after treatments stop
“Legacy effect”
Stop
Rx, diet, exercise
Natural History of Type 2 Diabetes
Diagram illustrating the natural history of diabetes
from progression from prediabetes to diabetes and
development of diabetes complications over time
with interventions that are titrated to keep glucose
and A1C levels in the normal range and are not
stopped
Philips LS et al. Diabetes Care 2014;37:2668–2676
Prediabetes Diabetes Complications
Dev
elop
men
t of
Dia
bete
s,
Dia
bete
s C
ompl
icat
ions
Start
Prediabetes is glucose > normal but not as high as diabetes
Obtain benefit for years
Don’t stop Continue
↓ progression and ↓ complications by ↓glucose
Systematic treatment
Rx, diet, exercise, Rx - ? More Rx
Natural History of Type 2 Diabetes
Cumulative diabetes incidence
in the DREAMstudy, where subjects with
prediabetes were given rosiglitazone
or placebo, including time
points before and after the primary
study was stopped
Philips LS et al. Diabetes Care 2014;37:2668–2676
Study ended, drug stopped
Benefit sustained
Control Rosiglitazone
Cum
ulat
ive
Dia
bete
s In
cide
nce
0.8
0.6
0.4
0.2
0.00 1 2 3 4 5 6
Years
DREAM = Diabetes Reduction Assessment With Ramipril and R osiglitazone Medication
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA4
Natural History of Type 2 Diabetes
Cumulative incidence of severe diabetic retinopathy
in the Da Qing IGT & Diabetes study,
showing subjects with prediabetes
who were randomized to
receive instruction in diet/exercise or to be
control subjects, including time points before and after the primary study was
stopped
Philips LS et al. Diabetes Care 2014;37:2668–2676
Control Diet + exercise
Inci
dent
sev
ere
retin
opat
hy (
%)
18
16
12
2
42Follow Up (Years)
14
10Study ended
Benefit sustained8
6
4
00 181612 141086 20
► In the Diabetes Prevention Project subject population, achieving normal glucose levels appeared to be particularly beneficial
► Among subjects who had not developed diabetes at the end of the primary study, those who achieved normal fasting and 2-h oral glucose tolerance test (OGTT) glucose levels at least once during the average 3.2 years of the primary study had a 56% decrease in development of diabetes during follow-up after the primary study ended
► It did not matter how normal glucose was achieved, as the reduction in the tendency to develop diabetes was comparable among subjects in the lifestyle change, metformin, and control groups who achieved normal glucose levels at least once
Natural History of Type 2 Diabetes
Philips LS et al. Diabetes Care 2014;37:2668–2676
Natural History of Type 2 Diabetes
Cumulative diabetes incidence
in the U.S. Diabetes
Prevention Project study, showing subjects with
prediabetes who were given
troglitazone or placebo, including time points before
and after the primary study was
stopped
Philips LS et al. Diabetes Care 2014;37:2668–2676
Control Troglitazone
Cum
ulat
ive
Dia
bete
s In
cide
nce
(%) 40
Years since randomization
- Drug stopped at 0.9 years -Study ended
(for these subjects)
Benefit sustained
02.0 3.0 4.01.00.0
30
20
10
0
During 0.9 years of treatment with
troglitazone, the diabetes incidence
rate was 3.0 cases/100 person-years, considerably
lower than the rate of 12.0 cases/100
person years with placebo
However, during the 3 years after
troglitazone was stopped, the diabetes incidence was virtually identical to that of the placebo group without evidence of “catch-up”
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA5
► As the natural history of diabetes – the tendency for the disease to get worse and for complications to develop –reflects underlying loss of β-cell function, which is due in part to glucotoxicity, treatment that normalizes glucose levels should help preserve β-cell function
► Indeed studies have shown that attaining normal glucose levels was predicted somewhat more strongly by better β-cell function than by better insulin sensitivity, although both were statistically significant
Natural History of Type 2 Diabetes
Philips LS et al. Diabetes Care 2014;37:2668–2676
