Diabetes Update 2017 · Diabetes Update—2017 Timothy C. Evans, MD PhD FACP Department of Medicine...
Transcript of Diabetes Update 2017 · Diabetes Update—2017 Timothy C. Evans, MD PhD FACP Department of Medicine...
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Diabetes Update—2017
Timothy C. Evans, MD PhD FACP
Department of Medicine
and MEDEX Northwest
University of Washington
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NCCPA Disclaimer
• I am on the Board of Directors (BOD) of NCCPA.
• The BOD is involved with strategic direction and policy.
• The BOD does not develop or review the exams.
• I have never taken nor seen the PANCE, PANRE, or
individual test items.
• In this lecture I am not speaking on behalf of the
NCCPA, nor with any knowledge of specific exam test
items.
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Topics
• Diagnosis/Standards of Care
• Diabetic Foot Evaluation
• Rx including New Drugs
• A Word About Thiazolidinediones
• What Should the Glucose Goal Be?
• Metabolic Syndrome and DM prevention
• What’s Next?
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Types of Diabetes
• Type 1—Autoimmune, insulin deficient, DKA
prone
• Type 2—Familial, insulin resistance and
abnormal insulin secretion
• Gestational
• Other—Drug induced, endocrinopathies,
genetic
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Diagnostic Criteria
• FPG ≥ 126 mg/dL
• Random PG ≥ 200 mg/dL in a patient with Sx of
hyperglycemia
• 2-hr PPG ≥ 200 mg/dL during OGTT
• ADA Rec: Screen high risk pts q 3 yrs
• HbA1c (2010, became an official diagnostic criterion)
– Prediabetes, 5.7–6.4%
– Diabetes, 6.5% or greater
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Who to Screen
• BMI > 25 kg/m2 (> 23 kg/m2 Asian Amer) and:
– Phys inact; +1st deg rel with DM; Hx GDM; HBP;
HDL < 35 mg/dL and/or TG > 250 mg/dL; women
with PCOS; HbA1c > 5.7%, IGT, IFG; cond assoc
with ins resist (severe obesity, acanthosis nigricans);
Hx CVD.
– Start at age 45 yrs
– Repeat q3yrs, more freq for pre-DM or other risks
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Standards of Care
• Diabetes Care (journal) Supplement, each
January
• Accessible at www.diabetes.org
• SoC 2016, Abridged for Primary Care
Providers at:
• http://clinical.diabetesjournals.org/site/misc/
2016Abridged-SOC.pdf
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Normal Goal
Additional
Action
Suggested
Whole blood values
Average preprandial glucose (mg/dl) <100 80–130 <80 or >140
Average bedtime glucose (mg/dl) <110 100–140 <100 or >160
Plasma values
Average preprandial glucose (mg/dl) <110 90–130 <90 or >150
Average bedtime glucose (mg/dl) <120 110–150 <110 or >180
HbA1c (%) <6 <7 >8
Standards of Care Glycemic Control
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Standards of Care Weight and Diet
• Diet: 50+% calories from carbohydrate,
< 30% calories from fat (mostly
monounsaturated, < 7% sat, < 200 mg chol, min
trans FA), 15-20% from protein (0.8 g/kg)
• Weight control for overwt or obese: 500–1000
kcal/d deficit. Inc insulin sensitivity in type 2.
