1. Diabetes: Where Are We Now?
25 March 2017
Diabetes: Where Are We Now?
Elaine M. Szewc, RN, BS, AALU, ALMI
Assistant Chief Medical Director
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2. Overview
25 March 2017
According to the 2011 National Diabetes Fact Sheet (released 1/26/2011):
25.8 million individuals (8.3% of the population) in the U.S. have diabetes
18.8 million have a diagnosis of diabetes
7.0 million are undiagnosed
1.9 million NEW cases of diabetes are diagnosed each year in individuals over age 20
79 million have “pre-diabetes”
Prevalence
2 million adolescents, age have “pre-diabetes”
25.6 million (11.3 %) over age 20
10.9 million (26.9%) over age 65
Source:
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3. Adults with Diagnosed Diabetes, US, 1980--2009

4. Overview (cont’d) Morbidity and Mortality:
25 March 2017
Morbidity and Mortality:
7th leading cause of death listed on U.S. death certificates in 2007 as “underlying cause of death”
In 2004, heart disease was noted on 68% of diabetes-related death certificates among individuals 65 and up, while stroke was noted on 16%
Diabetics with heart disease have 2 to 4 times higher death rates than adults without diabetes
Risk for stroke is 2 to 4 times higher among diabetics
Diabetes is the leading cause of new cases of blindness each year, with 12,000 to 24,000 new cases of diabetic retinopathy
Source:
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5. Overview (cont’d) Morbidity and Mortality (cont’d):
25 March 2017
Morbidity and Mortality (cont’d):
Diabetes is the leading cause of kidney failure, accounting for 44% of new cases in 2008
60 to 70% of individuals with diabetes will have mild to severe peripheral neuropathy as a result of their diabetes
60% of non-traumatic lower-limb amputations occur in individuals with diabetes
Source:
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6. IGT/IFG/Pre-Diabetes – Defined
25 March 2017
Impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) is now known as pre-diabetes
Pre-diabetes is the state that occurs when blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes
Just a name change
Clearer explanation of what it means to have higher than normal blood glucose levels
Individuals with pre-diabetes have 1.5 fold risk of CAD
Individuals with diabetes have 2 to 4 fold risk of CAD
Individuals with pre-diabetes can delay or prevent onset of diabetes through lifestyle changes
25% of individuals will progress to diabetes over 3 to 5 years
Those with family history, obesity are more likely to progress more rapidly
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7. IGT/IFG/Pre-Diabetes – Defined (cont’d)
25 March 2017
Undiagnosed diabetes can cause progressive microvascular disease
Approximately 20% of newly diagnosed patients with Type 2 DM have diabetic retinopathy and 10% have nephropathy (microvascular complications)
IGT/IFG/pre-diabetes are NOT clinical entities, but rather risk factors for diabetes as well as cardiovascular disease
Source:
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8. Diabetes - Defined 1997 – the ADA refined terms to describe diabetes
25 March 2017
1997 – the ADA refined terms to describe diabetes
Encouraged use of Type 1 or Type 2 and discouraged use of terms such as juvenile onset, insulin-dependent, non-insulin dependent, mature onset or adult onset
2003 – criteria for fasting plasma glucose level to define impaired fasting glucose (IFG) was lowered
Lowering level impacts many older age individuals
Allows early diagnosis and potential risk factor modifications to prevent micro and macrovascular risk
2010 – added A1c to diagnostic criteria
--the addition of the A1c as criteria added after testing assays have been standardized
--the addition of the A1c may decrease the proportion of patients identified as having diabetes, since some of these may actually have IFG
Source: Up-to-date, Diagnosis of diabetes mellitus, McCulloch David, updated August 2009
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9. Diabetes – Defined (cont’d)
25 March 2017
Criteria for the diagnosis of diabetes mellitus, 2010
A1c > 6.5% OR
FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours
2-h plasma glucose 200mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
Symptoms of diabetes and a random plasma glucose 200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss
A1C was added, summer of 2009 by International Expert Committee – prior concern with using A1C was based on lack of standardization of the assay
Those with abnormal A1C between 6.0 and 6.5% are at very high risk of developing diabetes
Individuals with A1C between 5.5 and 6.0% have a 5 year incidence of diabetes that ranges from 12 – 25%
In the absence of unequivocal hyperglycemia (plasma glucose levels 200 mg/dL) with symptoms, MUST repeat to confirm dx
Source: Up-to-date, Diagnosis of diabetes mellitus, McCulloch David, updated June 2011
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10. Diabetes – Defined (cont’d)
25 March 2017
Categories of increased risk for diabetes:
Impaired fasting glucose (IFG)
FPG > mg/dL