Changing the Natural History of Diabetes How Medical Practice Should Change
Philips LS et al. Diabetes Care 2014;37:2668–2676
► Screening to identify early diabetes and prediabetes should become routine
► Oral glucose tolerance tests - most sensitive, least convenient
► Fasting plasma glucose - lowest cost, intermediate sensitivity and convenience
► A1C - most convenient, least sensitive
► Patients who are at high risk and have health prospects justifying improved glucose control should have management aimed to keep glucose levels as close to normal as possible without causing hypoglycemia
► Begin with lifestyle change
Changing the Natural History of Diabetes How Medical Practice Should Change
Philips LS et al. Diabetes Care 2014;37:2668–2676
► Include medications if appropriate
► Begin with metformin for patients with diabetes
► Consider metformin for patients with prediabetes if there is:
► IFG and
► IGT and
► At least one risk factor for progression to diabetes (age < 60 years, BMI ≥ 35 kg/m2, a family history of diabetes, elevated triglycerides, reduced HDL-cholesterol, hypertension, or A1C > 6.0%)
► Other medications that may be appropriate (DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 analogs, α-glucosidase inhibitors, and possibly basal insulin and thiazolidinediones)
No FDA Indications
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA6
Changing the Natural History of Diabetes Stepped Care Strategy
Philips LS et al. Diabetes Care 2014;37:2668–2676
► Insulin is typically added relatively late in the natural history
► Use of home glucose monitoring to guide management varies and often is not initiated until patients are treated with insulin relatively late in the natural history
► All patients with prediabetes and early diabetes should have management of cardiovascular risk factors, use of aspirin (if appropriate), screening for eye and renal complications, and education in medical nutrition management
We believe we are at a time when we can change the natural history of type 2 diabetes
Doing so should benefit the health of millions of patients and might also benefit health care systems, by reducing
resource use and costs
CONCLUSIONS
► The prevalence of diabetes is increasing in all industrialized countries and its prevention has become a public health priority, however, the predictors of diabetes risk are insufficiently understood
► We identified novel biomarkers that were associated with the risk of clinically incident diabetes over and above the classic risk factors
► This gives new insights into the pathogenesis of diabetes and may help with targeting prevention and treatment
PLOS one 2014 5(4): e10100
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA7
► A score consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin almost doubled the relative risk of diabetes in the validation cohort (HR per one standard deviation increase 1.88, p = 2.8 e-5)
► It also improved discrimination of the model (IDI = 0.0149, p < 0.0001) and reclassification of diabetes risk [Net reclassification Index (NRI) = 11.8%, p = 0.006]
► Gender-specific analyses suggested that the best score differed between men and women
► Among men, the best results were obtained with the score of four biomarkers: adiponectin, apolipoprotein B, ferritin and interleukin-1 receptor antagonist, which gave an NRI of 25.4% (p<0.0001)
► Among women, the best score included adiponectin, apolipoprotein B, C-reactive protein and insulin which gave an NRI of 13.6% (p = 0.041)
Salomaa V et al. PLOS one 2014 5(4): e10100
Biomarker Testing for Clinically Incident Diabetes
Salomaa V et al. PLOS one 5(4): e10100
Biomarker Testing for Clinically Incident Diabetes
► The biomarker score, composed as a linear combination of four biomarkers, was associated with doubling of the relative hazard of diabetes in the independent validation cohort
► The prediction of absolute risk of diabetes produced a significantly improved net reclassification and discrimination, especially in gender-specific analyses, with the model including the biomarker score