• Bariatric surgery consider in BMI > 35kg/m2
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Standards of Care Exercise
• Attention to micro and macrovascular dis
• Gradual increase
• ETT if ≥ 10% 10-yr cardiac event risk
• 150+ min/wk mod ex (50–70 % max ht rt)
• Or 90+ min/wk vigorous aerobic ex (> 70% max ht rt)
• Spread over at least 3 d/wk, no more than 2 consecutive days of inactivity
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Prevention of Complications Hypertension
• Goal < 140/90 (lower?, JNC 8)
• Regimen should include ACEI or ARB,
esp if also nephropathy
• Add CCB, thiazide, others
• Lifestyle—smoking cessation, diet
(DASH, mod EtOH, sodium < 2.4 g/d),
physical activity (mod-vig 3-4 days/wk,
40 min/session)
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Prevention of Complications Dyslipidemia—ATP 4
• Four statin benefit groups
– Clinical ASCVD
– LDL > 190 mg/dL
– DM, 40-75 yrs, LDL 70-189 mg/dL
– 40-75 yrs, LDL 70-189 mg/dL, 10-yr risk 7.5%
or higher, no DM or ASCVD
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New Risk Calculator
• 10-yr risk for ages 40-75 years
• Similar risk factors to Framingham
– Sex, age, race, total cholesterol, HDL-
cholesterol, systolic BP, Rx for HBP, diabetes,
smoking
• Diabetes not an automatic ASCVD risk
equivalent
• http://clincalc.com/Cardiology/ASCVD/Poo
ledCohort.aspx
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Statin Intensity
• High—lowers LDL by > 50%
– atorv 40-80 mg, rosuv 20-40 mg
• Moderate—lowers LDL by 30 to < 50%
– atorv 10-20, rosuv 5-10, simva 20-40, similar
moderate doses for the other statins
• Low—lowers LDL by < 30%
– simva 10 mg, similar low doses other statins,
no atorv or rosuv
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ASCVD Risk
• 50 y/o, Tchol 250 mg/dL, HDL 38 mg/dL,
SysBP 145 mmHg, HTN Rx yes, smoker no
• DM no, 10-yr ASCVD risk 9.1%
• DM yes, 10-yr ASCVD risk 16.8%
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ASCVD Risk
• 50 y/o, Tchol 200 mg/dL, HDL 38 mg/dL,
SysBP 145 mmHg, HTN Rx yes, smoker no
• DM no, 10-yr ASCVD risk 6.7%
• DM yes, 10-yr ASCVD risk 12.5%
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ASCVD Risk
• 50 y/o, Tchol 200 mg/dL, HDL 40 mg/dL,
SysBP 125 mmHg, HTN Rx no, smoker no
• DM no, 10-yr ASCVD risk 4.2%
• DM yes, 10-yr ASCVD risk 7.9%
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Prevention of Complications Smoking Cessation & ASA Use
• Smoking—quit all tobacco products
• 1/4–1/2 ASA for 2º CVD prevention
• Use for 1º prevention in:
– > 50 y/o with other RF (+ FH, HBP, smoking,
dyslipidemia, albuminuria), or
– Pts with 10-yr CHD risk ≥ 10%
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Prevention of Complications Retinopathy
• Dilated exam by specialist
– Type 1 within 3-5 yrs of Dx
– Type 2 at Dx
– Before, during, and after pregnancy for
preexisting DM
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Mohamed, Q. et al. JAMA 2007;298:902-916.
Nonproliferative and Proliferative Diabetic Retinopathy
A: Moderate nonproliferative diabetic
retinopathy with microaneurysms,
retinal hemorrhages, and macular
edema characterized by increased
vascular permeability and deposition
of hard exudates at the central retina.
B: Proliferative diabetic
retinopathy with new vessels and
fibrous tractional bands arising
from the optic disc.
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Prevention of Complications Nephropathy
• Annual microalbuminuria and eGFR
– Type 1 after 5 years
– Type 2 at Dx
• Rx micro or macroalbuminuria
– ACEI or ARB
– Dietary protein, 0.8 mg/kg (~ 10% daily cal)
• Control BP also with ACEI, ARB, diuretics, CCB
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Prevention of Complications Neuropathy
• At Dx in type 2, after 5 yrs in type 1
• Foot exam
• Autonomic screening—hypoglycemic
unawareness, resting tachycardia, exercise
intolerance, orthostatic hypotension,
constipation, gastroparesis, erectile dysfunct
• Pain can be treated with pregabalin,
duloxetine, and tapentadol. For more severe:
amitriptyline, venlafaxine, gabapentin, opioids.
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Prevention of Complications Foot Care
• Exam — 10-gram monofilament;
vascularization; vibration; proprioception;
palpation; visual exam for callus, skin
atrophy or ulceration, infection, nail care,
hair distribution, deformity
• Pt education, glycemic control, D/C
smoking, orthotics
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Likelihood of Osteomyelitis
• Visible bone or ability to probe to bone
• Ulcer > 2 x 2 cm
• Ulcer duration > 1–2 wks
• ESR > 70 mm/hr
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The Primary Cause of Amputations
• Shoes and socks at clinic visits
• The time to take them off
• You can save limbs if you look at feet.
• Efficiency—Get the shoes and socks off before
you come into the room
– Train your patients
– Instruct the office staff
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Treatment—Insulin
• Type 1 DM—Multiple daily injections of
insulin, basal and prandial, with
individualization, multiple SMBG
• Type 2 DM—for very high blood sugars, as
augmentation for oral agents, basal or
multiple duration insulin. Individualize.
Insulin should be used more often than it is.