Impaired glucose tolerance (IGT)
2 hour PG (75g OGTT) > 140 – 199 mg/dL
A1c 5.7 – 6.4%
Normal fasting glucose < 100 mg/dL
Source: Up-to-date, Diagnosis of diabetes mellitus, McCulloch David, updated June 2011
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11. ADA Guidelines – IGT/IFG
25 March 2017
Goal of intervention in individuals with IGT or IFG includes prevention of diabetes and associated risk of cardiovascular disease
Lifestyle modifications are the primary intervention
Specific goals include:
Moderate weight loss (5 – 10% of body weight)
Moderate intensity exercise (30 minutes daily)
Smoking cessation
Pharmacologic agents (metformin) have demonstrated some ability to prevent or delay diabetes
Source: Up-To-Date, Prediction and prevention of type 2 diabetes mellitus, McCulloch David K MD, Robertson R Paul MD; updated June 2009
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12. ADA Treatment -- Diabetes
25 March 2017
Primary goal in treatment of diabetes is glycemic control (~ 7% for A1C) to reduce microvascular (retinopathy and nephropathy), and neuropathic complications, as well as macrovascular (cardiovascular, cerebrovascular) risk reduction
Less stringent control in subset of individuals with history of severe hypoglycemia, limited life expectancy (< 5 years), advanced microvascular or macrovascular complications and extensive co-morbid conditions
Risk factor modification to further reduce cardiovascular morbidity and risk of future cardiac events
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13. Diabetes and CAD
25 March 2017
Compared to individuals without diabetes, those with diabetes have a higher prevalence of CAD, a greater extent of coronary ischemia and are more likely to have a MI, and silent ischemia
--National cholesterol Education program report from the US consider type II DM to be a CHD equivalent
Source: Up-To-Date, Prevalence of and risk factors for coronary heart disease in diabetes mellitus, Nesto, Richard W. MD; updated September 2009
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14. Diabetes and CAD (cont’d)
25 March 2017
Based on results from Framingham Heart Study and MRFIT, diabetes remains a major independent cardiovascular risk factor even when adjusting for advancing age, hypertension, smoking, hypercholesterolemia and LVH
Presence of diabetes doubled the age-adjusted risk for cardiovascular disease in men and tripled it in women
Framingham study revealed in Type I diabetics that after age 30, CHD mortality increased rapidly
Cumulative CHD mortality was 35 % by age 55, compared to 8% for non-diabetic men
--both studies had predominately type II DM
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15. Diabetes and CAD (cont’d)
25 March 2017
TAMI trial provided cath data which revealed the diabetic patients had a significantly higher incidence of multivessel disease (66% versus 46%) and a greater number of diseased vessels then the non-diabetics
Multivessel disease is also common in asymptomatic individuals with Type 2 diabetes, particularly those with two or more coronary risk factors other then diabetes
Association between extent of coronary disease and the degree of glycemic control
--TAMI (thrombolysis and angioplasty in MI) cath date during acute MI, 148 diabetics and 923 nondiabetic patients, cath performed at 90 min and 7 to 10 days after thrombolytic therapy
--diabetics may have a blunted appreciation of ischemic pain, which may result in atypical anginal symtpoms, silent ischemia or even silent infarction
--silent ischemia in diabetes is thought to be caused at least inpart by autonomic denervation of the heart
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16. Diabetes and CAD (cont’d)
25 March 2017
ARIC study in US, large population based study revealed Type 2 diabetics without a prior infarction were at the same risk for MI (20% versus 19%) and coronary mortality (15% versus 16%) as non-diabetics with a prior MI
Diabetics are more likely to experience a complication associated with an MI, including post infarction angina and heart failure
--contributory factors are diabetic paitents are more likely to have multivessel disease and fewer coronary collateral vessels
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17. 42% diabetics vs 16% nondiab with prior MI
25 March 2017
--Diabetics with and without MI had > mortality from CAD then nondiabetics
42% diabetics vs 16% nondiab with prior MI
15% diabetics vs 2 % nondiab without prior MI
--Coronary death in diab same as nondiabetic with MI
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18. Diabetes and CAD (cont’d)
25 March 2017
Individuals with diabetes comprise as much as 25-30% of those individuals who undergo revascularization
PCI versus CABG
Diabetics having PCI have increased rates of both restenosis and progression of disease compared to non-diabetics
Drug-eluting stents (DES) are now used in preference to bare metal stents (BMS) due to marked reductions in incidence of restenosis
Long-term prognosis after CABG in patients with diabetes is worse then in non-diabetics
Future of PCI with DES versus CABG?