► This information may help with identifying individuals at high risk of developing diabetes
Progression of Insulin Resistance
Fasting Glucose & HbA1c
Fasting
Insulin
Lipoprotein
Abnormalities
Beta-Cell Function
TIME
(months to decades)
Prediabetes
FG = 100-125Diabetes
FG > 125 (mg/dL)
Beta-Cell Failure
Beta-Cell Strain Beta-Cell Dysfunction
Insulin
Resistance
↑LDL-P (apoB)↑ small LDL-P↑ sdLDL-C
↑Large VLDL-P↓ HDL-P↓HDL2-C
Bergenstal R et al. Diabetes Endocrinol 2005;7(2)
Lipoproteins in Diabetes Mellitus Jenkins, Toth, Ly ons. Humana Press 2014
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA8
Lipoprotein Dynamics in Insulin Resistant States
TG-rich VLDL
(CETP)
Large LDL
Large HDL
TG
(CETP)
TG
CE
CE
TG-enriched Cholesterol-depleted
particles
TG-depleted, cholesterol-rich
VLDL
Lipoprotein Lipase
Smaller cholesterol-rich VLDL remnants
Triglyceride Cholesteryl ester
There is now less cholesterol per LDL & HDL
particle than previously
LDL-C & HDL-C
VLDL-C
apoB
apoCII
apoE
Apo A-V
Dayspring T. Chapter 4 Lipoproteins in Diabetes Mellitus Jenkins, Toth, Lyons. Humana Press 2014
TG-rich VLDL
(CETP)
Large TG-rich LDL
Large HDL
TG
Small LDL
Hepatic Lipase(CETP)
TG
CE
CE
TG-enriched Cholesterol-depleted
particlesLipoprotein Lipase
Smaller cholesterol-rich VLDL remnants
~ LDL-C, ↑ sdLDL-C
Small & total LDL-P
Lipoprotein Dynamics in Insulin Resistant States
Triglyceride Cholesteryl esterDayspring T. Chapter 4 Lipoproteins in Diabetes Mellitus Jenkins, Toth, Lyons. Humana Press 2014
TG-rich VLDL
(CETP)
Large TG-rich LDL
Smaller HDL
Large TG-rich HDL
TG
Small LDL
Hepatic Lipase
Hepatic Lipase
(CETP)
TG
CE
CE
Lipoprotein Lipase
Smaller cholesterol-rich VLDL remnants
HDL-C
HDL2-C
HDL-P
ApoA-I
Triglyceride Cholesteryl ester
Lipoprotein Dynamics in Insulin Resistant States
Free apoA-I
Renal catabolism of apoA-I
TG-enriched cholesterol-depleted
HDL particles
Dayspring T. Chapter 4 Lipoproteins in Diabetes Mellitus Jenkins, Toth, Lyons. Humana Press 2014
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA9
► Insulin resistance leads to hepatic VLDL overproduc tion► Elevated TG, VLDL-C, non-HDL-C, VLDL-TG ► Elevated VLDL-P and large VLDL-P► Increased VLDL size► Increased remnants and remnant-cholesterol► Increased apoC-III
► Abnormal Remodeling of apoB particles►Variable LDL-C► Increased small and total LDL-P► Increased sd-LDL-C► Increased LDL-TG
► Abnormal remodeling of apoA-I particles►Low HDL-C►Decreased large and total HDL-P►Decreased HDL2-C
Lipoprotein Biomarkers: Insulin Resistance25
Dayspring T. Chapter 4 Lipoproteins in Diabetes Me llitus Jenkins, Toth, Lyons. Humana Press 2014
Incident Diabetes Biomarkers
Insulin Resistance
Pancreatic Beta-Cell DysfunctionInitial hyperinsulinemia
Later hypoinsulinemia
Hyperglycemia Dyslipidemia
Alpha-
hydroxybutyrateOleic Acid
Linoleoyl-
glycerophosphocholine
Ferritin
Proinsulin: C-peptide Ratio
C-peptide InsulinProinsulin
LeptinAdiponectin Leptin/BMI
Glucose HbA1c Fructosamine
1,5-Anhydroglucitol
Trigs HDL-C
LDL-PApo B
HDL-P
Proinsulin
Proinsulin
C-Peptide and
Insulin
Incident Diabetes and Beta-Cell Function
Enzymes cleave proinsulin into
With increasing demand for insulin (insulin resistance),
cleavage capacity becomes exhausted, resulting in
increased levels of proinsulin
Pre-Insulin
Proinsulin
Insulin
A-chain C-Peptide B-chain
A-chain
B-chainC-Peptide
Mature insulin 51 amino acids
An elevated
proinsulin/C-peptide
ratio is a marker related
to beta-cell strain*
inactive insulin precursor
(110 amino acids)
70 amino acids
*Diabetologica 2011;54(12):3047-54 Holt R. Essential Endocrinology & Diabetes 6 th Ed 2012 Swiley Blackwell
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA10
Biomarker testing 19 blood-based biomarkers and derived factors organized into three functional categories:
(1) glycemic control, (2) insulin resistance, and (3) pancreatic beta cell function can identify IR early, inform
treatment, and improve glycemic control in a enable andhigh proportion of patients