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Insulin
Preparations
Onset of Action Peak Action Duration of
Action
Lispro/Aspart 5–15 minutes 1–2 hours 4–6 hours
Human Regular 30–60 minutes 2–4 hours 6–10 hours
Human NPH 1–2 hours 4–8 hours 10–20 hours
Glargine/Detemir 1–2 hours Flat ~24 hours
Insulin preparations
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Treatment—Drugs
Oral Agents (type 2 DM):
• Insulin secretagogues
– Sulfonylureas
– Meglitinides
• Insulin sensitizers
– Metformin
– Thiazolidinediones
• Polysaccharide digestion inhibitors—alpha-glucosidase inhibitors
• Dipeptidyl peptidase IV (DPP-IV) inhibitors
• Sodium-glucose transporter 2 (SGLT 2) inhib
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Expected HbA1c Decrease
• TLC 1-2%
• Metformin 1-2% (slow)
• Sulfonylureas 1-2% (fast)
• Insulins 1.5-3.5% (fastest)
• TZDs 0.5-1.4% (slowest)
• GLP-1 agonists 0.5-0.8%
• α-glucosidase inhibs 0.5-0.8%
• DPP-IV inhibs 0.5-0.8%
• SLGT-2 inhibs 1%
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The Incretin Effect
• More rapid disposal of glucose load when
given by mouth than IV
• Greater insulin effect
• Glucagon inhibition
• Delayed gastric emptying
• Due to GI signaling and release of GI
hormones
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GI Hormones
and an Enzyme Inhibitor
• Glucagon-like peptide 1 (GLP-1),
injectable, nausea
– exenatide, ER-exenatide, liraglutide
• Amylin (↓ gastric emptying, ↑ satiety),
injectable, nausea
– pramlintide
• Dipeptidyl peptidase IV (DPP-IV, rapidly
degrades GLP-1 and GIP) inhibitors, oral
– sitagliptin, saxagliptin, linagliptin, alogliptin
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Na-Glucose Transporter Inhibitors
• SGLT-2 in proximal renal tubule
• Canagliflozin
• Accounts for 90% glucose reabsorption
• Decrease HbA1c by ~1%, BW and SBP
• Yeast vaginitis, UTI, polyuria, occas
hypoglycemia
• Contraindications—type 1 DM, severe renal
insufficiency
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Thiazolidinediones
• Cardiac Effects
• Bones
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Pioglitazone
• Pioglitazone meta-analysis
– 19 trials; 16,390 patients
– Decreased death, MI, CVA; HR 0.82 (0.72–0.94)
– Increased CHF; HR 1.41 (1.14–1.76)
– No change CHF mortality
• Prescribing information includes black box warning about CHF
JAMA. 2007;298:1180-88.
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Rosiglitazone
• Rosiglitazone meta-analysis
– 4 RCTs; 14,391 patients
– Increased MI; HR 1.42 (1.06-1.91)
– CHF; HR 2.09 (1.52-2.88)
– No change cardiac mortality; HR 0.90 (0.63-1.26)
• Prescribing information includes black box warning about CHF and myocardial ischemia
JAMA. 2007;298:1189-95.
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More Rosiglitazone
• Meta-analysis
– 42 trials
– Mean age 56 years
– Baseline HbA1c 8.2%
• MI odds ratio 1.43 (95% CI, 1.03-1.98,
P=0.03)
• CV death odds ratio 1.64 (95% CI, 0.98-
2.74, P=0.06) NEJM. 2007;356:2457-2471.
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Rosiglitazone vs Pioglitazone
• 227,571 Medicare patients, mean age 74.4 yrs
– Rosiglitazone or Pioglitazone for 3 years
• Acute MI, CVA, CHF, all-cause mortality,
composite of all
• 8667 endpoints, Rosi > Pio for CVA, CHF, death
• Composite risk 1.68 (95% CI, 1.27-2.08)
• NNH 60 Rx’d for 1 year
JAMA. 2010;304:411-418.
JAMA. 2010;304:469-471.
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Thiazolidinediones and Bones
• Risk of peripheral fractures
• Both pioglitazone and rosiglitazone
• FDA warnings in prescribing information
JAMA. 2007;297:1645.
Drug Saf. 2009;32:539-547.
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Thiazolidinediones
For Now
• Avoid in NYHA Class III and IV CHF
• Use with caution in Class I and II
• Prudent to avoid rosiglitazone in patients at significant risk of ischemic ht disease and instead consider metformin, SUs, or insulin
• Consider fracture risk
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How Low Should the Glucose Be?
• DCCT, UKPDS, and long-term benefits
• Steno-2 and long-term followup
• ACCORD—NEJM. 2008;358:2545-2559.
• ADVANCE—NEJM. 2008;358:2560-2572.
• VADT—NEJM. 2009;360:129-139.
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DCCT—Type 1 DM
NEJM. 1993;329:977–986.
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Epidemiology of Diabetes Interventions
and Complications (EDIC)
NEJM. 2005;353:2643–2653.