--maintaining of Hgb A1c of < 7 preprocedural and post procedural has lowered rate of restenosis
--diabetics who have CABG tend to have worse risk factor profile – tend to be older, more three-vessel disease and poor EF
--diabetics who undergo CABG have worse prognosis if internal mammary is not used for one of grafts
--with drug-eluting stents now being used predominately, future studies may reveal that the difference in mortality between PCI and CABG is not as significant in certain scenario
Source: Up-To-Date, Coronary artery revascularization inpatients with diabetes mellitus, Nesto, Richard w. MD, updated June 2009
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19. Diabetes and CAD (cont’d)
25 March 2017
BUT…………..
Improving trends over the last 50 years with incidence of cardiovascular disease declining
Framingham Heart Study
49% decline in cardiovascular events (MI, CAD death, stroke) in diabetics
35% decline in cardiovascular events in non-diabetics
BUT……………
Diabetes was still associated with a two-fold increase in risk
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20. Diabetes and Hypertension
25 March 2017
UKPDS (United Kingdom Prospective Diabetes Study) noted at nine-year follow-up:
Each 10 mmHg reduction in mean systolic pressure was associated with a 12% reduction in any complication related to diabetes (including cardiovascular disease)
Lowest risk occurred at systolic pressure < 120 mmHg
Similar relationship noted with fatal or non-fatal MI as incidence fell from 33.1% per 1,000 patient years at systolic pressure >160 mmHg to 18.4% per 1,000 patient years at systolic pressure <120 mmHg
Aggressive antihypertensive therapy with recommended goal blood pressure <130/80 mmHg
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21. 25 March 2017
--tighter bld pressure control reduces risk for microvascular complications
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22. Diabetes and Dyslipidemia
25 March 2017
With diabetes being considered a CHD equivalent
Goal LDL is <100 mg/dL in individuals without overt CAD – in those with CAD goal LDL is < 70 mg/dL
Triglyercide levels <150 mg/dL
HDL levels >40 mg/dL for men and >50 mg/dL for women
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23. Diabetes and Microalbuminuria
25 March 2017
Microalbuminuria is defined as persistent urinary albumin excretion between 30 and 300 mg/day
Microalbuminuria is the earliest clinical manifestation of diabetic nephropathy
Associated with an increase risk of cardiovascular disease in both diabetic and non-diabetic patients
Relative risk for all cause mortality was 1.9 compared to individuals with no evidence for microalbuminuria
Relative risk for cardiovascular and coronary heart disease mortality was 2.0 and 2.3 compared to individuals with no evidence for microalbuminuria
Macroalbuminuria is defined as albumin excretion above 300 mg/day
--presence of microalbuminuria in non-diabetic is associated with cardiovascular disease, mechanism of such is not well understood, appears to be a signal from the kidney that the vasculature particulary endothelium is not functioning normally
--type I diabetes first begins to appear 5 years after diagnosis and is correlated with diabetic nephropathy
--type II diabetes the presence of microalbuminuria is often present at diagnosis and may reflect underlying cardiovascular disease rather then diabetic nephropathy
--fever, vigorous exercise, heart failure and poor glycemic control are among factors that can cause transient microalbuminuria
Source: Up-To-Date, Microabluminuria in type 2 diabetes mellitus, McCulloch, David K. MD, Barkris, George L. MD; updated August 2009
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24. Diabetes and Microalbuminuria (cont’d)
25 March 2017
In individuals with Type 1 diabetes, the reported prevalence of microalbuminuria at 10 years is between 25-40%
Prevalence of microalbuminuria in Type 2 diabetes, varies with ethnicity, being higher in Asians and Hispanics than in whites (43% versus 33% in whites)