Biomarker Testing for Prediabetes
Evidence of insulin resistance and beta cell dysfunction in the normoglycemic patients is prevalent and heterogeneous
Of those patients classified as normoglycemic (glucose < 100 mg/dL and HbA1c <5.7, n=929), 82% demonstrated at least one high range biomarker of insulin resistance or beta cell function
Proportion of normoglycemic patients demonstrating high range values of each biomarker
40
30
20
10
0
J Cardiovasc Trans Res 2014;7(6):597-606
Biomarker Associated with Prediabetes
Varvel SA et al. J Cardiovasc Trans Res 2014;7(6):597 -606
Distribution of the total number of high range biomarker values observed
in normoglycemic patients
20
15
10
5
00 1 2 3 4 5 6 7 8 9 10 11 12 13
Number of IR and beta cell biomarkers in high range per patient
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA11
Urinary Microalbumin and hs-CRP in Predicting T2DM O nset
Brantsma AH, et al. Diabetes Care 28:2525–2530, 2005
Prevention of REnal and Vascular ENd Stage
Disease (PREVEND)
> 3
1-3
< 3< 1515-30
> 30
0
2
5
6
8
10
Inci
denc
e of
T2D
M (
%)
UAE (mg/24/hr)
CRP (mg/24/hr)
Incidence of T2DM after 4.2 years of follow
up by category of Urinary Albumin
Excretion (UAE) and CRP at baseline
LIFESTYLE THERAPY RISK STRATIFICATION FOR DIABETES COMPLICATIONS
1993
ACEEndocrinology
• Maintain optimal weight
• Calorie restriction
• Plant-based diet: high polyunsaturated and monounsaturated fatty acids
• Avoid trans fatty acids; limit saturated fatty acids
• 150 min/week moderate exertion (eg. walking, stair climbing)
• Strength training
• Increase as tolerated
• About 7 hours per night
• Community engagement
• Screen for mood disorders
• No tobacco products
Nutrition
Physical Activity
Sleep
Behavioral Support
Smoking Cessation
+
+
+
+
+
+
• Structured counseling
• Meal replacement
• Structured program
• Medical evaluation/ clearance
• Medical supervision
• Screen for sleep apnea
• Refer to mental healthcare professional
• Behavioral therapy
• Structured programs
INTENSITY STRATIFIED BY BURDEN OF DISEASE AND RELATED COMPLICATIONS
Endocrine Practice 2016;22(1):103-113
1993
ACEEndocrinology
PREDIABETES ALGORITHMIFG (100-125) IGT (140-199) METABOLIC SYNDRO ME (NCEP 2001)
TREAT ASCVD RISK FACTORS
LIFESTYLE THERAPY(including Medically Assisted Weight Loss)
WEIGHT LOSS THERAPIES
ANTIHYPERGLYCEMIC THERAPIESFPG > 100 2 Hour PG > 140
1 PRE-DM CRITERION
MULTIPLE PRE-DM CRITERIA
If glycemia not normalized
GLP-1 RA
TZD
PROCEED TO HYPOGLYCEMIA
ALGORITHM
DYSLIPIDEMIA ROUTE
HYPERTENSION ROUTE
CVD RISK FACTOR MODIFICATIONS ALGORITHM
NORMAL GLYCEMIA
PROGRESSION
OVERT DIABETES
LEGEND
Orlistat, lorcaserin, phentermine/topiramate ER, naltrexone/bupropion, liraglutide 3 mg, or bariatric surgery as indicated for obesity treatment
Intensify Weight Loss
Therapies
Low-risk Medications
Consider with Caution
Metformin
Acarbose
Endocrine Practice 2016;22(1):103-113
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA12
GLYCEMIC CONTROL ALGORITHM 1993
ACEEndocrinology
LIFESTYLE THERAPY (including Medically Assisted Weight Loss)
Entry A1c < 7.5% Entry A1c ≥ 7.5% Entry A1c ≥ 9.0%
Dual Therapy
NO
ADD OR INTENSIFY INSULLIN
MONOTHERAPY*DUAL THERAPY*
TRIPLE THERAPY*
√
√
√
√
√
√
METor other 1st-line agent
METor other 1st-line agent + 2nd-line agent
GLP-1 RA
DPP4i
SGLT-2i
Colesevelam
Bromocriptine QR
TZD
Basal Insulin
SU/GLN
AGi
If not at goal in 3 months proceed
to or intensify insulin therapy
If not at goal in 3 months proceed
to or intensify triple therapy
If not at goal in 3 months proceed to or
intensify double therapy
Bromocriptine QR
SYMPTOMS
Triple Therapy
YES
OR
Insulin ±
Other Agents
Refer to Insulin Algorithm
√Few adverse events and/or possible benefits
Use with caution
LEGEND
√ GLP-1 RA
√
√
√
√
√
Basal Insulin
Colesevelam
AGi
SU/GLN
TZD
SGLT-2i
DPP-4i
GLP-1 RA
SU/GLND
SGLT-2i
DPP-4i
AGi√
√
√
√
√ Metformin
!TZD
* Order of medications listed represents a suggested hierarchy of usage: length of line reflects strength of recommendation
PROGRESSION OF DISEASE
!