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UKPDS—Type 2 DM
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UKPDS 10 Years Later
• HbA1c differences gone after 1 year
• RR decrease in SU/insulin aggressive Rx
– 9% any DM endpoint
– 24% microvascular disease
– 15% MI
– 13% any cause death
• RR decrease in metformin aggressive Rx
– 21% any DM endpoint
– 33% MI
– 27% any cause death
NEJM. 2008;359:1577-1589.
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Steno-2 Study and Follow-Up
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ACCORD
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ADVANCE • 11,140 pts, RCT, HbA1c goal < 6.5%
• At 5 years—intensive 6.5%, std 7.3%
• Results
– Micro/macrovasc; HR 0.90 (0.82–0.98), 1º renal
– Major microvasc; HR 0.86 (0.77–0.97)
• 1º renal (HR 0.79; 0.66–0.93), no effect retinopathy
• No effect on major macrovasc, CV death, or any
cause death
• Gliclazide 90.5% vs 1.6%, TZD 16.8% vs 10.9%
• Insulin 40.5% vs 24.1%
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Veterans Affairs Diabetes Trial
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Glucose Control in the ICU
• Early studies showed benefit of tight control.
• More recent multicenter studies, in both
medical and surgical ICUs, show risk.
• Ideal is probably a compromise between risk of
out-of-control DM and hypoglycemia.
• 2016 SoC: 140-180 mg/dL in most critically ill
patients. Insulin is preferred treatment.
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Recommendations for Now
• HbA1c 7% remains standard of care
– Probably more to be gained from getting uncontrolled pts down to 7% than from lowering tightly controlled pts further
• Attention to healthy lifestyle
– Diet, exercise, weight control
• Aggressive BP control
• Aggressive dyslipidemia control
• Discontinue tobacco
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Metabolic Syndrome—NCEP (revised 2005, Circulation. 2005;112:2735-2752)
• Any three of five of the following
– Glucose intolerance/insulin resistance: FBS ≥ 110 mg/dL (≥ 100 mg/dL, or on drug Rx)
– Hypertension: BP ≥ 130/85 (or on drug Rx)
– Dyslipidemia
• TG ≥ 150 mg/dL (or on drug Rx)
• HDL < 40 mg/dL in men, < 50 mg/dL in women (or on drug Rx)
– Central adiposity: waist circ > 40” men, > 35” in women
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Metabolic Syndrome Prevalence
Third NHANES, 1988-1994
Arch Int Med. 2003:427-436.
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Metabolic Syndrome and
Cardiovascular Mortality JAMA. 2002;288:2709-2716.
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Metabolic Syndrome and
Cardiovascular Mortality JAMA. 2002;288:2709-2716.
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Metabolic Syndrome and
Cardiovascular Mortality JAMA. 2002;288:2709-2716.
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Finnish Diabetes Prevention Study
• Design
– 522 middle-aged overweight (BMI 31)
– 172 men and 350 women
– Mean duration 3.2 years
• Intervention Group: Individualized counseling
– Reducing weight, total intake of fat and saturated fat
– Increasing intake of fiber, physical activity
Tuomilehto J et al. N Engl J Med 2001;344:1343-1350.
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Treating the Metabolic Syndrome
Goals
Intervention Controls
P value % of subjects
Wt reduction >5% 43 13 0.001
Fat intake < 30%
energy 47 26 0.001
Sat fat
<10% energy 26 11 0.001
Fiber
>15 g/1000 kcal 25 12 0.001
Exercise > 4
hr/wk 86 71 0.001
Tuomilehto J et al. N Engl J Med 2001;344:1343-1350..
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Incidence of Diabetes during Follow-up
No. with Diabetes/Total no.
Intervention 5/13 10/66 9/69 2/38 0/25 0/24
Control 15/48 25/107 14/48 2/15 0/11 0/4
0
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Success Score
Control
Intervention
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Diabetes Prevention Program
NEJM. 2002;346:393–403.
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ADA Recommendations
• For patients with IGT or IFG
• Lifestyle intervention is primary
– Modest wt loss 5–10%
– Moderate exercise, 30 min daily
– Smoking cessation
• For patients with both IGT and IFG consider
adding metformin
– Consider OGTT in pts with IFG less than 60 y/o
and with BMI > 35
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Metabolic Syndrome
Summary
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What’s Next?
• Non-invasive glucose monitoring
• Type 1 — Islet and stem cell transplantation
• Type 2
– Rx the epidemic of obesity
– Increased understanding of weight homeostasis
• Mechanism of insulin resistance and the
connection with visceral adiposity
• Genetics of diabetes
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