Prevalence of microalbuminuria in elderly individuals with Type 2 diabetes is higher (? Due to hypertension, coronary disease etc)
Source: Up-To-Date, Microalbuminuria in type 2 diabetes mellitus, McCulloch, David K.MD, Bakris, George L. MD; updated August 2009
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25. Diabetes and Microalbuminuria (cont’d)
25 March 2017
HOPE (Heart Outcomes Prevention Evaluation) trial
9,000 participants
Presence of microalbuminuria was associated with an increased relative risk of primary aggregate end point (myocardial infarction, stroke, or cardiovascular death) in those with and without diabetes (1.97 and 1.61 respectively)
Risk of an adverse cardiovascular event increased progressively with increased absolute levels of microalbuminuria
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26. Diabetes and Microalbuminuria (cont’d)
25 March 2017
Rate of progression to macroalbuminuria is approximately 2.5% in Type 1 and 2.8% per year in Type 2
Higher baseline levels of albuminuria
Poor glycemic control
Inadequate blood pressure control
Smoking
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27. Diabetes and Microalbuminuria (cont’d)
25 March 2017
Regression to normoalbuminuria
Short duration of microalbuminuria
Better glycemic control (Hgb A1C < 7%)
Systolic blood pressure <129 mmHg
Use of ACE inhibitors or angiotensin II receptor blockers
Regression or at least 50% reduction in albumin excretion compared to no reduction was associated with significant reductions in death from and hospitalization for renal and cardiovascular events (adjusted risk 0.41)
Source: Up-To-Date, Microalbuminuria in type 2 diabetes mellitus, McCulloch, David K.MD, Bakris, George L. MD; updated August 2009
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28. Diabetes and Microalbuminuria (cont’d)
25 March 2017
Focus of treatment:
Glycemic control
Blood pressure control
Angiotension converting enzyme (ACE) inhibitors
Angiotensin II receptor blockers (ARBs)
Calcium channel blockers – primarily diltiazem and verapamil for the antiproteinuric effect
Goal is to reduce both microalbuminuria and prevent progression to macroalbuminuria
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29. Diabetes and Elderly Adults
25 March 2017
Prevalence of Type 2 diabetes continues to increase with increasing age
1.4% in ages 25-44
3.6% in ages 45-54
7.8% in ages 55-64
Over 10% in ages >65
Prevalence of Type 2 diabetes is likely to further increase with the new diagnostic criteria and current recommendations to screen individuals over age 45 once every three years
Source: Up-To-Date, Treatment of diabetes mellitus in elderly adults, McCulloch, David K. MD, Munshi, Medha, MD, updated June 2009
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30. Diabetes and Elderly Adults (cont’d)
25 March 2017
According to ADA, goals for glycemic control as well as risk factor management in the elderly adult should be based upon the overall health
Target A1C in a fit elderly individual with life expectancy >5 years, should be 7.0 to 8.0%
Somewhat higher if life expectancy is less or if multiple medical and functional co-morbidities
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31. Diabetes and Elderly Adults (cont’d)
25 March 2017
Managing elderly adults with diabetes and co-existing medical conditions is a challenge
Hypoglycemia & Hyperglycemia
Cognition difficulties
Increased risk for falls and injuries
Hypoglycemic episodes increase the risk of adverse cardiovascular events
Drug interactions from poly pharmacy
Start slow and go slow with medication changes or additions
Natural history of diabetic retinopathy may differ in elderly adults
Macular degeneration
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32. Diabetes and Elderly Adults (cont’d)
25 March 2017
Diabetic nephropathy
Renal artery stenosis
Diabetic neuropathy
Vascular conditions
Neurologic conditions
Cardiovascular risk reduction
Maintain risk factor modifications
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33. What has Changed in Underwriting Diabetes?