!
!
!
!
!
!
!
Endocrine Practice 2016;22(1):103-113
1993
ACEEndocrinology
ASCVD RISK FACTOR MODIFICATIONS ALGORITHM
DYSLIPIDEMIA HYPERTENSION
Lifestyle Therapy (Including Medically Assisted Weight Loss)
STATIN THERAPY If TG > 500 mg/dL, fibrates, omega 3 ethyl esters, niacin
ACEior
ARB
For initial blood pressure > 150/100 mm Hg: DUAL THERAPY
Try alternate statin, lower statin dose or frequency, or add non-statin LDL-C lowering therapies
Repeat lipid panel; assess adequacy, tolerance of therapy
LIPID PANEL; Assess ASCVD Risk
HIGHRISK LEVELS
√
+Thiazide
Calcium Channel Blockerβ-blocker
ACEior
ARB
If not at goal (2-3 months)
If not at goal (2-3 months)
If statin-intolerant
Add calcium channel blocker , β-blocker or or thiazide diuretic
Add next agent from above group, repeat
Additional choices (α-blockers, central agents, vasodilators,
aldosterone antagonists)
Achievement of target blood pressure is critical
If not at goal (2-3 months)
GOAL: SYSTOLIC ~ 130, DIASTOLIC ~ 80 mm Hg
DESIRABLE LEVELS DESIRABLE LEVELS
LDL-C (mg/dL)Non-HL-C (mg/dL)TG (mg/dL)
TC/HDL-C (mg/dL)
ApoB(mg/dL)
LDL-P (nmol/L)
< 100
< 130< 150< 3.5
< 90
< 1200
< 70< 100< 150< 3.0< 80
< 1000
Intensify lifestyle therapy (weight loss, physical activity, dietary changes) and glycemic control; consider additional therapy
IF NOT AT DESIRABLE LEVELS
TO LOWER LDL-C:
TO LOWER Non-HDL-C, TG:
TO LOWER ApoB, LDL-P:
Intensify statin, add ezetimibe, PCSK9i, &/or colesevelam or niacin Intensify statin and/or add Rx-grade OM3 fatty acid, fibrate and/or niacin Intensify statin and/or add ezetimibe, PCSK9i, colesevelam and/or niacin
Assess adequacy & tolerance of therapy with focused laboratory evaluations and patient follow-up
* EVEN MORE INTENSIVE THERAPY MIGHT BE WARRANTED
√
√
Intensify therapies to attain goals according to risk levels
VERY HIGHDM but no other major risk and/or age <40
DM + major CVD risk(s) (HTN, Fam Hx, low HDL-C, smoking) or ASCVD*
* EVEN MORE INTENSIVE THERAPY MIGHT BE WARRANTED ** FAMILIAL HYPERCHOLESTEROLEMIA
Endocrine Practice 2016;22(1):103-113
http://www.medpagetoday.com/Cardiology/Prevention/6 2307 accessed 1/26/2017
► Liraglutide (LEADER) and empagliflozin (EMPA-REG) and the novel drug semaglutide (SUSTAIN) reduced CV events
► Bernard Zinman: “who ever thought we'd have a diabetes therapy that reduces cardiovascular death?”
► Christopher Cannon: "that new diabetes mellitus drugs can actually improve cardiovascular outcomes" the top advance of 2016 in cardiology”
► The cardiology, unlike the endocrine community has rapidly embraced the idea of using diabetes drugs for cardiovascular risk reduction
► Steve Nissen: Greater involvement by cardiologists is essential to translating the benefits observed in clinical trials to the care of individual patients.
Cholesterol Synthesis and Absorption Markers
Thomas Dayspring MD, FACP, FNLA13
Summary Slide
Glycemic indices are the main target goal of insulin resistance therapy
Other biomarkers can be used to assess insulin resistance before glycemic abnormalities appear
Several lipid/lipoprotein biomarkers associate with IR
There is a beneficial legacy effect even with short term treatments
AACE guidelines stress lifestyle and pharmacologic algorithms to control weight, glycemia, dyslipidemia and hypertension