Type I diabetic
Life insurance coverage available!
Insulin Pumps
Pancreatic & islet transplantation
Type II diabetic
Increased prevalence
Use of insulin to control blood glucose
Changing focus of control, more emphasis on cardiovascular risk factor modifications

34. What’s New, What’s Pending
Insulin inhalers in clinical trials
Afrezza – ultra rapid acting inhaled insulin, absorbed through lungs, peaks 12 to 14 minutes after inhaled – short acting (3 hours) used at meal time to buffer the “glucose spikes”
Oral-lyn – rapid acting inhaled insulin, sprayed in mouth absorbed through buccal mucosa, used at meal time
PH20 – new ultrafast insulin analog – Phase 2 trials
Juvisnyc FDA approval 10/7/11 – combines Sitagliptin (Januvia) & simvastatin to treat high cholesterol and Type 2 diabetes
Insulin degludec – awaiting FDA approval -- long acting insulin, clinical trials have favorable results in lowering frequency of hypoglycemia especially during night

35. What’s New, What’s Pending (cont’d)
Awaiting FDA approval for clinical trials – wireless insulin delivery system that functions like a human pancreas – continuous glucose monitor, programmable insulin pump, computer algorithm that calculates how much insulin is need and when needed
Pending FDA approval – Iglucose, wirelessly collects, stores and transmits glucose readings from select glucose monitors to a secure HIPPA compliant database that can be sent to your healthcare provider
FDA approved iPro2 is a 3 day evaluation system for continuous glucose monitoring – glucose sensor inserted into patients skin, after 3 days sensor removed – helps identify nocturnal hypoglycemia or postprandial hyperglycemia
The list goes on…………………………

36. Controlling Diabetes
Disability and premature death are not inevitable consequence of diabetes
Physical activity, diet, medications can control effects of diabetes
Reducing A1c by 1% can reduce risk of eye, kidney, retinopathy by 40%
Controlling blood pressure can reduce risk of heart disease and stroke by 33 – 50%
Improving LDL cholesterol can reduce cardiovascular complications by 20 – 50%
Laser therapy for diabetic retinopathy can reduce risk of blindness by 50 – 60%
Foot care programs can reduce amputation rates by 45-85%

37. The Many Faces of Diabetes
25 March 2017
Can you identify who has diabetes?
Who has Type I, Type II?
Who has multiple complications?
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38. Diabetes Case Studies
25 March 2017
So, is diabetes with a little of this and a little of that really all that bad?
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39. Case Study #1 82 year-old female, Non-Smoker, informal $120,000 Exam:
25 March 2017
82 year-old female, Non-Smoker, informal $120,000
Exam:
5’3”, 192 lbs, 164/87 (exam average)
Type 2 DM, diet controlled
HBP on meds
^ lipids on meds
Neuropathy on neurontin
DWR 10/10
GUG 8 seconds
Drives, socially active with senior center, mows her own lawn
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40. Case Study #1 (cont’d) Labs: Glucose 81 mg/dL Fructosamine 2mmol/L
25 March 2017
Labs:
Glucose 81 mg/dL
Fructosamine 2mmol/L
BUN 19
Creatinine 0.7
Cholesterol 184 – ratio 4.6
proBNP 110 pg/mL
Urine:
Protein 7 mg
p/c ratio 0.12 mg/mg cr
Hemogloblin screen (+)
WBC 3
RBC 5
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41. Case Study #1 (cont’d) APS:
25 March 2017
APS:
Diabetes for last 5+ years, diet controlled
A1C in aps ranges from 6.0 to 7.1 (2/10 labs)
Hx of UTI in 3/09 and again in 2/10
Random urine MA in 3/09 35 ug/mL (normal to 17)
Serum creatinine range from 0.6 to 0.75 mg/dL
eGFR >59
Blood pressure average in APS was 120/80 over the last three years
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42. Case Study #1 (cont’d) Additional urine #1 Protein 2mg
25 March 2017
Additional urine #1
Protein 2mg
Creatinine 8.2 mg/dL
p/c ratio 0.24 mg/mg cr
Hemogloblin screen (-)
MA 0.7 mg/dL (normal <3)
Malb/creat ratio mg/Gcre (normal <30)
Opinion?
Additional urine #2
Protein 2mg
Creatinine 5.7 mg/dL
p/c ratio 0.35 mg/mg cr
Hemogloblin screen (-)
MA 0.6 mg/dL
Malb/creat ratio mg/Gcre
(+) urine MA with good KFT’s, good bld pressure control
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43. Case Study #1 (cont’d) Opinion?
25 March 2017
Opinion?
(+) urine MA with good KFT’s, good blood pressure control
Mild substandard to standard
(+) urine MA with good KFT’s, good bld pressure control
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44. Case Study #2 49 year-old male, Non-Smoker, formal $750,000 Exam:
25 March 2017
49 year-old male, Non-Smoker, formal $750,000
Exam:
6’2”, 200 lbs
DM since age 24
HBP
Meds – novolog, lantus, caduet, avalide
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45. Case Study #2 (cont’d) Labs: Glucose 117 mg/dL
25 March 2017
Labs:
Glucose 117 mg/dL
Fructosamine 2.94 mmol/L
A1C 9.2%
BUN 16 mg/dL
Creatinine 1.17 mg/dL
Urine:
Glucose g/dL
Protein 7 mg/dL
Creatinine 62 mg/dL
MA 4.3 mg/dL
MA/creatinine ratio mg/Gcre
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46. Case Study #2 (cont’d) APS:
25 March 2017
APS:
LOV 9/09, c/o pain tingling numbness bilateral feet
A1C difficult to control, occasional hypoglycemia
Hx syncopal episode secondary to hypoglycemia
5/09 episode hypoglycemia
A1c trends
09/09 8.5
05/09 8.5
12/08 9.0
07/08 8.9
Opinion?
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47. Case Study #2 (cont’d) Opinion? Type I diabetic Fair to poor control
25 March 2017
Opinion?
Type I diabetic
Fair to poor control
Syncopal episode due to hypoglycemia
Neuropathy
Microalbuminuria
Decline
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48. Case Study #3 75 year-old male, Non-Smoker, informal $5,000,000 Exam:
25 March 2017
75 year-old male, Non-Smoker, informal $5,000,000
Exam:
5’10’’, 185 lbs, 124/72
HBP on meds
^ lipids on meds
Type 2 DM, diagnosed 2 years ago, metformin
CABG 10 years ago to two vessels
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49. Case Study #3 (cont’d) Labs: Glucose 116 A1C 6.1
25 March 2017
Labs:
Glucose 116
A1C 6.1
Cholesterol 184, ratio 3.3
Urine:
MA 2.1
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50. Case Study #3 (cont’d) APS:
25 March 2017
APS:
2/00 cath due to abnormal perfusion study to evaluate chest pain
LM 40% distally
RCA 80%
Circumflex 50% with good collateral fill
3/00 CABG with LIMA to proximal LAD, sapphenous vein graft to mid RCA
Serial stress echo’s, last in 1/10 – exercised 9 min, achieved 10 METS, normal blood pressure response to exercise, normal wall motion, no evidence for ischemia, EF 60%
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51. Case Study #3 (cont’d) APS (cont’d):
25 March 2017
APS (cont’d):
2008 diagnosed with Type 2 diabetes, placed on metformin
A1C trends have been in the 6.2 to 7.5 range with the last A1C in 1/10 of 6.8
Exercises 3x per week at senior center
Opinion?
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52. Case Study #3 (cont’d) Opinion? Older age for onset of diabetes
25 March 2017
Opinion?
Older age for onset of diabetes
Good control of diabetes
CABG history ten years prior
Last stress test 2010 with good exercise capacity at 9 min, good EF, negative for ischemia
Mild substandard to standard
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53. Questions?